Sample records for early preneoplastic lesions

  1. Sequential occurrence of preneoplastic lesions and accumulation of loss of heterozygosity in patients with gallbladder stones suggest causal association with gallbladder cancer.

    PubMed

    Jain, Kajal; Mohapatra, Trilochan; Das, Prasenjit; Misra, Mahesh Chandra; Gupta, Siddhartha Datta; Ghosh, Manju; Kabra, Madhulika; Bansal, Virinder Kumar; Kumar, Subodh; Sreenivas, Vishnubhatla; Garg, Pramod Kumar

    2014-12-01

    Causal association of gallbladder stones with gallbladder cancer (GBC) is not yet well established. To study the frequency of occurrence of preneoplastic histological lesions and loss of heterozygosity (LOH) of tumor suppressor genes in patients with gallstones. All consecutive patients with gallstones undergoing cholecystectomy from 2007-2011 were included prospectively. Histological examination of the gallbladder specimens was done for preneoplastic lesions. LOH at 8 loci, that is 3p12, 3p14.2, 5q21, 9p21, 9q, 13q, 17p13, and 18q for tumor suppressor genes (DUTT1, FHIT, APC, p16, FCMD, RB1, p53, and DCC genes) that are associated with GBC was tested from microdissected preneoplastic lesions using microsatellite markers. These LOH were also tested in 30 GBC specimens. Of the 350 gallbladder specimens from gallstone patients, hyperplasia was found in 32%, metaplasia in 47.8%, dysplasia in 15.7%, and carcinoma in situ in 0.6%. Hyperplasia, metaplasia, and dysplasia alone were found in 11.7%, 24.6%, and 1.4% of patients, respectively. A combination of hyperplasia and dysplasia, metaplasia and dysplasia, and hyperplasia, metaplasia, and dysplasia was found in 3.4%, 6.3%, and 4.3% of patients, respectively. LOH was present in 2.1% to 47.8% of all the preneoplastic lesions at different loci. Fractional allelic loss was significantly higher in those with dysplasia compared with other preneoplastic lesions (0.31 vs 0.22; P = 0.042). No preneoplastic lesion or LOH was found in normal gallbladders. Patients with gallstones had a high frequency of preneoplastic lesions and accumulation of LOH at various tumor suppressor genes, suggesting a possible causal association of gallstones with GBC.

  2. Physical status of the E2 human papilloma virus 16 viral gene in cervical preneoplastic and neoplastic lesions.

    PubMed

    Tonon, S A; Picconi, M A; Bos, P D; Zinovich, J B; Galuppo, J; Alonio, L V; Teyssie, A R

    2001-05-01

    Integration of human papilloma virus (HPV) 16 DNA is considered an important genetic change in cervical lesion progression towards ICC. The viral E2 gene is often disrupted by this process, releasing suppression of viral E6/E7 oncogenes, a key factor for oncogenic progression. To evaluate the physical status of HPV 16 E2 gene in cervical preneoplastic and neoplastic lesions and its relation with lesion severity. A sensitive PCR approach for the detection of an intact E2 HPV 16 gene in infected epithelial cells from the cervix with low grade squamous intraepithelial lesion (LGSIL), high grade squamous intraepithelial lesion (HGSIL) and invasive cervical carcinoma (ICC) diagnosis was applied. The correlation between gene disruption and lesion stage was examined. Sixty-two LGSIL, 39 HGSIL and 24 ICC samples were analyzed. Fifty-seven LGSIL [92%], 13 HGSIL [33%] and 4 ICC [17%] showed results compatible with an intact E2 gene, while 5 LGSIL [8%], 26 HGSIL [67%] and 20 ICC [83%] samples gave no signal. HPV 16 E2 gene disruption showed a positive correlation with cervical lesion progression, particularly from LGSIL to HGSIL. Although additional genetic events are very likely to be needed for HGSIL to ICC progression, the E2 gene disruption is a putative early marker to consider in the prognostic analysis of HPV 16 chronically infected women.

  3. Modifying influence of swine-serum-induced liver fibrosis on development of preneoplastic lesions in rat liver.

    PubMed

    Wada, S; Kato, T; Mutai, M; Ozaki, K; Yamaguchi, S; Kim, D J; Baba-Toriyama, H; Asamoto, M; Ito, N; Tsuda, H

    1996-03-01

    Modifying effects of fibrosis or a cirrhotic state, caused by treatment with swine serum (SS), on the induction of preneoplastic focal lesions were assessed in a rat medium-term liver bioassay model for the detection of environmental carcinogens, in which the test compound is administered during the promotion phase after initiation with diethylnitrosamine. In experiment I, repeated intraperitoneal administration of SS concomitantly with the hepatopromoting agent deoxycholic acid (DCA) or phenobarbital (PB) resulted in a cirrhotic state and a significant increase in the number or size of preneoplastic glutathione S-transferase placental form (GST-P)-positive liver cell foci as compared to the corresponding DCA or PB alone groups. In experiment II, SS was given prior to commencement of the same medium-term bioassay system, in which a known hepatopromoting agent, DCA, 17-alpha-ethynylestradiol, or 2-acetylaminofluorene, was applied. In this case, the liver did not show obvious cirrhotic change and, rather than any enhancement, slight inhibition of promotion occurred. The results indicate that a coexisting, but not a pre-existing, cirrhotic condition acts to increase growth pressure on GST-P+ preneoplastic foci, and suggest that concomitant administration of SS with the promoting agent could be applied to improve the sensitivity of the assay protocol.

  4. [Microsatellite instability and human papilloma virus genotypes in preneoplastic and neoplastic uterine cervix lesions].

    PubMed

    Roa S, Juan Carlos; Martínez S, Ricardo; Montenegro, Sonia; Roa E, Iván; Capurro V, Italo; Ibacache S, Gilda; Melo A, Angélica

    2007-01-01

    The association between some specific human papilloma virus (HPV) types and cervix cancer is well known. However, the genetic conditions that favor the development of cervical cancer are less well known. To determine the presence of satellite instability (MSI) in preneoplastic and neoplastic lesions of the cervix and correlate these findings with HPV genotypes. Biopsy samples of cervical lesions were studied. Sixteen had low grade lesions, 22 had high grade lesions and 28 had an epidermoid cancer. Viral types were identified with polymerase chain reaction, dot-blot hybridization and restriction fragment length polymorphism. MSI was determined using a panel of eight highly informative microsatellites. Microsatellite instability in at least one locus was observed in 91, 56 and 69% of low grade lesions, high grade lesions and epidermoid carcinomas, respectively. MSI-High grade, MSI-Low grade instability and microsatellite stability were observed in 5, 60 and 46% of samples, respectively. Two of three samples with high grade instability had HPV 52 genotype. Other viral subtypes had frequencies that ranged from 78% to 100%, with the exception of HPV16 that was present in only 53% of samples with low grade instability. Two thirds of biopsy samples from cervical lesions had MSI, mechanism that can be involved in the first stages of cervical carcinogenesis. The low frequency of high grade instability, its association with HPV52 and the low frequency of HPV16 in samples with low grade instability, suggest different coadjutant mechanisms in cervical carcinogenesis.

  5. Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesis.

    PubMed

    Romualdo, Guilherme Ribeiro; Goto, Renata Leme; Henrique Fernandes, Ana Angélica; Cogliati, Bruno; Barbisan, Luis Fernando

    2016-10-01

    Although there is a concomitance of zinc deficiency and high incidence/mortality for hepatocellular carcinoma in certain human populations, there are no experimental studies investigating the modifying effects of zinc on hepatocarcinogenesis. Thus, we evaluated whether dietary zinc deficiency or supplementation alter the development of hepatocellular preneoplastic lesions (PNL). Therefore, neonatal male Balb/C mice were submitted to a diethylnitrosamine/2-acetylaminefluorene-induced hepatocarcinogenesis model. Moreover, mice were fed adequate (35 mg/kg diet), deficient (3 mg/kg) or supplemented (180 mg/kg) zinc diets. Mice were euthanized at 12 (early time-point) or 24 weeks (late time-point) after introducing the diets. At the early time-point, zinc deficiency decreased Nrf2 protein expression and GSH levels while increased p65 and p53 protein expression and the number of PNL/area. At the late time-point, zinc deficiency also decreased GSH levels while increased liver genotoxicity, cell proliferation into PNL and PNL size. In contrast, zinc supplementation increased antioxidant defense at both time-points but not altered PNL development. Our findings are the first to suggest that zinc deficiency predisposes mice to the PNL development in chemically-induced hepatocarcinogenesis. The decrease of Nrf2/GSH pathway and increase of liver genotoxicity, as well as the increase of p65/cell proliferation, are potential mechanisms to this zinc deficiency-mediated effect. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Preneoplastic lesions in gallbladder cancer.

    PubMed

    Roa, Iván; de Aretxabala, Xabier; Araya, Juan C; Roa, Juan

    2006-06-15

    Gallbladder cancer is an uncommon disease except in countries like Chile and areas of India and Japan. The knowledge regarding the etiology and mechanisms through which this neoplasia is developed is significantly less compared to other malignant tumors. The epithelial lesions involved in gallbladder carcinogenesis are dysplasia and adenomas that represent two biologically distinct carcinogenetic models. Dysplasia progresses to carcinoma in situ (CIS) and subsequently becomes invasive. Over 80% of invasive gallbladder cancers present areas adjacent to the CIS and epithelial dysplasia. Other authors have demonstrated adenomatous areas in carcinomas, or malignant transformation in an adenoma. The low incidence of gallbladder adenomas (0.14% of cholecystectomies) and the presence of adenomatous remnants in the neighboring mucosa to early carcinomas in less than 3% of the cases suggest the limited importance of this carcinogenic pathway. Epithelial dysplasia which is not associated with gallbladder cancer is observed in approximately 1% of cholecystectomies for symptomatic lithiasis. Metaplasia, dysplasia, and CIS are present in the mucosa adjacent to the cancer in 66%, 81.3%, and 69%, respectively. The average ages of patients with dysplasia not associated to cancer (51.9 years), early carcinomas (56.8 years), and advanced carcinomas (62.9 years) demonstrate a gradient which suggests the progression of these lesions. From the morphological point of view, the dysplasia-carcinoma sequence is the most plausible carcinogenic pathway for gallbladder cancer, a process which would require a period of approximately 10 years. Copyright 2006 Wiley-Liss, Inc.

  7. Association between Diverticular Disease and Pre-Neoplastic Colorectal Lesions in an Urban African-American Population.

    PubMed

    Ashktorab, Hassan; Panchal, Heena; Shokrani, Babak; Paydar, Mansour; Sanderson, Andrew; Lee, Edward L; Begum, Rehana; Haidary, Tahmineh; Laiyemo, Adeyinka O; McDonald-Pinkett, Shelly; Brim, Hassan; Nouraie, Mehdi

    2015-01-01

    It is unclear whether there is a shared pathway in the development of diverticular disease (DD) and potentially neoplastic colorectal lesions since both diseases are found in similar age groups and populations. To determine the association between DD and colorectal pre-neoplastic lesions in an African-American urban population. Data from 1986 patients who underwent colonoscopy at the Howard University Hospital from January 2012 through December 2012 were analyzed for this study. The presence of diverticula and polyps was recorded using colonoscopy reports. Polyps were further classified into adenoma or hyperplastic polyp based on histopathology reports. Multiple logistic regression was done to analyze the association between DD and colonic lesions. Of the 1986 study subjects, 1,119 (56%) were females, 35% had DD and 56% had at least one polyp. There was a higher prevalence of polyps (70 vs. 49%; OR = 2.3; 95% CI: 1.9-2.8) and adenoma (43 vs. 25%; OR = 2.0; 95% CI: 1.7-2.5) in the diverticular vs. non-diverticula patients. Among patients who underwent screening colonoscopy, the presence of diverticulosis was associated with increased odds of associated polyps (OR = 9.9; 95% CI: 5.4-16.8) and adenoma (OR = 5.1; 95% CI: 3.4-7.8). Patients with DD are more likely to harbor colorectal lesions. These findings call for more vigilance on the part of endoscopists during colonoscopy in patients known to harbor colonic diverticula. © 2015 S. Karger AG, Basel.

  8. Splenectomy reduces fibrosis and preneoplastic lesions with increased triglycerides and essential fatty acids in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet.

    PubMed

    Oishi, Toshiyuki; Terai, Shuji; Iwamoto, Takuya; Takami, Taro; Yamamoto, Naoki; Sakaida, Isao

    2011-05-01

      This study investigated whether splenectomy is of significance in non-alcoholic steatohepatitis (NASH).   Five-week-old Wistar rats were fed a choline-deficient diet for 8 weeks to create a NASH model. A sham-operation or splenectomy was then performed, and rats were killed 4 weeks later.   Liver fibrosis and liver preneoplastic lesions were significantly reduced in the splenectomy group compared to the sham-operation group, and α-smooth muscle actin (SMA) expression was significantly inhibited (liver fibrosis area: sham 8.63 ± 4.09%, splenectomy 5.45 ± 3.69%, P < 0.01; preneoplastic lesion size: sham 6.56 ± 3.68 ×10(6)  µm(2) /cm(2) , splenectomy 4.63 ± 3.27 ×10(6)  µm(2) /cm(2) , P < 0.05; the number of preneoplastic lesions: sham 8.33 ± 3.96/cm(2) , splenectomy 5.17 ± 1.80/cm(2) , P < 0.01; α-smooth muscle actin-positive area: sham 4.41 ± 2.48%, splenectomy 2.75 ± 1.66%, P < 0.01) On the other hand, liver triglycerides and essential fatty acids were significantly increased in the splenectomy group (liver triglycerides: sham 182 ± 35.0 mg/g, splenectomy 230 ± 35.0 mg/g, P < 0.05; liver linoleic acid: sham 17.2 ± 4.9 mg/g, splenectomy 23.3 ± 6.9 mg/g, P < 0.05; liver α-linolenic acid: sham 118 ± 36.6 µg/g, splenectomy 162 ± 51.4 µg/g, P < 0.05). In addition, expressions of hepatic fatty acid metabolism-related genes (e.g. acyl-CoA oxidase, liver carnitine palmitoyl-CoA transferase I, cytochrome P450 4A, long-chain acyl-CoA dehydrogenase and medium-chain acyl-CoA dehydrogenase) were significantly inhibited in the splenectomy group.   These findings suggest that spleen plays an important regulatory role in the fibrosis, preneoplastic lesion and lipid metabolism of liver in a rat choline-deficient L-amino acid model. © 2011 The Japan Society of Hepatology.

  9. Tumor suppression effects of bilberry extracts and enzymatically modified isoquercitrin in early preneoplastic liver cell lesions induced by piperonyl butoxide promotion in a two-stage rat hepatocarcinogenesis model.

    PubMed

    Hara, Shintaro; Morita, Reiko; Ogawa, Takashi; Segawa, Risa; Takimoto, Norifumi; Suzuki, Kazuhiko; Hamadate, Naobumi; Hayashi, Shim-Mo; Odachi, Ayano; Ogiwara, Isao; Shibusawa, Sakae; Yoshida, Toshinori; Shibutani, Makoto

    2014-08-01

    To investigate the protective effect of bilberry extracts (BBE) and enzymatically modified isoquercitrin (EMIQ) on the hepatocarcinogenic process involving oxidative stress responses, we used a two-stage hepatocarcinogenesis model in N-diethylnitrosamine-initiated and piperonyl butoxide (PBO)-promoted rats. We examined the modifying effect of co-administration with BBE or EMIQ on the liver tissue environment including oxidative stress responses, cell proliferation and apoptosis, and phosphatase and tensin homolog (PTEN)/Akt and transforming growth factor (TGF)-β/Smad signalings on the induction mechanism of preneoplastic lesions during early stages of hepatocellular tumor promotion. PBO increased the numbers and area of glutathione S-transferase placental form (GST-P)(+) liver cell foci and the numbers of Ki-67(+) proliferating cells within GST-P(+) foci. Co-administration of BBE or EMIQ suppressed these effects with the reductions of GST-P(+) foci (area) to 48.9-49.4% and Ki-67(+) cells to 55.5-61.4% of the PBO-promoted cases. Neither BBE nor EMIQ decreased microsomal reactive oxygen species induced by PBO. However, only EMIQ suppressed the level of thiobarbituric acid-reactive substances to 78.4% of the PBO-promoted cases. PBO increased the incidences of phospho-PTEN(-) foci, phospho-Akt substrate(+) foci, phospho-Smad3(-) foci and Smad4(-) foci in GST-P(+) foci. Both BBE and EMIQ decreased the incidences of phospho-PTEN(-) foci in GST-P(+) foci to 59.8-72.2% and Smad4(-) foci to 62.4-71.5% of the PBO-promoted cases, and BBE also suppressed the incidence of phospho-Akt substrate(+) foci in GST-P(+) foci to 75.2-75.7% of the PBO-promoted cases. These results suggest that PBO-induced tumor promotion involves facilitation of PTEN/Akt and disruptive TGF-β/Smad signalings without relation to oxidative stress responses, but this promotion was suppressed by co-treatment with BBE or EMIQ through suppression of cell proliferation activity of preneoplastic liver cells

  10. Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation.

    PubMed

    Bassett, Erin A; Tokarew, Nicholas; Allemano, Ema A; Mazerolle, Chantal; Morin, Katy; Mears, Alan J; McNeill, Brian; Ringuette, Randy; Campbell, Charles; Smiley, Sheila; Pokrajac, Neno T; Dubuc, Adrian M; Ramaswamy, Vijay; Northcott, Paul A; Remke, Marc; Monnier, Philippe P; Potter, David; Paes, Kim; Kirkpatrick, Laura L; Coker, Kenneth J; Rice, Dennis S; Perez-Iratxeta, Carol; Taylor, Michael D; Wallace, Valerie A

    2016-11-08

    The tumor microenvironment is a critical modulator of carcinogenesis; however, in many tumor types, the influence of the stroma during preneoplastic stages is unknown. Here we explored the relationship between pre-tumor cells and their surrounding stroma in malignant progression of the cerebellar tumor medulloblastoma (MB). We show that activation of the vascular regulatory signalling axis mediated by Norrin (an atypical Wnt)/Frizzled4 (Fzd4) inhibits MB initiation in the Ptch +/- mouse model. Loss of Norrin/Fzd4-mediated signalling in endothelial cells, either genetically or by short-term blockade, increases the frequency of pre-tumor lesions and creates a tumor-permissive microenvironment at the earliest, preneoplastic stages of MB. This pro-tumor stroma, characterized by angiogenic remodelling, is associated with an accelerated transition from preneoplasia to malignancy. These data expose a stromal component that regulates the earliest stages of tumorigenesis in the cerebellum, and a novel role for the Norrin/Fzd4 axis as an endogenous anti-tumor signal in the preneoplastic niche.

  11. Multiple Head and Neck Tumors Frequently Originate from a Single Preneoplastic Lesion

    PubMed Central

    Tabor, Maarten P.; Brakenhoff, Ruud H.; Ruijter-Schippers, Henrique J.; van der Wal, Jacqueline E.; Snow, Gordon B.; Leemans, C. René; Braakhuis, Boudewijn J. M.

    2002-01-01

    The development of second primary tumors has a negative impact on the prognosis of head and neck squamous cell carcinoma. Previously, we detected genetically altered and tumor-related mucosal lesions in the resection margins in 25% of unselected head and neck squamous cell carcinoma patients (Tabor MP, Brakenhoff RH, van Houten VMM, Kummer JA, Snel MHJ, Snijders PJF, Snow GB, Leemans CR, Braakhuis BJM: Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications. Clin Cancer Res 2001, 7: 1523–1532). The aim of this study was to determine whether first and second primary tumors are clonally related and originate from a single genetically altered field. From 10 patients we analyzed the first tumor of the oral cavity or oropharynx, the >3-cm remote second primary tumor, and the mucosa from the tumor-free margins from both resection specimens. We compared TP53 mutations and loss of heterozygosity profiles using 19 microsatellite markers at chromosomes 3p, 9p, 13q, and 17p. In all patients, genetically altered mucosal lesions were detected in at least one resection margin from both first and second primary tumor. Evidence for a common clonal origin of the first tumor, second primary tumor, and the intervening mucosa was found for at least 6 of 10 patients. Our results indicate that a proportion of multiple primary tumors have developed within a single preneoplastic field. Based on different etiology and clinical consequences, we propose that independent second primary tumors should be distinguished from second field tumors, that arise from the same genetically altered field the first tumor has developed from. PMID:12213734

  12. Suppressive Effect of Zinc on the Formation of Colonic Preneoplastic Lesions in the Mouse Fed High Levels of Dietary Iron

    PubMed Central

    Park, Hyunji; Kang, Bong Su; Kim, Dang Young; Yoon, Ja Seon; Jeong, Jae-Hwang; Nam, Sang Yoon; Yun, Young Won

    2012-01-01

    We investigated the effect of zinc on the formation of colonic aberrant crypt foci induced by azoxymethane (AOM) followed by dextran sodium sulfate (DSS) in mice with high iron diet (HFe; 450 ppm iron). Sixweek old ICR mice were fed on high iron diets with combination of three different levels of zinc in diets, low-zinc (LZn; 0.01 ppm), medium-zinc (MZn; 0.1 ppm), and high-zinc (HZn; 1 ppm) for 12 weeks. Animals were received weekly intraperitoneal injections of AOM (10 mg/kg B.W. in saline) for 3 weeks followed by 2% DSS (molecular weight 36,000~50,000) in the drinking water for a week. To confirm the iron storage in the body, the hepatic iron concentration has been determine chemically and compared with histological assessment visualized by Prussian blue reaction. Aberrant crypt (AC) and aberrant crypt foci (ACF) were analyzed in the colonic mucosa of mouse fed high dietary iron. Superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBARS) level were also investigated. Apoptosis in the preneoplastic lesion was determined by terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling (TUNEL). In addition, immunohistochemistry of β-catenin was also performed on the mucous membrane of colon. The number of large ACF (≥ 4 AC/ACF), which possess greater tumorigenic potential, was significantly lower in MZn and HZn groups compared with LZn group. Cytosolic SOD activity in the liver was significantly higher in HZn group compared with LZn group. Hepatic MDA level was decreased significantly in HZn group compared with MZn and LZn groups. Apoptotic index was significantly higher in HZn group. Taken together, these findings indicate that dietary zinc might exert a protective effect against colonic preneoplastic lesion induced by AOM/DSS in ICR mice with high iron status, and suggest that dietary supplement of zinc might play a role in suppressing colon carcinogenesis in mice. PMID:24278588

  13. Suppression of Medulloblastoma Lesions by Forced Migration of Preneoplastic Precursor Cells with Intracerebellar Administration of the Chemokine Cxcl3.

    PubMed

    Ceccarelli, Manuela; Micheli, Laura; Tirone, Felice

    2016-01-01

    Medulloblastoma (MB), tumor of the cerebellum, remains a leading cause of cancer-related mortality in childhood. We previously showed, in a mouse model of spontaneous MB ( Ptch1 +/- / Tis21 -/- ), that a defect of the migration of cerebellar granule neuron precursor cells (GCPs) correlates with an increased frequency of MB. This occurs because GCPs, rather than migrating internally and differentiating, remain longer in the proliferative area at the cerebellar surface, becoming targets of transforming insults. Furthermore, we identified the chemokine Cxcl3 as responsible for the inward migration of GCPs. As it is known that preneoplastic GCPs (pGCPs) can still migrate and differentiate like normal GCPs, thus exiting the neoplastic program, in this study we tested the hypothesis that pGCPs within a MB lesion could be induced by Cxcl3 to migrate and differentiate. We observed that the administration of Cxcl3 for 28 days within the cerebellum of 1-month-old Ptch1 +/- / Tis21 -/- mice, i.e., when MB lesions are already formed, leads to complete disappearance of the lesions. However, a shorter treatment with Cxcl3 (2 weeks) was ineffective, suggesting that the suppression of MB lesions is dependent on the duration of Cxcl3 application. We verified that the treatment with Cxcl3 causes a massive migration of pGCPs from the lesion to the internal granular layer, where they differentiate. Thus, the induction of migration of pGCPs in MB lesions may open new ways to treat MB that exploit the plasticity of the pGCPs, forcing their differentiation. It remains to be tested whether this plasticity continues at advanced stages of MB. If so, these findings would set a potential use of the chemokine Cxcl3 as therapeutic agent against MB development in human preclinical studies.

  14. Biological and genetic properties of the p53 null preneoplastic mammary epithelium

    NASA Technical Reports Server (NTRS)

    Medina, Daniel; Kittrell, Frances S.; Shepard, Anne; Stephens, L. Clifton; Jiang, Cheng; Lu, Junxuan; Allred, D. Craig; McCarthy, Maureen; Ullrich, Robert L.

    2002-01-01

    The absence of the tumor suppressor gene p53 confers an increased tumorigenic risk for mammary epithelial cells. In this report, we describe the biological and genetic properties of the p53 null preneoplastic mouse mammary epithelium in a p53 wild-type environment. Mammary epithelium from p53 null mice was transplanted serially into the cleared mammary fat pads of p53 wild-type BALB/c female to develop stable outgrowth lines. The outgrowth lines were transplanted for 10 generations. The outgrowths were ductal in morphology and progressed through ductal hyperplasia and ductal carcinoma in situ before invasive cancer. The preneoplastic outgrowth lines were immortal and exhibited activated telomerase activity. They are estrogen and progesterone receptor-positive, and aneuploid, and had various levels of tumorigenic potential. The biological and genetic properties of these lines are distinct from those found in most hyperplastic alveolar outgrowth lines, the form of mammary preneoplasia occurring in most traditional models of murine mammary tumorigenesis. These results indicate that the preneoplastic cell populations found in this genetically engineered model are similar in biological properties to a subset of precurser lesions found in human breast cancer and provide a unique model to identify secondary events critical for tumorigenicity and invasiveness.

  15. Genetic polymorphisms and protein expression of P53 and BRCA1 in preneoplastic and neoplastic rat mammary glands.

    PubMed

    Al-Dhaheri, Wafa; Hassouna, Imam; Karam, Sherif M

    2018-05-01

    Breast cancer is the most common type of cancer and the leading cause of cancer-related deaths among women in the United Arab Emirates and worldwide. Although many factors contribute to the high incidence of breast cancer, a considerable number of cases are related to environmental factors. In the present study, breast cancer was induced in female rats using a single dose, 80 mg/kg body wt, of the environmental carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). The aim of the present study, was to characterize some of the molecular changes that occur during breast cancer development in the DMBA-treated rat model. Mammary gland tissues of control and DMBA-treated rats were processed for: i) immunohistochemical probing using anti-BRCA1 antibody to characterize and correlate the localization of this cell cycle protein during progression to cancer, ii) western blotting to analyze the alteration of p53 protein expression in preneoplastic and neoplastic lesions of the mammary glands, and iii) polymerase chain reactions using primers specific for BRCA1 and P53 genes followed by single stranded conformational polymorphism (SSCP) or restriction fragment length polymorphism (RFLP) assays to detect possible mutations in these genes during development of breast cancer. Microscopic examination revealed a wide range of preneoplastic and neoplastic lesions providing a sequence representing the multistep process of breast cancer formation in DMBA-treated rats. Probing for BRCA1 protein revealed a gradual defect in its translocation from the cytoplasm to the nucleus during breast cancer progression. In control rats, BRCA1 was present in the nuclei of terminal duct epithelial cells. However, in the preneoplastic lesions, BRCA1 was localized in both the cytoplasm and nuclei of the epithelial duct cells. In all malignant lesions, BRCA1 was mostly found in the cytoplasm. Western blotting revealed initial downregulation in the expression of p53 protein during breast cancer

  16. Cervical (pre)neoplastic microenvironment promotes the emergence of tolerogenic dendritic cells via RANKL secretion

    PubMed Central

    Demoulin, Stéphanie A; Somja, Joan; Duray, Anaëlle; Guénin, Samuel; Roncarati, Patrick; Delvenne, Philippe O; Herfs, Michael F; Hubert, Pascale M

    2015-01-01

    The progression of genital human papillomavirus (HPV) infections into preneoplastic lesions suggests that infected/malignant cells are not adequately recognized by the immune system. In this study, we demonstrated that cervical/vulvar cancer cells secrete factor(s) that affect both the maturation and function of dendritic cells (DC) leading to a tolerogenic profile. Indeed, DC cocultured with cancer cell lines display both a partially mature phenotype after lipopolysaccharide (LPS) maturation and an altered secretory profile (IL-10high and IL-12p70low). In addition, tumor-converted DC acquire the ability to alter T-cell proliferation and to induce FoxP3+ suppressive T cells from naive CD4+ T cells. Among the immunosuppressive factors implicated in DC alterations in genital (pre)neoplastic microenvironment, we identified receptor activator of nuclear factor kappa-B ligand (RANKL), a TNF family member, as a potential candidate. For the first time, we showed that RANKL expression strongly increases during cervical progression. We also confirmed that RANKL is directly secreted by cancer cells and this expression is not related to HPV viral oncoprotein induction. Interestingly, the addition of osteoprotegerin (OPG) in coculture experiments reduces significantly the inhibition of DC maturation, the release of a tolerogenic cytokine profile (IL-12low IL-10high) and the induction of regulatory T (Treg) cells. Our findings suggest that the use of inhibitory molecules directed against RANKL in cervical/vulvar (pre)neoplastic lesions might prevent alterations of DC functionality and represent an attractive strategy to overcome immune tolerance in such cancers. PMID:26155412

  17. The flavonoid chrysin attenuates colorectal pathological remodeling reducing the number and severity of pre-neoplastic lesions in rats exposed to the carcinogen 1,2-dimethylhydrazine.

    PubMed

    Sequetto, Priscila L; Oliveira, Tânia T; Soares, Italo A C; Maldonado, Izabel R S C; Mello, Vanessa J; Pizziolo, Virginia R; Almeida, Márcia R; Novaes, Rômulo D

    2013-05-01

    Phenolic compounds are naturally occurring, bioactive substances with marked antioxidant and anti-inflammatory potential. The flavonoid chrysin, found in high levels in honey bee propolis, inhibits the activity of enzymes involved in carcinogenesis. We have investigated the effect of chrysin on pre-neoplastic colorectal lesions (ACF, aberrant crypt foci) in a rat model of chemical carcinogenesis induced by 1,2-dimethylhydrazine (DMH). Female Wistar rats weighing 137.2 ± 24.3 g received weekly one subcutaneous injection of DMH (20 mg/kg) for 10 weeks. The animals were divided into five groups each with seven animals: Group 1, 0.9% saline; Group 2, DMH+0.9% saline; Group 3, DMH+chrysin (10 mg/kg); Group 4, DMH+chrysin (100 mg/kg); Group 5, DMH+chrysin (200 mg/kg). Groups 2 and 3 showed a significant increase in ACF number, nucleolus organizer regions per enterocyte nucleus and nitrite/nitrate serum levels compared with Group 1. Groups 4 and 5 presented a significant reduction in all these parameters compared with Group 2. The levels of antioxidant minerals (copper, magnesium, selenium, zinc) and the number of enteroendocrine and mucin-producing cells were significantly reduced in Groups 2 and 3 but were similar in Groups 4 and 5 compared with Group 1. Chrysin, at 100 mg/kg and 200 mg/kg, was effective in attenuating pathological colorectal remodeling, reducing the number of pre-neoplastic lesions in rats exposed to DMH. Some of these effects might be attributable to the recovery of antioxidant mineral levels, a reduction in systemic nitrosative stress and an inhibition of the cellular proliferation induced by this flavonoid.

  18. Two types of putative preneoplastic lesions identified by hexosaminidase activity in whole-mounts of colons from F344 rats treated with carcinogen.

    PubMed

    Pretlow, T P; O'Riordan, M A; Spancake, K M; Pretlow, T G

    1993-06-01

    Previous studies identified as putative preneoplastic lesions 1) enzyme-altered foci in sections of methacrylate-embedded colon and 2) aberrant crypts in methylene blue-stained unembedded (whole-mount) colon and established that aberrant crypts embedded in methacrylate had enzyme alterations. We have now studied histochemically demonstrable hexosaminidase activity in unembedded or whole-mount preparations of colons from carcinogen-treated rats. These preparations have revealed two populations of crypts that are enzyme-altered: those that are morphologically altered or aberrant and those that are morphologically normal. Both populations can be quantified rigorously in less than an hour with whole-mount preparations reacted for hexosaminidase. The demonstration of phenotypic characteristics with histochemical techniques in whole-mount preparations should have wide applicability to functional studies in many normal and diseased tissues.

  19. Two types of putative preneoplastic lesions identified by hexosaminidase activity in whole-mounts of colons from F344 rats treated with carcinogen.

    PubMed Central

    Pretlow, T. P.; O'Riordan, M. A.; Spancake, K. M.; Pretlow, T. G.

    1993-01-01

    Previous studies identified as putative preneoplastic lesions 1) enzyme-altered foci in sections of methacrylate-embedded colon and 2) aberrant crypts in methylene blue-stained unembedded (whole-mount) colon and established that aberrant crypts embedded in methacrylate had enzyme alterations. We have now studied histochemically demonstrable hexosaminidase activity in unembedded or whole-mount preparations of colons from carcinogen-treated rats. These preparations have revealed two populations of crypts that are enzyme-altered: those that are morphologically altered or aberrant and those that are morphologically normal. Both populations can be quantified rigorously in less than an hour with whole-mount preparations reacted for hexosaminidase. The demonstration of phenotypic characteristics with histochemical techniques in whole-mount preparations should have wide applicability to functional studies in many normal and diseased tissues. Images Figure 1 PMID:8506941

  20. Tea polyphenols prevent lung from preneoplastic lesions and effect p53 and bcl-2 gene expression in rat lung tissues.

    PubMed

    Gu, Qihua; Hu, Chengping; Chen, Qiong; Xia, Ying

    2013-01-01

    Lung cancer is one of the cancers that have the highest incidence and the highest mortality rate, and it is of great interest to identify ways to prevent its occurrence. We had established an animal model by using 3,4-benzopyrene intra-pulmonary injection in our previous study, and had observed that the rats lung carcinoma incidence and multiplicity were significantly reduced by green tea administration. This study further investigated the effect of tea polyphenols on rat lung preneoplastic lesions using the lung carcinoma model established by 3,4-benzopyrene intra-pulmonary injection. Sprague-Dawley rats of the same age were randomly divided into 10 groups and treated with 3,4-benzopyrene by intra-pulmonary injection. Five groups were given 0.3% solution of tea polyphenols (equivalent to 1.2% of green tea) in drinking water, while the other 5 groups were given pure drinking water. The rats were sacrificed at 0, 1, 4, 8 and 16 weeks after carcinogen treatment. In the control groups of rats, local bronchial inflammation were observed at 1 week after 3,4-benzopyrene treatment. From 4 weeks to 16 weeks after carcinogen treatment, hyperplasia, cell hyperproliferation, heterogeneity were observed in the bronchial epithelium. Meanwhile, the expression of p53 mRNA and protein, as well as the level of bcl-2, increased in the bronchial epithelial lesion. Tea polyphenols treatment significantly alleviated the bronchial epithelial lesions. At the same time, tea polyphenols treatment enhanced p53 expression, but reduced bcl-2 expression. These results indicated that tea polyphenols may have preventive effect against lung preneoplasm lesions, possibly through regulating the expression of some critical genes such as p53 and bcl-2.

  1. Conservative approach to preneoplastic cervical lesions in postmenopause.

    PubMed

    Vetrano, Giuseppe; Aleandri, Vincenzo; Ciolli, Paola; Scardamaglia, Paola; Pacchiarotti, Arianna; Verrico, Monica; Carboni, Simona; Corosu, Roberto

    2008-01-01

    To evaluate the recurrence rate of high-grade squamous intraepithelial lesions in postmenopausal women previously submitted to laser CO2 conization and the role of persistent oncogenic HPV types. Fifty-five patients with a cytological diagnosis of high-grade squamous intraepithelial lesions were triaged with a standard colposcopy. Hormonal replacement therapy was considered as significative in influencing cervical trophism. Vaginal smears for microbiological examination were obtained. H-R HPV test was performed by PCR. The follow-up checks including cytology, colposcopy and HVP test were performed for a minimum of 5 years. Histological analysis revealed 19 CIN2 (cervical intraepithelial lesions) and 36 CIN3 lesions. The cumulative failure rate at first treatment was 14%. HPV test was positive for HPV 16 type in all patients. Forty-two patients during the follow up checks resulted negative to cytology, colposcopy and HR HPV test. At the one-year follow-up check, 7 patients revealed normal cytological and abnormal colposcopical findings and persistent positive HR HPV test. At the five-year follow-up check, 14 patients with a normal cytological smear had a recurrence of CIN2/3 and positive HR HPV test. In postmenopause, the correct management of H-R squamous intraepithelial lesions is still debated. However, a satisfactory follow-up is the main requirement for the conservative management. HPV typing in the follow-up is important to detect persistent types to identify women at risk of developing cervical abnormalities. The incidence of cervical neoplasia does not decrease with increasing age. Since HPV positivity predicted subsequent infection, testing postmenopausal patients for the virus may be a cost-effective method of disease prevention.

  2. Hypothalamic beta-endorphin neurons suppress preneoplastic and neoplastic lesions development in 1,2-dimethylhydrazine induced rat colon cancer model.

    PubMed

    Murugan, Sengottuvelan; Dave, Yatee; Rakhit, Ankush; Sarkar, Dipak K

    2017-01-01

    In recent years, experimental studies demonstrated negative impacts of impaired body stress response on colonic pathologies. In this study, we tested if reducing body stress response by the use of β-endorphin (BEP) neuronal transplants in the hypothalamus suppresses pre-neoplastic and neoplastic lesions. Colon cancer was induced by injecting 1,2-dimethylhydrazine (DMH) for sixteen weeks in Sprague Dawley rats with BEP neuron transplants or control neuron transplants, and their colonic histopathologies, colon tissue levels of pro-inflammatory cytokines and epithelial-mesenchymal transition (EMT) proteins and splenic levels of cytotoxic proteins were measured. Our results revealed that DMH induced tumors in colon at 100% incidence in control rats but failed to induce colonic tumors in 70% of animal with BEP neuronal transplants. The mean volume of tumor at the colon was smaller in BEP neurons transplanted rats than those in controls. Histopathologies of colon tissues revealed that BEP neurons transplanted animals had lesser tissue lesions such as aberrant crypt foci (ACF) and adenocarcinoma development in the colon than those in control groups. Immunohistochemical and western blot analyses identified reduced expression of Ki-67, TNF-α and NF-κB nuclear translocation in colonic tissues of BEP neurons transplanted rats than those in controls. BEP neurons transplanted rats also showed reduced expressions of transcription factors linked to EMT like Snail, Twist, and N-cadherin, but increased the levels of an epithelial cell marker E-cadherin in colon tissue. Furthermore, splenic NK cells cytolytic proteins such as perforin, granzyme B and IFN-γ levels in BEP neurons transplanted rats were higher than those in control rats. These data suggest that BEP neuron transplants suppress the growth and progression of colonic tumors possibly by decreasing inflammatory mileu and EMT via activation of innate immune responses.

  3. Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jin Haiyan; Department of Gastroenterology and Hepatology, Yanbian University Hospital, Yanji, Jilin; Yamamoto, Naoki

    2007-12-28

    Rennin-angiotensin system is involved in liver fibrogenesis through activating hepatic stellate cells (HSCs). Telmisartan (Tel) is an angiotensin II type 1 receptor antagonist, could function as a selective peroxisome proliferator-activated receptor {gamma} activator. Here we studied the effect of Tel on liver fibrosis, pre-neoplastic lesions in vivo and primary HSCs in vitro. In vivo study, we used the choline-deficient L-amino acid-defined (CDAA)-diet induced rat NASH model. The rats were fed the CDAA diet for 8 weeks to induce liver fibrosis and pre-neoplastic lesions, and then co-administrated with Tel for another 10 weeks. Tel prevented liver fibrogenesis and pre-neoplastic lesions bymore » down-regulating TGF{beta}1 and TIMP-1, 2 and increasing MMP-13 expression. Tel inhibited HSCs activation and proliferation. These results suggested that Tel could be a promising drug for NASH related liver fibrosis.« less

  4. Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet.

    PubMed

    Jin, Haiyan; Yamamoto, Naoki; Uchida, Koichi; Terai, Shuji; Sakaida, Isao

    2007-12-28

    Rennin-angiotensin system is involved in liver fibrogenesis through activating hepatic stellate cells (HSCs). Telmisartan (Tel) is an angiotensin II type 1 receptor antagonist, could function as a selective peroxisome proliferator-activated receptor gamma activator. Here we studied the effect of Tel on liver fibrosis, pre-neoplastic lesions in vivo and primary HSCs in vitro. In vivo study, we used the choline-deficient L-amino acid-defined (CDAA)-diet induced rat NASH model. The rats were fed the CDAA diet for 8 weeks to induce liver fibrosis and pre-neoplastic lesions, and then co-administrated with Tel for another 10 weeks. Tel prevented liver fibrogenesis and pre-neoplastic lesions by down-regulating TGFbeta1 and TIMP-1, 2 and increasing MMP-13 expression. Tel inhibited HSCs activation and proliferation. These results suggested that Tel could be a promising drug for NASH related liver fibrosis.

  5. Epithelial Membrane Protein-2 Expression is an Early Predictor of Endometrial Cancer Development

    PubMed Central

    Habeeb, Omar; Goodglick, Lee; Soslow, Robert A.; Rao, Rajiv; Gordon, Lynn K.; Schirripa, Osvaldo; Horvath, Steve; Braun, Jonathan; Seligson, David B.; Wadehra, Madhuri

    2010-01-01

    BACKGROUND Endometrial cancer (EC) is a common malignancy worldwide. It is often preceded by endometrial hyperplasia, whose management and risk of neoplastic progression vary. Previously, we have shown that the tetraspan protein Epithelial Membrane Protein-2 (EMP2) is a prognostic indicator for EC aggressiveness and survival. Here we validate the expression of EMP2 in EC, and further examine whether EMP2 expression within preneoplastic lesions is an early prognostic biomarker for EC development. METHODS A tissue microarray (TMA) was constructed with a wide representation of benign and malignant endometrial samples. The TMA contains a metachronous cohort of cases from individuals who either developed or did not develop EC. Intensity and frequency of EMP2 expression were assessed using immunohistochemistry. RESULTS There was a stepwise, statistically-significant increase in the average EMP2 expression from benign to hyperplasia to atypia to EC. Furthermore, detailed analysis of EMP2 expression in potentially premalignant cases demonstrated that EMP2 positivity was a strong predictor for EC development. CONCLUSION EMP2 is an early predictor of EC development in preneoplastic lesions. In addition, combined with our previous findings, these results validate that EMP2 as a novel biomarker for EC development. PMID:20578181

  6. Enhancement of preneoplastic lesion yield by Chios Mastic Gum in a rat liver medium-term carcinogenesis bioassay

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Doi, Kenichiro; Wei, Min; Kitano, Mitsuaki

    2009-01-01

    The mastic (Pistacia lentiscus var. chia) tree is native throughout the Mediterranean region and has long proved a source of food additives and medical treatments. To investigate the modifying effects of Chios Mastic Gum on rat liver carcinogenesis, 6-week-old male F344 rats were subjected to the established rat liver medium-term carcinogenesis bioassay (Ito-test). At the commencement, rats (groups 1-4) were intraperitoneally injected with 200 mg/kg body weight of diethylnitrosamine (DEN). After two weeks, mastic was added to CRF (Charles River Formula)-1 powdered basal diet at doses of 0, 0.01, 0.1 and 1% in groups 1-4, respectively. At week 3, allmore » rats were underwent two-thirds partial hepatectomy. The experiment was terminated at week 8. As results show, liver weights were significantly increased in a mastic dose-dependent manner among groups 1-4. The numbers (/cm{sup 2}) and the areas (mm{sup 2}/cm{sup 2}) of glutathione S-transferase placental form (GST-P)-positive cell foci ({>=} 0.2 mm in diameter) were significantly increased in the DEN-1% group compared to the DEN-alone group, along with the average areas per foci and larger-sized foci ({>=} 0.4 mm). 5-Bromo-2'-deoxyuridine (BrdU) + GST-P double-immunohistochemistry showed the highest BrdU-labeling indices within GST-P foci in the DEN-1% group. 8-hydroxydeoxyguanosine (8-OHdG) levels in liver DNA did not vary, while real-time quantitative polymerase chain reaction (PCR) analysis of livers revealed many up- or down-regulated genes in the DEN-1% group. In conclusion, this is the first report to display a promotion potential of Chios Mastic Gum on the formation of preneoplastic lesions in the established rat liver medium-term carcinogenesis bioassay.« less

  7. Advanced endoscopic imaging in gastric neoplasia and preneoplasia

    PubMed Central

    Lee, Jonathan W J; Lim, Lee Guan; Yeoh, Khay Guan

    2017-01-01

    Conventional white light endoscopy remains the current standard in routine clinical practice for early detection of gastric cancer. However, it may not accurately diagnose preneoplastic gastric lesions. The technological advancements in the field of endoscopic imaging for gastric lesions are fast growing. This article reviews currently available advanced endoscopic imaging modalities, in particular chromoendoscopy, narrow band imaging and confocal laser endomicroscopy, and their corresponding evidence shown to improve diagnosis of preneoplastic gastric lesions. Raman spectrometry and polarimetry are also introduced as promising emerging technologies. PMID:28176895

  8. Regulation of miRNA-29c and its downstream pathways in preneoplastic progression of triple-negative breast cancer

    PubMed Central

    Bhardwaj, Anjana; Singh, Harpreet; Rajapakshe, Kimal; Tachibana, Kazunoshin; Ganesan, Nivetha; Pan, Yinghong; Gunaratne, Preethi H.; Coarfa, Cristian; Bedrosian, Isabelle

    2017-01-01

    Little is understood about the early molecular drivers of triple-negative breast cancer (TNBC), making the identification of women at risk and development of targeted therapy for prevention significant challenges. By sequencing a TNBC cell line-based breast cancer progression model we have found that miRNA-29c is progressively lost during TNBC tumorigenesis. In support of the tumor suppressive role of miRNA 29c, we found that low levels predict poor overall patient survival and, conversely, that ectopic expression of miRNA-29c in preneoplastic cell models inhibits growth. miRNA-29c exerts its growth inhibitory effects through direct binding and regulation of TGFB-induced factor homeobox 2 (TGIF2), CAMP-responsive element binding protein 5 (CREB5), and V-Akt murine thymoma viral oncogene homolog 3 (AKT3). miRNA-29c regulation of these gene targets seems to be functionally relevant, as TGIF2, CREB5, and AKT3 were able to rescue the inhibition of cell proliferation and colony formation caused by ectopic expression of miRNA-29c in preneoplastic cells. AKT3 is an oncogene of known relevance in breast cancer, and as a proof of principle we show that inhibition of phosphoinositide 3-kinase (PI3K) activity, a protein upstream of AKT3, suppressed proliferation in TNBC preneoplastic cells. We explored additional opportunities for prevention of TNBC by studying the regulation of miRNA-29c and identified DNA methylation to have a role in the inhibition of miRNA-29c during TNBC tumorigenesis. Consistent with these observations, we found 5 aza-cytadine to relieve the suppression of miRNA-29c. Together, these results demonstrate that miRNA-29c loss plays a key role in the early development of TNBC. PMID:28160548

  9. Promoting effects of potassium dibasic phosphate on early-stage renal carcinogenesis in unilaterally nephrectomized rats treated with N-ethyl-N-hydroxyethylnitrosamine.

    PubMed

    Hiasa, Y; Konishi, N; Nakaoka, S; Nakamura, T; Nishii, K; Ohshima, M

    1992-07-01

    The effects of potassium dibasic phosphate (PDP), potassium aluminum sulfate (PAS) and copper sulfate (CS) on early-stage renal carcinogenesis were investigated in unilaterally nephrectomized male Wistar rats after N-ethyl-N-hydroxyethylnitrosamine (EHEN) administration. After feeding 1,000 ppm EHEN, or basal diet for 2 weeks and removal of the left kidney at week 3, male Wistar rats were divided into 8 groups of 20 rats each. These groups received the following dietary treatments: 50,000 ppm PDP, 50,000 ppm PAS, 5,000 ppm CS or basal diet, respectively, for 18 weeks from weeks 3 to 20. The average numbers of adenomatous hyperplasias counted as preneoplastic lesions in the EHEN with 50,000 ppm PDP group were significantly higher than in the EHEN alone group or the EHEN followed by 50,000 ppm PAS or 5,000 ppm CS group. The treatment with 50,000 ppm PDP induced renal calcification and promoted the development of preneoplastic lesions in unilaterally nephrectomized rats treated with EHEN, but that with 50,000 ppm PAS or 5,000 ppm CS did not.

  10. Food-grade TiO2 impairs intestinal and systemic immune homeostasis, initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon.

    PubMed

    Bettini, Sarah; Boutet-Robinet, Elisa; Cartier, Christel; Coméra, Christine; Gaultier, Eric; Dupuy, Jacques; Naud, Nathalie; Taché, Sylviane; Grysan, Patrick; Reguer, Solenn; Thieriet, Nathalie; Réfrégiers, Matthieu; Thiaudière, Dominique; Cravedi, Jean-Pierre; Carrière, Marie; Audinot, Jean-Nicolas; Pierre, Fabrice H; Guzylack-Piriou, Laurence; Houdeau, Eric

    2017-01-20

    Food-grade titanium dioxide (TiO 2 ) containing a nanoscale particle fraction (TiO 2 -NPs) is approved as a white pigment (E171 in Europe) in common foodstuffs, including confectionary. There are growing concerns that daily oral TiO 2 -NP intake is associated with an increased risk of chronic intestinal inflammation and carcinogenesis. In rats orally exposed for one week to E171 at human relevant levels, titanium was detected in the immune cells of Peyer's patches (PP) as observed with the TiO 2 -NP model NM-105. Dendritic cell frequency increased in PP regardless of the TiO 2 treatment, while regulatory T cells involved in dampening inflammatory responses decreased with E171 only, an effect still observed after 100 days of treatment. In all TiO 2 -treated rats, stimulation of immune cells isolated from PP showed a decrease in Thelper (Th)-1 IFN-γ secretion, while splenic Th1/Th17 inflammatory responses sharply increased. E171 or NM-105 for one week did not initiate intestinal inflammation, while a 100-day E171 treatment promoted colon microinflammation and initiated preneoplastic lesions while also fostering the growth of aberrant crypt foci in a chemically induced carcinogenesis model. These data should be considered for risk assessments of the susceptibility to Th17-driven autoimmune diseases and to colorectal cancer in humans exposed to TiO 2 from dietary sources.

  11. Food-grade TiO2 impairs intestinal and systemic immune homeostasis, initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon

    PubMed Central

    Bettini, Sarah; Boutet-Robinet, Elisa; Cartier, Christel; Coméra, Christine; Gaultier, Eric; Dupuy, Jacques; Naud, Nathalie; Taché, Sylviane; Grysan, Patrick; Reguer, Solenn; Thieriet, Nathalie; Réfrégiers, Matthieu; Thiaudière, Dominique; Cravedi, Jean-Pierre; Carrière, Marie; Audinot, Jean-Nicolas; Pierre, Fabrice H.; Guzylack-Piriou, Laurence; Houdeau, Eric

    2017-01-01

    Food-grade titanium dioxide (TiO2) containing a nanoscale particle fraction (TiO2-NPs) is approved as a white pigment (E171 in Europe) in common foodstuffs, including confectionary. There are growing concerns that daily oral TiO2-NP intake is associated with an increased risk of chronic intestinal inflammation and carcinogenesis. In rats orally exposed for one week to E171 at human relevant levels, titanium was detected in the immune cells of Peyer’s patches (PP) as observed with the TiO2-NP model NM-105. Dendritic cell frequency increased in PP regardless of the TiO2 treatment, while regulatory T cells involved in dampening inflammatory responses decreased with E171 only, an effect still observed after 100 days of treatment. In all TiO2-treated rats, stimulation of immune cells isolated from PP showed a decrease in Thelper (Th)-1 IFN-γ secretion, while splenic Th1/Th17 inflammatory responses sharply increased. E171 or NM-105 for one week did not initiate intestinal inflammation, while a 100-day E171 treatment promoted colon microinflammation and initiated preneoplastic lesions while also fostering the growth of aberrant crypt foci in a chemically induced carcinogenesis model. These data should be considered for risk assessments of the susceptibility to Th17-driven autoimmune diseases and to colorectal cancer in humans exposed to TiO2 from dietary sources. PMID:28106049

  12. Inhibitory effects of crude alpha-mangostin, a xanthone derivative, on two different categories of colon preneoplastic lesions induced by 1, 2-dimethylhydrazine in the rat.

    PubMed

    Nabandith, Viengvansay; Suzui, Masumi; Morioka, Takamitsu; Kaneshiro, Tatsuya; Kinjo, Tatsuya; Matsumoto, Kenji; Akao, Yukihiro; Iinuma, Munekazu; Yoshimi, Naoki

    2004-01-01

    The purpose of this study was to examine whether crude alpha-mangostin (a major xanthone derivative in mangosteen pericarp (Garcinia mangostana)) has short-term chemopreventive effects on putative preneoplastic lesions involved in rat colon carcinogenesis. The crude preparation was obtained by simple recrystallization of an ethylacetate extract of mangosteen pericarps. A total of 33 five-week-old male F344 rats were randomly divided into 5 experimental groups. Rats in groups 1-3 were given a subcutaneous injection of 1,2-dimethylhydrazine (DMH)(40 mg/kg body weight) once a week for 2 weeks. Starting one week before the first injection of DMH, rats in groups 2 and 3 were fed a diet containing 0.02% and 0.05% crude alpha-mangostin, respectively, for 5 weeks. Rats in group 4 also received the diet containing 0.05% crude alpha-mangostin, while rats in group 5 served as untreated controls. The experiment was terminated 5 weeks after the start. Dietary administration of crude alpha-mangostin at both doses significantly inhibited the induction and/or development of aberrant crypt foci (ACF) (P<0.05 for 0.02% crude alpha-mangostin, P<0.01 for 0.05% crude alpha-mangostin), when compared to the DMH-treated group (group 1). Moreover, treatment of rats with 0.05% crude alpha-mangostin significantly decreased dysplastic foci (DF) (P<0.05) and beta-catenin accumulated crypts (BCAC) (P<0.05), to below the group 1 values. The proliferating cell nuclear antigen (PCNA) labeling indices of colon epithelium and focal lesions in groups 2 and 3 were also significantly lower than in group 1 and this effect occurred in a dose dependent manner of the crude alpha-mangostin. This finding that crude alpha-mangostin has potent chemopreventive effects in our short-term colon carcinogenesis bioassay system suggests that longer exposure might result in suppression of tumor development.

  13. Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates

    PubMed Central

    Chitsazzadeh, Vida; Coarfa, Cristian; Drummond, Jennifer A.; Nguyen, Tri; Joseph, Aaron; Chilukuri, Suneel; Charpiot, Elizabeth; Adelmann, Charles H.; Ching, Grace; Nguyen, Tran N.; Nicholas, Courtney; Thomas, Valencia D.; Migden, Michael; MacFarlane, Deborah; Thompson, Erika; Shen, Jianjun; Takata, Yoko; McNiece, Kayla; Polansky, Maxim A.; Abbas, Hussein A.; Rajapakshe, Kimal; Gower, Adam; Spira, Avrum; Covington, Kyle R.; Xiao, Weimin; Gunaratne, Preethi; Pickering, Curtis; Frederick, Mitchell; Myers, Jeffrey N.; Shen, Li; Yao, Hui; Su, Xiaoping; Rapini, Ronald P.; Wheeler, David A.; Hawk, Ernest T.; Flores, Elsa R.; Tsai, Kenneth Y.

    2016-01-01

    Cutaneous squamous cell carcinoma (cuSCC) comprises 15–20% of all skin cancers, accounting for over 700,000 cases in USA annually. Most cuSCC arise in association with a distinct precancerous lesion, the actinic keratosis (AK). To identify potential targets for molecularly targeted chemoprevention, here we perform integrated cross-species genomic analysis of cuSCC development through the preneoplastic AK stage using matched human samples and a solar ultraviolet radiation-driven Hairless mouse model. We identify the major transcriptional drivers of this progression sequence, showing that the key genomic changes in cuSCC development occur in the normal skin to AK transition. Our data validate the use of this ultraviolet radiation-driven mouse cuSCC model for cross-species analysis and demonstrate that cuSCC bears deep molecular similarities to multiple carcinogen-driven SCCs from diverse sites, suggesting that cuSCC may serve as an effective, accessible model for multiple SCC types and that common treatment and prevention strategies may be feasible. PMID:27574101

  14. Clinical monitoring of early caries lesions using cross polarization optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Fried, Daniel; Staninec, Michal; Darling, Cynthia L.; Chan, Kenneth H.; Pelzner, Roger B.

    New methods are needed for the nondestructive measurement of tooth demineralization and remineralization and to monitor the progression of incipient caries lesions (tooth decay) for effective nonsurgical intervention and to evaluate the performance of anti-caries treatments such as chemical treatments or laser irradiation. Studies have shown that optical coherence tomography (OCT) has great potential to fulfill this role, since it can be used to measure the depth and severity of early lesions with an axial resolution exceeding 10-μm. It is easy to apply in vivo and it can be used to image the convoluted topography of tooth occlusal surfaces. In this paper we present early results from two clinical studies underway to measure the effect of fluoride intervention on early lesions. CP-OCT was used to monitor early lesions on enamel and root surfaces before and after intervention with fluoride varnish. The lesion depth and internal structure were resolved for all the lesions examined and some lesions had well defined surface zones of lower reflectivity that may be indicative of arrested lesions. Changes were also noted in the structure of some of the lesions after fluoride intervention.

  15. The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer

    PubMed Central

    Antonio, Nicole; Bønnelykke-Behrndtz, Marie Louise; Ward, Laura Chloe; Collin, John; Christensen, Ib Jarle; Steiniche, Torben; Schmidt, Henrik; Feng, Yi; Martin, Paul

    2015-01-01

    There is a long-standing association between wound healing and cancer, with cancer often described as a “wound that does not heal”. However, little is known about how wounding, such as following surgery, biopsy collection or ulceration, might impact on cancer progression. Here, we use a translucent zebrafish larval model of RasG12V-driven neoplasia to image the interactions between inflammatory cells drawn to a wound, and to adjacent pre-neoplastic cells. We show that neutrophils are rapidly diverted from a wound to pre-neoplastic cells and these interactions lead to increased proliferation of the pre-neoplastic cells. One of the wound-inflammation-induced trophic signals is prostaglandin E2 (PGE2). In an adult model of chronic wounding in zebrafish, we show that repeated wounding with subsequent inflammation leads to a greater incidence of local melanoma formation. Our zebrafish studies led us to investigate the innate immune cell associations in ulcerated melanomas in human patients. We find a strong correlation between neutrophil presence at sites of melanoma ulceration and cell proliferation at these sites, which is associated with poor prognostic outcome. PMID:26136213

  16. Multispectral near-IR reflectance imaging of simulated early occlusal lesions: Variation of lesion contrast with lesion depth and severity

    PubMed Central

    Simon, Jacob C.; Chan, Kenneth H.; Darling, Cynthia L.; Fried, Daniel

    2014-01-01

    Background and Objectives Early demineralization appears with high contrast at near-IR wavelengths due to a ten to twenty fold difference in the magnitude of light scattering between sound and demineralized enamel. Water absorption in the near-IR has a significant effect on the lesion contrast and the highest contrast has been measured in spectral regions with higher water absorption. The purpose of this study was to determine how the lesion contrast changes with lesion severity and depth for different spectral regions in the near-IR and compare that range of contrast with visible reflectance and fluorescence. Materials and Methods Forty-four human molars were used in this in vitro study. Teeth were painted with an acid-resistant varnish, leaving a 4×4 mm window on the occlusal surface of each tooth exposed for demineralization. Artificial lesions were produced in the unprotected windows after 12–48 hr exposure to a demineralizing solution at pH-4.5. Near-IR reflectance images were acquired over several near-IR spectral distributions, visible light reflectance, and fluorescence with 405-nm excitation and detection at wavelengths greater than 500-nm. Crossed polarizers were used for reflectance measurements to reduce interference from specular reflectance. Cross polarization optical coherence tomography (CP-OCT) was used to non-destructively assess the depth and severity of demineralization in each sample window. Matching two dimensional CP-OCT images of the lesion depth and integrated reflectivity were compared with the reflectance and fluorescence images to determine how accurately the variation in the lesion contrast represents the variation in the lesion severity. Results Artificial lesions appear more uniform on tooth surfaces exposed to an acid challenge at visible wavelengths than they do in the near-IR. Measurements of the lesion depth and severity using CP-OCT show that the lesion severity varies markedly across the sample windows and that the lesion

  17. Herbal medicine Inchin-ko-to (TJ-135) prevents liver fibrosis and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet.

    PubMed

    Sakaida, Isao; Tsuchiya, Masako; Kawaguchi, Kotarou; Kimura, Teruaki; Terai, Shuji; Okita, Kiwamu

    2003-06-01

    The herbal medicine Inchin-ko-to (TJ-135), extract power from three herbs, has recently been reported possessing anti-apoptotic activity. The aim of this study was to investigate whether TJ-135 has any influence on the development of preneoplastic lesions as well as liver fibrosis. The effects of the TJ-135 were examined using the choline-deficient L-amino acid-defined diet-induced liver fibrosis model. In addition, the effect of TJ-135 on mitogen-activated protein (MAP) kinase, type III procollagen mRNA expression and the medium N-terminal procollagen III propeptide (PIIINP) concentration in a hepatic stellate cell line (LI90) were examined. TJ-135 prevented fibrosis in a dose-dependent manner up to 1.5% (w/w). TJ-135 also reduced the expression of type III procollagen mRNA in the liver, as well as the number of activated stellate cells. Furthermore, TJ-135 reduced the area of preneoplastic lesions in the liver. With LI90 cells, TJ-135 reduced MAP kinase (ERK and JNK but not P38) activities resulting in reduced type III procollagen mRNA and PIIINP concentrations in the medium in a dose-dependent manner. These results indicate that although TJ-135 has anti-apoptotic activity, TJ-135 does not increase preneoplastic lesions but significantly reduces liver fibrosis through the inhibition of stellate cell activation without a reduction of hepatocyte cell death.

  18. Noninvasive Assessment of Early Dental Lesion Using a Dual-Contrast Photoacoustic Tomography

    PubMed Central

    Cheng, Renxiang; Shao, Jiaojiao; Gao, Xiaoxiang; Tao, Chao; Ge, Jiuyu; Liu, Xiaojun

    2016-01-01

    Dental hard tissue lesions, including caries, cracked-tooth, etc., are the most prevalent diseases of people worldwide. Dental lesions and correlative diseases greatly decrease the life quality of patients throughout their lifetime. It is still hard to noninvasively detect these dental lesions in their early stages. Photoacoustic imaging is an emerging hybrid technology combining the high spatial resolution of ultrasound in deep tissue with the rich optical contrasts. In this study, a dual-contrast photoacoustic tomography is applied to detect the early dental lesions. One contrast, named B-mode, is related to the optical absorption. It is good at providing the sharp image about the morphological and macro-structural features of the teeth. Another contrast, named S-mode, is associated with the micro-structural and mechanical properties of the hard tissue. It is sensitive to the change of tissue properties induced by the early dental lesions. Experiments show that the comprehensive analysis of dual-contrast information can provide reliable information of the early dental lesions. Moreover, the imaging parameter of S-mode is device-independent and it could measure tissue properties quantitatively. We expect that the proposed scheme could be beneficial for improving safety, accuracy and sensitivity of the clinical diagnosis of the dental lesion. PMID:26902394

  19. Noninvasive Assessment of Early Dental Lesion Using a Dual-Contrast Photoacoustic Tomography

    NASA Astrophysics Data System (ADS)

    Cheng, Renxiang; Shao, Jiaojiao; Gao, Xiaoxiang; Tao, Chao; Ge, Jiuyu; Liu, Xiaojun

    2016-02-01

    Dental hard tissue lesions, including caries, cracked-tooth, etc., are the most prevalent diseases of people worldwide. Dental lesions and correlative diseases greatly decrease the life quality of patients throughout their lifetime. It is still hard to noninvasively detect these dental lesions in their early stages. Photoacoustic imaging is an emerging hybrid technology combining the high spatial resolution of ultrasound in deep tissue with the rich optical contrasts. In this study, a dual-contrast photoacoustic tomography is applied to detect the early dental lesions. One contrast, named B-mode, is related to the optical absorption. It is good at providing the sharp image about the morphological and macro-structural features of the teeth. Another contrast, named S-mode, is associated with the micro-structural and mechanical properties of the hard tissue. It is sensitive to the change of tissue properties induced by the early dental lesions. Experiments show that the comprehensive analysis of dual-contrast information can provide reliable information of the early dental lesions. Moreover, the imaging parameter of S-mode is device-independent and it could measure tissue properties quantitatively. We expect that the proposed scheme could be beneficial for improving safety, accuracy and sensitivity of the clinical diagnosis of the dental lesion.

  20. Preneoplastic lesion growth driven by the death of adjacent normal stem cells

    PubMed Central

    Chao, Dennis L.; Eck, J. Thomas; Brash, Douglas E.; Maley, Carlo C.; Luebeck, E. Georg

    2008-01-01

    Clonal expansion of premalignant lesions is an important step in the progression to cancer. This process is commonly considered to be a consequence of sustaining a proliferative mutation. Here, we investigate whether the growth trajectory of clones can be better described by a model in which clone growth does not depend on a proliferative advantage. We developed a simple computer model of clonal expansion in an epithelium in which mutant clones can only colonize space left unoccupied by the death of adjacent normal stem cells. In this model, competition for space occurs along the frontier between mutant and normal territories, and both the shapes and the growth rates of lesions are governed by the differences between mutant and normal cells' replication or apoptosis rates. The behavior of this model of clonal expansion along a mutant clone's frontier, when apoptosis of both normal and mutant cells is included, matches the growth of UVB-induced p53-mutant clones in mouse dorsal epidermis better than a standard exponential growth model that does not include tissue architecture. The model predicts precancer cell mutation and death rates that agree with biological observations. These results support the hypothesis that clonal expansion of premalignant lesions can be driven by agents, such as ionizing or nonionizing radiation, that cause cell killing but do not directly stimulate cell replication. PMID:18815380

  1. Necrotizing lymphocytic folliculitis: the early lesion of acne necrotica (varioliformis).

    PubMed

    Kossard, S; Collins, A; McCrossin, I

    1987-05-01

    Skin biopsy specimens from four patients who had recurrent bouts of lesions conforming to the clinical description of acne necrotica were studied. The pathologic findings were dominated by lymphocytic inflammation around centrally placed follicles evolving to follicular necrosis that extended to the perifollicular epidermis and dermis. Early lesions showed the development of multiple individual necrotic keratinocytes within the follicular sheath and adjacent epidermis with lymphocytic exocytosis. Later lesions showed more intense necrosis and scale crust obscuring the central target but were still dominated by a peripheral lymphocytic infiltrate. The early pathologic findings of acne necrotica (varioliformis) are represented by a necrotizing lymphocytic folliculitis and differ from the pattern seen in association with nonspecific excoriations, acute bacterial folliculitis, classic comedogenic acne, or acnitis.

  2. Premalignant lesions in the kidney.

    PubMed

    Kirkali, Z; Yorukoglu, K

    2001-12-07

    Renal cell carcinoma (RCC) is the most malignant urologic disease. Different lesions, such as dysplasia in the tubules adjacent to RCC, atypical hyperplasia in the cyst epithelium of von Hippel-Lindau syndrome, and adenoma have been described for a number of years as possible premalignant changes or precursor lesions of RCC. In two recent papers, kidneys adjacent to RCC or removed from other causes were analyzed, and dysplastic lesions were identified and defined in detail. Currently renal intraepithelial neoplasia (RIN) is the proposed term for classification. The criteria for a lesion to be defined as premalignant are (1) morphological similarity; (2) spatial association; (3) development of microinvasive carcinoma; (4) higher frequency, severity, and extent then invasive carcinoma; (5) progression to invasive cancer; and (6) similar genetic alterations. RIN resembles the neoplastic cells of RCC. There is spatial association. Progression to invasive carcinoma is described in experimental cancer models, and in some human renal tumors. Similar molecular alterations are found in some putative premalignant changes. The treatment for RCC is radical or partial nephrectomy. Preneoplastic lesions may remain in the renal remnant in patients treated by partial nephrectomy and may be the source of local recurrences. RIN seems to be a biologic precursor of some RCCs and warrants further investigation. Interpretation and reporting of these lesions would reveal important resources for the biological nature and clinical significance. The management of RIN diagnosed in a renal biopsy and partial nephrectomy needs to be answered.

  3. Induction of proliferative lesions of the uterus, testes, and liver in swiss mice given repeated injections of sodium arsenate: possible estrogenic mode of action.

    PubMed

    Waalkes, M P; Keefer, L K; Diwan, B A

    2000-07-01

    Inorganic arsenic (As) is a human carcinogen but has not been unequivocally proven carcinogenic in rodents. For instance, one older study indicates that repeated iv injections of sodium arsenate might induce lymphomas in Swiss mice (58% incidence) (Osswald and Goerttler, Verh. Dtsch. Ges. Pathol. 55, 289-293, 1971), but it was considered inadequate for critical evaluation of carcinogenic potential largely because of issues in experimental design. Therefore, we studied repeated iv sodium arsenate injection and neoplastic response in male and female Swiss mice. Groups (n = 25) of mice received sodium arsenate (0.5 mg/kg, iv) or saline (control) once/week for 20 weeks and were observed for a total of 96 weeks when the study ended. Differences in survival and body weights were unremarkable. In females, arsenate induced marked increases in the incidence and severity of cystic hyperplasia of the uterus compared against controls. Arsenate also was associated with a rare adenocarcinoma of the uterus. Hyperplastic uterine epithelium from arsenate-exposed animals showed strong positive immunostaining for the proliferating cell nuclear antigen (PCNA). There was also an upregulation of estrogen receptor (ER) immunoreactive protein in the early lesions of uterine luminal and glandular hyperplasia, although a progressive decrease in its expression was seen in the severe hyperplastic or neoplastic epithelium. In common with the preneoplastic and neoplastic gynecological lesions in humans, the levels of immunoreactive inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine-containing proteins were greater in the uterine hyperplastic epidermis and their intensity was positively correlated with the severity of the lesions. Arsenate-induced uterine hyperplastic lesions also showed a strong upregulation of cyclin D1, an estrogen-associated gene product essential for progression through the G1 phase of the cell cycle. In other tissues, arsenate increased testicular interstitial cell

  4. Plasma Cholesterol–Induced Lesion Networks Activated before Regression of Early, Mature, and Advanced Atherosclerosis

    PubMed Central

    Björkegren, Johan L. M.; Hägg, Sara; Jain, Rajeev K.; Cedergren, Cecilia; Shang, Ming-Mei; Rossignoli, Aránzazu; Takolander, Rabbe; Melander, Olle; Hamsten, Anders; Michoel, Tom; Skogsberg, Josefin

    2014-01-01

    Plasma cholesterol lowering (PCL) slows and sometimes prevents progression of atherosclerosis and may even lead to regression. Little is known about how molecular processes in the atherosclerotic arterial wall respond to PCL and modify responses to atherosclerosis regression. We studied atherosclerosis regression and global gene expression responses to PCL (≥80%) and to atherosclerosis regression itself in early, mature, and advanced lesions. In atherosclerotic aortic wall from Ldlr−/−Apob 100/100 Mttp flox/floxMx1-Cre mice, atherosclerosis regressed after PCL regardless of lesion stage. However, near-complete regression was observed only in mice with early lesions; mice with mature and advanced lesions were left with regression-resistant, relatively unstable plaque remnants. Atherosclerosis genes responding to PCL before regression, unlike those responding to the regression itself, were enriched in inherited risk for coronary artery disease and myocardial infarction, indicating causality. Inference of transcription factor (TF) regulatory networks of these PCL-responsive gene sets revealed largely different networks in early, mature, and advanced lesions. In early lesions, PPARG was identified as a specific master regulator of the PCL-responsive atherosclerosis TF-regulatory network, whereas in mature and advanced lesions, the specific master regulators were MLL5 and SRSF10/XRN2, respectively. In a THP-1 foam cell model of atherosclerosis regression, siRNA targeting of these master regulators activated the time-point-specific TF-regulatory networks and altered the accumulation of cholesterol esters. We conclude that PCL leads to complete atherosclerosis regression only in mice with early lesions. Identified master regulators and related PCL-responsive TF-regulatory networks will be interesting targets to enhance PCL-mediated regression of mature and advanced atherosclerotic lesions. PMID:24586211

  5. Urothelial dysplasia and other flat lesions of the urinary bladder: clinicopathologic and molecular features.

    PubMed

    Hodges, Kurt B; Lopez-Beltran, Antonio; Davidson, Darrell D; Montironi, Rodolfo; Cheng, Liang

    2010-02-01

    The 2004 World Health Organization classification system for urothelial neoplasia classifies flat-related preneoplastic lesions as urothelial hyperplasia (flat and papillary), reactive urothelial atypia, urothelial atypia of unknown significance, urothelial dysplasia (low-grade intraurothelial neoplasia), and urothelial carcinoma in situ (high-grade intraurothelial neoplasia). Each lesion is defined with precise nomenclature and strict morphologic criteria. In many cases, morphologic features alone suffice for diagnosis. Other cases may require a panel of immunohistochemical antibodies consisting of cytokeratin 20, p53, and CD44 for diagnosis. Recent molecular studies have provided further insight into the premalignant potential of these urothelial lesions. Herein, we present a review of flat urothelial lesions of the urinary bladder as defined by the 2004 World Health Organization classification with focus on the clinicopathologic, immunohistochemical, and molecular features. Copyright 2010 Elsevier Inc. All rights reserved.

  6. [Value of narrow band imaging endoscopy in detection of early laryngeal squamous cell carcinoma].

    PubMed

    Staníková, L; Kučová, H; Walderová, R; Zeleník, K; Šatanková, J; Komínek, P

    2015-01-01

    Narrow band imaging (NBI) is an endoscopic method using filtered wavelengths in detection of microvascular abnormalities associated with preneoplastic and neoplastic changes of the mucosa. The aim of the study is to evaluate the value of NBI endoscopy in the dia-gnosis of laryngeal precancerous and early stages of cancerous lesions and to investigate impact of NBI method in prehistological diagnostics in vivo. One hundred patients were enrolled in the study and their larynx was investigated using white light HD endoscopy and narrow band imaging between 6/ 2013- 10/ 2014. Indication criteria included chronic laryngitis, hoarseness for more than three weeks or macroscopic laryngeal lesion. Features of mucosal lesions were evaluated by white light endoscopy and afterwards were compared with intra-epithelial papillary capillary loop changes, viewed using NBI endoscopy. Suspicious lesions (leukoplakia, exophytic tumors, recurrent respiratory papillomatosis and/ or malignant type of vascular network by NBI endoscopy) were evaluated by histological analysis, results were compared with prehistological NBI dia-gnosis. Using NBI endoscopy, larger demarcation of pathological mucosal features than in white light visualization were recorded in 32/ 100 (32.0%) lesions, in 4/ 100 (4.0%) cases even new lesions were detected only by NBI endoscopy. 63/ 100 (63.0%) suspected lesions were evaluated histologically -  malign changes (carcinoma in situ or invasive carcinoma) were observed in 25/ 63 (39.7%). Prehistological diagnostics of malignant lesions using NBI endoscopy were in agreement with results of histological examination in 23/ 25 (92.0%) cases. The sensitivity of NBI in detecting malignant lesions was 89.3%, specificity of this method was 94.9%. NBI endoscopy is a promising optical technique enabling in vivo differentiation of superficial neoplastic lesions. These results suggest endoscopic NBI may be useful in the early detection of laryngeal cancer and precancerous

  7. Anti-angiogenic drug loaded liposomes: Nanotherapy for early atherosclerotic lesions in mice

    PubMed Central

    Pont, Isabel; Calatayud-Pascual, Aracely; López-Castellano, Alicia; Albelda, Elena P.; García-España, Enrique; Martí-Bonmatí, Luis; Frias, Juan C.

    2018-01-01

    Fumagillin-loaded liposomes were injected into ApoE-KO mice. The animals were divided into several groups to test the efficacy of this anti-angiogenic drug for early treatment of atherosclerotic lesions. Statistical analysis of the lesions revealed a decrease in the lesion size after 5 weeks of treatment. PMID:29338009

  8. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Marengo, Barbara; Bottini, Consuelo; La Porta, C.A.M.

    Phosphatidylethanolamine N-methyltransferase (PEMT) is the enzyme that converts phosphatidylethanolamine (PE) into phosphatidylcholine. We have previously shown that PEMT suppressed hepatoma growth by triggering apoptosis. We investigate whether PEMT controlled cell death and cell proliferation triggered by fasting/refeeding and whether it is a marker of early preneoplastic lesions. The induction of programmed cell death and suppression of cell proliferation by fasting were associated with enhanced PEMT expression and activity, and with a decrease in CTP:phosphocholine cytidylyltransferase expression. Refeeding returned the liver growth and expression of CTP:phosphocholine cytidylyltransferase to control levels, while the expression of PEMT decreased to below control values. Aftermore » DENA administration, PEMT protein, evaluated by Western blotting, slightly increased, but it remained below control levels. The treatment with 20 mg/kg DENA to refed rats induced the appearance of initiated hepatocytes that were negative for PEMT expression. Present findings indicate that PEMT is a novel tumour marker for early liver preneoplastic lesions.« less

  9. Detection of Early-Stage Oral Cancer Lesions: A Survey of California Dental Hygienists.

    PubMed

    Barao, Dayna M Hashimoto; Essex, Gwen; Lazar, Ann A; Rowe, Dorothy J

    2016-12-01

    Purpose: To assess dental hygienists' knowledge of early-stage oral cancer lesions and their practices, attitudes, barriers, and facilitators related to early detection. Methods: A 20-item survey containing images of oral lesions and related multiple-choice questions was distributed electronically by the California Dental Hygienists' Association to all dental hygienists whose email addresses were in their database. Response frequencies were calculated per survey item. Logistic regression analysis was used to explore associations. Results: Seven hundred fifty-one dental hygienists responded, yielding a 12% response rate. Respondents' correct identification of the six images of oral lesions varied from 40%-97%. Most respondents reported conducting oral cancer examinations (OCE) at every dental hygiene appointment and performing palpation during OCE. Regions of the mouth varied regarding the frequency of palpation. Lymph node palpation was considered the most commonly omitted step. Those who conducted palpations were 3.3 (95% CI: 1.4 to 7.9, p=0.006) times more likely to report that they knew someone with oral cancer and had detected oral cancer lesions than those who did not. Knowing a person with a history of oral cancer and previously detecting a cancerous lesion were also reported as factors encouraging respondents to bring suspicious lesions to the attention of the dentist. Discouraging factors were mostly related to the dentist' behavior, such as not referring a suspicious lesion for biopsy that the respondent identified. Conclusion: Detection of early-stage oral cancer lesions by dental hygienists may be enhanced through more extensive education of visual appearances of lesions and the importance of palpation in a comprehensive OCE. Copyright © 2016 The American Dental Hygienists’ Association.

  10. Targeting Premalignant Lesions - Implications for Early Breast Cancer Detection and Intervention

    DTIC Science & Technology

    2017-04-01

    lesions. Peptide conjugated AgNP were injected intravenously in mice and mammary glands were isolated and analyzed for nanoparticle accumulation by silver ...Furthermore, these probes will be used to develop targeted therapeutic nanoparticles for early intervention in breast cancer. 2. KEYWORDS...cancer (Months 18-24) (To be done) Specific Aim 3: Target premalignant lesions utilizing peptide-conjugated nanoparticles to prevent/delay

  11. Newly defined aberrant crypt foci as a marker for dysplasia in the rat colon

    PubMed Central

    Ochiai, Masako; Hippo, Yoshitaka; Izumiya, Masashi; Watanabe, Masatoshi; Nakagama, Hitoshi

    2014-01-01

    Dysplasia represents a preneoplastic status in multistep colon carcinogenesis. Whereas laborious preparation of thin sections is required for its diagnosis, we here show that newly defined aberrant crypt foci (ACF) simply mark the majority of the dysplasia on the whole colon. Specifically, decoloring of the azoxymethane-treated rat colon after scoring classical ACF (cACF) resulted in visualization of a subset of aberrant crypts that remained densely stained. They were morphologically classified into three subtypes, of which two with compressed luminal openings proved highly correlated with dysplasia. Accordingly, we designated those foci harboring either of the two crypt subtypes as dysplasia-associated ACF (dACF). By serially applying different detection methods for known preneoplastic lesions to the same colon, we showed that most dACF had already been identified as cACF, and a few newly identified dACF contained an entire population of more advanced lesions, such as flat ACF and mucin-depleted foci. Consequently, integrative scoring of cACF and dACF enabled capture of all early lesions of the colon. Furthermore, 94% of the dACF showed dysplasia and 90% of the dysplastic lesions proved to be dACF. Thus, dACF is a promising marker for dysplasia, likely facilitating precise identification of the early stages of colon carcinogenesis. PMID:24827115

  12. Growth Hormone and Insulin-Like Growth Factor-I in the Transition from Normal Mammary Development to Preneoplastic Mammary Lesions

    PubMed Central

    Kleinberg, David L.; Wood, Teresa L.; Furth, Priscilla A.; Lee, Adrian V.

    2009-01-01

    Adult female mammary development starts at puberty and is controlled by tightly regulated cross-talk between a group of hormones and growth factors. Although estrogen is the initial driving force and is joined by luteal phase progesterone, both of these hormones require GH-induced IGF-I in the mammary gland in order to act. The same group of hormones, when experimentally perturbed, can lead to development of hyperplastic lesions and increase the chances, or be precursors, of mammary carcinoma. For example, systemic administration of GH or IGF-I causes mammary hyperplasia, and overproduction of IGF-I in transgenic animals can cause the development of usual or atypical hyperplasias and sometimes carcinoma. Although studies have clearly demonstrated the transforming potential of both GH and IGF-I receptor in cell culture and in animals, debate remains as to whether their main role is actually instructive or permissive in progression to cancer in vivo. Genetic imprinting has been shown to occur in precursor lesions as early as atypical hyperplasia in women. Thus, the concept of progression from normal development to cancer through precursor lesions sensitive to hormones and growth factors discussed above is gaining support in humans as well as in animal models. Indeed, elevation of estrogen receptor, GH, IGF-I, and IGF-I receptor during progression suggests a role for these pathways in this process. New agents targeting the GH/IGF-I axis may provide a novel means to block formation and progression of precursor lesions to overt carcinoma. A novel somatostatin analog has recently been shown to prevent mammary development in rats via targeted IGF-I action inhibition at the mammary gland. Similarly, pegvisomant, a GH antagonist, and other IGF-I antagonists such as IGF binding proteins 1 and 5 also block mammary gland development. It is, therefore, possible that inhibition of IGF-I action, or perhaps GH, in the mammary gland may eventually play a role in breast cancer

  13. Thermophotonic lock-in imaging of early demineralized and carious lesions in human teeth

    NASA Astrophysics Data System (ADS)

    Tabatabaei, Nima; Mandelis, Andreas; Amaechi, Bennett Tochukwu

    2011-07-01

    As an extension of frequency-domain photothermal radiometry, a novel dental-imaging modality, thermophotonic lock-in imaging (TPLI), is introduced. This methodology uses photothermal wave principles and is capable of detecting early carious lesions and cracks on occlusal and approximal surfaces as well as early caries induced by artificial demineralizing solutions. The increased light scattering and absorption within early carious lesions increases the thermal-wave amplitude and shifts the thermal-wave centroid, producing contrast between the carious lesion and the intact enamel in both amplitude and phase images. Samples with artificial and natural occlusal and approximal caries were examined in this study. Thermophotonic effective detection depth is controlled by the modulation frequency according to the well-known concept of thermal diffusion length. TPLI phase images are emissivity normalized and therefore insensitive to the presence of stains. Amplitude images, on the other hand, provide integrated information from deeper enamel regions. It is concluded that the results of our noninvasive, noncontacting imaging methodology exhibit higher sensitivity to very early demineralization than dental radiographs and are in agreement with the destructive transverse microradiography mineral density profiles.

  14. Oral precancerous lesions: Problems of early detection and oral cancer prevention

    NASA Astrophysics Data System (ADS)

    Gileva, Olga S.; Libik, Tatiana V.; Danilov, Konstantin V.

    2016-08-01

    The study presents the results of the research in the structure, local and systemic risk factors, peculiarities of the clinical manifestation, and quality of primary diagnosis of precancerous oral mucosa lesions (OMLs). In the study a wide range of OMLs and high (25.4%) proportion of oral precancerous lesions (OPLs) in their structure was indicated. The high percentage of different diagnostic errors and the lack of oncological awareness of dental practitioners, as well as the sharp necessity of inclusion of precancer/cancer early detection techniques into their daily practice were noted. The effectiveness of chemilumenescence system of early OPLs and oral cancer detection was demonstrated, the prospects of infrared thermography as a diagnostic tool were also discussed.

  15. Dolastatin 15, a mollusk linear peptide, and Celecoxib, a selective cyclooxygenase-2 inhibitor, prevent preneoplastic colonic lesions and induce apoptosis through inhibition of the regulatory transcription factor NF-κB and an inflammatory protein, iNOS.

    PubMed

    Piplani, Honit; Vaish, Vivek; Sanyal, Sankar Nath

    2012-11-01

    The marine ecosystem is a unique and enormously rich source of natural products with potential chemopreventive applications in cancer. In the present study, we explored the chemopreventive role and the molecular mechanism of Dolastatin, a linear peptide from an Indian Ocean mollusk, and Celecoxib, a well-established cyclooxygenase-2 (COX-2) inhibitor in an individual as well as in a combination regimen in 1,2-dimethylhydrazine dihydrochloride (DMH)-induced colon carcinogenesis in a rat model. After a 6-week treatment with DMH, morphological analysis revealed a marked occurrence of preneoplastic features in the colonic mucosa, whereas histologically well-characterized dysplasia and hyperplasia were observed in DMH-treated animals. Simultaneous administration of Celecoxib and Dolastatin reduced these features significantly. DMH treatment affected the number of apoptotic cells in colonic enterocytes, which reverted to the normal level with the use of Celecoxib and Dolastatin. Inflammation remains the dominant molecular mechanism in the development of multiple plaque lesions, the carcinogenic lesions in a DMH-induced process that may be mediated by COX-2. Western blot and immunofluorescence analysis revealed a higher expression of COX-2 and nuclear factor-κB, the transcription factors responsible for proinflammatory proteins such as TNFα, and also the inducible nitric oxide synthase in the DMH group, which was further recovered significantly with the use of Celecoxib and Dolastatin. In-silico molecular docking analysis of Dolastatin as a ligand with various regulatory proteins suggests that although the peptide failed to dock to COX-2, it successfully did so with inducible nitric oxide synthase, thereby indicating the potential of this inflammatory protein as a molecular anticancer target in colon carcinogenesis.

  16. Oral Lichen Planus as a Preneoplastic Inflammatory Model

    PubMed Central

    Georgakopoulou, Eleni A.; Achtari, Marina D.; Achtaris, Michael; Foukas, Periklis G.; Kotsinas, Athanassios

    2012-01-01

    Oral lichen planus (OLP) is a chronic oral inflammatory disease of unknown etiology. According to reports, 1-2% of OLP patients develop oral squamous cell carcinoma (OSCC) in the long run. While World Health Organization (WHO) classifies OLP as “a potentially malignant disorder,” it is still a matter of debate which mechanisms drive OLP to such a condition. The current hypothesis connecting OLP and OSCC is that chronic inflammation results in crucial DNA damage which over time results in cancer development. Initial studies investigating the OLP and OSCC link were mainly retrospective clinical studies. Over the past years, several amount of information has accumulated, mainly from molecular studies on the OLP malignant potential. This article is a critical review of whether OLP has a malignant potential and, therefore, represents a model of preneoplastic inflammation. PMID:22675259

  17. High-Resolution Chromosome 3p Allelotyping of Breast Carcinomas and Precursor Lesions Demonstrates Frequent Loss of Heterozygosity and a Discontinuous Pattern of Allele Loss

    PubMed Central

    Maitra, Anirban; Wistuba, Ignacio I.; Washington, Constance; Virmani, Arvind K.; Ashfaq, Raheela; Milchgrub, Sara; Gazdar, Adi F.; Minna, John D.

    2001-01-01

    We performed high-resolution allelotyping for loss of heterozygosity (LOH) analysis on microdissected samples from 45 primary breast cancers, 47 mammary preneoplastic epithelial foci, and 18 breast cancer cell lines, using a panel of 27 polymorphic chromosome 3p markers. Allele loss in some regions of chromosome 3p was detected in 39 of 45 (87%) primary breast tumors. The 3p21.3 region had the highest frequency of LOH (69%), followed by 3p22-24 (61%), 3p21.2-21.3 (58%), 3p25 (48%), 3p14.2 (45%), 3p14.3 (41%), and 3p12 (35%). Analysis of all of the data revealed at least nine discrete intervals showing frequent allele loss: D3S1511-D3S1284 (U2020/DUTT1 region centered on D3S1274 with a homozygous deletion), D3S1300-D3S1234 [fragile histidine triad (FHIT)/FRA3B region centered on D3S1300 with a homozygous deletion], D3S1076-D3S1573, D3S4624/Luca2.1-D3S4597/P1.5, D3S1478-D3S1029, D3S1029 (with a homozygous deletion), D3S1612-D3S1537, D3S1293-D3S1597, and D3S1597-telomere; it is more than likely that additional localized regions of LOH not examined in this study also exist on chromosome 3p. In multiple cases, there was discontinuous allele loss at several 3p sites in the same tumor. Twenty-one of 47 (45%) preneoplastic lesions demonstrated 3p LOH, including 12 of 13 (92%) ductal carcinoma in situ, 2 of 7 (29%) apocrine metaplasia, and 7 of 25 (28%) usual epithelial hyperplasia. The 3p21.3 region had the highest frequency of LOH in preneoplastic breast epithelium (36%), followed by 3p21.2-21.3 (20%), 3p14.2/FHIT region (11%), 3p25 (10%), and 3p22-24 (5%). In 39 3p loci showing LOH in both the tumor and accompanying preneoplasia, 34 (87%) showed loss of the same parental allele (P = 1.2 × 10−6, cumulative binomial test). In addition, when 21 preneoplastic samples showing LOH were compared to their accompanying cancers, 67% were clonally related, 20% were potentially clonally related but were divergent, and 13% were clonally unrelated. Overall this demonstrated the

  18. Detection of oral early cancerous lesion by using polarization-sensitive optical coherence tomography: mice model

    NASA Astrophysics Data System (ADS)

    Lee, Hong-Yi; Chen, Ping-Hsien; Lee, Tzu-Han; Chang, Kuo-Wei; Kuo, Wen-Chuan

    2018-02-01

    Oral cancer is the 11th most common cancer worldwide, especially in a male adult. The median age of death in oral cancer was 55 years, 10-20 years earlier than other cancers. Presently, oral cancer is often found in late stage, because the lesion is often flat in early stage and is difficult to diagnose under traditional white light imaging. The only definitive method for determining cancer is an invasive biopsy and then using histology examination. How to detect precancerous lesions or early malignant lesions is an important issue for improving prognosis of oral cancer. Optical coherence tomography (OCT) is a new optical tool for diagnosing early malignant lesions in the skin or gastrointestinal tract recently. Here we report a new method for detecting precancerous or early malignant oral lesions by using swept source polarization-sensitive optical coherence tomography (PS-OCT) with center-wavelength 1310 nm, bandwidth 110 nm and 100 kHz swept rate. We used all single-mode fiber design to detect the change of birefringence information in the epithelium structure. This system has an advantage that enables measurement of backscattered intensity and birefringence simultaneously with only one A-scan per transverse location. In preliminary result, we computed the slope of the every A-scan signal in tissue part using a linear-curve fitting in backscattered intensity and birefringence on the enface. In this research, we used an oral cancer mice model for observing the change of structure and birefringence properties in different stages of oral cancer mice. We presented the parametric enface imaging that can detect the early oral malignant lesions.

  19. Diffusion tensor imaging of early changes in corpus callosum after acute cerebral hemisphere lesions in newborns.

    PubMed

    Righini, Andrea; Doneda, Chiara; Parazzini, Cecilia; Arrigoni, Filippo; Matta, Ursula; Triulzi, Fabio

    2010-11-01

    The main purpose was to investigate any early diffusion tensor imaging (DTI) changes in corpus callosum (CC) associated with acute cerebral hemisphere lesions in term newborns. We retrospectively analysed 19 cases of term newborns acutely affected by focal or multi-focal lesions: hypoxic-ischemic encephalopathy, hypoglycaemic encephalopathy, focal ischemic stroke and deep medullary vein associated lesions. DTI was acquired at 1.5 Tesla with dedicated neonatal coil. DTI metrics (apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial λ(∐) and radial λ(⟂) diffusivity) were measured in the hemisphere lesions and in the CC. The control group included seven normal newborns. The following significant differences were found between patients and normal controls in the CC: mean ADC was lower in patients (0.88 SD 0.23 versus 1.18 SD 0.07 μm(2)/s) and so was mean FA (0.50 SD 0.1 versus 0.67 SD 0.05) and mean λ(∐) value (1.61 SD 0.52 versus 2.36 SD 0.14 μm(2)/s). In CC the percentage of ADC always diminished independently of lesion age (with one exception), whereas in hemisphere lesions, it was negative in earlier lesions, but exceeded normal values in the older lesions. CC may undergo early DTI changes in newborns with acute focal or multi-focal hemisphere lesions of different aetiology. Although a direct insult to CC cannot be totally ruled out, DTI changes in CC (in particular λ(∐)) may also be compatible with very early Wallerian degeneration or pre-Wallerian degeneration.

  20. Diagnostic criteria for proliferative hepatic lesions in brown bullhead Ameiurus nebulosus

    USGS Publications Warehouse

    Blazer, V.S.; Fournie, J.W.; Wolf, J.C.; Wolfe, M.J.

    2006-01-01

    Brown bullhead Ameiurus nebulosus is used as indicator species for contaminant effects at areas of concern (AOC) in the Great Lakes and other areas. One of the beneficial use impairments at numerous AOC is 'fish tumors and other deformities'. An impairment occurs when the prevalence of fish tumors and other deformities exceeds those at unimpacted or control sites or when survey data confirm the presence of neoplastic or preneoplastic liver lesions in bullhead or white sucker Catostomus commersonii. Numerous surveys have been conducted over the years assessing neoplasia in these fishes, both liver and skin tumors. However, a major problem in comparing the results has been a lack of consistent criteria for evaluating histological changes in bullhead livers. As individual AOC develop and implement remedial action plans, realistic and attainable delisting targets need to be specified. For this to occur and be consistent from site to site there must be standardization of the criteria being used to evaluate specific impairments. In this report, specific diagnostic criteria are provided for both non-neoplastic and neoplastic proliferative hepatocellular and biliary lesions. These criteria should assist fish pathologists in describing and categorizing proliferative liver lesions from brown bullhead. ?? Inter-Research 2006.

  1. NYU Lung Cancer Biomarker Center — EDRN Public Portal

    Cancer.gov

    A. SPECIFIC AIMS 1. To develop and prospectively follow a large cohort at high-risk for lung cancer. Individuals are recruited to one of two different study groups: The Screening Cohort includes people with and without increased risk for lung cancer. The Rule-Out Lung Cancer Patient Group is recruited from patients referred for evaluation of suspicious nodules. All individuals answer a questionnaire, obtain PFTs, chest CT scan, sputum induction and phlebotomy. For patients undergoing lung resections or biopsies, tissue samples are collected and banked. Individuals are recruited for research bronchoscopy. All participants are then followed prospectively. The specimens obtained are banked and used for biomarker discovery and validation studies. 2. To identify and validate biomarkers for the early detection of lung cancer, and to describe preneoplastic cellular changes and lesions. Biomarker studies include DNA adducts, DNA methylation, protein markers, and other collaborations. Preneoplasia studies include: fluorescence and Superdimension bronchoscopies to obtain biopsies of preneoplastic lesions and biomarker studies in individuals with preneoplasias.

  2. Early childhood caries lesions in preschool children in Kerala, India.

    PubMed

    Jose, Babu; King, Nigel M

    2003-01-01

    No data are available on possible risk indicators or the prevalence of caries lesions for preschool children under 4 years of age in Kerala, southern India. Therefore, the aims of this study were: (1) to gather data on caries lesion frequency and distribution; (2) to determine any possible associations with feeding habits and oral health care practices. A sample of 530 children, aged from 8 to 48 months (mean=2.5+/-0.96 years), who attended 13 day care centers were clinically examined for caries lesions using a disposable mouth mirror, tongue spatula, and a torch light. There were 513 dentate children. The caregiver of each child then completed, by interview, a structured questionnaire. Among the group of 252 girls and 278 boys, the dmft was 1.84+/-2.87 with 56% of the children being caries-lesion free. Fifty-nine (12%) were considered to have early childhood caries (ECC), based on the criteria that smooth surface caries lesions on all 4 maxillary incisor teeth indicated severe ECC. Breast-feeding was practiced by 99% of the mothers, and 5% did so exclusively. Generally, breast-feeding was on demand. Statistically significant correlations were found between caries lesions and the child's dental condition, as perceived by the mother or caregiver (P<.0001), the dental status of the caregiver (P=.0417), consumption of snacks (P=.0177), giving of sweets as a reward (P<.0001), cleaning of the child's mouth (P<.0001), oral hygiene status of the child (P<.0001) and low socioeconomic status, as measured by income (P<.0001). From the results of this study of preschool children in Kerala, the groups at high risk from dental caries lesions are: (1) those with poor oral hygiene status; (2) those who consume snacks and are given sweets as rewards; (3) those belonging to a lower socioeconomic class.

  3. Genetic inactivation of Nrf2 prevents clonal expansion of initiated cells in a nutritional model of rat hepatocarcinogenesis.

    PubMed

    Orrù, Claudia; Szydlowska, Marta; Taguchi, Keiko; Zavattari, Patrizia; Perra, Andrea; Yamamoto, Masayuki; Columbano, Amedeo

    2018-06-21

    Dysregulation of the Keap1-Nrf2 pathway has been observed in experimental and human tumors, suggesting possible roles of the pathway in cancer development. Herein, we examined whether Nrf2 (Nfe2l2) activation occurs at early steps of rat hepatocarcinogenesis, to assess critical contributions of Nrf2 to the onset of hepatocellular carcinoma (HCC). We used wild-type (WT) and Nrf2 knockout (Nrf2KO) rats treated with a single injection of diethylnitrosamine (DENA) followed by choline-devoid methionine-deficient (CMD) diet. This experimental model causes massive fatty liver and steatohepatitis with fibrosis and enables identification of early stages of hepatocarcinogenesis. We found that Nrf2 activation takes place in early preneoplastic lesions identified by the marker glutathione S-transferase placental form (GSTP). Nrf2 missense mutations, known to disrupt the Keap1-Nrf2 binding, were present in 65.7% of GSTP-positive foci. Nrf2KO rats were used to directly investigate whether Nrf2 is critical for initiation and/or clonal expansion of DENA-damaged hepatocytes. While Nrf2 genetic inactivation did not alter DENA-induced initiation, it led to increased liver injury and chronic compensatory hepatocyte regeneration when rats were fed a CMD diet. However, in spite of such a permissive environment, the livers of Nrf2KO rats did not display any preneoplastic lesion unlike those of WT rats. These results demonstrate that, in a model of hepatocarcinogenesis resembling human non-alcoholic fatty liver disease: i) Nrf2 is activated at early steps of the tumorigenic process and ii) Nrf2 is mandatory for the clonal expansion of initiated cells, indicating that Nrf2 is critical in the onset of HCC. Dysregulation of the Keap1-Nrf2 molecular pathway has been observed in human tumors. In a nutritional model of hepatocarcinogenesis, the protein Nrf2 is frequently mutated/activated at early steps of the tumorigenic process. Herein, we show that Nrf2 is mandatory for the development of

  4. Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding Chronic Active Lesions

    PubMed Central

    Hendrickx, Debbie A. E.; van Scheppingen, Jackelien; van der Poel, Marlijn; Bossers, Koen; Schuurman, Karianne G.; van Eden, Corbert G.; Hol, Elly M.; Hamann, Jörg; Huitinga, Inge

    2017-01-01

    In multiple sclerosis (MS), activated microglia and infiltrating macrophages phagocytose myelin focally in (chronic) active lesions. These demyelinating sites expand in time, but at some point turn inactive into a sclerotic scar. To identify molecular mechanisms underlying lesion activity and halt, we analyzed genome-wide gene expression in rim and peri-lesional regions of chronic active and inactive MS lesions, as well as in control tissue. Gene clustering revealed patterns of gene expression specifically associated with MS and with the presumed, subsequent stages of lesion development. Next to genes involved in immune functions, we found regulation of novel genes in and around the rim of chronic active lesions, such as NPY, KANK4, NCAN, TKTL1, and ANO4. Of note, the presence of many foamy macrophages in active rims was accompanied by a congruent upregulation of genes related to lipid binding, such as MSR1, CD68, CXCL16, and OLR1, and lipid uptake, such as CHIT1, GPNMB, and CCL18. Except CCL18, these genes were already upregulated in regions around active MS lesions, showing that such lesions are indeed expanding. In vitro downregulation of the scavenger receptors MSR1 and CXCL16 reduced myelin uptake. In conclusion, this study provides the gene expression profile of different aspects of MS pathology and indicates that early demyelination, mediated by scavenger receptors, is already present in regions around active MS lesions. Genes involved in early demyelination events in regions surrounding chronic active MS lesions might be promising therapeutic targets to stop lesion expansion. PMID:29312322

  5. Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding Chronic Active Lesions.

    PubMed

    Hendrickx, Debbie A E; van Scheppingen, Jackelien; van der Poel, Marlijn; Bossers, Koen; Schuurman, Karianne G; van Eden, Corbert G; Hol, Elly M; Hamann, Jörg; Huitinga, Inge

    2017-01-01

    In multiple sclerosis (MS), activated microglia and infiltrating macrophages phagocytose myelin focally in (chronic) active lesions. These demyelinating sites expand in time, but at some point turn inactive into a sclerotic scar. To identify molecular mechanisms underlying lesion activity and halt, we analyzed genome-wide gene expression in rim and peri-lesional regions of chronic active and inactive MS lesions, as well as in control tissue. Gene clustering revealed patterns of gene expression specifically associated with MS and with the presumed, subsequent stages of lesion development. Next to genes involved in immune functions, we found regulation of novel genes in and around the rim of chronic active lesions, such as NPY, KANK4, NCAN, TKTL1 , and ANO4 . Of note, the presence of many foamy macrophages in active rims was accompanied by a congruent upregulation of genes related to lipid binding, such as MSR1, CD68, CXCL16 , and OLR1 , and lipid uptake, such as CHIT1, GPNMB , and CCL18 . Except CCL18 , these genes were already upregulated in regions around active MS lesions, showing that such lesions are indeed expanding. In vitro downregulation of the scavenger receptors MSR1 and CXCL16 reduced myelin uptake. In conclusion, this study provides the gene expression profile of different aspects of MS pathology and indicates that early demyelination, mediated by scavenger receptors, is already present in regions around active MS lesions. Genes involved in early demyelination events in regions surrounding chronic active MS lesions might be promising therapeutic targets to stop lesion expansion.

  6. Spatial distribution of early red lesions is a risk factor for development of vision-threatening diabetic retinopathy.

    PubMed

    Ometto, Giovanni; Assheton, Phil; Calivá, Francesco; Chudzik, Piotr; Al-Diri, Bashir; Hunter, Andrew; Bek, Toke

    2017-12-01

    Diabetic retinopathy is characterised by morphological lesions related to disturbances in retinal blood flow. It has previously been shown that the early development of retinal lesions temporal to the fovea may predict the development of treatment-requiring diabetic maculopathy. The aim of this study was to map accurately the area where lesions could predict progression to vision-threatening retinopathy. The predictive value of the location of the earliest red lesions representing haemorrhages and/or microaneurysms was studied by comparing their occurrence in a group of individuals later developing vision-threatening diabetic retinopathy with that in a group matched with respect to diabetes type, age, sex and age of onset of diabetes mellitus who did not develop vision-threatening diabetic retinopathy during a similar observation period. The probability of progression to vision-threatening diabetic retinopathy was higher in a circular area temporal to the fovea, and the occurrence of the first lesions in this area was predictive of the development of vision-threatening diabetic retinopathy. The calculated peak value showed that the risk of progression was 39.5% higher than the average. There was no significant difference in the early distribution of lesions in participants later developing diabetic maculopathy or proliferative diabetic retinopathy. The location of early red lesions in diabetic retinopathy is predictive of whether or not individuals will later develop vision-threatening diabetic retinopathy. This evidence should be incorporated into risk models used to recommend control intervals in screening programmes for diabetic retinopathy.

  7. Development of monoclonal antibodies to human microsomal epoxide hydrolase and analysis of “preneoplastic antigen”-like molecules

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Duan, Hongying; Yoshimura, Kazunori; Kobayashi, Nobuharu

    2012-04-01

    Microsomal epoxide hydrolase (mEH) is a drug metabolizing enzyme which resides on the endoplasmic reticulum (ER) membrane and catalyzes the hydration of reactive epoxide intermediates that are formed by cytochrome P450s. mEH is also thought to have a role in bile acid transport on the plasma membrane of hepatocytes. It is speculated that efficient execution of such multiple functions is secured by its orientation and association with cytochrome P450 enzymes on the ER membrane and formation of a multiple transport system on the plasma membrane. In certain disease status, mEH loses its association with the membrane and can be detectedmore » as distinct antigens in the cytosol of preneoplastic foci of liver (preneoplastic antigen), in the serum in association with hepatitis C virus infection (AN antigen), or in some brain tumors. To analyze the antigenic structures of mEH in physiological and pathological conditions, we developed monoclonal antibodies against different portions of mEH. Five different kinds of antibodies were obtained: three, anti-N-terminal portions; one anti-C-terminal; and one, anti-conformational epitope. By combining these antibodies, we developed antigen detection methods which are specific to either the membrane-bound form or the linearized form of mEH. These methods detected mEH in the culture medium released from a hepatocellular carcinoma cell line and a glioblastoma cell line, which was found to be a multimolecular complex with a unique antigenic structure different from that of the membrane-bound form of mEH. These antibodies and antigen detection methods may be useful to study pathological changes of mEH in various human diseases. -- Highlights: ► Monoclonal antibodies against different portions of mEH were developed. ► They discriminate between the membrane-bound and the linearized forms of mEH. ► We analyze the antigenic structure of the altered form of mEH in tumor cells. ► Preneoplastic antigen is a multimolecular complex of

  8. Automated detection of dark and bright lesions in retinal images for early detection of diabetic retinopathy.

    PubMed

    Akram, Usman M; Khan, Shoab A

    2012-10-01

    There is an ever-increasing interest in the development of automatic medical diagnosis systems due to the advancement in computing technology and also to improve the service by medical community. The knowledge about health and disease is required for reliable and accurate medical diagnosis. Diabetic Retinopathy (DR) is one of the most common causes of blindness and it can be prevented if detected and treated early. DR has different signs and the most distinctive are microaneurysm and haemorrhage which are dark lesions and hard exudates and cotton wool spots which are bright lesions. Location and structure of blood vessels and optic disk play important role in accurate detection and classification of dark and bright lesions for early detection of DR. In this article, we propose a computer aided system for the early detection of DR. The article presents algorithms for retinal image preprocessing, blood vessel enhancement and segmentation and optic disk localization and detection which eventually lead to detection of different DR lesions using proposed hybrid fuzzy classifier. The developed methods are tested on four different publicly available databases. The presented methods are compared with recently published methods and the results show that presented methods outperform all others.

  9. The serrated neoplasia pathway of colorectal tumors: Identification of MUC5AC hypomethylation as an early marker of polyps with malignant potential.

    PubMed

    Renaud, Florence; Mariette, Christophe; Vincent, Audrey; Wacrenier, Agnès; Maunoury, Vincent; Leclerc, Julie; Coppin, Lucie; Crépin, Michel; Van Seuningen, Isabelle; Leteurtre, Emmanuelle; Buisine, Marie-Pierre

    2016-03-15

    The serrated neoplasia pathway accounts for 20-30% of colorectal cancers (CRC), which are characterized by extensive methylation (CpG island methylation phenotype, CIMP), frequent BRAF mutation and high microsatellite instability (MSI). We recently identified MUC5AC mucin gene hypomethylation as a specific marker of MSI CRC. The early identification of preneoplastic lesions among serrated polyps is currently challenging. Here, we performed a detailed pathological and molecular analysis of a large series of colorectal serrated polyps and evaluated the usefulness of mucin genes MUC2 and MUC5AC to differentiate serrated polyps and to identify lesions with malignant potential. A series of 330 colorectal polyps including 218 serrated polyps [42 goblet cell-rich hyperplastic polyps (GCHP), 68 microvesicular hyperplastic polyps (MVHP), 100 sessile serrated adenoma (SSA) and eight traditional serrated adenoma (TSA)] and 112 conventional adenomas was analyzed for BRAF/KRAS mutations, MSI, CIMP, MLH1 and MGMT methylation, and MUC2 and MUC5AC expression and methylation. We show that MUC5AC hypomethylation is an early event in the serrated neoplasia pathway, and specifically detects MVHP and SSA, arguing for a filiation between MVHP, SSA and CIMP-H/MSI CRC, whereas GCHP and TSA arise from a distinct pathway. Moreover, MUC5AC hypomethylation specifically identified serrated lesions with BRAF mutation, CIMP-H or MSI, suggesting that it may be useful to identify serrated neoplasia pathway-related precursor lesions. Our data suggest that MVHP should be recognized among HP and require particular attention. © 2015 UICC.

  10. Alterations in leucocyte subsets and histomorphology in normal-appearing perilesional skin and early and chronic hidradenitis suppurativa lesions.

    PubMed

    van der Zee, H H; de Ruiter, L; Boer, J; van den Broecke, D G; den Hollander, J C; Laman, J D; Prens, E P

    2012-01-01

    Current insight into the histopathological course of events during disease progression in hidradenitis suppurativa (HS) is fragmentary. To identify histological alterations and leucocyte subsets in normal-appearing perilesional skin, and early and chronic HS lesions. In this observational study we examined eight perilesional skin samples, and six early and 10 chronic prototypic HS lesions, as well as skin samples from four healthy donors using in situ immunostaining. Perilesional skin showed mild psoriasiform hyperplasia and follicular plugging as well as a low-grade influx of tryptase-positive mast cells, CD3+ T cells, CD138+ plasma cells and factor XIIIa+ dendritic cells. In early HS lesions, neutrophilic abscess formation and influx of mainly macrophages, monocytes and dendritic cells predominated. In chronic disease, the infiltrate expanded with markedly increased frequencies of CD20+ and CD79a+ B cells and CD138+ plasma cells. As in early lesions, free keratin fibres were detected in the dermis and within giant cells. Single detached keratinocytes and strands of follicular epithelium were observed in the dermis, the latter frequently expressing Ki67, indicative of active proliferation. Psoriasiform hyperplasia, follicular plugging and low-grade leucocytic infiltration are already present in normal-appearing perilesional skin. Keratin fibres in the dermis are associated with clinical disease. Early lesions are characterized by neutrophilic abscess formation and influx of mainly histiocytes, and chronic lesions mainly by expansion of B cells and plasma cells in 'pseudo' follicles. Proliferating strands of follicular epithelium may initiate fistula formation. Mast cells are increased in all stages of HS including perilesional skin. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

  11. HPV and oral lesions: preventive possibilities, vaccines and early diagnosis of malignant lesions

    PubMed Central

    TESTI, D.; NARDONE, M.; MELONE, P.; CARDELLI, P.; OTTRIA, L.; ARCURI, C.

    2015-01-01

    SUMMARY The importance of HPV in world healthy is high, in fact high-risk HPV types contribute significantly to viral associated neoplasms. In this article we will analyze vary expression of HPV in oral cavity both benign and malignant, their prevalence and the importance in early diagnosis and prevention. The classical oral lesions associated with human papillomavirus are squamous cell papilloma, condyloma acuminatum, verruca vulgaris and focal epithelial hyperplasia. Overall, HPV types 2, 4, 6, 11, 13 and 32 have been associated with benign oral lesions while HPV types 16 and 18 have been associated with malignant lesions, especially in cancers of the tonsils and elsewhere in the oropharynx. Transmission of the virus can occur with direct contact, genital contact, anal and oral sex; latest studies suggest a salivary transmission and from mother to child during delivery. The number of lifetime sexual partners is an important risk factor for the development of HPV-positive head-neck cancer. Oral/oropharyngeal cancer etiologically associated with HPV having an increased survival and a better prognostic (85%–90% to five years). There is no cure for the virus. There are two commercially available prophylactic vaccines against HPV today: the bivalent (16 and 18) Cervarix® and the tetravalent (6, 11, 16 and 18) Gardasil® and new vaccine Gardasil 9 (6, 11, 16, 18, 31, 33, 45, 52, 58) was approved in the United States. To be effective, such vaccination should start before “sexual puberty”. The vaccine could be an important preventive strategy, in fact the scientific community is in agreement on hypothesis that blocking the contagion it may also limit the distance complications as the oropharyngeal cancer. PMID:27555904

  12. HPV and oral lesions: preventive possibilities, vaccines and early diagnosis of malignant lesions.

    PubMed

    Testi, D; Nardone, M; Melone, P; Cardelli, P; Ottria, L; Arcuri, C

    2015-01-01

    The importance of HPV in world healthy is high, in fact high-risk HPV types contribute significantly to viral associated neoplasms. In this article we will analyze vary expression of HPV in oral cavity both benign and malignant, their prevalence and the importance in early diagnosis and prevention. The classical oral lesions associated with human papillomavirus are squamous cell papilloma, condyloma acuminatum, verruca vulgaris and focal epithelial hyperplasia. Overall, HPV types 2, 4, 6, 11, 13 and 32 have been associated with benign oral lesions while HPV types 16 and 18 have been associated with malignant lesions, especially in cancers of the tonsils and elsewhere in the oropharynx. Transmission of the virus can occur with direct contact, genital contact, anal and oral sex; latest studies suggest a salivary transmission and from mother to child during delivery. The number of lifetime sexual partners is an important risk factor for the development of HPV-positive head-neck cancer. Oral/oropharyngeal cancer etiologically associated with HPV having an increased survival and a better prognostic (85%-90% to five years). There is no cure for the virus. There are two commercially available prophylactic vaccines against HPV today: the bivalent (16 and 18) Cervarix® and the tetravalent (6, 11, 16 and 18) Gardasil® and new vaccine Gardasil 9 (6, 11, 16, 18, 31, 33, 45, 52, 58) was approved in the United States. To be effective, such vaccination should start before "sexual puberty". The vaccine could be an important preventive strategy, in fact the scientific community is in agreement on hypothesis that blocking the contagion it may also limit the distance complications as the oropharyngeal cancer.

  13. Comparison of diagnosis of early retinal lesions of diabetic retinopathy between a computer system and human experts.

    PubMed

    Lee, S C; Lee, E T; Kingsley, R M; Wang, Y; Russell, D; Klein, R; Warn, A

    2001-04-01

    To investigate whether a computer vision system is comparable with humans in detecting early retinal lesions of diabetic retinopathy using color fundus photographs. A computer system has been developed using image processing and pattern recognition techniques to detect early lesions of diabetic retinopathy (hemorrhages and microaneurysms, hard exudates, and cotton-wool spots). Color fundus photographs obtained from American Indians in Oklahoma were used in developing and testing the system. A set of 369 color fundus slides were used to train the computer system using 3 diagnostic categories: lesions present, questionable, or absent (Y/Q/N). A different set of 428 slides were used to test and evaluate the system, and its diagnostic results were compared with those of 2 human experts-the grader at the University of Wisconsin Fundus Photograph Reading Center (Madison) and a general ophthalmologist. The experiments included comparisons using 3 (Y/Q/N) and 2 diagnostic categories (Y/N) (questionable cases excluded in the latter). In the training phase, the agreement rates, sensitivity, and specificity in detecting the 3 lesions between the retinal specialist and the computer system were all above 90%. The kappa statistics were high (0.75-0.97), indicating excellent agreement between the specialist and the computer system. In the testing phase, the results obtained between the computer system and human experts were consistent with those of the training phase, and they were comparable with those between the human experts. The performance of the computer vision system in diagnosing early retinal lesions was comparable with that of human experts. Therefore, this mobile, electronically easily accessible, and noninvasive computer system, could become a mass screening tool and a clinical aid in diagnosing early lesions of diabetic retinopathy.

  14. Geminin deficiency enhances survival in a murine medulloblastoma model by inducing apoptosis of preneoplastic granule neuron precursors

    PubMed Central

    Sankar, Savita; Patterson, Ethan; Lewis, Emily M.; Waller, Laura E.; Tong, Caili; Dearborn, Joshua; Wozniak, David; Rubin, Joshua B.; Kroll, Kristen L.

    2017-01-01

    Medulloblastoma is the most common malignant brain cancer of childhood. Further understanding of tumorigenic mechanisms may define new therapeutic targets. Geminin maintains genome fidelity by controlling re-initiation of DNA replication within a cell cycle. In some contexts, Geminin inhibition induces cancer-selective cell cycle arrest and apoptosis and/or sensitizes cancer cells to Topoisomerase IIα inhibitors such as etoposide, which is used in combination chemotherapies for medulloblastoma. However, Geminin's potential role in medulloblastoma tumorigenesis remained undefined. Here, we found that Geminin is highly expressed in human and mouse medulloblastomas and in murine granule neuron precursor (GNP) cells during cerebellar development. Conditional Geminin loss significantly enhanced survival in the SmoA1 mouse medulloblastoma model. Geminin loss in this model also reduced numbers of preneoplastic GNPs persisting at one postnatal month, while at two postnatal weeks these cells exhibited an elevated DNA damage response and apoptosis. Geminin knockdown likewise impaired human medulloblastoma cell growth, activating G2 checkpoint and DNA damage response pathways, triggering spontaneous apoptosis, and enhancing G2 accumulation of cells in response to etoposide treatment. Together, these data suggest preneoplastic and cancer cell-selective roles for Geminin in medulloblastoma, and suggest that targeting Geminin may impair tumor growth and enhance responsiveness to Topoisomerase IIα-directed chemotherapies. PMID:29234490

  15. Extra-prostatic Transgene-associated Neoplastic Lesions in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Mice

    PubMed Central

    Berman-Booty, Lisa D.; Thomas-Ahner, Jennifer M.; Bolon, Brad; Oglesbee, Michael J.; Clinton, Steven K.; Kulp, Samuel K.; Chen, Ching-Shih; La Perle, Krista

    2014-01-01

    Male transgenic adenocarcinoma of the mouse prostate (TRAMP) mice are frequently used in prostate cancer research because their prostates consistently develop a series of pre-neoplastic and neoplastic lesions. Disease progression in TRAMP mouse prostates culminates in metastatic, poorly differentiated carcinomas with neuroendocrine features. The androgen dependence of the rat probasin promoter largely limits transgene expression to the prostatic epithelium. However, extra-prostatic transgene-positive lesions have been described in TRAMP mice, including renal tubulo-acinar carcinomas, neuroendocrine carcinomas of the urethra, and phyllodes-like tumors of the seminal vesicle. Here we describe the histologic and immunohistochemical features of two novel extra-prostatic lesions in TRAMP mice: primary anaplastic tumors of uncertain cell origin in the midbrain, and poorly differentiated adenocarcinomas of the submandibular salivary gland. These newly characterized tumors apparently result from transgene expression in extra-prostatic locations rather than representing metastatic prostate neoplasms because lesions were identified in both male and female mice as well as in male TRAMP mice without histologically apparent prostate tumors. In this paper we also calculate the incidences of the urethral carcinomas and renal tubulo-acinar carcinomas, further elucidate the biological behavior of the urethral carcinomas, and demonstrate the critical importance of complete necropsies even when evaluating presumably well characterized phenotypes in genetically engineered mice. PMID:24742627

  16. Extra-prostatic transgene-associated neoplastic lesions in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice.

    PubMed

    Berman-Booty, Lisa D; Thomas-Ahner, Jennifer M; Bolon, Brad; Oglesbee, Michael J; Clinton, Steven K; Kulp, Samuel K; Chen, Ching-Shih; La Perle, Krista M D

    2015-02-01

    Male transgenic adenocarcinoma of the mouse prostate (TRAMP) mice are frequently used in prostate cancer research because their prostates consistently develop a series of preneoplastic and neoplastic lesions. Disease progression in TRAMP mouse prostates culminates in metastatic, poorly differentiated carcinomas with neuroendocrine features. The androgen dependence of the rat probasin promoter largely limits transgene expression to the prostatic epithelium. However, extra-prostatic transgene-positive lesions have been described in TRAMP mice, including renal tubuloacinar carcinomas, neuroendocrine carcinomas of the urethra, and phyllodes-like tumors of the seminal vesicle. Here, we describe the histologic and immunohistochemical features of 2 novel extra-prostatic lesions in TRAMP mice: primary anaplastic tumors of uncertain cell origin in the midbrain and poorly differentiated adenocarcinomas of the submandibular salivary gland. These newly characterized tumors apparently result from transgene expression in extra-prostatic locations rather than representing metastatic prostate neoplasms because lesions were identified in both male and female mice and in male TRAMP mice without histologically apparent prostate tumors. In this article, we also calculate the incidences of the urethral carcinomas and renal tubuloacinar carcinomas, further elucidate the biological behavior of the urethral carcinomas, and demonstrate the critical importance of complete necropsies even when evaluating presumably well characterized phenotypes in genetically engineered mice. © 2014 by The Author(s).

  17. Identification of early cancerous lesion of esophagus with endoscopic images by hyperspectral image technique (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Huang, Shih-Wei; Chen, Shih-Hua; Chen, Weichung; Wu, I.-Chen; Wu, Ming Tsang; Kuo, Chie-Tong; Wang, Hsiang-Chen

    2016-03-01

    This study presents a method to identify early esophageal cancer within endoscope using hyperspectral imaging technology. The research samples are three kinds of endoscopic images including white light endoscopic, chromoendoscopic, and narrow-band endoscopic images with different stages of pathological changes (normal, dysplasia, dysplasia - esophageal cancer, and esophageal cancer). Research is divided into two parts: first, we analysis the reflectance spectra of endoscopic images with different stages to know the spectral responses by pathological changes. Second, we identified early cancerous lesion of esophagus by principal component analysis (PCA) of the reflectance spectra of endoscopic images. The results of this study show that the identification of early cancerous lesion is possible achieve from three kinds of images. In which the spectral characteristics of NBI endoscopy images of a gray area than those without the existence of the problem the first two, and the trend is very clear. Therefore, if simply to reflect differences in the degree of spectral identification, chromoendoscopic images are suitable samples. The best identification of early esophageal cancer is using the NBI endoscopic images. Based on the results, the use of hyperspectral imaging technology in the early endoscopic esophageal cancer lesion image recognition helps clinicians quickly diagnose. We hope for the future to have a relatively large amount of endoscopic image by establishing a hyperspectral imaging database system developed in this study, so the clinician can take this repository more efficiently preliminary diagnosis.

  18. Functional Topography of Early Periventricular Brain Lesions in Relation to Cytoarchitectonic Probabilistic Maps

    ERIC Educational Resources Information Center

    Staudt, Martin; Ticini, Luca F.; Grodd, Wolfgang; Krageloh-Mann, Ingeborg; Karnath, Hans-Otto

    2008-01-01

    Early periventricular brain lesions can not only cause cerebral palsy, but can also induce a reorganization of language. Here, we asked whether these different functional consequences can be attributed to topographically distinct portions of the periventricular white matter damage. Eight patients with pre- and perinatally acquired left-sided…

  19. Modulation by metformin of molecular and histopathological alterations in the lung of cigarette smoke-exposed mice

    PubMed Central

    Izzotti, Alberto; Balansky, Roumen; D'Agostini, Francesco; Longobardi, Mariagrazia; Cartiglia, Cristina; Micale, Rosanna T; La Maestra, Sebastiano; Camoirano, Anna; Ganchev, Gancho; Iltcheva, Marietta; Steele, Vernon E; De Flora, Silvio

    2014-01-01

    The anti-diabetic drug metformin is endowed with anti-cancer properties. Epidemiological and experimental studies, however, did not provide univocal results regarding its role in pulmonary carcinogenesis. We used Swiss H mice of both genders in order to detect early molecular alterations and tumors induced by mainstream cigarette smoke. Based on a subchronic toxicity study, oral metformin was used at a dose of 800 mg/kg diet, which is 3.2 times higher than the therapeutic dose in humans. Exposure of mice to smoke for 4 months, starting at birth, induced a systemic clastogenic damage, formation of DNA adducts, oxidative DNA damage, and extensive downregulation of microRNAs in lung after 10 weeks. Preneoplastic lesions were detectable after 7.5 months in both lung and urinary tract along with lung tumors, both benign and malignant. Modulation by metformin of 42 of 1281 pulmonary microRNAs in smoke-free mice highlighted a variety of mechanisms, including modulation of AMPK, stress response, inflammation, NFκB, Tlr9, Tgf, p53, cell cycle, apoptosis, antioxidant pathways, Ras, Myc, Dicer, angiogenesis, stem cell recruitment, and angiogenesis. In smoke-exposed mice, metformin considerably decreased DNA adduct levels and oxidative DNA damage, and normalized the expression of several microRNAs. It did not prevent smoke-induced lung tumors but inhibited preneoplastic lesions in both lung and kidney. In conclusion, metformin was able to protect the mouse lung from smoke-induced DNA and microRNA alterations and to inhibit preneoplastic lesions in lung and kidney but failed to prevent lung adenomas and malignant tumors induced by this complex mixture. PMID:24683044

  20. Seminal epithelium in prostate biopsy can mimic malignant and premalignant prostatic lesions.

    PubMed

    Arista-Nasr, J; Trolle-Silva, A; Aguilar-Ayala, E; Martínez-Benítez, B

    2016-01-01

    In most prostate biopsies, the seminal epithelium is easily recognised because it meets characteristic histological criteria. However, some biopsies can mimic malignant or premalignant prostatic lesions. The aims of this study were to analyse the histological appearance of the biopsies that mimic adenocarcinomas or preneoplastic prostatic lesions, discuss the differential diagnosis and determine the frequency of seminal epithelia in prostate biopsies. We consecutively reviewed 500 prostate puncture biopsies obtained using the sextant method and selected those cases in which we observed seminal vesicle or ejaculatory duct epithelium. In the biopsies in which the seminal epithelium resembled malignant or premalignant lesions, immunohistochemical studies were conducted that included prostate-specific antigen and MUC6. The most important clinical data were recorded. Thirty-six (7.2%) biopsies showed seminal epithelium, and 7 of them (1.4%) resembled various prostate lesions, including high-grade prostatic intraepithelial neoplasia, atypical acinar proliferations, adenocarcinomas with papillary patterns and poorly differentiated carcinoma. The seminal epithelium resembled prostate lesions when the lipofuscin deposit, the perinuclear vacuoles or the nuclear pseudoinclusions were inconspicuous or missing. Five of the 7 biopsies showed mild to moderate cellular atypia with small and hyperchromatic nuclei, and only 2 showed cellular pleomorphism. The patients were alive and asymptomatic after an average of 6 years of progression. The seminal epithelium resembles prostatic intraepithelial neoplasia, atypical acinar proliferations and various types of prostatic adenocarcinomas in approximately 1.4% of prostate biopsies. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Helicobacter pylori and microRNAs: Relation with innate immunity and progression of preneoplastic conditions

    PubMed Central

    Libânio, Diogo; Dinis-Ribeiro, Mário; Pimentel-Nunes, Pedro

    2015-01-01

    The accepted paradigm for intestinal-type gastric cancer pathogenesis is a multistep progression from chronic gastritis induced by Helicobacter pylori (H. pylori) to gastric atrophy, intestinal metaplasia, dysplasia and ultimately gastric cancer. The genetic and molecular mechanisms underlying disease progression are still not completely understood as only a fraction of colonized individuals ever develop neoplasia suggesting that bacterial, host and environmental factors are involved. MicroRNAs are noncoding RNAs that may influence H. pylori-related pathology through the regulation of the transcription and expression of various genes, playing an important role in inflammation, cell proliferation, apoptosis and differentiation. Indeed, H. pylori have been shown to modify microRNA expression in the gastric mucosa and microRNAs are involved in the immune host response to the bacteria and in the regulation of the inflammatory response. MicroRNAs have a key role in the regulation of inflammatory pathways and H. pylori may influence inflammation-mediated gastric carcinogenesis possibly through DNA methylation and epigenetic silencing of tumor suppressor microRNAs. Furthermore, microRNAs influenced by H. pylori also have been found to be involved in cell cycle regulation, apoptosis and epithelial-mesenchymal transition. Altogether, microRNAs seem to have an important role in the progression from gastritis to preneoplastic conditions and neoplastic lesions and since each microRNA can control the expression of hundreds to thousands of genes, knowledge of microRNAs target genes and their functions are of paramount importance. In this article we present a comprehensive review about the role of microRNAs in H. pylori gastric carcinogenesis, identifying the microRNAs downregulated and upregulated in the infection and clarifying their biological role in the link between immune host response, inflammation, DNA methylation and gastric carcinogenesis. PMID:26468448

  2. Orofacial hereditary haemorrhagic telangiectasia: high power diode laser in early and advanced lesion treatment

    NASA Astrophysics Data System (ADS)

    Tempesta, Angela; Franco, Simonetta; Miccoli, Simona; Suppressa, Patrizia; De Falco, Vincenzo; Crincoli, Vito; Lacaita, Mariagrazia; Giuliani, Michele; Favia, Gianfranco

    2014-01-01

    Hereditary Haemorrhagic Telangiectasia (HHT) is a muco-cutaneous inherited disease. Symptoms are epistaxis, visceral arterio-venous malformations, multiple muco-cutaneous telangiectasia with the risk of number increasing enlargement, bleeding, and super-infection. The aim of this work is to show the dual Diode Laser efficacy in preventive treatment of Early Lesions (EL < 2mm) and therapeutic treatment of Advanced Lesions (AL < 2mm). 21 patients affected by HHT with 822 muco-cutaneous telangiectatic nodules have been treated in several sessions with local anaesthesia and cooling of treated sites. EL preventive treatment consists of single Laser impulse (fibre 320) in ultrapulsed mode (2 mm single point spot). AL therapeutic treatment consists of repeated Laser impulses in pulsed mode (on 200ms / off 400ms). According to the results, Diode Laser used in pulsed and ultra-pulsed mode is very effective as noninvasive treatment both in early and advanced oral and perioral telangiectasia.

  3. Early serum biomarker networks in infants with distinct retinochoroidal lesion status of congenital toxoplasmosis.

    PubMed

    de Araújo, Thádia Evelyn; Coelho-Dos-Reis, Jordana Grazziela; Béla, Samantha Ribeiro; Carneiro, Ana Carolina Aguiar Vasconcelos; Machado, Anderson Silva; Cardoso, Ludmila Melo; Ribeiro, Ágata Lopes; Dias, Michelle Hallais França; Queiroz Andrade, Gláucia Manzan; Vasconcelos-Santos, Daniel Vitor; Januário, José Nélio; Teixeira-Carvalho, Andréa; Vitor, Ricardo Wagner Almeida; Ferro, Eloisa Amália Vieira; Martins-Filho, Olindo Assis

    2017-07-01

    The present study characterized the early changes in the serum chemokines/cytokine signatures and networks in infants with congenital-toxoplasmosis/(TOXO) as compared to non-infected-controls/(NI). TOXO were subgrouped according to the retinochoroidal lesion status as no-lesion/(NL), active-lesion/(ARL), active/cicatricial-lesion/(ACRL) and cicatricial-lesion/(CRL). The results showed that TOXO display prominent chemokine production mediated by IL-8/CXCL8, MIG/CXCL9, IP-10/CXCL10 and RANTES/CCL5. Additionally, TOXO is accompanied by mixed proinflammatory/regulatory cytokine pattern mediated by IL-6, IFN-γ, IL-4, IL-5 and IL-10. While TNF appears as a putative biomarker for NL and IFN-γ/IL-5 as immunological features for ARL, IL-10 emerges as a relevant mediator in ACRL/CRL. IL-8/CXCL8 and IP-10/CXCL10 are broad-spectrum indicators of ocular disease, whereas TNF is a NL biomarker, IFN-γ and MIG/CXCL9 point out to ARL; and IL-10 is highlighted as a genuine serum biomarker of ACRL/CRL. The network analysis demonstrated a broad chemokine/cytokine crosstalk with divergences in the molecular signatures in patients with different ocular lesions during congenital toxoplasmosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Detection of human papillomavirus in intraepithelial lesions and carcinoma of the cervix uteri in southern Thai women.

    PubMed

    Tungsinmunkong, Kobkul; Suwiwat, Supaporn; Sriplung, Hutcha

    2006-01-01

    To evaluate the prevalence of high-risk type human papillomavirus (HR-HPV) in preneoplastic lesions and invasive squamous cell carcinoma (SCC) of the cervix uteri in southern Thai women. A total of 148 formalin-fixed, paraffin-embedded blocks of cervix tissue were retrieved from the files of the Department of Pathology, Prince of Songkla University Hospital. They were classified as negative for intraepithelial lesion (NIL) in 37 cases, low grade lesion (LGL) in 58 cases, high grade lesion (HGL) in 39 cases and SCC in 14 cases. HR-HPV DNA was tested with an Amplicor HPV (Roche Diagnostics) detection kit. Of the 111 cases, 42 of 58 LGLs (72.4%), 34 of 39 HGLs (87.2%) and 13 of 14 SCCs (92.9%) were positive for HR-HPV DNA. In 37 cases of histologically normal cervix, there were 15 cases that showed the presence of HR-HPV DNA. Applying the HR-HPV results for NILs to the general population, the age standardized incidence rate of HR-HPV infection in the normal Thai population was 12.8%. HR-HPV DNA can be found in all grades of intraepithelial lesions and carcinoma of the cervix uteri, even in the histologically "normal" looking cervix. These results provide strong evidence for a role in carcinogenesis of the cervix uteri and the existence of a non-productive or latent period of HPV infection.

  5. Arrested development: early prefrontal lesions impair the maturation of moral judgement.

    PubMed

    Taber-Thomas, Bradley C; Asp, Erik W; Koenigs, Michael; Sutterer, Matthew; Anderson, Steven W; Tranel, Daniel

    2014-04-01

    Learning to make moral judgements based on considerations beyond self-interest is a fundamental aspect of moral development. A deficit in such learning is associated with poor socialization and criminal behaviour. The neural systems required for the acquisition and maturation of moral competency are not well understood. Here we show in a unique sample of neurological patients that focal lesions involving ventromedial prefrontal cortex, acquired during development, result in an abnormally egocentric pattern of moral judgement. In response to simple hypothetical moral scenarios, the patients were more likely than comparison participants to endorse self-interested actions that involved breaking moral rules or physically harming others in order to benefit themselves. This pattern (which we also found in subjects with psychopathy) differs from that of patients with adult-onset ventromedial prefrontal cortex lesions--the latter group showed normal rejection of egocentric rule violations. This novel contrast of patients with ventromedial prefrontal cortex lesions acquired during development versus during adulthood yields new evidence suggesting that the ventromedial prefrontal cortex is a critical neural substrate for the acquisition and maturation of moral competency that goes beyond self-interest to consider the welfare of others. Disruption to this affective neural system early in life interrupts moral development.

  6. Disruption of Smad-dependent signaling for growth of GST-P-positive lesions from the early stage in a rat two-stage hepatocarcinogenesis model

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ichimura, Ryohei, E-mail: red0828@hotmail.co.j; Mizukami, Sayaka, E-mail: non_sugar_life@hotmail.co.j; Takahashi, Miwa, E-mail: mtakahashi@nihs.go.j

    2010-08-01

    To clarify the involvement of signaling of transforming growth factor (TGF)-{beta} during the hepatocarcinogenesis, the immunohistochemical distribution of related molecules was analyzed in relation with liver cell lesions expressing glutathione S-transferase placental form (GST-P) during liver tumor promotion by fenbendazole, phenobarbital, piperonyl butoxide, or thioacetamide, using rats. Our study focused on early-stage promotion (6 weeks after starting promotion) and late-stage promotion (57 weeks after starting promotion). With regard to Smad-dependent signaling, cytoplasmic accumulation of phosphorylated Smad (phospho-Smad)-2/3 - identified as Smad3 by later immunoblot analysis - increased in the subpopulation of GST-P{sup +} foci, while Smad4, a nuclear transporter ofmore » Smad2/3, decreased during early-stage promotion. By late-stage promotion, GST-P{sup +} lesions lacking phospho-Smad2/3 had increased in accordance with lesion development from foci to carcinomas, while Smad4 largely disappeared in most proliferative lesions. With regard to Smad-independent mitogen-activated protein kinases, GST-P{sup +} foci that co-expressed phospho-p38 mitogen-activated protein kinase increased during early-stage promotion; however, p38-downstream phospho-activating transcriptional factor (ATF)-2, ATF3, and phospho-c-Myc, were inversely downregulated without relation to promotion. By late-stage promotion, proliferative lesions downregulated phospho-ATF2 and phospho-c-Myc along with lesion development, as with downregulation of phospho-p38 in all lesions. These results suggest that from the early stages, carcinogenic processes were facilitated by disruption of tumor suppressor functions of Smad-dependent signaling, while Smad-independent activation of p38 was an early-stage phenomenon. GST-P{sup -} foci induced by promotion with agonists of peroxisome proliferator-activated receptor-{alpha} did not change Smad expression, suggesting an aberration in the Smad

  7. iROLL: does 3-D radioguided occult lesion localization improve surgical management in early-stage breast cancer?

    PubMed

    Bluemel, Christina; Cramer, Andreas; Grossmann, Christoph; Kajdi, Georg W; Malzahn, Uwe; Lamp, Nora; Langen, Heinz-Jakob; Schmid, Jan; Buck, Andreas K; Grimminger, Hanns-Jörg; Herrmann, Ken

    2015-10-01

    To prospectively evaluate the feasibility of 3-D radioguided occult lesion localization (iROLL) and to compare iROLL with wire-guided localization (WGL) in patients with early-stage breast cancer undergoing breast-conserving surgery and sentinel lymph node biopsy (SLNB). WGL (standard procedure) and iROLL in combination with SLNB were performed in 31 women (mean age 65.1 ± 11.2 years) with early-stage breast cancer and clinically negative axillae. Patient comfort in respect of both methods was assessed using a ten point scale. SLNB and iROLL were guided by freehand SPECT (fhSPECT). The results of the novel 3-D image-based method were compared with those of WGL, ultrasound-based lesion localization, and histopathology. iROLL successfully detected the malignant primary and at least one sentinel lymph node in 97% of patients. In a single patient (3%), only iROLL, and not WGL, enabled lesion localization. The variability between fhSPECT and ultrasound-based depth localization of breast lesions was low (1.2 ± 1.4 mm). Clear margins were achieved in 81% of the patients; however, precise prediction of clear histopathological surgical margins was not feasible using iROLL. Patients rated iROLL as less painful than WGL with a pain score 0.8 ± 1.2 points (p < 0.01) lower than the score for iROLL. iROLL is a well-tolerated and feasible technique for localizing early-stage breast cancer in the course of breast-conserving surgery, and is a suitable replacement for WGL. As a single image-based procedure for localization of breast lesions and sentinel nodes, iROLL may improve the entire surgical procedure. However, no advantages of the image-guided procedure were found with regard to prediction of complete tumour resection.

  8. Defining the ATM-mediated barrier to tumorigenesis in somatic mammary cells following ErbB2 activation.

    PubMed

    Reddy, Jay P; Peddibhotla, Sirisha; Bu, Wen; Zhao, Jing; Haricharan, Svasti; Du, Yi-Chieh Nancy; Podsypanina, Katrina; Rosen, Jeffrey M; Donehower, Larry A; Li, Yi

    2010-02-23

    p53, apoptosis, and senescence are frequently activated in preneoplastic lesions and are barriers to progression to malignancy. These barriers have been suggested to result from an ATM-mediated DNA damage response (DDR), which may follow oncogene-induced hyperproliferation and ensuing DNA replication stress. To elucidate the currently untested role of DDR in breast cancer initiation, we examined the effect of oncogene expression in several murine models of breast cancer. We did not observe a detectable DDR in early hyperplastic lesions arising in transgenic mice expressing several different oncogenes. However, DDR signaling was strongly induced in preneoplastic lesions arising from individual mammary cells transduced in vivo by retroviruses expressing either PyMT or ErbB2. Thus, activation of an oncogene after normal tissue development causes a DDR. Furthermore, in this somatic ErbB2 tumor model, ATM, and thus DDR, is required for p53 stabilization, apoptosis, and senescence. In palpable tumors in this model, p53 stabilization and apoptosis are lost, but unexpectedly senescence remains in many tumor cells. Thus, this murine model fully recapitulates early DDR signaling; the eventual suppression of its endpoints in tumorigenesis provides compelling evidence that ErbB2-induced aberrant mammary cell proliferation leads to an ATM-mediated DDR that activates apoptosis and senescence, and at least the former must be overcome to progress to malignancy. This in vivo study also uncovers an unexpected effect of ErbB2 activation previously known for its prosurvival roles, and suggests that protection of the ATM-mediated DDR-p53 signaling pathway may be important in breast cancer prevention.

  9. Impact of Prostate Inflammation on Lesion Development in the POET3+Pten+/− Mouse Model of Prostate Carcinogenesis

    PubMed Central

    Burcham, Grant N.; Cresswell, Gregory M.; Snyder, Paul W.; Chen, Long; Liu, Xiaoqi; Crist, Scott A.; Henry, Michael D.; Ratliff, Timothy L.

    2015-01-01

    Evidence linking prostatitis and prostate cancer development is contradictory. To study this link, the POET3 mouse, an inducible model of prostatitis, was crossed with a Pten-loss model of prostate cancer (Pten+/−) containing the ROSA26 luciferase allele to monitor prostate size. Prostatitis was induced, and prostate bioluminescence was tracked over 12 months, with lesion development, inflammation, and cytokine expression analyzed at 4, 8, and 12 months and compared with mice without induction of prostatitis. Acute prostatitis led to more proliferative epithelium and enhanced bioluminescence. However, 4 months after initiation of prostatitis, mice with induced inflammation had lower grade pre-neoplastic lesions. A trend existed toward greater development of carcinoma 12 months after induction of inflammation, including one of two mice with carcinoma developing perineural invasion. Two of 18 mice at the later time points developed lesions with similarities to proliferative inflammatory atrophy, including one mouse with associated carcinoma. Pten+/− mice developed spontaneous inflammation, and prostatitis was similar among groups of mice at 8 and 12 months. Analyzed as one cohort, lesion number and grade were positively correlated with prostatitis. Specifically, amounts of CD11b+Gr1+ cells were correlated with lesion development. These results support the hypothesis that myeloid-based inflammation is associated with lesion development in the murine prostate, and previous bouts of CD8-driven prostatitis may promote invasion in the Pten+/− model of cancer. PMID:25455686

  10. Comfrey (Symphytum Officinale. l.) and Experimental Hepatic Carcinogenesis: A Short-term Carcinogenesis Model Study

    PubMed Central

    Gomes, Maria Fernanda Pereira Lavieri; de Oliveira Massoco, Cristina; Xavier, José Guilherme

    2010-01-01

    Comfrey or Symphytum officinale (L.) (Boraginaceae) is a very popular plant used for therapeutic purposes. Since the 1980s, its effects have been studied in long-term carcinogenesis studies, in which Comfrey extract is administered at high doses during several months and the neoplastic hepatic lesions are evaluated. However, the literature on this topic is very poor considering the studies performed under short-term carcinogenesis protocols, such as the ‘resistant hepatocyte model’ (RHM). In these studies, it is possible to observe easily the phenomena related to the early phases of tumor development, since pre-neoplastic lesions (PNLs) rise in about 1–2 months of chemical induction. Herein, the effects of chronic oral treatment of rats with 10% Comfrey ethanolic extract were evaluated in a RHM. Wistar rats were sequentially treated with N-nitrosodiethylamine (ip) and 2-acetilaminofluorene (po), and submitted to hepatectomy to induce carcinogenesis promotion. Macroscopic/microscopic quantitative analysis of PNL was performed. Non-parametric statistical tests (Mann–Whitney and χ2) were used, and the level of significance was set at P ≤ 0.05. Comfrey treatment reduced the number of pre-neoplastic macroscopic lesions up to 1 mm (P ≤ 0.05), the percentage of oval cells (P = 0.0001) and mitotic figures (P = 0.007), as well as the number of Proliferating Cell Nuclear Antigen (PCNA) positive cells (P = 0.0001) and acidophilic pre-neoplastic nodules (P = 0.05). On the other hand, the percentage of cells presenting megalocytosis (P = 0.0001) and vacuolar degeneration (P = 0.0001) was increased. Scores of fibrosis, glycogen stores and the number of nucleolus organizing regions were not altered. The study indicated that oral treatment of rats with 10% Comfrey alcoholic extract reduced cell proliferation in this model. PMID:18955295

  11. Visually evoked responses in extrastriate area MT after lesions of striate cortex in early life.

    PubMed

    Yu, Hsin-Hao; Chaplin, Tristan A; Egan, Gregory W; Reser, David H; Worthy, Katrina H; Rosa, Marcello G P

    2013-07-24

    Lesions of striate cortex [primary visual cortex (V1)] in adult primates result in blindness. In contrast, V1 lesions in neonates typically allow much greater preservation of vision, including, in many human patients, conscious perception. It is presently unknown how this marked functional difference is related to physiological changes in cortical areas that are spared by the lesions. Here we report a study of the middle temporal area (MT) of adult marmoset monkeys that received unilateral V1 lesions within 6 weeks of birth. In contrast with observations after similar lesions in adult monkeys, we found that virtually all neurons in the region of MT that was deprived of V1 inputs showed robust responses to visual stimulation. These responses were very similar to those recorded in neurons with receptive fields outside the lesion projection zones in terms of firing rate, signal-to-noise ratio, and latency. In addition, the normal retinotopic organization of MT was maintained. Nonetheless, we found evidence of a very specific functional deficit: direction selectivity, a key physiological characteristic of MT that is known to be preserved in many cells after adult V1 lesions, was absent. These results demonstrate that lesion-induced reorganization of afferent pathways is sufficient to develop robust visual function in primate extrastriate cortex, highlighting a likely mechanism for the sparing of vision after neonatal V1 lesions. However, they also suggest that interactions with V1 in early postnatal life are critical for establishing stimulus selectivity in MT.

  12. Association of malignancy with rapid growth in early lesions induced by irradiation of rat skin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McGregor, J.F.

    1979-04-01

    Epithelial lesions induced by irradiation of rat skin were studied to determine (a) the relationship of malignancy to dose, (b) the types of lesions and circumstances leading to overt malignancy, and (c) the growth rates of lesions progressing to malignancy versus those of lesions remaining benign. High doses of radiation were shown to be associated with the production of epidermal cancers, the maximum yield being obtained at 6,400 rads. Conversely, a peak yield of noncancerous lesions was obtained at 1,600 rads. This association between malignancy and high dose was consistent for cancers evolving from warts, cysts, and chronic ulcers. Althoughmore » the proportion of warts among the induced lesions was much higher than that of the cysts or chronic ulcers (76, 14, and 10%, respectively), the likelihood of warts becoming cancerous was substantially lower (14, 23, and 21%). The combined data for all doses showed that the latency period of the epidermal cancers was significantly (P = 0.015) shorter than that of the benign tumors. Rapid growth rates were observed for warts, cysts, and chronic ulcers progressing to overt cancer, and these did not overlap at any point on the growth scale with rates for benign tumors. This finding suggested that the potential for malignant development had been established early in the carcinogenic process, very likely at induction.« less

  13. Mammary Tumor Development: Stromal-Epithelial Interactions in Oncogenesis.

    DTIC Science & Technology

    1996-09-01

    differentiation, prolif- erative preneoplastic lesions, or invasive adenocarcinomas , depending on the promoter con- struct used and the animal’s age when...Zn). Virgin RSV-SGF transgenic mice showed marked preneoplastic MG ductal proliferation by 6 mo. By 8 mo., 1/3 had developed adenocarcinoma . Virgin...fat pRSGF Constitutively expressed Highly abnormal. None Normal Observed at 8 1/3 of mice show months of age invasive secretory adenocarcinoma SGF

  14. The value of cyclooxygenase-2 expression in differentiating between early melanomas and histopathologically difficult types of benign human skin lesions.

    PubMed

    Kuźbicki, Łukasz; Lange, Dariusz; Strączyńska-Niemiec, Anita; Chwirot, Barbara W

    2012-02-01

    Early cutaneous melanomas may present a substantial diagnostic challenge. We have already reported that expression of cyclooxygenase-2 (COX-2) may be useful for differentiating between cutaneous melanomas and naevi. The purpose of this study was to examine the value of COX-2 in a challenging task of differential diagnosis of early melanomas and melanocytic naevi considered by histopathologists as morphologically difficult to unequivocally diagnose as benign lesions. The material for the study comprised formalin-fixed paraffin-embedded samples of 46 naevi (including 27 cases of dysplastic, Spitz and Reed naevi) and 30 early human cutaneous melanomas. The expression of COX-2 was detected immunohistochemically. Melanomas expressed COX-2 significantly more strongly compared with naevi. The test, on the basis of determination of the percentage fractions of COX-2-positive cells, allows for differentiation of early skin melanomas and naevi with high sensitivity and specificity. Receiver operating characteristic analysis of the test results yielded areas under receiver operating characteristics curves (AUC)=0.946±0.030 for central regions and AUC=0.941±0.031 for the peripheries of the lesions. The performance of the test in differentiating between melanomas and the naevi group comprising dysplastic, Spitz and Reed naevi was also good, with AUC=0.933±0.034 and 0.923±0.037 for the central and the border regions of the lesions, respectively. Using a more complex diagnostic algorithm also accounting for the staining intensity did not result in an improvement in the resolving power of the assay. A diagnostic algorithm using differences in the percentage fractions of cells expressing COX-2 may serve as a useful tool in aiding the differential diagnosis of 'histopathologically difficult' benign melanocytic skin lesions and early melanomas.

  15. Defining the ATM-mediated barrier to tumorigenesis in somatic mammary cells following ErbB2 activation

    PubMed Central

    Reddy, Jay P.; Peddibhotla, Sirisha; Bu, Wen; Zhao, Jing; Haricharan, Svasti; Du, Yi-Chieh Nancy; Podsypanina, Katrina; Rosen, Jeffrey M.; Donehower, Larry A.; Li, Yi

    2010-01-01

    p53, apoptosis, and senescence are frequently activated in preneoplastic lesions and are barriers to progression to malignancy. These barriers have been suggested to result from an ATM-mediated DNA damage response (DDR), which may follow oncogene-induced hyperproliferation and ensuing DNA replication stress. To elucidate the currently untested role of DDR in breast cancer initiation, we examined the effect of oncogene expression in several murine models of breast cancer. We did not observe a detectable DDR in early hyperplastic lesions arising in transgenic mice expressing several different oncogenes. However, DDR signaling was strongly induced in preneoplastic lesions arising from individual mammary cells transduced in vivo by retroviruses expressing either PyMT or ErbB2. Thus, activation of an oncogene after normal tissue development causes a DDR. Furthermore, in this somatic ErbB2 tumor model, ATM, and thus DDR, is required for p53 stabilization, apoptosis, and senescence. In palpable tumors in this model, p53 stabilization and apoptosis are lost, but unexpectedly senescence remains in many tumor cells. Thus, this murine model fully recapitulates early DDR signaling; the eventual suppression of its endpoints in tumorigenesis provides compelling evidence that ErbB2-induced aberrant mammary cell proliferation leads to an ATM-mediated DDR that activates apoptosis and senescence, and at least the former must be overcome to progress to malignancy. This in vivo study also uncovers an unexpected effect of ErbB2 activation previously known for its prosurvival roles, and suggests that protection of the ATM-mediated DDR-p53 signaling pathway may be important in breast cancer prevention. PMID:20133707

  16. Predicting Outcome after Pediatric Traumatic Brain Injury by Early Magnetic Resonance Imaging Lesion Location and Volume

    PubMed Central

    Smitherman, Emily; Hernandez, Ana; Stavinoha, Peter L.; Huang, Rong; Kernie, Steven G.; Diaz-Arrastia, Ramon

    2016-01-01

    Abstract Brain lesions after traumatic brain injury (TBI) are heterogeneous, rendering outcome prognostication difficult. The aim of this study is to investigate whether early magnetic resonance imaging (MRI) of lesion location and lesion volume within discrete brain anatomical zones can accurately predict long-term neurological outcome in children post-TBI. Fluid-attenuated inversion recovery (FLAIR) MRI hyperintense lesions in 63 children obtained 6.2±5.6 days postinjury were correlated with the Glasgow Outcome Scale Extended-Pediatrics (GOS-E Peds) score at 13.5±8.6 months. FLAIR lesion volume was expressed as hyperintensity lesion volume index (HLVI)=(hyperintensity lesion volume / whole brain volume)×100 measured within three brain zones: zone A (cortical structures); zone B (basal ganglia, corpus callosum, internal capsule, and thalamus); and zone C (brainstem). HLVI-total and HLVI-zone C predicted good and poor outcome groups (p<0.05). GOS-E Peds correlated with HLVI-total (r=0.39; p=0.002) and HLVI in all three zones: zone A (r=0.31; p<0.02); zone B (r=0.35; p=0.004); and zone C (r=0.37; p=0.003). In adolescents ages 13–17 years, HLVI-total correlated best with outcome (r=0.5; p=0.007), whereas in younger children under the age of 13, HLVI-zone B correlated best (r=0.52; p=0.001). Compared to patients with lesions in zone A alone or in zones A and B, patients with lesions in all three zones had a significantly higher odds ratio (4.38; 95% confidence interval, 1.19–16.0) for developing an unfavorable outcome. PMID:25808802

  17. Non-Whipple Operations in the Management of Benign, Premalignant and Early Cancerous Duodenal Lesions.

    PubMed

    Papalampros, Alexandros; Moris, Demetrios; Petrou, Athanasios; Dimitrokallis, Nikolaos; Karavokyros, Ioannis; Schizas, Dimitrios; Delladetsima, Ioanna; Pappas, Theodore N; Felekouras, Evangelos

    2017-03-01

    We reviewed our 20-year experience with non-Whipple operations (pancreas-preserving duodenectomy and transduodenal ampullectomy) for the treatment of benign, premalignant or early-stage malignant duodenal lesions. Twenty-four patients who underwent non-Whipple operations between January 1996 and December 2015 were identified from an institutional database and retrospectively analyzed. Between 1996 and 2015, 10 patients underwent pancreas-preserving duodenectomy and 14 patients underwent transduodenal ampullectomy. The mean follow-up was 25.8 months (range=6-54 months) and no patient was lost to follow-up. Eighteen patients had preoperative diagnosis of duodenal adenomatosis, three patients had preoperative diagnosis of duodenal adenocarcinoma, one had a bleeding polyp and two had localized inflammation. Average operative time was 145 min (range=127-168 min) for transduodenal ampullectomy and 183 min (range=173-200 min) for pancreas-preserving duodenectomy (p<0.05). The estimated blood loss for transduodenal ampullectomy was 85 vs. 125 ml for pancreas-preserving duodenectomy (p<0.05). Early postoperative complications were noted in 13 cases (54.17%). There were no postoperative (90-day) deaths observed in this series and there were no recurrences during follow-up for the patients operated on with neoplastic lesions. For carefully selected patients, transduodenal ampullectomy and pancreas-preserving duodenectomy may be used in place of the Whipple operation for benign and occasionally early-stage malignant (Tis and T1) duodenal and ampullary disease. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  18. Analysis of spatial heterogeneity in normal epithelium and preneoplastic alterations in mouse prostate tumor models

    PubMed Central

    Valkonen, Mira; Ruusuvuori, Pekka; Kartasalo, Kimmo; Nykter, Matti; Visakorpi, Tapio; Latonen, Leena

    2017-01-01

    Cancer involves histological changes in tissue, which is of primary importance in pathological diagnosis and research. Automated histological analysis requires ability to computationally separate pathological alterations from normal tissue with all its variables. On the other hand, understanding connections between genetic alterations and histological attributes requires development of enhanced analysis methods suitable also for small sample sizes. Here, we set out to develop computational methods for early detection and distinction of prostate cancer-related pathological alterations. We use analysis of features from HE stained histological images of normal mouse prostate epithelium, distinguishing the descriptors for variability between ventral, lateral, and dorsal lobes. In addition, we use two common prostate cancer models, Hi-Myc and Pten+/− mice, to build a feature-based machine learning model separating the early pathological lesions provoked by these genetic alterations. This work offers a set of computational methods for separation of early neoplastic lesions in the prostates of model mice, and provides proof-of-principle for linking specific tumor genotypes to quantitative histological characteristics. The results obtained show that separation between different spatial locations within the organ, as well as classification between histologies linked to different genetic backgrounds, can be performed with very high specificity and sensitivity. PMID:28317907

  19. Early dynamic imaging in 68Ga- PSMA-11 PET/CT allows discrimination of urinary bladder activity and prostate cancer lesions.

    PubMed

    Uprimny, Christian; Kroiss, Alexander Stephan; Decristoforo, Clemens; Fritz, Josef; Warwitz, Boris; Scarpa, Lorenza; Roig, Llanos Geraldo; Kendler, Dorota; von Guggenberg, Elisabeth; Bektic, Jasmin; Horninger, Wolfgang; Virgolini, Irene Johanna

    2017-05-01

    PET/CT with 68 Ga-labelled prostate-specific membrane antigen (PSMA)-ligands has been proven to establish a promising imaging modality in the work-up of prostate cancer (PC) patients with biochemical relapse. Despite a high overall detection rate, the visualisation of local recurrence may be hampered by high physiologic tracer accumulation in the urinary bladder on whole body imaging, usually starting 60 min after injection. This study sought to verify whether early dynamic 68 Ga-PSMA-11 (HBED-CC)PET/CT can differentiate pathologic PC-related tracer uptake from physiologic tracer accumulation in the urinary bladder. Eighty consecutive PC patients referred to 68 Ga -PSMA-11 PET/CT were included in this retrospective analysis (biochemical relapse: n = 64; primary staging: n = 8; evaluation of therapy response/restaging: n = 8). In addition to whole-body PET/CT acquisition 60 min post injection early dynamic imaging of the pelvis in the first 8 min after tracer injection was performed. SUV max of pathologic lesions was calculated and time-activity curves were generated and compared to those of urinary bladder and areas of physiologic tracer uptake. A total of 55 lesions consistent with malignancy on 60 min whole body imaging exhibited also pathologic 68 Ga-PSMA-11 uptake during early dynamic imaging (prostatic bed/prostate gland: n = 27; lymph nodes: n = 12; bone: n = 16). All pathologic lesions showed tracer uptake within the first 3 min, whereas urinary bladder activity was absent within the first 3 min of dynamic imaging in all patients. Suv max was significantly higher in PC lesions in the first 6 min compared to urinary bladder accumulation (p < 0.001). In the subgroup of PC patients with biochemical relapse the detection rate of local recurrence could be increased from 20.3 to 29.7%. Early dynamic imaging in 68 Ga-PSMA-11 PET/CT reliably enables the differentiation of pathologic tracer uptake in PC lesions from physiologic

  20. PCBs, liver lesions, and biomarker responses in adult walleye (Stizostedium vitreum vitreum) collected from Green Bay, Wisconsin

    USGS Publications Warehouse

    Barron, Mace G.; Anderson, Michael J.; Cacela, Dave; Lipton, Joshua; Teh, Swee J.; Hinton, David E.; Zelikoff, Judith T.; Dikkeboom, Audrey L.; Tillitt, Donald E.; Holey, Mark; Denslow, Nancy

    2000-01-01

    Adult walleye were collected from several locations in the Lower Fox River and Green Bay, Wisconsin (the assessment area) and two relatively uncontaminated reference locations (Lake Winnebago and Patten Lake, Wisconsin) between July and October in 1996 and 1997. Whole body and liver samples collected in 1996 were analyzed for total PCBs, PCB congeners, and liver histological lesions. Follow-up sampling in 1997 included examination of liver histopathology, PCBs in liver samples, measurement of ethoxyresorufin-O-deethylase (EROD) activity, immunological evaluation of kidney and blood samples, measurement of plasma vitellogenin, and examination of tissues for parasites as well as bacterial and viral infections. Mean PCB concentrations in whole body and liver samples were elevated in assessment area walleye (4.6 to 8.6 and 3.6 to 6.4 mg/kg wet weight, respectively) compared to PCB concentrations in reference areas (0.04 mg/kg in walleye fillets from Lake Winnebago). A significant (p < 0.01) elevation was observed in the prevalence (26%) of hepatic preneoplastic foci of cellular alteration (FCA) and neoplasms in 5 to 8 year old walleye collected from the assessment area, compared to reference area fish (6% prevalence). Walleye from the assessment area also contained multiple FCA and hepatic tumors per liver sample, whereas no tumors and a reduced prevalence of FCA were observed in reference area walleye. Both tumors and FCA were more prevalent in female fish than in male fish within the 5 to 8 year age classes. There were no remarkable effects on immunological parameters in assessment area walleye, although hematocrit was elevated and blood monocyte counts were 40% lower than those of reference area fish. The data did not show any clear distinctions in the prevalence of disease between reference and assessment area walleye. EROD activity was similar in assessment area and reference area walleye. Plasma vitellogenin was elevated in female walleye from eastern Green Bay

  1. Vaccination for treatment and prevention of cancer in animal models.

    PubMed

    Cavallo, Federica; Offringa, Rienk; van der Burg, Sjoerd H; Forni, Guido; Melief, Cornelis J M

    2006-01-01

    Two approaches to immunological intervention in tumor-host interactions in mouse models are discussed in this review. The first is described with reference to experiments in which CD8(+) T lymphocytes are used to kill established transplantable tumors. Peptides and their optimal presentation by dendritic cells and intervention in immune regulatory mechanisms are the key issues for efficient induction of T-killer cell-mediated tumor eradication. The time frame of tumor therapy and the threat imposed by tumor growth in transplantable models and cancer patients require the induction of a robust T-cell reaction. Prevention of the progression of small preneoplastic lesions, on the other hand, requires the significant and prolonged immune protection sought in the second approach. This is based on antibody production and the coordinated activation of multiple low-avidity cell-mediated mechanisms elicited by DNA vaccination in genetically modified cancer-prone mice, transgenic for a mutant Her-2/neu growth factor receptor expressed at the plasma membrane surface of preneoplastic mammary gland epithelial cells. Vaccination with appropriate DNA formulations results in prolonged immune inhibition of the progression of preneoplastic mammary lesions but is ineffective against established tumors. The use of molecularly defined adjuvants and intervention in immune regulatory mechanisms are critical in both the elicitation of an effective T-cell mediated reaction required for tumor debulking in the first set of models and the induction by vaccination of a sustained immune memory able to prevent the expansion of preneoplastic lesions in genetically cancer-prone mice.

  2. Characterization of Mouse Models of Early Pancreatic Lesions Induced by Alcohol and Chronic Pancreatitis.

    PubMed

    Xu, Shiping; Chheda, Chintan; Ouhaddi, Yassine; Benhaddou, Hajar; Bourhim, Mouloud; Grippo, Paul J; Principe, Daniel R; Mascariñas, Emman; DeCant, Brian; Tsukamoto, Hidekazu; Pandol, Stephen J; Edderkaoui, Mouad

    2015-08-01

    We describe the first mouse model of pancreatic intraepithelial neoplasia (PanIN) lesions induced by alcohol in the presence and absence of chronic pancreatitis. Pdx1-Cre;LSL-K-ras mice were exposed to Lieber-DeCarli alcohol diet for 6 weeks with cerulein injections. The PanIN lesions and markers of fibrosis, inflammation, histone deacetylation, epithelial-to-mesenchymal transition (EMT), and cancer stemness were measured by immunohistochemistry and Western. Exposure of Pdx1-Cre;LSL-K-ras mice to an alcohol diet significantly stimulated fibrosis and slightly but not significantly increased the level of PanIN lesions associated with an increase in tumor-promoting M2 macrophages. Importantly, the alcohol diet did not increase activation of stellate cells. Alcohol diet and cerulein injections resulted in synergistic and additive effects on PanIN lesion and M2 macrophage phenotype induction, respectively. Cerulein pancreatitis caused stellate cell activation, EMT, and cancer stemness in the pancreas. Pancreatitis caused histone deacetylation, which was promoted by the alcohol diet. Pancreatitis increased EMT and cancer stemness markers, which were not further affected by the alcohol diet. The results suggest that alcohol has independent effects on promotion of PDAC associated with fibrosis formed through a stellate cell-independent mechanism and that it further promotes early PDAC and M2 macrophage induction in the context of chronic pancreatitis.

  3. The significance of fluorescein angiography in the early diagnosis of lesions on ocular fundus at pseudoxanthoma elasticum patients.

    PubMed

    Bogdanowski, T; Gluza, J; Rasiewicz, D

    1977-05-27

    The role of fluorescein angiography in early diagnosis of lesions on fundus of the eye at pseudoxanthoma elasticum patients has been shown. The authors show angiographic changes on the basis of three cases of pseudoxanthoma elasticum patients.

  4. Inhibitory effects of astaxanthin on azoxymethane-induced colonic preneoplastic lesions in C57/BL/KsJ-db/db mice.

    PubMed

    Kochi, Takahiro; Shimizu, Masahito; Sumi, Takafumi; Kubota, Masaya; Shirakami, Yohei; Tanaka, Takuji; Moriwaki, Hisataka

    2014-12-17

    Obesity and related metabolic abnormalities, including excess oxidative stress and chronic inflammation, are associated with colorectal carcinogenesis. Astaxanthin, a xanthophyll carotenoid found in aquatic animals, is known to possess antioxidant, anti-inflammatory, and antineoplastic properties. The present study examined the effects of astaxanthin on the development of azoxymethane (AOM)-induced colonic premalignant lesions in C57BL/KsJ-db/db (db/db) obese mice. Male db/db mice were administered 4 weekly subcutaneous injections of AOM (15 mg/kg body weight) from 5 weeks of age and subsequently, from 1 week after the last injection of AOM, were fed a diet containing 200 ppm astaxanthin throughout the experiment (8 weeks). The development of colonic premalignant lesions, i.e., aberrant crypt foci and β-catenin accumulated crypts, was significantly inhibited in mice treated with astaxanthin than in mice fed the basal diet. Astaxanthin administration markedly reduced urinary levels of 8-OHdG and serum levels of d-ROMs, which are oxidative stress markers, while increasing the expression of mRNA for the antioxidant enzymes GPx1, SOD1, and CAT in the colonic mucosa of AOM-treated db/db mice. The expression levels of IL-1β, IL-6, F4/80, CCL2, and CXCL2 mRNA in the colonic mucosa of AOM-treated mice were significantly decreased by astaxanthin. Dietary feeding with astaxanthin also resulted in a reduction in the numbers of NF-κB- and PCNA-positive cells that were increased by AOM exposure, in the colonic epithelium. These findings suggest that astaxanthin inhibits the development of colonic premalignant lesions in an obesity-related colorectal carcinogenesis model by reducing oxidative stress, attenuating chronic inflammation, and inhibiting NF-κB activation and cell proliferation in the colonic mucosa. Astaxanthin, therefore, may be a potential candidate as a chemoprevention agent against colorectal carcinogenesis in obese individuals.

  5. Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib.

    PubMed

    Yamamoto, Naoki; Yamasaki, Takahiro; Takami, Taro; Uchida, Koichi; Fujisawa, Koichi; Matsumoto, Toshihiko; Saeki, Issei; Terai, Shuji; Sakaida, Isao

    2016-05-01

    Although sorafenib is expected to have a chemopreventive effect on hepatocellular carcinoma (HCC) recurrence, there are limitations to its use because of adverse effects, including effects on liver function. We have reported that the iron chelator, deferoxamine can prevent liver fibrosis and preneoplastic lesions. We investigated the influence of administering a new oral iron chelator, deferasirox (DFX), on the effects of sorafenib. We used the choline-deficient l-amino acid-defined (CDAA) diet-induced rat liver fibrosis and HCC model. We divided rats into four groups: CDAA diet only (control group), CDAA diet with sorafenib (sorafenib group), CDAA diet with DFX (DFX group), and CDAA diet with DFX and sorafenib (DFX + sorafenib group). Liver fibrosis and development of preneoplastic lesions were assessed. In addition, we assessed adverse effects such as changes in body and liver weight, skin damage (eruption, dryness, and hair loss), which is defined as hand-foot skin syndrome, in the sorafenib and DFX + sorafenib groups. The combination of DFX + sorafenib markedly prevented liver fibrosis and preneoplastic lesions better than the other treatments. Furthermore, the combination therapy significantly decreased adverse effects compared with the sorafenib group. In conclusion, the combination therapy with DFX and sorafenib may be a useful adjuvant therapy to prevent recurrence after curative treatment of HCC.

  6. Prevalence and features of colorectal lesions among Hispanics: A hospital-based study.

    PubMed

    Ashktorab, Hassan; Laiyemo, Adeyinka O; Lee, Edward; Cruz-Correa, Marcia; Ghuman, Amita; Nouraie, Mehdi; Brim, Hassan

    2015-12-14

    To evaluate the prevalence and characteristics of colorectal adenoma and carcinoma in an inner city Hispanic population. We reviewed the reports of 1628 Hispanic patients who underwent colonoscopy at Howard University from 2000 to 2010. Advanced adenoma was defined as adenoma ≥ 1 cm in size, adenomas with villous histology, high grade dysplasia and/or invasive cancer. Statistical analysis was performed using χ(2) statistics and t-test. The median age of the patients was 54 years, 64.2% were females. Polyps were observed in 489 (30.0%) of patients. Adenoma prevalence was 16.8% (n = 273), advanced adenoma 2.4% (n = 39), and colorectal cancer 0.4% (n = 7). Hyperplastic polyps were seen in 6.6% of the cohort (n = 107). Adenomas predominantly exhibited a proximal colonic distribution (53.7%, n = 144); while hyperplastic polyps were mostly located in the distal colon (70%, n = 75). Among 11.7% (n = 191) patients who underwent screening colonoscopy, the prevalence of colorectal lesions was 21.4% adenoma, 2.6% advanced adenoma; and 8.3% hyperplastic polyps. Our data showed low colorectal cancer prevalence among Hispanics in the Washington DC area. However, the pre-neoplastic pattern of colonic lesions in Hispanics likely points toward a shift in this population that needs to be monitored closely through large epidemiological studies.

  7. Prevalence and features of colorectal lesions among Hispanics: A hospital-based study

    PubMed Central

    Ashktorab, Hassan; Laiyemo, Adeyinka O; Lee, Edward; Cruz-Correa, Marcia; Ghuman, Amita; Nouraie, Mehdi; Brim, Hassan

    2015-01-01

    AIM: To evaluate the prevalence and characteristics of colorectal adenoma and carcinoma in an inner city Hispanic population. METHODS: We reviewed the reports of 1628 Hispanic patients who underwent colonoscopy at Howard University from 2000 to 2010. Advanced adenoma was defined as adenoma ≥ 1 cm in size, adenomas with villous histology, high grade dysplasia and/or invasive cancer. Statistical analysis was performed using χ2 statistics and t-test. RESULTS: The median age of the patients was 54 years, 64.2% were females. Polyps were observed in 489 (30.0%) of patients. Adenoma prevalence was 16.8% (n = 273), advanced adenoma 2.4% (n = 39), and colorectal cancer 0.4% (n = 7). Hyperplastic polyps were seen in 6.6% of the cohort (n = 107). Adenomas predominantly exhibited a proximal colonic distribution (53.7%, n = 144); while hyperplastic polyps were mostly located in the distal colon (70%, n = 75). Among 11.7% (n = 191) patients who underwent screening colonoscopy, the prevalence of colorectal lesions was 21.4% adenoma, 2.6% advanced adenoma; and 8.3% hyperplastic polyps. CONCLUSION: Our data showed low colorectal cancer prevalence among Hispanics in the Washington DC area. However, the pre-neoplastic pattern of colonic lesions in Hispanics likely points toward a shift in this population that needs to be monitored closely through large epidemiological studies. PMID:26673447

  8. Transcriptome Assessment of Erythema Migrans Skin Lesions in Patients With Early Lyme Disease Reveals Predominant Interferon Signaling.

    PubMed

    Marques, Adriana; Schwartz, Ira; Wormser, Gary P; Wang, Yanmei; Hornung, Ronald L; Demirkale, Cumhur Y; Munson, Peter J; Turk, Siu-Ping; Williams, Carla; Lee, Chyi-Chia Richard; Yang, Jun; Petzke, Mary M

    2017-12-27

    The most common clinical manifestation of early Lyme disease is the erythema migrans (EM) skin lesion that develops at the tick bite site typically between 7 and 14 days after infection with Borreliella burgdorferi. The host-pathogen interactions that occur in the skin may have a critical role in determining outcome of infection. Gene arrays were used to characterize the global transcriptional alterations in skin biopsy samples of EM lesions from untreated adult patients with Lyme disease in comparison to controls. The transcriptional pattern in EM biopsies consisted of 254 differentially regulated genes (180 induced and 74 repressed) characterized by the induction of chemokines, cytokines, Toll-like receptors, antimicrobial peptides, monocytoid cell activation markers, and numerous genes annotated as interferon (IFN)-inducible. The IFN-inducible genes included 3 transcripts involved in tryptophan catabolism (IDO1, KMO, KYNU) that play a pivotal role in immune evasion by certain other microbial pathogens by driving the differentiation of regulatory T cells. This is the first study to globally assess the human skin transcriptional response during early Lyme disease. Borreliella burgdorferi elicits a predominant IFN signature in the EM lesion, suggesting a potential mechanism for spirochetal dissemination via IDO1-mediated localized immunosuppression. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  9. Assessment of the "fish tumors or other deformities" beneficial use impairment in brown bullhead (Ameiurus nebulosus): II. Liver neoplasia

    USGS Publications Warehouse

    Blazer, V.S.; Rafferty, S.D.; Baumman, P.C.; Smith, S.B.; Obert, E.C.

    2009-01-01

    Liver pathology of fishes, including neoplastic and preneoplastic lesions, is widely used as an indicator of exposure to anthropogenic contaminants. By definition, the "fish tumor or other deformities" beneficial use impairment (BUI) at Great Lakes Areas of Concern (AOC) includes neoplastic and preneoplastic liver lesions in brown bullhead (Ameiurus nebulosus) or suckers. Unfortunately, adequate guidelines for defining neoplastic and preneoplastic liver lesions or determining rates at unimpacted control sites were not provided and different criteria have been used. In some cases, only neoplastic changes were used to calculate tumor prevalence, in some both neoplastic and preneoplastic changes and in some it is difficult to determine which changes were included. Using standardized criteria, the prevalence of liver neoplasia was compared at eight AOC during 1998-2000. The Cuyahoga River had the highest prevalence (25.0%), while the Maumee River had the lowest (3.9%). The Buffalo (4.8%), Detroit (5.9%), Ashtabula (6.8%), Niagara (7.5%) and Black (8.9%) rivers were intermediate, as was Presque Isle Bay (7.1%). From 2002 to 2007 the prevalence of liver neoplasia at Presque Isle Bay ranged from a low of 2.1% (2002) to a high of 12.0% (2007). Non-AOC sites, as potential reference sites, also were monitored during this time. By combining years and sites, the prevalence of liver neoplasia in bullhead (aged 2 to 12 years) at inland lakes was 0.7%, at bays/harbors was 1.6% and at tributary sites was 4.1%. This is the same trend (inland lakes < bays/harbors < tributaries < Presque Isle Bay) noted for orocutaneous neoplasms.

  10. Comparison of spatula and cytobrush cytological techniques in early detection of oral malignant and premalignant lesions: a prospective and blinded study.

    PubMed

    Nanayakkara, P G C L; Dissanayaka, W L; Nanayakkara, B G; Amaratunga, E A P D; Tilakaratne, W M

    2016-04-01

    The use of oral cytology to diagnose malignant and premalignant lesions at an early stage is considered crucial. The aim of this study was to evaluate the diagnoses of the spatula and the cytobrush techniques compared with the gold standard histopathological findings, analysed according to different diagnostic criteria. Cytological smears were obtained from 76 suspicious oral malignant lesions and 116 oral leukoplakia lesions using two techniques: cytobrush plus cell collector and metal spatula. Subsequently, a surgical biopsy was performed on each lesion to achieve a histopathological diagnosis. Evaluation was conducted with respect to three different diagnostic criteria. The sensitivity for diagnosing carcinoma in clinically malignant cases was 89.58% and 60.42% for cytobrush and spatula techniques, respectively. Inclusion of severe dysplastic cases for 'high-risk' lesions increased the sensitivity up to 96.36% and 78.18% for two techniques, respectively. In leukoplakia lesions, malignant and severely dysplastic cells were diagnosed at a sensitivity of 88.89% in the cytobrush and 55.56% in the spatula techniques. Extending the criteria by defining malignant or any dysplastic findings as positive, sensitivity was increased to 98.02% and 89.11% for the spatula and the cytobrush techniques, respectively. Specificity for both techniques increased to 100%. The difference between the diagnoses of histopathology and the spatula cytology was statistically significant (P < 0.01), while no such difference was found with the cytobrush technique (P > 0.1). The cytobrush, unlike the spatula, is a useful screening instrument for early diagnosis of suspicious oral lesions and could therefore contribute to improved oral cancer prognosis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Development and psychometric testing of the 'Motivation and Self-Efficacy in Early Detection of Skin Lesions' index.

    PubMed

    Dyson, Judith; Cowdell, Fiona

    2014-12-01

    To develop and psychometrically test the Motivation and Self-Efficacy in Early Detection of Skin Lesions Index. Skin cancer is the most frequently diagnosed cancer worldwide. The primary strategy used to prevent skin cancer is promotion of sun avoidance and the use of sun protection. However, despite costly and extensive campaigns, cases of skin cancer continue to increase. If found and treated early, skin cancer is curable. Early detection is, therefore, very important. The study was conducted in 2013. Instrument Development. A literature review and a survey identified barriers (factors that hinder) and levers (factors that help) to skin self-examination. These were categorized according to a the Theoretical Domains Framework and this formed the basis of an instrument, which was tested for validity and reliability using confirmatory factor analysis and Cronbach's alpha respectively. A five-factor 20-item instrument was used that tested well for reliability and construct validity. Test-retest reliability was good for all items and domains. The five factors were: (i) Outcome expectancies; (ii) Intention; (iii) Self-efficacy; (iv) Social influences; (v) Memory. The Motivation and Self-Efficacy in Early Detection of Skin Lesions Index provides a reliable and valid method of assessing barriers and levers to skin self-examination. The next step is to design a theory-based intervention that can be tailored according to individual determinants to behaviour change identified by this instrument. © 2014 John Wiley & Sons Ltd.

  12. Comparison of Knoop and Vickers surface microhardness and transverse microradiography for the study of early caries lesion formation in human and bovine enamel.

    PubMed

    Lippert, F; Lynch, R J M

    2014-07-01

    The aims of the present laboratory study were twofold: a) to investigate the suitability of Knoop and Vickers surface microhardness (SMH) in comparison to transverse microradiography (TMR) to investigate early enamel caries lesion formation; b) to compare the kinetics of caries lesion initiation and progression between human and bovine enamel. Specimens (90×bovine and 90×human enamel) were divided into six groups (demineralization times of 8/16/24/32/40/48h) of 15 per enamel type and demineralized using a partially saturated lactic acid solution. SMH was measured before and after demineralization and changes in indentation length (ΔIL) calculated. Lesions were characterized using TMR. Data were analyzed (two-way ANOVA) and Pearson correlation coefficients calculated. ΔIL increased with increasing demineralization times but plateaued after 40h, whereas lesion depth (L) and integrated mineral loss (ΔZ) increased almost linearly throughout. No differences between Knoop and Vickers SMH in their ability to measure enamel demineralization were observed as both correlated strongly. Overall, ΔIL correlated strongly with ΔZ and L but only moderately with the degree of surface zone mineralization, whereas ΔZ and L correlated strongly. Bovine demineralized faster than human enamel (all techniques). Lesions in bovine formed faster than in human enamel, although the resulting lesions were almost indistinguishable in their mineral distribution characteristics. Early caries lesion demineralization can be sufficiently studied by SMH, but its limitations on the assessment of the mineral status of more demineralized lesions must be considered. Ideally, complementary techniques to assess changes in both physical and chemical lesion characteristics would be employed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Insights into the Virulence Traits of Streptococcus mutans in Dentine Carious Lesions of Children with Early Childhood Caries.

    PubMed

    Bezerra, Daniela S; Stipp, Rafael N; Neves, Beatriz G; Guedes, Sarah F F; Nascimento, Marcelle M; Rodrigues, Lidiany K A

    2016-01-01

    Streptococcus mutans is an oral bacterium considered to play a major role in the development of dental caries. This study aimed to investigate the prevalence of S. mutans in active and arrested dentine carious lesions of children with early childhood caries and to examine the expression profile of selected S. mutans genes associated with survival and virulence, within the same carious lesions. Dentine samples were collected from 29 active and 16 arrested carious lesions that were diagnosed in preschool children aged 2-5 years. Total RNA was extracted from the dentine samples, and reverse transcription quantitative real-time PCR analyses were performed for the quantification of S. mutans and for analyses of the expression of S. mutans genes associated with bacterial survival (atpD, nox, pdhA) and virulence (fabM and aguD). There was no statistically significant difference in the prevalence of S. mutans between active and arrested carious lesions. Expression of the tested genes was detected in both types of carious dentine. The pdhA (p = 0.04) and aguD (p = 0.05) genes were expressed at higher levels in arrested as compared to active lesions. Our findings revealed that S. mutans is part of the viable microbial community in active and arrested dentine carious lesions. The increase in expression of the pdhA and aguD genes in arrested lesions is likely due to the unfavourable environmental conditions for microbial growth, inherent to this type of lesions. © 2016 S. Karger AG, Basel.

  14. Recent studies on the developing human hepatocellular carcinoma.

    PubMed

    Gerber, M A

    1986-01-01

    From our knowledge of characteristic phenotypic changes of the preneoplastic lesions during the stepwise evolution of hepatocellular carcinoma (HCC) in experimental models, we are now beginning to define the structural, histochemical, biochemical, antigenic and molecular properties of early HCC and of the putative preneoplastic changes in human liver. Histological, ultrastructural, morphometric and immunohistochemical studies suggest that adenomatous nodules of regenerating and hyperplastic hepatocytes are more likely to represent direct precursors of HCC than dysplastic hepatocytes. Histochemical and immunomorphological investigations show appreciable functional and phenotypic heterogeneity of human HCC as previously recognized in experimental hepatocarcinogenesis. Studies of altered expression of oncogenes in the regenerating liver and HCC are beginning to define the molecular mechanisms in cell growth and malignant transformation. Although integration of Hepadna viral DNA sequences frequently occurs during persistent infection in man and animals, the exact mechanism of viral oncogenesis remains to be elucidated. It is likely that the development of monoclonal antibodies to surface antigens on transformed hepatocytes will be useful for exploring lineage relationships between the cell populations involved in hepatocarcinogenesis.

  15. Dynamic landscape of pancreatic carcinogenesis reveals early molecular networks of malignancy.

    PubMed

    Kong, Bo; Bruns, Philipp; Behler, Nora A; Chang, Ligong; Schlitter, Anna Melissa; Cao, Jing; Gewies, Andreas; Ruland, Jürgen; Fritzsche, Sina; Valkovskaya, Nataliya; Jian, Ziying; Regel, Ivonne; Raulefs, Susanne; Irmler, Martin; Beckers, Johannes; Friess, Helmut; Erkan, Mert; Mueller, Nikola S; Roth, Susanne; Hackert, Thilo; Esposito, Irene; Theis, Fabian J; Kleeff, Jörg; Michalski, Christoph W

    2018-01-01

    The initial steps of pancreatic regeneration versus carcinogenesis are insufficiently understood. Although a combination of oncogenic Kras and inflammation has been shown to induce malignancy, molecular networks of early carcinogenesis remain poorly defined. We compared early events during inflammation, regeneration and carcinogenesis on histological and transcriptional levels with a high temporal resolution using a well-established mouse model of pancreatitis and of inflammation-accelerated Kras G12D -driven pancreatic ductal adenocarcinoma. Quantitative expression data were analysed and extensively modelled in silico. We defined three distinctive phases-termed inflammation, regeneration and refinement-following induction of moderate acute pancreatitis in wild-type mice. These corresponded to different waves of proliferation of mesenchymal, progenitor-like and acinar cells. Pancreas regeneration required a coordinated transition of proliferation between progenitor-like and acinar cells. In mice harbouring an oncogenic Kras mutation and challenged with pancreatitis, there was an extended inflammatory phase and a parallel, continuous proliferation of mesenchymal, progenitor-like and acinar cells. Analysis of high-resolution transcriptional data from wild-type animals revealed that organ regeneration relied on a complex interaction of a gene network that normally governs acinar cell homeostasis, exocrine specification and intercellular signalling. In mice with oncogenic Kras, a specific carcinogenic signature was found, which was preserved in full-blown mouse pancreas cancer. These data define a transcriptional signature of early pancreatic carcinogenesis and a molecular network driving formation of preneoplastic lesions, which allows for more targeted biomarker development in order to detect cancer earlier in patients with pancreatitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. C/EBPα-dependent preneoplastic tumor foci are the origin of hepatocellular carcinoma and aggressive pediatric liver cancer.

    PubMed

    Cast, Ashley; Valanejad, Leila; Wright, Mary; Nguyen, Phuong; Gupta, Anita; Zhu, Liqin; Shin, Soona; Timchenko, Nikolai

    2018-05-01

    Recent publications show that classic hepatoblastoma (HBL) is the result of failure of hepatic stem cells to differentiate into hepatocytes, while hepatocellular carcinoma (HCC) is caused by the dedifferentiation of hepatocytes into cancer stem cells. However, the mechanisms of aggressive HBL and the mechanisms that cause dedifferentiation of hepatocytes into cancer stem cells are unknown. We found that, similar to HCC but opposite to classic HBL, aggressive HBL is the result of dedifferentiation of hepatocytes into cancer stem cells. In both cases of liver cancer, the dephosphorylation of tumor suppressor protein CCAAT/enhancer binding protein α (C/EBPα) at Ser193 (Ser190 in human protein) or mutation of Ser193 to Ala results in a modified protein with oncogenic activities. We have investigated liver cancer in a mouse model C/EBPα-S193A, in a large cohort of human HBL samples, and in Pten/p53 double knockout mice and found that these cancers are characterized by elevation of C/EBPα that is dephosphorylated at Ser190/193. We found that dephosphorylated C/EBPα creates preneoplastic foci with cancer stem cells that give rise to HCC and aggressive HBL. C/EBPα-dependent dedifferentiation of hepatocytes into cancer stem cells includes increased proliferation of hepatocytes, followed by generation of multinucleated hepatocytes and subsequent appearance of hepatocytes with delta-like 1 homolog-positive intranuclear inclusions. We further isolated C/EBPα-dependent multinucleated hepatocytes and found that they possess characteristics of tumor-initiating cells, including elevation of stem cell markers. C/EBPα-dependent cancer stem cells are observed in patients with aggressive HBL and in patients with a predisposition for liver cancer. The earliest steps of adult HCC and aggressive pediatric liver cancer have identical features that include conversion of the tumor suppressor C/EBPα into an oncogenic isoform, which further creates preneoplastic foci where

  17. Morphological, structural, and functional alterations of the prefrontal cortex and the basolateral amygdala after early lesion of the rat mediodorsal thalamus.

    PubMed

    Ouhaz, Zakaria; Ba-M'hamed, Saadia; Bennis, Mohamed

    2017-08-01

    Early postnatal damage to the mediodorsal thalamus (MD) produces deficits in cognition and behavior believed to be associated with early prefrontal cortical maldevelopment. We assessed the role of MD afferents during development on the morphological and functional maturation of the prefrontal cortex (PFC) and the basolateral amygdala (BLA). Sprague-Dawley rat pups (n = 56) received a bilateral electrolytic lesion of the MD or a MD Sham lesion on postnatal day 4. 7 weeks later, all rats were tested in anxiety-related and cognitive paradigms using the elevated plus maze and novel object recognition tests. Following behavioral testing (P70), rats were killed and the baseline expression of C-Fos protein and the number of GABAergic neurons were evaluated in the PFC and the BLA. The dendritic morphology and spine density in the PFC using Golgi-Cox staining was also evaluated. Adult rats with early postnatal bilateral MD damage exhibited disrupted recognition memory and increased anxiety-like behaviors. The lesion also caused a significant diminution of C-Fos immunolabeling and an increase of the number of GABAergic neurons in the PFC. In the BLA, the number of GABAergic neurons was significantly reduced, associated with an increase in C-Fos immunolabeling. Furthermore, in the PFC the lesion induced a significant reduction in dendritic branching and spine density. Our data are consistent with the hypothesis that the MD plays a role in the development of the PFC and, therefore, may be a good animal model to investigate cognitive symptoms associated with schizophrenia.

  18. Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib

    PubMed Central

    Yamamoto, Naoki; Yamasaki, Takahiro; Takami, Taro; Uchida, Koichi; Fujisawa, Koichi; Matsumoto, Toshihiko; Saeki, Issei; Terai, Shuji; Sakaida, Isao

    2016-01-01

    Although sorafenib is expected to have a chemopreventive effect on hepatocellular carcinoma (HCC) recurrence, there are limitations to its use because of adverse effects, including effects on liver function. We have reported that the iron chelator, deferoxamine can prevent liver fibrosis and preneoplastic lesions. We investigated the influence of administering a new oral iron chelator, deferasirox (DFX), on the effects of sorafenib. We used the choline-deficient l-amino acid-defined (CDAA) diet-induced rat liver fibrosis and HCC model. We divided rats into four groups: CDAA diet only (control group), CDAA diet with sorafenib (sorafenib group), CDAA diet with DFX (DFX group), and CDAA diet with DFX and sorafenib (DFX + sorafenib group). Liver fibrosis and development of preneoplastic lesions were assessed. In addition, we assessed adverse effects such as changes in body and liver weight, skin damage (eruption, dryness, and hair loss), which is defined as hand-foot skin syndrome, in the sorafenib and DFX + sorafenib groups. The combination of DFX + sorafenib markedly prevented liver fibrosis and preneoplastic lesions better than the other treatments. Furthermore, the combination therapy significantly decreased adverse effects compared with the sorafenib group. In conclusion, the combination therapy with DFX and sorafenib may be a useful adjuvant therapy to prevent recurrence after curative treatment of HCC. PMID:27257345

  19. The origin of pre-neoplastic metaplasia in the stomach: Chief cells emerge from the Mist

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Goldenring, James R., E-mail: jim.goldenring@vanderbilt.edu; Departments of Surgery and Cell and Developmental Biology, Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, TN; Nam, Ki Taek

    2011-11-15

    The digestive-enzyme secreting, gastric epithelial chief (zymogenic) cell is remarkable and underappreciated. Here, we discuss how all available evidence suggests that mature chief cells in the adult, mammalian stomach are postmitotic, slowly turning over cells that arise via a relatively long-lived progenitor, the mucous neck cell, The differentiation of chief cells from neck cells does not involve cell division, and the neck cell has its own distinct pattern of gene expression and putative physiological function. Thus, the ontogeny of the normal chief cell lineage exemplifies transdifferentiation. Furthermore, under pathophysiogical loss of acid-secreting parietal cell, the chief cell lineage can itselfmore » trasndifferentiate into a mucous cell metaplasia designated Spasmolytic Polypeptide Expressing Metaplasia (SPEM). Especially in the presence of inflammation, this metaplastic lineage can regain proliferative capacity and, in humans may also further differentiate into intestinal metaplasia. The results indicate that gastric fundic lineages display remarkable plasticity in both physiological ontogeny and pathophysiological pre-neoplastic metaplasia.« less

  20. Visual recognition and visually guided action after early bilateral lesion of occipital cortex: a behavioral study of a 4.6-year-old girl.

    PubMed

    Amicuzi, Ileana; Stortini, Massimo; Petrarca, Maurizio; Di Giulio, Paola; Di Rosa, Giuseppe; Fariello, Giuseppe; Longo, Daniela; Cannatà, Vittorio; Genovese, Elisabetta; Castelli, Enrico

    2006-10-01

    We report the case of a 4.6-year-old girl born pre-term with early bilateral occipital damage. It was revealed that the child had non-severely impaired basic visual abilities and ocular motility, a selective perceptual deficit of figure-ground segregation, impaired visual recognition and abnormal navigating through space. Even if the child's visual functioning was not optimal, this was the expression of adaptive anatomic and functional brain modifications that occurred following the early lesion. Anatomic brain structure was studied with anatomic MRI and Diffusor Tensor Imaging (DTI)-MRI. This behavioral study may provide an important contribution to understanding the impact of an early lesion of the visual system on the development of visual functions and on the immature brain's potential for reorganisation related to when the damage occurred.

  1. Oral Lesions in Neonates

    PubMed Central

    Rao, Roopa S; Majumdar, Barnali; Jafer, Mohammed; Maralingannavar, Mahesh; Sukumaran, Anil

    2016-01-01

    ABSTRACT Oral lesions in neonates represent a wide range of diseases often creating apprehension and anxiety among parents. Early examination and prompt diagnosis can aid in prudent management and serve as baseline against the future course of the disease. The present review aims to enlist and describe the diagnostic features of commonly encountered oral lesions in neonates. How to cite this article: Patil S, Rao RS, Majumdar B, Jafer M, Maralingannavar M, Sukumaran A. Oral Lesions in Neonates. Int J Clin Pediatr Dent 2016;9(2):131-138. PMID:27365934

  2. Development of ferret as a human lung cancer model by injecting 4-(Nmethyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK).

    PubMed

    Aizawa, Koichi; Liu, Chun; Veeramachaneni, Sudipta; Hu, Kang-Quan; Smith, Donald E; Wang, Xiang-Dong

    2013-12-01

    Development of new animal lung cancer models that are relevant to human lung carcino-genesis is important for lung cancer research. Previously we have shown the induction of lung tumor in ferrets (Mustela putorius furo) exposed to both tobacco smoke and a tobacco carcinogen (4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone, NNK). In the present study, we investigated whether NNK treatment alone induces both preneoplastic and neoplastic lesions in the lungs of ferrets. We exposed ferrets to NNK by i.p. injection of NNK (50 mg/kg BW) once a month for four consecutive months and then followed up for 24, 26 and 32 weeks. The incidences of pulmonary pre-neoplastic and neoplastic lesions were assessed by histopathological examination. The expressions of 7 nicotinic acetylcholine receptor ( 7 nAChR, which has been shown to promote lung carcinogenesis)and its related molecular biomarkers in lungs were examined by immunohistochemistry and/or Western blotting analysis. Ferrets exposed to NNK alone developed both preneoplastic lesions (squamous metaplasia, dysplasia and atypical adenomatous hyperplasia) and tumors (squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma), which are commonly seen in humans. The incidence of tumor induced by NNK was time-dependent in the ferrets (16.7%, 40.0% and 66.7% for 24, 26 and 32 weeks, respectively). 7 nAChR is highly expressed in the ferret bronchial/bronchiolar epithelial cells, and alveolar macrophages in ferrets exposed to NNK, and in both squamous cell carcinoma and adenocarcinoma of the ferrets. In addition, we observed the tendency for an increase in phospho-ERK and cyclin D1 protein levels (p = 0.081 and 0.080, respectively) in the lungs of ferrets exposed to NNK. The development of both preneoplastic and neoplastic lesions in ferret lungs by injecting NNK alone provides a simple and highly relevant non-rodent model for studying biomarkers/molecular targets for the prevention, detection and treatment of lung

  3. Cytokine Signatures Associated With Early Onset, Active Lesions and Late Cicatricial Events of Retinochoroidal Commitment in Infants With Congenital Toxoplasmosis.

    PubMed

    Carneiro, Ana Carolina Aguiar Vasconcelos; Machado, Anderson Silva; Béla, Samantha Ribeiro; Costa, Julia Gatti Ladeia; Andrade, Gláucia Manzan Queiroz; Vasconcelos-Santos, Daniel Vitor; Januário, José Nélio; Coelho-Dos-Reis, Jordana Grazziela; Ferro, Eloisa Amália Vieira; Teixeira-Carvalho, Andréa; Vitor, Ricardo Wagner Almeida; Martins-Filho, Olindo Assis

    2016-06-15

    Ocular toxoplasmosis is a prominent and severe condition of high incidence in Brazil. The current study provides new insights into the immunological events that can be associated with retinochoroiditis in the setting of congenital toxoplasmosis in human infants. Flow cytometry of intracytoplasmic cytokines in leukocyte subsets following in vitro short-term antigenic recall in infants with congenital T. gondii infection. Our data demonstrates that whereas neutrophils and monocytes from T. gondii-infected infants display a combination of proinflammatory and regulatory cytokine profiles, natural killer cells showed a predominantly proinflammatory profile upon in vitro T. gondii stimulation. The proinflammatory response of CD4(+) and CD8(+) T cells, characterized by the production of interferon γ (IFN-γ) and interleukin 17 in patients with an active retinochoroidal lesion, revealed the presence of IFN-γ and tumor necrosis factor α during early and late immunological events. This specific proinflammatory pattern is associated with early events and active retinochoroidal lesion, whereas a robust monocyte-derived interleukin 10-mediated profile is observed in children with cicatricial ocular lesions. These findings support the existence of a progressive immunological environment concomitant with the initial, apical, and cicatricial phases in the process of retinochoroidal lesion formation in infants with congenital toxoplasmosis that may be relevant in the establishment of stage-specific clinical management. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  4. Expression profiles of cancer stem cell markers: CD133, CD44, Musashi-1 and EpCAM in the cardiac mucosa-Barrett's esophagus-early esophageal adenocarcinoma-advanced esophageal adenocarcinoma sequence.

    PubMed

    Mokrowiecka, Anna; Veits, Lothar; Falkeis, Christina; Musial, Jacek; Kordek, Radzislaw; Lochowski, Mariusz; Kozak, Jozef; Wierzchniewska-Lawska, Agnieszka; Vieth, Michael; Malecka-Panas, Ewa

    2017-03-01

    Barrett's esophagus (BE), which develops as a result of gastroesophageal reflux disease, is a preneoplastic condition for esophageal adenocarcinoma (EAC). A new hypothesis suggests that cancer is a disease of stem cells, however, their expression and pathways in BE - EAC sequence are not fully elucidated yet. We used a panel of putative cancer stem cells markers to identify stem cells in consecutive steps of BE-related cancer progression. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded blocks from 58 patients with normal cardiac mucosa (n=5), BE (n=14), early EAC (pT1) from mucosal resection (n=17) and advanced EAC (pT1-T4) from postoperative specimens (n=22). Expression of the CD133, CD44, Musashi-1 and EpCAM was analyzed using respective monoclonal antibodies. All markers showed a heterogeneous expression pattern, mainly at the base of the crypts of Barrett's epithelium and EAC, with positive stromal cells in metaplastic and dysplastic lesions. Immuno-expression of EpCAM, CD44 and CD133 in cardiac mucosa was significantly lower (mean immunoreactivity score (IRS)=1.2; 0.0; 0.4; respectively) compared to their expression in Barrett's metaplasia (mean IRS=4.3; 0.14; 0.7; respectively), in early adenocarcinoma (mean IRS=4.4; 0.29; 1.3; respectively) and in advanced adenocarcinoma (mean IRS=6.6; 0.7; 2.7; respectively) (p<0.05). On the contrary, Musashi-1 expression was higher in BE and early ADC compared to GM and advanced ADC (NS). Our results suggest that the stem cells could be present in premalignant lesions. EpCAM, CD44 and CD133 expression could be candidate markers for BE progression, whereas Musashi-1 may be a marker of the small intestinal features of Barrett's mucosa. Copyright © 2016 Elsevier GmbH. All rights reserved.

  5. Quantum mechanical model for the anticarcinogenic effect of extremely-low-frequency electromagnetic fields on early chemical hepatocarcinogenesis

    NASA Astrophysics Data System (ADS)

    Godina-Nava, Juan José; Torres-Vega, Gabino; López-Riquelme, Germán Octavio; López-Sandoval, Eduardo; Samana, Arturo Rodolfo; García Velasco, Fermín; Hernández-Aguilar, Claudia; Domínguez-Pacheco, Arturo

    2017-02-01

    Using the conventional Haberkorn approach, it is evaluated the recombination of the radical pair (RP) singlet spin state to study theoretically the cytoprotective effect of an extremely-low-frequency electromagnetic field (ELF-EMF) on early stages of hepatic cancer chemically induced in rats. The proposal is that ELF-EMF modulates the interconversion rate of singlet and triplet spin states of the RP populations modifying the products from the metabolization of carcinogens. Previously, we found that the daily treatment with ELF-EMF 120 Hz inhibited the number and area of preneoplastic lesions in chemical carcinogenesis. The singlet spin population is evaluated diagonalizing the spin density matrix through the Lanczos method in a radical pair mechanism (RPM). Using four values of the interchange energy, we have studied the variations over the singlet population. The low magnetic field effect as a test of the influence over the enzymatic chemical reaction is evaluated calculating the quantum yield. Through a bootstrap technique the range is found for the singlet decay rate for the process. Applying the quantum measurements concept, we addressed the impact toward hepatic cells. The result contributes to improving our understanding of the chemical carcinogenesis process affected by charged particles that damage the DNA.

  6. SIV Encephalitis Lesions Are Composed of CD163+ Macrophages Present in the Central Nervous System during Early SIV Infection and SIV-Positive Macrophages Recruited Terminally with AIDS

    PubMed Central

    Nowlin, Brian T.; Burdo, Tricia H.; Midkiff, Cecily C.; Salemi, Marco; Alvarez, Xavier; Williams, Kenneth C.

    2016-01-01

    Macrophage recruitment to the central nervous system (CNS) during AIDS pathogenesis is poorly understood. We measured the accumulation of brain perivascular (CD163+) and inflammatory (MAC387+) macrophages in SIV-infected monkeys. Monocyte progenitors were 5-bromo-2′-deoxyuridine (BrdU) labeled in bone marrow, and CNS macrophages were labeled serially with fluorescent dextrans injected into the cisterna magna. MAC387+ macrophages accumulated in the meninges and choroid plexus in early inflammation and in the perivascular space and SIV encephalitis (SIVE) lesions late. CD163+ macrophages accumulated in the perivascular space and SIVE lesions with late inflammation. Most of the BrdU+ cells were MAC387+; however, CD163+BrdU+ macrophages were present in the meninges and choroid plexus with AIDS. Most (81.6% ± 1.8%) of macrophages in SIVE lesions were present in the CNS before SIVE lesion formation. There was a 2.9-fold increase in SIVp28+ macrophages entering the CNS late compared with those entering early (P < 0.05). The rate of CD163+ macrophage recruitment to the CNS inversely correlated with time to death (P < 0.03) and increased with SIVE. In SIVE animals, soluble CD163 correlated with CD163+ macrophage recruitment (P = 0.02). Most perivascular macrophages that comprise SIVE lesions and multinucleated giant cells are present in the CNS early, before SIVE lesions are formed. Most SIV-infected macrophages traffic to the CNS terminally with AIDS. PMID:25963554

  7. The Role of Epilepsy in Early Language Development in a Child with a Congenital Lesion in the Right Hemisphere

    ERIC Educational Resources Information Center

    Mayor-Dubois, C.; Maeder-Ingvar, M.; Deonna, T.; Roulet-Perez, E.

    2008-01-01

    Early epilepsy is known to worsen the developmental prognosis of young children with a congenital focal brain lesion, but its direct role is often very difficult to delineate from the other variables. This requires prolonged periods of follow-up with simultaneous serial electrophysiological and developmental assessments which are rarely obtained.…

  8. The war on cancer.

    PubMed

    Sporn, M B

    1996-05-18

    25 years ago, then President Nixon "declared" War on Cancer. In this personal commentary, the war is reviewed. There have been obvious triumphs, for instance in cure of acute lymphocytic leukaemia and other childhood cancers, Hodgkin's disease, and testicular cancer. However, substantial advances in molecular oncology have yet to impinge on mortality statistics. Too many adults still die from common epithelial cancers. Failure to appreciate that local invasion and distant metastasis rather then cell proliferation itself are lethal, obsession with cure of advanced disease rather than prevention of early disease, and neglect of the need to arrest preneoplastic lesions may all have served to make victory elusive.

  9. The war on cancer: a review.

    PubMed

    Sporn, M B

    1997-12-29

    Twenty-five years ago, then President Nixon "declared war" on cancer. In this personal commentary, the war is reviewed. There have been obvious triumphs, for instance in cure of acute lymphocytic leukemia and other forms of childhood cancer, Hodgkin's disease, and testicular cancer. However, substantial advances in molecular oncology have yet to impinge on mortality statistics. Too many adults still die from common epithelial cancers. Failure to appreciate that local invasion and distant metastasis rather then cell proliferation itself are lethal, obsession with cure of advanced disease rather than prevention of early disease, and neglect of the need to arrest preneoplastic lesions, may all have served to make victory elusive.

  10. Ki-67 expression in early prostate cancer and associated pathological lesions.

    PubMed Central

    Feneley, M R; Young, M P; Chinyama, C; Kirby, R S; Parkinson, M C

    1996-01-01

    AIM: To assess cell proliferation in early prostate cancer and associated pathological lesions. METHODS: Using the Ki-67 antibody, the cell proliferation index was measured in early stage prostatic carcinoma in 37 incidental tumours diagnosed at transurethral prostatectomy (TURP) and in 20 low volume cancers treated by radical prostatectomy. Proliferation indexes have also been measured in areas of normal peripheral zone, transition zone hyperplasia, atrophic appearing lobules, and high grade prostatic intraepithelial neoplasia in the radical prostatectomy cases. RESULTS: In the TURP series the proliferation index correlated with grade and stage. Logistic regression analysis, however, showed that Gleason grade was the most reliable predictor of biopsy proven residual disease and clinical progression. In the radical series transition zone carcinoma the proliferation index was half that of peripheral zone carcinoma. The atrophic lobules also showed a high proliferation index of the same order as seen in the peripheral zone carcinoma. Normal peripheral zone showed the lowest proliferation index and in hyperplastic transition zone it was also less than the other areas. CONCLUSIONS: There is only limited support for the correlation of proliferation index with grade in early stage prostatic carcinoma. The findings do not suggest that proliferation index adds to the prognostic information given by grade and stage in pT1 disease. The significant difference in proliferation index in transition zone and peripheral zone carcinomas supports the morphological distinction of these tumour types and is consistent with differences in biological behaviour. The high proliferation index in lobules considered morphologically atrophic is reminiscent of previous observations in which carcinoma was spatially associated with atrophy. Images PMID:9038759

  11. Use of flexible hollow-core CO2 laser in microsurgical resection of CNS lesions: early surgical experience.

    PubMed

    Killory, Brendan D; Chang, Steve W; Wait, Scott D; Spetzler, Robert F

    2010-06-01

    The CO2 laser has a long history in both experimental and clinical neurosurgery. However, its use over the past decade has been limited by its cumbersome design and bulky set-up of the micromanipulator. These limitations are amplified when it is used with the operating microscope. These restrictions are addressed by the Omniguide fiber, which delivers the beam through flexible hollow-core photonic bandgap mirror fibers and allows the laser to be wielded like any other surgical instrument. The attending neurosurgeon prospectively assessed the usefulness of the laser in its first 45 consecutive uses at our institution based on a scale of 1 to 5. The series included 11 cavernous malformations, 14 meningiomas, 7 ependymomas, 3 metastases, 3 astrocytomas, and 7 miscellaneous lesions. The laser was set up 91 times and used in 45 cases. The Omniguide fiber failed 5 times. No adverse events involving patients or staff were associated with laser use. The mean utility score was 3.7 +/- 0.8 (range, 2-5). The laser was most helpful in debulking fibrous lesions too tough for ultrasonic aspiration and lesions adherent to delicate neurovascular structures. The laser was not helpful with highly vascular tumors. In our early experience, the Omniguide laser was very helpful in selected cases in resecting specific types of lesions without complications; we have added the device to our neurosurgical armamentarium.

  12. Methylene Blue as a Diagnostic Aid in the Early Detection of Potentially Malignant and Malignant Lesions of Oral Mucosa.

    PubMed

    Lejoy, Abraham; Arpita, Rai; Krishna, Burde; Venkatesh, Naikmasur

    2016-05-01

    In vivo stains are the prompt resources, which have emerged in recent years to aid as clinical diagnostic tools in detecting early potentially malignant and malignant lesions. Toluidine blue, by its property of retaining in the increased DNA and RNA cellular activity areas, aids in delineating the suspicious areas. However, it is hazardous if swallowed, and has been shown to have toxicity to fibroblasts. Methylene blue has a similar chemical structure and exhibits similar physicochemical properties as toluidine blue. It is less toxic to the human body and has recently been proposed for screening some gastrointestinal or prostate tumors. The application of this material in detecting oral lesions has so far not been addressed. The objective of this study was to evaluate the sensitivity and reliability of in vivo staining with methylene blue as a diagnostic adjunct in screening for oral malignant or potentially malignant lesions. The present study involved the examination of 75 patients suspected of having oral malignant or potentially malignant lesions by methylene blue staining. The results of methylene blue uptake were compared with a simultaneous biopsy of these lesions. The overall sensitivity was 95% (100% for malignancy and 92% for potentially malignant lesions) and specificity was 70%. The positive predictive value was 91% and negative predictive value of 80% was observed in the study. We consider that methylene blue staining is a useful diagnostic adjunct in a large, community-based oral cancer screening program for high-risk individuals.

  13. MRI in early prostate cancer detection: how to manage indeterminate or equivocal PI-RADS 3 lesions?

    PubMed

    Schoots, Ivo G

    2018-02-01

    This review focuses on indeterminate lesions on prostate magnetic resonance imaging (MRI), assigned as PI-RADS category 3. The prevalence of PI-RADS 3 index lesion in the diagnostic work-up is significant, varying between one in three (32%) to one in five (22%) men, depending on patient cohort of first biopsies, previously negative biopsies, and active surveillance biopsies. A management strategy must be developed for this group of men with an indeterminate suspicion of having clinically significant prostate cancer (csPCa). Currently available data show that the actual prevalence of csPCa after targeted biopsy in PI-RADS 3 lesions vary between patients groups from one in five (21%) to one in six (16%), depending on previous biopsy status. Although this prevalence is lower in comparison to PI-RADS 4 and PI-RADS 5 lesions, still a considerable proportion of men harbor significant disease. Men with such a PI-RADS 3 lesion should therefore be adequately managed. In general, the clinical approach of using a threshold of PI-RADS ≥4 instead of PI-RADS ≥3 to select MRI for targeted biopsies is not supported by data from our explorative literature search using current definitions of csPCa. A possible adaptation to the threshold of PI-RADS ≥4 in combination with other clinical markers could be considered within an active surveillance protocol, where the balance between the individual risk of missing csPCa and the constant process of repeating prostate biopsies is crucial. In the future, improvements in MR imaging and interpretation, combined with molecular biomarkers and multivariate risk models will all be employed in prostate cancer detection and monitoring. These combinations will aid decision-making in challenging circumstances, such as unclear and diagnostic equivocal results for csPCa at early detection.

  14. Proteomic Profiling of Paraffin-Embedded Samples Identifies Metaplasia-Specific and Early-Stage Gastric Cancer Biomarkers

    PubMed Central

    Sousa, Josane F.; Ham, Amy-Joan L.; Whitwell, Corbin; Nam, Ki Taek; Lee, Hyuk-Joon; Yang, Han-Kwang; Kim, Woo Ho; Zhang, Bing; Li, Ming; LaFleur, Bonnie; Liebler, Daniel C.; Goldenring, James R.

    2013-01-01

    Early diagnosis and curative resection are the predominant factors associated with increased survival in patients with gastric cancer. However, most gastric cancer cases are still diagnosed at later stages. Since most pathologic specimens are archived as FFPE samples, the ability to use them to generate expression profiles can greatly improve cancer biomarker discovery. We sought to uncover new biomarkers for stomach preneoplastic metaplasias and neoplastic lesions by generating proteome profiles using FFPE samples. We combined peptide isoelectric focusing and liquid chromatography–tandem mass spectrometry analysis to generate proteomic profiles from FFPE samples of intestinal-type gastric cancer, metaplasia, and normal mucosa. The expression patterns of selected proteins were analyzed by immunostaining first in single tissue sections from normal stomach, metaplasia, and gastric cancer and later in larger tissue array cohorts. We detected 60 proteins up-regulated and 87 proteins down-regulated during the progression from normal mucosa to metaplasia to gastric cancer. Two of the up-regulated proteins, LTF and DMBT1, were validated as specific markers for spasmolytic polypeptide–expressing metaplasia and intestinal metaplasia, respectively. In cancers, significantly lower levels of DMBT1 or LTF correlated with more advanced disease and worse prognosis. Thus, proteomic profiling using FFPE samples has led to the identification of two novel markers for stomach metaplasias and gastric cancer prognosis. PMID:22944598

  15. Investigating the Role of Cooperative Interactions Between the Neu Protooncogene and the Other erbB Family Members in Rat Mammary Carcinogenesis

    DTIC Science & Technology

    1999-07-01

    antiestrogen tamoxifen or the monoterpene perillyl alcohol can prevent the formation of neu associated mammary cancers in this transgenic model. II...general breast cancer prevention agents; the monoterpenes (perillyl alcohol) and determine if the number of preneoplastic lesions and cancers

  16. Karyometry of the colonic mucosa.

    PubMed

    Alberts, David S; Einspahr, Janine G; Krouse, Robert S; Prasad, Anil; Ranger-Moore, James; Hamilton, Peter; Ismail, Ayaaz; Lance, Peter; Goldschmid, Steven; Hess, Lisa M; Yozwiak, Michael; Bartels, Hubert G; Bartels, Peter H

    2007-12-01

    The study summarizes results of karyometric measurements in epithelial cells of the colorectal mucosa to document evidence of a field effect of preneoplastic development among patients with colorectal adenocarcinoma or adenoma. Karyometric analyses were done on high-resolution images of histologic sections from 48 patients with colorectal adenocarcinomas and 44 patients with adenomas and on images from matching normal-appearing mucosa directly adjacent to such lesions, at a 1-cm and 10-cm distance from the lesions or from the rectal mucosa of adenoma patients, as well as from 24 healthy normal controls with no family history of colonic disease. The nuclei recorded in the histologically normal-appearing mucosa of patients with either colorectal adenoma or adenocarcinoma exhibited differences in karyometric features in comparison with nuclei recorded in rectal mucosa from patients who were free of a colonic lesion. These differences were expressed to the same extent in tissue adjacent to the lesions and in normal-appearing tissue as distant as the rectum. The nuclear chromatin pattern may serve as an integrating biomarker for a preneoplastic development. The field effect might provide an end point in chemopreventive intervention trials.

  17. Comparison of Reversibility of Rat Forestomach Lesions Induced by Genotoxic and Non‐genotoxic Carcinogens

    PubMed Central

    Kagawa, Masataka; Hakoi, Kazuo; Yamamoto, Atsushi; Futakuchi, Mitsuru

    1993-01-01

    Reversibility of forestomach lesions induced by genotoxic and non‐genotoxic carcinogens was compared histopathologically. Groups of 30 to 33 male F344 rats were given dietary 0.1% 8‐nitroquinoline, dietary 0.4–0.2% 2‐(2‐furyl)‐3‐(5‐nitro‐2‐furyl)acrylamide, an intragastric dose of 20 mg/kg body weight N‐methyl‐N′‐nitro‐N‐nitrosoguanidine once a week, or 20 ppm N‐methylnitrosourethane in the drinking water as a genotoxic carcinogen, or 2% butylated hydroxyanisole, 2% caffeic acid, 2% sesamol or 2% 4‐methoxyphenol in the diet as a non‐genotoxic carcinogen for 24 weeks. Ten or 11 rats in each group were killed at week 24. Half of the remainder were maintained on basal diet alone for an additional 24 weeks and the other half were given the same chemical for 48 weeks, and then killed. Forestomach lesions induced by genotoxic carcinogens did not regress after removal of carcinogens. In contrast, simple or papillary hyperplasia (SPH), but not basal cell hyperplasia (BCH), induced by non‐genotoxic carcinogens clearly regressed after cessation of insult. SFH labeling indices in the non‐genotoxic carcinogen‐treated cases decreased after removal of the carcinogenic stimulus whereas BCH values were low irrespective of treatment. Atypical hyperplasia (AH), observed at high incidences in rats treated with genotoxic carcinogens, was also evident in animals receiving non‐genotoxic agents, even after their withdrawal, albeit at low incidences. AH labeling indices remained high even without continued insult. These results indicate that even with non‐genotoxic carcinogens, heritable alterations at the DNA level could occur during strong cell proliferation and result in AH development. This putative preneoplastic lesion might then progress to produce carcinomas. PMID:8276717

  18. Preventive effects of curcumin on the development of azoxymethane-induced colonic preneoplastic lesions in male C57BL/KsJ-db/db obese mice.

    PubMed

    Kubota, Masaya; Shimizu, Masahito; Sakai, Hiroyasu; Yasuda, Yoichi; Terakura, Daishi; Baba, Atsushi; Ohno, Tomohiko; Tsurumi, Hisashi; Tanaka, Takuji; Moriwaki, Hisataka

    2012-01-01

    Obesity-related metabolic abnormalities include a state of chronic inflammation and adipocytokine imbalance, which increase the risk of colon cancer. Curcumin, a component of turmeric, exerts both cancer preventive and antiinflammatory properties. Curcumin is also expected to have the ability to reverse obesity-related metabolic derangements. The present study examined the effects of curcumin on the development of azoxymethane (AOM)-induced colonic premalignant lesions in C57BL/KsJ-db/db (db/db) obese mice. Feeding with a diet containing 0.2% and 2.0% curcumin caused a significant reduction in the total number of colonic premalignant lesions compared with basal diet-fed mice. The expression levels of tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2 (COX-2) mRNAs on the colonic mucosa of AOM-treated mice were significantly decreased by curcumin administration. Dietary feeding with curcumin markedly activated AMP-activated kinase, decreased the expression of COX-2 protein, and inhibited nuclear factor-κB activity on the colonic mucosa of AOM-treated mice. Curcumin also increased the serum levels of adiponectin while conversely decreasing the serum levels of leptin and the weights of fat. In conclusion, curcumin inhibits the development of colonic premalignant lesions in an obesity-related colorectal carcinogenesis model, at least in part, by attenuating chronic inflammation and improving adipocytokine imbalance. Curcumin may be useful in the chemoprevention of colorectal carcinogenesis in obese individuals.

  19. Early growth hormone (GH) treatment promotes relevant motor functional improvement after severe frontal cortex lesion in adult rats.

    PubMed

    Heredia, Margarita; Fuente, A; Criado, J; Yajeya, J; Devesa, J; Riolobos, A S

    2013-06-15

    A number of studies, in animals and humans, describe the positive effects of the growth hormone (GH) treatment combined with rehabilitation on brain reparation after brain injury. We examined the effect of GH treatment and rehabilitation in adult rats with severe frontal motor cortex ablation. Thirty-five male rats were trained in the paw-reaching-for-food task and the preferred forelimb was recorded. Under anesthesia, the motor cortex contralateral to the preferred forelimb was aspirated or sham-operated. Animals were then treated with GH (0.15 mg/kg/day, s.c) or vehicle during 5 days, commencing immediately or 6 days post-lesion. Rehabilitation was applied at short- and long-term after GH treatment. Behavioral data were analized by ANOVA following Bonferroni post hoc test. After sacrifice, immunohistochemical detection of glial fibrillary acid protein (GFAP) and nestin were undertaken in the brain of all groups. Animal group treated with GH immediately after the lesion, but not any other group, showed a significant improvement of the motor impairment induced by the motor lesion, and their performances in the motor test were no different from sham-operated controls. GFAP immunolabeling and nestin immunoreactivity were observed in the perilesional area in all injured animals; nestin immunoreactivity was higher in GH-treated injured rats (mainly in animals GH-treated 6 days post-lesion). GFAP immunoreactivity was similar among injured rats. Interestingly, nestin re-expression was detected in the contralateral undamaged motor cortex only in GH-treated injured rats, being higher in animals GH-treated immediately after the lesion than in animals GH-treated 6 days post-lesion. Early GH treatment induces significant recovery of the motor impairment produced by frontal cortical ablation. GH effects include increased neurogenesis for reparation (perilesional area) and for increased brain plasticity (contralateral motor area). Copyright © 2013 Elsevier B.V. All rights

  20. MYC and gastric adenocarcinoma carcinogenesis

    PubMed Central

    Calcagno, Danielle Queiroz; Leal, Mariana Ferreira; Assumpção, Paulo Pimentel; Smith, Marília de Arruda Cardoso; Burbano, Rommel Rodríguez

    2008-01-01

    MYC is an oncogene involved in cell cycle regulation, cell growth arrest, cell adhesion, metabolism, ribosome biogenesis, protein synthesis, and mitochondrial function. It has been described as a key element of several carcinogenesis processes in humans. Many studies have shown an association between MYC deregulation and gastric cancer. MYC deregulation is also seen in gastric preneoplastic lesions and thus it may have a role in early gastric carcinogenesis. Several studies have suggested that amplification is the main mechanism of MYC deregulation in gastric cancer. In the present review, we focus on the deregulation of the MYC oncogene in gastric adenocarcinoma carcinogenesis, including its association with Helicobacter pylori (H pylori) and clinical applications. PMID:18932273

  1. JAM3 methylation status as a biomarker for diagnosis of preneoplastic and neoplastic lesions of the cervix

    PubMed Central

    Yin, Aijun; Zhang, Qing; Kong, Xiangnan; Jia, Lin; Yang, Ziyan; Meng, Lihua; Li, Li; Wang, Xiao; Qiao, Yunbo; Lu, Nan; Yang, Qifeng; Shen, Keng; Kong, Beihua

    2015-01-01

    DNA methylation is clinically relevant to important tumorigenic mechanisms. This study evaluated the methylation status of candidate genes in cervical neoplasia and determined their diagnostic performance in clinical practice. Cervical cancer and normal cervix tissue was used to select the top 5 discriminating loci among 27 loci in 4 genes (CCNA1, CADM1, DAPK1, JAM3), and one locus of JAM3 (region M4) was identified and confirmed with 267 and 224 cervical scrapings from 2 independent colposcopy referral studies. For patients with atypical squamous cells of unknown significance and those with low-grade squamous intraepithelial lesion, with JAM3-M4 compared to a triage marker of hrHPV testing, the specificity for cervical intraepithelial neoplasia 3 CIN3 and cancer cases (CIN3+) / no neoplasia and CIN1 (CIN1−) was significantly increased, from 21.88 to 81.82 and 15.38 to 85.18, respectively. The corresponding positive predictive value (PPV) was increased from 26.47 to 57.14 and 18.52 to 63.64, respectively. For hrHPV-positive patients, compared to a triage marker of cytology testing, JAM3-M4 showed increased specificity and PPV, from 30.67 to 87.65 and 38.82 to 82.14, respectively. We assessed whether JAM3-M4 could distinguish productive from transforming CIN2; the coincidence rate of JAM3-M4 and P16 was as high as 60.5%. PMID:26517242

  2. Accuracy in clinically evaluating pigmented lesions.

    PubMed Central

    Curley, R. K.; Cook, M. G.; Fallowfield, M. E.; Marsden, R. A.

    1989-01-01

    OBJECTIVE--To determine the ability of three doctors experienced in managing melanocytic lesions to diagnose correctly melanoma, dysplastic naevi, and various benign pigmented lesions. DESIGN--Independent clinical evaluation and histopathological assessment. SETTING--Pigmented lesion clinic, which patients attend without an appointment for early diagnosis of melanoma. PATIENTS--86 Patients with lesions that were judged to be benign by at least one of the three doctors. INTERVENTIONS--The lesions were excised under local anaesthesia and sent for histopathological examination in coded bottles without clinical details. MAIN OUTCOME MEASURE--Comparison of clinical with histopathological diagnosis for each lesion. RESULTS--A total of 120 lesions were evaluated by at least two of the three doctors. The histopathological diagnoses were made by the same pathologist. The overall sensitivity (diagnostic accuracy) for the three doctors for all types of lesion was 50%. Of the 39 dysplastic naevi, only 19 were identified correctly by all observers, and a further 24 banal lesions were wrongly diagnosed as dysplastic by at least one doctor. Particular difficulty was experienced with small (less than 5 mm), flat lesions, which can be banal or potentially malignant. CONCLUSIONS--Critical diagnosis and management decisions concerning pigmented lesions should always be based on a combination of clinical and histopathological assessments and the history of the patient. PMID:2503192

  3. Anal HPV genotypes and related displasic lesions in Italian and foreign born high-risk males.

    PubMed

    Orlando, Giovanna; Beretta, Rosangela; Fasolo, M Michela; Amendola, Antonella; Bianchi, Silvia; Mazza, Francesca; Rizzardini, Giuliano; Tanzi, Elisabetta

    2009-05-29

    Anal intraepithelial neoplasia and anal cancer are closely related to infection from high-risk Human Papilloma Virus (HPV) genotypes. Since HPVs involved in disease progression are reported to vary by geographical regions, this study focuses on HPV genotypes spectrum in 289 males attending a Sexual Transmitted Diseases (STD) unit according to their nationality. Anal cytology, Digene Hybrid Capture Assay (HC2) and HPV genotyping were evaluated in 226 Italian (IT) and 63 foreign born (FB) subjects, recruited between January 2003 and December 2006. FB people were younger (median 32y-IQR 27-35 vs 36y-IQR 31-43, respectively; Mann-Whitney test p<0.0001) and had a higher rate of abnormal results (>or=atypical squamous cells of undetermined significance (ASCUS)) on anal cytology (95.0% vs 84.04%) (p=0.032; OR 3.61; 95% CI 1.04-1.23). HPV-16 is by far the most common genotype found in anal cytological samples independently from nationality while differences in distribution of other HPV genotypes were observed. The probability of infection from high-risk HPVs was higher in FB (OR 1.69; 95% CI 1.07-2.68) and is due to a higher rate of HPV-58 (OR 4.98; 95% CI 2.06-12.04), to a lower rate of HPV-11 (OR 0.35; 95% CI 0.16-0.77), to the presence of other high-risk genotypes (HPV-45, HPV-66, HPV-69). Multiple infections rate was high and comparable between IT and FB people. The relative contribution of each HPV genotype in the development of pre-neoplastic disease to an early age in the FB group cannot be argued by this study and more extensive epidemiological evaluations are needed to define the influence of each genotype and the association with the most prevalent high-risk HPVs on cytological intraepithelial lesions development.

  4. Distribution of HPV Genotypes and Involvement of Risk Factors in Cervical Lesions and Invasive Cervical Cancer: A Study in an Indian Population

    PubMed Central

    Srivastava, Shikha; Shahi, U P; Dibya, Arti; Gupta, Sadhana; Roy, Jagat K

    2014-01-01

    Human papilloma virus (HPV) is considered as the main sexually transmitted etiological agent for the cause and progression of preneoplastic cervical lesions to cervical cancer. This study is discussing the prevalence of HPV and its genotypes in cervical lesions and invasive cervical cancer tissues and their association with various risk factors in women from Varanasi and its adjoining areas in India. A total of 122 cervical biopsy samples were collected from SS Hospital and Indian Railways Cancer Institute and Research Centre, Varanasi and were screened for HPV infection by PCR using primers from L1 consensus region of the viral genome. HPV positive samples were genotyped by type-specific PCR and sequencing. The association of different risk factors with HPV infection in various grades of cervical lesion was evaluated by chi-square test. A total of 10 different HPV genotypes were observed in women with cervicitis, CIN, invasive squamous cell cervical carcinoma and adenocarcinoma. Increased frequency of HPV infection with increasing lesion grade (p=0.002) was observed. HPV16 being the predominant type was found significantly associated with severity of the disease (p=0.03). Various socio- demographic factors other than HPV including high parity (p<0.0001), rural residential area (p<0.0001), elder age (p<0.0001), low socio-economic status (p<0.0001) and women in postmenopausal group (p<0.0001) were also observed to be associated with cervical cancer.These findings show HPV as a direct cause of cervical cancer suggesting urgent need of screening programs and HPV vaccination in women with low socio-economic status and those residing in rural areas. PMID:25035855

  5. Targeting Premalignant Lesions: Implications for Early Breast Cancer Detection and Intervention

    DTIC Science & Technology

    2016-04-01

    prostate, lung, colon and pancreas and have been also reported in the premalignant lesions. This peptide could provide us with an opportunity to...including those of the breast, prostate, lung, colon and pancreas and have been also reported in the premalignant lesions (Erez N, et. al Cancer Cell

  6. Pediatric Awake Craniotomy for Brain Lesions.

    PubMed

    Akay, Ali; Rükşen, Mete; Çetin, H Yurday; Seval, H Özer; İşlekel, Sertaç

    2016-01-01

    Awake craniotomy is a special method to prevent motor deficits during the resection of lesions that are located in, or close to, functional areas. Although it is more commonly performed in adult patients, reports of pediatric cases undergoing awake craniotomy are limited in the literature. In our clinic, where we frequently use awake craniotomy in adult patients, we performed this method in 2 selected pediatric cases for lesion surgery. At an early age, these 2 cases diagnosed with epilepsy presented cerebral lesions, but since the lesions enclosed functional areas, surgical resection was not regarded as a treatment option at this time. In these 2 pediatric cases, we successfully completed lesion surgery with awake craniotomy. The method and the techniques employed during surgery are presented concomitant with other reports in the literature. © 2016 S. Karger AG, Basel.

  7. Inflammatory and vascular placental lesions are associated with neonatal amplitude integrated EEG recording in early premature neonates

    PubMed Central

    Goshen, Sharon; Richardson, Justin; Drunov, VIadimir; Staretz Chacham, Orna; Shany, Eilon

    2017-01-01

    the first 3 days of life (P = 0.007). Conclusions Depressed neonatal aEEG patterns are associated with placental lesions consistent with maternal under perfusion, and amniotic fluid infection of fetal type, but not with fetal thrombo-oclusive vascular disease of inflammatory type. Our findings highlight the association between the intrauterine mechanisms leading to preterm parturition and subsequent depressed neonatal cerebral function early after birth, which eventually may put premature infants at risk for abnormal neurodevelopmental outcome. PMID:28644831

  8. Optical Assessment of Caries Lesion Structure and Activity

    NASA Astrophysics Data System (ADS)

    Lee, Robert Chulsung

    New, more sophisticated diagnostic tools are needed for the detection and characterization of caries lesions in the early stages of development. It is not sufficient to simply detect caries lesions, methods are needed to assess the activity of the lesion and determine if chemical or surgical intervention is needed. Previous studies have demonstrated that polarization sensitive optical coherence tomography (PS-OCT) can be used to nondestructively image the subsurface lesion structure and measure the thickness of the highly mineralized surface zone. Other studies have demonstrated that the rate of dehydration can be correlated with the lesion activity and that the rate can be measured using optical methods. The main objective of this work was to test the hypothesis that optical methods can be used to assess lesion activity on tooth coronal and root surfaces. Simulated caries models were used to develop and validate an algorithm for detecting and measuring the highly mineralized surface layer using PS-OCT. This work confirmed that the algorithm was capable of estimating the thickness of the highly mineralized surface layer with high accuracy. Near-infrared (NIR) reflectance and thermal imaging methods were used to assess activity of caries lesions by measuring the state of lesion hydration. NIR reflectance imaging performed the best for artificial enamel and natural coronal caries lesion samples, particularly at wavelengths coincident with the water absorption band at 1460-nm. However, thermal imaging performed the best for artificial dentin and natural root caries lesion samples. These novel optical methods outperformed the conventional methods (ICDAS II) in accurately assessing lesion activity of natural coronal and root caries lesions. Infrared-based imaging methods have shown potential for in-vivo applications to objectively assess caries lesion activity in a single examination. It is likely that if future clinical trials are a success, this novel imaging

  9. Periapical implant lesion: A systematic review

    PubMed Central

    Blaya-Tárraga, Juan-Antonio; Cervera-Ballester, Juan; Peñarrocha-Oltra, David; Peñarrocha-Diago, Miguel

    2017-01-01

    Background The aim of this study was to systematically review the evidence for periapical implant lesion, which makes a patient more susceptible to the periapical lesion, frequency, symptoms, signs (including radiological findings) and possible treatment options. Material and Methods A systematic literature review and analysis of publications included in PubMed, Embase and Cochrane; articles published until March 2016; with a populations, exposures and outcomes (PEO) search strategy was performed, focused on the issue: “In patients with periapical lesion to the implant during the osseointegration, what symptoms, signs, and changes in complementary examination manifested, for according to that stage, be intervened with the appropriate approach?”. The set criteria for inclusion were peer-reviewed articles. Results From a total of 212 papers identified, 36 studies were included in this systematic review, with 15461 implants evaluated and 183 periapical implant lesions. Which 8 papers included more than 5 cases and 28 included equal or less than 5 cases. Analysis of the papers revealed that periapical implant lesion is classified according to evolution stages into acute (non-suppurated and suppurated) and subacute (or suppurated-fistulized). In the acute stage and in the subacute if there is no loss of implant stability, the correct treatment approach is implant periapical surgery. In the subacute stage associated with implant mobility the implant must be removed. Conclusions Evidence on the subject is very limited, there are few studies with small sample, without homogeneity of criteria for diagnosing the disease and without design of scientific evidence. Currently etiology lacks consensus. The early diagnosis of periapical implant periapical lesions during the osseointegration phase and early treatment, will lead to a higher survival rate of implants treated, hence preventing the need for implant extraction. Key words:Apical peri-implantitis, retrograde peri

  10. BRCA1-IRIS overexpression promotes and maintains the tumor initiating phenotype: implications for triple negative breast cancer early lesions

    PubMed Central

    Sullivan, Lisa M.; Sims, Hillary; Bastawisy, Ahmed El; Yousef, Hend F.; Zekri, Abdel-Rahman N.; Bahnassy, Abeer A.; ElShamy, Wael M.

    2017-01-01

    Tumor-initiating cells (TICs) are cancer cells endowed with self-renewal, multi-lineage differentiation, increased chemo-resistance, and in breast cancers the CD44+/CD24-/ALDH1+ phenotype. Triple negative breast cancers show lack of BRCA1 expression in addition to enhanced basal, epithelial-to-mesenchymal transition (EMT), and TIC phenotypes. BRCA1-IRIS (hereafter IRIS) is an oncogene produced by the alternative usage of the BRCA1 locus. IRIS is involved in induction of replication, transcription of selected oncogenes, and promoting breast cancer cells aggressiveness. Here, we demonstrate that IRIS overexpression (IRISOE) promotes TNBCs through suppressing BRCA1 expression, enhancing basal-biomarkers, EMT-inducers, and stemness-enforcers expression. IRISOE also activates the TIC phenotype in TNBC cells through elevating CD44 and ALDH1 expression/activity and preventing CD24 surface presentation by activating the internalization pathway EGFR→c-Src→cortactin. We show that the intrinsic sensitivity to an anti-CD24 cross-linking antibody-induced cell death in membranous CD24 expressing/luminal A cells could be acquired in cytoplasmic CD24 expressing IRISOE TNBC/TIC cells through IRIS silencing or inactivation. We show that fewer IRISOE TNBC/TICs cells form large tumors composed of TICs, resembling TNBCs early lesions in patients that contain metastatic precursors capable of disseminating and metastasizing at an early stage of the disease. IRIS-inhibitory peptide killed these IRISOE TNBC/TICs, in vivo and prevented their dissemination and metastasis. We propose IRIS inactivation could be pursued to prevent dissemination and metastasis from early TNBC tumor lesions in patients. PMID:28052035

  11. Liver histopathology in Baltic eelpout (Zoarces viviparus) - A baseline study for use in marine environmental monitoring.

    PubMed

    Fricke, Nicolai F; Stentiford, Grant D; Feist, Stephen W; Lang, Thomas

    2012-12-01

    The use of liver histopathology in various fish species as a biomarker in marine monitoring programmes to assess the biological effect of exposure to anthropogenic contaminants is well established. However, although the eelpout (Zoarces viviparus) has repeatedly been recommended as an appropriate bioindicator for monitoring purposes in the Baltic Sea, information on histopathological liver alterations of this species is scarce. In order to obtain an overview, a total of 1070 eelpout, collected in the period between spring 2001 and winter 2010 from 34 sampling sites distributed over large parts of the Baltic Sea, were histologically analyzed. Liver lesions were recorded and classified according to established liver lesion categories. A high prevalence of non-specific and early toxicopathic non-neoplastic hepatic lesions was recorded. In contrast, pre-neoplastic lesions were observed only in rare cases and neoplastic changes were absent. A comparison with published data on other fish species revealed that the observed alterations may indicate effects of environmental stressors including contaminants. The results of the present study, thus, support the application of eelpout liver histopathology in environmental monitoring. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Selective amplification of T-cell receptor variable region species is demonstrable but not essential in early lesions of psoriasis vulgaris: analysis by anchored polymerase chain reaction and hypervariable region size spectratyping.

    PubMed

    Vekony, M A; Holder, J E; Lee, A J; Horrocks, C; Eperon, I C; Camp, R D

    1997-07-01

    Several groups have investigated the role of T cells in the pathogenesis of psoriasis by determination of T-cell receptor (TCR) B-chain variable (V) region usage, both in chronic plaque (psoriasis vulgaris) and guttate forms, with various results. Because there are no data on TCR expression in early psoriasis vulgaris, when specific cellular immune events may be expected to be most pronounced, we have analyzed early lesions (less than 3 wk old) of ten patients, with highly reproducible results. We have developed a highly controlled anchored polymerase chain reaction (PCR) method in which TCR beta chain species are all amplified with the same primer pair and products are quantified by dot blot hybridization with BV family-specific oligonucleotide probes. Overexpression of certain TCR BV genes was observed in the majority of lesional biopsies, but in samples in which the expanded BV family formed more than 10% of total lesional BV (half of the samples analyzed), BV2 and BV6 predominated. The consistency of overexpression of these BV species between patients was much less than in previous studies of TCRBV usage in established chronic plaque psoriasis lesions. Complementarity-determining region 3 (CDR3) size spectratyping demonstrated evidence for selective clonal T cell accumulation in less than half of the lesional samples showing BV expansion. These results indicate that selective amplification of TCRBV species occurs in early psoriasis vulgaris but is not essential to the pathogenic process and may be more important in the maintenance or expansion of chronic lesions.

  13. [Iatrogenic biliary lesions and stenosis].

    PubMed

    Latteri, S; Vecchio, R; Angilello, A

    1997-01-01

    Pathogenetic, diagnostic and therapeutic aspects of postoperative bile duct injuries are reviewed. Treatment options are discussed in relation to the time of diagnosis. Lesions detected during the same operation must be immediately repaired through an end-to-end biliary anastomosis or a bilioenteric anastomosis. In limited lesions of the bile duct a T-tube placement should be sufficient. Bile duct lesions recognized postoperatively can be managed through a multimodal surgical, endoscopic, and radiologic approach. In the early postoperative period, surgery is indicated when a complete section of the biliary tract or a severe peritonitis is recognized, or when endoscopic and radiologic treatment has failed. Surgery is also the treatment of choice in the late complete stenosis of the bile duct. Roux-en-Y hepatico-jejunostomy is the most common surgical procedure for the treatment of bile duct lesions and strictures. However, in high bile duct lesions, especially if the risk of anastomotic dehiscence is increased the Authors emphasize the Rodney-Smith technique for the reconstruction of the biliary tract.

  14. Aberrant crypt formation accompanies an increase of opportunistic pathogens/bacteria in the inflammatory gut of C57BL/6 mice fed a high-fat diet

    USDA-ARS?s Scientific Manuscript database

    Obesity and high fat diet are risk factors for colon cancer, but the mechanism of this relationship remains to be determined. We tested the hypothesis that a high fat diet promotes the formation of aberrant crypt foci (ACF, preneoplastic lesions) in a manner associated with changes in hindgut bacter...

  15. [Bile duct lesions in laparoscopic cholecystectomy].

    PubMed

    Siewert, J R; Ungeheuer, A; Feussner, H

    1994-09-01

    Laparoscopic cholecystectomy is both resulting in a slightly higher incidence of biliary lesions and a change of prevalence of the type of lesions. Damage to the biliary system occurs in 4 different types: The most severe case is the lesion with a structural defect of the hepatic or common bile duct with (IVa) or without (IVb) vascular injury. Tangential lesions without structural loss of the duct should be denominated as type III (IIIa with additional lesion to the vessels, type IIIb without). Type II comprehends late strictures without obvious intraoperative trauma to the duct. Type I includes immediate biliary fistulae of usually good prognosis. The increasing prevalence of structural defects of the bile ducts appears to be a peculiarity of laparoscopic cholecystectomy necessitating highly demanding operative repair. In the majority of cases, hepatico-jejunostomy or even intraparenchymatous anastomoses are required. Adaptation of well proven principles of open surgery is the best prevention of biliary lesions in laparoscopic cholecystectomy as well as the readiness to convert early to the open procedure.

  16. Imaging inflammatory acne: lesion detection and tracking

    NASA Astrophysics Data System (ADS)

    Cula, Gabriela O.; Bargo, Paulo R.; Kollias, Nikiforos

    2010-02-01

    It is known that effectiveness of acne treatment increases when the lesions are detected earlier, before they could progress into mature wound-like lesions, which lead to scarring and discoloration. However, little is known about the evolution of acne from early signs until after the lesion heals. In this work we computationally characterize the evolution of inflammatory acne lesions, based on analyzing cross-polarized images that document acne-prone facial skin over time. Taking skin images over time, and being able to follow skin features in these images present serious challenges, due to change in the appearance of skin, difficulty in repositioning the subject, involuntary movement such as breathing. A computational technique for automatic detection of lesions by separating the background normal skin from the acne lesions, based on fitting Gaussian distributions to the intensity histograms, is presented. In order to track and quantify the evolution of lesions, in terms of the degree of progress or regress, we designed a study to capture facial skin images from an acne-prone young individual, followed over the course of 3 different time points. Based on the behavior of the lesions between two consecutive time points, the automatically detected lesions are classified in four categories: new lesions, resolved lesions (i.e. lesions that disappear completely), lesions that are progressing, and lesions that are regressing (i.e. lesions in the process of healing). The classification our methods achieve correlates well with visual inspection of a trained human grader.

  17. Border preserving skin lesion segmentation

    NASA Astrophysics Data System (ADS)

    Kamali, Mostafa; Samei, Golnoosh

    2008-03-01

    Melanoma is a fatal cancer with a growing incident rate. However it could be cured if diagnosed in early stages. The first step in detecting melanoma is the separation of skin lesion from healthy skin. There are particular features associated with a malignant lesion whose successful detection relies upon accurately extracted borders. We propose a two step approach. First, we apply K-means clustering method (to 3D RGB space) that extracts relatively accurate borders. In the second step we perform an extra refining step for detecting the fading area around some lesions as accurately as possible. Our method has a number of novelties. Firstly as the clustering method is directly applied to the 3D color space, we do not overlook the dependencies between different color channels. In addition, it is capable of extracting fine lesion borders up to pixel level in spite of the difficulties associated with fading areas around the lesion. Performing clustering in different color spaces reveals that 3D RGB color space is preferred. The application of the proposed algorithm to an extensive data-base of skin lesions shows that its performance is superior to that of existing methods both in terms of accuracy and computational complexity.

  18. [Vascular lesions of vocal folds--part 1: horizontal vascular lesions].

    PubMed

    Voigt-Zimmermann, S; Arens, C

    2014-12-01

    In recent decades, the endoscopic methods and technologies for laryngeal examination have improved so much that not only epithelial changes, but also vascular changes are recognizable at earlier stages. When comparing newer and older literature, the associated increasingly differentiated descriptions of such visible vascular changes of the vocal folds lead to terminological blurring and shifts of meaning. This complicates the technical-scientific discourse. The aim of the present work is a theoretical and conceptual clarification of early vascular changes of vocal folds. Horizontal changes of benigne vascular diseases, e. g. vessel ectasia, meander, increasing number and branching of vessels, change of direction may develop in to manifest vascular lesions, like varicosis, polyps and in case of ruptures to haemorrhages of vocal folds. These beginning and reversible vascular changes, when early detected and discussed basing on etiological knowledge, may lead to more differentiated prognostic statements and adequate therapeutic decisions, e. g. phonosurgery, functional voice therapy, voice hygiene and voice rest. Vertical vascular changes, like vessel loops, occur primarily in laryngeal papilloma, pre-cancerous and cancerous changes of the vocal folds. Already in small cancerous lesions of the vocal folds the vascular architecture is completely destroyed. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Quantitative bone scan lesion area as an early surrogate outcome measure indicative of overall survival in metastatic prostate cancer.

    PubMed

    Brown, Matthew S; Kim, Grace Hyun J; Chu, Gregory H; Ramakrishna, Bharath; Allen-Auerbach, Martin; Fischer, Cheryce P; Levine, Benjamin; Gupta, Pawan K; Schiepers, Christiaan W; Goldin, Jonathan G

    2018-01-01

    A clinical validation of the bone scan lesion area (BSLA) as a quantitative imaging biomarker was performed in metastatic castration-resistant prostate cancer (mCRPC). BSLA was computed from whole-body bone scintigraphy at baseline and week 12 posttreatment in a cohort of 198 mCRPC subjects (127 treated and 71 placebo) from a clinical trial involving a different drug from the initial biomarker development. BSLA computation involved automated image normalization, lesion segmentation, and summation of the total area of segmented lesions on bone scan AP and PA views as a measure of tumor burden. As a predictive biomarker, treated subjects with baseline BSLA [Formula: see text] had longer survival than those with higher BSLA ([Formula: see text] and [Formula: see text]). As a surrogate outcome biomarker, subjects were categorized as progressive disease (PD) if the BSLA increased by a prespecified 30% or more from baseline to week 12 and non-PD otherwise. Overall survival rates between PD and non-PD groups were statistically different ([Formula: see text] and [Formula: see text]). Subjects without PD at week 12 had longer survival than subjects with PD: median 398 days versus 280 days. BSLA has now been demonstrated to be an early surrogate outcome for overall survival in different prostate cancer drug treatments.

  20. Penile intraepithelial neoplasia and other premalignant lesions of the penis.

    PubMed

    Crispen, Paul L; Mydlo, Jack H

    2010-08-01

    Invasive penile cancer is an aggressive malignancy that often requires partial or complete penile amputation. Premalignant penile lesions, such as penile intraepithelial neoplasia, will have been present prior to the development of invasive disease in a substantial percentage of patients. Early detection and treatment of premalignant penile lesions may prevent malignant progression while avoiding penile amputation. This review focuses on premalignant penile lesions and the associations of these lesions with the development of invasive penile cancer. Copyright 2010 Elsevier Inc. All rights reserved.

  1. PROPOSED DIAGNOSTIC CRITERIA FOR PROLIFERATIVE THYROID LESIONS IN BONY FISHES

    EPA Science Inventory

    Distinguishing hyperplastic lesions from neoplasia in the thyroid of bony fishes has been debated by scientists for about one hundred years. As early as the first decade of the last century, the histological interpretation of some of the striking proliferative lesions observed in...

  2. [High-risk HPV genotyping PCR testing as a means of cervical cancer and precancerous lesions early screening].

    PubMed

    Ma, Li; Cong, Xiao; Bian, Meilu; Shi, Mai; Wang, Xiuhong; Liu, Jun; Liu, Haiyan

    2015-04-01

    To explored high-risk HPV genotyping PCR testing whether as a feasible means for the early screening of cervical cancer and precancerous lesions. From January 2013 to June 2014, 15,192 outpatients in China-Japan Friendship Hospital voluntary were tested by high-risk type HPV genotyping PCR. The average age of them were (33±8) years old. High-risk HPV types genotyping PCR tested by fluorescence PCR technology, in which 13 kinds of high-risk HPV subtypes were detected, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68. A total of 4,315 cases of them were tested by the liquid-based cytology (LCT), among them with positive of high-risk HPV genotyping tested by PCR (n=2,366) were biopsy under colposcope (648 cases) in those LCT results were positive or LCT negative but HPV16 positive or LCT negative but had the clear clinical symptoms or and non-HPV16 positive but with clear clinical symptoms. (1) Analysis high-risk HPV infection status of 15 192 women. (2) As the pathological diagnosis was the gold standard in the diagnosis of cervical lesions, analysis of the relationship among high-risk HPV infection, virus loads and cervical lesions. (3) To evaluated the value of high-risk HPV genotyping PCR tested method in screening of cervical cancer and precancerous lesions. ⑴ Of 15,192 cases tested by high-risk HPV genotyping PCR, 2,366 cases were HPV positive (HPV infection), the overall infection rate was 15.57% (2,366/15,192), in which a single subtype of HPV infection in 1,767 cases, infection rate was 11.63% (1,767/15,192), and multiple subtypes of HPV infection (two and more subtypes HPV infection) in 599 cases, infection rate was 3.94% (599/15,192). The HPV16, 52 and 58 infections were the most common HPV subtypes in 13 subtypes, the infection rate was 3.95% (600/15,192), 2.86% (435/15,192) and 2.67% (406/15,192), respectively. (2) The most relevant subtypes with cervical intraepithelial neoplasia (CIN) II and even higher lesion were HPV16, 52 and 58

  3. The microbiome modulates the tumor macroenvironment.

    PubMed

    Erdman, Susan E; Poutahidis, Theofilos

    2014-01-01

    Earlier investigations of the tumor microenvironment unveiled systemic networks presenting novel therapeutic opportunities. It has been recently shown that gut microbes modulate whole host immune and neuroendocrine factors impacting the fate of distant preneoplastic lesions toward malignancy or regression. These findings establish a new paradigm of holobiont therapeutic engineering in emerging tumor macroenvironments.

  4. Lymphangioma circumscriptum of the penis mimicking venereal lesions.

    PubMed

    Gupta, S; Radotra, B D; Javaheri, S M; Kumar, B

    2003-09-01

    Lymphangioma circumscriptum (LC) involving the penis is rare. We report two patients with penile LC. The lesions developed in early infancy in one patient, and during puberty in the other. The lesions resembled molluscum contagiosum in one and genital warts in the other. The first patient was previously treated with a diagnosis of venereal disease. A literature search found only 4 LC patients with penile lesions reported in the English literature. These cases are presented for their rarity, and to increase diagnostic vigilance and desirability of non-intervention.

  5. Early dynamic 18F-FDG PET to detect hyperperfusion in hepatocellular carcinoma liver lesions.

    PubMed

    Schierz, Jan-Henning; Opfermann, Thomas; Steenbeck, Jörg; Lopatta, Eric; Settmacher, Utz; Stallmach, Andreas; Marlowe, Robert J; Freesmeyer, Martin

    2013-06-01

    In addition to angiographic data on vascularity and vascular access, demonstration of hepatocellular carcinoma (HCC) liver nodule hypervascularization is a prerequisite for certain intrahepatic antitumor therapies. Early dynamic (ED) (18)F-FDG PET/CT could serve this purpose when the current standard method, contrast-enhanced (CE) CT, or other CE morphologic imaging modalities are unsuitable. A recent study showed ED (18)F-FDG PET/CT efficacy in this setting but applied a larger-than-standard (18)F-FDG activity and an elaborate protocol likely to hinder routine use. We developed a simplified protocol using standard activities and easily generated visual and descriptive or quantitative endpoints. This pilot study assessed the ability of these endpoints to detect HCC hyperperfusion and, thereby, evaluated the suitability in of the protocol everyday practice. Twenty-seven patients with 34 HCCs (diameter ≥ 1.5 cm) with hypervascularization on 3-phase CE CT underwent liver ED (18)F-FDG PET for 240 s, starting with (18)F-FDG (250-MBq bolus injection). Four frames at 15-s intervals, followed by 3 frames at 60-s intervals were reconstructed. Endpoints included focal tracer accumulation in the first 4 frames (60 s), subsequent focal washout, and visual and quantitative differences between tumor and liver regions of interest in maximum and mean ED standardized uptake value (ED SUVmax and ED SUVmean, respectively) 240-s time-activity curves. All 34 lesions were identified by early focal (18)F-FDG accumulation and faster time-to-peak ED SUVmax or ED SUVmean than in nontumor tissue. Tumor peak ED SUVmax and ED SUVmean exceeded liver levels in 85% and 53%, respectively, of lesions. Nadir tumor signal showed no consistent pattern relative to nontumor signal. HCC had a significantly shorter time to peak and significantly faster rate to peak for both ED SUVmax and ED SUVmean curves and a significantly higher peak ED SUVmax but not peak ED SUVmean than the liver. This pilot study

  6. CCR4 is expressed on infiltrating cells in lesional skin of early mycosis fungoides and atopic dermatitis.

    PubMed

    Sugaya, Makoto; Morimura, Sohshi; Suga, Hiraku; Kawaguchi, Makiko; Miyagaki, Tomomitsu; Ohmatsu, Hanako; Fujita, Hideki; Sato, Shinichi

    2015-06-01

    CCR4 is expressed on tumor cells of mycosis fungoides (MF) and Sézary syndrome (SS). In MF, most infiltrating cells in patches and plaques express CXCR3, while tumor cells express CCR4 in advanced stages. Poteligeo Test IHC (CCR4 staining kit) is a newly developed staining kit that can examine the presence of CCR4 expressed on tumor cells of adult T-cell leukemia/lymphoma, peripheral T-cell lymphoma and cutaneous T-cell lymphoma before treatment of anti-CCR4 antibody using paraffin-embedded samples. In this study, we analyzed CCR4 expression in lesional skin of MF, SS, atopic dermatitis (AD) and psoriasis with this new kit. CCR4 was expressed on infiltrating cells in lesional skin of patch, plaque, tumor MF and SS, and the number of positive cells increased as the disease progressed. Immunohistochemistry with frozen sections also showed some positive cells scattered in the dermis, although the quality was not high enough to quantify positive cells. There were significant positive correlations between CCR4(+) cells and serum lactate dehydrogenase levels. Interestingly, CCR4(+) cells were also detected in AD skin, whose number was larger than that in psoriatic skin. Previous studies showed only scattered CCR4(+) cells in skin samples by standard immunohistochemical staining. The new, sensitive CCR4 staining kit has revealed that CCR4 is expressed on infiltrating cells in lesional skin of early MF and AD as well as advanced MF and SS. These cells can be therapeutic targets for patients who are resistant to standard treatments. © 2015 Japanese Dermatological Association.

  7. Quantitative susceptibility mapping of multiple sclerosis lesions at various ages.

    PubMed

    Chen, Weiwei; Gauthier, Susan A; Gupta, Ajay; Comunale, Joseph; Liu, Tian; Wang, Shuai; Pei, Mengchao; Pitt, David; Wang, Yi

    2014-04-01

    To assess multiple sclerosis (MS) lesions at various ages by using quantitative susceptibility mapping (QSM) and conventional magnetic resonance (MR) imaging. Retrospectively selected were 32 clinically confirmed MS patients (nine men and 23 women; 39.3 years ± 10.9) who underwent two MR examinations (interval, 0.43 years ± 0.16) with three-dimensional gradient-echo sequence from August 2011 to August 2012. To estimate the ages of MS lesions, MR examinations performed 0.3-10.6 years before study examinations were studied. Hyperintensity on T2-weighted images was used to define MS lesions. QSM images were reconstructed from gradient-echo data. Susceptibility of MS lesions and temporal rates of change were obtained from QSM images. Lesion susceptibilities were analyzed by t test with intracluster correlation adjustment and Bonferroni correction in multiple comparisons. MR imaging of 32 patients depicted 598 MS lesions, of which 162 lesions (27.1%) in 23 patients were age measurable and six (1.0%) were only visible at QSM. The susceptibilities relative to normal-appearing white matter (NAWM) were 0.53 ppb ± 3.34 for acute enhanced lesions, 38.43 ppb ± 13.0 (positive; P < .01) for early to intermediately aged nonenhanced lesions, and 4.67 ppb ± 3.18 for chronic nonenhanced lesions. Temporal rates of susceptibility changes relative to cerebrospinal fluid were 12.49 ppb/month ± 3.15 for acute enhanced lesions, 1.27 ppb/month ± 2.31 for early to intermediately aged nonenhanced lesions, and -0.004 ppb/month ± 0 for chronic nonenhanced lesions. Magnetic susceptibility of MS lesions increased rapidly as it changed from enhanced to nonenhanced, it attained a high susceptibility value relative to NAWM during its initial few years (approximately 4 years), and it gradually dissipated back to susceptibility similar to that of NAWM as it aged, which may provide new insight into pathophysiologic features of MS lesions. Online supplemental material is available for this

  8. [Precancerous conditions and lesions of the stomach].

    PubMed

    Falt, P; Hanousek, M; Kundrátová, E; Urban, O

    2013-01-01

    Gastric carcinoma is a common malignant disease associated with an unfavorable prognosis in the case of late dia-gnosis. The most significant precancerous condition is chronic atrophic gastritis and intestinal metaplasia caused by Helicobacter pylori infection. These longlasting changes may lead to formation of dysplastic precancerous lesions. Upper endoscopy and histologic examination of forceps bio-psy specimens play a key role in the dia-gnosis of gastric precancerous conditions and lesions. Helicobacter pylori eradication therapy and endoscopic surveillance are main therapeutic modalities of gastric precancerous conditions. Localized precancerous lesions and early gastric neoplasia without the risk of lymphatic spread could be cured by means of endoscopic resection techniques.

  9. Supplementation with branched-chain amino acids inhibits azoxymethane-induced colonic preneoplastic lesions in male C57BL/KsJ-db/db mice.

    PubMed

    Shimizu, Masahito; Shirakami, Yohei; Iwasa, Junpei; Shiraki, Makoto; Yasuda, Yoichi; Hata, Kazuya; Hirose, Yoshinobu; Tsurumi, Hisashi; Tanaka, Takuji; Moriwaki, Hisataka

    2009-05-01

    Obesity and related metabolic abnormalities, including insulin resistance and activation of the insulin-like growth factor (IGF)/IGF-I receptor (IGF-IR) axis, are risk factors for colon cancer. Supplementation with branched-chain amino acids (BCAA) reduces the risk of liver cancer in cirrhotic patients who are obese, and this has been associated with an improvement of insulin resistance. The present study examined the effects of BCAA on the development of azoxymethane (AOM)-initiated colonic premalignant lesions in C57BL/KsJ-db/db (db/db) mice that were obese and had hyperinsulinemia. Male db/db mice were given 4 weekly s.c. injections of AOM (15 mg/kg of body weight) and then they were fed a diet containing 3.0% BCAA or casein, a nitrogenc content-matched control diet, for 7 weeks. Feeding with BCAA caused a significant reduction in the number of total aberrant crypt foci and beta-catenin accumulated crypts, both of which are premalignant lesions of the colon, compared with the control diet-fed groups. BCAA supplementation caused a marked decrease in the expression of IGF-IR, the phosphorylated form of IGF-IR, phosphorylated glycogen synthase kinase 3beta, phosphorylated Akt, and cyclooxygenase-2 proteins on the colonic mucosa of AOM-treated mice. The serum levels of insulin, IGF-I, IGF-II, triglyceride, total cholesterol, and leptin were also decreased by supplementation with BCAA. BCAA supplementation in diet improves insulin resistance and inhibits the activation of the IGF/IGF-IR axis, thereby preventing the development of colonic premalignancies in an obesity-related colon cancer model that was also associated with hyperlipidemia and hyperinsulinemia. BCAA, therefore, may be a useful chemoprevention modality for colon cancer in obese people.

  10. Autofluorescence bronchoscopy with white light bronchoscopy compared with white light bronchoscopy alone for the detection of precancerous lesions: a European randomised controlled multicentre trial.

    PubMed

    Häussinger, K; Becker, H; Stanzel, F; Kreuzer, A; Schmidt, B; Strausz, J; Cavaliere, S; Herth, F; Kohlhäufl, M; Müller, K-M; Huber, R-M; Pichlmeier, U; Bolliger, Ch T

    2005-06-01

    The potential of autofluorescence bronchoscopy (AFB) to detect precancerous lesions in the central airways and its role in lung cancer screening is uncertain. A study was undertaken to evaluate the prevalence of moderate/severe dysplasia (dysplasia II-III) and carcinoma in situ (CIS) using a newly developed AFB system in comparison with conventional white light bronchoscopy (WLB) alone. In a prospective randomised multicentre trial, smokers > or = 40 years of age (> or = 20 pack-years) were stratified into four different risk groups and investigated with either WLB+AFB (arm A) or WLB alone (arm B). 1173 patients (916 men) of mean age 58.7 years were included. Overall (arms A and B), preinvasive lesions (dysplasia II-III and CIS) were detected in 3.9% of the patients. The prevalence of patients with preinvasive lesions in the WLB arm was 2.7% compared with 5.1% in the WLB+AFB arm (p = 0.037). For patients with dysplasia II-III, WLB+AFB increased the detection rate by a factor of 2.1 (p = 0.03), while for CIS the factor was only 1.24 (p = 0.75). The biopsy based sensitivity of WLB alone and WLB+AFB for detecting dysplasia II-III and CIS was 57.9% compared with 82.3% (1.42-fold increase). The corresponding specificity was 62.1% compared with 58.4% (0.94-fold decrease). This first randomised study of AFB showed that the combination of WLB+AFB was significantly superior to WLB alone in detecting preneoplastic lesions. Our findings do not support the general use of AFB as a screening tool for lung cancer, but suggest that it may be of use in certain groups. The precise indications await further study.

  11. Autofluorescence bronchoscopy with white light bronchoscopy compared with white light bronchoscopy alone for the detection of precancerous lesions: a European randomised controlled multicentre trial

    PubMed Central

    Haussinger, K; Becker, H; Stanzel, F; Kreuzer, A; Schmidt, B; Strausz, J; Cavaliere, S; Herth, F; Kohlhaufl, M; Muller, K; Huber, R; Pichlmeier, U; Bolliger, C.

    2005-01-01

    Background: The potential of autofluorescence bronchoscopy (AFB) to detect precancerous lesions in the central airways and its role in lung cancer screening is uncertain. A study was undertaken to evaluate the prevalence of moderate/severe dysplasia (dysplasia II–III) and carcinoma in situ (CIS) using a newly developed AFB system in comparison with conventional white light bronchoscopy (WLB) alone. Methods: In a prospective randomised multicentre trial, smokers ⩾40 years of age (⩾20 pack-years) were stratified into four different risk groups and investigated with either WLB+AFB (arm A) or WLB alone (arm B). Results: 1173 patients (916 men) of mean age 58.7 years were included. Overall (arms A and B), preinvasive lesions (dysplasia II–III and CIS) were detected in 3.9% of the patients. The prevalence of patients with preinvasive lesions in the WLB arm was 2.7% compared with 5.1% in the WLB+AFB arm (p = 0.037). For patients with dysplasia II–III, WLB+AFB increased the detection rate by a factor of 2.1 (p = 0.03), while for CIS the factor was only 1.24 (p = 0.75). The biopsy based sensitivity of WLB alone and WLB+AFB for detecting dysplasia II–III and CIS was 57.9% compared with 82.3% (1.42-fold increase). The corresponding specificity was 62.1% compared with 58.4% (0.94-fold decrease). Conclusions: This first randomised study of AFB showed that the combination of WLB+AFB was significantly superior to WLB alone in detecting preneoplastic lesions. Our findings do not support the general use of AFB as a screening tool for lung cancer, but suggest that it may be of use in certain groups. The precise indications await further study. PMID:15923251

  12. Circulating microRNA-22-3p Predicts the Malignant Progression of Precancerous Gastric Lesions from Intestinal Metaplasia to Early Adenocarcinoma.

    PubMed

    Chen, Tsung-Hsing; Chiu, Cheng-Tang; Lee, Chieh; Chu, Yin-Yi; Cheng, Hao-Tsai; Hsu, Jun-Te; Wu, Ren-Chin; Yeh, Ta-Sen; Lin, Kwang-Huei

    2018-05-07

    Gastric cancer has a poor outcome and identifying useful biomarkers from peripheral blood or tissue could allow its early detection, or potentially precancerous changes, thus improving the curative rates. MicroRNAs (miRNAs) have been shown to offer great potential in cancer diagnosis and prediction. Here, we investigated the role of plasma miRNAs in the natural course of gastric cancer, from intestinal metaplasia to early cancer. The findings were used to understand whether patients at a high risk of malignancy could be given appropriate interventions in the early disease process, such as using endoscopic submucosal dissection to treat gastric dysplasia or early gastric cancer. Participants were divided into healthy control, intestinal metaplasia (IM), and dysplasia/early cancer (pT1a/b) groups. Microarray was used to select potential markers in tissue. Quantitative real-time polymerase chain reaction data showed circulating miRNA-22-3p had significantly different expression in patients with precancerous lesions or gastric adenocarcinoma. The areas under the curve of incomplete IM versus healthy control, low-grade/high-grade dysplasia, early gastric cancer, and GED were 0.8080, 0.8040, 0.8494, and 0.8095, respectively (all P values < 0.05). Circulating miRNA-22-3p could be a potential biomarker for gastric precancerous dysplasia and early cancer detection.

  13. The microbiome modulates the tumor macroenvironment

    PubMed Central

    Erdman, Susan E; Poutahidis, Theofilos

    2014-01-01

    Earlier investigations of the tumor microenvironment unveiled systemic networks presenting novel therapeutic opportunities. It has been recently shown that gut microbes modulate whole host immune and neuroendocrine factors impacting the fate of distant preneoplastic lesions toward malignancy or regression. These findings establish a new paradigm of holobiont therapeutic engineering in emerging tumor macroenvironments. PMID:25050199

  14. Promoting Effects of Potassium Dibasic Phosphate on Early‐stage Renal Carcinogenesis in Unilaterally Nephrectomized Rats Treated with N‐Ethyl‐N‐hydroxyethylnitrosamine

    PubMed Central

    Konishi, Noboru; Nakaoka, Shingo; Nakamura, Toshimitsu; Nishii, Kiyoji; Ohshima, Masato

    1992-01-01

    The effects of potassium dibasic phosphate (PDP), potassium aluminum sulfate (PAS) and copper sulfate (CS) on early‐stage renal carcinogenesis were investigated in unilaterally nephrectomized male Wistar rats after N‐ethyl‐N‐hydroxyethylnitrosamine (EHEN) administration. After feeding 1,000 ppm EHEN, or basal diet for 2 weeks and removal of the left kidney at week 3, male Wistar rats were divided into 8 groups of 20 rats each. These groups received the following dietary treatments: 50,000 ppm PDP, 50,000 ppm PAS, 5,000 ppm CS or basal diet, respectively, for 18 weeks from weeks 3 to 20. The average numbers of adenomatous hyperplasias counted as preneoplastic lesions in the EHEN with 50,000 ppm PDP group were significantly higher than in the EHEN alone group or the EHEN followed by 50,000 ppm PAS or 5,000 ppm CS group. The treatment with 50,000 ppm PDP induced renal calcification and promoted the development of preneoplastic lesions in unilaterally nephrectomized rats treated with EHEN, but that with 50,000 ppm PAS or 5,000 ppm CS did not. PMID:1517146

  15. Diode laser treatment and clinical management of multiple oral lesions in patients with hereditary haemorrhagic telangiectasia.

    PubMed

    Favia, G; Tempesta, A; Limongelli, L; Suppressa, P; Sabbà, C; Maiorano, E

    2016-05-01

    Hereditary haemorrhagic telangiectasia (HHT) is rare, and characterised by vascular dysplasia that leads to various symptoms including visceral arteriovenous malformations and mucocutaneous telangiectatic lesions. Our aim was to describe the clinical features and options for the treatment of multiple oral lesions, and to illustrate the efficacy of the diode laser in the treatment of early (<2mm) and advanced lesions (2mm or more). We report 24 patients with 1200 oral telangiectatic lesions, which were often associated with regular bleeding (from monthly to daily), superinfection, pain, and swelling, and treated with multiple sessions of laser according to the number and size of the lesions. Early lesions were treated with a single laser impulse in ultrapulsed mode, and advanced lesions with repeated laser impulses in pulsed mode (t-on 200ms/t-off 500ms), at a power of 8W. Early lesions healed completely after laser photocoagulation with no operative or postoperative complications, while advanced lesions improved with a remarkable reduction in size but more discomfort. Protective occlusal plates were sometimes used to reduce the incidence of new lesions caused by dental trauma. The treatment of oral telangiectatic lesions is still being debated, and it is important to improve quality of life for patients. Diode laser surgery could be an effective treatment for oral lesions in those with hereditary haemorrhagic telangiectasia. Copyright © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  16. Remineralization of early enamel caries lesions using different bioactive elements containing toothpastes: An in vitro study.

    PubMed

    Wang, Yu; Mei, Li; Gong, Lin; Li, Jialing; He, Shaowei; Ji, Yan; Sun, Weibin

    2016-09-14

    found in surface hardness and roughness between Colgate Sensitive Pro-Relief and NovaMin® during the pH-cycling test and acid resistance test (P= 0.45 and P= 0.83, respectively). Colgate Sensitive Pro-Relief and NovaMin® present an advantage in enhancing remineralization and inhibiting demineralization for early enamel carious lesions in comparison with GC Tooth Mousse.

  17. A Retrospective Study of the Prevalence and Classification of Intestinal Neoplasia in Zebrafish (Danio Rerio)

    PubMed Central

    Paquette, Colleen E.; Buchner, Cari; Tanguay, Robert L.; Guillemin, Karen; Mason, Timothy J.; Peterson, Tracy S.

    2013-01-01

    Abstract For over a decade, spontaneous intestinal neoplasia has been observed in zebrafish (Danio rerio) submitted to the ZIRC (Zebrafish International Resource Center) diagnostic service. In addition, zebrafish displayed preneoplastic intestinal changes including hyperplasia, dysplasia, and enteritis. A total of 195 zebrafish, representing 2% of the total fish submitted to the service, were diagnosed with these lesions. Neoplastic changes were classified either as adenocarcinoma or small cell carcinoma, with a few exceptions (carcinoma not otherwise specified, tubular adenoma, and tubulovillous adenoma). Tumor prevalence appeared similarly distributed between sexes and generally occurred in zebrafish greater than 1 year of age, although neoplastic changes were observed in fish 6 months of age. Eleven lines displayed these preneoplastic and neoplastic changes, including wild-types and mutants. Affected zebrafish originated from 18 facilities, but the majority of fish were from a single zebrafish research facility (hereafter referred to as the primary facility) that has submitted numerous samples to the ZIRC diagnostic service. Zebrafish from the primary facility submitted as normal sentinel fish demonstrate that these lesions are most often subclinical. Fish fed the diet from the primary facility and held at another location did not develop intestinal lesions, indicating that diet is not the etiologic agent. PMID:23544991

  18. Oral mucosal lesions during orthodontic treatment.

    PubMed

    Baricevic, Marinka; Mravak-Stipetic, Marinka; Majstorovic, Martina; Baranovic, Marijan; Baricevic, Denis; Loncar, Bozana

    2011-03-01

    Oral mucosal lesions can result from irritation caused by orthodontic appliances or malocclusion, but their frequency is not known. To examine the frequency of oral mucosal lesions in wearers of orthodontic appliances in comparison to children with malocclusion. This study comprised 111 subjects: 60 wearers of orthodontic appliances and 51 controls (aged between 6 and 18 years). Type and severity of mucosal lesions, their topography, gingival inflammation, and oral hygiene status were determined by using clinical indices. Mucosal lesions were more present in wearers of orthodontic appliances than in children with malocclusion. Gingival inflammation, erosion, ulceration, and contusion were the most common findings in orthodontic patients. The severity of gingival inflammation was in correlation with oral hygiene status; the poorer oral hygiene, the more severe gingival inflammation was. Better oral hygiene status was found in children during orthodontic treatment than in children with malocclusion. Orthodontic treatment carries a higher risk of mucosal lesions and implies greater awareness of better oral hygiene as shown by the results of this study. Oral hygiene instructions and early treatment of oral lesions are important considerations in better patient's motivation, treatment planning, and successful outcome. © 2010 The Authors. International Journal of Paediatric Dentistry © 2010 BSPD, IAPD and Blackwell Publishing Ltd.

  19. [Vascular Lesions of Vocal Folds - Part 2: Perpendicular Vascular Lesions].

    PubMed

    Arens, C; Glanz, H; Voigt-Zimmermann, S

    2015-11-01

    The present work aims at a systematic pathogenetic description of perpendicular vascular changes in the vocal folds. Unlike longitudinal vascular changes, like ectasia and meander, perpendicular vascular changes can be observed in bening lesions. They predominantly occur as typical vascular loops in exophytic lesions, especially in recurrent respiratory papillomatosis (RRP), pre-cancerous and cancerous diseases of the larynx and vocal folds. Neoangiogenesis is caused by an epithelial growth stimulus in the early phase of cancerous genesis. In RRP the VVC impress by a single, long vessel loop with a narrow angle turning point in the each single papilla of the papilloma. In pre- and cancerous lesions the vascular loop is located directly underneath the epithelium. During progressive tumor growth, vascular loops develop an increasingly irregular, convoluted, spirally shape. The arrangement of the vascular loops is primarily still symmetrical. In the preliminary stage of tumor development occurs by neoangiogenesis to a microvascular compression. In advanced vocal fold carcinoma the regular vascular vocal fold structure is destroyed. The various stages of tumor growth are also characterized by typical primary epithelial and secondary connective tissue changes. The characteristic triad of vascular, epithelial and connective tissue changes therefore plays an important role in differential diagnosis. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Chrysin abrogates early hepatocarcinogenesis and induces apoptosis in N-nitrosodiethylamine-induced preneoplastic nodules in rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Khan, Mahaboob S.; Department of Biochemistry, Govt. Home Science College, Panjab University, Chandigarh; Devaraj, Halagowder

    Flavonoids possess strong anti-oxidant and cancer chemopreventive activities. Chrysin (5,7-dihydroxyflavone) occurs naturally in many plants, honey, and propolis. In vitro, chrysin acts as a general anti-oxidant, causes cell cycle arrest and promotes cell death. However, the mechanism by which chrysin inhibits cancer cell growth and the subcellular pathways activated remains poorly understood. Effect of dietary supplementation with chrysin on proliferation and apoptosis during diethylnitrosamine (DEN)-induced early hepatocarcinogenesis was investigated in male Wistar rats. To induce hepatocarcinogenesis, rats were given DEN injections (i.p., 200 mg/kg) three times at a 15 day interval. An oral dose of chrysin (250 mg/kg bodyweight) wasmore » given three times weekly for 3 weeks, commencing 1 week after the last dose of DEN. Changes in the mRNA expression of COX-2, NFkB p65, p53, Bcl-xL and {beta}-arrestin-2 were assessed by quantitative real-time PCR. Changes in the protein levels were measured by western blotting. Chrysin administration significantly (P < 0.001) reduced the number and size of nodules formed. Also, a significant (P < 0.01) reduction in serum activities of AST, ALT, ALP, LDH and {gamma}GT was noticed. Expression of COX-2 and NFkB p65 was significantly reduced whereas that of p53, Bax and caspase 3 increased at the mRNA and protein levels. Likewise, a decrease in levels of {beta}-arrestin and the anti-apoptotic marker Bcl-xL was also noted. These findings suggest that chrysin exerts global hepato-protective effect and its chemopreventive activity is associated with p53-mediated apoptosis during early hepatocarcinogenesis.« less

  1. Red lesion detection using background estimation and lesions characteristics in diabetic retinal image

    NASA Astrophysics Data System (ADS)

    Zhang, Dongbo; Peng, Yinghui; Yi, Yao; Shang, Xingyu

    2013-10-01

    Detection of red lesions [hemorrhages (HRs) and microaneurysms (MAs)] is crucial for the diagnosis of early diabetic retinopathy. A method based on background estimation and adapted to specific characteristics of HRs and MAs is proposed. Candidate red lesions are located by background estimation and Mahalanobis distance measure and then some adaptive postprocessing techniques, which include vessel detection, nonvessel exclusion based on shape analysis, and noise points exclusion by double-ring filter (only used for MAs detection), are conducted to remove nonlesion pixels. The method is evaluated on our collected image dataset, and experimental results show that it is better than or approximate to other previous approaches. It is effective to reduce the false-positive and false-negative results that arise from incomplete and inaccurate vessel structure.

  2. Automated detection of red lesions from digital colour fundus photographs.

    PubMed

    Jaafar, Hussain F; Nandi, Asoke K; Al-Nuaimy, Waleed

    2011-01-01

    Earliest signs of diabetic retinopathy, the major cause of vision loss, are damage to the blood vessels and the formation of lesions in the retina. Early detection of diabetic retinopathy is essential for the prevention of blindness. In this paper we present a computer-aided system to automatically identify red lesions from retinal fundus photographs. After pre-processing, a morphological technique was used to segment red lesion candidates from the background and other retinal structures. Then a rule-based classifier was used to discriminate actual red lesions from artifacts. A novel method for blood vessel detection is also proposed to refine the detection of red lesions. For a standarised test set of 219 images, the proposed method can detect red lesions with a sensitivity of 89.7% and a specificity of 98.6% (at lesion level). The performance of the proposed method shows considerable promise for detection of red lesions as well as other types of lesions.

  3. Flow Cytometric Analysis of Hepatocytes from Normal, PFDA, and PH/DEN/ PB-Treated Rats

    DTIC Science & Technology

    1989-12-31

    SUB-GROUP’ Perfluorodecanoic acid ( PFDA ); hepatocarcinogenesis; preneoplastic lesions; flow cytometry; imunotoxicitYyc3 1%&STRACT (Continue on...effects of perfluorodecanoic acid ( PFDA ). Flow cytometric evaluation of hepatocytes from PEDA-treated rats revealed an increase in size and granularity...was designed to generate preliminary information regarding the toxic and potential carcinogenic effects of perfluorodecanoic acid ( PFDA ) on rat

  4. The most common mistakes on dermatoscopy of melanocytic lesions

    PubMed Central

    Kamińska-Winciorek, Grażyna

    2015-01-01

    Dermatoscopy is a method of in vivo evaluation of the structures within the epidermis and dermis. Currently, it may be the most precise pre-surgical method of diagnosing melanocytic lesions. Diagnostic errors may result in unnecessary removal of benign lesions or what is even worse, they can cause early and very early melanomas to be overlooked. Errors in assessment of dermatoscopy can be divided into those arising from failure to maintain proper test procedures (procedural and technical errors) and knowledge based mistakes related to the lack of sufficient familiarity and experience in dermatoscopy. The article discusses the most common mistakes made by beginner or inexperienced dermatoscopists. PMID:25821425

  5. Casein phosphopeptide-amorphous calcium phosphate remineralization of primary teeth early enamel lesions.

    PubMed

    Zhou, Chunhua; Zhang, Dongliang; Bai, Yuxing; Li, Song

    2014-01-01

    Early childhood caries (ECC) is a serious problem that progresses rapidly and often goes untreated. Current traumatic treatments may be replaced by safe and effective remineralization at very early stages. The aim of this in vitro study was to evaluate the remineralization effects of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) paste on enamel lesions by assessing ultrastructure, nanomechanical properties, and compound and elemental analysis. Enamel specimens from 6-year-old children were divided into groups: (1) native enamel; (2) water as negative control; (3) 500ppm NaF as positive control; and (4-7) CPP-ACP paste for 4, 8, 12, and 24h, as test groups. Ultrastructure and roughness were observed by atomic force microscopy (AFM); nanohardness and elastic modulus were measured by nanoindentation; compound and crystal size of enamel surface patterns were investigated by X-ray diffractometer (XRD). An electron microprobe (EPMA) was used for element analysis. Data were analyzed using one-way ANOVA. The CPP-ACP paste repaired the microstructure of enamel, including prism and interprism, through significantly increased hydroxyapatite crystal size (12.06±0.21nm) and Ca/P molar ratios (1.637±0.096) as compared with NaF (8.56±0.13nm crystal size and 1.397±0.086 Ca/P, p<0.01). Both CPP-ACP and NaF decrease roughness, and increase the nanohardness and elastic modulus, with no significant differences between the materials. The CPP-ACP paste is more suitable for children than NaF, due to advantages for remineralization. The AFM, nanoindentation, EPMA, and XRD are very helpful methods for further understanding of microscale and nanoscale remineralization mechanisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Efficacy of the ViziLite system in the identification of oral lesions.

    PubMed

    Oh, Esther S; Laskin, Daniel M

    2007-03-01

    Early detection of oral cancer is crucial in improving survival rate. To improve early detection, the use of a dilute acetic acid rinse and observation under a chemiluminescent light (ViziLite; Zila Pharmaceuticals, Phoenix, AZ) has been recommended. However, to date, the contributions of the individual components of the system have not been studied. The present study was done to investigate the efficacy of the individual components of the ViziLite system in providing improved visualization of early oral mucosal lesions. A total of 100 patients, 39 males and 61 females, age 18 to 93 years (mean age, 44 years), who presented to the Virginia Commonwealth University School of Dentistry for dental screening were examined. There were 58 Caucasians, 29 African-Americans, 5 Hispanics, 6 Asians, and 2 of mixed ethnicity. Thirty-five patients smoked, 53 used alcohol, and 25 both smoked and drank. After written consent, the oral cavity was examined under incandescent light for soft tissue abnormalities. After 1-minute rinse with 1% acetic acid, the mouth was re-examined for additional mucosal abnormalities. Then, the mouth was examined once again using the ViziLite system's chemiluminescent light. Any lesions detected by these 3 examinations that were clinically undiagnosable were brush biopsied (Oral CDx) for determination of cellular representation. In the original examination of the 100 patients, 57 clinically diagnosable benign lesions (eg, linea alba, leukoedema) and 29 clinically undiagnosable lesions were detected. After the rinse, 6 additional diagnosable lesions (linea alba) and 3 undiagnosable lesions were found. No additional lesions were detected with the chemiluminescent light. Of the 32 undiagnosable lesions that were brush biopsied, 2 were positive for atypical cellular characterization and warranted further investigation with a scalpel biopsy. Neither of these lesions was found to be premalignant or malignant. Although the acid rinse accentuated some lesions

  7. Exhaustive physical exercise increases the number of colonic preneoplastic lesions in untrained rats treated with a chemical carcinogen.

    PubMed

    Demarzo, Marcelo Marcos Piva; Garcia, Sérgio Britto

    2004-12-08

    Aberrant crypt foci (ACF) have been used for early detection of factors that influence colorectal carcinogenesis in rats. It has been observed that exhaustive exercise increases free radical DNA oxidative damage and depresses immune function, events also related to the increased risk for cancer development. Fifteen days after a single exhaustive swimming bout in untrained rats treated with a colon carcinogen, we observed a statistically significant increased number of ACF when compared to the non-exercised group. Thus, we concluded that exhaustive exercise increased the susceptibility for colon cancer in rats. From our finding and literature data, we hypothesize that, similarly to the suggested relationship between exercise and infections, exercise could be protective against cancer or it could increase the risk for this disease depending on its type, dose and duration.

  8. Frequency and characteristics of dual pathology in patients with lesional epilepsy.

    PubMed

    Cendes, F; Cook, M J; Watson, C; Andermann, F; Fish, D R; Shorvon, S D; Bergin, P; Free, S; Dubeau, F; Arnold, D L

    1995-11-01

    We studied 167 patients who had identifiable lesions and temporal or extratemporal partial epilepsy. Pathology included neuronal migration disorders (NMDs) (48), low-grade tumors (52), vascular malformations (34), porencephalic cysts (16), and gliotic lesions as a result of cerebral insults early in life (17). MRI volumetric studies using thin (1.5- or 3-mm) coronal images were performed in all patients and in 44 age-matched normal controls. An atrophic hippocampal formation (HF), indicating dual pathology, was present in 25 patients (15%). Abnormal HF volumes were present in those with lesions involving temporal (17%) but also extratemporal (14%) areas. Age at onset and duration of epilepsy did not influence the presence of HF atrophy. However, febrile seizures in early childhood were more frequently, although not exclusively, found in patients with hippocampal atrophy. The frequency of hippocampal atrophy in our patients with low-grade tumors (2%) and vascular lesions (9%) was low. Dual pathology was far more common in patients with NMDs (25%), porencephalic cysts (31%), and reactive gliosis (23.5%). Some structural lesions, such as NMDs, are more likely to be associated with hippocampal atrophy, independent of the distance of the lesion from the HF. In other types of lesions, such as vascular malformations, dual pathology was found when the lesion was close to the HF. A common pathogenic mechanism during pre- or perinatal development may explain the occurrence of concomitant mesial temporal sclerosis and other structural lesions because of either (1) associated developmental abnormalities or (2) predisposition to prolonged febrile convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Silica-induced Chronic Inflammation Promotes Lung Carcinogenesis in the Context of an Immunosuppressive Microenvironment12

    PubMed Central

    Freire, Javier; Ajona, Daniel; de Biurrun, Gabriel; Agorreta, Jackeline; Segura, Victor; Guruceaga, Elizabeth; Bleau, Anne-Marie; Pio, Ruben; Blanco, David; Montuenga, Luis M

    2013-01-01

    The association between inflammation and lung tumor development has been clearly demonstrated. However, little is known concerning the molecular events preceding the development of lung cancer. In this study, we characterize a chemically induced lung cancer mouse model in which lung cancer developed in the presence of silicotic chronic inflammation. Silica-induced lung inflammation increased the incidence and multiplicity of lung cancer in mice treated with N-nitrosodimethylamine, a carcinogen found in tobacco smoke. Histologic and molecular analysis revealed that concomitant chronic inflammation contributed to lung tumorigenesis through induction of preneoplastic changes in lung epithelial cells. In addition, silica-mediated inflammation generated an immunosuppressive microenvironment in which we observed increased expression of programmed cell death protein 1 (PD-1), transforming growth factor-β1, monocyte chemotactic protein 1 (MCP-1), lymphocyte-activation gene 3 (LAG3), and forkhead box P3 (FOXP3), as well as the presence of regulatory T cells. Finally, the K-RAS mutational profile of the tumors changed from Q61R to G12D mutations in the inflammatory milieu. In summary, we describe some of the early molecular changes associated to lung carcinogenesis in a chronic inflammatory microenvironment and provide novel information concerning the mechanisms underlying the formation and the fate of preneoplastic lesions in the silicotic lung. PMID:23908592

  10. Histogenesis of splenic lesions in Hodgkin's disease.

    PubMed

    Yam, L T; Li, C Y

    1976-12-01

    Histochemical markers were used to identify the various cellular and structural components of the human spleen, and to investigate the histogenesis of the splenic lesions of Hodgkin's disease. The early lesions appear in areas near the central artery (periarterial lymphatic sheath) in the white pulp. The white pulp becomes hypertrophic. The lesions enlarge, extend into the red pulp, and compress the sinuses and the cords of Billroth. The derivations of various "histiocytes" contained with the lesions are differentiated by using cytochemical stains for lysosomal enzymes and for granulocytes. The epithelioid cells in the granulomas are rich in those lysosomal enzymes typically seen in phagocytic histiocytes, suggesting that they are indeed true histiocytes. The malignant "histiocytes," including the mononuclear Hodgkin cells, the binucleated Sternberg-Reed cells, and the multinucleated giant cells, do not contain significant amounts of lysosomal enzymes and more closely resemble stimulated lymphocytes. The splenic lesions in Hodkin's disease may be the result of a lymphocytic and histiocytic cellular response to an unknown agent, which reaches the spleen through the central artery in the white pulp.

  11. Traumatic lesions of the posterior urethra.

    PubMed

    Velarde-Ramos, L; Gómez-Illanes, R; Campos-Juanatey, F; Portillo-Martín, J A

    2016-11-01

    The posterior urethral lesions are associated with pelvis fractures in 5-10% of cases. The posterior urethra is attached to the pelvis bone by puboprostatic ligaments and the perineal membrane, which explains why disruption of the pelvic ring can injure the urethra at this level. To identify suspected cases of posterior urethral trauma and to perform the diagnosis and its immediate or deferred management. Search in PubMed of articles related to traumatic posterior urethral lesions, written in English or Spanish. We reviewed the relevant publications including literature reviews and chapters from books related to the topic. With patients with pelvis fractures, we must always rule out posterior urethral lesions. The diagnostic examination of choice is retrograde urethrography, which, along with the severity of the condition, will determine the management in the acute phase and whether the treatment will be performed immediately or deferred. Early diagnosis and proper acute management decrease the associated complications, such as strictures, urinary incontinence and erectile dysfunction. Despite the classical association between posterior urethral lesions and pelvic fractures, the management of those lesions (whether immediate or deferred) remains controversial. Thanks to the growing interest in urethral disease, there are an increasing number of studies that help us achieve better management of these lesions. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Probiotic Dahi containing Lactobacillus acidophilus and Bifidobacterium bifidum modulates the formation of aberrant crypt foci, mucin-depleted foci, and cell proliferation on 1,2-dimethylhydrazine-induced colorectal carcinogenesis in Wistar rats.

    PubMed

    Mohania, Dheeraj; Kansal, Vinod K; Kruzliak, Peter; Kumari, Archana

    2014-08-01

    Aberrant crypt foci (ACF) and mucin-depleted foci (MDF) are pre-neoplastic lesions identified in the colon of carcinogen-treated rodents and in humans at high risk for colon cancer. The present study was carried out to divulge the protective potential of the probiotic Dahi containing Lactobacillus acidophilus LaVK2 and Bifidobacterium bifidum BbVK3 alone or in combination with piroxicam (PXC) on the development of early biomarkers of colorectal carcinogenesis in male Wistar rats administered 1,2-dimethylhydrazine (DMH). DMH was injected subcutaneously at the rate of 40 mg/kg body weight per animal twice a week for 2 weeks. A total of 120 male Wistar rats were randomly allocated to five groups, each group having 24 animals. The rats were fed with buffalo milk or probiotic supplement (20 grams) alone or as an adjunct with PXC in addition to a basal diet ad libitum for 32 weeks. Group I was offered buffalo milk (BM) and served as the control group. Group II was administered DMH along with BM and served as the DMH-control group; group III was administered BM-DMH-PXC, in which besides administering BM-DMH, PXC was also offered. Group IV was offered probiotic LaBb Dahi and DMH, and group V was offered both probiotic LaBb Dahi and PXC along with DMH. The rats were euthanized at the 8(th), 16(th), and 32(nd) week of the experiment and examined for development of ACF, aberrant crypts per ACF (AC/ACF), mucin-depleted foci (MDF), large MDF, and proliferating cell nuclear antigen (PCNA) labeling index. Administration of DMH in rats induced pre-neoplastic lesions (ACF and MDF) and increased the PCNA index in colorectal tissue. A significant (p<0.05) reduction in the number of ACF, AC/ACF, MDF, large MDF, and PCNA labeling index were observed in the probiotic LaBb Dahi group compared with the DMH control group. Feeding rats with LaBb Dahi or treatment with PXC diminished the initiation and progression of DMH-induced pre-neoplastic lesions and the PCNA index, and treatment with

  13. pH imaging reveals worsened tissue acidification in diffusion kurtosis lesion than the kurtosis/diffusion lesion mismatch in an animal model of acute stroke.

    PubMed

    Wang, Enfeng; Wu, Yin; Cheung, Jerry S; Zhou, Iris Yuwen; Igarashi, Takahiro; Zhang, XiaoAn; Sun, Phillip Zhe

    2017-10-01

    Diffusion weighted imaging (DWI) has been commonly used in acute stroke examination, yet a portion of DWI lesion may be salvageable. Recently, it has been shown that diffusion kurtosis imaging (DKI) defines the most severely damaged DWI lesion that does not renormalize following early reperfusion. We postulated that the diffusion and kurtosis lesion mismatch experience heterogeneous hemodynamic and/or metabolic injury. We investigated tissue perfusion, pH, diffusion, kurtosis and relaxation from regions of the contralateral normal area, diffusion lesion, kurtosis lesion and their mismatch in an animal model of acute stroke. Our study revealed significant kurtosis and diffusion lesion volume mismatch (19.7 ± 10.7%, P < 0.01). Although there was no significant difference in perfusion and diffusion between the kurtosis lesion and kurtosis/diffusion lesion mismatch, we showed lower pH in the kurtosis lesion (pH = 6.64 ± 0.12) from that of the kurtosis/diffusion lesion mismatch (6.84 ± 0.11, P < 0.05). Moreover, pH in the kurtosis lesion and kurtosis/diffusion mismatch agreed well with literature values for regions of ischemic core and penumbra, respectively. Our work documented initial evidence that DKI may reveal the heterogeneous metabolic derangement within the commonly used DWI lesion.

  14. Mesenchyme-derived factors enhance preneoplastic growth by non-genotoxic carcinogens in rat liver.

    PubMed

    Nejabat, Marzieh; Riegler, Teresa; Reitinger, Tabea; Subosits, Sandra; Römer, Michael; Eichner, Johannes; Bilban, Martin; Zell, Andreas; Huber, Wolfgang W; Schulte-Hermann, Rolf; Grasl-Kraupp, Bettina

    2018-02-01

    Many frequently prescribed drugs are non-genotoxic carcinogens (NGC) in rodent liver. Their mode of action and health risks for humans remain to be elucidated. Here, we investigated the impact of two model NGC, the anti-epileptic drug phenobarbital (PB) and the contraceptive cyproterone acetate (CPA), on intrahepatic epithelial-mesenchymal crosstalk and on growth of first stages of hepatocarcinogenesis. Unaltered hepatocytes (HC) and preneoplastic HC (HC PREN ) were isolated from rat liver for primary culture. DNA replication of HC and HC PREN was increased by in vitro treatment with 10 µM CPA, but not 1 mM PB. Next, mesenchymal cells (MC) obtained from liver of rats treated with either PB (50 mg/kg bw/day) or CPA (100 mg/kg bw/day), were cultured. Supernatants from both types of MC raised DNA synthesis of HC and HC PREN . This indicates that PB induces replication of HC and HC PREN only indirectly, via growth factors secreted by MC. CPA, however, acts on HC and HC PREN directly as well as indirectly via mesenchymal factors. Transcriptomics and bio-informatics revealed that PB and CPA induce extensive changes in the expression profile of MC affecting many growth factors and pathways. MC from PB-treated rats produced and secreted enhanced levels of HBEGF and GDF15, factors found to suppress apoptosis and/or induce DNA synthesis in cultured HC and HC PREN . MC from CPA-treated animals showed enhanced expression and secretion of HGF, which strongly raised DNA replication of HC and HC PREN . In conclusion, our findings reveal profound effects of two prototypical NGC on the hepatic mesenchyme. The resulting release of factors, which suppress apoptosis and/or enhance cell replication preferentially in cancer prestages, appears to be crucial for tumor promotion by NGC in the liver.

  15. Systematic alphanumeric-coded endoscopy versus chromoendoscopy for the detection of precancerous gastric lesions and early gastric cancer in subjects at average risk for gastric cancer.

    PubMed

    Pérez-Mendoza, A; Zárate-Guzmán, Á M; Galvis García, E S; Sobrino Cossío, S; Djamus Birch, J

    Gastric cancer is one of the main causes of cancer worldwide, but there is currently no global screening strategy for the disease. Endoscopy is the screening method of choice in some Asian countries, but no standardized technique has been recognized. Systematic alphanumeric-coded endoscopy can increase gastric lesion detection. The aim of the present article was to compare the usefulness of systematic alphanumeric-coded endoscopy with conventional endoscopy for the detection of premalignant lesions and early gastric cancer in subjects at average risk for gastric cancer. A cross-sectional, comparative, prospective, randomized study was conducted on patients at average risk for gastric cancer (40-50 years of age, no history of H. pylori infection, intestinal metaplasia, gastric atrophy, or gastrointestinal surgery). Before undergoing endoscopy, the patients had gastric preparation (200mg of oral acetylcysteine or 50mg of oral dimethicone). Conventional chromoendoscopy was performed with indigo carmine dye for contrast enhancement. Fifty consecutive cases (mean age 44.4 ± 3.34 years, 60% women, BMI 27.6 ± 5.82 kg/m 2 ) were evaluated. Endoscopic imaging quality was satisfactory in all the cases, with no differences between methods (p = 0.817). The detection rate of premalignant lesions and early gastric cancer was 14% (6 cases of intestinal metaplasia and one case of gastric adenocarcinoma). Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 100, 95, 80, 100 and 96%, respectively, for systematic alphanumeric-coded endoscopy, and 100, 45, 20, 100, and 52%, respectively, for conventional endoscopy. Lesion detection through systematic alphanumeric-coded endoscopy was superior to that of conventional endoscopy (p = 0.003; OR = 12). Both techniques were effective, but systematic alphanumeric-coded endoscopy significantly reduced the false positive rate. Copyright © 2018 Asociación Mexicana de

  16. Laser speckle imaging for lesion detection on tooth

    NASA Astrophysics Data System (ADS)

    Gavinho, Luciano G.; Silva, João. V. P.; Damazio, João. H.; Sfalcin, Ravana A.; Araujo, Sidnei A.; Pinto, Marcelo M.; Olivan, Silvia R. G.; Prates, Renato A.; Bussadori, Sandra K.; Deana, Alessandro M.

    2018-02-01

    Computer vision technologies for diagnostic imaging applied to oral lesions, specifically, carious lesions of the teeth, are in their early years of development. The relevance of this public problem, dental caries, worries countries around the world, as it affects almost the entire population, at least once in the life of each individual. The present work demonstrates current techniques for obtaining information about lesions on teeth by segmentation laser speckle imagens (LSI). Laser speckle image results from laser light reflection on a rough surface, and it was considered a noise but has important features that carry information about the illuminated surface. Even though these are basic images, only a few works have analyzed it by application of computer vision methods. In this article, we present the latest results of our group, in which Computer vision techniques were adapted to segment laser speckle images for diagnostic purposes. These methods are applied to the segmentation of images between healthy and lesioned regions of the tooth. These methods have proven to be effective in the diagnosis of early-stage lesions, often imperceptible in traditional diagnostic methods in the clinical practice. The first method uses first-order statistical models, segmenting the image by comparing the mean and standard deviation of the intensity of the pixels. The second method is based on the distance of the chi-square (χ2 ) between the histograms of the image, bringing a significant improvement in the precision of the diagnosis, while a third method introduces the use of fractal geometry, exposing, through of the fractal dimension, more precisely the difference between lesioned areas and healthy areas of a tooth compared to other methods of segmentation. So far, we can observe efficiency in the segmentation of the carious regions. A software was developed for the execution and demonstration of the applicability of the models

  17. Early malignant syphilis*

    PubMed Central

    Ortigosa, Yara Martins; Bendazzoli, Paulo Salomão; Barbosa, Angela Marques; Ortigosa, Luciena Cegatto Martins

    2016-01-01

    Early malignant syphilis is a rare and severe variant of secondary syphilis. It is clinically characterized by lesions, which can suppurate and be accompanied by systemic symptoms such as high fever, asthenia, myalgia, and torpor state. We report a diabetic patient with characteristic features of the disease showing favorable evolution of the lesions after appropriate treatment. PMID:28300925

  18. Surgical induction, histological evaluation, and MRI identification of cartilage necrosis in the distal femur in goats to model early lesions of osteochondrosis.

    PubMed

    Tóth, F; Nissi, M J; Wang, L; Ellermann, J M; Carlson, C S

    2015-02-01

    Identify and interrupt the vascular supply to portions of the distal femoral articular-epiphyseal cartilage complex (AECC) in goat kids to induce cartilage necrosis, characteristic of early lesions of osteochondrosis (OC); then utilize magnetic resonance imaging (MRI) to identify necrotic areas of cartilage. Distal femora were perfused and cleared in goat kids of various ages to visualize the vascular supply to the distal femoral AECC. Vessels located on the axial aspect of the medial femoral condyle (MFC) and on the abaxial side of the lateral trochlear ridge were transected in eight 4- to 5-day-old goats to induce cartilage necrosis. Goats were euthanized 1, 2, 3, 4, 5, 6, 9, and 10 weeks post operatively and operated stifles were harvested. Adiabatic T1ρ relaxation time maps of the harvested distal femora were generated using a 9.4 T MR scanner, after which samples were evaluated histologically. Interruption of the vascular supply to the MFC caused lesions of cartilage necrosis in 6/8 goat kids that were demonstrated histologically. Adiabatic T1ρ relaxation time mapping identified these areas of cartilage necrosis in 5/6 cases. No significant findings were detected after transection of perichondrial vessels supplying the lateral trochlear ridge. Cartilage necrosis, characteristic of early OC, can be induced by interrupting the vascular supply to the distal femoral AECC in goat kids. The ability of high field MRI to identify these areas of cartilage necrosis in the AECC using the adiabatic T1ρ sequence suggests that this technique may be useful in the future for the early diagnosis of OC. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  19. Reactive oral lesions associated with dental implants. A systematic review.

    PubMed

    Atarbashi-Moghadam, Fazele; Atarbashi-Moghadam, Saede; Namdari, Mahshid; Shahrabi-Farahani, Shokoufeh

    2018-05-11

    Reactive lesion formation around dental implants a complication that has been given much consideration. These lesions can lead to marginal bone loss, and consequently, implant failure. In the present systematic review, all reported reactive lesions associated with dental implants in the literature were assessed. An electronic search was performed using PubMed Central, Scopus, Google Scholar, and Science Direct. The search strategy was limited to human studies (case reports and case series), full-text English language articles, published until May 2017. A total of 19 articles reporting 27 lesions in 25 cases were included. Peripheral giant cell granuloma and pyogenic granuloma were the most reactive lesions found around dental implants. The mean age of the patients was 51.28 ± 14.48 years, with a slight female predilection. Posterior mandibular gingiva was the most common location for these lesions. The recurrence rate of lesions was 33.33%, and the chance of implant removal was 29.62%. Due to the clinical significance of these lesions, early histopathologic examination is recommended to exclude the presence of such pathological lesions. © 2018 John Wiley & Sons Australia, Ltd.

  20. The clonal origin and clonal evolution of epithelial tumours

    PubMed Central

    Garcia, Sergio Britto; Novelli, Marco; Wright, Nicholas A

    2000-01-01

    While the origin of tumours, whether from one cell or many, has been a source of fascination for experimental oncologists for some time, in recent years there has been a veritable explosion of information about the clonal architecture of tumours and their antecedents, stimulated, in the main, by the ready accessibility of new molecular techniques. While most of these new results have apparently confirmed the monoclonal origin of human epithelial (and other) tumours, there are a significant number of studies in which this conclusion just cannot be made. Moreover, analysis of many articles show that the potential impact of such considerations as patch size and clonal evolution on determinations of clonality have largely been ignored, with the result that a number of these studies are confounded. However, the clonal architecture of preneoplastic lesions provide some interesting insights — many lesions which might have been hitherto regarded as hyperplasias are apparently clonal in derivation. If this is indeed true, it calls into some question our hopeful corollary that a monoclonal origin presages a neoplastic habitus. Finally, it is clear, for many reasons, that methods of analysis which involve the disaggregation of tissues, albeit microdissected, are far from ideal and we should be putting more effort into techniques where the clonal architecture of normal tissues, preneoplastic and preinvasive lesions and their derivative tumours can be directly visualized in situ. PMID:10762440

  1. Thermographic diagnostics to discriminate skin lesions: a clinical study

    NASA Astrophysics Data System (ADS)

    Stringasci, Mirian Denise; Moriyama, Lilian Tan; Salvio, Ana Gabriela; Bagnato, Vanderlei Salvador; Kurachi, Cristina

    2015-06-01

    Cancer is responsible for about 13% of all causes of death in the world. Over 7 million people die annually of this disease. In most cases, the survival rates are greater when diagnosed in early stages. It is known that tumor lesions present a different temperature compared with the normal tissues. Some studies have been performed in an attempt to establish new diagnosis methods, targeting this temperature difference. In this study, we aim to investigate the use of a handheld thermographic camera to discriminate skin lesions. The patients presenting Basal Cell Carcinoma, Squamous Cell Carcinoma, Actinic Keratosis, Pigmented Seborrheic Keratosis, Melanoma or Intradermal Nevus lesions have been investigated at the Skin Departament of Amaral Carvalho Hospital. Patients are selected by a dermatologist, and the lesion images are recorded using an infrared camera. The images are evaluated taken into account the temperature level, and differences into lesion areas, borders, and between altered and normal skin. The present results show that thermography may be an important tool for aiding in the clinical diagnostics of superficial skin lesions.

  2. Automatic Classification of Specific Melanocytic Lesions Using Artificial Intelligence.

    PubMed

    Jaworek-Korjakowska, Joanna; Kłeczek, Paweł

    2016-01-01

    Given its propensity to metastasize, and lack of effective therapies for most patients with advanced disease, early detection of melanoma is a clinical imperative. Different computer-aided diagnosis (CAD) systems have been proposed to increase the specificity and sensitivity of melanoma detection. Although such computer programs are developed for different diagnostic algorithms, to the best of our knowledge, a system to classify different melanocytic lesions has not been proposed yet. In this research we present a new approach to the classification of melanocytic lesions. This work is focused not only on categorization of skin lesions as benign or malignant but also on specifying the exact type of a skin lesion including melanoma, Clark nevus, Spitz/Reed nevus, and blue nevus. The proposed automatic algorithm contains the following steps: image enhancement, lesion segmentation, feature extraction, and selection as well as classification. The algorithm has been tested on 300 dermoscopic images and achieved accuracy of 92% indicating that the proposed approach classified most of the melanocytic lesions correctly. A proposed system can not only help to precisely diagnose the type of the skin mole but also decrease the amount of biopsies and reduce the morbidity related to skin lesion excision.

  3. All-optical photoacoustic imaging and detection of early-stage dental caries

    NASA Astrophysics Data System (ADS)

    Sampathkumar, Ashwin; Hughes, David A.; Longbottom, Chris; Kirk, Katherine J.

    2015-02-01

    Dental caries remain one of the most common oral diseases in the world. Current detection methods, such as dental explorer and X-ray radiography, suffer from poor sensitivity and specificity at the earliest (and reversible) stages of the disease because of the small size (< 100 microns) of early-stage lesions. We have developed a fine-resolution (480 nm), ultra-broadband (1 GHz), all-optical photoacoustic imaging (AOPAI) system to image and detect early stages of tooth decay. This AOPAI system provides a non-contact, non-invasive and non-ionizing means of detecting early-stage dental caries. Ex-vivo teeth exhibiting early-stage, white-spot lesions were imaged using AOPAI. Experimental scans targeted each early-stage lesion and a reference healthy enamel region. Photoacoustic (PA) signals were generated in the tooth using a 532-nm pulsed laser and the light-induced broadband ultrasound signal was detected at the surface of the tooth with an optical path-stabilized Michelson interferometer operating at 532 nm. The measured time-domain signal was spatially resolved and back-projected to form 2D and 3D maps of the lesion using k-wave reconstruction methods. Experimental data collected from areas of healthy and diseased enamel indicate that the lesion generated a larger PA response compared to healthy enamel. The PA-signal amplitude alone was able to detect a lesion on the surface of the tooth. However, time- reversal reconstructions of the PA scans also quantitatively depicted the depth of the lesion. 3D PA reconstruction of the diseased tooth indicated a sub-surface lesion at a depth of 0.6 mm, in addition to the surface lesion. These results suggest that our AOPAI system is well suited for rapid clinical assessment of early-stage dental caries. An overview of the AOPAI system, fine-resolution PA and histology results of diseased and healthy teeth will be presented.

  4. Automatic colonic lesion detection and tracking in endoscopic videos

    NASA Astrophysics Data System (ADS)

    Li, Wenjing; Gustafsson, Ulf; A-Rahim, Yoursif

    2011-03-01

    The biology of colorectal cancer offers an opportunity for both early detection and prevention. Compared with other imaging modalities, optical colonoscopy is the procedure of choice for simultaneous detection and removal of colonic polyps. Computer assisted screening makes it possible to assist physicians and potentially improve the accuracy of the diagnostic decision during the exam. This paper presents an unsupervised method to detect and track colonic lesions in endoscopic videos. The aim of the lesion screening and tracking is to facilitate detection of polyps and abnormal mucosa in real time as the physician is performing the procedure. For colonic lesion detection, the conventional marker controlled watershed based segmentation is used to segment the colonic lesions, followed by an adaptive ellipse fitting strategy to further validate the shape. For colonic lesion tracking, a mean shift tracker with background modeling is used to track the target region from the detection phase. The approach has been tested on colonoscopy videos acquired during regular colonoscopic procedures and demonstrated promising results.

  5. THE SIGNIFICANCE OF LESIONS IN PERIPHERAL GANGLIA IN CHIMPANZEE AND IN HUMAN POLIOMYELITIS

    PubMed Central

    Bodian, David; Howe, Howard A.

    1947-01-01

    1. The peripheral ganglia of eighteen inoculated chimpanzees and thirteen uninoculated controls, and of eighteen fatal human poliomyelitis cases, were studied for histopathological evidence of the route of transmission of virus from the alimentary tract to the CNS. 2. Lesions thought to be characteristic of poliomyelitis in inoculated chimpanzees could not be sharply differentiated from lesions of unknown origin in uninoculated control animals. Moreover, although the inoculated animals as a group, in comparison with the control animals, had a greater number of infiltrative lesions in sympathetic as well as in sensory ganglia, it was not possible to make satisfactory correlations between the distribution of these lesions and the routes of inoculation. 3. In sharp contrast with chimpanzees, the celiac and stellate ganglia of the human poliomyelitis cases were free of any but insignificant infiltrative lesions. Lesions in human trigeminal and spinal sensory ganglia included neuronal damage as well as focal and perivascular inflitrative lesions, as is well known. In most ganglia, as in monkey and chimpanzee sensory ganglia, these were correlated in intensify with the degree of severity of lesions in the region of the CNS receiving their axons. This suggested that lesions in sensory ganglia probably resulted from spread of virus centrifugally from the CNS, in accord with considerable experimental evidence. 4. Two principal difficulties in the interpretation of histopathological findings in peripheral ganglia were revealed by this study. The first is that the specificity of lesions in sympathetic ganglia has not been established beyond doubt as being due to poliomyelitis. The second is that the presence of characteristic lesions in sensory ganglia does not, and cannot, reveal whether the virus reached the ganglia from the periphery or from the central nervous system, except in very early preparalytic stages or in exceptional cases of early arrest of virus spread and of

  6. Differentiation of early from advanced coronary atherosclerotic lesions: systematic comparison of CT, intravascular US, and optical frequency domain imaging with histopathologic examination in ex vivo human hearts.

    PubMed

    Maurovich-Horvat, Pál; Schlett, Christopher L; Alkadhi, Hatem; Nakano, Masataka; Stolzmann, Paul; Vorpahl, Marc; Scheffel, Hans; Tanaka, Atsushi; Warger, William C; Maehara, Akiko; Ma, Shixin; Kriegel, Matthias F; Kaple, Ryan K; Seifarth, Harald; Bamberg, Fabian; Mintz, Gary S; Tearney, Guillermo J; Virmani, Renu; Hoffmann, Udo

    2012-11-01

    To establish an ex vivo experimental setup for imaging coronary atherosclerosis with coronary computed tomographic (CT) angiography, intravascular ultrasonography (US), and optical frequency domain imaging (OFDI) and to investigate their ability to help differentiate early from advanced coronary plaques. All procedures were performed in accordance with local and federal regulations and the Declaration of Helsinki. Approval of the local Ethics Committee was obtained. Overall, 379 histologic cuts from nine coronary arteries from three donor hearts were acquired, coregistered among modalities, and assessed for the presence and composition of atherosclerotic plaque. To assess the discriminatory capacity of the different modalities in the detection of advanced lesions, c statistic analysis was used. Interobserver agreement was assessed with the Cohen κ statistic. Cross sections without plaque at coronary CT angiography and with fibrous plaque at OFDI almost never showed advanced lesions at histopathologic examination (odds ratio [OR]: 0.02 and 0.06, respectively; both P<.0001), while mixed plaque at coronary CT angiography, calcified plaque at intravascular US, and lipid-rich plaque at OFDI were associated with advanced lesions (OR: 2.49, P=.0003; OR: 2.60, P=.002; and OR: 31.2, P<.0001, respectively). OFDI had higher accuracy for discriminating early from advanced lesions than intravascular US and coronary CT angiography (area under the receiver operating characteristic curve: 0.858 [95% confidence interval {CI}: 0.802, 0.913], 0.631 [95% CI: 0.554, 0.709], and 0.679 [95% CI: 0.618, 0.740]; respectively, P<.0001). Interobserver agreement was excellent for OFDI and coronary CT angiography (κ=0.87 and 0.85, respectively) and was good for intravascular US (κ=0.66). Systematic and standardized comparison between invasive and noninvasive modalities for coronary plaque characterization in ex vivo specimens demonstrated that coronary CT angiography and intravascular US are

  7. Commensal bacteria modulate the tumor microenvironment.

    PubMed

    Poutahidis, Theofilos; Erdman, Susan E

    2016-09-28

    It has been recently shown that gut microbes modulate whole host immune and hormonal factors impacting the fate of distant preneoplastic lesions toward malignancy or regression. This raises the possibility that the tumor microenvironment interacts with broader systemic microbial-immune networks. These accumulated findings suggest novel therapeutic opportunities for holobiont engineering in emerging tumor microenvironments. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Lesion progression in post-treatment persistent endodontic lesions.

    PubMed

    Yu, Victoria Soo Hoon; Messer, Harold Henry; Shen, Liang; Yee, Robert; Hsu, Chin-ying Stephen

    2012-10-01

    Radiographic lesions related to root-filled teeth may persist for long periods after treatment and are considered to indicate failure of initial treatment. Persistent lesions are found in a proportion of cases, but information on lesion progression is lacking. This study examined the incidence of lesion improvement, remaining unchanged, and deterioration among persistent lesions in a group of patients recruited from a university-based clinic and identified potential predictors for lesion progression. Patients of a university clinic with persistent endodontic lesions at least 4 years since treatment and with original treatment radiographs available were recruited with informed consent. Data were obtained by interview and from dental records and clinical and radiographic examinations. Univariate and multivariate statistical analyses were carried out by using SPSS (version 19). One hundred fifty-one persistent lesions were identified in 114 patients. A majority of the lesions (107, 70.9%) received treatment between 4 and 5 years prior. Eighty-six lesions (57.0%) improved, 18 (11.9%) remained unchanged, and 47 (31.1%) deteriorated since treatment. Potential predictors for lesions that did not improve included recall lesion size, pain on biting at recall examination, history of a postobturation flare-up, and a non-ideal root-filling length (P < .05). Lesions that had persisted for a longer period appeared less likely to be improving (relative risk, 1.038; 95% confidence interval, 1.000-1.077). A specific time interval alone should not be used to conclude that a lesion will not resolve without intervention. This study identified several clinical factors that are associated with deteriorating persistent lesions, which should aid in identifying lesions that require further intervention. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  9. Computer-Aided Diagnosis of Micro-Malignant Melanoma Lesions Applying Support Vector Machines.

    PubMed

    Jaworek-Korjakowska, Joanna

    2016-01-01

    Background. One of the fatal disorders causing death is malignant melanoma, the deadliest form of skin cancer. The aim of the modern dermatology is the early detection of skin cancer, which usually results in reducing the mortality rate and less extensive treatment. This paper presents a study on classification of melanoma in the early stage of development using SVMs as a useful technique for data classification. Method. In this paper an automatic algorithm for the classification of melanomas in their early stage, with a diameter under 5 mm, has been presented. The system contains the following steps: image enhancement, lesion segmentation, feature calculation and selection, and classification stage using SVMs. Results. The algorithm has been tested on 200 images including 70 melanomas and 130 benign lesions. The SVM classifier achieved sensitivity of 90% and specificity of 96%. The results indicate that the proposed approach captured most of the malignant cases and could provide reliable information for effective skin mole examination. Conclusions. Micro-melanomas due to the small size and low advancement of development create enormous difficulties during the diagnosis even for experts. The use of advanced equipment and sophisticated computer systems can help in the early diagnosis of skin lesions.

  10. Global aphasia without hemiparesis: language profiles and lesion distribution

    PubMed Central

    Hanlon, R.; Lux, W.; Dromerick, A.

    1999-01-01

    OBJECTIVES—Global aphasia without hemiparesis (GAWH) is an uncommon stroke syndrome involving receptive and expressive language impairment, without the hemiparesis typically manifested by patients with global aphasia after large left perisylvian lesions. A few cases of GAWH have been reported with conflicting conclusions regarding pathogenesis, lesion localisation, and recovery. The current study was conducted to attempt to clarify these issues.
METHODS—Ten cases of GAWH were prospectively studied with language profiles and lesion analysis; five patients had multiple lesions, four patients had a single lesion, and one had a subarachnoid haemorrhage. Eight patients met criteria for cardioembolic ischaemic stroke.
RESULTS—Cluster analysis based on acute language profiles disclosed three subtypes of patients with GAWH; these clusters persisted on follow up language assessment. Each cluster evolved into a different aphasia subtype: persistent GAWH, Wernicke's aphasia, or transcortical motor aphasia (TCM). Composite lesion analysis showed that persistent GAWH was related to lesioning of the left superior temporal gyrus. Patients with acute GAWH who evolved into TCM type aphasia had common lesioning of the left inferior frontal gyrus and adjacent subcortical white matter. Patients with acute GAWH who evolved into Wernicke's type aphasia were characterised by lesioning of the left precentral and postcentral gyri. Recovery of language was poor in all but one patient.
CONCLUSIONS—Although patients with acute GAWH are similar on neurological examination, they are heterogeneous with respect to early aphasia profile, language recovery, and lesion profile.

 PMID:10084536

  11. Early storage lesions in apheresis platelets are induced by the activation of the integrin αIIbβ₃ and focal adhesion signaling pathways.

    PubMed

    Thiele, Thomas; Iuga, Cristina; Janetzky, Susann; Schwertz, Hansjorg; Gesell Salazar, Manuela; Fürll, Birgit; Völker, Uwe; Greinacher, Andreas; Steil, Leif

    2012-12-05

    Production and storage of platelet concentrates (PC) induce protein changes in platelets leading to impaired platelet function. This study aimed to identify signaling pathways involved in the development of early platelet storage lesions in apheresis-PCs stored in plasma or additive solution (PAS). Apheresis-PCs from four donors were stored in plasma or in PAS at 22°C (n=4 each). Platelets were analyzed at day 0 (production day) and after 1, 6 and 9 days of storage. Platelet response to agonists (TRAP, collagen, ADP) and to hypotonic shock decreased, CD62P expression increased in both storage media over time. Using DIGE 1550 protein spots were monitored and compared to baseline values at day 0. Platelets in plasma displayed changes in 352 spots (166/day 1, 263/day 6 and 201/day 9); in PAS 325 spots changed (202/day 1, 221/day 6, 200/day 9). LC-ESI-MS/MS analysis of 405 platelet proteins revealed 32 proteins changed during storage in plasma (9/day 1, 15/day 6 and 26/day 9) and 28 in PAS (5/day 1, 20/day 6, 26/day 9). Ingenuity pathway analysis found integrin-αII(b)β(3) and focal adhesion signaling pathways involved in early alterations, being confirmed by Western blotting. Corresponding mRNAs in platelets were identified by next generation sequencing for 84 changed proteins. Integrin-αII(b)β(3) and focal adhesion signaling cause irreversible early storage lesions in apheresis platelets. This article is part of a Special Issue entitled: Integrated omics. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Oral mucosal lesions in Anorexia Nervosa, Bulimia Nervosa and EDNOS.

    PubMed

    Panico, Rene; Piemonte, Eduardo; Lazos, Jerónimo; Gilligan, Gerardo; Zampini, Anibal; Lanfranchi, Héctor

    2018-01-01

    The aim of this study is to describe oral lesions in patients with eating disorders (ED), including Anorexia Nervosa (AN), Bulimia Nervosa (BN) and eating disorders not otherwise specified (EDNOS). A prospective case-control study was carried out from April 2003 to May 2004. Inclusion criteria for the study group were individuals with a diagnosis of ED; age and sex-matched individuals without ED were included as controls. Clinical data regarding ED, medical complications and oral examination were performed by previously calibrated professionals. Study group (n = 65) presented 46 cases of BN (71%), 13 of EDNOS (20%) and 6 of AN (9%); also, 94% (n = 61) showed oral lesions. The most common were: labial erythema, exfoliative cheilitis, orange-yellow palate, hemorrhagic lesions, lip-cheek biting and non-specific oral atrophies. Only two patients of the study group had dental erosions, and no case of major salivary gland swelling was found. ED display a wide array of oral mucosal lesions that can be regarded as their early manifestations. The dentist could be the first professional to detect symptoms of eating disorders, potentially improving early detection and treatment of ED. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Local Immune Responsiveness of Mice Bearing Premalignant Oral Lesions to PD-1 Antibody Treatment.

    PubMed

    Levingston, Corinne A; Young, M Rita I

    2017-06-02

    A carcinogen-induced premalignant oral lesion model that progresses to oral cancer was used to examine the immunological impact of a 5-week treatment regimen to block programmed cell death protein 1 (PD-1). PD-1 antibody treatment resulted in concurrent, but transient, increases in interleukin (IL)-2, IFN-γ and IL-17, and delayed increases in IL-6 and IL-10 within the lesion-bearing tongue epithelium. In contrast, cytokine secretion by lymph node cells of PD-1 antibody-treated mice was lower than for mice treated with control antibodies, with the exception of interferon (IFN)-γ, whose secretion increased late in the treatment period. This delayed secretion of IFN-γ coincided with an increase in CD4⁺ lymph node cells expressing IFN-γ. Lymph node cells of PD-1 antibody-treated mice reacted to a challenge with lysates of lesions or cancer by early production of IFN-γ, but this rapidly subsided. There also was increased production IL-17 and tumor necrosis factor (TNF)-α in response to the challenge, but the response was greatest by cells of control lesion-bearing mice. Clinical assessment showed an early but transient, stabilization of disease in mice treated with PD-1 antibody. These results show an early beneficial, but time-limited, response to PD-1 antibody treatment, which then fails with continued lesion progression.

  14. A clinicopathologic and epidemiologic study of chronic white lesions in the oral mucosa.

    PubMed

    Ghosh, Sampurna; Pal, Sudipta; Ghatak, Soumya; Saha, Somnath; Biswas, Surajit; Srivastava, Prabha

    2017-08-01

    Invasive oral squamous cell carcinoma is often preceded by the presence of clinically identifiable premalignant changes of the oral mucosa, including white lesions. We conducted a cross-sectional, observational study to assess the clinicopathologic and epidemiologic aspects of chronic oral mucosal white lesions to determine the necessity of early biopsy in these cases. Our study population was made up of 77 patients-50 males and 27 females, aged 15 to 70 years (mean: 42.9)-who presented with white lesions persisting for at least 4 weeks. All but 3 patients underwent a biopsy; the 3 exceptions were diagnosed with smear-proven candidiasis. Patients with moderate or severe dysplasia underwent an excision biopsy. The buccal mucosa was the single most common site of white lesions, occurring in 15 patients (19.5%), although 21 patients (27.3%) exhibited a diffuse involvement of the oral mucosa. Of the 77 patients, 59 (76.6%) had concerning findings: premalignant lesions in 45 patients (58.4%) and malignant lesions in 14 (18.2%). Also, dysplasia was seen in 8 patients (10.4%), all of whom had premalignant lesions. Tobacco chewing (p = 0.008) and betel quid chewing (p = 0.029) were significantly associated with the development of premalignant and malignant lesions; a longer duration of tobacco chewing (≥10 yr) was significantly associated with a higher risk of malignant but not premalignant lesions (p = 0.031). Finally, illiteracy was a significant risk factor for premalignant and malignant lesions (p = 0.03). Our findings support the necessity of biopsy in every case. Early detection of oral carcinoma by biopsy of all oral white lesions would not only prevent patients from undergoing disfiguring surgery and chemoradiation, but it also would increase the 5-year survival rate.

  15. [Penile fracture with associated urethra lesion: case report and bibliographic review].

    PubMed

    García Marchiñena, Patricio; Capiel, Leandro; Juarez, Diego; Liyo, Juan; Giudice, Carlos; Gueglio, Guillermo; Damia, Oscar

    2008-10-01

    Penile fracture is a rare lesion that occurs almost exclusively during erection. This lesion may be associated with rupture of the urethra in 20-30% of the cases. We describe a case that has been treated at our institution and review the literature. A-42-year-old patient suffered fracture of penis, with urethral section, during sexual intercourse. The patient underwent surgical exploration, the lesions of the corporal bodies and urethra were identified. Both lesions were repaired. patient's recovery was satisfactory without complications or esthetical or functional sequelae. Penile fracture with urethral section is an exceptional disease, the most frequent cause of which in occident is violent sexual activity. For diagnosis it is necessary in most cases a correct anamnesis and physical examination. Early surgical approach and closure of the albuginea's lesion and repair of the urethral lesion is the best way of treatment.

  16. Morel-Lavallée lesion: A closed degloving injury that requires real attention.

    PubMed

    Nair, Anirudh V; Nazar, Pk; Sekhar, Resmi; Ramachandran, Pv; Moorthy, Srikanth

    2014-07-01

    Morel-Lavallée lesions are post-traumatic, closed degloving injuries occurring deep to subcutaneous plane due to disruption of capillaries resulting in an effusion containing hemolymph and necrotic fat. Magnetic resonance imaging (MRI) is the modality of choice in the evaluation of Morel-Lavallée lesion. Early diagnosis and management is essential as any delay in diagnosis or missed lesion will lead to the effusion becoming infected or leading to extensive skin necrosis.

  17. Relationship between somatosensory deficit and brain somatosensory system after early brain lesion: A morphometric study.

    PubMed

    Perivier, Maximilien; Delion, Matthieu; Chinier, Eva; Loustau, Sebastien; Nguyen, Sylvie; Ter Minassian, Aram; Richard, Isabelle; Dinomais, Mickael

    2016-05-01

    Cerebral Palsy (CP) is a group of permanent motor disorders due to non-progressive damage to the developing brain. Poor tactile discrimination is common in children with unilateral CP. Previous findings suggest the crucial role of structural integrity of the primary (S1) and secondary (S2) somatosensory areas located in the ipsilesional hemisphere for somatosensory function processing. However, no focus on the relationship between structural characteristics of ipsilesional S1 and S2 and tactile discrimination function in paretic hands has been proposed. Using structural MRI and a two-point discrimination assessment (2 PD), we explore this potential link in a group of 21 children (mean age 13 years and 7 months) with unilateral CP secondary to a periventricular white matter injury (PWMI) or middle cerebral artery infarct (MCA). For our whole sample there was a significant negative correlation between the 2 PD and the gray matter volume in the ipsilesional S2 (rho = -0.50 95% confidence interval [-0.76, -0.08], one-tailed p-value = 0.0109) and in the ipsilesional S1 (rho = -0.57, 95% confidence interval [-0.81, -0.19], one-tailed p-value = 0.0032). When studying these relationships with regard to the lesion types, we found these correlations were non-significant in the patients with PWMI but stronger in patients with MCA. According to our results, the degree of sensory impairment is related to the spared gray matter volume in ipsilesional S1 and S2 and is marked after an MCA stroke. Our work contributes to a better understanding of why some patients with CP have variable somatosensory deficit following an early brain lesion. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  18. The formation of inflammatory demyelinated lesions in cerebral white matter

    PubMed Central

    Maggi, Pietro; Cummings Macri, Sheila M.; Gaitán, María I.; Leibovitch, Emily; Wholer, Jillian E; Knight, Heather L.; Ellis, Mary; Wu, Tianxia; Silva, Afonso C.; Massacesi, Luca; Jacobson, Steven; Westmoreland, Susan; Reich, Daniel S.

    2016-01-01

    Objective Vascular permeability and inflammatory demyelination are intimately linked in the brain, but what is their temporal relationship? We aimed to determine the radiological correlates of the earliest tissue changes accompanying demyelination in a primate model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in the common marmoset. Methods At 7 tesla MRI, T1 maps, proton density and T2-weighted images were acquired before and after EAE induction in 5 marmosets (every other week before lesions appeared, weekly thereafter). From scans before and after intravenous injection of contrast material, we measured the evolution of lesional blood-brain-barrier (BBB) permeability, comparing in vivo MRI to postmortem tissue examination. Results On average, BBB permeability increased 3.5 fold (p<0.0001) over the 4 weeks prior to lesion appearance. Permeability gradually decreased after lesion appearance, with attendant changes in the distribution of inflammatory cells (predominantly macrophages and microglia) and demyelination. On tissue analysis, we also identified small perivascular foci of microglia and T cells without blood-derived macrophages or demyelination. These foci had no visible MRI correlates, though permeability within the foci, but not outside, increased in the weeks before the animals died (p<0.0001). Interpretation This study provides compelling evidence that in marmoset EAE, which forms lesions strongly resembling those of MS, early changes in vascular permeability are associated with perivascular inflammatory cuffing and parenchymal microglial activation but precede the arrival of blood-derived monocytes that accompany demyelination. Prospective detection of transient permeability changes could afford an opportunity for early intervention to forestall tissue damage in newly forming lesions. PMID:25088017

  19. The formation of inflammatory demyelinated lesions in cerebral white matter.

    PubMed

    Maggi, Pietro; Macri, Sheila M Cummings; Gaitán, María I; Leibovitch, Emily; Wholer, Jillian E; Knight, Heather L; Ellis, Mary; Wu, Tianxia; Silva, Afonso C; Massacesi, Luca; Jacobson, Steven; Westmoreland, Susan; Reich, Daniel S

    2014-10-01

    Vascular permeability and inflammatory demyelination are intimately linked in the brain, but what is their temporal relationship? We aimed to determine the radiological correlates of the earliest tissue changes accompanying demyelination in a primate model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in the common marmoset. By 7T magnetic resonance imaging (MRI), T1 maps, proton density, and T2-weighted images were acquired before and after EAE induction in 5 marmosets (every other week before lesions appeared, weekly thereafter). From scans before and after intravenous injection of contrast material, we measured the evolution of lesional blood-brain barrier (BBB) permeability, comparing in vivo MRI to postmortem tissue examination. On average, BBB permeability increased 3.5-fold (p < 0.0001) over the 4 weeks prior to lesion appearance. Permeability gradually decreased after lesion appearance, with attendant changes in the distribution of inflammatory cells (predominantly macrophages and microglia) and demyelination. On tissue analysis, we also identified small perivascular foci of microglia and T cells without blood-derived macrophages or demyelination. These foci had no visible MRI correlates, although permeability within the foci, but not outside, increased in the weeks before the animals died (p < 0.0001). This study provides compelling evidence that in marmoset EAE, which forms lesions strongly resembling those of MS, early changes in vascular permeability are associated with perivascular inflammatory cuffing and parenchymal microglial activation but precede the arrival of blood-derived monocytes that accompany demyelination. Prospective detection of transient permeability changes could afford an opportunity for early intervention to forestall tissue damage in newly forming lesions. © 2014 American Neurological Association.

  20. Postoperative MRI Evaluation of a Radiofrequency Cordotomy Lesion for Intractable Cancer Pain

    PubMed Central

    Vedantam, A.; Hou, P.; Chi, T.L.; Hess, K.R; Dougherty, P.M.; Bruera, E.; Viswanathan, A.

    2017-01-01

    BACKGROUND AND PURPOSE There are limited data on the use of postoperative imaging to evaluate the cordotomy lesion. We aimed to describe the cordotomy lesion by using postoperative MR imaging in patients after percutaneous cordotomy for intractable cancer pain. MATERIALS AND METHODS Postoperative MR imaging and clinical outcomes were prospectively obtained for 10 patients after percutaneous cordotomy for intractable cancer pain. Area, signal intensity, and location of the lesion were recorded. Clinical outcomes were measured by using the Visual Analog Scale and the Brief Pain Inventory–Short Form, and correlations with MR imaging metrics were evaluated. RESULTS Ten patients (5 men, 5 women; mean age, 58.5 ± 9.6 years) were included in this study. The cordotomy lesion was hyperintense with central hypointense foci on T2-weighted MR imaging, and it was centered in the anterolateral quadrant at the C1–C2 level. The mean percentage of total cord area lesioned was 24.9% ± 7.9%, and most lesions were centered in the dorsolateral region of the anterolateral quadrant (66% of the anterolateral quadrant). The number of pial penetrations correlated with the percentage of total cord area that was lesioned (r = 0.78; 95% CI, 0.44–0.89; P = .008) and the length of T2-weighted hyperintensity (r = 0.85; 95% CI, 0.54–0.89; P = .002). No significant correlations were found between early clinical outcomes and quantitative MR imaging metrics. CONCLUSIONS We describe qualitative and quantitative characteristics of a cordotomy lesion on early postoperative MR imaging. The size and length of the lesion on MR imaging correlate with the number of pial penetrations. Larger studies are needed to further investigate the clinical correlates of MR imaging metrics after percutaneous cordotomy. PMID:28209581

  1. Visual navigation in adolescents with early periventricular lesions: knowing where, but not getting there.

    PubMed

    Pavlova, Marina; Sokolov, Alexander; Krägeloh-Mann, Ingeborg

    2007-02-01

    Visual navigation in familiar and unfamiliar surroundings is an essential ingredient of adaptive daily life behavior. Recent brain imaging work helps to recognize that establishing connectivity between brain regions is of importance for successful navigation. Here, we ask whether the ability to navigate is impaired in adolescents who were born premature and suffer congenital bilateral periventricular brain damage that might affect the pathways interconnecting subcortical structures with cortex. Performance on a set of visual labyrinth tasks was significantly worse in patients with periventricular leukomalacia (PVL) as compared with premature-born controls without lesions and term-born adolescents. The ability for visual navigation inversely relates to the severity of motor disability, leg-dominated bilateral spastic cerebral palsy. This agrees with the view that navigation ability substantially improves with practice and might be compromised in individuals with restrictions in active spatial exploration. Visual navigation is negatively linked to the volumetric extent of lesions over the right parietal and frontal periventricular regions. Whereas impairments of visual processing of point-light biological motion are associated in patients with PVL with bilateral parietal periventricular lesions, navigation ability is specifically linked to the frontal lesions in the right hemisphere. We suggest that more anterior periventricular lesions impair the interrelations between the right hippocampus and cortical areas leading to disintegration of neural networks engaged in visual navigation. For the first time, we show that the severity of right frontal periventricular damage and leg-dominated motor disorders can serve as independent predictors of the visual navigation disability.

  2. Automatic Classification of Specific Melanocytic Lesions Using Artificial Intelligence

    PubMed Central

    Jaworek-Korjakowska, Joanna; Kłeczek, Paweł

    2016-01-01

    Background. Given its propensity to metastasize, and lack of effective therapies for most patients with advanced disease, early detection of melanoma is a clinical imperative. Different computer-aided diagnosis (CAD) systems have been proposed to increase the specificity and sensitivity of melanoma detection. Although such computer programs are developed for different diagnostic algorithms, to the best of our knowledge, a system to classify different melanocytic lesions has not been proposed yet. Method. In this research we present a new approach to the classification of melanocytic lesions. This work is focused not only on categorization of skin lesions as benign or malignant but also on specifying the exact type of a skin lesion including melanoma, Clark nevus, Spitz/Reed nevus, and blue nevus. The proposed automatic algorithm contains the following steps: image enhancement, lesion segmentation, feature extraction, and selection as well as classification. Results. The algorithm has been tested on 300 dermoscopic images and achieved accuracy of 92% indicating that the proposed approach classified most of the melanocytic lesions correctly. Conclusions. A proposed system can not only help to precisely diagnose the type of the skin mole but also decrease the amount of biopsies and reduce the morbidity related to skin lesion excision. PMID:26885520

  3. Vesiculobullous lesions in lipoid proteinosis: a case report.

    PubMed

    Rao, Raghavendra; Prabhu, Smitha Smitha; Sripathi, H; Gupta, Sachi

    2008-07-15

    Vesiculobullous disorders in a child can be a diagnostic challenge. Common causes of blisters in early childhood include genodermatoses like epidermolysis bullosa and infections like herpes simplex. Lipoid proteinosis may rarely present with vesiculobullous lesions in childhood. We report a child, who presented in early childhood with blistering dermatosis. On long term follow-up, typical features of lipoid proteinosis developed. A high index of suspicion is required when one deals with blistering dermatosis in a child.

  4. [Early flat colorectal cancer].

    PubMed

    Castelletto, R H; Chiarenza, C; Ottino, A; Garay, M L

    1991-01-01

    We report three cases of flat early colorectal carcinoma which were detected during the examination of 51 surgical specimens of colorectal resection. Two of them were endoscopically diagnosed, but the smallest one was not seen in the luminal instrumental examination. From the bibliographic analysis and our own experience we deduce the importance of flat lesions in the development of early colorectal carcinoma, either originated from pre-existent adenoma or de novo. Flat variants of adenoma, and presumably flush or depressed ones, must be considered as important factors in the early sequence adenoma-cancer. An appropriate endoscopic equipment with employment of additional staining techniques (such as carmine indigo and methylene blue) and the correct investigation during inflation-deflation procedures facilitates the identification of small lesions, their eradication and prevention from advanced forms of colorectal carcinoma.

  5. Absence of the BRAF mutation in HBME1+ and CK19+ atypical cell clusters in Hashimoto thyroiditis: supportive evidence against preneoplastic change.

    PubMed

    Nasr, Michel R; Mukhopadhyay, Sanjay; Zhang, Shengle; Katzenstein, Anna-Luise A

    2009-12-01

    An association between Hashimoto thyroiditis and papillary thyroid carcinoma has been postulated for decades. We undertook this study to identify potential precursors of papillary thyroid carcinoma in Hashimoto thyroiditis using a combination of morphologic, immunohistochemical, and molecular techniques. For the study, samples from 59 cases of Hashimoto thyroiditis were stained with antibodies to HBME1 and cytokeratin (CK)19. Tiny HBME1+ and CK19+ atypical cell clusters were identified and analyzed for the BRAF mutation by the colorimetric Mutector assay and allele-specific polymerase chain reaction. HBME1+ and CK19+ atypical cell clusters were identified in 12 (20%) of 59 cases. The minute size (<1 mm) of the clusters and the incomplete nuclear changes precluded a diagnosis of papillary microcarcinoma. The atypical cell clusters from all 12 cases were negative for BRAF. The absence of the BRAF mutation in these atypical cell clusters suggests that they may not be preneoplastic. Caution should be exercised in interpreting positive HBME1 or CK19 staining in Hashimoto thyroiditis.

  6. Skin Lesion Analysis towards Melanoma Detection Using Deep Learning Network

    PubMed Central

    2018-01-01

    Skin lesions are a severe disease globally. Early detection of melanoma in dermoscopy images significantly increases the survival rate. However, the accurate recognition of melanoma is extremely challenging due to the following reasons: low contrast between lesions and skin, visual similarity between melanoma and non-melanoma lesions, etc. Hence, reliable automatic detection of skin tumors is very useful to increase the accuracy and efficiency of pathologists. In this paper, we proposed two deep learning methods to address three main tasks emerging in the area of skin lesion image processing, i.e., lesion segmentation (task 1), lesion dermoscopic feature extraction (task 2) and lesion classification (task 3). A deep learning framework consisting of two fully convolutional residual networks (FCRN) is proposed to simultaneously produce the segmentation result and the coarse classification result. A lesion index calculation unit (LICU) is developed to refine the coarse classification results by calculating the distance heat-map. A straight-forward CNN is proposed for the dermoscopic feature extraction task. The proposed deep learning frameworks were evaluated on the ISIC 2017 dataset. Experimental results show the promising accuracies of our frameworks, i.e., 0.753 for task 1, 0.848 for task 2 and 0.912 for task 3 were achieved. PMID:29439500

  7. Skin Lesion Analysis towards Melanoma Detection Using Deep Learning Network.

    PubMed

    Li, Yuexiang; Shen, Linlin

    2018-02-11

    Skin lesions are a severe disease globally. Early detection of melanoma in dermoscopy images significantly increases the survival rate. However, the accurate recognition of melanoma is extremely challenging due to the following reasons: low contrast between lesions and skin, visual similarity between melanoma and non-melanoma lesions, etc. Hence, reliable automatic detection of skin tumors is very useful to increase the accuracy and efficiency of pathologists. In this paper, we proposed two deep learning methods to address three main tasks emerging in the area of skin lesion image processing, i.e., lesion segmentation (task 1), lesion dermoscopic feature extraction (task 2) and lesion classification (task 3). A deep learning framework consisting of two fully convolutional residual networks (FCRN) is proposed to simultaneously produce the segmentation result and the coarse classification result. A lesion index calculation unit (LICU) is developed to refine the coarse classification results by calculating the distance heat-map. A straight-forward CNN is proposed for the dermoscopic feature extraction task. The proposed deep learning frameworks were evaluated on the ISIC 2017 dataset. Experimental results show the promising accuracies of our frameworks, i.e., 0.753 for task 1, 0.848 for task 2 and 0.912 for task 3 were achieved.

  8. Early Diagnosis and Early Intervention in Cerebral Palsy

    PubMed Central

    Hadders-Algra, Mijna

    2014-01-01

    This paper reviews the opportunities and challenges for early diagnosis and early intervention in cerebral palsy (CP). CP describes a group of disorders of the development of movement and posture, causing activity limitation that is attributed to disturbances that occurred in the fetal or infant brain. Therefore, the paper starts with a summary of relevant information from developmental neuroscience. Most lesions underlying CP occur in the second half of gestation, when developmental activity in the brain reaches its summit. Variations in timing of the damage not only result in different lesions but also in different neuroplastic reactions and different associated neuropathologies. This turns CP into a heterogeneous entity. This may mean that the best early diagnostics and the best intervention methods may differ for various subgroups of children with CP. Next, the paper addresses possibilities for early diagnosis. It discusses the predictive value of neuromotor and neurological exams, neuroimaging techniques, and neurophysiological assessments. Prediction is best when complementary techniques are used in longitudinal series. Possibilities for early prediction of CP differ for infants admitted to neonatal intensive care and other infants. In the former group, best prediction is achieved with the combination of neuroimaging and the assessment of general movements, in the latter group, best prediction is based on carefully documented milestones and neurological assessment. The last part reviews early intervention in infants developing CP. Most knowledge on early intervention is based on studies in high-risk infants without CP. In these infants, early intervention programs promote cognitive development until preschool age; motor development profits less. The few studies on early intervention in infants developing CP suggest that programs that stimulate all aspects of infant development by means of family coaching are most promising. More research is urgently needed

  9. When are circular lesions square? A national clinical education skin lesion audit and study.

    PubMed

    Miranda, Benjamin H; Herman, Katie A; Malahias, Marco; Juma, Ali

    2014-09-01

    Skin cancer is the most prevalent cancer by organ type and referral accuracy is vital for diagnosis and management. The British Association of Dermatologists (BAD) and literature highlight the importance of accurate skin lesion examination, diagnosis and educationally-relevant studies. We undertook a review of the relevant literature, a national audit of skin lesion description standards and a study of speciality training influences on these descriptions. Questionnaires (n=200), with pictures of a circular and an oval lesion, were distributed to UK dermatology/plastic surgery consultants and speciality trainees (ST), general practitioners (GP), and medical students (MS). The following variables were analysed against a pre-defined 95% inclusion accuracy standard: site, shape, size, skin/colour, and presence of associated scars. There were 250 lesion descriptions provided by 125 consultants, STs, GPs, and MSs. Inclusion accuracy was greatest for consultants over STs (80% vs. 68%; P<0.001), GPs (57%) and MSs (46%) (P<0.0001), for STs over GPs (P<0.010) and MSs (P<0.0001) and for GPs over MSs (P<0.010), all falling below audit standard. Size description accuracy sub-analysis according to circular/oval dimensions was as follows: consultants (94%), GPs (80%), STs (73%), MSs (37%), with the most common error implying a quadrilateral shape (66%). Addressing BAD guidelines and published requirements for more empirical performance data to improve teaching methods, we performed a national audit and studied skin lesion descriptions. To improve diagnostic and referral accuracy for patients, healthcare professionals must strive towards accuracy (a circle is not a square). We provide supportive evidence that increased speciality training improves this process and propose that greater focus is placed on such training early on during medical training, and maintained throughout clinical practice.

  10. Comprehensive Molecular Profiling of African-American Prostate Cancer to Inform on Prognosis and Disease Biology

    DTIC Science & Technology

    2016-10-01

    prostate cancer through sequencing xenografts and tissue samples. Qualify novel drivers of AR- prostate cancer through in vitro models. Develop novel...ability of RNASEH2A to modulate radio-sensitivity in prostate cancer cell lines and xenograft models. 3: Investigate RNASEH2A as a marker of radio...lung cancer clinical management. List of the Specific Aims: Aim 1: To establish patient-derived xenografts (PDX) models of pre-neoplastic lesions

  11. The Impact of Quantitative Data Provided by a Multi-spectral Digital Skin Lesion Analysis Device on Dermatologists'Decisions to Biopsy Pigmented Lesions.

    PubMed

    Farberg, Aaron S; Winkelmann, Richard R; Tucker, Natalie; White, Richard; Rigel, Darrell S

    2017-09-01

    BACKGROUND: Early diagnosis of melanoma is critical to survival. New technologies, such as a multi-spectral digital skin lesion analysis (MSDSLA) device [MelaFind, STRATA Skin Sciences, Horsham, Pennsylvania] may be useful to enhance clinician evaluation of concerning pigmented skin lesions. Previous studies evaluated the effect of only the binary output. OBJECTIVE: The objective of this study was to determine how decisions dermatologists make regarding pigmented lesion biopsies are impacted by providing both the underlying classifier score (CS) and associated probability risk provided by multi-spectral digital skin lesion analysis. This outcome was also compared against the improvement reported with the provision of only the binary output. METHODS: Dermatologists attending an educational conference evaluated 50 pigmented lesions (25 melanomas and 25 benign lesions). Participants were asked if they would biopsy the lesion based on clinical images, and were asked this question again after being shown multi-spectral digital skin lesion analysis data that included the probability graphs and classifier score. RESULTS: Data were analyzed from a total of 160 United States board-certified dermatologists. Biopsy sensitivity for melanoma improved from 76 percent following clinical evaluation to 92 percent after quantitative multi-spectral digital skin lesion analysis information was provided ( p <0.0001). Specificity improved from 52 percent to 79 percent ( p <0.0001). The positive predictive value increased from 61 percent to 81 percent ( p <0.01) when the quantitative data were provided. Negative predictive value also increased (68% vs. 91%, p<0.01), and overall biopsy accuracy was greater with multi-spectral digital skin lesion analysis (64% vs. 86%, p <0.001). Interrater reliability improved (intraclass correlation 0.466 before, 0.559 after). CONCLUSION: Incorporating the classifier score and probability data into physician evaluation of pigmented lesions led to both

  12. Factors affecting the palpability of breast lesion by self-examination.

    PubMed

    Lam, W W M; Chan, C P; Chan, C F; Mak, C C C; Chan, C F; Chong, K W H; Leung, M H J; Tang, M H

    2008-03-01

    This study aims to assess the accuracy of detection of breast lesion by breast self-examination and to assess different factors affecting the accuracy. All consecutive Chinese female patients, who attended our breast imaging unit in 2001, completed our questionnaire, had retrievable hard copy films, and had more than three years clinical follow-up, were recruited for this study. Different factors, such as age, menopausal status, previous experience of breastfeeding, family history of breast cancer, previous history of mastectomy or lumpectomy, hormonal therapy, oral contraceptive pills and previous history of mammography, were correlated with accuracy in self-detection of breast lesions retrospectively. The nature, size and location of the lesion, and breast size based on imaging, were also correlated with the accuracy in self-detection of breast lesions. A total of 163 questionnaires were analysed. 111 patients detected a breast lesion themselves and 24 of these lesions were false-positives. A total of 173 lesions (27 cancerous, 146 benign lesions) were documented by either ultrasonography and/or mammography, and confirmed by either histology or three-year clinical follow-up. The overall sensitivity in detecting both benign and malignant breast lesions was 71% when number of breast lesions was used as the denominator, and up to 78% sensitivity was achieved when number of patients was used as the denominator. History of mastectomy, and size and nature of the lesions were found to affect the accuracy of self-detection of breast lesions. Overall, breast self-examinations were effective in the detection of breast lesions and factors such as size of lesion, nature of the lesion and history of mastectomy affect the accuracy of the detections. Breast self-examination should be promoted for early detection of breast cancer.

  13. Transforming Growth Factor-Beta Inhibition Reduces Progression of Early Choroidal Neovascularization Lesions in Rats: P17 and P144 Peptides

    PubMed Central

    Zarranz-Ventura, Javier; Fernández-Robredo, Patricia; Recalde, Sergio; Salinas-Alamán, Angel; Borrás-Cuesta, Francisco; Dotor, Javier; García-Layana, Alfredo

    2013-01-01

    The purpose of this study was to assess the effects of transforming growth factor beta (TGF-β) inhibitor peptides (P17 & P144) on early laser-induced choroidal neovascularization (LI-CNV) lesions in rats, two weeks after laser CNV induction. Seventy-one Long Evans rats underwent diode laser application in an established LI-CNV model. Baseline fluorescein angiography (FA) was performed 14 days following laser procedure, and treatments were administered 16 days post-laser application via different administration routes. Intravenous groups included control (IV-Control), P17 (IV-17), and P144 (IV-144) groups, whereas intravitreal groups included P17 (IVT-17), P144 (IVT-144), and a mixture of both peptides (IVT-17+144) (with fellow eyes receiving vehicle alone). CNV evolution was assessed using FA performed weekly for four weeks after treatment. Following sacrifice, VEGF, TGF-β, COX-2, IGF-1, PAI-1, IL-6, MMP-2, MMP-9, and TNF-α gene expression was assessed using RT-PCR. VEGF and p-SMAD2 protein levels were also assessed by western-blot, while MMP-2 activity was assessed with gelatin zymography. Regarding the FA analysis, the mean CNV area was lower from the 3rd week in IVT-17 and IVT-144 groups, and also from the 2nd week in IVT-17+144. Biochemical analysis revealed that gene expression was lower for VEGF and COX-2 genes in IV-17 and IV-144 groups, VEGF gene in IVT-17+144 group and MMP-2 gene in IVT-17 and IVT-144 groups. VEGF protein expression was also decreased in IV-17, IV-144, IVT-17 and IVT-144, whereas pSMAD-2 levels were lower in IV-17, IV-144 and IVT-17+144 groups. Zymogram analysis revealed decreased MMP-2 activity in IV-17, IV-144, IVT-17 and IVT-144 groups. These data suggest that the use of TGF-β inhibitor peptides (P17 & P144) decrease the development of early CNV lesions by targeting different mediators than those typically affected using current anti-angiogenic therapies. Its potential role in the treatment of early CNV appears promising as a single

  14. Molecular pathogenesis of precursor lesions of pancreatic ductal adenocarcinoma.

    PubMed

    Biankin, Andrew V; Kench, James G; Dijkman, Floriaan P; Biankin, Sandra A; Henshall, Susan M

    2003-02-01

    Precursor lesions are assuming greater importance in the study of pancreatic ductal adenocarcinoma. As pancreatic cancer is almost universally fatal due to late clinical presentation and biological aggressiveness, characterisation of its precursor lesions may create scope for early diagnosis and improved outcome with conventional therapies as well as the development of novel therapeutic and preventative strategies. Pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous tumours (IPMTs) are thought to be precursor lesions of ductal adenocarcinoma of the pancreas. Recent work has focused on the molecular aberrations associated with these lesions leading to the formulation of a progression model for pancreatic cancer. Progressive histopathological changes along the progression model are associated with aberrations of cell cycle regulatory and growth factor signalling molecules that occur in pancreatic cancer at high frequency and are common to many cancers. Characterisation of these molecular aberrations provides scope for the development of novel diagnostic and treatment strategies that will ultimately impact on the outcome for people who develop pancreatic cancer.

  15. Textural analysis of early-phase spatiotemporal changes in contrast enhancement of breast lesions imaged with an ultrafast DCE-MRI protocol.

    PubMed

    Milenković, Jana; Dalmış, Mehmet Ufuk; Žgajnar, Janez; Platel, Bram

    2017-09-01

    New ultrafast view-sharing sequences have enabled breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to be performed at high spatial and temporal resolution. The aim of this study is to evaluate the diagnostic potential of textural features that quantify the spatiotemporal changes of the contrast-agent uptake in computer-aided diagnosis of malignant and benign breast lesions imaged with high spatial and temporal resolution DCE-MRI. The proposed approach is based on the textural analysis quantifying the spatial variation of six dynamic features of the early-phase contrast-agent uptake of a lesion's largest cross-sectional area. The textural analysis is performed by means of the second-order gray-level co-occurrence matrix, gray-level run-length matrix and gray-level difference matrix. This yields 35 textural features to quantify the spatial variation of each of the six dynamic features, providing a feature set of 210 features in total. The proposed feature set is evaluated based on receiver operating characteristic (ROC) curve analysis in a cross-validation scheme for random forests (RF) and two support vector machine classifiers, with linear and radial basis function (RBF) kernel. Evaluation is done on a dataset with 154 breast lesions (83 malignant and 71 benign) and compared to a previous approach based on 3D morphological features and the average and standard deviation of the same dynamic features over the entire lesion volume as well as their average for the smaller region of the strongest uptake rate. The area under the ROC curve (AUC) obtained by the proposed approach with the RF classifier was 0.8997, which was significantly higher (P = 0.0198) than the performance achieved by the previous approach (AUC = 0.8704) on the same dataset. Similarly, the proposed approach obtained a significantly higher result for both SVM classifiers with RBF (P = 0.0096) and linear kernel (P = 0.0417) obtaining AUC of 0.8876 and 0.8548, respectively

  16. Transoral Laser Microsurgery in Early Glottic Lesions.

    PubMed

    Sjögren, E V

    2017-01-01

    To give an overview of the evolvement of transoral laser microsurgery (TLM) in the treatment of early glottic carcinoma and highlight the contribution of recent literature. The indications and limits of TLM have been well specified. Effects on swallowing have been well documented. Introduction of narrow-band imaging (NBI) and diffusion-weighted magnetic resonance has been shown of additional value for outcome. The first reports on transoral robotic surgery show that it may be of added value in the future. TLM for early glottic carcinoma (Tis-T2) has very good oncological outcomes with indications of higher larynx preservation in TLM than that in radiotherapy. The anterior commissure is a risk factor if involved in the cranio-caudal plane, and reduced vocal fold mobility is a risk factor when this is due to arytenoid involvement. The best voice results are achieved when the anterior commissure can be left intact along with part of the vocal fold muscle although even in larger resections, patient self-reported voice handicap is still limited.

  17. On the stability of lung parenchymal lesions with applications to early pneumothorax diagnosis.

    PubMed

    Bhandarkar, Archis R; Banerjee, Rohan; Seshaiyer, Padmanabhan

    2013-01-01

    Spontaneous pneumothorax, a prevalent medical challenge in most trauma cases, is a form of sudden lung collapse closely associated with risk factors such as lung cancer and emphysema. Our work seeks to explore and quantify the currently unknown pathological factors underlying lesion rupture in pneumothorax through biomechanical modeling. We hypothesized that lesion instability is closely associated with elastodynamic strain of the pleural membrane from pulsatile air flow and collagen-elastin dynamics. Based on the principles of continuum mechanics and fluid-structure interaction, our proposed model coupled isotropic tissue deformation with pressure from pulsatile air motion and the pleural fluid. Next, we derived mathematical instability criteria for our ordinary differential equation system and then translated these mathematical instabilities to physically relevant structural instabilities via the incorporation of a finite energy limiter. The introduction of novel biomechanical descriptions for collagen-elastin dynamics allowed us to demonstrate that changes in the protein structure can lead to a transition from stable to unstable domains in the material parameter space for a general lesion. This result allowed us to create a novel streamlined algorithm for detecting material instabilities in transient lung CT scan data via analyzing deformations in a local tissue boundary.

  18. Estrogen-dependent gallbladder carcinogenesis in LXRbeta-/- female mice.

    PubMed

    Gabbi, Chiara; Kim, Hyun-Jin; Barros, Rodrigo; Korach-Andrè, Marion; Warner, Margaret; Gustafsson, Jan-Ake

    2010-08-17

    Gallbladder cancer is a highly aggressive disease with poor prognosis that is two to six times more frequent in women than men. The development of gallbladder cancer occurs over a long time (more than 15 y) and evolves from chronic inflammation to dysplasia/metaplasia, carcinoma in situ, and invasive carcinoma. In the present study we found that, in female mice in which the oxysterol receptor liver X receptor-beta (LXRbeta) has been inactivated, preneoplastic lesions of the gallbladder developed and evolved to cancer in old animals. LXRbeta is a nuclear receptor involved in the control of lipid homeostasis, glucose metabolism, inflammation, proliferation, and CNS development. LXRbeta(-/-) female gallbladders were severely inflamed, with regions of dysplasia and high cell density, hyperchromasia, metaplasia, and adenomas. No abnormalities were evident in male mice, nor in LXRalpha(-/-) or LXRalpha(-/-)beta(-/-) animals of either sex. Interestingly, the elimination of estrogens with ovariectomy prevented development of preneoplastic lesions in LXRbeta(-/-) mice. The etiopathological mechanism seems to involve TGF-beta signaling, as the precancerous lesions were characterized by strong nuclear reactivity of phospho-SMAD-2 and SMAD-4 and loss of E-cadherin expression. Upon ovariectomy, E-cadherin was reexpressed on the cell membranes and immunoreactivity of pSMAD-2 in the nuclei was reduced. These findings suggest that LXRbeta in a complex interplay with estrogens and TGF-beta could play a crucial role in the malignant transformation of the gallbladder epithelium.

  19. Clinical scoring system to detect malignant and premalignant vulval lesions.

    PubMed

    Tyagi, Shakun; Tripathi, Reva; Batra, Swaraj

    2014-02-01

    To construct a simple clinical scoring system for evaluation of vulval lesions that will be helpful in clinically detecting the premalignant or malignant lesions of vulva. Seventy women referred for vulval examination at a tertiary care centre in north India were examined over a period of 2 years. Biopsy was performed in 66 consenting women. Association of high-grade vulval lesion with various clinical parameters such as age, duration of symptoms, presenting complaints, the presence of depigmentation, ulceration, hyperkeratosis, acetowhite changes on acetic acid application, asymmetrical distribution of the lesion, surface elevation on naked eye or colposcopy, induration on palpation and toluidine blue stain retention was studied. The significantly associated factors were assigned a value of 0 or 1 depending on whether they were present or absent. Score was then formulated for detection of high-grade lesion defined as moderate to severe dysplasia and early malignancy. Histopathology. Out of the various parameters that were studied, duration of symptoms more than 6 months, hyperkeratosis, asymmetrical distribution of the lesion, surface elevation on naked eye or colposcopy, induration on palpation and positive toluidine blue stain retention of the lesion were found to be significantly associated with a malignant or premalignant lesion. It was found that a score of equal to or greater than 3/6 was significantly associated with a malignant or premalignant lesion. This simple scoring system has a potential to identify the high-grade lesions and can be used to identify the vulval lesion requiring a biopsy or further referral to higher centre.

  20. Pineal gland function is required for colon antipreneoplastic effects of physical exercise in rats.

    PubMed

    Frajacomo, F T T; de Paula Garcia, W; Fernandes, C R; Garcia, S B; Kannen, V

    2015-10-01

    Light-at-night exposure enhances the risk of cancer. Colon cancer is among the most dangerous tumors affecting humankind. Physical exercise has shown positive effects against colon cancer. Here, we investigated whether pineal gland modulates antipreneoplastic effects of physical exercise in the colon. Surgical and non-surgical pineal impairments were performed to clarify the relationship between the pineal gland activity and manifestation of colonic preneoplastic lesions. Next, a progressive swimming training was applied in rats exposed or not to either non-surgical pineal impairment or carcinogen treatment for 10 weeks. Both surgical and non-surgical pineal impairments increased the development of colon preneoplasia. It was further found that impairing the pineal gland function, higher rates of DNA damage were induced in colonic epithelial and enteric glial cells. Physical exercise acted positively against preneoplasia, whereas impairing the pineal function with constant light exposure disrupts its positive effects on the development of preneoplastic lesions in the colon. This was yet related to increased DNA damage in glial cells and enteric neuronal activation aside from serum melatonin levels. Our findings suggest that protective effects of physical exercise against colon cancer are dependent on the pineal gland activity. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Developmental outcomes after early prefrontal cortex damage.

    PubMed

    Eslinger, Paul J; Flaherty-Craig, Claire V; Benton, Arthur L

    2004-06-01

    The neuropsychological bases of cognitive, social, and moral development are minimally understood, with a seemingly wide chasm between developmental theories and brain maturation models. As one approach to bridging ideas in these areas, we review 10 cases of early prefrontal cortex damage from the clinical literature, highlighting overall clinical profiles and real life developmental outcomes. Based on these cases, there is preliminary evidence to support distinctive developmental differences after: (1) dorsolateral, (2) mesial, and (3) orbital-polar prefrontal lesions, for more profound impairments after bilateral damage, and possibly for recovery differences after very early vs. later childhood lesion onset. Further case and group studies are needed to confirm reliable effects of specific lesion locations, the influence of age of lesion onset, and related experiential and treatment variables in determining adult outcomes. Rather than a single underlying deficit associated with early prefrontal cortex damage, we interpret the findings to suggest that it is the altered integration and interplay of cognitive, emotional, self-regulatory, and executive/metacognitive deficits that contribute to diverse developmental frontal lobe syndromes. The findings support the fundamental importance of prefrontal cortex maturation in protracted cognitive, social-emotional, and moral development.

  2. Accumulation of Extracellular Matrix in Advanced Lesions of Canine Distemper Demyelinating Encephalitis

    PubMed Central

    Seehusen, Frauke; Al-Azreg, Seham A.; Raddatz, Barbara B.; Haist, Verena; Puff, Christina; Spitzbarth, Ingo; Ulrich, Reiner; Baumgärtner, Wolfgang

    2016-01-01

    In demyelinating diseases, changes in the quality and quantity of the extracellular matrix (ECM) may contribute to demyelination and failure of myelin repair and axonal sprouting, especially in chronic lesions. To characterize changes in the ECM in canine distemper demyelinating leukoencephalitis (DL), histochemical and immunohistochemical investigations of formalin-fixed paraffin-embedded cerebella using azan, picrosirius red and Gomori`s silver stain as well as antibodies directed against aggrecan, type I and IV collagen, fibronectin, laminin and phosphacan showed alterations of the ECM in CDV-infected dogs. A significantly increased amount of aggrecan was detected in early and late white matter lesions. In addition, the positive signal for collagens I and IV as well as fibronectin was significantly increased in late lesions. Conversely, the expression of phosphacan was significantly decreased in early and more pronounced in late lesions compared to controls. Furthermore, a set of genes involved in ECM was extracted from a publically available microarray data set and was analyzed for differential gene expression. Gene expression of ECM molecules, their biosynthesis pathways, and pro-fibrotic factors was mildly up-regulated whereas expression of matrix remodeling enzymes was up-regulated to a relatively higher extent. Summarized, the observed findings indicate that changes in the quality and content of ECM molecules represent important, mainly post-transcriptional features in advanced canine distemper lesions. Considering the insufficiency of morphological regeneration in chronic distemper lesions, the accumulated ECM seems to play a crucial role upon regenerative processes and may explain the relatively small regenerative potential in late stages of this disease. PMID:27441688

  3. Accumulation of Extracellular Matrix in Advanced Lesions of Canine Distemper Demyelinating Encephalitis.

    PubMed

    Seehusen, Frauke; Al-Azreg, Seham A; Raddatz, Barbara B; Haist, Verena; Puff, Christina; Spitzbarth, Ingo; Ulrich, Reiner; Baumgärtner, Wolfgang

    2016-01-01

    In demyelinating diseases, changes in the quality and quantity of the extracellular matrix (ECM) may contribute to demyelination and failure of myelin repair and axonal sprouting, especially in chronic lesions. To characterize changes in the ECM in canine distemper demyelinating leukoencephalitis (DL), histochemical and immunohistochemical investigations of formalin-fixed paraffin-embedded cerebella using azan, picrosirius red and Gomori`s silver stain as well as antibodies directed against aggrecan, type I and IV collagen, fibronectin, laminin and phosphacan showed alterations of the ECM in CDV-infected dogs. A significantly increased amount of aggrecan was detected in early and late white matter lesions. In addition, the positive signal for collagens I and IV as well as fibronectin was significantly increased in late lesions. Conversely, the expression of phosphacan was significantly decreased in early and more pronounced in late lesions compared to controls. Furthermore, a set of genes involved in ECM was extracted from a publically available microarray data set and was analyzed for differential gene expression. Gene expression of ECM molecules, their biosynthesis pathways, and pro-fibrotic factors was mildly up-regulated whereas expression of matrix remodeling enzymes was up-regulated to a relatively higher extent. Summarized, the observed findings indicate that changes in the quality and content of ECM molecules represent important, mainly post-transcriptional features in advanced canine distemper lesions. Considering the insufficiency of morphological regeneration in chronic distemper lesions, the accumulated ECM seems to play a crucial role upon regenerative processes and may explain the relatively small regenerative potential in late stages of this disease.

  4. Challenges and Limitations in Early Intervention

    ERIC Educational Resources Information Center

    Hadders-Algra, Mijna

    2011-01-01

    Research over the past three decades has shown that early intervention in infants biologically at risk of developmental disorders, irrespective of the presence of a brain lesion, is associated with improved cognitive development in early childhood without affecting motor development. However, at present it is unknown whether early intervention is…

  5. Chronology in lesion tolerance gives priority to genetic variability

    PubMed Central

    Naiman, Karel; Philippin, Gaëlle; Fuchs, Robert P.; Pagès, Vincent

    2014-01-01

    The encounter of a replication fork with a blocking DNA lesion is a common event that cells need to address properly to preserve genome integrity. Cells possess two main strategies to tolerate unrepaired lesions: potentially mutagenic translesion synthesis (TLS) and nonmutagenic damage avoidance (DA). Little is known about the partitioning between these two strategies. Because genes involved in DA mechanisms (i.e., recA) are expressed early and genes involved in TLS (i.e., Pol V) are expressed late during the bacterial SOS response, it has long been thought that TLS was the last recourse to bypass DNA lesions when repair and nonmutagenic DA mechanisms have failed. By using a recently described methodology, we followed the fate of a single replication-blocking lesion introduced in the Escherichia coli genome during acute genotoxic stress. We show that lesion tolerance events (i) only occur when the SOS response is fully induced and (ii) are executed in chronological order, with TLS coming first, followed by DA. Therefore, in response to genotoxic stress, bacterial cells give priority to TLS, a minor pathway able to generate genetic diversity before implementing the major nonmutagenic pathway that ensures survival. PMID:24706928

  6. Automatic lesion boundary detection in dermoscopy images using gradient vector flow snakes

    PubMed Central

    Erkol, Bulent; Moss, Randy H.; Stanley, R. Joe; Stoecker, William V.; Hvatum, Erik

    2011-01-01

    Background Malignant melanoma has a good prognosis if treated early. Dermoscopy images of pigmented lesions are most commonly taken at × 10 magnification under lighting at a low angle of incidence while the skin is immersed in oil under a glass plate. Accurate skin lesion segmentation from the background skin is important because some of the features anticipated to be used for diagnosis deal with shape of the lesion and others deal with the color of the lesion compared with the color of the surrounding skin. Methods In this research, gradient vector flow (GVF) snakes are investigated to find the border of skin lesions in dermoscopy images. An automatic initialization method is introduced to make the skin lesion border determination process fully automated. Results Skin lesion segmentation results are presented for 70 benign and 30 melanoma skin lesion images for the GVF-based method and a color histogram analysis technique. The average errors obtained by the GVF-based method are lower for both the benign and melanoma image sets than for the color histogram analysis technique based on comparison with manually segmented lesions determined by a dermatologist. Conclusions The experimental results for the GVF-based method demonstrate promise as an automated technique for skin lesion segmentation in dermoscopy images. PMID:15691255

  7. Children with severe early childhood caries: streptococci genetic strains within carious and white spot lesions.

    PubMed

    Gilbert, Kenneth; Joseph, Raphael; Vo, Alex; Patel, Trusha; Chaudhry, Samiya; Nguyen, Uyen; Trevor, Amy; Robinson, Erica; Campbell, Margaret; McLennan, John; Houran, Farielle; Wong, Tristan; Flann, Kendra; Wages, Melissa; Palmer, Elizabeth A; Peterson, John; Engle, John; Maier, Tom; Machida, Curtis A

    2014-01-01

    Mutans streptococci (MS) are one of the major microbiological determinants of dental caries. The objectives of this study are to identify distinct MS and non-MS streptococci strains that are located at carious sites and non-carious enamel surfaces in children with severe early childhood caries (S-ECC), and assess if cariogenic MS and non-cariogenic streptococci might independently exist as primary bacterial strains on distinct sites within the dentition of individual children. Dental plaque from children (N=20; aged 3-6) with S-ECC was collected from carious lesions (CLs), white spot lesions (WSLs) and non-carious enamel surfaces. Streptococcal isolates (N=10-20) from each site were subjected to polymerase chain reaction (PCR) to identify MS, and arbitrarily primed-PCR for assignment of genetic strains. Primary strains were identified as ≥50% of the total isolates surveyed at any site. In several cases, strains were characterized for acidurity using ATP-driven bioluminescence and subjected to PCR-determination of potential MS virulence products. Identification of non-MS was determined by 16S rRNA gene sequencing. Sixty-four independent MS or non-MS streptococcal strains were identified. All children contained 1-6 strains. In many patients (N=11), single primary MS strains were identified throughout the dentition. In other patients (N=4), primary MS strains were identified within CLs that were distinct from primary strains found on enamel. Streptococcus gordonii strains were identified as primary strains on enamel or WSLs in four children, and in general were less aciduric than MS strains. Many children with S-ECC contained only a single primary MS strain that was present in both carious and non-carious sites. In some cases, MS and non-cariogenic S. gordonii strains were found to independently exist as dominant strains at different locations within the dentition of individual children, and the aciduric potential of these strains may influence susceptibility in the

  8. [Endometrial carcinomas and precursor lesions--new aspects].

    PubMed

    Schmidt, D

    2009-07-01

    Endometrial carcinomas can be separated into two groups which are designated as type I and type II carcinomas today. Both groups of tumors are clearly different with regard to conventional light microscopy, immunohistochemistry, molecular pathology and clinical features. Only type I carcinomas are associated with hyperestrogenism. The group of type I carcinomas consists of endometrioid carcinoma and its variants, and mucinous carcinoma. The prototypes of type II carcinomas are serous and clear cell carcinoma. Not all carcinomas, however, can be assigned to one of the two groups, because there are hybrid tumors and mixed carcinomas, e.g. endometrioid carcinoma with a serous component. The precursor lesions of the endometrioid carcinoma and the serous carcinoma are well characterized morphologically and by molecular pathology. Atypical hyperplasia is the precursor lesion of endometrioid carcinoma, whereas endometrial intraepithelial carcinoma (EIC) is the precursor lesion of serous carcinoma. No precursor lesion has as yet been identified for clear cell carcinoma. Immunohistochemical markers for endometrial carcinoma are CK7 and vimentin, for serous carcinoma markers are p53 and p16. Correct typing is of essential prognostic necessity in endometrial carcinoma. Of utmost importance is the detection of a serous component, because serous carcinoma leads to early tumor spread with the necessity of radical surgery, chemotherapy and radiotherapy.

  9. Inhibition of cell proliferation by nobiletin, a dietary phytochemical, associated with apoptosis and characteristic gene expression, but lack of effect on early rat hepatocarcinogenesis in vivo.

    PubMed

    Ohnishi, Hiroyuki; Asamoto, Makoto; Tujimura, Kazunari; Hokaiwado, Naomi; Takahashi, Satoru; Ogawa, Kumiko; Kuribayashi, Masanori; Ogiso, Tadashi; Okuyama, Harumi; Shirai, Tomoyuki

    2004-12-01

    Dietary phytochemicals can inhibit the development of certain types of tumors. We here investigated the effects of nobiletin (Nob), garcinol (Gar), auraptene (Aur), beta-cryptoxanthin- and hesperidine-rich pulp (CHRP) and 1,1'-acetoxychavicol acetate (ACA) on hepatocarcinogenesis in a rat medium-term liver bioassay, and also examined their influence on cell proliferation, cell cycle kinetics, apoptosis and cell invasion of rat and human hepatocellular carcinoma (HCC) cells, MH1C1 and HepG2, respectively. While there were no obvious suppressive effects on the development of putative preneoplastic liver lesions, inhibition of hepatocarcinoma cell proliferation was evident in the Nob group. Nob also caused G2/M cell cycle arrest and apoptosis. Microarray analysis identified a set of genes specifically regulated by Nob, and these are likely to be involved in the observed growth suppression of HCC cells. These results suggest that phytochemicals might have chemopreventive potential in late stages of hepatocarcinogenesis.

  10. Bad and Bid - potential background players in preneoplastic to neoplastic shift in human endometrium.

    PubMed

    Driak, D; Dvorska, M; Bolehovska, P; Svandova, I; Novotny, J; Halaska, M

    2014-01-01

    The most common malignancies of the female genital tract are endometrial carcinomas, whose are generally proceeded by hyperplasia. The maintenance of tissue homeostasis is to great extent governed by apoptosis, whose defects can lead to the preneoplastic and/or cancerous changes. Endometrial apoptosis involves among others three groups of proteins of the Bcl-2 family. First group contains anti-apoptotic proteins (e. g. Bcl-2, Bcl-xL). The other two groups belong to the pro-apoptotic proteins with three (e. g. Bax, Bak) or one (e. g. Bad, Bid) so-called BH domains. Bad and Bid trigger the oligomerization of Bak and Bax protein, which permeabilize the outer mitochondrial wall. Unlike Bid, Bad cannot directly trigger apoptosis. Instead, Bad lowers the threshold at which apoptosis is induced, by binding anti-apoptotic Bcl-2 proteins. However, their mutual counterbalance or synergism in the human endometrium has not been reported yet.In this study, the levels of Bid and Bad were measured using SDS-PAGE and Western blotting with specific antibodies, with the aim to analyse expression of Bid and Bad proteins in normal (NE), hyperplastic (HE) and cancerous (CE) endometrium. We demonstrated that Bid expression in CE reached only 47% and 50% of this observed in NE and HE. Conversely, Bad expression in HE reached only 40% and 36% of this observed in NE and CE, respectively. We detected no significant changes of Bid expression between HE and NE, and levels of Bad protein were not different between CE and NE.Trend of Bid and Bad protein expression is clearly opposite in HE and CE. We hypothesise that disrupted apoptotic program in CE seems to be reduced further by lowering levels of direct apoptotic trigger protein Bid. We suggest that the adenocarcinoma tissue of human endometrium thus tries to strengthen its apoptotic effort by lowering the apoptotic threshold via higher Bad levels.

  11. Detection and classification of retinal lesions for grading of diabetic retinopathy.

    PubMed

    Usman Akram, M; Khalid, Shehzad; Tariq, Anam; Khan, Shoab A; Azam, Farooque

    2014-02-01

    Diabetic Retinopathy (DR) is an eye abnormality in which the human retina is affected due to an increasing amount of insulin in blood. The early detection and diagnosis of DR is vital to save the vision of diabetes patients. The early signs of DR which appear on the surface of the retina are microaneurysms, haemorrhages, and exudates. In this paper, we propose a system consisting of a novel hybrid classifier for the detection of retinal lesions. The proposed system consists of preprocessing, extraction of candidate lesions, feature set formulation, and classification. In preprocessing, the system eliminates background pixels and extracts the blood vessels and optic disc from the digital retinal image. The candidate lesion detection phase extracts, using filter banks, all regions which may possibly have any type of lesion. A feature set based on different descriptors, such as shape, intensity, and statistics, is formulated for each possible candidate region: this further helps in classifying that region. This paper presents an extension of the m-Mediods based modeling approach, and combines it with a Gaussian Mixture Model in an ensemble to form a hybrid classifier to improve the accuracy of the classification. The proposed system is assessed using standard fundus image databases with the help of performance parameters, such as, sensitivity, specificity, accuracy, and the Receiver Operating Characteristics curves for statistical analysis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Detection of Helicobacter pylori in Oral Lesions

    PubMed Central

    Irani, Soussan; Monsef Esfahani, Alireza; Bidari Zerehpoush, Farahnaz

    2013-01-01

    Background and aims. Helicobacter pylori is a microaerophilic gram-negative spiral organism. It is recognized as the etiologic factor for peptic ulcers, gastric adenocarcinoma and gastric lymphoma. Recently, it has been isolated from dental plaque and the dorsum of the tongue. This study was designed to assess the association between H. pylori and oral lesions such as ulcerative/inflammatory lesions, squamous cell carcinoma (SCC) and primary lymphoma. Materials and methods. A total of 228 biopsies diagnosed as oral ulcerative/inflammatory lesions, oral squamous cell carcinoma (OSCC) and oral primary lymphoma were selected from the archives of the Pathology Department. Thirty-two samples that were diagnosed as being without any pathological changes were selected as the control group. All the paraffin blocks were cut for hematoxylin and eosin staining to confirm the diagnoses and then the samples were prepared for immunohistochemistry staining. Data were collected and analyzed. Results. Chi-squared test showed significant differences between the frequency of H. pylori positivity in normal tissue and the lesions were examined (P=0.000). In addition, there was a statistically significant difference between the lesions examined (P=0.042). Chi-squared test showed significant differences between H. pylori positivity and different tissue types except inside the muscle layer as follows: in epithelium and in lamina propria (P=0.000), inside the blood vessels (P=0.003), inside the salivary gland duct (P=0.036), and muscle layer (P=0.122). Conclusion. There might be a relation between the presence of H. pylori and oral lesions. Therefore, early detection and eradication of H. pylori in high-risk patients are suggested. PMID:24578822

  13. A single-photon fluorescence and multi-photon spectroscopic study of atherosclerotic lesions

    NASA Astrophysics Data System (ADS)

    Smith, Michael S. D.; Ko, Alex C. T.; Ridsdale, Andrew; Schattka, Bernie; Pegoraro, Adrian; Hewko, Mark D.; Shiomi, Masashi; Stolow, Albert; Sowa, Michael G.

    2009-06-01

    In this study we compare the single-photon autofluorescence and multi-photon emission spectra obtained from the luminal surface of healthy segments of artery with segments where there are early atherosclerotic lesions. Arterial tissue was harvested from atherosclerosis-prone WHHL-MI rabbits (Watanabe heritable hyperlipidemic rabbit-myocardial infarction), an animal model which mimics spontaneous myocardial infarction in humans. Single photon fluorescence emission spectra of samples were acquired using a simple spectrofluorometer set-up with 400 nm excitation. Samples were also investigated using a home built multi-photon microscope based on a Ti:sapphire femto-second oscillator. The excitation wavelength was set at 800 nm with a ~100 femto-second pulse width. Epi-multi-photon spectroscopic signals were collected through a fibre-optics coupled spectrometer. While the single-photon fluorescence spectra of atherosclerotic lesions show minimal spectroscopic difference from those of healthy arterial tissue, the multi-photon spectra collected from atherosclerotic lesions show marked changes in the relative intensity of two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) signals when compared with those from healthy arterial tissue. The observed sharp increase of the relative SHG signal intensity in a plaque is in agreement with the known pathology of early lesions which have increased collagen content.

  14. Plasticity during Early Brain Development Is Determined by Ontogenetic Potential.

    PubMed

    Krägeloh-Mann, Ingeborg; Lidzba, Karen; Pavlova, Marina A; Wilke, Marko; Staudt, Martin

    2017-04-01

    Two competing hypotheses address neuroplasticity during early brain development: the "Kennard principle" describes the compensatory capacities of the immature developing CNS as superior to those of the adult brain, whereas the "Hebb principle" argues that the young brain is especially sensitive to insults. We provide evidence that these principles are not mutually exclusive. Following early brain lesions that are unilateral, the brain can refer to homotopic areas of the healthy hemisphere. This potential for reorganization is unique to the young brain but available only when, during ontogenesis of brain development, these areas have been used for the functions addressed. With respect to motor function, ipsilateral motor tracts can be recruited, which are only available during early brain development. Language can be reorganized to the right after early left hemispheric lesions, as the representation of the language network is initially bilateral. However, even in these situations, compensatory capacities of the developing brain are found to have limitations, probably defined by early determinants. Thus, plasticity and adaptivity are seen only within ontogenetic potential; that is, axonal or cortical structures cannot be recruited beyond early developmental possibilities. The young brain is probably more sensitive and vulnerable to lesions when these are bilateral. This is shown here for bilateral periventricular white matter lesions that clearly have an impact on cortical architecture and function, thus probably interfering with early network building. Georg Thieme Verlag KG Stuttgart · New York.

  15. Monitoring of enamel lesion remineralization by optical coherence tomography: an alternative approach towards signal analysis

    NASA Astrophysics Data System (ADS)

    Sadr, Alireza; Mandurah, Mona; Nakashima, Syozi; Shimada, Yasushi; Kitasako, Yuichi; Tagami, Junji; Sumi, Yasunori

    Early detection, monitoring and remineralization repair of enamel lesions are top research priorities in the modern dentistry focusing on minimal intervention concept for caries management. We investigate the use of swept-source optical coherence tomography system (SS-OCT) without polarization-sensing at 1319 nm wavelength developed for clinical dentistry (Dental OCT System Prototype 2, Panasonic Healthcare Co., Ltd., Japan) in quantitative assessment of artificial enamel lesions and their remineralization. Bovine enamel blocks were subjected to demineralization to create subsurface lesions approximately 130 μm in depth over 2 weeks, and subjected to remineralization in solution containing bioavailable calcium and 1ppm fluoride at pH 6.5 for 2 weeks. Cross-sectional images of sound, demineralized and remineralized specimens were captured under hydrated conditions by the OCT. Finally, the specimens were cut into sections for nanoindentation to measure hardness through the lesion under 2mN load. Reflectivity had increased with demineralization. OCT images of lesions showed a boundary closely suggesting the lesion depth that gradually progressed with demineralization time. After remineralization, the boundary depth gradually decreased and nanoindentation showed over 60% average hardness recovery rate. A significant negative correlation was found between the slope power-law regression as a measure of attenuation and overall nanohardness for a range of data covering sound, demineralized and remineralized areas. In conclusion, OCT could provide clear images of early enamel lesion extent and signal attenuation could indicate its severity and recovery. Clinical data of natural lesions obtained using Dental OCT and analyzed by this approach will also be presented. Study supported by GCOE IRCMSTBD and NCGG.

  16. Parietal lesion effects on cued recall following pair associate learning.

    PubMed

    Ben-Zvi, Shir; Soroker, Nachum; Levy, Daniel A

    2015-07-01

    We investigated the involvement of the posterior parietal cortex in episodic memory in a lesion-effects study of cued recall following pair-associate learning. Groups of patients who had experienced first-incident stroke, generally in middle cerebral artery territory, and exhibited damage that included lateral posterior parietal regions, were tested within an early post-stroke time window. In three experiments, patients and matched healthy comparison groups executed repeated study and cued recall test blocks of pairs of words (Experiment 1), pairs of object pictures (Experiment 2), or pairs of object pictures and environmental sounds (Experiment 3). Patients' brain CT scans were subjected to quantitative analysis of lesion volumes. Behavioral and lesion data were used to compute correlations between area lesion extent and memory deficits, and to conduct voxel-based lesion-symptom mapping. These analyses implicated lateral ventral parietal cortex, especially the angular gyrus, in cued recall deficits, most pronouncedly in the cross-modal picture-sound pairs task, though significant parietal lesion effects were also found in the unimodal word pairs and picture pairs tasks. In contrast to an earlier study in which comparable parietal lesions did not cause deficits in item recognition, these results indicate that lateral posterior parietal areas make a substantive contribution to demanding forms of recollective retrieval as represented by cued recall, especially for complex associative representations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. MicroRNAs for Detection of Pancreatic Neoplasia

    PubMed Central

    Vila-Navarro, Elena; Vila-Casadesús, Maria; Moreira, Leticia; Duran-Sanchon, Saray; Sinha, Rupal; Ginés, Àngels; Fernández-Esparrach, Glòria; Miquel, Rosa; Cuatrecasas, Miriam; Castells, Antoni; Lozano, Juan José; Gironella, Meritxell

    2017-01-01

    Objective: The aim of our study was to analyze the miRNome of pancreatic ductal adenocarcinoma (PDAC) and its preneoplastic lesion intraductal papillary mucinous neoplasm (IPMN), to find new microRNA (miRNA)-based biomarkers for early detection of pancreatic neoplasia. Objective: Effective early detection methods for PDAC are needed. miRNAs are good biomarker candidates. Methods: Pancreatic tissues (n = 165) were obtained from patients with PDAC, IPMN, or from control individuals (C), from Hospital Clínic of Barcelona. Biomarker discovery was done using next-generation sequencing in a discovery set of 18 surgical samples (11 PDAC, 4 IPMN, 3 C). MiRNA validation was carried out by quantitative reverse transcriptase PCR in 2 different set of samples. Set 1—52 surgical samples (24 PDAC, 7 IPMN, 6 chronic pancreatitis, 15 C), and set 2—95 endoscopic ultrasound-guided fine-needle aspirations (60 PDAC, 9 IPMN, 26 C). Results: In all, 607 and 396 miRNAs were significantly deregulated in PDAC and IPMN versus C. Of them, 40 miRNAs commonly overexpressed in both PDAC and IPMN were selected for further validation. Among them, significant up-regulation of 31 and 30 miRNAs was confirmed by quantitative reverse transcriptase PCR in samples from set 1 and set 2, respectively. Conclusions: miRNome analysis shows that PDAC and IPMN have differential miRNA profiles with respect to C, with a large number of deregulated miRNAs shared by both neoplastic lesions. Indeed, we have identified and validated 30 miRNAs whose expression is significantly increased in PDAC and IPMN lesions. The feasibility of detecting these miRNAs in endoscopic ultrasound-guided fine-needle aspiration samples makes them good biomarker candidates for early detection of pancreatic cancer. PMID:27232245

  18. [Karyometry of BBN-induced precancerosis of the urothelium : An experimental analysis].

    PubMed

    Dahm, H H; Lehnen-Holtum, V; Rübben, H

    2016-10-01

    The morphology of experimental precancerous lesions of the urinary bladder has been interpreted quite differently by various authors. The aim of this investigation was to quantify these lesions by karyometry and, thus, to gain a more reliable understanding of the process. A total of 60 Wistar rats were fed with N‑butyl-N-(4-hydroxybutyl)nitrosamine (BBN) at a concentration of 0.05 % in their drinking water to induce preneoplastic changes of the urothelium. After the second week of BBN exposition, 6 animals were killed every 2 weeks up to week 20. Smears of the scraped off urothelium of 3 urinary bladders of each group were analyzed cytologically and karyometrically. BBN exposition led to statistically significant changes of the karyometric values using the χ 2 test to differentiate the control animals from the ones that had ingested BBN and the 2‑week groups from each other. These changes consisted mainly in significant deviations of the size of the nuclear area within the different groups. Morphological and karyometrical analysis showed that biologically relevant stages in the development of chemically induced urothelial precancerous lesions could be realized much earlier than had been assumed in recent publications. Karyometric analysis offered a valid basis to describe the early morphologic alterations of carcinogenesis.

  19. Bronchial airway gene expression signatures in mouse lung squamous cell carcinoma and their modulation by cancer chemopreventive agents

    PubMed Central

    Szabo, Eva; Miller, Mark Steven; Lubet, Ronald A.; You, Ming; Wang, Yian

    2017-01-01

    Due to exposure to environmental toxicants, a “field cancerization” effect occurs in the lung resulting in the development of a field of initiated but morphologically normal appearing cells in the damaged epithelium of bronchial airways with dysregulated gene expression patterns. Using a mouse model of lung squamous cell carcinoma (SCC), we performed transcriptome sequencing (RNA-Seq) to profile bronchial airway gene expression and found activation of the PI3K and Myc signaling networks in cytologically normal bronchial airway epithelial cells of mice with preneopastic lung SCC lesions, which was reversed by treatment with the PI3K Inhibitor XL-147 and pioglitazone, respectively. Activated MYC signaling was also present in premalignant and tumor tissues from human lung SCC patients. In addition, we identified a key microRNA, mmu-miR-449c-5p, whose suppression significantly up-regulated Myc expression in the normal bronchial airway epithelial cells of mice with early stage SCC lesions. We developed a novel bronchial genomic classifier in mice and validated it in humans. In the classifier, Ppbp (pro-platelet basic protein) was overexpressed 115 fold in the bronchial airways of mice with preneoplastic lung SCC lesions. This is the first report that demonstrates Ppbp as a novel biomarker in the bronchial airway for lung cancer diagnosis. PMID:27935865

  20. Laser-induced fluorescence spectroscopy of benign and malignant cutaneous lesions

    NASA Astrophysics Data System (ADS)

    Borisova, Ekaterina G.; Troyanova, P. P.; Stoyanova, V. P.; Avramov, Lachezar A.

    2005-04-01

    The goals of this work were investigation of pigmented skin lesions by the method of laser-induced fluorescence spectroscopy. Fluorescence spectra were obtained from malignant and benign skin lesions after excitation with nitrogen laser at 337 nm, namely: benign nevi, dysplastic nevi, malignant melanoma (MM), keratopapilloma, base-cell papilloma and base-cell carcinoma, as well as from healthy skin areas near to the lesion that were used posteriori to reveal changes between healthy and lesion skin spectra. Initially lesions were classified by ABCD-dermatscopic method. All suspicious lesions were excised and were investigated histologically. Spectrum of healthy skin consists of one main maximum at 470-500 nm spectral region and secondary maxima at in the regions round 400 and 440 nm. In the cases of nevi and melanoma significant decrease of fluorescence intensity, which correlated with the type of pigment lesion was observed. This reduction of the signal is related to the accumulation of melanin in the lesions that re-absorb strongly the fluorescence from native skin fluorophores in whole visible spectral region. In cases of papilloma and base-cell carcinoma an intensity decrease was also observed, related to accumulation of pigments in these cutaneous lesions. An relative increase of the fluorescence peak at 440 nm were registered in the case of base-cell carcinoma, and appearance of green fluorescence, related to increase of keratin content in benign papilloma lesions were detected. The results, obtained in this investigation of the different pigment lesions could be used for better comprehension of the skin optical properties. The fluorescence spectroscopy of the human skin are very prominent for early diagnosis and differentiation of cutaneous diseases and gives a wide range of possibilities related to real-time determination of existing pathological condition.

  1. A systematic approach to magnetic resonance imaging evaluation of epiphyseal lesions.

    PubMed

    Thawait, Shrey K; Thawait, Gaurav K; Frassica, Frank J; Andreisek, Gustav; Carrino, John A; Chhabra, Avneesh

    2013-04-01

    Magnetic Resonance Imaging (MRI) is the preferred modality of choice to image epiphyseal lesions. It provides excellent soft tissue resolution and extent of disease. A wide spectrum of tumor and tumor like lesions can involve the epiphysis. Early and accurate diagnosis as well as appropriate management of epiphyseal lesions is critical as these conditions may lead to disabling complications such as, limb length discrepancy, angular or joint surface deformities and secondary osteoarthritis. In this article, we discuss the role of conventional sequences, such as T1W, fluid sensitive T2W and intravenous (IV) Gadolinium enhanced sequences as well as the additional value of problem solving MRI sequences such as, chemical shift and diffusion weighted imaging. Based on the imaging findings on various MRI sequences and lesion characteristics, a systematic approach directed to the diagnoses of epiphyseal lesions is presented and discussed. MRI features of clinically and biopsy proven examples of the epiphyseal lesions, such as osteomyelitis, intra-osseous abscess, infiltrative malignancy, metastases, transient osteoporosis, subchondral insufficiency fracture, avascular necrosis, osteochondral fracture, osteochondritis dissecans, eosinophilic granuloma and geode are demonstrated. Using this systematic approach, the reader will be able to better characterize epiphyseal lesions with a potential to positively affect patient management. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Satellite lesions in congenital melanocytic nevi--time for a change of name.

    PubMed

    Kinsler, Veronica

    2011-01-01

    The term "satellite lesions" is used in many conditions in dermatology, generally to describe smaller lesions near the edges of a principal lesion. An online medical dictionary gives the definition "a smaller lesion accompanying a main one and situated nearby," and this can apply both macroscopically and microscopically. The implication is that the smaller lesions have spread from the parent lesion. Given this definition and usual understanding of the term its use is not apt in the case of congenital melanocytic nevi (CMN). In the vast majority of cases where the patient is said to have satellite lesions these are not restricted to the area around or near the edge of the principal lesion, and are not necessarily significantly smaller. It seems likely that the early use of the term in this condition is an adaptation of the established and correct use in the context of melanoma. Not only is the term not apt clinically but has no known etiological basis. This leaves us with the question of what to call these lesions in cases of CMN. This proposal is to categorize cases into single or multiple CMN, where multiple is 2 or more nevi of any size at birth. An accurate count or good estimate of the number of lesions at birth should also be recorded, and the largest lesion classified as usual with respect to projected adult size. © 2011 Wiley Periodicals, Inc.

  3. A Case of Generalized Auditory Agnosia with Unilateral Subcortical Brain Lesion

    PubMed Central

    Suh, Hyee; Kim, Soo Yeon; Kim, Sook Hee; Chang, Jae Hyeok; Shin, Yong Beom; Ko, Hyun-Yoon

    2012-01-01

    The mechanisms and functional anatomy underlying the early stages of speech perception are still not well understood. Auditory agnosia is a deficit of auditory object processing defined as a disability to recognize spoken languages and/or nonverbal environmental sounds and music despite adequate hearing while spontaneous speech, reading and writing are preserved. Usually, either the bilateral or unilateral temporal lobe, especially the transverse gyral lesions, are responsible for auditory agnosia. Subcortical lesions without cortical damage rarely causes auditory agnosia. We present a 73-year-old right-handed male with generalized auditory agnosia caused by a unilateral subcortical lesion. He was not able to repeat or dictate but to perform fluent and comprehensible speech. He could understand and read written words and phrases. His auditory brainstem evoked potential and audiometry were intact. This case suggested that the subcortical lesion involving unilateral acoustic radiation could cause generalized auditory agnosia. PMID:23342322

  4. Voxel-based lesion mapping of meningioma: a comprehensive lesion location mapping of 260 lesions.

    PubMed

    Hirayama, Ryuichi; Kinoshita, Manabu; Arita, Hideyuki; Kagawa, Naoki; Kishima, Haruhiko; Hashimoto, Naoya; Fujimoto, Yasunori; Yoshimine, Toshiki

    2018-06-01

    OBJECTIVE In the present study the authors aimed to determine preferred locations of meningiomas by avoiding descriptive analysis and instead using voxel-based lesion mapping and 3D image-rendering techniques. METHODS Magnetic resonance images obtained in 248 treatment-naïve meningioma patients with 260 lesions were retrospectively and consecutively collected. All images were registered to a 1-mm isotropic, high-resolution, T1-weighted brain atlas provided by the Montreal Neurological Institute (the MNI152), and a lesion frequency map was created, followed by 3D volume rendering to visualize the preferred locations of meningiomas in 3D. RESULTS The 3D lesion frequency map clearly showed that skull base structures such as parasellar, sphenoid wing, and petroclival regions were commonly affected by the tumor. The middle one-third of the superior sagittal sinus was most commonly affected in parasagittal tumors. Substantial lesion accumulation was observed around the leptomeninges covering the central sulcus and the sylvian fissure, with very few lesions observed at the frontal, parietal, and occipital convexities. CONCLUSIONS Using an objective visualization method, meningiomas were shown to be located around the middle third of the superior sagittal sinus, the perisylvian convexity, and the skull base. These observations, which are in line with previous descriptive analyses, justify further use of voxel-based lesion mapping techniques to help understand the biological nature of this disease.

  5. The method for detecting small lesions in medical image based on sliding window

    NASA Astrophysics Data System (ADS)

    Han, Guilai; Jiao, Yuan

    2016-10-01

    At present, the research on computer-aided diagnosis includes the sample image segmentation, extracting visual features, generating the classification model by learning, and according to the model generated to classify and judge the inspected images. However, this method has a large scale of calculation and speed is slow. And because medical images are usually low contrast, when the traditional image segmentation method is applied to the medical image, there is a complete failure. As soon as possible to find the region of interest, improve detection speed, this topic attempts to introduce the current popular visual attention model into small lesions detection. However, Itti model is mainly for natural images. But the effect is not ideal when it is used to medical images which usually are gray images. Especially in the early stages of some cancers, the focus of a disease in the whole image is not the most significant region and sometimes is very difficult to be found. But these lesions are prominent in the local areas. This paper proposes a visual attention mechanism based on sliding window, and use sliding window to calculate the significance of a local area. Combined with the characteristics of the lesion, select the features of gray, entropy, corner and edge to generate a saliency map. Then the significant region is segmented and distinguished. This method reduces the difficulty of image segmentation, and improves the detection accuracy of small lesions, and it has great significance to early discovery, early diagnosis and treatment of cancers.

  6. Detection of white spot lesions by segmenting laser speckle images using computer vision methods.

    PubMed

    Gavinho, Luciano G; Araujo, Sidnei A; Bussadori, Sandra K; Silva, João V P; Deana, Alessandro M

    2018-05-05

    This paper aims to develop a method for laser speckle image segmentation of tooth surfaces for diagnosis of early stages caries. The method, applied directly to a raw image obtained by digital photography, is based on the difference between the speckle pattern of a carious lesion tooth surface area and that of a sound area. Each image is divided into blocks which are identified in a working matrix by their χ 2 distance between block histograms of the analyzed image and the reference histograms previously obtained by K-means from healthy (h_Sound) and lesioned (h_Decay) areas, separately. If the χ 2 distance between a block histogram and h_Sound is greater than the distance to h_Decay, this block is marked as decayed. The experiments showed that the method can provide effective segmentation for initial lesions. We used 64 images to test the algorithm and we achieved 100% accuracy in segmentation. Differences between the speckle pattern of a sound tooth surface region and a carious region, even in the early stage, can be evidenced by the χ 2 distance between histograms. This method proves to be more effective for segmenting the laser speckle image, which enhances the contrast between sound and lesioned tissues. The results were obtained with low computational cost. The method has the potential for early diagnosis in a clinical environment, through the development of low-cost portable equipment.

  7. Multispectral near-infrared reflectance and transillumination imaging of occlusal carious lesions: variations in lesion contrast with lesion depth

    NASA Astrophysics Data System (ADS)

    Simon, Jacob C.; Curtis, Donald A.; Darling, Cynthia L.; Fried, Daniel

    2018-02-01

    In vivo and in vitro studies have demonstrated that near-infrared (NIR) light at λ=1300-1700-nm can be used to acquire high contrast images of enamel demineralization without interference of stains. The objective of this study was to determine if a relationship exists between the NIR image contrast of occlusal lesions and the depth of the lesion. Extracted teeth with varying amounts of natural occlusal decay were measured using a multispectral-multimodal NIR imaging system which captures λ=1300-nm occlusal transillumination, and λ=1500-1700-nm cross-polarized reflectance images. Image analysis software was used to calculate the lesion contrast detected in both images from matched positions of each imaging modality. Samples were serially sectioned across the lesion with a precision saw, and polarized light microscopy was used to measure the respective lesion depth relative to the dentinoenamel junction. Lesion contrast measured from NIR crosspolarized reflectance images positively correlated (p<0.05) with increasing lesion depth and a statistically significant difference between inner enamel and dentin lesions was observed. The lateral width of pit and fissures lesions measured in both NIR cross-polarized reflectance and NIR transillumination positively correlated with lesion depth.

  8. Topical photosan-mediated photodynamic therapy for DMBA-induced hamster buccal pouch early cancer lesions: an in vivo study

    NASA Astrophysics Data System (ADS)

    Hsu, Yih-Chih; Chang, Walter Hong-Shong; Chang, Junn-Liang; Liu, Kuang-Ting; Chiang, Chun-Pin; Liu, Chung-Ji; Chen, Chih-Ping

    2011-03-01

    Oral cancer has becomes the most prominent cancer disease in recent years in Taiwan. The reason is the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people results in oral cancer becomes the fastest growth incident cancer amongst other major cancer diseases. In previous studies showed that photosan, haematoporphyrin derivative (HPD), has demonstrated effective PDT results on human head and neck disease studies. To avoid the systemic phototoxic effect of photosan, this study was designed to use a topical photosan-mediated PDT for treatment of DMBA-induced hamster buccal pouch cancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical photosan-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when photosan reached its peak level in the lesional epithelial cells after topical application of photosan gel. We found that photosan reached its peak level in cancerous lesions about 13.5 min after topical application of photosan gel. The cancerous lesions in hamsters were then treated with topical photosan-mediated PDT (fluence rate: 600 mW/cm2; light exposure dose 200 J/cm2) using the portable Lumacare 635 nm fiber-guided light device. Visual examination demonstrated that topical photosan-mediated PDT was an applicable treatment modality for DMBA-induced hamster buccal pouch cancerous lesions.

  9. CONCENTRIC DECILE SEGMENTATION OF WHITE AND HYPOPIGMENTED AREAS IN DERMOSCOPY IMAGES OF SKIN LESIONS ALLOWS DISCRIMINATION OF MALIGNANT MELANOMA

    PubMed Central

    Dalal, Ankur; Moss, Randy H.; Stanley, R. Joe; Stoecker, William V.; Gupta, Kapil; Calcara, David A.; Xu, Jin; Shrestha, Bijaya; Drugge, Rhett; Malters, Joseph M.; Perry, Lindall A.

    2011-01-01

    Dermoscopy, also known as dermatoscopy or epiluminescence microscopy (ELM), permits visualization of features of pigmented melanocytic neoplasms that are not discernable by examination with the naked eye. White areas, prominent in early malignant melanoma and melanoma in situ, contribute to early detection of these lesions. An adaptive detection method has been investigated to identify white and hypopigmented areas based on lesion histogram statistics. Using the Euclidean distance transform, the lesion is segmented in concentric deciles. Overlays of the white areas on the lesion deciles are determined. Calculated features of automatically detected white areas include lesion decile ratios, normalized number of white areas, absolute and relative size of largest white area, relative size of all white areas, and white area eccentricity, dispersion, and irregularity. Using a back-propagation neural network, the white area statistics yield over 95% diagnostic accuracy of melanomas from benign nevi. White and hypopigmented areas in melanomas tend to be central or paracentral. The four most powerful features on multivariate analysis are lesion decile ratios. Automatic detection of white and hypopigmented areas in melanoma can be accomplished using lesion statistics. A neural network can achieve good discrimination of melanomas from benign nevi using these areas. Lesion decile ratios are useful white area features. PMID:21074971

  10. Clinical Monitoring of Smooth Surface Enamel Lesions Using CP-OCT During Nonsurgical Intervention

    PubMed Central

    Chan, Kenneth H.; Tom, Henry; Lee, Robert C.; Kang, Hobin; Simon, Jacob C.; Staninec, Michal; Darling, Cynthia L.; Pelzner, Roger B.; Fried, Daniel

    2017-01-01

    Introduction Studies have shown that cross-polarization optical coherence tomography (CP-OCT) can be used to image the internal structure of carious lesions in vivo. The objective of this study was to show that CP-OCT can be used to monitor changes in the internal structure of early active carious lesions on smooth surfaces during non-surgical intervention with fluoride. Methods Lesions on the smooth surfaces of teeth were imaged using CP-OCT on 17 test subjects. Lesion structural changes were monitored during fluoride varnish application at 6-week intervals for 30 weeks. The lesion depth (Ld), integrated reflectivity (ΔR), and surface zone thickness (Sz) were monitored. Results A distinct transparent surface zone that may be indicative of lesion arrestment was visible in CP-OCT images on 62/63 lesions before application of fluoride varnish. The lesion depth and internal structure were resolved for all the lesions. The overall change in the mean values for Ld, ΔR, and Sz for all the lesions was minimal and was not significant during the study (P > 0.05). Only 5/63 lesions manifested a significant increase in Sz during intervention. Conclusion Even though it appears that most of the lesions manifested little change with fluoride varnish application in the 30 weeks of the study, CP-OCT was able to measure the depth and internal structure of all the lesions including the thickness of the important transparent surface zone located at the surface of the lesions, indicating that CP-OCT is ideally suited for monitoring lesion severity in vivo. PMID:26955902

  11. Imaging resin infiltration into non-cavitated carious lesions by optical coherence tomography.

    PubMed

    Schneider, Hartmut; Park, Kyung-Jin; Rueger, Claudia; Ziebolz, Dirk; Krause, Felix; Haak, Rainer

    2017-05-01

    Visualisation of the etching process and resin penetration at white spot carious lesions by spectral domain optical coherence tomography (SD-OCT). The non-cavitated carious lesions (ICDAS code 2) of four visually preselected extracted human molars and premolars were verified as enamel lesions by micro computed tomography (μCT). One region of interest (ROI) per tooth was marked by two drill-holes in occlusal-cervical direction. The lesions were imaged by SD-OCT. Lesions were infiltrated (Icon, DMG) according to the manufacturer's instructions. During each treatment step and after light curing of the infiltrant, the ROIs were imaged again by SD-OCT. Teeth were sectioned through the ROIs and section layers were imaged by scanning electron microscopy in order to compare with the OCT images. The image sequences for etching and infiltration were viewed in time lapse. During the etching process, numerous bubbles formed on the lesion surface. Using OCT, the process of resin penetration into the carious lesion body became visible. The early enamel carious lesion was completely infiltrated by the resin whereas infiltration of the advanced enamel carious lesion was incomplete and inhomogeneous. Resin infiltration can be increased by optimizing the etching process. Optical coherence tomography provides information about the process and degree of resin infiltration. Active acid application before resin infiltration is recommendable. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Molecular detection of bacteria associated to caries activity in dentinal lesions.

    PubMed

    Neves, Beatriz Gonçalves; Stipp, Rafael Nóbrega; da Silva Bezerra, Daniela; de Figueiredo Guedes, Sarah Florindo; Rodrigues, Lidiany Karla Azevedo

    2017-07-01

    This study aimed at identifying and quantifying Actinomyces naeslundii, Bifidobacterium spp., Streptococcus mitis group, Lactobacillus acidophilus, Lactobacillus casei group, Streptococcus gordonii, and Streptococcus mutans in active and inactive carious dentine lesions of children with early childhood caries by using quantitative polymerase chain reaction. Fifty-six dentin lesion samples, classified as active (n = 39) or inactive (n = 17), were collected from children aged from 2 to 5 years old. Dentinal-cavitated lesions were evaluated by Nyvad criteria for the assessment of caries lesion activity. Relative quantification revealed that Bifidobacterium spp. and the L. casei group were significantly more abundant in active dentin lesions (p < 0.05). Concentrations of A. naeslundii, S. mitis group, and S. gordonii were not significantly different when comparing dentin lesion activity. The relative proportion of S. mutans was significantly greater in inactive than in active lesions (p < 0.05). Bifidobacterium spp. and L. casei group demonstrated a positive correlation (p = 0.001) in active lesions. The positive detection of L. acidophilus (odds ratio = 15.1) and S. gordonii (odds ratio = 7.7) was significantly associated to the active lesions. The data indicate that higher detection levels of Bifidobacterium spp. and the L. casei group may be linked to dentin lesion activity. Additionally, the presence of L. acidophilus and S. gordonii was associated with lesion activity. Considering that information about the oral microbiota related to dentin caries activity status is relevant, this study provides insights to better understand the differences in the microbiotas between active and arrested dentin cavities.

  13. Early dissemination seeds metastasis in breast cancer

    PubMed Central

    Hosseini, Hedayatollah; Obradović, Milan M.S.; Hoffmann, Martin; Harper, Kathryn; Sosa, Maria Soledad; Werner-Klein, Melanie; Nanduri, Lahiri Kanth; Werno, Christian; Ehrl, Carolin; Maneck, Matthias; Patwary, Nina; Haunschild, Gundula; Gužvić, Miodrag; Reimelt, Christian; Grauvogl, Michael; Eichner, Norbert; Weber, Florian; Hartkopf, Andreas; Taran, Florin-Andrei; Brucker, Sara Y.; Fehm, Tanja; Rack, Brigitte; Buchholz, Stefan; Spang, Rainer; Meister, Gunter; Aguirre-Ghiso, Julio A.; Klein, Christoph A.

    2016-01-01

    Accumulating data suggest that metastatic dissemination often occurs early during tumour formation but the mechanisms of early metastatic spread have not yet been addressed. Here, we studied metastasis in a HER2-driven mouse breast cancer model and found that progesterone-induced signalling triggered migration of cancer cells from early lesions shortly after HER2 activation, but promoted proliferation in advanced primary tumour cells. The switch from migration to proliferation was regulated by elevated HER2 expression and increased tumour cell density involving miRNA-mediated progesterone receptor (PGR) down-regulation and was reversible. Cells from early, low-density lesions displayed more stemness features than cells from dense, advanced tumours, migrated more and founded more metastases. Strikingly, we found that at least 80% of metastases were derived from early disseminated cancer cells (DCC). Karyotypic and phenotypic analysis of human disseminated cancer cells and primary tumours corroborated the relevance of these findings for human metastatic dissemination. PMID:27974799

  14. Contrast-enhanced magnetic resonance imaging of pulmonary lesions: description of a technique aiming clinical practice.

    PubMed

    Koenigkam-Santos, Marcel; Optazaite, Elzbieta; Sommer, Gregor; Safi, Seyer; Heussel, Claus Peter; Kauczor, Hans-Ulrich; Puderbach, Michael

    2015-01-01

    To propose a technique for evaluation of pulmonary lesions using contrast-enhanced MRI; to assess morphological patterns of enhancement and correlate quantitative analysis with histopathology. Thirty-six patients were prospectively studied. Volumetric-interpolated T1W images were obtained during consecutive breath holds after bolus triggered contrast injection. Volume coverage of first three acquisitions was limited (higher temporal resolution) and last acquisition obtained at 4th min. Two radiologists individually evaluated the patterns of enhancement. Region-of-interest-based signal intensity (SI)-time curves were created to assess quantitative parameters. Readers agreed moderately to substantially concerning lesions' enhancement pattern. SI-time curves could be created for all lesions. In comparison to benign, malignant lesions showed higher values of maximum enhancement, early peak, slope and 4th min enhancement. Early peak >15% showed 100% sensitivity to detect malignancy, maximum enhancement >40% showed 100% specificity. The proposed technique is robust, simple to perform and can be applied in clinical scenario. It allows visual evaluation of enhancement pattern/progression together with creation of SI-time curves and assessment of derived quantitative parameters. Perfusion analysis was highly sensitive to detect malignancy, in accordance to what is recommended by most recent guidelines on imaging evaluation of pulmonary lesions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Regression of Human Papillomavirus Intraepithelial Lesions Is Induced by MVA E2 Therapeutic Vaccine

    PubMed Central

    López-Contreras, Mario; Rosales, Carlos; Magallanes-Molina, Jose-Roberto; Gonzalez-Vergara, Roberto; Arroyo-Cazarez, Jose Martin; Ricardez-Arenas, Antonio; del Follo-Valencia, Armando; Padilla-Arriaga, Santiago; Guerrero, Miriam Veronica; Pirez, Miguel Angel; Arellano-Fiore, Claudia; Villarreal, Freddy

    2014-01-01

    Abstract Human papilloma viruses can induce warts, condylomas, and other intraepithelial cervical lesions that can progress to cancer. Cervical cancer is a serious problem in developing countries because early detection is difficult, and thus proper early treatment is many times missing. In this phase III clinical trial, we evaluated the potential use of MVA E2 recombinant vaccinia virus to treat intraepithelial lesions associated with papillomavirus infection. A total of 1176 female and 180 male patients with intraepithelial lesions were studied. They were injected with 107 MVA E2 virus particles directly into their uterus, urethra, vulva, or anus. Patients were monitored by colposcopy and cytology. Immune response was determined by measuring the antibody titer against MVA E2 virus and by analyzing the cytotoxic activity against cancer cells bearing papillomavirus DNA. Papillomavirus was determined by the Hybrid Capture method or by polymerase chain reaction analysis. By histology, 1051 (89.3%) female patients showed complete elimination of lesions after treatment with MVA E2. In 28 (2.4%) female patients, the lesion was reduced to CIN 1. Another 97 (8.3%) female patients presented isolated koilocytes after treatment. In men, all lesions were completely eliminated. All MVA E2–treated patients developed antibodies against the MVA E2 vaccine and generated a specific cytotoxic response against papilloma-transformed cells. Papillomavirus DNA was not detected after treatment in 83% of total patients treated. MVA E2 did not generate any apparent side effects. These data suggest that therapeutic vaccination with MVA E2 vaccine is an excellent candidate to stimulate the immune system and generate regression in intraepithelial lesions when applied locally. PMID:25275724

  16. Comparison of two models of hemispheric specialization with unilaterally lesioned patients: material-specific impairment vs response-bias distortion.

    PubMed

    Guimond, Anik; Braun, Claude M J; Daigneault, Sylvie; Farmer, Jean-Pierre

    2013-10-01

    Validity of two models of hemispheric specialization was compared. The "material-specific impairment" model was radicalized as postulating that left hemisphere (LH) lesions impair processing of verbal material and that right hemisphere (RH) lesions impair processing of visuospatial material, independently of response-bias distortions. The "response-bias distortion" model was radicalized as postulating that LH lesions distort response style toward omissiveness and that RH lesions distort response style toward commissiveness, regardless of material-specific impairments. Participants had comparable left (N=27) or right (N=24) hemisphere cortical lesions having occurred between birth and early adolescence. Four cognitive neuropsychological tests were adjusted to optimize applicability and comparability of the two theoretical models: Rey Complex Figure, Kimura's Recurring Figures, the Story Recall subtest of the Children's Memory Scale, and the California Verbal Learning Test. Both models significantly, independently, and equally distinguished the LH from the RH patients. Both these forms of hemispheric specialization seemed to be implemented very early in life and very rigidly. Intrahemispheric lesion sites, e.g., frontal vs nonfrontal, held no significant relation to the effects described above. © 2013 Elsevier Inc. All rights reserved.

  17. MRI criteria differentiating asymptomatic PML from new MS lesions during natalizumab pharmacovigilance.

    PubMed

    Wijburg, Martijn T; Witte, Birgit I; Vennegoor, Anke; Roosendaal, Stefan D; Sanchez, Esther; Liu, Yaou; Martins Jarnalo, Carine O; Uitdehaag, Bernard Mj; Barkhof, Frederik; Killestein, Joep; Wattjes, Mike P

    2016-10-01

    Differentiation between progressive multifocal leukoencephalopathy (PML) and new multiple sclerosis (MS) lesions on brain MRI during natalizumab pharmacovigilance in the absence of clinical signs and symptoms is challenging but is of substantial clinical relevance. We aim to define MRI characteristics that can aid in this differentiation. Reference and follow-up brain MRIs of natalizumab-treated patients with MS with asymptomatic PML (n=21), or asymptomatic new MS lesions (n=20) were evaluated with respect to characteristics of newly detected lesions by four blinded raters. We tested the association with PML for each characteristic and constructed a multivariable prediction model which we analysed using a receiver operating characteristic (ROC) curve. Presence of punctate T2 lesions, cortical grey matter involvement, juxtacortical white matter involvement, ill-defined and mixed lesion borders towards both grey and white matter, lesion size of >3 cm, and contrast enhancement were all associated with PML. Focal lesion appearance and periventricular localisation were associated with new MS lesions. In the multivariable model, punctate T2 lesions and cortical grey matter involvement predict for PML, while focal lesion appearance and periventricular localisation predict for new MS lesions (area under the curve: 0.988, 95% CI 0.977 to 1.0, sensitivity: 100%, specificity: 80.6%). The MRI characteristics of asymptomatic natalizumab-associated PML lesions proved to differ from new MS lesions. This led to a prediction model with a high discriminating power. Careful assessment of the presence of punctate T2 lesions, cortical grey matter involvement, focal lesion appearance and periventricular localisation allows for an early diagnosis of PML. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  18. Satellite Lesions in Congenital Melanocytic Nevi—Time for a Change of Name

    PubMed Central

    KINSLER, VERONICA

    2011-01-01

    Abstract The term “satellite lesions” is used in many conditions in dermatology, generally to describe smaller lesions near the edges of a principal lesion. An online medical dictionary gives the definition “a smaller lesion accompanying a main one and situated nearby,” and this can apply both macroscopically and microscopically. The implication is that the smaller lesions have spread from the parent lesion. Given this definition and usual understanding of the term its use is not apt in the case of congenital melanocytic nevi (CMN). In the vast majority of cases where the patient is said to have satellite lesions these are not restricted to the area around or near the edge of the principal lesion, and are not necessarily significantly smaller. It seems likely that the early use of the term in this condition is an adaptation of the established and correct use in the context of melanoma. Not only is the term not apt clinically but has no known etiological basis. This leaves us with the question of what to call these lesions in cases of CMN. This proposal is to categorise cases into single or multiple CMN, where multiple is 2 or more nevi of any size at birth. An accurate count or good estimate of the number of lesions at birth should also be recorded, and the largest lesion classified as usual with respect to projected adult size. PMID:21418289

  19. Debulking Surgery for High-grade Serous Endometrial Cancer with Disseminated Peritoneal Lesions

    PubMed Central

    BACALBASA, NICOLAE; BALESCU, IRINA; FILIPESCU, ALEXANDRU

    2017-01-01

    Endometrial cancer is one of the most common malignancies in postmenopausal women with good results in terms of survival, especially when diagnosed in early stages. However, prognosis significantly worseness when disseminated lesions are found. We present the case of a 60-year-old patient who presented with diffuse abdominal pain and weight loss. The patient was diagnosed with endometrial cancer with disseminated lesions and successfully submitted to debulking surgery. At two-year follow-up, the patient presents no recurrent disease. PMID:28652446

  20. Imaging early demineralization with PS-OCT

    NASA Astrophysics Data System (ADS)

    Kang, Hobin; Jiao, Jane J.; Lee, Chulsung; Darling, Cynthia L.; Fried, Daniel

    2010-02-01

    New methods are needed for the nondestructive measurement of tooth demineralization and remineralization to monitor the progression of incipient caries lesions (tooth decay) for effective nonsurgical intervention and to evaluate the performance of anti-caries treatments such as chemical treatments or laser irradiation. Studies have shown that optical coherence tomography (OCT) has great potential to fulfill this role since it can be used to measure the depth and severity of early lesions with an axial resolution exceeding 10-μm, it is easy to apply in vivo and it can be used to image the convoluted topography of tooth occlusal surfaces. In this paper we attempt to determine the earliest stage at which we can detect significant differences in lesion severity. Automated methods of analysis were used to measure the depth and severity of demineralized bovine enamel produced using a simulated caries model that emulates demineralization in the mouth. Significant differences in the depth and integrated reflectivity from the lesions were detected after only a few hours of demineralization. These results demonstrate that cross polarization OCT is ideally suited for the nondestructive assessment of early demineralization.

  1. Histopathological lesions and DNA adducts in the liver of European flounder (Platichthys flesus) collected in the Seine estuary versus two reference estuarine systems on the French Atlantic coast.

    PubMed

    Cachot, Jérôme; Cherel, Yan; Larcher, Thibaut; Pfohl-Leszkowicz, Annie; Laroche, Jean; Quiniou, Louis; Morin, Jocelyne; Schmitz, Julien; Burgeot, Thierry; Pottier, Didier

    2013-02-01

    . Flounders from the Bay of Veys had relatively few liver lesions as compared to flounders from the two other estuaries. Flounders from the Ster estuary exhibited the highest prevalence of parasites (37.2 %) and inflammations (51.1 %). Finally, FCA and liver tumors occurred at very similar levels in both flounder populations from the Seine and the Ster estuaries. Group 0 flounders inhabiting the upper Seine estuary were more prone to parasitic and pre-neoplastic hepatic lesions and had higher levels of liver DNA adducts than the older ones living downstream. It was postulated that group 0 European flounders may serve as valuable bioindicators for assessing the quality of estuarine waters and the health status of euryhaline fish populations.

  2. Carcinoma ex pleomorphic adenoma, with particular emphasis on early lesions.

    PubMed

    Di Palma, Silvana

    2013-07-01

    Carcinoma ex pleomorphic adenoma (CXPA) is a broad category of carcinomas of the salivary glands which includes at least 2 clinically relevant categories; one is referred here as early CXPA (ECXPA), the other as widely invasive CXPA. The former includes several histological patterns ranging from non-invasive/in situ/intraductal/intratubular, early invasive/extratubular/intracapsular and extracapsular (up to 6 mm). The latter includes any CXPA with invasion of >6 mm. The clinical behaviour of ECXPA is not aggressive and tends to overlap that of a pleomorphic adenoma (PA) which makes the histological report of carcinoma contradictory. These early malignant changes in PA are known since the 1970s but it has been the use of immunohistochemical and molecular genetic analysis for HER-2 and TP53 gene in the last decade that has clarified the genuine malignant nature of the cells. HER-2 and TP53 gene and protein are involved in the early stages of malignant transformation of PA. Moreover the immunohistochemical over-expression HER-2, p53 protein and Mib-1 proliferation marker may be useful markers to identify malignant areas in PA.

  3. Clinical monitoring of smooth surface enamel lesions using CP-OCT during nonsurgical intervention.

    PubMed

    Chan, Kenneth H; Tom, Henry; Lee, Robert C; Kang, Hobin; Simon, Jacob C; Staninec, Michal; Darling, Cynthia L; Pelzner, Roger B; Fried, Daniel

    2016-12-01

    Studies have shown that cross-polarization optical coherence tomography (CP-OCT) can be used to image the internal structure of carious lesions in vivo. The objective of this study was to show that CP-OCT can be used to monitor changes in the internal structure of early active carious lesions on smooth surfaces during non-surgical intervention with fluoride. Lesions on the smooth surfaces of teeth were imaged using CP-OCT on 17 test subjects. Lesion structural changes were monitored during fluoride varnish application at 6-week intervals for 30 weeks. The lesion depth (L d ), integrated reflectivity (ΔR), and surface zone thickness (S z ) were monitored. A distinct transparent surface zone that may be indicative of lesion arrestment was visible in CP-OCT images on 62/63 lesions before application of fluoride varnish. The lesion depth and internal structure were resolved for all the lesions. The overall change in the mean values for L d , ΔR, and S z for all the lesions was minimal and was not significant during the study (P > 0.05). Only 5/63 lesions manifested a significant increase in S z during intervention. Even though it appears that most of the lesions manifested little change with fluoride varnish application in the 30 weeks of the study, CP-OCT was able to measure the depth and internal structure of all the lesions including the thickness of the important transparent surface zone located at the surface of the lesions, indicating that CP-OCT is ideally suited for monitoring lesion severity in vivo. Lasers Surg. Med. 48:915-923, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Effects of flaxseed lignan secoisolariciresinol diglucoside on preneoplastic biomarkers of cancer progression in a model of simultaneous breast and ovarian cancer development

    PubMed Central

    Delman, Devora M.; Fabian, Carol J.; Kimler, Bruce F.; Yeh, Henry; Petroff, Brian K.

    2016-01-01

    Breast cancer prevention efforts are focused increasingly on potentially beneficial dietary modifications due to their ease of implementation and wide acceptance. Secoisolariciresinol diglucoside (SDG) is a lignan found in high concentration in flaxseed that may have selective estrogen receptor modulator (SERM)-like effects resulting in antiestrogenic activity in a high estrogen environment. In parallel with a human phase II prevention trial, female ACI rats (n=8–10/group) received 0, 10 or 100 ppm SDG in the feed. The 100 ppm SDG treatment produced similar blood lignan levels as those observed in our human pilot study. Mammary and ovarian cancer progression were induced using local ovarian DMBA treatment and subcutaneous sustained release 17β-estradiol administered starting at 7 weeks of age. Mammary gland and ovarian tissues were collected at 3 months after initiation of treatment and examined for changes in epithelial cell proliferation (Ki-67, cell counts), histopathology and dysplasia scores as well as expression of selected genes involved in proliferation, estrogen signaling and cell adhesion. Treatment with SDG normalized several biomarkers in mammary gland tissue (dysplasia, cell number, and expression of several genes) that had been altered by carcinogen. There is no indication that SDG promotes pre-neoplastic progression in the ovarian epithelium. PMID:26010915

  5. The development of object recognition memory in rhesus macaques with neonatal lesions of the perirhinal cortex.

    PubMed

    Zeamer, Alyson; Richardson, Rebecca L; Weiss, Alison R; Bachevalier, Jocelyne

    2015-02-01

    To investigate the role of the perirhinal cortex on the development of recognition measured by the visual paired-comparison (VPC) task, infant monkeys with neonatal perirhinal lesions and sham-operated controls were tested at 1.5, 6, 18, and 48 months of age on the VPC task with color stimuli and intermixed delays of 10 s, 30 s, 60 s, and 120 s. Monkeys with neonatal perirhinal lesions showed an increase in novelty preference between 1.5 and 6 months of age similar to controls, although at these two ages, performance remained significantly poorer than that of control animals. With age, performance in animals with neonatal perirhinal lesions deteriorated as compared to that of controls. In contrast to the lack of novelty preference in monkeys with perirhinal lesions acquired in adulthood, novelty preference in the neonatally operated animals remained above chance at all delays and all ages. The data suggest that, although incidental recognition memory processes can be supported by the perirhinal cortex in early infancy, other temporal cortical areas may support these processes in the absence of a functional perirhinal cortex early in development. The neural substrates mediating incidental recognition memory processes appear to be more widespread in early infancy than in adulthood. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Signal transduction disturbance related to hepatocarcinogenesis in mouse by prolonged exposure to Nanjing drinking water.

    PubMed

    Zhang, Rui; Sun, Jie; Zhang, Yan; Cheng, Shupei; Zhang, Xiaowei

    2013-09-01

    Toxicogenomic approaches were used to investigate the potential hepatocarcinogenic effects on mice by oral exposure to Nanjing drinking water (NJDW). Changes in the hepatic transcriptome of 3 weeks male mice (Mus musculus) were monitored and dissected after oral exposure to NJDW for 90 days. No preneoplastic and neoplastic lesions were observed in the hepatic tissue by the end of NJDW exposure. However, total of 746 genes were changed transcriptionally. Thirty-one percent of differentially expressed genes (DEGs) were associated with the functional categories of cell cycle regulation, adhesion, growth, apoptosis, and signal transduction, which are closely implicated in tumorigenesis and progression. Interrogation of Kyoto Encyclopedia of Genes and Genomes revealed that 43 DEGs were mapped to several crucial signaling pathways implicated in the pathogenesis of hepatocellular carcinoma (HCC). In signal transduction network constructed via Genes2Networks software, Egfr, Akt1, Atf2, Ctnnb1, Hras, Mapk1, Smad2, and Ccnd1 were hubs. Direct gene-disease relationships obtained from Comparative Toxicogenomics Database and scientific literatures revealed that the hubs have direct mechanism or biomarker relationships with hepatocellular preneoplastic lesions or hepatocarcinogenesis. Therefore, prolonged intake of NJDW without employing any indoor water treatment strategy might predispose mouse to HCC. Furthermore, Egfr, Akt1, Ctnnb1, Hras, Mapk1, Smad2, and Ccnd1 were identified as promising biomarkers of the potential combined hepatocarcinogenicity.

  7. Personalized immune-interception of cancer and the battle of two adaptive systems--when is the time right?

    PubMed

    Dhodapkar, Madhav V

    2013-03-01

    A growing body of evidence points to a coevolutionary model of cancer, wherein the cross-talk between tumor cells (or their subclones) and the host determine the malignant potential of individual tumors. Most of this natural history is clinically invisible and includes preneoplastic states. The capacity of the immune system to recognize these incipient lesions provides the basis for targeting them immunologically to arrest the development of preneoplasia toward clinical cancer. Kimura and colleagues provide evidence of immunogenicity of a potential cancer vaccine in patients with a history of advanced colon adenomas. These studies provide proof-of-principle or feasibility of such an approach in the clinic. Here, we discuss emerging opportunities and challenges in harnessing the immune system to "intercept" the precursor or preneoplastic lesions. Both cancer cells as well as the immune system represent independent and complex systems with plasticity and adaptive potential. It is therefore likely that specific aspects of the cross-talk between tumor cells and host may differ between individual tumors and determine the evolution of both tumors and the host response. We try to make the case to consider individualized approaches based on the genetic make-up of tumor cells and properties of the host response. Such strategies may be needed to optimally position the immune system to prevent cancers. ©2013 AACR.

  8. Attenuation of insulin-resistance-based hepatocarcinogenesis and angiogenesis by combined treatment with branched-chain amino acids and angiotensin-converting enzyme inhibitor in obese diabetic rats.

    PubMed

    Yoshiji, Hitoshi; Noguchi, Ryuichi; Kaji, Kosuke; Ikenaka, Yasuhide; Shirai, Yusaku; Namisaki, Tadashi; Kitade, Mitsuteru; Tsujimoto, Tatsuhiro; Kawaratani, Hideto; Fukui, Hiroshi

    2010-04-01

    Insulin resistance (IR) is reportedly involved in the progression of hepatocellular carcinoma (HCC). Because neovascularization plays an important role in HCC, including hepatocarcinogenesis, an angiostatic therapy would be a promising approach for chemoprevention against HCC. The aim of the present study was to examine the combined effect of clinically used branched-chain amino acids (BCAAs) and an angiotensin-converting enzyme inhibitor (ACE-I), in conjunction with neovascularization, on hepatocarcinogenesis under the condition of IR. The combined effect of the treatment on the development of liver enzyme-altered preneoplastic lesions, angiogenesis, and several indices was elucidated in obese diabetic rats. We also performed several sets of in vitro experiments to examine the mechanisms involved. When used individually, both BCAAs and ACE-I at clinically comparable low doses significantly attenuated the development of preneoplastic lesions, along with the suppression of both angiogenesis and vascular endothelial growth factor (VEGF) expression. The combination treatment with both agents exerted a more potent inhibitory effect than that of either single agent. Our in vitro study showed a similar combined effect on endothelial cell tubule formation. This combination regimen showed a marked chemopreventive effect against hepatocarcinogenesis, along with suppression of neovascularization and VEGF expression, in obese diabetic rats. Because both BCAAs and ACE-Is are widely used in clinical practice, this combination therapy may represent a potential new strategy for chemoprevention against IR-based HCC in the future.

  9. Near-IR and CP-OCT Imaging of Suspected Occlusal Caries Lesions

    PubMed Central

    Simon, Jacob C.; Kang, Hobin; Staninec, Michal; Jang, Andrew T.; Chan, Kenneth H.; Darling, Cynthia L.; Lee, Robert C.; Fried, Daniel

    2017-01-01

    Introduction Radiographic methods have poor sensitivity for occlusal lesions and by the time the lesions are radiolucent they have typically progressed deep into the dentin. New more sensitive imaging methods are needed to detect occlusal lesions. In this study, cross-polarization optical coherence tomography (CP-OCT) and near-IR imaging were used to image questionable occlusal lesions (QOC's) that were not visible on radiographs but had been scheduled for restoration on 30 test subjects. Methods Near-IR reflectance and transillumination probes incorporating a high definition InGaAs camera and near-IR broadband light sources were used to acquire images of the lesions before restoration. The reflectance probe utilized cross-polarization and operated at wavelengths from 1500–1700-nm where there is an increase in water absorption for higher contrast. The transillumination probe was operated at 1300-nm where the transparency of enamel is highest. Tomographic images (6×6×7 mm3) of the lesions were acquired using a high-speed swept-source CP-OCT system operating at 1300-nm before and after removal of the suspected lesion. Results Near-IR reflectance imaging at 1500–1700-nm yielded significantly higher contrast (p<0.05) of the demineralization in the occlusal grooves compared with visible reflectance imaging. Stains in the occlusal grooves greatly reduced the lesion contrast in the visible range yielding negative values. Only half of the 26 lesions analyzed showed the characteristic surface demineralization and increased reflectivity below the dentinal-enamel junction (DEJ) in 3D OCT images indicative of penetration of the lesion into the dentin. Conclusion This study demonstrates that near-IR imaging methods have great potential for improving the early diagnosis of occlusal lesions. PMID:28339115

  10. Automated diagnosis of focal liver lesions using bidirectional empirical mode decomposition features.

    PubMed

    Acharya, U Rajendra; Koh, Joel En Wei; Hagiwara, Yuki; Tan, Jen Hong; Gertych, Arkadiusz; Vijayananthan, Anushya; Yaakup, Nur Adura; Abdullah, Basri Johan Jeet; Bin Mohd Fabell, Mohd Kamil; Yeong, Chai Hong

    2018-03-01

    Liver is the heaviest internal organ of the human body and performs many vital functions. Prolonged cirrhosis and fatty liver disease may lead to the formation of benign or malignant lesions in this organ, and an early and reliable evaluation of these conditions can improve treatment outcomes. Ultrasound imaging is a safe, non-invasive, and cost-effective way of diagnosing liver lesions. However, this technique has limited performance in determining the nature of the lesions. This study initiates a computer-aided diagnosis (CAD) system to aid radiologists in an objective and more reliable interpretation of ultrasound images of liver lesions. In this work, we have employed radon transform and bi-directional empirical mode decomposition (BEMD) to extract features from the focal liver lesions. After which, the extracted features were subjected to particle swarm optimization (PSO) technique for the selection of a set of optimized features for classification. Our automated CAD system can differentiate normal, malignant, and benign liver lesions using machine learning algorithms. It was trained using 78 normal, 26 benign and 36 malignant focal lesions of the liver. The accuracy, sensitivity, and specificity of lesion classification were 92.95%, 90.80%, and 97.44%, respectively. The proposed CAD system is fully automatic as no segmentation of region-of-interest (ROI) is required. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Limitations on the Developing Preterm Brain: Impact of Periventricular White Matter Lesions on Brain Connectivity and Cognition

    ERIC Educational Resources Information Center

    Pavlova, Marina A.; Krageloh-Mann, Ingeborg

    2013-01-01

    Brain lesions to the white matter in peritrigonal regions, periventricular leukomalacia, in children who were born prematurely represent an important model for studying limitations on brain development. The lesional pattern is of early origin and bilateral, that constrains the compensatory potential of the brain. We suggest that (i) topography and…

  12. Example based lesion segmentation

    NASA Astrophysics Data System (ADS)

    Roy, Snehashis; He, Qing; Carass, Aaron; Jog, Amod; Cuzzocreo, Jennifer L.; Reich, Daniel S.; Prince, Jerry; Pham, Dzung

    2014-03-01

    Automatic and accurate detection of white matter lesions is a significant step toward understanding the progression of many diseases, like Alzheimer's disease or multiple sclerosis. Multi-modal MR images are often used to segment T2 white matter lesions that can represent regions of demyelination or ischemia. Some automated lesion segmentation methods describe the lesion intensities using generative models, and then classify the lesions with some combination of heuristics and cost minimization. In contrast, we propose a patch-based method, in which lesions are found using examples from an atlas containing multi-modal MR images and corresponding manual delineations of lesions. Patches from subject MR images are matched to patches from the atlas and lesion memberships are found based on patch similarity weights. We experiment on 43 subjects with MS, whose scans show various levels of lesion-load. We demonstrate significant improvement in Dice coefficient and total lesion volume compared to a state of the art model-based lesion segmentation method, indicating more accurate delineation of lesions.

  13. Spinal cord lesions in Bangladesh: an epidemiological study 1994 - 1995.

    PubMed

    Hoque, M F; Grangeon, C; Reed, K

    1999-12-01

    Spinal Cord Lesions are a major public health problem in Bangladesh. This epidemiological study was undertaken in order to identify the causes of spinal cord lesions and thus to allow prevention and control programs to be developed. The records of 247 patients with spinal cord lesions admitted to The Centre for the Rehabilitation of the Paralysed (CRP), Savar, Dhaka from January 1994 to June 1995 were reviewed retrospectively. Comparisons were made with the reports of studies from other countries, both developing and developed. The most common cause of traumatic lesions was a fall from a height followed by falling when carrying a heavy weight on the head and road traffic accidents. Most of the patients were between 20 - 40 years old and the overall age group ranged from 10 - 70 years. The male:female ratio was 7.5 : 1.0. Among the traumatic spinal cord lesions, 60% were paraplegics and 40% tetraplegics. Among the non-traumatic spinal cord lesions cases 84% were paraplegics and 16% tetraplegics. The leading cause of death resulted from respiratory complications and these deaths occurred in the very early period of admission. From the results it can be deduced that the high incidence of spinal cord lesion as a result from falls from a height, and from falling when carrying a heavy weight on the head, can be explained by the mainly agricultural based economy of Bangladesh. The most common age group (10 - 40 years) of patients reflects the socio-economic conditions of Bangladesh. The male:female ratio (7.5 : 1.0) of patients with a spinal cord lesion is due to the socio-economic status and to the traditional culture of the society.

  14. Pulmonary adenocarcinoma: A renewed entity in 2011

    PubMed Central

    Kadara, Humam; Kabbout, Mohamed; Wistuba, Ignacio I.

    2014-01-01

    Lung cancer, of which non-small-cell lung cancer comprises the majority, is the leading cause of cancer-related deaths in the United States and worldwide. Lung adenocarcinomas are a major subtype of non-small-cell lung cancers, are increasing in incidence globally in both males and females and in smokers and non-smokers, and are the cause for almost 50% of deaths attributable to lung cancer. Lung adenocarcinoma is a tumour with complex biology that we have recently started to understand with the advent of various histological, transcriptomic, genomic and proteomic technologies. However, the histological and molecular pathogenesis of this malignancy is still largely unknown. This review will describe advances in the molecular pathology of lung adenocarcinoma with emphasis on genomics and DNA alterations of this disease. Moreover, the review will discuss recognized lung adenocarcinoma preneoplastic lesions and current concepts of the early pathogenesis and progression of the disease. We will also portray the field cancerization phenomenon and lineage-specific oncogene expression pattern in lung cancer and how both remerging concepts can be exploited to increase our understanding of lung adenocarcinoma pathogenesis for subsequent development of biomarkers for early detection of adenocarcinomas and possibly personalized prevention. PMID:22040022

  15. Treating vascular lesions.

    PubMed

    Astner, Susanne; Anderson, R Rox

    2005-01-01

    The treatment of acquired vascular lesions is one of the most commonly requested and performed cutaneous laser procedures. Furthermore, every year, 40,000 children are born in the United States each with congenital vascular lesions and malformations. Laser treatment of vascular lesion is based on the principle of selective photothermolysis, conceived in the 1980s. A variety of different lasers and light sources have since been used in the treatment of vascular lesions: lasers with wavelengths between green and yellow, near infrared lasers, and broadband light sources. Despite limitations, this remains the treatment of choice today. This publication addresses acquired and congenital vascular lesions as different entities and proposes a separation of vascular lesions into those that can easily be treated from those where clearance is difficult. Different treatment modalities and the various endpoints of individual vascular lesions will be discussed.

  16. Aurora-A over-expression in high-grade PIN lesions and prostate cancer.

    PubMed

    Buschhorn, Holly McKlveen; Klein, Robert R; Chambers, Susan M; Hardy, Margaret C; Green, Sylvan; Bearss, David; Nagle, Raymond B

    2005-09-01

    Over-expression of Aurora-A (Aurora 2 kinase, STK-15), a protein found in centrosomes thought to be associated with genetic instability, has been previously documented in prostate cancer [Pihan et al.: Cancer Res 61(5):2212-2219, 2001]. It is unknown if this protein is also over-expressed in high-grade prostatic intraepithelial neoplasia (PIN) lesions. PIN lesions were examined for increased Aurora-A using immunohistochemical staining on archival paraffin embedded prostatectomy tissue. Aurora-A expression was scored using size, number, and staining intensity. Protein expression was examined and compared between stromal cells, normal glands, high-grade PIN lesions, and invasive cancer. Immunohistochemistry shows an increased expression of Aurora-A in 96% of high-grade PIN cases, and 98% in cancer lesions. Twenty-nine percent of cases of normal glands from cancerous prostates also showed increased Aurora-A expression. Over-expression of Aurora-A is present in some normal and the majority of high-grade PIN lesions indicating that this may be an early event that leads to the genetic instability seen in prostate carcinogenesis. Copyright 2005 Wiley-Liss, Inc.

  17. Endoscopic fluorescence imaging for early assessment of anastomotic recurrence of Crohn's disease

    NASA Astrophysics Data System (ADS)

    Mordon, Serge R.; Maunoury, Vincent; Geboes, K.; Klein, Olivier; Desreumaux, P.; Debaert, A.; Colombel, Jean-Frederic

    1999-02-01

    Crohn's disease is an inflammatory bowel disease of unknown etiology. The mechanism of the initial mucosal alterations is still unclear: ulcerations overlying lymphoid follicles and/or vasculitis have been proposed as the early lesions. We have developed a new and original method combining endoscopy of fluorescence angiography for identifying the early pathological lesions, occurring in the neo-terminal ileum after right ileocolonic resection. The patient population consisted of 10 subjects enrolled in a prospective protocol of endoscopic follow-up at 3 and 12 months after surgery. Fluorescence imaging showed small spots giving a bright fluorescence distributed singly in mucosa which appeared normal in routine endoscopy. Histopathological examination demonstrated that the fluorescence of small spots originated from small, usually superficial, erosive lesions. In several cases, these erosive lesions occurred over lymphoid follicles. Endoscopic fluorescence imaging provides a suitable means of investigating the initial aspect of the Crohn's disease process in displaying some correlative findings between fluorescent aspects and early pathological mucosal alterations.

  18. IL-17/Th17 Pathway Is Activated in Acne Lesions

    PubMed Central

    Kelhälä, Hanna-Leena; Palatsi, Riitta; Fyhrquist, Nanna; Lehtimäki, Sari; Väyrynen, Juha P.; Kallioinen, Matti; Kubin, Minna E.; Greco, Dario; Tasanen, Kaisa; Alenius, Harri; Bertino, Beatrice; Carlavan, Isabelle; Mehul, Bruno; Déret, Sophie; Reiniche, Pascale; Martel, Philippe; Marty, Carine; Blume-Peytavi, Ulrike; Voegel, Johannes J.; Lauerma, Antti

    2014-01-01

    The mechanisms of inflammation in acne are currently subject of intense investigation. This study focused on the activation of adaptive and innate immunity in clinically early visible inflamed acne lesions and was performed in two independent patient populations. Biopsies were collected from lesional and non-lesional skin of acne patients. Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed at the RNA and also protein level with real-time PCR (RT-PCR) and Luminex technology. Cytokines involved in Th17 lineage differentiation (IL-1β, IL-6, TGF-β, IL23p19) were remarkably induced at the RNA level. In addition, proinflammatory cytokines and chemokines (TNF-α, IL-8, CSF2 and CCL20), Th1 markers (IL12p40, CXCR3, T-bet, IFN-γ), T regulatory cell markers (Foxp3, IL-10, TGF-β) and IL-17 related antimicrobial peptides (S100A7, S100A9, lipocalin, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL-17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway is activated and may play a pivotal role in the disease process, possibly offering new targets of therapy. PMID:25153527

  19. Strategic Lesions in the Anterior Thalamic Radiation and Apathy in Early Alzheimer's Disease

    PubMed Central

    Torso, Mario; Serra, Laura; Giulietti, Giovanni; Spanò, Barbara; Tuzzi, Elisa; Koch, Giacomo; Caltagirone, Carlo; Cercignani, Mara; Bozzali, Marco

    2015-01-01

    Background Behavioural disorders and psychological symptoms of Dementia (BPSD) are commonly observed in Alzheimer’s disease (AD), and strongly contribute to increasing patients' disability. Using voxel-lesion-symptom mapping (VLSM), we investigated the impact of white matter lesions (WMLs) on the severity of BPSD in patients with amnestic mild cognitive impairment (a-MCI). Methods Thirty-one a-MCI patients (with a conversion rate to AD of 32% at 2 year follow-up) and 26 healthy controls underwent magnetic resonance imaging (MRI) examination at 3T, including T2-weighted and fluid-attenuated-inversion-recovery images, and T1-weighted volumes. In the patient group, BPSD was assessed using the Neuropsychiatric Inventory-12. After quantitative definition of WMLs, their distribution was investigated, without an a priori anatomical hypothesis, against patients’ behavioural symptoms. Unbiased regional grey matter volumetrics was also used to assess the contribution of grey matter atrophy to BPSD. Results Apathy, irritability, depression/dysphoria, anxiety and agitation were shown to be the most common symptoms in the patient sample. Despite a more widespread anatomical distribution, a-MCI patients did not differ from controls in WML volumes. VLSM revealed a strict association between the presence of lesions in the anterior thalamic radiations (ATRs) and the severity of apathy. Regional grey matter atrophy did not account for any BPSD. Conclusions This study indicates that damage to the ATRs is strategic for the occurrence of apathy in patients with a-MCI. Disconnection between the prefrontal cortex and the mediodorsal and anterior thalamic nuclei might represent the pathophysiological substrate for apathy, which is one of the most common psychopathological symptoms observed in dementia. PMID:25932637

  20. B-Spline Filtering for Automatic Detection of Calcification Lesions in Mammograms

    NASA Astrophysics Data System (ADS)

    Bueno, G.; Sánchez, S.; Ruiz, M.

    2006-10-01

    Breast cancer continues to be an important health problem between women population. Early detection is the only way to improve breast cancer prognosis and significantly reduce women mortality. It is by using CAD systems that radiologist can improve their ability to detect, and classify lesions in mammograms. In this study the usefulness of using B-spline based on a gradient scheme and compared to wavelet and adaptative filtering has been investigated for calcification lesion detection and as part of CAD systems. The technique has been applied to different density tissues. A qualitative validation shows the success of the method.

  1. Old lower stem bark lesions apparently caused by unsuccessful spruce beetle attacks still evident on live spruce trees years later

    Treesearch

    John S. Hard; Ken P. Zogas

    2010-01-01

    We examined old bark lesions on Lutz spruce in young stands on the Kenai Peninsula, Alaska, to determine their cause. Distribution of these lesions along lower stems was similar to the distribution of spruce beetle attacks during epidemics. These lesions apparently resulted from unsuccessful attacks by spruce beetles during the late 1980s and early 1990s and appear to...

  2. Arsenic exacerbates atherosclerotic lesion formation and inflammation in ApoE-/- mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Srivastava, Sanjay, E-mail: sanjay@louisville.ed; Center for Environmental Genomics and Integrative Biology, University of Louisville, Louisville, KY 40202; Vladykovskaya, Elena N.

    2009-11-15

    Exposure to arsenic-contaminated water has been shown to be associated with cardiovascular disease, especially atherosclerosis. We examined the effect of arsenic exposure on atherosclerotic lesion formation, lesion composition and nature in ApoE-/- mice. Early post-natal exposure (3-week-old mice exposed to 49 ppm arsenic as NaAsO{sub 2} in drinking water for 7 weeks) increased the atherosclerotic lesion formation by 3- to 5-fold in the aortic valve and the aortic arch, without affecting plasma cholesterol. Exposure to arsenic for 13 weeks (3-week-old mice exposed to 1, 4.9 and 49 ppm arsenic as NaAsO{sub 2} in drinking water) increased the lesion formation andmore » macrophage accumulation in a dose-dependent manner. Temporal studies showed that continuous arsenic exposure significantly exacerbated the lesion formation throughout the aortic tree at 16 and 36 weeks of age. Withdrawal of arsenic for 12 weeks after an initial exposure for 21 weeks (to 3-week-old mice) significantly decreased lesion formation as compared with mice continuously exposed to arsenic. Similarly, adult exposure to 49 ppm arsenic for 24 weeks, starting at 12 weeks of age increased lesion formation by 2- to 3.6-fold in the aortic valve, the aortic arch and the abdominal aorta. Lesions of arsenic-exposed mice displayed a 1.8-fold increase in macrophage accumulation whereas smooth muscle cell and T-lymphocyte contents were not changed. Expression of pro-inflammatory chemokine MCP-1 and cytokine IL-6 and markers of oxidative stress, protein-HNE and protein-MDA adducts were markedly increased in lesions of arsenic-exposed mice. Plasma concentrations of MCP-1, IL-6 and MDA were also significantly elevated in arsenic-exposed mice. These data suggest that arsenic exposure increases oxidative stress, inflammation and atherosclerotic lesion formation.« less

  3. Early and late effects of aspirin and naproxen on microRNAs in the lung and blood of mice, either unexposed or exposed to cigarette smoke

    PubMed Central

    Izzotti, Alberto; Balansky, Roumen; Ganchev, Gancho; Iltcheva, Marietta; Longobardi, Mariagrazia; Pulliero, Alessandra; Camoirano, Anna; D'Agostini, Francesco; Geretto, Marta; Micale, Rosanna T.; La Maestra, Sebastiano; Miller, Mark Steven; Steele, Vernon E.; De Flora, Silvio

    2017-01-01

    We recently showed that nonsteroidal anti-inflammatory drugs (NSAIDs) are able to inhibit the lung tumors induced by cigarette smoke, either mainstream (MCS) or environmental (ECS), in female mice. We used subsets of mice to analyze the expression of 1135 microRNAs in both lung and blood serum, as related to the whole-body exposure to smoke and/or oral administration of either aspirin or naproxen. In a first study, we evaluated early microRNA alterations in A/J mice exposed to ECS for 10 weeks, starting at birth, and/or treated with NSAIDs for 6 weeks, starting after weaning. At that time, when no histopathological change were apparent, ECS caused a considerable downregulation of pulmonary microRNAs affecting both adaptive mechanisms and disease-related pathways. Aspirin and naproxen modulated, with intergender differences, the expression of microRNAs having a variety of functions, also including regulation of cyclooxygenases and inflammation. In a second study, we evaluated late microRNA alterations in Swiss H mice exposed to MCS during the first 4 months of life and treated with NSAIDs after weaning until 7.5 months of life, when tumors were detected in mouse lung. Modulation of pulmonary microRNAs by the two NSAIDs was correlated with their ability to prevent preneoplastic lesions (microadenomas) and adenomas in the lung. In both studies, exposure to smoke and/or treatment with NSAIDs also modulated microRNA profiles in the blood serum. However, their levels were poorly correlated with those of pulmonary microRNAs, presumably because circulating microRNAs reflect the contributions from multiple organs and not only from lung. PMID:29156752

  4. Characterization of oral precancerous lesions based on higher-harmonic generation microscopy

    NASA Astrophysics Data System (ADS)

    Lin, Chen-Yu; Lin, Chih-Feng; Sun, Chi-Kuang

    2013-03-01

    It is generally accepted that oral cancer arises in the presence of oral precancerous lesions. However, the clinical courses of these lesions are quite unpredictable, and a fundamental enigma remains that when and how these lesions turn to malignant growth. Characterization of these potentially malignant lesions is thus important and could serve as early indicators of this neoplastic transformation process, potentially facilitates the treatment outcome and improves the survival rate. Higher harmonic generation microscope (HGM), providing images with a <500nm lateral resolution at a 300μm penetration depth without leaving photodamages in the tissues, was used for this purpose. Oral cavity biopsies were obtained from 18 patients with clinical suspected oral precancerous lesions scheduled for surgical biopsy. HGM images were compared with histological images to determine the results. By visualization of subtle cellular and morphological changes, the preliminary result of this HGM image discloses excellent consistency with traditional histolopathology studies, without the need for fixation, sectioning and staining. More specifically speaking, the keratin thickness was found to be increased comparing with normal adjacent controls. In some cases, variations in cell size, nuclear size and increased nuclear/cytoplasmic ratio, and increased size of nucleoli were identified, indicating different stages of malignant transformation. These results together indicated that HGM provides the capability to characterize features of oral precancerous lesions as well as oral cancer progression, and holds the greatest potential as an ideal tool for clinical screening and surveillance of suspicious oral lesions.

  5. Debulking Surgery for High-grade Serous Endometrial Cancer with Disseminated Peritoneal Lesions.

    PubMed

    Bacalbasa, Nicolae; Balescu, Irina; Filipescu, Alexandru

    2017-01-01

    Endometrial cancer is one of the most common malignancies in postmenopausal women with good results in terms of survival, especially when diagnosed in early stages. However, prognosis significantly worseness when disseminated lesions are found. We present the case of a 60-year-old patient who presented with diffuse abdominal pain and weight loss. The patient was diagnosed with endometrial cancer with disseminated lesions and successfully submitted to debulking surgery. At two-year follow-up, the patient presents no recurrent disease. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  6. Laboratory management of cervical intraepithelial neoplasia: proposing a new paradigm.

    PubMed

    Herfs, Michael; Crum, Christopher P

    2013-03-01

    Since the discovery of human papillomavirus (HPV) type 16 in early 80s, the link between HPV and cervical cancer has been established with certainty, a function of the discovery and cloning of a range of HPV types associated with both cancer precursors (cervical intraepithelial neoplasia or CIN) and carcinomas and extensive epidemiologic, clinical, pathologic, and experimental data. These accumulated results have culminated in new paradigms of cancer prevention through screening and triage. Despite this, the management of women with CIN is still suboptimal and the overtreatment of these conditions still occurs, largely due to the lack of clarity regarding which precancerous lesions are most likely to progress in grade. Recently, a discrete population of cuboidal cells was discovered at the cervical squamocolumnar junction, the anatomic site where the large majority of HPV-related (pre)neoplastic lesions develop. These cells seem to be embryonic in nature and participate both in benign metaplasias and the initial phase of precancer development. This review summarizes the historical evolution of precursor management, assesses the potential role of this and other discoveries in segregating lower from higher-risk precursors, and examines their potential impact on the management of women with real or potential cervical cancer precursors.

  7. Sweet-spot training for early esophageal cancer detection

    NASA Astrophysics Data System (ADS)

    van der Sommen, Fons; Zinger, Svitlana; Schoon, Erik J.; de With, Peter H. N.

    2016-03-01

    Over the past decade, the imaging tools for endoscopists have improved drastically. This has enabled physicians to visually inspect the intestinal tissue for early signs of malignant lesions. Besides this, recent studies show the feasibility of supportive image analysis for endoscopists, but the analysis problem is typically approached as a segmentation task where binary ground truth is employed. In this study, we show that the detection of early cancerous tissue in the gastrointestinal tract cannot be approached as a binary segmentation problem and it is crucial and clinically relevant to involve multiple experts for annotating early lesions. By employing the so-called sweet spot for training purposes as a metric, a much better detection performance can be achieved. Furthermore, a multi-expert-based ground truth, i.e. a golden standard, enables an improved validation of the resulting delineations. For this purpose, besides the sweet spot we also propose another novel metric, the Jaccard Golden Standard (JIGS) that can handle multiple ground-truth annotations. Our experiments involving these new metrics and based on the golden standard show that the performance of a detection algorithm of early neoplastic lesions in Barrett's esophagus can be increased significantly, demonstrating a 10 percent point increase in the resulting F1 detection score.

  8. The learning curve for narrow-band imaging in the diagnosis of precancerous gastric lesions by using Web-based video.

    PubMed

    Dias-Silva, Diogo; Pimentel-Nunes, Pedro; Magalhães, Joana; Magalhães, Ricardo; Veloso, Nuno; Ferreira, Carlos; Figueiredo, Pedro; Moutinho, Pedro; Dinis-Ribeiro, Mário

    2014-06-01

    A simplified narrow-band imaging (NBI) endoscopy classification of gastric precancerous and cancerous lesions was derived and validated in a multicenter study. This classification comes with the need for dissemination through adequate training. To address the learning curve of this classification by endoscopists with differing expertise and to assess the feasibility of a YouTube-based learning program to disseminate it. Prospective study. Five centers. Six gastroenterologists (3 trainees, 3 fully trained endoscopists [FTs]). Twenty tests provided through a Web-based program containing 10 randomly ordered NBI videos of gastric mucosa were taken. Feedback was sent 7 days after every test submission. Measures of accuracy of the NBI classification throughout the time. From the first to the last 50 videos, a learning curve was observed with a 10% increase in global accuracy, for both trainees (from 64% to 74%) and FTs (from 56% to 65%). After 200 videos, sensitivity and specificity of 80% and higher for intestinal metaplasia were observed in half the participants, and a specificity for dysplasia greater than 95%, along with a relevant likelihood ratio for a positive result of 7 to 28 and likelihood ratio for a negative result of 0.21 to 0.82, were achieved by all of the participants. No constant learning curve was observed for the identification of Helicobacter pylori gastritis and sensitivity to dysplasia. The trainees had better results in all of the parameters, except specificity for dysplasia, compared with the FTs. Globally, participants agreed that the program's structure was adequate, except on the feedback, which should have consisted of a more detailed explanation of each answer. No formal sample size estimate. A Web-based learning program could be used to teach and disseminate classifications in the endoscopy field. In this study, an NBI classification for gastric mucosal features seems to be easily learned for the identification of gastric preneoplastic

  9. L-selenomethionine does not protect against testosterone plus 17β-estradiol-induced oxidative stress and preneoplastic lesions in the prostate of NBL rats.

    PubMed

    Özten, Nur; Schlicht, Michael; Diamond, Alan M; Bosland, Maarten C

    2014-01-01

    Previous animal studies examining dietary selenium effects on prostatic carcinogenesis did not show preventive benefit, including 1 study in a rat model involving testosterone (T) and estradiol (E2)-induced prostatic oxidative stress. Here, we examined modulation of T + E2-induced prostatic oxidative stress, dysplasia, and inflammation by L-selenomethionine at 1.5 or 3.0 mg selenium/kg in NIH-07 diet in Noble (Nbl)/Crl rats treated with T + E2 for 16 wk. Hormone treatment increased immunohistochemical staining for 8-hydroxydeoxyguanosine (8-OHdG) in the prostatic sites of T + E2-induced preneoplasia (P < 0.05), but selenomethionine did not attenuate 8-OHdG staining and dysplasia in the lateral prostate. Glutathione-peroxidase activity (P < 0.05) and mRNA expression were induced by T + E2 (P < 0.0001) but not changed by selenomethionine. Selenomethionine did not cause significant responses in expression and activity of glutathione-peroxidase and MnSOD, except for a reduction of MnSOD protein expression in the lateral prostate (P < 0.01). The absence of reduction of oxidative stress and dysplasia and the minimal effects on antioxidant enzymes caused by selenomethionine are consistent with the null effects observed in selenium supplementation animal studies and clinical trials. Significant (P < 0.01) opposite apoptosis/cell proliferation balance responses to selenomethionine and to T + E2 occurred in the lateral and dorsal prostate, explaining why T + E2 induces lesions selectively in the lateral lobe of NBL rats.

  10. Detection of atherosclerotic lesions and intimal macrophages using CD36-targeted nanovesicles.

    PubMed

    Nie, Shufang; Zhang, Jia; Martinez-Zaguilan, Raul; Sennoune, Souad; Hossen, Md Nazir; Lichtenstein, Alice H; Cao, Jun; Meyerrose, Gary E; Paone, Ralph; Soontrapa, Suthipong; Fan, Zhaoyang; Wang, Shu

    2015-12-28

    Current approaches to the diagnosis and therapy of atherosclerosis cannot target lesion-determinant cells in the artery wall. Intimal macrophage infiltration promotes atherosclerotic lesion development by facilitating the accumulation of oxidized low-density lipoproteins (oxLDL) and increasing inflammatory responses. The presence of these cells is positively associated with lesion progression, severity and destabilization. Hence, they are an important diagnostic and therapeutic target. The objective of this study was to noninvasively assess the distribution and accumulation of intimal macrophages using CD36-targeted nanovesicles. Soy phosphatidylcholine was used to synthesize liposome-like nanovesicles. 1-(Palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine was incorporated on their surface to target the CD36 receptor. All in vitro data demonstrate that these targeted nanovesicles had a high binding affinity for the oxLDL binding site of the CD36 receptor and participated in CD36-mediated recognition and uptake of nanovesicles by macrophages. Intravenous administration into LDL receptor null mice of targeted compared to non-targeted nanovesicles resulted in higher uptake in aortic lesions. The nanovesicles co-localized with macrophages and their CD36 receptors in aortic lesions. This molecular target approach may facilitate the in vivo noninvasive imaging of atherosclerotic lesions in terms of intimal macrophage accumulation and distribution and disclose lesion features related to inflammation and possibly vulnerability thereby facilitate early lesion detection and targeted delivery of therapeutic compounds to intimal macrophages. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. The effects of neonatal amygdala or hippocampus lesions on adult social behavior.

    PubMed

    Bliss-Moreau, Eliza; Moadab, Gilda; Santistevan, Anthony; Amaral, David G

    2017-03-30

    The present report details the final phase of a longitudinal evaluation of the social behavior in a cohort of adult rhesus monkeys that received bilateral neurotoxic lesions of the amygdala or hippocampus, or sham operations at 2 weeks of age. Results were compared to previous studies in which adult animals received amygdala lesions and were tested in a similar fashion. Social testing with four novel interaction partners occurred when the animals were between 7 and 8 years of age. Experimental animals interacted with two male and two female partners in two conditions - one in which physical access was restricted (the constrained social access condition) and a second in which physical access was unrestricted (the unconstrained social access condition). Across conditions and interaction partners, there were no significant effects of lesion condition on the frequency or duration of social interactions. As a group, the hippocampus-lesioned animals generated the greatest number of communicative signals during the constrained social access condition. Amygdala-lesioned animals generated more frequent stress-related behaviors and were less exploratory. Amygdala and hippocampus-lesioned animals demonstrated greater numbers of stereotypies than control animals. Subtle, lesion-based differences in the sequencing of behaviors were observed. These findings suggest that alterations of adult social behavior are much less prominent when damage to the amygdala occurs early in life rather than in adulthood. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. [Helicobacter pylori-related diseases].

    PubMed

    Gisbert, Javier P

    2013-10-01

    This article summarizes the main conclusions drawn from the presentations on Helicobacter pylori at Digestive Disease Week 2013. Knowledge of this infection among the general population continues to be extremely limited. H. pylori is the main cause of "aging" of the human stomach. In developed countries, the prevalence of H. pylori infection has decreased but continues to be considerable. In most countries, clarithromycin and metronidazole resistance rates are markedly high. H. pylori eradication improves the symptoms of functional dyspepsia, but only in a minority of patients. The frequency of idiopathic peptic ulcers seems to be rising and their prognosis is worse. Most patients with gastric cancer have, or have had, prior H. pylori infection. The risk of developing preneoplastic lesions depends on the type (strain) of the microorganism. To prevent the development of gastric cancer, eradication therapy should be administered early (before the development of intestinal metaplasia). Among H. pylori-infected patients, those who receive long-term treatment with proton pump inhibitors more frequently develop preneoplastic lesions. In patients who undergo endoscopic resection of early gastric cancer, H. pylori eradication reduces the incidence of metachronous tumors. Eradication therapy induces regression of MALT lymphoma in most patients and tumoral recurrence in the long term is exceptional; eradication is a reasonable option even when H. pylori infection has not been identified in patients with MALT lymphoma. Several diagnostic innovations were presented, such as some polymerase chain reaction techniques for use in gastric biopsy specimens or gastric juice. The efficacy of triple standard therapy is clearly inadequate. The superiority of "sequential" therapy over standard triple therapy has not been definitively established. "Concomitant" therapy is more effective and is simpler than "sequential" therapy. After failure of standard triple therapy, second

  13. Electromagnetic Navigation Bronchoscopy-directed Pleural Tattoo to Aid Surgical Resection of Peripheral Pulmonary Lesions.

    PubMed

    Tay, Jun H; Wallbridge, Peter D; Larobina, Marco; Russell, Prudence A; Irving, Louis B; Steinfort, Daniel P

    2016-07-01

    Limited (wedge) resection of pulmonary lesions is frequently performed as a diagnostic/therapeutic procedure. Some lesions may be difficult to locate thoracoscopically with conversion to open thoracotomy or incomplete resection being potential limitations to this approach. Multiple methods have been described to aid video-assisted thoracoscopic surgical (VATS) wedge resection of pulmonary nodules, including hookwire localization, percutaneous tattoo, or intraoperative ultrasound. We report on our experience using electromagnetic navigation bronchoscopic dye marking of small subpleural lesions to aid VATS wedge resection. A retrospective cohort study of consecutive patients undergoing VATS wedge resection of peripheral lesions. Preoperative bronchoscopy with electromagnetic navigation was utilized to guide a 25 G needle to within/adjacent to the target lesion with injection of 1 mL of methylene blue or indigo carmine under fluoroscopic vision. Six patients underwent bronchoscopic marking of peripheral pulmonary lesions, navigation deemed successful in all patients, with no procedural complications. Surgery was performed within 24 hours of bronchoscopic marking. Pleural staining by dye was visible thoracoscopically in all 6 lesions either adjacent to or overlying the lesion. All lesions were fully excised with wedge resection. Pathologic examination confirmed accuracy of dye staining. Electromagnetic navigation bronchoscopic dye marking of peripheral lesions is feasible, without complications commonly associated with percutaneous marking procedures. Further experience is required but early findings suggest that this method may have utility in aiding minimally invasive resection of small subpleural lesions.

  14. Characterization of enamel caries lesions in rat molars using synchrotron X-ray microtomography

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Free, R. D.; DeRocher, K.; Stock, S. R.

    Dental caries is a ubiquitous infectious disease with a nearly 100% lifetime prevalence. Rodent caries models are widely used to investigate the etiology, progression and potential prevention or treatment of the disease. To explore the suitability of these models for deeper investigations of intact surface zones during enamel caries, the structures of early-stage carious lesions in rats were characterized and compared with previous reports on white spot enamel lesions in humans. Synchrotron X-ray microcomputed tomography non-destructively mapped demineralization in carious rat molar specimens across a range of caries severity, identifying 52 lesions across the 30 teeth imaged. Of these lesions,more » 13 were shown to have intact surface zones. Depth profiles of fractional mineral density were qualitatively similar to lesions in human teeth. However, the thickness of the surface zone in the rat model ranges from 10 to 58 µm, and is therefore significantly thinner than in human enamel. These results indicate that a fraction of lesions in rat caries possess an intact surface zone and are qualitatively similar to human lesions at the micrometer scale. This suggests that rat caries models may be a suitable analog through which to investigate the structure of surface zone enamel and its role during dental caries.« less

  15. Density-based parallel skin lesion border detection with webCL

    PubMed Central

    2015-01-01

    addition, we tested parallel code on 100 dermoscopy images and showed the execution speedups with respect to the serial version. Results indicate that parallel (WebCL) version and serial version of density based lesion border detection methods generate the same accuracy rates for 100 dermoscopy images, in which mean of border error is 6.94%, mean of recall is 76.66%, and mean of precision is 99.29% respectively. Moreover, WebCL version's speedup factor for 100 dermoscopy images' lesion border detection averages around ~491.2. Conclusions When large amount of high resolution dermoscopy images considered in a usual clinical setting along with the critical importance of early detection and diagnosis of melanoma before metastasis, the importance of fast processing dermoscopy images become obvious. In this paper, we introduce WebCL and the use of it for biomedical image processing applications. WebCL is a javascript binding of OpenCL, which takes advantage of GPU computing from a web browser. Therefore, WebCL parallel version of density based skin lesion border detection introduced in this study can supplement expert dermatologist, and aid them in early diagnosis of skin lesions. While WebCL is currently an emerging technology, a full adoption of WebCL into the HTML5 standard would allow for this implementation to run on a very large set of hardware and software systems. WebCL takes full advantage of parallel computational resources including multi-cores and GPUs on a local machine, and allows for compiled code to run directly from the Web Browser. PMID:26423836

  16. Density-based parallel skin lesion border detection with webCL.

    PubMed

    Lemon, James; Kockara, Sinan; Halic, Tansel; Mete, Mutlu

    2015-01-01

    parallel code on 100 dermoscopy images and showed the execution speedups with respect to the serial version. Results indicate that parallel (WebCL) version and serial version of density based lesion border detection methods generate the same accuracy rates for 100 dermoscopy images, in which mean of border error is 6.94%, mean of recall is 76.66%, and mean of precision is 99.29% respectively. Moreover, WebCL version's speedup factor for 100 dermoscopy images' lesion border detection averages around ~491.2. When large amount of high resolution dermoscopy images considered in a usual clinical setting along with the critical importance of early detection and diagnosis of melanoma before metastasis, the importance of fast processing dermoscopy images become obvious. In this paper, we introduce WebCL and the use of it for biomedical image processing applications. WebCL is a javascript binding of OpenCL, which takes advantage of GPU computing from a web browser. Therefore, WebCL parallel version of density based skin lesion border detection introduced in this study can supplement expert dermatologist, and aid them in early diagnosis of skin lesions. While WebCL is currently an emerging technology, a full adoption of WebCL into the HTML5 standard would allow for this implementation to run on a very large set of hardware and software systems. WebCL takes full advantage of parallel computational resources including multi-cores and GPUs on a local machine, and allows for compiled code to run directly from the Web Browser.

  17. Influence of stains on lesion contrast in the pits and fissures of tooth occlusal surfaces from 800-1600-nm

    NASA Astrophysics Data System (ADS)

    Almaz, Elias C.; Simon, Jacob C.; Fried, Daniel; Darling, Cynthia L.

    2016-02-01

    For over one hundred years, x-rays have served as a cornerstone of dentistry. Dental radiographic imaging technologies have constantly improved, however, detecting occlusal lesions remains as one of the greatest challenges due to the low sensitivity of radiographs and the overlap of enamel. Once detected, occlusal lesions have penetrated far into the dentin, necessitating invasive restorative treatment. The adoption of near-infrared (NIR) systems in dentistry introduces the potential for early detection of occlusal lesions. Commercially available NIR systems for intra-oral applications currently operate near 800-nm; however, extrinsic stains may interfere with the detection of demineralization of the underlying enamel surface. Higher wavelengths such as 1300-nm render stains nearly transparent and enhances the contrast of sound enamel to demineralized enamel. This novel finding promotes minimally invasive dentistry and allows oral health professionals the ability to detect, image, track, and monitor early lesions without repeated exposure to ionizing radiation nor invasive treatment.

  18. Influence of stains on lesion contrast in the pits and fissures of tooth occlusal surfaces from 800-1600-nm.

    PubMed

    Almaz, Elias C; Simon, Jacob C; Fried, Daniel; Darling, Cynthia L

    2016-02-13

    For over one hundred years, x-rays have served as a cornerstone of dentistry. Dental radiographic imaging technologies have constantly improved, however, detecting occlusal lesions remains as one of the greatest challenges due to the low sensitivity of radiographs and the overlap of enamel. Once detected, occlusal lesions have penetrated far into the dentin, necessitating invasive restorative treatment. The adoption of near-infrared (NIR) systems in dentistry introduces the potential for early detection of occlusal lesions. Commercially available NIR systems for intra-oral applications currently operate near 800-nm; however, extrinsic stains may interfere with the detection of demineralization of the underlying enamel surface. Higher wavelengths such as 1300-nm render stains nearly transparent and enhances the contrast of sound enamel to demineralized enamel. This novel finding promotes minimally invasive dentistry and allows oral health professionals the ability to detect, image, track, and monitor early lesions without repeated exposure to ionizing radiation nor invasive treatment.

  19. Lack of effect of habenula lesion on heroin self-administration in rats.

    PubMed

    Wang, Yuhong; Zhang, Fuqiang; Tang, Shuaien; Lai, Miaojun; Hao, Wei; Zhang, Yong; Yang, Jianli; Zhou, Wenhua

    2009-09-18

    We examined the effects of bilateral electric lesion of the habenula (Hb) on the acquisition and maintenance of heroin self-administration. The rats were trained to self-administer heroin (0.05 mg/kg/infusion) under FR1 schedule in daily 4h sessions. A progressive ratio schedule (PR3-4) was used to evaluate the relative motivational value of heroin reinforcement. Compared with the controls, neither pre-training nor post-training of Hb lesions had any effects on the total amount of infusions and motivational value of heroin reward. However, pre-training Hb lesion caused transient active and inactive nose-poke responding in the early phase of training, suggesting increased locomotor exploration. The results suggest that Hb might not play an important role in mediating the acute reinforcing effect of heroin.

  20. Gingival pemphigus vulgaris preceding cutaneous lesion: A rare case report

    PubMed Central

    Rath, Saroj K.; Reenesh, M.

    2012-01-01

    Pemphigus is a group of autoimmune diseases characterized by formation of intraepithelial bullae in skin and the mucous membrane. Pemphigus vulgaris affects the oral mucosa in nearly all cases. Pemphigus vulgaris is characterized by auto antibodies directed against desmosome-associated protein antigens (desmoglein-3) found in epithelial and epidermal intercellular substance. We report here a case of pemphigus vulgaris of gingiva in an adult female patient at an early stage followed by dermatologic involvement. Perilesional incision was taken and histopathological and direct immunofluorescence was done for identification of specific antibodies. The oral lesions were treated with 0.1% Triamcinolone acetonide ointment and Prednisolone 20 mg twice daily with multivitamins was administered systemically for skin lesion. PMID:23493851

  1. Lesions of the Islets of Langerhans in Encephalomyocarditis Virus-Infected Mice with Diabetes Mellitus-Like Disease

    PubMed Central

    Craighead, J. E.; Kanich, R. E.; Kessler, J. B.

    1974-01-01

    Mice infected with the M variant of the encephalomyocarditis (EMC) virus develop lesions of the islets of Langerhans associated with a diabetes mellitus-like disease. Ultrastructural alterations become evident in capillaries and beta cells at a time when large amounts of virus are present in the pancreatic tissue. Although some beta cells become necrotic, degranulation and contraction of intact cells is the prominent lesion. Changes in the capillaries appear early in the course of the infection and later are associated with interstitial fibrosis in and around the islets. During early convalescence, beta cells are degranulated and exhibit striking alterations of cytoplasmic organelles. These changes appear to be consequent to increased metabolic activity by the residual insular tissue. Interestingly enough, specific lesions of the alpha cells are not observed. ImagesFig 9Fig 10Fig 11Fig 12Fig 13Fig 1Fig 2Figs 3 and 4Fig 5Figs 6 and 7p[297]-aFig 8 PMID:4359734

  2. A multi-mineral natural product inhibits liver tumor formation in C57BL/6 mice

    PubMed Central

    Aslam, Muhammad N.; Bergin, Ingrid; Naik, Madhav; Hampton, Anna; Allen, Ron; Kunkel, Steven L.; Rush, Howard; Varani, James

    2012-01-01

    C57BL/6 mice were maintained for up to 18-months on high-fat and low-fat diets with or without a multi-mineral-supplement derived from the skeletal remains of the red marine algae Lithothamnion calcareum. Numerous grossly observable liver masses were visible in animals on the “western-style” high-fat diet sacrificed at 12 and 18 months. The majority of the masses were in male mice (20 out of 100 males versus 3 out of 100 females; p=0.0002). There were more liver masses in animals on the high-fat diet than on the low-fat diet (15 out of 50 on high-fat versus 5 out of 50 on low-fat; p=0.0254). The multi-mineral supplement reduced the number of liver masses in mice on both diets (3 out of 25 male mice in the low-fat diet group without the supplement versus 1 out of 25 mice with supplement; 12 of 25 male mice in the high-fat diet group without the supplement versus 3 of 25 mice with supplement [p=0.0129]). Histological evaluation revealed a total of 17 neoplastic lesions (9 adenomas and 8 hepatocellular carcinomas), and 18 pre-neoplastic lesions. Out of 8 hepatocellular carcinomas, 7 were found in unsupplemented diet groups. Steatosis was widely observed in livers with and without grossly observable masses, but the multi-mineral supplement had no effect on the incidence of steatosis or its severity. Taken together, these findings suggest that a multi-mineral-rich natural product can protect mice against neoplastic and pre-neoplastic proliferative liver lesions that may develop in the face of steatosis. PMID:22222483

  3. Quantitative analysis of enhanced malignant and benign lesions on contrast-enhanced spectral mammography.

    PubMed

    Deng, Chih-Ying; Juan, Yu-Hsiang; Cheung, Yun-Chung; Lin, Yu-Ching; Lo, Yung-Feng; Lin, GiGin; Chen, Shin-Cheh; Ng, Shu-Hang

    2018-02-27

    To retrospectively analyze the quantitative measurement and kinetic enhancement among pathologically proven benign and malignant lesions using contrast-enhanced spectral mammography (CESM). We investigated the differences in enhancement between 44 benign and 108 malignant breast lesions in CESM, quantifying the extent of enhancements and the relative enhancements between early (between 2-3 min after contrast medium injection) and late (3-6 min) phases. The enhancement was statistically stronger in malignancies compared to benign lesions, with good performance by the receiver operating characteristic curve [0.877, 95% confidence interval (0.813-0.941)]. Using optimal cut-off value at 220.94 according to Youden index, the sensitivity was 75.9%, specificity 88.6%, positive likelihood ratio 6.681, negative likelihood ratio 0.272 and accuracy 82.3%. The relative enhancement patterns of benign and malignant lesions, showing 29.92 vs 73.08% in the elevated pattern, 7.14 vs 92.86% in the steady pattern, 5.71 vs 94.29% in the depressed pattern, and 80.00 vs 20.00% in non-enhanced lesions (p < 0.0001), respectively. Despite variations in the degree of tumour angiogenesis, quantitative analysis of the breast lesions on CESM documented the malignancies had distinctive stronger enhancement and depressed relative enhancement patterns than benign lesions. Advances in knowledge: To our knowledge, this is the first study evaluating the feasibility of quantifying lesion enhancement on CESM. The quantities of enhancement were informative for assessing breast lesions in which the malignancies had stronger enhancement and more relative depressed enhancement than the benign lesions.

  4. Cholecystokinin receptor antagonist halts progression of pancreatic cancer precursor lesions and fibrosis in mice.

    PubMed

    Smith, Jill P; Cooper, Timothy K; McGovern, Christopher O; Gilius, Evan L; Zhong, Qing; Liao, Jiangang; Molinolo, Alfredo A; Gutkind, J Silvio; Matters, Gail L

    2014-10-01

    Exogenous administration of cholecystokinin (CCK) induces hypertrophy and hyperplasia of the pancreas with an increase in DNA content. We hypothesized that endogenous CCK is involved in the malignant progression of pancreatic intraepithelial neoplasia (PanIN) lesions and the fibrosis associated with pancreatic cancer. The presence of CCK receptors in early PanIN lesions was examined by immunohistochemistry in mouse and human pancreas. Pdx1-Cre/LSL-Kras transgenic mice were randomized to receive either untreated drinking water or water supplemented with a CCK receptor antagonist (proglumide, 0.1 mg/mL). Pancreas from the mice were removed and examined histologically for number and grade of PanINs after 1, 2, or 4 months of antagonist therapy. Both CCK-A and CCK-B receptors were identified in early stage PanINs from mouse and human pancreas. The grade of PanIN lesions was reversed, and progression to advanced lesions arrested in mice treated with proglumide compared with the controls (P = 0.004). Furthermore, pancreatic fibrosis was significantly reduced in antagonist-treated animals compared with vehicle (P < 0.001). These findings demonstrate that endogenous CCK is in part responsible for the development and progression of pancreatic cancer. The use of CCK receptor antagonists may have a role in cancer prophylaxis in high-risk subjects and may reduce fibrosis in the microenvironment.

  5. CHOLECYSTOKININ RECEPTOR ANTAGONIST HALTS PROGRESSION OF PANCREATIC CANCER PRECURSOR LESIONS AND FIBROSIS IN MICE

    PubMed Central

    Smith, Jill P.; Cooper, Timothy K.; McGovern, Christopher O.; Gilius, Evan L.; Zhong, Qing; Liao, Jiangang; Molinolo, Alfredo A.; Gutkind, J. Silvio; Matters, Gail L.

    2014-01-01

    Objectives Exogenous administration of cholecystokinin (CCK) induces hypertrophy and hyperplasia of the pancreas with an increase in DNA content. We hypothesized that endogenous CCK is involved with the malignant progression of pancreatic intraepithelial neoplasia (PanIN) lesions and the fibrosis associated with pancreatic cancer. Methods The presence of CCK receptors in early PanIN lesions was examined by immunohistochemistry in mouse and human pancreas. Pdx1-Cre/LSL-KrasG12D transgenic mice were randomized to receive either untreated drinking water or water supplemented with a CCK-receptor antagonist (proglumide, 0.1mg/ml). Pancreas from mice were removed and examined histologically for number and grade of PanINs after 1, 2 or 4 months of antagonist therapy. Results Both CCK-A and CCK-B receptors were identified in early stage PanINs from mouse and human pancreas. The grade of PanIN lesions was reversed and progression to advanced lesions arrested in mice treated with proglumide compared to controls (p=0.004). Furthermore, pancreatic fibrosis was significantly reduced in antagonist-treated animals compared to vehicle (pitalic>0.001). Conclusions These findings demonstrate that endogenous CCK is in part responsible for the development and progression of pancreatic cancer. Use of CCK-receptor antagonists may have a role in cancer prophylaxis in high risk subjects, and may reduce fibrosis in the microenvironment. PMID:25058882

  6. Visualization of dermal alteration in skin lesions with discoid lupus erythematosus by multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Lin, L. H.; Yu, H. B.; Zhu, X. Q.; Zhuo, S. M.; Wang, Y. Y.; Yang, Y. H.; Chen, J. X.

    2013-04-01

    Discoid lupus erythematosus (DLE) is a chronic dermatological disease which lacks valid methods for early diagnosis and therapeutic monitoring. Considering the collagen and elastin disorder due to mucin deposition of DLE, multiphoton microscopy (MPM) imaging techniques were employed to obtain high-resolution collagen and elastin images from the dermis. The content and distribution of collagen and elastin were quantified to characterize the dermal pathological status of skin lesions with DLE in comparison with normal skin. Our results showed a significant difference between skin lesions with DLE and normal skin in terms of the morphological structure of collagen and elastin in the dermis, demonstrating the possibility of MPM for noninvasively tracking the pathological process of DLE even in its early stages and evaluating the therapeutic efficacy at the molecular level.

  7. Post-weaning high-fat diet results in growth cartilage lesions in young male rats

    PubMed Central

    Haysom, Samuel S.; Vickers, Mark H.; Yu, Lennex H.; Reynolds, Clare M.; Firth, Elwyn C.

    2017-01-01

    To determine if a high-fat diet (HF) from weaning would result in a pro-inflammatory state and affect joint cartilage, we fed male rats either HF or Chow diet post-weaning, and voluntary wheel exercise (EX) or cage only activity (SED) after 9 weeks of age. At 17 weeks body composition, plasma biomarkers and histomorphology scores of femoro-tibial cartilages of HF-SED, HF-EX, Chow-SED and Chow-EX groups were compared. Food intake and activity were not significantly different between groups. HF diet resulted in significantly higher weight gain, %fat, fat:lean ratio, and plasma leptin, insulin and TNFα concentrations, with significant interactions between diet and exercise. No abnormal features were detected in the hyaline articular cartilage or in the metaphyseal growth plate in all four groups. However, collagen type X- positive regions of retained epiphyseal growth cartilage (EGC) was present in all HF-fed animals and significantly greater than that observed in Chow-fed sedentary rats. Most lesions were located in the lateral posterior aspect of the tibia and/or femur. The severity of lesions was greater in HF-fed animals. Although exercise had a significantly greater effect in reducing adiposity and associated systemic inflammation in HF-fed rats, it had no effect on lesion incidence or severity. Lesion incidence was also significantly associated with indices of obesity and plasma markers of chronic inflammation. Clinically, EGC lesions induced by HF feeding in rats from very early in life, and possibly by insufficient activity, is typical of osteochondrosis in animals. Such lesions may be the precursor of juvenile osteochondritis dissecans requiring surgery in children/adolescents, conservative management of which could benefit from improved understanding of early changes in cellular and gene expression. PMID:29166409

  8. [Total brain T2-hyperintense lesion-volume and the axonal damage in the normal-appearing white matter of brainstem in early lapsing-remitting multiple sclerosis].

    PubMed

    Pascual-Lozano, A M; Martínez-Bisbal, M C; Boscá-Blasco, I; Valero-Merino, C; Coret-Ferrer, F; Martí-Bonmatí, L; Martínez-Granados, B; Celda, B; Casanova-Estruch, B

    To evaluate the relationship between the total brain T2-hyperintense lesion volume (TBT2LV) and the axonal damage in the normal-appearing white matter of brainstem measured by 1H-MRS in a group of early relapsing-remitting multiple sclerosis patients. 40 relapsing-remitting multiple sclerosis patients and ten sex- and age-matched healthy subjects were prospectively studied for two years. T2-weighted MR and 1H-MRS imaging were acquired at time of recruitment and at year two. The TBT2LV was calculated with a semiautomatic program; N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) resonances areas were integrated with jMRUI program and the ratios were calculated for four volume elements that represented the brainstem. At basal study we obtained an axonal loss (as a decrement of NAA/ Cho ratio) in the group of patients compared with controls (p = 0.017); this axonal loss increased at the second year of the follow-up for patients (NAA/Cho decrease, p = 0.004, and NAA/Cr decrease, p = 0.002) meanwhile control subjects had no significant metabolic changes. Higher lesion load was correlated with a poor clinical outcome, being the correlation between the basal TBT2LV and the Expanded Disability Status Scale at second year (r = 0.299; p = 0.05). Besides, axonal loss was not homogeneous for all multiple sclerosis patients, being stronger in the subgroup of patients with high basal TBT2LV (p = 0.043; ANOVA). Our data suggest that axonal damage is early in multiple sclerosis and higher in patients high basal TBT2LV, suggesting a possible relationship between these two phenomena.

  9. A computerized scheme of SARS detection in early stage based on chest image of digital radiograph

    NASA Astrophysics Data System (ADS)

    Zheng, Zhong; Lan, Rihui; Lv, Guozheng

    2004-05-01

    A computerized scheme for early severe acute respiratory syndrome(SARS) lesion detection in digital chest radiographs is presented in this paper. The total scheme consists of two main parts: the first part is to determine suspect lesions by the theory of locally orderless images(LOI) and their spatial features; the second part is to select real lesions among these suspect ones by their frequent features. The method we used in the second part is firstly developed by Katsuragawa et al with necessary modification. Preliminary results indicate that these features are good criterions to tell early SARS lesions apart from other normal lung structures.

  10. Patellar cartilage lesions: comparison of magnetic resonance imaging and T2 relaxation-time mapping.

    PubMed

    Hannila, I; Nieminen, M T; Rauvala, E; Tervonen, O; Ojala, R

    2007-05-01

    To evaluate the detection and the size of focal patellar cartilage lesions in T2 mapping as compared to standard clinical magnetic resonance imaging (MRI) at 1.5T. Fifty-five consecutive clinical patients referred to knee MRI were imaged both with a standard knee MRI protocol (proton-density-weighted sagittal and axial series, T2-weighted sagittal and coronal series, and T1-weighted coronal series) and with an axial multislice multi-echo spin-echo measurement to determine the T2 relaxation time of the patellar cartilage. MR images and T2 maps of patellar cartilage were evaluated for focal lesions. The lesions were evaluated for lesion width (mm), lesion depth (1/3, 2/3, or 3/3 of cartilage thickness), and T2 value (20-40 ms, 40-60 ms, or 60-80 ms) based on visual evaluation. Altogether, 36 focal patellar cartilage lesions were detected from 20 human subjects (11 male, nine female, mean age 40+/-15 years). Twenty-eight lesions were detected both on MRI and T2 maps, while eight lesions were only visible on T2 maps. Cartilage lesions were significantly wider (P = 0.001) and thicker (P<0.001) on T2 maps as compared to standard knee MRI. Most lesions 27 had moderately (T2 40-60 ms) increased T2 values, while two lesions had slightly (T2 20-40 ms) and seven lesions remarkably (T2 60-80 ms) increased T2 relaxation times. T2 mapping of articular cartilage is feasible in the clinical setting and may reveal early cartilage lesions not visible with standard clinical MRI.

  11. Functional organization of the medial temporal lobe memory system following neonatal hippocampal lesion in rhesus monkeys.

    PubMed

    Chareyron, Loïc J; Banta Lavenex, Pamela; Amaral, David G; Lavenex, Pierre

    2017-12-01

    Hippocampal damage in adult humans impairs episodic and semantic memory, whereas hippocampal damage early in life impairs episodic memory but leaves semantic learning relatively preserved. We have previously shown a similar behavioral dissociation in nonhuman primates. Hippocampal lesion in adult monkeys prevents allocentric spatial relational learning, whereas spatial learning persists following neonatal lesion. Here, we quantified the number of cells expressing the immediate-early gene c-fos, a marker of neuronal activity, to characterize the functional organization of the medial temporal lobe memory system following neonatal hippocampal lesion. Ninety minutes before brain collection, three control and four adult monkeys with bilateral neonatal hippocampal lesions explored a novel environment to activate brain structures involved in spatial learning. Three other adult monkeys with neonatal hippocampal lesions remained in their housing quarters. In unlesioned monkeys, we found high levels of c-fos expression in the intermediate and caudal regions of the entorhinal cortex, and in the perirhinal, parahippocampal, and retrosplenial cortices. In lesioned monkeys, spatial exploration induced an increase in c-fos expression in the intermediate field of the entorhinal cortex, the perirhinal, parahippocampal, and retrosplenial cortices, but not in the caudal entorhinal cortex. These findings suggest that different regions of the medial temporal lobe memory system may require different types of interaction with the hippocampus in support of memory. The caudal perirhinal cortex, the parahippocampal cortex, and the retrosplenial cortex may contribute to spatial learning in the absence of functional hippocampal circuits, whereas the caudal entorhinal cortex may require hippocampal output to support spatial learning.

  12. Scar modulation in subacute and chronic CNS lesions: Effects on axonal regeneration.

    PubMed

    Stichel, Christine C.; Lausberg, Friederike; Hermanns, Susanne; Müller, Hans Werner

    1999-01-01

    After injury of the adult mammalian CNS axonal regeneration across or around the lesion scar is negligible. Previously, we have shown that the lesion-induced basal membrane (BM) within the lesion center participates in a growth barrier for axon regeneration and that its reduction by means of pharmacological or immunochemical treatment is a prerequisite and sufficient condition for regrowing axons to cross the lesion site. The present study was designed to further investigate this observation by analyzing the effect of a delayed treatment on the regeneration of both subacutely and chronically lesioned axons.Adult rats underwent unilateral transection of the postcommissural fornix. At one to five days after transection one group of animals received a local injection of 2, 2'-dipyridyl (DPY), an inhibitor of collagen triple helix formation and synthesis. Another group received a second transection within the former lesion site followed by an immediate DPY-injection at five days or 4 weeks after transection. Six weeks after the last surgery BM deposition and axonal regeneration were analysed using immunocytochemical methods.A local injection of DPY clearly reduced the lesion-induced BM deposition when applied within the first 3 days after transection. Under these conditions regrowing axons still crossed the former impermeable lesion site and regenerated within their normal pathway up to their former target, the mammillary body. However, in late subacute (5 d) and chronic stages (4 w) the double transection+injection paradigm failed to reduce BM deposition and, in consequence, also to induce axonal regeneration.These results demonstrate the potential of the collagen IV-reducing strategy to promote axonal regeneration across the lesion scar not only in acute but also in early subacute traumatic injuries.

  13. Cryotherapy of Renal Lesions: Enhancement on Contrast-Enhanced Sonography on Postoperative Day 1 Does Not Imply Viable Tissue Persistence.

    PubMed

    Bertolotto, Michele; Siracusano, Salvatore; Cicero, Calogero; Iannelli, Mariano; Silvestri, Tommaso; Celia, Antonio; Guarise, Alessandro; Stacul, Fulvio

    2017-02-01

    To investigate whether persistent enhancement detected on contrast-enhanced sonography at postoperative day 1 (early contrast-enhanced sonography) after cryoablation of renal tumors implies the presence of residual viable tumor tissue, defined as residual enhancing tissue on reference imaging (computed tomography or magnetic resonance imaging) performed 6 months after the procedure. Seventy-four patients with percutaneous cryoablation of renal tumors had early contrast-enhanced sonography from November 2011 to August 2015. Two independent readers evaluated early contrast-enhanced sonographic findings and contrast-enhanced sonographic investigations performed 1 month after cryoablation of lesions that displayed enhancement on early contrast-enhanced sonography. They scored intralesional enhancement in 4 groups: no enhancement, few intralesional vessels, focal enhancing areas, and diffuse enhancement. Inter-reader agreement in evaluating lesion vascularity on early contrast-enhanced sonography was assessed with weighted κ statistics. Computed tomography or magnetic resonance imaging performed 6 months after the treatment was the reference procedure for assessing the absence or presence of residual disease. Inter-reader agreement in assessing intratumoral vascularization on early contrast-enhanced sonography was very good (κ = 0.90). Enhancement was absent for both readers in 33 of 74 cases; only a few intralesional vessels were visible in 21; whereas diffuse or focal enhancement was present in 13. In the remaining 7 patients, there were differences. Four lesions with focal enhancement on early contrast-enhanced sonography and 1 that was considered avascular had residual tumors on reference imaging. Ablation was successful in the remaining 69 of 74 patients (93%). After cryoablation, intratumoral enhancement on early contrast-enhanced sonography does not imply tumor cell viability. © 2016 by the American Institute of Ultrasound in Medicine.

  14. Differential diagnosis of an unusual shoulder articular lesion in an ancient domestic dog (Canis lupus familiaris L., 1758).

    PubMed

    Lawler, D F; Rubin, D A; Evans, R H; Hildebolt, C F; Smith, K E; Widga, C; Martin, T J; Siegel, M; Sackman, J E; Smith, G K; Patel, T K

    2013-12-01

    A proximal humeral articular surface from an ancient domestic dog deliberate burial was examined during survey of small mammal bones from a prehistoric early Late Woodland archeological site. An unusual lesion on the caudolateral articular surface prompted micro-computed tomography to define detailed structure. Results indicate cortical or immature woven bone arising subchondrally, replacing normal trabeculae, extending through a breach in the cortical surface, and having sharp transition with surrounding normal bone. Organized bone within the lesion indicates that the dog lived for months-to-years following insult. Differential diagnoses initially included: sharp penetrating trauma; intrinsic or extrinsic blunt fracturing force; osteochondrosis or complication of an osteochondral lesion; unusual osteoarthritis; and neoplasia. Computed tomography ruled out normal or unusual osteoarthritis, and neoplasia. The nature and small size of the lesion, relatively small size of the dog, and lack of evidence for complicating infection, suggest against sharp penetrating trauma as a sole cause. The most plausible differential diagnoses include: uncommon fracture-producing force in a companion animal, and blunt intrinsic or extrinsic force causing fracture at a weak point, such as an early osteochondral lesion, that was obliterated by healing. Combined gross examination, micro-computed tomography, and archeological-anthropological influences facilitated refinement of differential diagnosis. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Early Sonographic Diagnosis of Neurocutaneous Melanosis in a Newborn

    PubMed Central

    Yakut, Zeynep Ilerisoy; Bas, Ahmet Yagmur; Turan, Aynur; Demirel, Nihal; Demirkan, Tulin Hakan

    2014-01-01

    Neurocutaneous melanosis (NCM) is a rare, congenital non-hereditary syndrome, characterized by multiple pigmented nevi. We report the radiologic findings of a newborn who had extensive cutaneous melanotic nevus with satellite lesions in the brain. Ultrasound showed multiple echogenic foci in the cerebral parenchyma. Subsequent MRI confirmed these lesions as characteristic deposits of melanin. The infant was asymptomatic, but presence of risk factors such as malign transformation or neurological manifestations makes early diagnosis very important. We present this case to emphasize on the radiological findings of this syndrome in order to reach an early diagnosis. PMID:25780540

  16. Anatomic Site Based Ploidy Analysis of Oral Premalignant Lesions

    PubMed Central

    Islam, M. N.; Kornberg, L.; Veenker, E.; Cohen, D. M.

    2009-01-01

    The location of oral leukoplakia correlates strongly with the probability of finding dysplastic or malignant alterations at biopsy. It is well established that early detection can dramatically improve the 5-year survival rates for oral squamous cell carcinomas. Since aneuploidy is predictive of future conversion to malignancy, we hypothesized that dysplastic lesions from high-risk sites (floor of mouth, tongue and lips) would exhibit greater aneuploidy than low-risk sites (palate, gingiva and buccal mucosa). Epithelial sections from 60 archival samples diagnosed as mild dysplasia (36 females, 20 males) from various high/low risk locations were stained with Blue Feulgen Stain for DNA Ploidy Analysis (Clarient, Aliso Viejo, CA) and ploidy was analyzed using a ChromaVision ACIS II (Clarient, ALiso Viejo, CA) Image cytometry system. A DNA histogram was generated using an image analyzing software that evaluated the amount of Feulgen stain which is proportional to the amount of nuclear DNA. An ANOVA analysis followed by the Student’s‘t’ test revealed significant differences between means (P ≤ 0.05). Lesions originating from lateral/ventral tongue (85%), floor of mouth (50%) and soft palate (44%) exhibited a higher frequency of aneuploidy than lesions from gingiva (22%) and lower lip (25%). This pilot study demonstrates that dysplastic lesions from high-risk sites such as the floor of the mouth and lateral/ventral tongue have higher frequency of aneuploidy. PMID:20237983

  17. Effects of neck and circumoesophageal connective lesions on posture and locomotion in the cockroach.

    PubMed

    Ridgel, Angela L; Ritzmann, Roy E

    2005-06-01

    Few studies in arthropods have documented to what extent local control centers in the thorax can support locomotion in absence of inputs from head ganglia. Posture, walking, and leg motor activity was examined in cockroaches with lesions of neck or circumoesophageal connectives. Early in recovery, cockroaches with neck lesions had hyper-extended postures and did not walk. After recovery, posture was less hyper-extended and animals initiated slow leg movements for multiple cycles. Neck lesioned individuals showed an increase in walking after injection of either octopamine or pilocarpine. The phase of leg movement between segments was reduced in neck lesioned cockroaches from that seen in intact animals, while phases in the same segment remained constant. Neither octopamine nor pilocarpine initiated changes in coordination between segments in neck lesioned individuals. Animals with lesions of the circumoesophageal connectives had postures similar to intact individuals but walked in a tripod gait for extended periods of time. Changes in activity of slow tibial extensor and coxal depressor motor neurons and concomitant changes in leg joint angles were present after the lesions. This suggests that thoracic circuits are sufficient to produce leg movements but coordinated walking with normal motor patterns requires descending input from head ganglia.

  18. Application of cytology and molecular biology in diagnosing premalignant or malignant oral lesions

    PubMed Central

    Mehrotra, Ravi; Gupta, Anurag; Singh, Mamta; Ibrahim, Rahela

    2006-01-01

    Early detection of a premalignant or cancerous oral lesion promises to improve the survival and the morbidity of patients suffering from these conditions. Cytological study of oral cells is a non-aggressive technique that is well accepted by the patient, and is therefore an attractive option for the early diagnosis of oral cancer, including epithelial atypia and squamous cell carcinoma. However its usage has been limited so far due to poor sensitivity and specificity in diagnosing oral malignancies. Lately it has re-emerged due to improved methods and it's application in oral precancer and cancer as a diagnostic and predictive method as well as for monitoring patients. Newer diagnostic techniques such as "brush biopsy" and molecular studies have been developed. Recent advances in cytological techniques and novel aspects of applications of scraped or exfoliative cytology for detecting these lesions and predicting their progression or recurrence are reviewed here. PMID:16556320

  19. A Microbeam Small-Angle X-ray Scattering Study on Enamel Crystallites in Subsurface Lesion

    NASA Astrophysics Data System (ADS)

    Yagi, N.; Ohta, N.; Matsuo, T.; Tanaka, T.; Terada, Y.; Kamasaka, H.; Kometani, T.

    2010-10-01

    The early caries lesion in bovine tooth enamel was studied by two different X-ray diffraction systems at the SPring-8 third generation synchrotron radiation facility. Both allowed us simultaneous measurement of the small and large angle regions. The beam size was 6μm at BL40XU and 50μm at BL45XU. The small-angle scattering from voids in the hydroxyapatite crystallites and the wide-angle diffraction from the hydroxyapatite crystals were observed simultaneously. At BL40XU an X-ray image intensifier was used for the small-angle and a CMOS flatpanel detector for the large-angle region. At BL45XU, a large-area CCD detector was used to cover both regions. A linear microbeam scan at BL40XU showed a detailed distribution of voids and crystals and made it possible to examine the structural details in the lesion. The two-dimensional scan at BL45XU showed distribution of voids and crystals in a wider region in the enamel. The simultaneous small- and wide-angle measurement with a microbeam is a powerful tool to elucidate the mechanisms of demineralization and remineralization in the early caries lesion.

  20. Detection of early osteoarthritis in the centrodistal joints of Icelandic horses: Evaluation of radiography and low-field magnetic resonance imaging.

    PubMed

    Ley, C J; Björnsdóttir, S; Ekman, S; Boyde, A; Hansson, K

    2016-01-01

    Validated noninvasive detection methods for early osteoarthritis (OA) are required for OA prevention and early intervention treatment strategies. To evaluate radiography and low-field magnetic resonance imaging (MRI) for the detection of early stage OA osteochondral lesions in equine centrodistal joints using microscopy as the reference standard. Prospective imaging of live horses and imaging and microscopy of cadaver tarsal joints. Centrodistal (distal intertarsal) joints of 38 Icelandic research horses aged 27-29 months were radiographed. Horses were subjected to euthanasia approximately 2 months later and cadaver joints examined with low-field MRI. Osteochondral joint specimens were classified as negative or positive for OA using light microscopy histology or scanning electron microscopy. Radiographs and MRIs were evaluated for osteochondral lesions and results compared with microscopy. Forty-two joints were classified OA positive with microscopy. Associations were detected between microscopic OA and the radiography lesion categories; mineralisation front defect (P<0.0001), joint margin lesion (P<0.0001), central osteophyte (P = 0.03) and the low-field MRI lesion categories; mineralisation front defect (P = 0.01), joint margin lesion (P = 0.02) and articular cartilage lesion (P = 0.0003). The most frequent lesion category detected in microscopic OA positive joints was the mineralisation front defect in radiographs (28/42 OA positive joints, specificity 97%, sensitivity 67%). No significant differences were detected between the sensitivity and specificity of radiography and low-field MRI pooled lesion categories, but radiography was often superior when individual lesion categories were compared. Early stage centrodistal joint OA changes may be detected with radiography and low-field MRI. Detection of mineralisation front defects in radiographs may be a useful screening method for detection of early OA in centrodistal joints of young Icelandic horses. © 2015 EVJ

  1. Brief Report: Course of Active Inflammatory and Fatty Lesions in Patients With Early Axial Spondyloarthritis Treated With Infliximab Plus Naproxen as Compared to Naproxen Alone: Results From the Infliximab As First Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial.

    PubMed

    Poddubnyy, Denis; Listing, Joachim; Sieper, Joachim

    2016-08-01

    To investigate the course of active inflammatory and fatty lesions seen on magnetic resonance imaging (MRI) in patients with early axial spondyloarthritis (SpA) treated with the tumor necrosis factor (TNF) inhibitor infliximab added to naproxen as compared to those treated with naproxen alone. A total of 158 patients with active axial SpA were randomized (2:1) to receive 28 weeks of treatment with either infliximab 5 mg/kg plus naproxen 1,000 mg/day or placebo plus naproxen 1,000 mg/day. MRI of the sacroiliac (SI) joints and of the spine was performed at baseline and week 28. Images were scored for active inflammation and for fatty lesions. After 28 weeks, there was a significant reduction of inflammation in the spine and in the SI joints in both treatment groups, which was, however, more prominent in the infliximab plus naproxen group (mean ± SD spine osteitis change score -2.9 ± 5.1, versus -2.0 ± 4.2 in the placebo plus naproxen group [P < 0.001]; SI joint osteitis change score -4.3 ± 5.2 in the infliximab plus naproxen group versus -3.9 ± 3.7 in the placebo plus naproxen group [P = 0.003]). Similarly, there was a significant increase in the fatty lesion score after 28 weeks in both groups; this change did not, however, differ significantly between groups (spine fatty lesion change score 0.8 ± 1.7 in the infliximab plus naproxen group versus 1.0 ± 1.8 in the placebo plus naproxen group [P = 0.72]; SI joint fatty lesion change score 1.7 ± 2.7 in the infliximab plus naproxen group versus 1.4 ± 2.6 in the placebo plus naproxen group [P = 0.86]). These findings indicate that effective antiinflammatory treatment of axial SpA is associated with an increase in fatty lesion scores, independent of concomitant treatment with or without anti-TNF. © 2016, American College of Rheumatology.

  2. The development and nature of femoral head cam lesions following acetabular fractures.

    PubMed

    Berber, Onur; Foote, Julian; Sabharwal, Sanjeeve; Datta, Gorav; Bircher, Martin D

    2014-01-01

    The aim of acetabular fracture fixation is to restore joint congruity with restoration of the articular surface. Poor outcomes are seen where this has not been achieved. Letournel reported a collarette osteophyte seen postoperatively in a proportion of patients, which he suggested was an early precursor to the development of osteoarthritis. This is a retrospective study of patients treated at a tertiary referral unit who developed this lesion. The triangular index was measured in 48 of these patients and then correlated with their clinical findings, Oxford Hip Score and the presence of osteoarthritis. Length of follow-up, fracture classification, and joint congruency were also recorded. Results showed a statistically significant relationship between cam lesion size and the development of osteoarthritis (P = 0.008), cam lesion size and length of follow-up (P = 0.01), and between groin pain and postoperative joint congruency (LR = 0.035). These findings suggest that the appearance of a cam lesion is a poor long-term prognostic marker for the development of osteoarthritis in patients with an acetabular fracture.

  3. Pre-Cancerous Lesions in the Oral and Maxillofacial Region: A Literature Review with Special Focus on Etiopathogenesis

    PubMed Central

    Irani, Soussan

    2016-01-01

    Many types of cancers develop in the oral and maxillofacial region. Squamous cell carcinoma is the most common cancer and constitutes over 90 percent of these tumors. Malignant transformation is a genetic process, which later makes a phenotyping change at the cellular level. Some cancers such as oral squamous cell carcinomas (OSCCs) develop from pre-malignant lesions and conditions. Despite advances in the treatment of OSCC, the 5-year survival rate remains approximately 50% due to inability of early detection of OSCC and precursor lesions. Early detection of oral cancer, especially in the premalignant stage, can decrease mortality and morbidity significantly. This article reviews some clinical, histopathological features and etiopathogenesis of pre-cancerous lesions of the oral cavity and skin of face and lip vermilion. A relevant English literature search in Pubmed, Science Direct, and Google Scholar was performed from 1930 to 2015. Full text of 191 articles met the specific inclusion criteria for this review. PMID:28855922

  4. No Promoting Effect of Ethyl Tertiary-butyl Ether (ETBE) on Rat Urinary Bladder Carcinogenesis Initiated with N-Butyl-N-(4-hydroxybutyl)nitrosamine

    PubMed Central

    Hagiwara, Akihiro; Imai, Norio; Doi, Yuko; Suguro, Mayuko; Kawabe, Mayumi; Furukawa, Fumio; Nagano, Kasuke; Fukushima, Shoji

    2013-01-01

    The effects of ethyl tertiary-butyl ether (ETBE) on two-stage urinary bladder carcinogenesis in male F344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were investigated at various dose levels with regard to possible promoting activity. Groups of 30 rats were given drinking water containing 500 ppm BBN, as an initiator, for 4 weeks and starting one week thereafter received ETBE by gavage (daily, 7 days/week) at dose levels of 0 (control), 100, 300, 500 or 1000 mg/kg/day until experimental week 36. No statistically significant differences in incidences of preneoplastic lesions, papillomas, and carcinomas of the urinary bladder were evident in rats treated with 100–1000 mg/kg/day ETBE as compared with control values. Furthermore, the average numbers of preneoplastic or neoplastic lesions per unit length of basement membrane in rats given 100–1000 mg/kg/day ETBE were also comparable to control values. However, papillomatosis of the urinary bladder was found in 4 out of 30 rats (13%) in the group given 1000 mg/kg/day ETBE, and soft stones in the urinary bladder were found in 3 out of these 4 rats. The results thus demonstrated that ETBE did not exert promotional activity on urinary bladder carcinogenesis. However, papillomatosis of the urinary bladder developed in small numbers of the rats given ETBE at 1000 mg/kg/day but not in rats given 500 mg/kg/day or lower doses. PMID:24526807

  5. Early osteoarthritis of the patellofemoral joint.

    PubMed

    Arendt, Elizabeth A; Berruto, Massimo; Filardo, Giuseppe; Ronga, Mario; Zaffagnini, Stefano; Farr, Jack; Ferrua, Paolo; Grassi, Alberto; Condello, Vincenzo

    2016-06-01

    Patellofemoral joint cartilage lesions are associated with a variety of clinical situations including blunt trauma, lateral patella dislocations, or as a secondary development in the setting of abnormal joint loading. There is a need for more clarity on how to best address these lesions. Most specifically, when is it necessary to surgically treat these lesions of the patella and trochlea and which technique to use? This review will focus on the spectrum of patellofemoral disease/injury and their treatment strategies, with special emphasis on cartilage damage and early osteoarthritis. Chapter sections will review the most common scenarios of cartilage damage in the patellofemoral joint, with an attempt to summarize current treatment, their outcomes, remaining challenges and unanswered questions.

  6. Vibrational mapping of sinonasal lesions by Fourier transform infrared imaging spectroscopy

    NASA Astrophysics Data System (ADS)

    Giorgini, Elisabetta; Sabbatini, Simona; Conti, Carla; Rubini, Corrado; Rocchetti, Romina; Re, Massimo; Vaccari, Lisa; Mitri, Elisa; Librando, Vito

    2015-12-01

    Fourier transform infrared imaging (FTIRI) is a powerful tool for analyzing biochemical changes in tumoral tissues. The head and neck region is characterized by a great variety of lesions, with different degrees of malignancy, which are often difficult to diagnose. Schneiderian papillomas are sinonasal benign neoplasms arising from the Schneiderian mucosa; they can evolve into malignant tumoral lesions (squamous cell carcinoma). In addition, they can sometimes be confused with the more common inflammatory polyps. Therefore, an early and definitive diagnosis of this pathology is mandatory. Progressing in our research on the study of oral cavity lesions, 15 sections consisting of inflammatory sinonasal polyps, benign Schneiderian papillomas, and sinonasal undifferentiated carcinomas were analyzed using FTIRI. To allow a rigorous description of these pathologies and to gain objective diagnosis, the epithelial layer and the adjacent connective tissue of each section were separately investigated by following a multivariate analysis approach. According to the nature of the lesion, interesting modifications were detected in the average spectra of the different tissue components, above all in the lipid and protein patterns. Specific band-area ratios acting as spectral markers of the different pathologies were also highlighted.

  7. Temporal Plasticity Involved in Recovery from Manual Dexterity Deficit after Motor Cortex Lesion in Macaque Monkeys

    PubMed Central

    Higo, Noriyuki; Hayashi, Takuya; Nishimura, Yukio; Sugiyama, Yoko; Oishi, Takao; Tsukada, Hideo; Isa, Tadashi; Onoe, Hirotaka

    2015-01-01

    The question of how intensive motor training restores motor function after brain damage or stroke remains unresolved. Here we show that the ipsilesional ventral premotor cortex (PMv) and perilesional primary motor cortex (M1) of rhesus macaque monkeys are involved in the recovery of manual dexterity after a lesion of M1. A focal lesion of the hand digit area in M1 was made by means of ibotenic acid injection. This lesion initially caused flaccid paralysis in the contralateral hand but was followed by functional recovery of hand movements, including precision grip, during the course of daily postlesion motor training. Brain imaging of regional cerebral blood flow by means of H215O-positron emission tomography revealed enhanced activity of the PMv during the early postrecovery period and increased functional connectivity within M1 during the late postrecovery period. The causal role of these areas in motor recovery was confirmed by means of pharmacological inactivation by muscimol during the different recovery periods. These findings indicate that, in both the remaining primary motor and premotor cortical areas, time-dependent plastic changes in neural activity and connectivity are involved in functional recovery from the motor deficit caused by the M1 lesion. Therefore, it is likely that the PMv, an area distant from the core of the lesion, plays an important role during the early postrecovery period, whereas the perilesional M1 contributes to functional recovery especially during the late postrecovery period. PMID:25568105

  8. Near-infrared transillumination at 1310-nm for the imaging of early dental decay

    NASA Astrophysics Data System (ADS)

    Jones, Robert S.; Huynh, Gigi D.; Jones, Graham C.; Fried, Daniel

    2003-09-01

    New imaging technologies are needed for the early detection of dental caries (decay) in the interproximal contact sites between teeth. Previous measurements have demonstrated that dental enamel is highly transparent in the near-IR at 1300-nm. In this study, a near-IR imaging system operating at 1300-nm was used to acquire images through tooth sections of varying thickness and whole teeth in order to demonstrate the utility of a near-IR dental transillumination system for the imaging of early dental caries (decay). Simulated lesions, which model the optical scattering of natural dental caries, were placed in plano-parallel dental enamel sections. The contrast ratio between the simulated lesions and surrounding sound enamel was calculated from analysis of acquired projection images. The results show significant contrast between the lesion and the enamel (>0.35) and a spatial line profile that clearly resolves the lesion in samples as thick as 6.75-mm. This study clearly demonstrates that a near-IR transillumination system has considerable potential for the imaging of early dental decay.

  9. Near-infrared transillumination at 1310-nm for the imaging of early dental decay.

    PubMed

    Jones, Robert; Huynh, Gigi; Jones, Graham; Fried, Daniel

    2003-09-08

    New imaging technologies are needed for the early detection of dental caries (decay) in the interproximal contact sites between teeth. Previous measurements have demonstrated that dental enamel is highly transparent in the near-IR at 1300-nm. In this study, a near-IR imaging system operating at 1300-nm was used to acquire images through tooth sections of varying thickness and whole teeth in order to demonstrate the utility of a near-IR dental transillumination system for the imaging of early dental caries (decay). Simulated lesions, which model the optical scattering of natural dental caries, were placed in plano-parallel dental enamel sections. The contrast ratio between the simulated lesions and surrounding sound enamel was calculated from analysis of acquired projection images. The results show significant contrast between the lesion and the enamel (>0.35) and a spatial line profile that clearly resolves the lesion in samples as thick as 6.75-mm. This study clearly demonstrates that a near-IR transillumination system has considerable potential for the imaging of early dental decay.

  10. Five myofibrillar lesion types in eccentrically challenged, unloaded rat adductor longus muscle--a test model

    NASA Technical Reports Server (NTRS)

    Thompson, J. L.; Balog, E. M.; Fitts, R. H.; Riley, D. A.

    1999-01-01

    calcium homeostasis loss (focal contraction lesions) and "thick-filament-centering" failure of titin (wide A-band lesions) in the early stages of lesion development.

  11. L-Selenomethionine Does not Protect Against Testosterone Plus 17β-Estradiol-Induced Oxidative Stress and Pre-Neoplastic Lesions in the Prostate of NBL Rats

    PubMed Central

    Özten, Nur; Schlicht, Michael; Diamond, Alan M.; Bosland, Maarten C.

    2014-01-01

    Previous animal studies examining dietary selenium effects on prostatic carcinogenesis did not show preventive benefit, including one study in a rat model involving testosterone (T) and estradiol (E2)-induced prostatic oxidative stress. Here, we examined modulation of T+E2-induced prostatic oxidative stress, dysplasia, and inflammation by L-selenomethionine at 1.5 or 3.0 mg selenium/kg in NIH-07 diet in Nbl/Crl rats treated with T+E2 for 16 weeks. Hormone treatment increased immunohistochemical staining for 8-hydroxydeoxyguanosine (8-OHdG) in the prostatic sites of T+E2-induced preneoplasia (p<0.05), but selenomethionine did not attenuate 8-OHdG staining and dysplasia in the lateral prostate. Glutathione-peroxidase activity and mRNA expression were induced by T+E2 (p<0.05–p<0.0001) but not changed by selenomethionine. Selenomethionine did not cause significant responses in expression and activity of glutathione-peroxidase and MnSOD, except for a reduction of MnSOD protein expression in the lateral prostate (p<0.01). The absence of reduction of oxidative stress and dysplasia and the minimal effects on antioxidant enzymes caused by selenomethionine are consistent with the null effects observed in selenium supplementation animal studies and clinical trials. Significant (p<0.01) opposite apoptosis/cell proliferation balance responses to selenomethionine and to T+E2 occurred in the lateral and dorsal prostate, explaining why T+E2 induces lesions selectively in the lateral lobe of NBL rats. PMID:24773027

  12. Immunohistochemical study of DNA topoisomerase I, DNA topoisomerase II alpha, p53, and Ki-67 in oral preneoplastic lesions and oral squamous cell carcinomas.

    PubMed

    Hafian, Hilal; Venteo, Lydie; Sukhanova, Alyona; Nabiev, Igor; Lefevre, Benoît; Pluot, Michel

    2004-06-01

    Human DNA topoisomerase I (topo I) is the molecular target of the camptothecin group of anticancer drugs. Laboratory studies have shown that the cellular response to topo I-targeted drugs depends on the topo I expression and DNA replication rate and the apoptotic pathway activity. In this study, we tested potential indicators of the sensitivity of topo I-targeted drugs in 36 cases of oral squamous cell carcinoma (OSCC). Formalin-fixed, paraffin-embedded tissue sections were immunostained with monoclonal antibodies against Ki-67, p53, and topo I, and with polyclonal antibodies against DNA topoisomerase II-alpha (topo II-alpha). These markers were also tested in 18 epithelial hyperplastic lesions and 18 mild dysplasias. Immunostaining was quantified by the percentage of stained nuclei in each sample (the labeling index); 200 immunoreactive epithelial nuclei were counted per case for each antibody. The results support the possibility of using topo II-alpha staining for assessing the proliferative activity. High expression of topo II-alpha and topo I in OSCCs suggests that they may serve as potential indicators of sensitivity to topo I inhibitors. However, the apoptotic pathway assessed by p53 immunostaining was found to be uninformative. Analysis of the relationship between immunohistochemical results and clinical and pathologic parameters (the T and N stages and differentiation) showed that only the differentiation parameter correlated with the topo I expression rate. Thus, significant increase in the topo I expression in the poorly differentiated OSCCs suggests their higher sensitivity to drug treatment.

  13. [The Efficiency and Complications of ESD and ESTD in the Treatment of Large Esophageal Mucosal Lesions].

    PubMed

    Wang, Jin; Qin, Jin-yu; Guo, Tian-jiao; Gan, Tao; Wang, Yi-ping; Wu, Jun-chao

    2015-11-01

    To study the efficiency and complications of endoscopic submucosal dissection (ESD) and endoscopic submucosal tunnel dissection (ESTD) in the treatment of large esophageal mucosal lesions. The clinical data were collected from the patients who received ESD or ESTD for the treatment of early esophageal lesions in our hospital during January 1, 2014 to July 15, 2015, including the en bloc resection rate, curative resection rate, postoperative complication rate, the risk factors of complications were explored by univariate and multivariate analysis. A total of 50 patients were involved in the study, ESD or ESTD were performed successfully in 53 times, including 6 cases of ESD,47 cases of ESTD, The average age was (61.9 +/- 6.8) yr., the average operating time was (83.57 +/- 32.33) min, the average dissected lesion was (14.82 +/- 3.18) cm2, En bloc resection rate was 94.34%, the curative rate was 84.90%. There were 1 case of bleeding, 1 case of perforation, 45 (84.90%) cases of fever, 13 cases (24.53%) of esophageal stricture. The severity of stricture was associated with the operation time Codds ratio (OR) = 1.040, 95% confidence interal (CI): 1.007-1.075) and esophageal circumference (OR=9.972, 95% CI: 1.221-81.416). The residual resection margin appeared in 8 patients, and the lesion area (OR=1.145, 95% CI: 1.013-1.294) was the only risk factor. ESD and ESTD are safe and effective in the treatment of early esophageal lesions, but seems have relatively high incidence of esopgageal stricture and residual resection margin in the treatment of large esophageal lesions.

  14. Unrepaired clustered DNA lesions induce chromosome breakage in human cells

    PubMed Central

    Asaithamby, Aroumougame; Hu, Burong; Chen, David J.

    2011-01-01

    Clustered DNA damage induced by ionizing radiation is refractory to repair and may trigger carcinogenic events for reasons that are not well understood. Here, we used an in situ method to directly monitor induction and repair of clustered DNA lesions in individual cells. We showed, consistent with biophysical modeling, that the kinetics of loss of clustered DNA lesions was substantially compromised in human fibroblasts. The unique spatial distribution of different types of DNA lesions within the clustered damages, but not the physical location of these damages within the subnuclear domains, determined the cellular ability to repair the damage. We then examined checkpoint arrest mechanisms and yield of gross chromosomal aberrations. Induction of nonrepairable clustered damage affected only G2 accumulation but not the early G2/M checkpoint. Further, cells that were released from the G2/M checkpoint with unrepaired clustered damage manifested a spectrum of chromosome aberrations in mitosis. Difficulties associated with clustered DNA damage repair and checkpoint release before the completion of clustered DNA damage repair appear to promote genome instability that may lead to carcinogenesis. PMID:21527720

  15. Biopsy guided by dermoscopy in cutaneous pigmented lesion - Case report*

    PubMed Central

    Bomm, Lislaine; Benez, Marcela Duarte Villela; Maceira, Juan Manuel Piñeiro; Succi, Isabel Cristina Brasil; Scotelaro, Maria de Fatima Guimarães

    2013-01-01

    It may be clinically difficult to differentiate early-stage melanoma from benign tumors, specially pigmented seborrheic keratosis. Dermoscopy can help; however, the findings are not always conclusive. Therefore, histopathology may be necessary for a correct diagnosis. We describe a melanocytic lesion with dubious clinic and dermoscopic findings. An incisional biopsy of a suspicious area, guided by dermoscopy, was performed to clarify the findings. PMID:23539018

  16. Flow Cytometric Ploidy Determination of Oral Premalignant and Malignant Lesions

    DTIC Science & Technology

    1990-01-01

    could advantageously influence patient management. REVIEW OF LITERATURE 3 ORAL PRECANCER As early as 1957 the World Health Organization 1 (WHO...euploid lichenoid mucositis was combined with eosinophilia 88 as the diagnosis of the intermediate lesion in case 6 and occurred a year after the...International Histological Classification of Tumours, No. 4. Geneva, World Health Organization, 1971, p. 23. 3. Pindborg, J.J.: Premalignant and malignant

  17. Colon preneoplasia after carcinogen exposure is enhanced and colonic serotonergic system is suppressed by food deprivation.

    PubMed

    Kannen, Vinicius; Fernandes, Cleverson R; Stopper, Helga; Zanette, Dalila L; Ferreira, Frederico R; Frajacomo, Fernando T; Carvalho, Milene C; Brandão, Marcus L; Elias Junior, Jorge; Jordão Junior, Alceu Afonso; Uyemura, Sérgio Akira; Waaga-Gasser, Ana Maria; Garcia, Sérgio B

    2013-10-04

    Calorie restriction regimens usually promote health and extend life-span in mammals. This is partially related to their preventive effects against malignancies. However, certain types of nutritional restriction failed to induce beneficial effects. The American Institute of Nutrition defines calorie restriction as diets which have only 40% fewer calories, but provide normal amounts of necessary food components such as protein, vitamins and minerals; whereas, food restriction means 40% less of all dietary ingredients plus 40% less calories. Our study aimed to test the hypothesis that the latter type of food deprivation (40% less food than consumed by standard fed rats) might increase cancer risk instead of reducing it, as is generally assumed for all dietary restrictive regimens. Since the endogenous modulation of the colon serotonergic system has been observed to play a role during the early steps of carcinogenesis we also investigated whether the serotoninergic system could be involved in the food intake modulation of cancer risk. For this, rats were exposed to a carcinogen and subjected to food deprivation for 56 days. Triglyceride levels and visceral adipose tissue were reduced while hepatic and colonic lipid peroxidation was increased. This dietary restriction also decreased serotonin levels in colon, and gene expression of its intestinal transporter and receptors. Finally, the numbers of preneoplastic lesions in the colon tissue of carcinogen-exposed rats were increased. Our data suggest that food deprivation enhances formation of early tumorigenic lesions by suppressing serotonergic activity in colon tissue. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. Morphogenesis of early stage melanoma

    NASA Astrophysics Data System (ADS)

    Chatelain, Clément; Amar, Martine Ben

    2015-08-01

    Melanoma early detection is possible by simple skin examination and can insure a high survival probability when successful. However it requires efficient methods for identifying malignant lesions from common moles. This paper provides an overview first of the biological and physical mechanisms controlling melanoma early evolution, and then of the clinical tools available today for detecting melanoma in vivo at an early stage. It highlights the lack of diagnosis methods rationally linking macroscopic observables to the microscopic properties of the tissue, which define the malignancy of the tumor. The possible inputs of multiscale models for improving these methods are shortly discussed.

  19. In vivo characterization of cortical and white matter neuroaxonal pathology in early multiple sclerosis.

    PubMed

    Granberg, Tobias; Fan, Qiuyun; Treaba, Constantina Andrada; Ouellette, Russell; Herranz, Elena; Mangeat, Gabriel; Louapre, Céline; Cohen-Adad, Julien; Klawiter, Eric C; Sloane, Jacob A; Mainero, Caterina

    2017-11-01

    Neuroaxonal pathology is a main determinant of disease progression in multiple sclerosis; however, its underlying pathophysiological mechanisms, including its link to inflammatory demyelination and temporal occurrence in the disease course are still unknown. We used ultra-high field (7 T), ultra-high gradient strength diffusion and T1/T2-weighted myelin-sensitive magnetic resonance imaging to characterize microstructural changes in myelin and neuroaxonal integrity in the cortex and white matter in early stage multiple sclerosis, their distribution in lesional and normal-appearing tissue, and their correlations with neurological disability. Twenty-six early stage multiple sclerosis subjects (disease duration ≤5 years) and 24 age-matched healthy controls underwent 7 T T2*-weighted imaging for cortical lesion segmentation and 3 T T1/T2-weighted myelin-sensitive imaging and neurite orientation dispersion and density imaging for assessing microstructural myelin, axonal and dendrite integrity in lesional and normal-appearing tissue of the cortex and the white matter. Conventional mean diffusivity and fractional anisotropy metrics were also assessed for comparison. Cortical lesions were identified in 92% of early multiple sclerosis subjects and they were characterized by lower intracellular volume fraction (P = 0.015 by paired t-test), lower myelin-sensitive contrast (P = 0.030 by related-samples Wilcoxon signed-rank test) and higher mean diffusivity (P = 0.022 by related-samples Wilcoxon signed-rank test) relative to the contralateral normal-appearing cortex. Similar findings were observed in white matter lesions relative to normal-appearing white matter (all P < 0.001), accompanied by an increased orientation dispersion (P < 0.001 by paired t-test) and lower fractional anisotropy (P < 0.001 by related-samples Wilcoxon signed-rank test) suggestive of less coherent underlying fibre orientation. Additionally, the normal-appearing white matter in multiple sclerosis

  20. In vitro caries lesion rehardening and enamel fluoride uptake from fluoride varnishes as a function of application mode.

    PubMed

    Lippert, Frank; Hara, Anderson T; Martinez-Mier, Esperanza Angeles; Zero, Domenick T

    2013-04-01

    To study the laboratory predicted anticaries efficacy of five commercially available fluoride varnishes (FV) by determining their ability to reharden and to deliver fluoride to an early caries lesion when applied directly or in close vicinity to the lesion (halo effect). Early caries lesions were created in 80 polished bovine enamel specimens. Specimens were allocated to five FV groups (n = 16) based on Knoop surface microhardness (KHN) after lesion creation. All tested FV claimed to contain 5% sodium fluoride and were: CavityShield, Enamel Pro, MI Varnish, Prevident and Vanish. FV were applied (10 +/- 2 mg per lesion) to eight specimens per FV group (direct application); the remaining eight specimens received no FV but were later exposed to fluoride released from specimens which received a FV treatment (indirect application). Specimens were paired again and placed into containers (one per FV). Artificial saliva was added and containers placed into an incubator (27 hours at 37 degrees C). Subsequently, FV was carefully removed using chloroform. Specimens were exposed to fresh artificial saliva again (67 hours at 37 degrees C). KHN was measured and differences to baseline values calculated. Enamel fluoride uptake (EFU) was determined using the acid etch technique. Data were analyzed using two-way ANOVA. The two-way ANOVA highlighted significant interactions between FV vs. application mode, for both deltaKHN and EFU (P < 0.001). All FV were able to reharden and deliver fluoride to caries lesions, but to different degrees. Furthermore, considerable differences were found for both variables between FV when applied either directly or in close vicinity to the lesion: MI Varnish and Enamel Pro exhibited greater fluoride efficacy when applied in vicinity rather than directly to the lesion, whereas CavityShield and Vanish did not differ. Prevident exhibited a higher EFU when applied directly, but little difference in rehardening.

  1. A Rare Case of Cavitary Lesion of the Lung Caused by Mycoplasma pneumoniae in an Immunocompetent Patient

    PubMed Central

    Dudekula, Rizwan Ahmed

    2017-01-01

    Mycoplasma pneumoniae is an atypical bacterium that most commonly causes upper respiratory tract infections, but it can also cause pneumonia, referred to as “walking pneumonia.” Although cavitary lesions are present in a wide variety of infectious and noninfectious processes, those attributable to M. pneumoniae are extremely uncommon; thus, to date, epidemiological studies are lacking. Here, we present a rare case of a 20-year-old male, referred to us from a psychiatric facility for evaluation of a cough, who was found to have a cavitary lesion in the right upper lobe. An extensive workup for cavitary lesion was negative, but his mycoplasma IgM level was high. A computed tomography (CT) of the chest confirmed the presence of a cavitary lesion. After treatment with levofloxacin antibiotics, a follow-up CT showed complete resolution of the lesion. Our case is a rare presentation of mycoplasma pneumonia as a cavitary lesion in a patient without any known risk factors predisposing to mycoplasma infection. Early recognition and treatment with an appropriate antibiotic may lead to complete resolution of the cavitary lesion. PMID:28912822

  2. Accurate GM atrophy quantification in MS using lesion-filling with co-registered 2D lesion masks☆

    PubMed Central

    Popescu, V.; Ran, N.C.G.; Barkhof, F.; Chard, D.T.; Wheeler-Kingshott, C.A.; Vrenken, H.

    2014-01-01

    Background In multiple sclerosis (MS), brain atrophy quantification is affected by white matter lesions. LEAP and FSL-lesion_filling, replace lesion voxels with white matter intensities; however, they require precise lesion identification on 3DT1-images. Aim To determine whether 2DT2 lesion masks co-registered to 3DT1 images, yield grey and white matter volumes comparable to precise lesion masks. Methods 2DT2 lesion masks were linearly co-registered to 20 3DT1-images of MS patients, with nearest-neighbor (NNI), and tri-linear interpolation. As gold-standard, lesion masks were manually outlined on 3DT1-images. LEAP and FSL-lesion_filling were applied with each lesion mask. Grey (GM) and white matter (WM) volumes were quantified with FSL-FAST, and deep gray matter (DGM) volumes using FSL-FIRST. Volumes were compared between lesion mask types using paired Wilcoxon tests. Results Lesion-filling with gold-standard lesion masks compared to native images reduced GM overestimation by 1.93 mL (p < .001) for LEAP, and 1.21 mL (p = .002) for FSL-lesion_filling. Similar effects were achieved with NNI lesion masks from 2DT2. Global WM underestimation was not significantly influenced. GM and WM volumes from NNI, did not differ significantly from gold-standard. GM segmentation differed between lesion masks in the lesion area, and also elsewhere. Using the gold-standard, FSL-FAST quantified as GM on average 0.4% of the lesion area with LEAP and 24.5% with FSL-lesion_filling. Lesion-filling did not influence DGM volumes from FSL-FIRST. Discussion These results demonstrate that for global GM volumetry, precise lesion masks on 3DT1 images can be replaced by co-registered 2DT2 lesion masks. This makes lesion-filling a feasible method for GM atrophy measurements in MS. PMID:24567908

  3. Multimodality imaging of ovarian cystic lesions: Review with an imaging based algorithmic approach

    PubMed Central

    Wasnik, Ashish P; Menias, Christine O; Platt, Joel F; Lalchandani, Usha R; Bedi, Deepak G; Elsayes, Khaled M

    2013-01-01

    Ovarian cystic masses include a spectrum of benign, borderline and high grade malignant neoplasms. Imaging plays a crucial role in characterization and pretreatment planning of incidentally detected or suspected adnexal masses, as diagnosis of ovarian malignancy at an early stage is correlated with a better prognosis. Knowledge of differential diagnosis, imaging features, management trends and an algorithmic approach of such lesions is important for optimal clinical management. This article illustrates a multi-modality approach in the diagnosis of a spectrum of ovarian cystic masses and also proposes an algorithmic approach for the diagnosis of these lesions. PMID:23671748

  4. Temporal changes in sarcomere lesions of rat adductor longus muscles during hindlimb reloading

    NASA Technical Reports Server (NTRS)

    Krippendorf, B. B.; Riley, D. A.

    1994-01-01

    Focal sarcomere disruptions were previously observed in adductor longus muscles of rats flown approximately two weeks aboard the Cosmos 1887 and 2044 biosatellite flights. These lesions, characterized by breakage and loss of myofilaments and Z-line streaming, resembled damage induced by unaccustomed exercise that includes eccentric contractions in which muscles lengthen as they develop tension. We hypothesized that sarcomere lesions in atrophied muscles of space flow rats were not produced in microgravity by muscle unloading but resulted from muscle reloading upon re-exposure to terrestrial gravity. To test this hypothesis, we examined temporal changes in sarcomere integrity of adductor longus muscles from rats subjected to 12.5 days of hindlimb suspension unloading and subsequent reloading by return to vivarium cages for 0, 6, 12, or 48 hours of normal weightbearing. Our ultrastructural observations suggested that muscle unloading (0 h reloading) induced myofibril misalignment associated with myofiber atrophy. Muscle reloading for 6 hours induced focal sarcomere lesions in which cross striations were abnormally widened. Such lesions were electron lucent due to extensive myofilament loss. Lesions in reloaded muscles showed rapid restructuring. By 12 hours of reloading, lesions were moderately stained foci and by 48 hours darkly stained foci in which the pattern of cross striations was indistinct at the light and electron microscopic levels. These lesions were spanned by Z-line-like electron dense filamentous material. Our findings suggest a new role for Z-line streaming in lesion restructuring: rather than an antecedent to damage, this type of Z-line streaming may be indicative of rapid, early sarcomere repair.

  5. Oral mucosal lesions and risk habits among men in an Italian study population.

    PubMed

    Campisi, G; Margiotta, V

    2001-01-01

    A randomly selected study population of 118 male subjects (> or = 40 years) living on the Mediterranean island of Pantelleria (southwest of Sicily, Italy) was examined for the presence of oral mucosal lesions, with particular emphasis on the early diagnosis of oral precancerous and cancerous lesions. The study population was interviewed for socioeconomic and behavioural information, and clinically examined using WHO criteria. The prevalence of oral mucosal lesions observed, and data obtained about oral hygiene, tobacco smoking, alcohol drinking and exposure to actinic radiation, were analysed. Alcohol drinking was the most common habit in the study population (73%), followed by tobacco smoking (58.5%, of whom 96% were cigarette smokers). Only 3% showed good oral hygiene and 25% were edentate. Oral lesions were observed in 81.3% of the study group, mainly coated tongue (51.4%), leukoplakia (13.8%), traumatic oral lesions (traumatic ulcers and frictional white lesions) in 9.2%, actinic cheilitis (4.6%), and squamous cell carcinoma in one case (0.9%). Statistically significant associations were found between the prevalence of coated tongue and tobacco smoking (P<0.0001), and between the prevalence of actinic cheilitis and tobacco smoking/alcohol drinking (P<0.05). Analysis of clinical and anamnestic data underlined the effective presence, in the population examined, of the behavioural risk factors for oral precancerous and cancerous lesions, and the lack of cultural motivation towards primary prevention activities, such as the elimination of risk habits.

  6. Loss of corticospinal tract integrity in early MS disease stages

    PubMed Central

    Neumann, Jens; Kaufmann, Jörn; Heidel, Jan; Stadler, Erhard; Sweeney-Reed, Catherine; Sailer, Michael; Schreiber, Stefanie

    2017-01-01

    Objective: We investigated corticospinal tract (CST) integrity in the absence of white matter (WM) lesions using diffusion tensor imaging (DTI) in early MS disease stages. Methods: Our study comprised 19 patients with clinically isolated syndrome (CIS), 11 patients with relapsing-remitting MS (RRMS), and 32 age- and sex-matched healthy controls, for whom MRI measures of CST integrity (fractional anisotropy [FA], mean diffusivity [MD]), T1- and T2-based lesion load, and brain volumes were available. The mean (SD) disease duration was 3.5 (2.1) months, and disability score was low (median Expanded Disability Status Scale 1.5) at the time of the study. Results: Patients with CIS and RRMS had significantly lower CST FA and higher CST MD values compared with controls. These findings were present, irrespective of whether WM lesions affected the CST. However, no group differences in the overall gray or WM volume were identified. Conclusions: In early MS disease stages, CST integrity is already affected in the absence of WM lesions or brain atrophy. PMID:28959706

  7. Quantitative Susceptibility Mapping and R2* Measured Changes during White Matter Lesion Development in Multiple Sclerosis: Myelin Breakdown, Myelin Debris Degradation and Removal, and Iron Accumulation.

    PubMed

    Zhang, Y; Gauthier, S A; Gupta, A; Chen, W; Comunale, J; Chiang, G C-Y; Zhou, D; Askin, G; Zhu, W; Pitt, D; Wang, Y

    2016-09-01

    Quantitative susceptibility mapping and R2* are sensitive to myelin and iron changes in multiple sclerosis lesions. This study was designed to characterize lesion changes on quantitative susceptibility mapping and R2* at various gadolinium-enhancement stages. This study included 64 patients with MS with different enhancing patterns in white matter lesions: nodular, shell-like, nonenhancing < 1 year old, and nonenhancing 1-3 years old. These represent acute, late acute, early chronic, and late chronic lesions, respectively. Susceptibility values measured on quantitative susceptibility mapping and R2* values were compared among the 4 lesion types. Their differences were assessed with a generalized estimating equation, controlling for Expanded Disability Status Scale score, age, and disease duration. We analyzed 203 lesions: 80 were nodular-enhancing, of which 77 (96.2%) were isointense on quantitative susceptibility mapping; 33 were shell-enhancing, of which 30 (90.9%) were hyperintense on quantitative susceptibility mapping; and 49 were nonenhancing lesions < 1 year old and 41 were nonenhancing lesions 1-3 years old, all of which were hyperintense on quantitative susceptibility mapping. Their relative susceptibility/R2* values were 0.5 ± 4.4 parts per billion/-5.6 ± 2.9 Hz, 10.2 ± 5.4 parts per billion/-8.0 ± 2.6 Hz, 20.2 ± 7.8 parts per billion/-3.1 ± 2.3 Hz, and 33.2 ± 8.2 parts per billion/-2.0 ± 2.6 Hz, respectively, and were significantly different (P < .005). Early active MS lesions with nodular enhancement show R2* decrease but no quantitative susceptibility mapping change, reflecting myelin breakdown; late active lesions with peripheral enhancement show R2* decrease and quantitative susceptibility mapping increase in the lesion center, reflecting further degradation and removal of myelin debris; and early or late chronic nonenhancing lesions show both quantitative susceptibility mapping and R2* increase, reflecting iron accumulation. © 2016 by

  8. Uterine Vascular Lesions

    PubMed Central

    Vijayakumar, Abhishek; Srinivas, Amruthashree; Chandrashekar, Babitha Moogali; Vijayakumar, Avinash

    2013-01-01

    Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management. PMID:24340126

  9. Frequency and characteristics of melanomas missed at a pigmented lesion clinic: a registry-based study.

    PubMed

    Carli, Paolo; Nardini, Paolo; Crocetti, Emanuele; De Giorgi, Vincenzo; Giannotti, Benvenuto

    2004-10-01

    To ensure the removal of all melanomas at an early phase, a number of benign lesions are currently excised for diagnostic evaluation. Nevertheless, little is known about the frequency of melanomas missed (neither recognized nor excised for diagnostic verification) by early detection practices. This study aimed to investigate the diagnostic performance of a specialized pigmented lesion clinic (PLC) through linkage with a local cancer registry. In 1997, 1741 individuals resident in the area of Florence and Prato, Italy, the catchment area of the Tuscany Cancer Registry (RTT), were consecutively examined at a specialized PLC that has been running since 1992 at the Department of Dermatology of Florence. The outcomes of dermatological consultations retrieved from PLC case notes were compared with all the diagnoses of both in situ and invasive melanoma recorded by the RTT until 31 December 1999. The performance of the PLC in detecting cutaneous melanoma was evaluated in terms of sensitivity, specificity and predictive values, with the RTT data as the gold standard. In the population examined at the PLC, 15 newly incident melanomas, all histologically demonstrated, were recorded by the RTT. In 13 of the 15 cases, excision of the lesion had been recommended by PLC staff, while two melanomas, one in situ and one level II 0.60 mm thick invasive, were missed and were subsequently excised 586 and 824 days, respectively, after the first PLC examination. The clinical and dermoscopic features of the invasive lesion were in agreement with a 'featureless' melanoma, and lacked the well-established parameters of malignancy. A total of 67 benign pigmented skin lesions were excised for diagnostic evaluation. Thus the PLC showed a sensitivity in detecting cutaneous melanoma of 86.7% (95% confidence interval [CI] 85.1-88.3%), a specificity of 95.4% (95% CI 94.3-96.3%), a positive predictive value of 13.7% (95% CI 12.1-15.3%) and a negative predictive value of 99.9% (95% CI 99

  10. Altered growth pattern, not altered growth per se, is the hallmark of early lesions preceding cancer development.

    PubMed

    Doratiotto, S; Marongiu, F; Faedda, S; Pani, P; Laconi, E

    2009-01-01

    Many human solid cancers arise from focal proliferative lesions that long precede the overt clinical appearance of the disease. The available evidence supports the notion that cancer precursor lesions are clonal in origin, and this notion forms the basis for most of the current theories on the pathogenesis of neoplastic disease. In contrast, far less attention has been devoted to the analysis of the phenotypic property that serves to define these focal lesions, i.e. their altered growth pattern. In fact, the latter is often considered a mere morphological by-product of clonal growth, with no specific relevance in the process. In the following study, evidence will be presented to support the concept that focal growth pattern is an inherent property of altered cells, independent of clonal growth; furthermore, it will be discussed how such a property, far from being merely descriptive, might indeed play a fundamental role in the sequence of events leading to the development of cancer. Within this paradigm, the earliest steps of neoplasia should be considered and analysed as defects in the mechanisms of tissue pattern formation.

  11. Multimodality approach to optical early detection and mapping of oral neoplasia

    NASA Astrophysics Data System (ADS)

    Ahn, Yeh-Chan; Chung, Jungrae; Wilder-Smith, Petra; Chen, Zhongping

    2011-07-01

    Early detection of cancer remains the best way to ensure patient survival and quality of life. Squamous cell carcinoma is usually preceded by dysplasia presenting as white, red, or mixed red and white epithelial lesions on the oral mucosa (leukoplakia, erythroplakia). Dysplastic lesions in the form of erythroplakia can carry a risk for malignant conversion of 90%. A noninvasive diagnostic modality would enable monitoring of these lesions at regular intervals and detection of treatment needs at a very early, relatively harmless stage. The specific aim of this work was to test a multimodality approach [three-dimensional optical coherence tomography (OCT) and polarimetry] to noninvasive diagnosis of oral premalignancy and malignancy using the hamster cheek pouch model (nine hamsters). The results were compared to tissue histopathology. During carcinogenesis, epithelial down grow, eventual loss of basement membrane integrity, and subepithelial invasion were clearly visible with OCT. Polarimetry techniques identified a four to five times increased retardance in sites with squamous cell carcinoma, and two to three times greater retardance in dysplastic sites than in normal tissues. These techniques were particularly useful for mapping areas of field cancerization with multiple lesions, as well as lesion margins.

  12. Concurrent fibroadenoma and intraductal papilloma - A recurring complex lesion in a premenarcheal girl.

    PubMed

    Alessandrini, Lara; Gobbi, Dalia; Zanon, Giovanni Franco; Dall'Igna, Patrizia; Cecchetto, Giovanni; Alaggio, Rita

    2013-02-15

    Breast diseases are rare in childhood and adolescence, most lesions being fibroadenomas and papillomas. We report the case of an 11-year old girl with a complex breast lesion with hybrid features of fibroadenoma and intraductal papilloma with an early recurrence. Microscopically, the lesion was composed of dilated ducts showing intraluminal papillary projections with small to broad fibrovascular stalks. The typical leaf-like appearance of fibroadenoma was determined by the presence at the periphery of ducts compressed and distorted by the prominent stromal component. Despite its florid epithelial hyperplasia and mild cytological atypia (more evident in the relapse), immunohistochemical staining for p63 and smooth muscle actin highlighted a continuum outer myoepithelial layer, confirming the non-invasive appearance of the lesion. Two pathogenetic links have been hypothesized: one is based on the morphological continuum between these two entities, which may represent different evolutive stages in the same lesion; the other is based on epithelial/mesenchymal interactions. The possible malignant transformation of such complex lesion is also discussed, along with its differential diagnoses. The relevance of this case lies in its rarity, as well as in the therapeutic strategies related to its biological potential and to the necessity of a conservative treatment, due to the young age of the patient. Copyright © 2012. Published by Elsevier GmbH.

  13. Calcium and α-tocopherol suppress cured-meat promotion of chemically induced colon carcinogenesis in rats and reduce associated biomarkers in human volunteers123

    PubMed Central

    Martin, Océane CB; Santarelli, Raphaelle L; Taché, Sylviane; Naud, Nathalie; Guéraud, Françoise; Audebert, Marc; Dupuy, Jacques; Meunier, Nathalie; Attaix, Didier; Vendeuvre, Jean-Luc; Mirvish, Sidney S; Kuhnle, Gunter CG; Cano, Noel; Corpet, Denis E

    2013-01-01

    Background: Processed meat intake has been associated with increased colorectal cancer risk. We have shown that cured meat promotes carcinogen-induced preneoplastic lesions and increases specific biomarkers in the colon of rats. Objectives: We investigated whether cured meat modulates biomarkers of cancer risk in human volunteers and whether specific agents can suppress cured meat–induced preneoplastic lesions in rats and associated biomarkers in rats and humans. Design: Six additives (calcium carbonate, inulin, rutin, carnosol, α-tocopherol, and trisodium pyrophosphate) were added to cured meat given to groups of rats for 14 d, and fecal biomarkers were measured. On the basis of these results, calcium and tocopherol were kept for the following additional experiments: cured meat, with or without calcium or tocopherol, was given to dimethylhydrazine-initiated rats (47% meat diet for 100 d) and to human volunteers in a crossover study (180 g/d for 4 d). Rat colons were scored for mucin-depleted foci, putative precancer lesions. Biomarkers of nitrosation, lipoperoxidation, and cytotoxicity were measured in the urine and feces of rats and volunteers. Results: Cured meat increased nitroso compounds and lipoperoxidation in human stools (both P < 0.05). Calcium normalized both biomarkers in rats and human feces, whereas tocopherol only decreased nitro compounds in rats and lipoperoxidation in feces of volunteers (all P < 0.05). Last, calcium and tocopherol reduced the number of mucin-depleted foci per colon in rats compared with nonsupplemented cured meat (P = 0.01). Conclusion: Data suggest that the addition of calcium carbonate to the diet or α-tocopherol to cured meat may reduce colorectal cancer risk associated with cured-meat intake. This trial was registered at clinicaltrials.gov as NCT00994526. PMID:24025632

  14. Early ultrasonographic diagnosis of hereditary retinoblastoma.

    PubMed

    Pierro, L; Capoferri, C; Brancato, R

    1991-01-01

    A hereditary retinoblastoma (RTB) was identified by ocular echography in a newborn, whose predisposition to RTB had been assessed based on the family history and DNA testing of the chorionic villi at the eighth week of pregnancy. Ultrasonography was performed during pregnancies without an abnormality being demonstrated. On the third day of life a B-scan examination showed a small membranous lesion in the nasal parapapillary area, whilst on A-scan, the lesion appeared as a hyperreflective peak. Thanks to its early identification, the tumor was successfully treated by photocoagulation.

  15. Accuracy of dentists in the clinical diagnosis of oral lesions.

    PubMed

    Kondori, Ida; Mottin, Roberta W; Laskin, Daniel M

    2011-01-01

    Dentists play an important role in the early diagnosis and treatment of oral lesions. However, treatment based solely on a clinical impression of the diagnosis, without histologic confirmation, can result in serious consequences, particularly when the lesion is precancerous or cancerous. The purpose of this study was to determine the overall accuracy of clinical diagnoses made by dentists as well as to compare the diagnostic ability of general practitioners with members of various dental specialties. The biopsy reports of 976 specimens submitted to the Department of Oral and Maxillofacial Pathology, Virginia Commonwealth University School of Dentistry, between January 2009 and January 2010 were reviewed. The presumptive clinical diagnosis made by the practitioner and the final histologic diagnosis on each specimen were recorded in addition to whether the submitting dentist was a general practitioner or a specialist. Of the clinical diagnoses made by the submitting dentists, 43% were incorrect. General dentists misdiagnosed 45.9%, oral and maxillofacial surgeons 42.8%, endodontists 42.2%, and periodontists 41.2% of the time. The most commonly missed clinical diagnoses were hyperkeratosis (16%), focal inflammatory fibrous hyperplasia (10%), fibroma (8%), periapical granuloma (7%), and radicular cyst (6%). Cancerous lesions were misdiagnosed 5.6% of the time. The high rates of clinical misdiagnosis by dental practitioners indicate that all excised lesions should to be submitted for histologic diagnosis.

  16. Paradoxical ictal EEG lateralization in children with unilateral encephaloclastic lesions.

    PubMed

    Garzon, Eliana; Gupta, Ajay; Bingaman, William; Sakamoto, Americo C; Lüders, Hans

    2009-09-01

    Describe an ictal EEG pattern of paradoxical lateralization in children with unilateral encephaloclastic hemispheric lesion acquired early in life. Of 68 children who underwent hemispherectomy during 2003-2005, scalp video-EEG and brain MRI of six children with an ictal scalp EEG pattern discordant to the clinical and imaging data were reanalyzed. Medical charts were reviewed for clinical findings and seizure outcome. Age of seizure onset was 1 day-4 years. The destructive MRI lesion was an ischemic stroke in 2, a post-infectious encephalomalacia in 2, and a perinatal trauma and hemiconvulsive-hemiplegic syndrome in one patient each. Ictal EEG pattern was characterized by prominent ictal rhythms with either 3-7 Hz spike and wave complexes or beta frequency sharp waves (paroxysmal fast) over the unaffected (contralesional) hemisphere. Scalp video-EEG was discordant, however, other findings of motor deficits (hemiparesis; five severe, one mild), seizure semiology (4/6), interictal EEG abnormalities (3/6), and unilateral burden of MRI lesion guided the decision for hemispherectomy. After 12-39 months of post-surgery follow up, five of six patients were seizure free and one has brief staring spells. We describe a paradoxical lateralization of the EEG to the "good" hemisphere in children with unihemispheric encephaloclastic lesions. This EEG pattern is compatible with seizure free outcome after surgery, provided other clinical findings and tests are concordant with origin from the abnormal hemisphere.

  17. Global Gene Expression Profiling of Hyperkeratotic Skin Lesions from Inner Mongolians Chronically Exposed to Arsenic

    EPA Science Inventory

    The skin is an organ that is highly sensitive to chronic arsenic exposure. Skin lesions such as hyperkeratoses (HKs), which are characterized by hyperproliferation and aberrations in terminal epidermal differentiation, are common early manifestations of arsenicosis in humans. H...

  18. Retrospective review of pediatric oral lesions from a dental school biopsy service.

    PubMed

    Shah, Suhani K; Le, Mary C; Carpenter, William M

    2009-01-01

    This report presents a review of the results from 5457 biopsies of patients, 0-16 years of age, received over 15 years at the University of the Pacific School of Dentistry (Pacific Oral and Maxillofacial Pathology Laboratory). To carry out the largest and most up to date U.S. survey of oral specimens from children. The computerized data was retrieved and compiled for age and diagnoses. The lesions were divided by the MIND classification system into 1) Metabolic 2) Inflammatory 3) Neoplastic and 4) Developmental. Inflammatory lesions formed the largest group of biopsies (2758, 51%) followed by Developmental conditions (1928, 35%) and Neoplasms (734, 13%). Dentigerous cysts were the most common lesions, followed by the mucous retention phenomenon (mucocele). The 15 most frequently occurring lesions accounted for 80% of all biopsies. Eight malignancies and 22 benign aggressive tumors were also included. 1. Pathoses increase with age. 2. Results from our study are similar to most of the other studies. 3. More serious pathoses occur in some countries where there is limited access to care, resulting in patients seeking care only when symptomatic. 4. Oral malignancies are rare, but as with any malignancy, early diagnosis renders a more favorable prognosis.

  19. Influence of Bleeding Pattern on Ischemic Lesions After Spontaneous Hypertensive Intracerebral Hemorrhage with Intraventricular Hemorrhage.

    PubMed

    Rivera-Lara, Lucia; Murthy, Santosh B; Nekoovaght-Tak, Saman; Ali, Hasan; McBee, Nichol; Dlugash, Rachel; Ram, Malathi; Thompson, Richard; Awad, Issam A; Hanley, Daniel F; Ziai, Wendy C

    2018-03-27

    Concomitant acute ischemic lesions are detected in up to a quarter of patients with spontaneous intracerebral hemorrhage (ICH). Influence of bleeding pattern and intraventricular hemorrhage (IVH) on risk of ischemic lesions has not been investigated. Retrospective study of all 500 patients enrolled in the CLEAR III randomized controlled trial of thrombolytic removal of obstructive IVH using external ventricular drainage. The primary outcome measure was radiologically confirmed ischemic lesions, as reported by the Safety Event Committee and confirmed by two neurologists. We assessed predictors of ischemic lesions including analysis of bleeding patterns (ICH, IVH and subarachnoid hemorrhage) on computed tomography scans (CT). Secondary outcomes were blinded assessment of mortality and modified Rankin scale (mRS) at 30 and 180 days. Ischemic lesions occurred in 23 (4.6%) during first 30 days after ICH. Independent risk factors associated with ischemic lesions in logistic regression models adjusted for confounders were higher IVH volume (p = 0.004) and persistent subarachnoid hemorrhage on CT scan (p = 0.03). Patients with initial IVH volume ≥ 15 ml had five times the odds of concomitant ischemic lesions compared to IVH volume < 15 ml. Patients with ischemic lesions had significantly higher odds of death at 1 and 6 months (but not poor outcome; mRS 4-6) compared to patients without concurrent ischemic lesions. Occurrence of ischemic lesions in the acute phase of IVH is not uncommon and is significantly associated with increased early and late mortality. Extra-parenchymal blood (larger IVH and visible subarachnoid hemorrhage) is a strong predictor for development of concomitant ischemic lesions after ICH.

  20. The functional organization of trial-related activity in lexical processing after early left hemispheric brain lesions: An event-related fMRI study

    PubMed Central

    Fair, Damien A.; Choi, Alexander H.; Dosenbach, Yannic B.L.; Coalson, Rebecca S.; Miezin, Francis M.; Petersen, Steven E.; Schlaggar, Bradley L.

    2009-01-01

    Children with congenital left hemisphere damage due to perinatal stroke are capable of acquiring relatively normal language functions despite experiencing a cortical insult that in adults often leads to devastating lifetime disabilities. Although this observed phenomenon accepted, its neurobiological mechanisms are not well characterized. In this paper we examined the functional neuroanatomy of lexical processing in 13 children/adolescents with perinatal left hemispheric damage. In contrast to many previous perinatal infarct fMRI studies, we use an event-related design, which allowed us to isolate trial related activity and examine correct and error trials separately. Using both group and single subject analysis techniques we attempt to address several methodological factors that may contribute to some discrepancies in the perinatal lesion literature. These methodological factors include making direct statistical comparisons, using common stereotactic space, using both single-subject and group analyses, and accounting for performance differences. Our group analysis, investigating correct trial related activity (separately from error trials), showed very few statistical differences in the non-involved right hemisphere between patients and performance matched controls. The single subject analysis revealed atypical regional activation patterns in several patients; however, the location of these regions identified in individual patients often varied across subjects. These results are consistent with the idea that alternative functional organization of trial-related activity after left hemisphere lesions is in large part unique to the individual. In addition, reported differences between results obtained with event-related designs and blocked designs may suggest diverging organizing principles for sustained and trial-related activity after early childhood brain injuries. PMID:19819000

  1. [Caries patterns and diet in early childhood caries].

    PubMed

    Faye, M; Ba, A A; Yam, A A; Ba, I

    2006-01-01

    Early childhood caries (EEC) are multiple carious lesions affecting the primary teeth of infants and preschool children. They are related to a prolonged and night bottle-feeding rich in fermentable carbohydrates. The carious lesions characterised by their patterns and the rapidity of their process can lead to a widespread tooth destruction. The aim of this study was to evaluate the patterns of the carious lesions and their relationship to the diet. This prospective study was carried out in Dakar in public heath structures that have a dental office. It has included 68 children of both sex aged from two to 6 years consisted of 35 boys (51% of the sample) and 33 girls (49%) with the predominance of the 5-year-old children. These children were examined using a plan mouth mirror and probes and their mothers were interviewed. The observed carious lesions were distributed on all tooth surfaces but the complete coronal destruction was the most common lesions observed and represented 25 of the lesions, followed by lesions in three faces of the tooth (17%). The most frequently affected tooth was the association maxillar incisors and molars and the mandibular molars (32.4%). The incisor alone represented 22.1% of the affected teeth. The children were breast-fed associated with either pap or with hard food (52.9%). The bottle was added to this association in 32.4% of the cases and 10% of the children were exclusively breast-fed. The carious lesions were more severe and more frequent in children fed with breast associated with pap and hard food and in those fed with breast associated with the bottle pap and food than to children exclusively breast-fed. These differences were not statistically significant (p = 0.73 > 0.05). Early childhood caries are related to a diet rich in carbon hydrate. They lead to severe tooth destruction. The treatments cost are very high thus prevention by information on the bad effects of sugar on diet and the baby bottle are of great interest.

  2. Autofluorescence guided diagnostic evaluation of suspicious oral mucosal lesions: opportunities, limitations, and pitfalls

    NASA Astrophysics Data System (ADS)

    Vigneswaran, Nadarajah

    2011-03-01

    Wide-filed autofluorescence examination is currently considered as a standard of care for screening and diagnostic evaluation of early neoplastic changes of the skin, cervix, lung, bladder, gastrointestinal tract and oral cavity. Naturally occurring fluorophores within the tissue absorb UV and visible light and can re-emit some of this light at longer wavelengths in the form of fluorescence. This non-invasive tissue autofluorescence imaging is used in optical diagnostics, especially in the early detection of cancer. Usually, malignant transformation is associated with thickening of the epithelium, enhanced cellular density due to increased nuclear cytoplasmic ratio which may attenuate the excitation leading to a decrease in collagen autofluorescence. Hence, dysplastic and cancerous tissues often exhibit decreased blue-green autofluorescence and appear darker compared to uninvolved mucosa. Currently, there are three commercially available devices to examine tissue autofluorescence in the oral cavity. In this study we used the oral cancer screening device IdentafiTM 3000 to examine the tissue reflectance and autofluorescence of PML and confounding lesions of the oral cavity. Wide-field autofluorescence imaging enables rapid inspection of large mucosal surfaces, to aid in recognition of suspicious lesions and may also help in discriminate the PML (class 1) from some of the confounding lesions (class II). However, the presence of inflammation or pigments is also associated with loss of stromal autofluorescence, and may give rise to false-positive results with widefield fluorescence imaging. Clinicians who use these autofluorescence based oral cancer screening devices should be aware about the benign oral mucosal lesions that may give false positivity so that unnecessary patient's anxiety and the need for scalpel biopsy can be eliminated.

  3. Inhibition of beta-catenin and KRAS expressions by Piper betle in azoxymethane-induced colon cancer of male Fischer 344 rats.

    PubMed

    Esa, Faezah; Ngah, Wan Zurinah Wan; Jamal, A Rahman A; Mohd Yusof, Yasmin Anum

    2013-12-01

    To investigate the chemopreventive effect of Piper betle (PB) on preneoplastic lesions (aberrant crypt foci [ACF]) induced by azoxymethane (AOM) in rats and its effect on colorectal cancer biomarkers (beta-catenin, KRAS, p53 and p21). A total of 32 male Fischer 344 rats were divided into phase 1 and phase 2 groups (8 and 24 weeks of AOM administration, respectively). Each phase was divided into 4 groups: control or normal saline (NS) (1 mL/kg), AOM (15 mg/kg body weight, once weekly for 2 weeks), PB (75 mg/kg body weight) and AOM + PB. PB was force-fed to rats a week after the second dose of AOM and NS. The colon was cut open longitudinally for methylene blue and immunohistochemistry staining. AOM administration showed formation of ACF at 8 and 24 weeks. PB, however, did not reduce ACF formation at either week, but it managed to reduce beta-catenin expression and KRAS found highly expressed in the AOM group of phase 1 rats. No immunoreactivities of p53 and p21 were detected in phase 2 rats, but instead inflammatory cells were visible in between the lesions. PB may act as a potential chemopreventive agent in the early stage of colon carcinogenesis by suppressing the expressions of beta-catenin and KRAS.

  4. Microbiome Analysis of Stool Samples from African Americans with Colon Polyps

    PubMed Central

    Brim, Hassan; Yooseph, Shibu; Zoetendal, Erwin G.; Lee, Edward; Torralbo, Manolito; Laiyemo, Adeyinka O.; Shokrani, Babak; Nelson, Karen; Ashktorab, Hassan

    2013-01-01

    Background Colonic polyps are common tumors occurring in ~50% of Western populations with ~10% risk of malignant progression. Dietary agents have been considered the primary environmental exposure to promote colorectal cancer (CRC) development. However, the colonic mucosa is permanently in contact with the microbiota and its metabolic products including toxins that also have the potential to trigger oncogenic transformation. Aim To analyze fecal DNA for microbiota composition and functional potential in African Americans with pre-neoplastic lesions. Materials & Methods We analyzed the bacterial composition of stool samples from 6 healthy individuals and 6 patients with colon polyps using 16S ribosomal RNA-based phylogenetic microarray; the Human intestinal Tract Chip (HITChip) and 16S rRNA gene barcoded 454 pyrosequencing. The functional potential was determined by sequence-based metagenomics using 454 pyrosequencing. Results Fecal microbiota profiling of samples from the healthy and polyp patients using both a phylogenetic microarraying (HITChip) and barcoded 454 pyrosequencing generated similar results. A distinction between both sets of samples was only obtained when the analysis was performed at the sub-genus level. Most of the species leading to the dissociation were from the Bacteroides group. The metagenomic analysis did not reveal major differences in bacterial gene prevalence/abundances between the two groups even when the analysis and comparisons were restricted to available Bacteroides genomes. Conclusion This study reveals that at the pre-neoplastic stages, there is a trend showing microbiota changes between healthy and colon polyp patients at the sub-genus level. These differences were not reflected at the genome/functions levels. Bacteria and associated functions within the Bacteroides group need to be further analyzed and dissected to pinpoint potential actors in the early colon oncogenic transformation in a large sample size. PMID:24376500

  5. Reliability of Early Magnetic Resonance Imaging (MRI) and Necessity of Repeating MRI in Noncooled and Cooled Infants With Neonatal Encephalopathy.

    PubMed

    Chakkarapani, Elavazhagan; Poskitt, Kenneth J; Miller, Steven P; Zwicker, Jill G; Xu, Qi; Wong, Darren S T; Roland, Elke H; Hill, Alan; Chau, Vann

    2016-04-01

    In cooled newborns with encephalopathy, although late magnetic resonance imaging (MRI) scan (10-14 days of age) is reliable in predicting long-term outcome, it is unknown whether early scan (3-6 days of life) is. We compared the predominant pattern and extent of lesion between early and late MRI in 89 term neonates with neonatal encephalopathy. Forty-three neonates (48%) were cooled. The predominant pattern of lesions and the extent of lesion in the watershed region agreed near perfectly in noncooled (kappa = 0.94; k = 0.88) and cooled (k = 0.89; k = 0.87) infants respectively. There was perfect agreement in the extent of lesion in the basal nuclei in noncooled infants (k = 0.83) and excellent agreement in cooled infants (k = 0.67). Changes in extent of lesions on late MRI occurred in 19 of 89 infants, with higher risk in infants with hypoglycemia and moderate-severe lesions in basal nuclei. In most term neonates with neonatal encephalopathy, early MRI (relative to late scan) robustly predicts the predominant pattern and extent of injury. © The Author(s) 2015.

  6. Early lesion of palisaded neutrophilic granulomatous dermatitis in ulcerative colitis.

    PubMed

    Asahina, Akihiko; Fujita, Hideki; Fukunaga, Yuki; Kenmochi, Yasuko; Ikenaka, Tatsuo; Mitomi, Hiroyuki

    2007-01-01

    Palisaded neutrophilic granulomatous dermatitis (PNGD) is a rare clinical entity of unknown cause. It often coexists with various autoimmune or immunoreactive systemic diseases, and thus it has been reported under multiple names. We describe a patient with quiescent ulcerative colitis, who presented with recurrent small tender papules, nodules and erythematous plaques, located mainly on her hands, together with finger swelling and polyarthralgia. The histopathologic picture indicated an early stage of PNGD with focal degeneration of collagen fibers but without distinct granuloma formation. The differentiation from neutrophilic dermatoses was necessary because of dense and diffuse infiltration of neutrophils with leukocytoclastic debris throughout the dermis, and the association of ulcerative colitis. Dapsone monotherapy was effective in improving the clinical symptoms. PNGD is only rarely associated with ulcerative colitis, and this case suggests that the concept of PNGD, especially in its early stages, might be considered in the wide spectrum of neutrophilic dermatoses.

  7. A cavernous sinus lesion clinically responsive to steroids.

    PubMed

    Ruff, M W; Carabenciov, I D; Johnson, D R; Pollock, B E; Parisi, J E; Klaas, J P

    2018-04-20

    Tolosa Hunt syndrome (THS) is characterized by painful ophthalmoplegia secondary to idiopathic granulomatous inflammation of the cavernous sinus. The characteristic finding on MRI is an enhancing T1 isointense and T2 hypo- or hyperintense cavernous sinus mass lesion, which may result in focal narrowing of the ipsilateral internal carotid artery. Although the incidence is quite rare, it is a common diagnostic consideration in cases that present with multiple cranial neuropathies. However, the differential diagnosis for a unilateral cavernous sinus lesion in adults is broad and includes neoplastic, inflammatory (such as sarcoidosis and immunoglobulin G4-related disease [IgG4-RD]), infectious etiologies (such as syphilis and leprosy), as well as vascular lesions. We describe a patient presenting with neurologic symptoms referable to a persistent unilateral cavernous sinus MRI abnormality, initially thought to be consistent with Tolosa-Hunt syndrome, that was clinically but not radiographically responsive to steroids. Following reevaluation due to the presence of new symptoms, pathology revealed that the abnormality was most consistent with chordoma, a rare skull based tumor. In patients with a presumed diagnosis of Tolosa-Hunt syndrome, close clinical and radiographic follow-up is imperative, with early consideration for biopsy in patients that fail to respond to treatment both clinically and radiographically. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Herpesviral Hematopoietic Necrosis in Goldfish in Switzerland: Early Lesions in Clinically Normal Goldfish (Carassius auratus).

    PubMed

    Giovannini, S; Bergmann, S M; Keeling, C; Lany, C; Schütze, H; Schmidt-Posthaus, H

    2016-07-01

    Cyprinid herpesvirus 2 is a pathogen of goldfish, inducing a disease referred to as herpesviral hematopoietic necrosis. The disease is described so far in Japan, North America, Taiwan, Australia, the United Kingdom, and recently also Italy. Here the authors describe histologic lesions in clinically affected fish in comparison with clinically normal but virus DNA-positive goldfish in Switzerland. While necrosis or enhanced single-cell necrosis in the hematopoietic tissue in the pronephros or mesonephros was evident in dead and sick animals, in clinically normal goldfish, only single-cell necrosis was observed. Virus DNA was demonstrated in dead as well as clinically affected and subclinically infected goldfish by polymerase chain reaction and in situ hybridization. This study identifies the presence of goldfish herpesvirus in Switzerland and highlights the fact that the virus might be more widespread than assumed, as clinically normal goldfish can also carry cyprinid herpesvirus 2, showing histologically similar lesions but of lesser extent and severity. © The Author(s) 2015.

  9. Prevention and Treatment of White Spot Lesions During and After Treatment with Fixed Orthodontic Appliances: a Systematic Literature Review.

    PubMed

    Lopatiene, Kristina; Borisovaite, Marija; Lapenaite, Egle

    2016-01-01

    The aim of the systematic literature review is to update the evidence for the prevention of white spot lesions, using materials containing fluoride and/or casein phosphopeptide-amorphous calcium phosphate during and after treatment with fixed orthodontic appliances. Information search for controlled studies on humans published between January 2008 and February 2016 was performed in PubMed, ScienceDirect, Embase, The Cochrane Library. Inclusion criteria were: the English language, study on humans, patients undergoing orthodontic treatment with fixed appliances, randomized or quasi-randomized controlled clinical studies fluoride-containing product or casein derivates used throughout the appliance therapy or straightaway after debonding. 326 articles were reviewed (Embase 141, PubMed 129, ScienceDirect 41, Cochrane 15). Twelve clinical studies fulfilled all inclusion criteria. Use of fluoridated toothpaste had a remineralizing effect on white spot lesions (WSLs) (P < 0.05); fluoride varnish and casein supplements were effective in prevention and early treatment of WSLs (P < 0.05). Early detection of white spot lesions during orthodontic treatment would allow implementing preventive measures to control the demineralization process before lesions progress. The systemic review has showed that the usage of fluoride and casein supplements in ameliorating white spot lesions during and after fixed orthodontic treatment is significantly effective. However the use of casein phosphopeptide-amorphous calcium phosphate can be more beneficial than fluoride rinse in the reduction of demineralization spots.

  10. Extraction of breast lesions from ultrasound imagery: Bhattacharyya gradient flow approach

    NASA Astrophysics Data System (ADS)

    Torkaman, Mahsa; Sandhu, Romeil; Tannenbaum, Allen

    2018-03-01

    Breast cancer is one of the most commonly diagnosed neoplasms among American women and the second leading cause of death among women all over the world. In order to reduce the mortality rate and cost of treatment, early diagnosis and treatment are essential. Accurate and reliable diagnosis is required in order to ensure the most effective treatment and a second opinion is often advisable. In this paper, we address the problem of breast lesion detection from ultrasound imagery by means of active contours, whose evolution is driven by maximizing the Bhattacharyya distance1 between the probability density functions (PDFs). The proposed method was applied to ultrasound breast imagery, and the lesion boundary was obtained by maximizing the distance-based energy functional such that the maximum (optimal contour) is attained at the boundary of the potential lesion. We compared the results of the proposed method quantitatively using the Dice coefficient (similarity index)2 to well-known GrowCut segmentation method3 and demonstrated that Bhattacharyya approach outperforms GrowCut in most of the cases.

  11. Nuclear microscopic investigations into the elemental changes in the substantia nigra of unilaterally MPTP-lesioned Parkinsonian monkeys

    NASA Astrophysics Data System (ADS)

    Thong, P. S. P.; He, Y.; Lee, T.; Watt, F.

    1997-07-01

    Various transition metals, particularly iron, have been implicated in the aetiology of the neurodegenerative disease, Parkinson's disease, in which there is a characteristic loss of cells in the substantia nigra (SN) region of the brain. In this study, monkeys were unilaterally lesioned with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) to obtain primate models of parkinsonism, with the non-lesioned side of the brain serving as controls. The monkeys were sacrificed at one day, one week, two weeks, one month and one year after lesioning to investigate the time dependent elemental changes in the parkinsonian SN. Sections of the brain encompassing both the lesioned and non-lesioned SNs were analysed using the National University of Singapore nuclear microscope. Adjacent sections were tyrosine hydroxylase (TH) immunohistochemically stained to provide complementary information on dopaminergic cell loss and to facilitate definition of the SN boundaries during data analysis. In one-day and one-week monkeys (representing early stages of the disease), there were no changes in elemental concentrations within experimental errors and the adjacent TH-stained sections did not show apparent cell loss in the SN. At two weeks, cell loss was seen in the lesioned SN compared to the control SN. Although there was no bulk increase in SN iron, localised accumulation of iron in granules containing up to 15% by weight iron was observed in the lesioned SN of one of the two-week monkeys. An average 15% increase in nigral iron, significant at the 90% confidence level ( p < 0.1), was seen in the one-month monkeys. TH-stained sections for the one-month monkeys showed cell loss in the lesioned SN. In one-year samples (representing the advanced stage of the disease) there was a significant ( p < 0.05) 56% increase in iron, 14% increase in phosphorous and a 20% decrease in copper. Here an almost complete loss of cells in the lesioned SN was apparent from the adjacent TH

  12. Imaging review of lipomatous musculoskeletal lesions

    PubMed Central

    Burt, Ashley M.; Huang, Brady K.

    2017-01-01

    Lipomatous lesions are common musculoskeletal lesions that can arise within the soft tissues, bone, neurovascular structures, and synovium. The majority of these lesions are benign, and many of the benign lesions can be diagnosed by radiologic evaluation. However, radiologic differences between benign and malignant lipomatous lesions may be subtle and pathologic correlation is often needed. The use of sonography, computed tomography (CT), and magnetic resonance imaging (MRI) is useful not only in portraying fat within the lesion, but also for evaluating the presence and extent of soft tissue components. Lipomas make up most soft tissue lipomatous lesions, but careful evaluation must be performed to distinguish these lesions from a low-grade liposarcoma. In addition to the imaging appearance, the location of the lesion and the patient demographics can be utilized to help diagnose other soft tissue lipomatous lesions, such as elastofibroma dorsi, angiolipoma, lipoblastoma, and hibernoma. Osseous lipomatous lesions such as a parosteal lipoma and intraosseous lipoma occur less commonly as their soft tissue counterpart, but are also benign. Neurovascular and synovial lipomatous lesions are much rarer lesions but demonstrate more classic radiologic findings, particularly on MRI. A review of the clinical, radiologic, and pathologic characteristics of these lesions is presented. PMID:28474576

  13. Contact Endoscopy of mucosal lesions of oral cavity – Preliminary experience

    PubMed Central

    Mishra, Awadhesh Kumar; Nilakantan, Ajith; Sahai, Kavita; Datta, Rakesh; Malik, Ajay

    2014-01-01

    Background Contact Endoscopy is a non invasive tool to visualise alterations in cell architecture in vivo. In this study we investigated the diagnostic accuracy of Contact Endoscopy in detecting malignancy in oral mucosal lesions. Methods 76 patients with oral mucosal lesions requiring biopsy were included. Contact Endoscopy was performed by Otolaryngologist before biopsy and findings recorded. The lesion was then biopsied and sent for histopathological examination by Pathologist who was blinded to Contact Endoscopy findings. Findings of Contact Endoscopy were compared with histopathological findings taking the latter as the gold standard. Two biopsies were reported as ‘inconclusive’ on histopathological examination and hence excluded from the final analysis. Data of the remaining 74 patients is presented here. Results Clinically lesions were diagnosed as ulcero-proliferative lesions in 34 patients, Leukoplakia in 19, Erythroplakia in 9, Lichen planus in 5 and Submucous fibrosis in 7 patients. Histopathological examination revealed presence of malignancy in 97.06% of ulcero-proliferative mucosal lesions, 10.53% of leukoplakia and 33.33% of erythroplakia while corresponding figures on Contact Endoscopy were 94.12%, 5.26% and 11.11% respectively. No malignancy was detected in lichen planus and submucous fibrosis by either technique. When compared with histopathological examination, CE showed sensitivity of 84.21%, specificity of 94.44% and accuracy of 89.19%. No adverse effects on the patients were seen due to the procedure or stain. Conclusion Contact Endoscopy may be useful in determining cellular structure in vivo without biopsy to detect oral malignancy early. Further studies are suggested. PMID:25378780

  14. Laser-induced autofluorescence properties of base-cell lesions: analysis and algorithms for diagnosis and differentiation

    NASA Astrophysics Data System (ADS)

    Borisova, E.; Troyanova, P.; Avramov, L.

    2006-09-01

    The goals of this work were investigation of base-cell skin lesions by the method of laser-induced autofluorescence spectroscopy. Fluorescence spectra were obtained from benign base-cell papilloma and malignant base-cell carcinoma, as well as from healthy skin areas near to the lesions that were used posteriori to reveal changes between healthy and lesion skin spectra. Preliminarily lesions were classified by dermatoscopic method (MoleMax II, DERMA Instruments). All suspicious lesions were excised and were investigated histologically. The experimental set-up consists of a nitrogen laser (337 nm, 14 μJ, 10 Hz), lenses, filters, optical fibers, and a microspectrometer (PC2000, "Ocean Optics"). A computer controls this system. Spectrum of healthy skin consists of one main maximum at 470-500 nm spectral region and secondary maxima at in the regions around 400 and 440 nm. In cases of papilloma and base-cell carcinoma an intensity decrease was observed, related to accumulation of pigments in these cutaneous lesions. An relative increase of the fluorescence peak at 440 nm were registered in the case of base-cell carcinoma, related to metabolism activity increase, and appearance of green fluorescence, related to increase of keratin content in benign papilloma lesions were detected. The results, obtained were used to develop multispectral diagnostic algorithm of these base-cell lesions. An sensitivity of 89,4% and 91,0% and specificity of 99,6% and 97,4% for differentiation between normal skin and papilloma and carcinoma respectively were obtained. The capability of the human skin fluorescence spectroscopy for early diagnosis and differentiation of cutaneous lesions is shown.

  15. Hock lesions and free-stall design.

    PubMed

    Weary, D M; Taszkun, I

    2000-04-01

    We compared the prevalence and severity of skin lesions on the hocks of lactating dairy cows in southern British Columbia, comparing 20 farms using three common bedding surfaces: sawdust, sand, and geotextile mattresses. Skin lesions were scored at five positions on the hock. For each position we noted if the lesion showed inflammatory attributes, and then assigned a severity score. Of the 1752 lactating cows scored, 1267 cows (73%) had at least one hock lesion. Of those cows with lesions, 87% had lesions on both legs, 76% had lesions on more than one location on the hock, and 78% had a lesion of at least moderate severity (i.e., evidence of skin breakage or an area of hair loss >10 cm2). Lesions were most prevalent on farms that used geotextile mattresses (91% of cows) and least common on farms that used sand (24% of cows). Moreover, lesions on cows from farms using mattresses were more numerous and more severe than those on cows from sand-bedded farms. The prevalence and severity of lesions on farms using sawdust was intermediate. Lesions also varied in relation to location on the hock. For farms using geotextile mattresses, lesions were more common and more severe on the lateral surfaces of both the tuber calcis and the tarsal joint. On farms using sawdust, lesions were common on the dorsal surface of the tuber calcis and the lateral surfaces of both the tuber calcis and the tarsal joint. Lesions were rare on all five positions for cows from sand-bedded farms. Among the 10 farms sampled using sawdust, we found a significant negative relationship between the length of the stall and severity of lesions. For cows with lesions, the number and severity of lesions increased with age.

  16. Repair-Resistant DNA Lesions

    PubMed Central

    2017-01-01

    The eukaryotic global genomic nucleotide excision repair (GG-NER) pathway is the major mechanism that removes most bulky and some nonbulky lesions from cellular DNA. There is growing evidence that certain DNA lesions are repaired slowly or are entirely resistant to repair in cells, tissues, and in cell extract model assay systems. It is well established that the eukaryotic DNA lesion-sensing proteins do not detect the damaged nucleotide, but recognize the distortions/destabilizations in the native DNA structure caused by the damaged nucleotides. In this article, the nature of the structural features of certain bulky DNA lesions that render them resistant to NER, or cause them to be repaired slowly, is compared to that of those that are good-to-excellent NER substrates. Understanding the structural features that distinguish NER-resistant DNA lesions from good NER substrates may be useful for interpreting the biological significance of biomarkers of exposure of human populations to genotoxic environmental chemicals. NER-resistant lesions can survive to replication and cause mutations that can initiate cancer and other diseases. Furthermore, NER diminishes the efficacy of certain chemotherapeutic drugs, and the design of more potent pharmaceuticals that resist repair can be advanced through a better understanding of the structural properties of DNA lesions that engender repair-resistance. PMID:28750166

  17. [Human Papilloma virus in Quechua women from Jujuy with high frequency of cervical cancer: viral types and HPV-16 variants].

    PubMed

    Picconi, Maria Alejandra; Gronda, Jorge; Alonio, Lidia V; Villa, Luisa L; Sichero, Laura; Miranda, Sergio; Barcena, Martin; Teyssie, Angelica

    2002-01-01

    Human Papillomaviruses (HPVs) are etiologically associated to cervical carcinoma. In order to evaluate HPV infection and its relationship with the high frequency of this neoplasia in Quechua women from Jujuy (Argentina), 271 cervical samples from preneoplastic and neoplastic lesions (biopsies) and normal controls (cytologies) were studied. Detection and typing were performed using PCR-RFLP or PCR-hybridization and the HPV-16 variability in L1 and E6 genes (by PCR-hybridization) was analysed. HPV was detected in 52% of controls, 91% of low-grade lesions, 97% of high-grade lesions and 100% of invasive carcinomas, corresponding 55% to HPV-16. HPV-16 European variants were predominant, most of them being non-prototypic strains. The high frequency of high risk infection types and the raised proportion of HPV-16 non-prototypic variants related to a greater oncogenic potential could explain, in part, the high cervical cancer frequency of this native population. These data may contribute to disease control and vaccinal formulation.

  18. Random forest learning of ultrasonic statistical physics and object spaces for lesion detection in 2D sonomammography

    NASA Astrophysics Data System (ADS)

    Sheet, Debdoot; Karamalis, Athanasios; Kraft, Silvan; Noël, Peter B.; Vag, Tibor; Sadhu, Anup; Katouzian, Amin; Navab, Nassir; Chatterjee, Jyotirmoy; Ray, Ajoy K.

    2013-03-01

    Breast cancer is the most common form of cancer in women. Early diagnosis can significantly improve lifeexpectancy and allow different treatment options. Clinicians favor 2D ultrasonography for breast tissue abnormality screening due to high sensitivity and specificity compared to competing technologies. However, inter- and intra-observer variability in visual assessment and reporting of lesions often handicaps its performance. Existing Computer Assisted Diagnosis (CAD) systems though being able to detect solid lesions are often restricted in performance. These restrictions are inability to (1) detect lesion of multiple sizes and shapes, and (2) differentiate between hypo-echoic lesions from their posterior acoustic shadowing. In this work we present a completely automatic system for detection and segmentation of breast lesions in 2D ultrasound images. We employ random forests for learning of tissue specific primal to discriminate breast lesions from surrounding normal tissues. This enables it to detect lesions of multiple shapes and sizes, as well as discriminate between hypo-echoic lesion from associated posterior acoustic shadowing. The primal comprises of (i) multiscale estimated ultrasonic statistical physics and (ii) scale-space characteristics. The random forest learns lesion vs. background primal from a database of 2D ultrasound images with labeled lesions. For segmentation, the posterior probabilities of lesion pixels estimated by the learnt random forest are hard thresholded to provide a random walks segmentation stage with starting seeds. Our method achieves detection with 99.19% accuracy and segmentation with mean contour-to-contour error < 3 pixels on a set of 40 images with 49 lesions.

  19. Unilateral lesion of dorsal hippocampus in adult rats impairs contralateral long-term potentiation in vivo and spatial memory in the early postoperative phase.

    PubMed

    Li, Hongjie; Wu, Xiaoyan; Bai, Yanrui; Huang, Yan; He, Wenting; Dong, Zhifang

    2012-05-01

    It is well documented that bilateral hippocampal lesions or unilateral hippocampal lesion at birth causes impairment of contralateral LTP and long-term memory. However, effects of unilateral hippocampal lesion in adults on contralateral in vivo LTP and memory are not clear. We here examined the influence of unilateral electrolytic dorsal hippocampal lesion in adult rats on contralateral LTP in vivo and spatial memory during different postoperative phases. We found that acute unilateral hippocampal lesion had no effect on contralateral LTP. However, contralateral LTP was impaired at 1 week after lesion, and was restored to the control level at postoperative week 4. Similarly, spatial memory was also impaired at postoperative week 1, and was restored at postoperative week 4. In addition, the rats at postoperative week 1 showed stronger spatial exploratory behavior in a novel open-field environment. The sham operation had no effects on contralateral LTP, spatial memory and exploration at either postoperative week 1 or week 4. These results suggest that unilateral dorsal hippocampal lesion in adult rats causes transient contralateral LTP impairment and spatial memory deficit. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. An improved strategy for skin lesion detection and classification using uniform segmentation and feature selection based approach.

    PubMed

    Nasir, Muhammad; Attique Khan, Muhammad; Sharif, Muhammad; Lali, Ikram Ullah; Saba, Tanzila; Iqbal, Tassawar

    2018-02-21

    Melanoma is the deadliest type of skin cancer with highest mortality rate. However, the annihilation in early stage implies a high survival rate therefore, it demands early diagnosis. The accustomed diagnosis methods are costly and cumbersome due to the involvement of experienced experts as well as the requirements for highly equipped environment. The recent advancements in computerized solutions for these diagnoses are highly promising with improved accuracy and efficiency. In this article, we proposed a method for the classification of melanoma and benign skin lesions. Our approach integrates preprocessing, lesion segmentation, features extraction, features selection, and classification. Preprocessing is executed in the context of hair removal by DullRazor, whereas lesion texture and color information are utilized to enhance the lesion contrast. In lesion segmentation, a hybrid technique has been implemented and results are fused using additive law of probability. Serial based method is applied subsequently that extracts and fuses the traits such as color, texture, and HOG (shape). The fused features are selected afterwards by implementing a novel Boltzman Entropy method. Finally, the selected features are classified by Support Vector Machine. The proposed method is evaluated on publically available data set PH2. Our approach has provided promising results of sensitivity 97.7%, specificity 96.7%, accuracy 97.5%, and F-score 97.5%, which are significantly better than the results of existing methods available on the same data set. The proposed method detects and classifies melanoma significantly good as compared to existing methods. © 2018 Wiley Periodicals, Inc.

  1. Microenvironments and Signaling Pathways Regulating Early Dissemination, Dormancy, and Metastasis

    DTIC Science & Technology

    2016-09-01

    all these cell types in all tissues and we have used intravital imaging to document intravasation in early cancer lesions (see also partnering PI...report we showed how we optimized a mammary gland imaging window to perform intravital imaging and detect P-TMEM function during early stages of...MECs) assemble primary Tumor Microenvironment of Metastasis structures (P-TMEM) during early dissemination. SA1.1. Objective: Use intravital

  2. [Managing focal incidental renal lesions].

    PubMed

    Nicolau, C; Paño, B; Sebastià, C

    2016-01-01

    Incidental renal lesions are relatively common in daily radiological practice. It is important to know the different diagnostic possibilities for incidentally detected lesions, depending on whether they are cystic or solid. The management of cystic lesions is guided by the Bosniak classification. In solid lesions, the goal is to differentiate between renal cancer and benign tumors such as fat-poor angiomyolipoma and oncocytoma. Radiologists need to know the recommendations for the management of these lesions and the usefulness of the different imaging techniques and interventional procedures in function of the characteristics of the incidental lesion and the patient's life expectancy. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  3. Atheroprotection through SYK inhibition fails in established disease when local macrophage proliferation dominates lesion progression.

    PubMed

    Lindau, Alexandra; Härdtner, Carmen; Hergeth, Sonja P; Blanz, Kelly Daryll; Dufner, Bianca; Hoppe, Natalie; Anto-Michel, Nathaly; Kornemann, Jan; Zou, Jiadai; Gerhardt, Louisa M S; Heidt, Timo; Willecke, Florian; Geis, Serjosha; Stachon, Peter; Wolf, Dennis; Libby, Peter; Swirski, Filip K; Robbins, Clinton S; McPheat, William; Hawley, Shaun; Braddock, Martin; Gilsbach, Ralf; Hein, Lutz; von zur Mühlen, Constantin; Bode, Christoph; Zirlik, Andreas; Hilgendorf, Ingo

    2016-03-01

    Macrophages in the arterial intima sustain chronic inflammation during atherogenesis. Under hypercholesterolemic conditions murine Ly6C(high) monocytes surge in the blood and spleen, infiltrate nascent atherosclerotic plaques, and differentiate into macrophages that proliferate locally as disease progresses. Spleen tyrosine kinase (SYK) may participate in downstream signaling of various receptors that mediate these processes. We tested the effect of the SYK inhibitor fostamatinib on hypercholesterolemia-associated myelopoiesis and plaque formation in Apoe(-/-) mice during early and established atherosclerosis. Mice consuming a high cholesterol diet supplemented with fostamatinib for 8 weeks developed less atherosclerosis. Histologic and flow cytometric analysis of aortic tissue showed that fostamatinib reduced the content of Ly6C(high) monocytes and macrophages. SYK inhibition limited Ly6C(high) monocytosis through interference with GM-CSF/IL-3 stimulated myelopoiesis, attenuated cell adhesion to the intimal surface, and blocked M-CSF stimulated monocyte to macrophage differentiation. In Apoe(-/-) mice with established atherosclerosis, however, fostamatinib treatment did not limit macrophage accumulation or lesion progression despite a significant reduction in blood monocyte counts, as lesional macrophages continued to proliferate. Thus, inhibition of hypercholesterolemia-associated monocytosis, monocyte infiltration, and differentiation by SYK antagonism attenuates early atherogenesis but not established disease when local macrophage proliferation dominates lesion progression.

  4. PR-Set7 is degraded in a conditional Cul4A transgenic mouse model of lung cancer

    DOE PAGES

    Wang, Yang; Xu, Zhidong; Mao, Jian -Hua; ...

    2015-06-01

    Background and objective. Maintenance of genomic integrity is essential to ensure normal organismal development and to prevent diseases such as cancer. PR-Set7 (also known as Set8) is a cell cycle regulated enzyme that catalyses monomethylation of histone 4 at Lys20 (H4K20me1) to promote chromosome condensation and prevent DNA damage. Recent studies show that CRL4CDT2-mediated ubiquitylation of PR-Set7 leads to its degradation during S phase and after DNA damage. This might occur to ensure appropriate changes in chromosome structure during the cell cycle or to preserve genome integrity after DNA damage. Methods. We developed a new model of lung tumor developmentmore » in mice harboring a conditionally expressed allele of Cul4A. We have therefore used a mouse model to demonstrate for the first time that Cul4A is oncogenic in vivo. With this model, staining of PR-Set7 in the preneoplastic and tumor lesions in AdenoCre-induced mouse lungs was performed. Meanwhile we identified higher protein level changes of γ-tubulin and pericentrin by IHC. Results. The level of PR-Set7 down-regulated in the preneoplastic and adenocarcinomous lesions following over-expression of Cul4A. We also identified higher levels of the proteins pericentrin and γ-tubulin in Cul4A mouse lungs induced by AdenoCre. Conclusion. PR-Set7 is a direct target of Cul4A for degradation and involved in the formation of lung tumors in the conditional Cul4A transgenic mouse model.« less

  5. PR-Set7 is degraded in a conditional Cul4A transgenic mouse model of lung cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Yang; Xu, Zhidong; Mao, Jian -Hua

    Background and objective. Maintenance of genomic integrity is essential to ensure normal organismal development and to prevent diseases such as cancer. PR-Set7 (also known as Set8) is a cell cycle regulated enzyme that catalyses monomethylation of histone 4 at Lys20 (H4K20me1) to promote chromosome condensation and prevent DNA damage. Recent studies show that CRL4CDT2-mediated ubiquitylation of PR-Set7 leads to its degradation during S phase and after DNA damage. This might occur to ensure appropriate changes in chromosome structure during the cell cycle or to preserve genome integrity after DNA damage. Methods. We developed a new model of lung tumor developmentmore » in mice harboring a conditionally expressed allele of Cul4A. We have therefore used a mouse model to demonstrate for the first time that Cul4A is oncogenic in vivo. With this model, staining of PR-Set7 in the preneoplastic and tumor lesions in AdenoCre-induced mouse lungs was performed. Meanwhile we identified higher protein level changes of γ-tubulin and pericentrin by IHC. Results. The level of PR-Set7 down-regulated in the preneoplastic and adenocarcinomous lesions following over-expression of Cul4A. We also identified higher levels of the proteins pericentrin and γ-tubulin in Cul4A mouse lungs induced by AdenoCre. Conclusion. PR-Set7 is a direct target of Cul4A for degradation and involved in the formation of lung tumors in the conditional Cul4A transgenic mouse model.« less

  6. Monitoring Autophagy Immunohistochemically and Ultrastructurally during Human Head and Neck Carcinogenesis. Relationship with the DNA Damage Response Pathway †

    PubMed Central

    Havaki, Sophia; Vlachou, Vassiliki; Zampetidis, Christos P.; Selemenakis, Platonas; Kotsinas, Athanassios; Mavrogonatou, Eleni; Rizou, Sophia V.; Kyrodimos, Euthymios; Evangelou, Konstantinos; Kletsas, Dimitris; Giatromanolaki, Alexandra; Gorgoulis, Vassilis G.

    2017-01-01

    Autophagy is a catabolic process that preserves cellular homeostasis. Its exact role during carcinogenesis is not completely defined. Specifically in head and neck cancer, such information from clinical settings that comprise the whole spectrum of human carcinogenesis is very limited. Towards this direction, we examined the in situ status of the autophagy-related factors, Beclin-1, microtubule-associated protein 1 light chain 3, member B (LC3B) and sequestosome 1/p62 (p62) in clinical material covering all histopathological stages of human head and neck carcinogenesis. This material is unique as each panel of lesions is derived from the same patient and moreover we have previously assessed it for the DNA damage response (DDR) activation status. Since Beclin-1, LC3B and p62 reflect the nucleation, elongation and degradation stages of autophagy, respectively, their combined immunohistochemical (IHC) expression profiles could grossly mirror the autophagic flux. This experimental approach was further corroborated by ultrastructural analysis, applying transmission electron microscopy (TEM). The observed Beclin-1/LC3B/p62 IHC patterns, obtained from serial sections analysis, along with TEM findings are suggestive of a declined authophagic activity in preneoplastic lesions that was restored in full blown cancers. Correlating these findings with DDR status in the same pathological stages are indicative of: (i) an antitumor function of autophagy in support to that of DDR, possibly through energy deprivation in preneoplastic stages, thus preventing incipient cancer cells from evolving; and (ii) a tumor-supporting role in the cancerous stage. PMID:28880214

  7. Monitoring Autophagy Immunohistochemically and Ultrastructurally during Human Head and Neck Carcinogenesis. Relationship with the DNA Damage Response Pathway.

    PubMed

    Havaki, Sophia; Vlachou, Vassiliki; Zampetidis, Christos P; Selemenakis, Platonas; Kotsinas, Athanassios; Mavrogonatou, Eleni; Rizou, Sophia V; Kyrodimos, Euthymios; Evangelou, Konstantinos; Kletsas, Dimitris; Giatromanolaki, Alexandra; Gorgoulis, Vassilis G

    2017-09-07

    Autophagy is a catabolic process that preserves cellular homeostasis. Its exact role during carcinogenesis is not completely defined. Specifically in head and neck cancer, such information from clinical settings that comprise the whole spectrum of human carcinogenesis is very limited. Towards this direction, we examined the in situ status of the autophagy-related factors, Beclin-1, microtubule-associated protein 1 light chain 3, member B (LC3B) and sequestosome 1/p62 (p62) in clinical material covering all histopathological stages of human head and neck carcinogenesis. This material is unique as each panel of lesions is derived from the same patient and moreover we have previously assessed it for the DNA damage response (DDR) activation status. Since Beclin-1, LC3B and p62 reflect the nucleation, elongation and degradation stages of autophagy, respectively, their combined immunohistochemical (IHC) expression profiles could grossly mirror the autophagic flux. This experimental approach was further corroborated by ultrastructural analysis, applying transmission electron microscopy (TEM). The observed Beclin-1/LC3B/p62 IHC patterns, obtained from serial sections analysis, along with TEM findings are suggestive of a declined authophagic activity in preneoplastic lesions that was restored in full blown cancers. Correlating these findings with DDR status in the same pathological stages are indicative of: (i) an antitumor function of autophagy in support to that of DDR, possibly through energy deprivation in preneoplastic stages, thus preventing incipient cancer cells from evolving; and (ii) a tumor-supporting role in the cancerous stage.

  8. Reversible splenial lesion syndrome associated with encephalitis/encephalopathy presenting with great clinical heterogeneity.

    PubMed

    Zhu, Yuanzhao; Zheng, Junjun; Zhang, Ling; Zeng, Zhenguo; Zhu, Min; Li, Xiaobin; Lou, Xiaoliang; Wan, Hui; Hong, Daojun

    2016-04-18

    Reversible splenial lesion syndrome (RESLES) is a disorder radiologically characterized by reversible lesion in the splenium of the corpus callosum (SCC). Most of patients with RESLES associated with encephalitis/encephalopathy were identified in Japanese population, but almost no Chinese patients were diagnosed as RESLES associated with encephalitis/encephalopathy. Possible patients with reversible isolated SCC lesions were retrieved from January 2012 to July 2015 using keyword "restricted diffusion and isolated SCC lesion" in MRI report system from a large academic center. The clinical, laboratory and radiological data were summarized. A total of 15 encephalitis/encephalopathy patients (9 males and 6 females) were identified with a reversible isolated SCC lesion. Except for 13 patients with fever symptom, 8 patients also had cold symptoms before the onset of neurological symptoms. The neurological symptoms included headache, vertigo, seizure, disturbance of consciousness, and delirious behavior. Thirteen patients completely recovered within 1 month, but 2 patients who were subjected to mechanical ventilation had persistent neurological deficits. The initial MRI features showed isolated ovoid or extending SCC lesions with homogeneous hyperintense on diffusion weighted imaging (DWI) and decreased apparent diffusion coefficient (ADC) values. The follow-up MRI revealed that isolated SCC lesions with diffuse restriction disappeared at 10 to 32 days after the initial MRI study. Fractional anisotropy map revealed the decreased value of SCC lesion in a severe case with poor prognosis. RESLES associated with encephalitis/encephalopathy is a reversible syndrome with an excellent prognosis in most patients, while a few patients required ventilator supporting at the early stage might have severe neurological sequelae. Reversible signal changes on DWI and ADC are identified in all patients, but fractional anisotropy values can be decreased in severe patient with neurological

  9. Lesion network localization of criminal behavior

    PubMed Central

    Darby, R. Ryan; Horn, Andreas; Fox, Michael D.

    2018-01-01

    Following brain lesions, previously normal patients sometimes exhibit criminal behavior. Although rare, these cases can lend unique insight into the neurobiological substrate of criminality. Here we present a systematic mapping of lesions with known temporal association to criminal behavior, identifying 17 lesion cases. The lesion sites were spatially heterogeneous, including the medial prefrontal cortex, orbitofrontal cortex, and different locations within the bilateral temporal lobes. No single brain region was damaged in all cases. Because lesion-induced symptoms can come from sites connected to the lesion location and not just the lesion location itself, we also identified brain regions functionally connected to each lesion location. This technique, termed lesion network mapping, has recently identified regions involved in symptom generation across a variety of lesion-induced disorders. All lesions were functionally connected to the same network of brain regions. This criminality-associated connectivity pattern was unique compared with lesions causing four other neuropsychiatric syndromes. This network includes regions involved in morality, value-based decision making, and theory of mind, but not regions involved in cognitive control or empathy. Finally, we replicated our results in a separate cohort of 23 cases in which a temporal relationship between brain lesions and criminal behavior was implied but not definitive. Our results suggest that lesions in criminals occur in different brain locations but localize to a unique resting state network, providing insight into the neurobiology of criminal behavior. PMID:29255017

  10. Inter-algorithm lesion volumetry comparison of real and 3D simulated lung lesions in CT

    NASA Astrophysics Data System (ADS)

    Robins, Marthony; Solomon, Justin; Hoye, Jocelyn; Smith, Taylor; Ebner, Lukas; Samei, Ehsan

    2017-03-01

    The purpose of this study was to establish volumetric exchangeability between real and computational lung lesions in CT. We compared the overall relative volume estimation performance of segmentation tools when used to measure real lesions in actual patient CT images and computational lesions virtually inserted into the same patient images (i.e., hybrid datasets). Pathologically confirmed malignancies from 30 thoracic patient cases from Reference Image Database to Evaluate Therapy Response (RIDER) were modeled and used as the basis for the comparison. Lesions included isolated nodules as well as those attached to the pleura or other lung structures. Patient images were acquired using a 16 detector row or 64 detector row CT scanner (Lightspeed 16 or VCT; GE Healthcare). Scans were acquired using standard chest protocols during a single breath-hold. Virtual 3D lesion models based on real lesions were developed in Duke Lesion Tool (Duke University), and inserted using a validated image-domain insertion program. Nodule volumes were estimated using multiple commercial segmentation tools (iNtuition, TeraRecon, Inc., Syngo.via, Siemens Healthcare, and IntelliSpace, Philips Healthcare). Consensus based volume comparison showed consistent trends in volume measurement between real and virtual lesions across all software. The average percent bias (+/- standard error) shows -9.2+/-3.2% for real lesions versus -6.7+/-1.2% for virtual lesions with tool A, 3.9+/-2.5% and 5.0+/-0.9% for tool B, and 5.3+/-2.3% and 1.8+/-0.8% for tool C, respectively. Virtual lesion volumes were statistically similar to those of real lesions (< 4% difference) with p >.05 in most cases. Results suggest that hybrid datasets had similar inter-algorithm variability compared to real datasets.

  11. Imaging of cerebellopontine angle lesions: an update. Part 2: intra-axial lesions, skull base lesions that may invade the CPA region, and non-enhancing extra-axial lesions.

    PubMed

    Bonneville, Fabrice; Savatovsky, Julien; Chiras, Jacques

    2007-11-01

    Computed tomography (CT) and magnetic resonance (MR) imaging reliably demonstrate typical features of vestibular schwannomas or meningiomas in the vast majority of mass lesions responsible for cerebellopontine angle (CPA) syndrome. However, a large variety of unusual lesions can also be encountered in the CPA. Covering the entire spectrum of lesions potentially found in the CPA, these articles explain the pertinent neuroimaging features that radiologists need to know to make clinically relevant diagnoses in these cases, including data from diffusion- and perfusion-weighted imaging or MR spectroscopy, when available. A diagnostic algorithm based on the lesion's site of origin, shape and margins, density, signal intensity and contrast material uptake is also proposed. Non-enhancing extra-axial CPA masses are cystic (epidermoid cyst, arachnoid cyst, neurenteric cyst) or contain fat (dermoid cyst, lipoma). Tumours can also extend into the CPA by extension from the skull base (paraganglioma, chondromatous tumours, chordoma, cholesterol granuloma, endolymphatic sac tumour). Finally, brain stem or ventricular tumours can present with a significant exophytic component in the CPA that may be difficult to differentiate from an extra-axial lesion (lymphoma, hemangioblastoma, choroid plexus papilloma, ependymoma, glioma, medulloblastoma, dysembryoplastic neuroepithelial tumour).

  12. Dual time point fluorodeoxyglucose positron emission tomography/computed tomography in differentiation between malignant and benign lesions in cancer patients. Does it always work?

    PubMed

    Saleh Farghaly, Hussein Rabie; Mohamed Sayed, Mohamed Hosny; Nasr, Hatem Ahmed; Abdelaziz Maklad, Ahmed Marzok

    2015-01-01

    Assess the added value of dual time point F-18-fluorodeoxyglucose positron emission tomography/computed tomography (DTP F-18-FDG-PET/CT) in the differentiation of malignant from a benign lesion in cancer patients. Totally, 140 F-18-FDG PET/CT scans of 60 cancer patients who underwent DTP protocol (early whole body PET/CT [E] at 60 min [range, 45-76 min] and delayed limited PET/CT [D] on areas of interest at 120 min [range, 108-153 min] after the tracer injection) were retrospectively reviewed. Visual and semi-quantitative analysis was performed on both early and delayed images. All findings were confirmed by histopathology and/or at least 3 months follow-up (F-18-FDG PET/CT, CT, or magnetic resonance imaging). The result was considered true positive (TP) if delayed standardized uptake value (SUV) of suspicious lesions increased and confirmed to be malignant, false positive (FP) if delayed SUV increased and confirmed to be benign, true negative (TN) if delayed SUV unchanged or decreased and confirmed to be benign, and false negative (FN) if delayed SUV unchanged or decreased and confirmed to be malignant. A total of 164 suspicious lesions were detected (20 presacral lesions, 18 lung nodules, 18 Hodgkin's disease (HD) lesions, 16 rectal lesions, 16 head and neck (H and N) lesions, 14 hepatic lesions, 14 non-Hodgkin's lymphoma (NHL) lesions, 12 mediastinal lymph nodes (LNs), 10 focal gastric uptake, 10 soft tissue lesions, 8 breast lesions, 4 peritoneal nodule, and 4 others). Sixty-four lesions were pathologically confirmed, and 100 lesions were confirmed based on 3-6 months follow-up. There were 62 TP lesions, 44 FP, 58 TN and no FN results. The overall sensitivity was 100% of DTP F-18-FDG PET/CT in detecting suspicious lesions. The specificity was 57% in differentiating malignant from benign lesions, and the accuracy was 73%. Positive predictive value was 59%, negative predictive value (NPV) 100%. All hepatic lesions were TP. Accuracy in metastatic hepatic lesions

  13. A computer system to be used with laser-based endoscopy for quantitative diagnosis of early gastric cancer.

    PubMed

    Miyaki, Rie; Yoshida, Shigeto; Tanaka, Shinji; Kominami, Yoko; Sanomura, Yoji; Matsuo, Taiji; Oka, Shiro; Raytchev, Bisser; Tamaki, Toru; Koide, Tetsushi; Kaneda, Kazufumi; Yoshihara, Masaharu; Chayama, Kazuaki

    2015-02-01

    To evaluate the usefulness of a newly devised computer system for use with laser-based endoscopy in differentiating between early gastric cancer, reddened lesions, and surrounding tissue. Narrow-band imaging based on laser light illumination has come into recent use. We devised a support vector machine (SVM)-based analysis system to be used with the newly devised endoscopy system to quantitatively identify gastric cancer on images obtained by magnifying endoscopy with blue-laser imaging (BLI). We evaluated the usefulness of the computer system in combination with the new endoscopy system. We evaluated the system as applied to 100 consecutive early gastric cancers in 95 patients examined by BLI magnification at Hiroshima University Hospital. We produced a set of images from the 100 early gastric cancers; 40 flat or slightly depressed, small, reddened lesions; and surrounding tissues, and we attempted to identify gastric cancer, reddened lesions, and surrounding tissue quantitatively. The average SVM output value was 0.846 ± 0.220 for cancerous lesions, 0.381 ± 0.349 for reddened lesions, and 0.219 ± 0.277 for surrounding tissue, with the SVM output value for cancerous lesions being significantly greater than that for reddened lesions or surrounding tissue. The average SVM output value for differentiated-type cancer was 0.840 ± 0.207 and for undifferentiated-type cancer was 0.865 ± 0.259. Although further development is needed, we conclude that our computer-based analysis system used with BLI will identify gastric cancers quantitatively.

  14. Duodenum-preserving total pancreatic head resection for benign cystic neoplastic lesions.

    PubMed

    Beger, Hans G; Schwarz, Michael; Poch, Bertram

    2012-11-01

    Cystic neoplasms of the pancreas are diagnosed frequently due to early use of abdominal imaging techniques. Intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, and serous pseudopapillary neoplasia are considered pre-cancerous lesions because of frequent transformation to cancer. Complete surgical resection of the benign lesion is a pancreatic cancer preventive treatment. The application for a limited surgical resection for the benign lesions is increasingly used to reduce the surgical trauma with a short- and long-term benefit compared to major surgical procedures. Duodenum-preserving total pancreatic head resection introduced for inflammatory tumors in the pancreatic head transfers to the patient with a benign cystic lesion located in the pancreatic head, the advantages of a minimalized surgical treatment. Based on the experience of 17 patients treated for cystic neoplastic lesions with duodenum-preserving total pancreatic head resection, the surgical technique of total pancreatic head resection for adenoma, borderline tumors, and carcinoma in situ of cystic neoplasm is presented. A segmental resection of the peripapillary duodenum is recommended in case of suspected tissue ischemia of the peripapillary duodenum. In 305 patients, collected from the literature by PubMed search, in about 40% of the patients a segmental resection of the duodenum and 60% a duodenum and common bile duct-preserving total pancreatic head resection has been performed. Hospital mortality of the 17 patients was 0%. In 305 patients collected, the hospital mortality was 0.65%, 13.2% experienced a delay of gastric emptying and a pancreatic fistula in 18.2%. Recurrence of the disease was 1.5%. Thirty-two of 175 patients had carcinoma in situ. Duodenum-preserving total pancreatic head resection for benign cystic neoplastic lesions is a safe surgical procedure with low post-operative morbidity and mortality.

  15. Estimation of Fractal Dimension in Differential Diagnosis of Pigmented Skin Lesions

    NASA Astrophysics Data System (ADS)

    Aralica, Gorana; Milošević, Danko; Konjevoda, Paško; Seiwerth, Sven; Štambuk, Nikola

    Medical differential diagnosis is a method of identifying the presence of a particular entity (disease) within a set of multiple possible alternatives. The significant problem in dermatology and pathology is the differential diagnosis of malignant melanoma and other pigmented skin lesions, especially of dysplastic nevi. Malignant melanoma is the most malignant skin neoplasma, with increasing incidence in various parts of the world. It is hoped that the methods of quantitative pathology, i.e. morphometry, can help objectification of the diagnostic process, since early discovery of melanoma results in 10-year survival rate of 90%. The aim of the study was to use fractal dimension calculated from the perimeter-area relation of the cell nuclei as a tool for the differential diagnosis of pigmented skin lesions. We analyzed hemalaun-eosin stained pathohistological slides of pigmented skin lesions: intradermal naevi (n = 45), dysplastic naevi (n = 47), and malignant melanoma (n = 50). It was found that fractal dimension of malignant melanoma cell nuclei differs significantly from the intradermal and dysplastic naevi (p ≤ 0. 001, Steel-Dwass Multiple Comparison Test). Additionaly, ROC analysis confirmed the value of fractal dimension based evaluation. It is suggested that the estimation of fractal dimension from the perimeter-area relation of the cell nuclei may be a potentially useful morphometric parameter in the medical differential diagnosis of pigmented skin lesions.

  16. Optical fiber Raman-based spectroscopy for oral lesions characterization: a pilot study

    NASA Astrophysics Data System (ADS)

    Carvalho, Luis Felipe C. S.; Neto, Lázaro P. M.; Oliveira, Inajara P.; Rangel, João. Lucas; Ferreira, Isabelle; Kitakawa, Dárcio; Martin, Airton A.

    2016-03-01

    In the clinical daily life various lesions of the oral cavity have shown different aspects, generating an inconclusive or doubtful diagnosis. In general, oral injuries are diagnosed by histopathological analysis from biopsy, which is an invasive procedure and does not gives immediate results. In the other hand, Raman spectroscopy technique it is a real time and minimal invasive analytical tool, with notable diagnostic capability. This study aims to characterize, by optical fiber Raman-based spectroscopy (OFRS), normal, inflammatory, potentially malignant, benign and malign oral lesions. Raman data were collected by a Holospec f / 1.8 spectrograph (Kayser Optical Systems) coupled to an optical fiber, with a 785nm laser line source and a CCD Detector. The data were pre-processed and vector normalized. The average analysis and standard deviation was performed associated with cluster analysis and compared to the histopalogical results. Samples of described oral pathological processes were used in the study. The OFRS was efficient to characterized oral lesions and normal mucosa, in which biochemical information related to vibrational modes of proteins, lipids, nucleic acids and carbohydrates were observed. The technique (OFRS) is able to demonstrate biochemical information concern different types of oral lesions showing that Raman spectroscopy could be useful for an early and minimal invasive diagnosis.

  17. The functional organization of trial-related activity in lexical processing after early left hemispheric brain lesions: An event-related fMRI study.

    PubMed

    Fair, Damien A; Choi, Alexander H; Dosenbach, Yannic B L; Coalson, Rebecca S; Miezin, Francis M; Petersen, Steven E; Schlaggar, Bradley L

    2010-08-01

    Children with congenital left hemisphere damage due to perinatal stroke are capable of acquiring relatively normal language functions despite experiencing a cortical insult that in adults often leads to devastating lifetime disabilities. Although this observed phenomenon is accepted, its neurobiological mechanisms are not well characterized. In this paper we examined the functional neuroanatomy of lexical processing in 13 children/adolescents with perinatal left hemispheric damage. In contrast to many previous perinatal infarct fMRI studies, we used an event-related design, which allowed us to isolate trial-related activity and examine correct and error trials separately. Using both group and single subject analysis techniques we attempt to address several methodological factors that may contribute to some discrepancies in the perinatal lesion literature. These methodological factors include making direct statistical comparisons, using common stereotactic space, using both single subject and group analyses, and accounting for performance differences. Our group analysis, investigating correct trial-related activity (separately from error trials), showed very few statistical differences in the non-involved right hemisphere between patients and performance matched controls. The single subject analysis revealed atypical regional activation patterns in several patients; however, the location of these regions identified in individual patients often varied across subjects. These results are consistent with the idea that alternative functional organization of trial-related activity after left hemisphere lesions is in large part unique to the individual. In addition, reported differences between results obtained with event-related designs and blocked designs may suggest diverging organizing principles for sustained and trial-related activity after early childhood brain injuries. 2009 Elsevier Inc. All rights reserved.

  18. Breast cancer risk accumulation starts early: prevention must also.

    PubMed

    Colditz, Graham A; Bohlke, Kari; Berkey, Catherine S

    2014-06-01

    Nearly one in four breast cancers is diagnosed before the age of 50, and many early-stage premalignant lesions are present but not yet diagnosed. Therefore, we review evidence to support the strategy that breast cancer prevention efforts must begin early in life. This study follows the literature review methods and format. Exposures during childhood and adolescence affect a woman's long-term risk of breast cancer, but have received far less research attention than exposures that occur later in life. Breast tissue undergoes rapid cellular proliferation between menarche and first full-term pregnancy, and risk accumulates rapidly until the terminal differentiation that accompanies first pregnancy. Evidence on childhood diet and growth in height, and adolescent alcohol intake, among other adolescent factors is related to breast cancer risk and risk of premalignant proliferative benign lesions. Breast cancer prevention efforts will have the greatest effect when initiated at an early age and continued over a lifetime. Gaps in knowledge are identified and deserve increase attention to inform prevention.

  19. [Treatment of traumatic lesions of the bursa olecrani and chronic bursitis olecrani].

    PubMed

    Saul, D; Dresing, K

    2017-06-01

    Complete olecranon bursectomy with debridement, protection of veins and nerves. Risk-adapted antibiotic therapy and early functional aftercare. Acute, traumatic laceration of the bursa olecrani, chronic therapy-resistant bursitis olecrani. For traumatic bursa injuries: general contraindications for anesthesia and surgery; chronic bursitis: initially not closable skin defect (plastic surgery required), hemodynamically instable patient (e.g. systemic inflammatory response syndrome [SIRS] or sepsis), pre-existing skin infection. Local anesthesia beyond the lesion, careful debridement, identification and removal of the entire bursa, excision of contaminated skin, lavage, drain insertion (Redon, Easy-flow, Penrose). Wound closure, elastic bandage, and splint. Elastic bandage for 2 days, followed by drain removal. Wound assessment, early functional aftercare without splint, antibiotic therapy in septic bursitis for 2 weeks, PRICE scheme. Removal of stitches after 10-12 days. Over 5 years, 138 cases of traumatic bursa lesion or chronic bursitis olecrani were treated in our clinic, 82 patients underwent surgery. Ten patients were treated with vacuum-assisted closure therapy and consecutive wound healing; fistulae occurred in two patients and in another two dehiscence developed. All of the defects could be closed without flaps.

  20. Advances in Bio-Optical Imaging for the Diagnosis of Early Oral Cancer

    PubMed Central

    Olivo, Malini; Bhuvaneswari, Ramaswamy; Keogh, Ivan

    2011-01-01

    Oral cancer is among the most common malignancies worldwide, therefore early detection and treatment is imperative. The 5-year survival rate has remained at a dismal 50% for the past several decades. The main reason for the poor survival rate is the fact that most of the oral cancers, despite the general accessibility of the oral cavity, are not diagnosed until the advanced stage. Early detection of the oral tumors and its precursor lesions may be the most effective means to improve clinical outcome and cure most patients. One of the emerging technologies is the use of non-invasive in vivo tissue imaging to capture the molecular changes at high-resolution to improve the detection capability of early stage disease. This review will discuss the use of optical probes and highlight the role of optical imaging such as autofluorescence, fluorescence diagnosis (FD), laser confocal endomicroscopy (LCE), surface enhanced Raman spectroscopy (SERS), optical coherence tomography (OCT) and confocal reflectance microscopy (CRM) in early oral cancer detection. FD is a promising method to differentiate cancerous lesions from benign, thus helping in the determination of adequate resolution of surgical resection margin. LCE offers in vivo cellular imaging of tissue structures from surface to subsurface layers and has demonstrated the potential to be used as a minimally invasive optical biopsy technique for early diagnosis of oral cancer lesions. SERS was able to differentiate between normal and oral cancer patients based on the spectra acquired from saliva of patients. OCT has been used to visualize the detailed histological features of the oral lesions with an imaging depth down to 2–3 mm. CRM is an optical tool to noninvasively image tissue with near histological resolution. These comprehensive diagnostic modalities can also be used to define surgical margin and to provide a direct assessment of the therapeutic effectiveness. PMID:24310585

  1. Prevention and Treatment of White Spot Lesions During and After Treatment with Fixed Orthodontic Appliances: a Systematic Literature Review

    PubMed Central

    Lopatiene, Kristina; Lapenaite, Egle

    2016-01-01

    ABSTRACT Objectives The aim of the systematic literature review is to update the evidence for the prevention of white spot lesions, using materials containing fluoride and/or casein phosphopeptide-amorphous calcium phosphate during and after treatment with fixed orthodontic appliances. Material and Methods Information search for controlled studies on humans published between January 2008 and February 2016 was performed in PubMed, ScienceDirect, Embase, The Cochrane Library. Inclusion criteria were: the English language, study on humans, patients undergoing orthodontic treatment with fixed appliances, randomized or quasi-randomized controlled clinical studies fluoride-containing product or casein derivates used throughout the appliance therapy or straightaway after debonding. Results 326 articles were reviewed (Embase 141, PubMed 129, ScienceDirect 41, Cochrane 15). Twelve clinical studies fulfilled all inclusion criteria. Use of fluoridated toothpaste had a remineralizing effect on white spot lesions (WSLs) (P < 0.05); fluoride varnish and casein supplements were effective in prevention and early treatment of WSLs (P < 0.05). Conclusions Early detection of white spot lesions during orthodontic treatment would allow implementing preventive measures to control the demineralization process before lesions progress. The systemic review has showed that the usage of fluoride and casein supplements in ameliorating white spot lesions during and after fixed orthodontic treatment is significantly effective. However the use of casein phosphopeptide-amorphous calcium phosphate can be more beneficial than fluoride rinse in the reduction of demineralization spots. PMID:27489605

  2. Gut Microbiota and the Paradox of Cancer Immunotherapy

    PubMed Central

    Poutahidis, Theofilos; Kleinewietfeld, Markus; Erdman, Susan E.

    2014-01-01

    It is recently shown that beneficial environmental microbes stimulate integrated immune and neuroendocrine factors throughout the body, consequently modulating regulatory T-lymphocyte phenotypes, maintaining systemic immune balance, and determining the fate of preneoplastic lesions toward regression while sustaining whole body good health. Stimulated by a gut microbiota-centric systemic homeostasis hypothesis, we set out to explore the influence of the gut microbiome to explain the paradoxical roles of regulatory T-lymphocytes in cancer development and growth. This paradigm shift places cancer prevention and treatment into a new broader context of holobiont engineering to cultivate a tumor-suppressive macroenvironment. PMID:24778636

  3. Gut microbiota and the paradox of cancer immunotherapy.

    PubMed

    Poutahidis, Theofilos; Kleinewietfeld, Markus; Erdman, Susan E

    2014-01-01

    It is recently shown that beneficial environmental microbes stimulate integrated immune and neuroendocrine factors throughout the body, consequently modulating regulatory T-lymphocyte phenotypes, maintaining systemic immune balance, and determining the fate of preneoplastic lesions toward regression while sustaining whole body good health. Stimulated by a gut microbiota-centric systemic homeostasis hypothesis, we set out to explore the influence of the gut microbiome to explain the paradoxical roles of regulatory T-lymphocytes in cancer development and growth. This paradigm shift places cancer prevention and treatment into a new broader context of holobiont engineering to cultivate a tumor-suppressive macroenvironment.

  4. Narrative discourse in children with early focal brain injury.

    PubMed

    Reilly, J S; Bates, E A; Marchman, V A

    1998-02-15

    Children with early brain damage, unlike adult stroke victims, often go on to develop nearly normal language. However, the route and extent of their linguistic development are still unclear, as is the relationship between lesion site and patterns of delay and recovery. Here we address these questions by examining narratives from children with early brain damage. Thirty children (ages 3:7-10:10) with pre- or perinatal unilateral focal brain damage and their matched controls participated in a storytelling task. Analyses focused on linguistic proficiency and narrative competence. Overall, children with brain damage scored significantly lower than their age-matched controls on both linguistic (morphological and syntactic) indices and those targeting broader narrative qualities. Rather than indicating that children with brain damage fully catch up, these data suggest that deficits in linguistic abilities reassert themselves as children face new linguistic challenges. Interestingly, after age 5, site of lesion does not appear to be a significant factor and the delays we have witnessed do not map onto the lesion profiles observed in adults with analogous brain injuries.

  5. Chorioretinal Lesions Presumed Secondary to Zika Virus Infection in an Immunocompromised Adult.

    PubMed

    Henry, Christopher R; Al-Attar, Luma; Cruz-Chacón, Alexis M; Davis, Janet L

    2017-04-01

    Zika virus has spread rapidly throughout the Americas since 2015. The public health implications of Zika virus infection lend special importance to identifying the virus in unsuspected hosts. To describe relevant imaging studies and clinical features of chorioretinal lesions that are presumably associated with Zika virus and that share analogous features with chorioretinal lesions reported in cases of Dengue fever and West Nile virus. This is a case report from an academic referral center in Miami, Florida, of a woman in her 60s from Guaynabo, Puerto Rico, who presented with reduced visual acuity and bilateral diffuse, subretinal, confluent, placoid, and multifocal chorioretinal lesions. The patient was observed over a 5-month period. Visual acuity, clinical course, and multimodal imaging study results. Fluorescein angiography revealed early hypofluorescence and late staining of the chorioretinal lesions. Optical coherence tomography demonstrated outer retinal disruption in the placoid macular lesions. Zika RNA was detected in a plasma sample by real-time reverse transcription polymerase chain reaction testing and was suspected to be the cause of chorioretinal lesions after other viral and infectious causes were ruled out. Three weeks after the onset of symptoms, the patient's visual acuity had improved to 20/60 OD and 20/25 OS, with intraocular pressures of 18 mm Hg OD and 19 mm Hg OS. In 6 weeks, the chorioretinal lesions had healed and visual acuity had improved to 20/25 OD and 20/20 OS. Follow-up optical coherence tomography demonstrated interval recovery of the outer retina and photoreceptors. Acute-onset, self-resolving, placoid, or multifocal nonnecrotizing chorioretinal lesions may be a feature of active Zika virus chorioretinitis, as reported in other Flavivirus infections in adults. Similar findings in potentially exposed adults suggest that clinicians should consider IgM antibody or polymerase chain reaction testing for Zika virus as well as diagnostic

  6. Skull base lesions: extracranial origins.

    PubMed

    Mosier, Kristine M

    2013-10-01

    A number of extracranial anatomical sites, including the nasopharynx, paranasal sinuses, and masticator space, may give rise to lesions involving the skull base. Implicit in the nature of an invasive lesion, the majority of these lesions are malignant. Accordingly, for optimal patient outcomes and treatment planning, it is imperative to include a search pattern for extracranial sites and to assess accurately the character and extent of these diverse lesions. Of particular importance to radiologists are lesions arising from each extracranial site, the search patterns, and relevant information important to convey to the referring clinician. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Osteochondral lesions in distal tarsal joints of Icelandic horses reveal strong associations between hyaline and calcified cartilage abnormalities.

    PubMed

    Ley, C J; Ekman, S; Hansson, K; Björnsdóttir, S; Boyde, A

    2014-03-25

    Osteochondral lesions in the joints of the distal tarsal region of young Icelandic horses provide a natural model for the early stages of osteoarthritis (OA) in low-motion joints. We describe and characterise mineralised and non-mineralised osteochondral lesions in left distal tarsal region joint specimens from twenty-two 30 ±1 month-old Icelandic horses. Combinations of confocal scanning light microscopy, backscattered electron scanning electron microscopy (including, importantly, iodine staining) and three-dimensional microcomputed tomography were used on specimens obtained with guidance from clinical imaging. Lesion-types were described and classified into groups according to morphological features. Their locations in the hyaline articular cartilage (HAC), articular calcified cartilage (ACC), subchondral bone (SCB) and the joint margin tissues were identified and their frequency in the joints recorded. Associations and correlations between lesion-types were investigated for centrodistal joints only. In centrodistal joints the lesion-types HAC chondrocyte loss, HAC fibrillation, HAC central chondrocyte clusters, ACC arrest and ACC advance had significant associations and strong correlations. These lesion-types had moderate to high frequency in centrodistal joints but low frequencies in tarsometatarsal and talocalcaneal-centroquartal joints. Joint margin lesion-types had no significant associations with other lesion-types in the centrodistal joints but high frequency in both the centrodistal and tarsometatarsal joints. The frequency of SCB lesion-types in all joints was low. Hypermineralised infill phase lesion-types were detected. Our results emphasise close associations between HAC and ACC lesions in equine centrodistal joints and the importance of ACC lesions in the development of OA in low-motion compression-loaded equine joints.

  8. Diagnosis and Management of Closed Internal Degloving Injuries: The Morel-Lavallée Lesion.

    PubMed

    Jalota, Leena; Ukaigwe, Anene; Jain, Shashank

    2015-07-01

    Morel-Lavallée (ML) lesions are closed degloving injuries described as posttraumatic subcutaneous fluid collections. They are most commonly seen in the proximal thigh. They can present several days to months after the inciting event. A 55-year-old woman with a recent admission for trauma presented to the Emergency Department with increasing swelling and pain in the right thigh for the previous 3 days. Ultrasound of the thigh was negative. Magnetic resonance imaging performed to further evaluate for leg swelling revealed a "Morel-Lavallée lesion" of the thigh that required drainage. The patient recovered completely after the surgery. WHY SHOULD THE EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should be aware of these rare lesions because they are often mistaken for tumors or hematomas. Early recognition may avoid subsequent complications and help in obtaining prompt specialist care. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Central talar dome lesions: a unique surgical approach with incorporation of a talar allograft for joint reconstitution and restoration of function.

    PubMed

    Dobbs, Bruce M; Cazzell, Shawn M; Dini, Monara

    2011-01-01

    Osteochondral lesions of the talus have been documented, reported, and studied since as early as the 19th century. The evolution of classification systems has allowed surgeons to better manage osseous lesions. Most osteochondral lesions of the talus have been categorized as anterolateral, posteromedial, or central with respect to the talar dome and its articulating surface. The complexity of the aforementioned lesions each present their own set of obstacles and, hence, management. Specifically, surgery on a central talar dome lesion is complicated by poor exposure and limited access, proving to be a challenging operation. Preoperative planning, including exhaustive imaging before any talar dome surgery, is imperative. We present a case study that involves the need for a distal tibial chevron (wedge) talus, with incorporation of a cadaveric allograft to fill the defect.

  10. Role of Lipotropes in Mammary Carcinogenesis

    DTIC Science & Technology

    1996-09-01

    preneoplastic hepatocyte nodules and a 51% incidence of hepatocellular carcinoma (19). To date, the exact mechanism responsible for the effects of lipotrope...rats fed choline deficient diets exhibit an altered liver response to DL-ethionine which leads to an early and enhanced induction of hepatocellular ... carcinoma (37). In addition to the promoting action of lipotropes on chemically induced carcinomas, dietary deficiencies of choline and methionine have

  11. Imaging of cerebellopontine angle lesions: an update. Part 1: enhancing extra-axial lesions.

    PubMed

    Bonneville, Fabrice; Savatovsky, Julien; Chiras, Jacques

    2007-10-01

    Computed tomography (CT) and magnetic resonance (MR) imaging reliably demonstrate typical features of vestibular schwannomas or meningiomas in the vast majority of mass lesions in the cerebellopontine angle (CPA). However, a large variety of unusual lesions can also be encountered in the CPA. Covering the entire spectrum of lesions potentially found in the CPA, these articles explain the pertinent neuroimaging features that radiologists need to know to make clinically relevant diagnoses in these cases, including data from diffusion and perfusion-weighted imaging or MR spectroscopy, when available. A diagnostic algorithm based on the lesion's site of origin, shape and margins, density, signal intensity and contrast material uptake is also proposed. Part 1 describes the different enhancing extra-axial CPA masses primarily arising from the cerebellopontine cistern and its contents, including vestibular and non-vestibular schwannomas, meningioma, metastasis, aneurysm, tuberculosis and other miscellaneous meningeal lesions.

  12. Breast lesion characterization using whole-lesion histogram analysis with stretched-exponential diffusion model.

    PubMed

    Liu, Chunling; Wang, Kun; Li, Xiaodan; Zhang, Jine; Ding, Jie; Spuhler, Karl; Duong, Timothy; Liang, Changhong; Huang, Chuan

    2018-06-01

    Diffusion-weighted imaging (DWI) has been studied in breast imaging and can provide more information about diffusion, perfusion and other physiological interests than standard pulse sequences. The stretched-exponential model has previously been shown to be more reliable than conventional DWI techniques, but different diagnostic sensitivities were found from study to study. This work investigated the characteristics of whole-lesion histogram parameters derived from the stretched-exponential diffusion model for benign and malignant breast lesions, compared them with conventional apparent diffusion coefficient (ADC), and further determined which histogram metrics can be best used to differentiate malignant from benign lesions. This was a prospective study. Seventy females were included in the study. Multi-b value DWI was performed on a 1.5T scanner. Histogram parameters of whole lesions for distributed diffusion coefficient (DDC), heterogeneity index (α), and ADC were calculated by two radiologists and compared among benign lesions, ductal carcinoma in situ (DCIS), and invasive carcinoma confirmed by pathology. Nonparametric tests were performed for comparisons among invasive carcinoma, DCIS, and benign lesions. Comparisons of receiver operating characteristic (ROC) curves were performed to show the ability to discriminate malignant from benign lesions. The majority of histogram parameters (mean/min/max, skewness/kurtosis, 10-90 th percentile values) from DDC, α, and ADC were significantly different among invasive carcinoma, DCIS, and benign lesions. DDC 10% (area under curve [AUC] = 0.931), ADC 10% (AUC = 0.893), and α mean (AUC = 0.787) were found to be the best metrics in differentiating benign from malignant tumors among all histogram parameters derived from ADC and α, respectively. The combination of DDC 10% and α mean , using logistic regression, yielded the highest sensitivity (90.2%) and specificity (95.5%). DDC 10% and α mean derived from

  13. Electromagnetic navigation diagnostic bronchoscopy for small peripheral lung lesions.

    PubMed

    Makris, D; Scherpereel, A; Leroy, S; Bouchindhomme, B; Faivre, J-B; Remy, J; Ramon, P; Marquette, C-H

    2007-06-01

    The present study prospectively evaluated the diagnostic yield and safety of electromagnetic navigation-guided bronchoscopy biopsy, for small peripheral lung lesions in patients where standard techniques were nondiagnostic. The study was conducted in a tertiary medical centre on 40 consecutive patients considered unsuitable for straightforward surgery or computed tomography (CT)-guided transthoracic needle aspiration biopsy, due to comorbidities. The lung lesion diameter was mean+/-sem 23.5+/-1.5 mm and the depth from the visceral-costal pleura was 14.9+/-2 mm. Navigation was facilitated by an electromagnetic tracking system which could detect a position sensor incorporated into a flexible catheter advanced through a bronchoscope. Information obtained during bronchoscopy was superimposed on previously acquired CT data. Divergence between CT data and data obtained during bronchoscopy was calculated by the system's software as a measure of navigational accuracy. All but one of the target lesions was reached and the overall diagnostic yield was 62.5% (25-40). Diagnostic yield was significantly affected by CT-to-body divergence; yield was 77.2% when estimated divergence was early diagnosis of lung cancer, particularly in nonoperable patients.

  14. Multimodal Integration After Unilateral Labyrinthine Lesion: Single Vestibular Nuclei Neuron Responses and Implications for Postural Compensation

    PubMed Central

    Sadeghi, Soroush G.; Minor, Lloyd B.

    2011-01-01

    Plasticity in neuronal responses is necessary for compensation following brain lesions and adaptation to new conditions and motor learning. In a previous study, we showed that compensatory changes in the vestibuloocular reflex (VOR) following unilateral vestibular loss were characterized by dynamic reweighting of inputs from vestibular and extravestibular modalities at the level of single neurons that constitute the first central stage of VOR signal processing. Here, we studied another class of neurons, i.e., the vestibular-only neurons, in the vestibular nuclei that mediate vestibulospinal reflexes and provide information for higher brain areas. We investigated changes in the relative contribution of vestibular, neck proprioceptive, and efference copy signals in the response of these neurons during compensation after contralateral vestibular loss in Macaca mulata monkeys. We show that the time course of recovery of vestibular sensitivity of neurons corresponds with that of lower extremity muscle and tendon reflexes reported in previous studies. More important, we found that information from neck proprioceptors, which did not influence neuronal responses before the lesion, were unmasked after lesion. Such inputs influenced the early stages of the compensation process evidenced by faster and more substantial recovery of the resting discharge in proprioceptive-sensitive neurons. Interestingly, unlike our previous study of VOR interneurons, the improvement in the sensitivity of the two groups of neurons did not show any difference in the early or late stages after lesion. Finally, neuronal responses during active head movements were not different before and after lesion and were attenuated relative to passive movements over the course of recovery, similar to that observed in control conditions. Comparison of compensatory changes observed in the vestibuloocular and vestibulospinal pathways provides evidence for similarities and differences between the two classes of

  15. Multimodal integration after unilateral labyrinthine lesion: single vestibular nuclei neuron responses and implications for postural compensation.

    PubMed

    Sadeghi, Soroush G; Minor, Lloyd B; Cullen, Kathleen E

    2011-02-01

    Plasticity in neuronal responses is necessary for compensation following brain lesions and adaptation to new conditions and motor learning. In a previous study, we showed that compensatory changes in the vestibuloocular reflex (VOR) following unilateral vestibular loss were characterized by dynamic reweighting of inputs from vestibular and extravestibular modalities at the level of single neurons that constitute the first central stage of VOR signal processing. Here, we studied another class of neurons, i.e., the vestibular-only neurons, in the vestibular nuclei that mediate vestibulospinal reflexes and provide information for higher brain areas. We investigated changes in the relative contribution of vestibular, neck proprioceptive, and efference copy signals in the response of these neurons during compensation after contralateral vestibular loss in Macaca mulata monkeys. We show that the time course of recovery of vestibular sensitivity of neurons corresponds with that of lower extremity muscle and tendon reflexes reported in previous studies. More important, we found that information from neck proprioceptors, which did not influence neuronal responses before the lesion, were unmasked after lesion. Such inputs influenced the early stages of the compensation process evidenced by faster and more substantial recovery of the resting discharge in proprioceptive-sensitive neurons. Interestingly, unlike our previous study of VOR interneurons, the improvement in the sensitivity of the two groups of neurons did not show any difference in the early or late stages after lesion. Finally, neuronal responses during active head movements were not different before and after lesion and were attenuated relative to passive movements over the course of recovery, similar to that observed in control conditions. Comparison of compensatory changes observed in the vestibuloocular and vestibulospinal pathways provides evidence for similarities and differences between the two classes of

  16. Congenital lesions of epithelial origin.

    PubMed

    Hills, Susannah E; Maddalozzo, John

    2015-02-01

    Defects of embryologic development give rise to a variety of congenital lesions arising from the epithelium and are among the most common congenital lesions of the head and neck in the pediatric population. This article presents several congenital lesions of epithelial origin, including congenital midline cervical cleft, pilomatrixoma, dermoid, foregut duplication cysts, and preauricular sinuses and pits. In addition, the management of these lesions is reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Simultaneous improvement and worsening of vitiligo lesions during the course of NB-UVB phototherapy; vitiligo may not act as one unit.

    PubMed

    Anbar, Tag; Abdel-Rahman, Amal; Hegazy, Rehab; El-Khayyat, Mohamed; Ragaie, Maha

    2017-01-01

    Re-pigmentation and stabilization are the two ultimate goals of any re-pigmenting plan designed for vitiligo management. Furthermore, whether the improvement of some vitiligo lesions could be considered a guarantee for a similar response and/or stabilization of the rest of the lesions or not, remains to be clarified. To evaluate the behavior of non-segmental vitiligo (NSV), while on narrow band-ultraviolet B (NB-UVB) phototherapy. 25 patients with stable generalized NSV were included and received NB-UVB twice weekly. For the sake of ensuring accuracy of follow up, up to four lesions were randomly chosen in each patient and regularly measured using the point counting technique. The over-all point counting technique of all included patients showed a significant reduction (18.5 ± 8.4 cm 2 to 8.2± 3.1 cm 2 ) after 6 months of therapy (p < .001). Nine patients (36%), showed mixed response in the different lesions. Improvement was documented in some lesions, while other lesions showed no response or even worsening. No significant correlations were detected between the behavior of vitiligo during NB-UVB and any of the demographic or clinical data of the patients. NB-UVB is a pillar in the management of vitiligo, however close follow-up of the patient as a whole and his lesions, by both subjective and objective measures are mandatory to detect activity as early as possible, as vitiligo at many times may not act as one unit. This early detection of activity and the subsequent change in the treatment policy may ultimately change the final outcome of treatment. © 2016 Wiley Periodicals, Inc.

  18. Concordance between fine-needle aspiration and core biopsies for osseous lesions by lesion imaging appearance and CT attenuation.

    PubMed

    Li, John; Weissberg, Zoe; Bevilacqua, Thomas A; Yu, Gordon; Weber, Kristy; Sebro, Ronnie

    2018-04-01

    To compare the concordance between fine-needle aspiration and core biopsies for osseous lesions by lesion imaging appearance and CT attenuation. Retrospective review of 215 FNAs of osseous lesions performed in conjunction with core biopsy at our institution over a 6-year period (2011-2016). FNAs were interpreted independently of core biopsies. We assessed if FNA in conjunction with core biopsy increased diagnostic accuracy compared to core biopsy alone. We also calculated the concordance between FNA and core biopsy by lesion appearance, lesion CT attenuation, lesion histology, lesion location and FNA needle gauge size. Core biopsy alone provided the diagnosis in 207/215 cases (96.3%), however, the FNA provided the diagnosis in the remaining 8/215 cases (3.7%) where the core biopsy was non-diagnostic. There were 154 (71.6%) lytic lesions, 21 (9.8%) blastic lesions, 25 (11.6%) mixed lytic and blastic lesions and 15 (7.0%) lesions that were neither lytic nor blastic. The concordance between FNA and core biopsy for lytic osseous lesions (136/154 cases, 88.3%) was statistically significantly higher than that for blastic osseous lesions (13/21 cases, 61.9%) [P = 4.2 × 10 -3 ; 95% CI (0.02, 0.50)]. The concordance between FNA and core biopsy was higher for low-attenuation- (110/126) than high-attenuation (58/77) lesions (P = 0.028). The concordance between FNA and core biopsy was also higher for metastases (102/119 cases, 85.7%) than non-metastases (78/96, 81.3%) [P = 0.487; 95% CI (- 0.15, 0.065)]. There was no difference in the rate of concordance between FNA and core biopsy by lesion location or FNA needle gauge size (P > 0.05). FNA with core biopsy increases diagnostic rate compared to core biopsy alone or FNA alone. The concordance between FNA and core biopsy is higher for lytic lesions than for blastic lesions; and higher for low-attenuation lesions than for high-attenuation lesions.

  19. Epidermal hydrogen peroxide is not increased in lesional and non-lesional skin of vitiligo.

    PubMed

    Zailaie, Mohammad Z

    2017-01-01

    It is widely believed that the loss of the epidermal melanocytes in vitiligo is basically due to excessive oxidative stress. Previous research work described abnormal elevation of the absolute concentration of the epidermal hydrogen peroxide (H 2 O 2 ) in lesional and non-lesional skin of vitiligo. Based on this finding, our primary research objective was to use this feature as a screening marker in individuals at a great risk of developing vitiligo. Ninety-six patients of non-segmental vitiligo (NSV) of varying durations, skin phototypes, and treatment modalities (psoralen UVA-, narrow band UVB-treated) were recruited for this study. Raman spectroscopic measurements, using an external probehead, of the lesional and non-lesional skin were obtained, and the resulting spectra were analyzed using the Opus software package of the MultiRam spectrometer and the intensity of the peak at 875 cm -1 that represents the absolute concentration of H 2 O 2 was calculated. Contrary to previous reports, in patients of skin phototype IV, the absolute concentrations of H 2 O 2 in non-lesional and lesional NSV of all groups were non-significantly decreased compared to normal control. In patients of NSV of skin phototype V, the decrease in the absolute concentrations of H 2 O 2 was not significant in the untreated group, and a slight non-significant increase in the NBUVB-treated group was noted. However, in the PUVA-treated group, the non-lesional skin demonstrated significant increase in the absolute concentration of H 2 O 2 , whereas the lesional skin showed only a slight non-significant increase compared to normal control. In NSV patients of skin phototype VI who were previously treated with PUVA, the non-lesional skin showed a slight non-significant increase in the absolute concentration of H 2 O 2 ; however, the lesional skin showed a marked significant decrease compared to normal control and the non-lesional skin. Thereof, one can conclude that the epidermal H 2 O 2 is not

  20. Gastric subepithelial lesion complicated with abscess: Case report and literature review

    PubMed Central

    Kim, Sung Bum; Oh, Myung Jin; Lee, Si Hyung

    2015-01-01

    Gastric abscess is a localized pyogenic inflammation of the gastric wall, which is a rare form of suppurative gastritis. The rarity of gastric abscess may be associated with the difficulty of early diagnosis and high mortality as a result. In general, subepithelial lesions (SELs) of the stomach are incidentally detected during the course of upper endoscopy without specific clinical symptoms and signs. However, some gastric SELs present rarely as a form of hemorrhage, obstruction, perforation, and abscess. Here we report a 45-year-old man with gastric SEL presenting as a gastric abscess, which was diagnosed as an ectopic pancreas of the stomach, along with a review of the literature. Although gastric SEL presenting as an abscess is known as a serious and life-threatening lesion, the patient made a complete recovery through surgical resection as well as medical treatment. PMID:26034377

  1. Imaging and detection of early stage dental caries with an all-optical photoacoustic microscope

    NASA Astrophysics Data System (ADS)

    Hughes, D. A.; Sampathkumar, A.; Longbottom, C.; Kirk, K. J.

    2015-01-01

    Tooth decay, at its earliest stages, manifests itself as small, white, subsurface lesions in the enamel. Current methods for detection in the dental clinic are visual and tactile investigations, and bite-wing X-ray radiographs. These techniques suffer from poor sensitivity and specificity at the earliest (and reversible) stages of the disease due to the small size (<100μm) of the lesion. A fine-resolution (600 nm) ultra-broadband (200 MHz) all-optical photoacoustic microscopy system was is used to image the early signs of tooth decay. Ex-vivo tooth samples exhibiting white spot lesions were scanned and were found to generate a larger (one order of magnitude) photoacoustic (PA) signal in the lesion regions compared to healthy enamel. The high contrast in the PA images potentially allows lesions to be imaged and measured at a much earlier stage than current clinical techniques allow. PA images were cross referenced with histology photographs to validate our experimental results. Our PA system provides a noncontact method for early detection of white-spot lesions with a high detection bandwidth that offers advantages over previously demonstrated ultrasound methods. The technique provides the sensing depth of an ultrasound system, but with the spatial resolution of an optical system.

  2. Covalently Linked Tandem Lesions in DNA

    PubMed Central

    Patrzyc, Helen B.; Dawidzik, Jean B.; Budzinski, Edwin E.; Freund, Harold G.; Wilton, John H.; Box, Harold C.

    2013-01-01

    Reactive oxygen species (ROS) generate a type of DNA damage called tandem lesions, two adjacent nucleotides both modified. A subcategory of tandem lesions consists of adjacent nucleotides linked by a covalent bond. Covalently linked tandem lesions generate highly characteristic liquid chromotography-tandem mass spectrometry (LC-MS/MS) elution profiles. We have used this property to comprehensively survey X-irradiated DNA for covalently linked tandem lesions. A total of 15 tandem lesions were detected in DNA irradiated in deoxygenated aqueous solution, five tandem lesions were detected in DNA that was irradiated in oxygenated solution. PMID:23106212

  3. Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of white matter lesions on MRI: the evaluation of vascular care in Alzheimer's disease (EVA) study.

    PubMed

    Richard, Edo; Gouw, Alida A; Scheltens, Philip; van Gool, Willem A

    2010-03-01

    White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs and prevents occurrence of new infarcts. A randomized controlled clinical trial, including 123 subjects, compared vascular care with standard care in patients with Alzheimer disease with cerebrovascular lesions on MRI. Progression of WMLs, lacunes, medial temporal lobe atrophy, and global cortical atrophy were semiquantitatively scored after 2-year follow-up. Sixty-five subjects (36 vascular care, 29 standard care) had a baseline and a follow-up MRI and in 58 subjects, a follow-up scan could not be obtained due to advanced dementia or death. Subjects in the vascular care group had less progression of WMLs as measured with the WML change score (1.4 versus 2.3, P=0.03). There was no difference in the number of new lacunes or change in global cortical atrophy or medial temporal lobe atrophy between the 2 groups. Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs. Treatment aimed at vascular risk factors in patients with early Alzheimer disease may be beneficial, possibly in an even earlier stage of the disease.

  4. Discrimination of premalignant lesions and cancer tissues from normal gastric tissues using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Luo, Shuwen; Chen, Changshui; Mao, Hua; Jin, Shaoqin

    2013-06-01

    The feasibility of early detection of gastric cancer using near-infrared (NIR) Raman spectroscopy (RS) by distinguishing premalignant lesions (adenomatous polyp, n=27) and cancer tissues (adenocarcinoma, n=33) from normal gastric tissues (n=45) is evaluated. Significant differences in Raman spectra are observed among the normal, adenomatous polyp, and adenocarcinoma gastric tissues at 936, 1003, 1032, 1174, 1208, 1323, 1335, 1450, and 1655 cm-1. Diverse statistical methods are employed to develop effective diagnostic algorithms for classifying the Raman spectra of different types of ex vivo gastric tissues, including principal component analysis (PCA), linear discriminant analysis (LDA), and naive Bayesian classifier (NBC) techniques. Compared with PCA-LDA algorithms, PCA-NBC techniques together with leave-one-out, cross-validation method provide better discriminative results of normal, adenomatous polyp, and adenocarcinoma gastric tissues, resulting in superior sensitivities of 96.3%, 96.9%, and 96.9%, and specificities of 93%, 100%, and 95.2%, respectively. Therefore, NIR RS associated with multivariate statistical algorithms has the potential for early diagnosis of gastric premalignant lesions and cancer tissues in molecular level.

  5. Effect of Lesion Baseline Severity and Mineral Distribution on Remineralization and Progression of Human and Bovine Dentin Caries Lesions.

    PubMed

    Lippert, Frank; Churchley, David; Lynch, Richard J

    2015-01-01

    The aims of this laboratory study were to compare the effects of lesion baseline severity, mineral distribution and substrate on remineralization and progression of caries lesions created in root dentin. Lesions were formed in dentin specimens prepared from human and bovine dentin using three protocols, each utilizing three demineralization periods to create lesions of different mineral distributions (subsurface, moderate softening, extreme softening) and severity within each lesion type. Lesions were then either remineralized or demineralized further and analyzed using transverse microradiography. At lesion baseline, no differences were found between human and bovine dentin for integrated mineral loss (x0394;Z). Differences in mineral distribution between lesion types were apparent. Human dentin lesions were more prone to secondary demineralization (x0394;x0394;Z) than bovine dentin lesions, although there were no differences in x0394;L. Likewise, smaller lesions were more susceptible to secondary demineralization than larger ones. Subsurface lesions were more acid-resistant than moderately and extremely softened lesions. After remineralization, differences between human and bovine dentin lesions were not apparent for x0394;x0394;Z although bovine dentin lesions showed greater reduction in lesion depth L. For lesion types, responsiveness to remineralization (x0394;x0394;Z) was in the order extremely softened>moderately softened>subsurface. More demineralized lesions exhibited greater remineralization than shallower ones. In summary, some differences exist between human and bovine dentin and their relative responsiveness to de- and remineralization. These differences, however, were overshadowed by the effects of lesion baseline mineral distribution and severity. Thus, bovine dentin appears to be a suitable substitute for human dentin in mechanistic root caries studies. © 2015 S. Karger AG, Basel.

  6. HPV16 early gene E5 specifically reduces miRNA-196a in cervical cancer cells

    PubMed Central

    Liu, Chanzhen; Lin, Jianfei; Li, Lianqin; Zhang, Yonggang; Chen, Weiling; Cao, Zeyi; Zuo, Huancong; Chen, Chunling; Kee, Kehkooi

    2015-01-01

    High-risk human papillomavirus (HPV) type 16, which is responsible for greater than 50% of cervical cancer cases, is the most prevalent and lethal HPV type. However, the molecular mechanisms of cervical carcinogenesis remain elusive, particularly the early steps of HPV infection that may transform normal cervical epithelium into a pre-neoplastic state. Here, we report that a group of microRNAs (microRNAs) were aberrantly decreased in HPV16-positive normal cervical tissues, and these groups of microRNAs are further reduced in cervical carcinoma. Among these miRNAs, miR196a expression is the most reduced in HPV16-infected tissues. Interestingly, miR196a expression is low in HPV16-positive cervical cancer cell lines but high in HPV16-negative cervical cancer cell lines. Furthermore, we found that only HPV16 early gene E5 specifically down-regulated miRNA196a in the cervical cancer cell lines. In addition, HoxB8, a known miR196a target gene, is up-regulated in the HPV16 cervical carcinoma cell line but not in HPV18 cervical cancer cell lines. Various doses of miR196a affected cervical cancer cell proliferation and apoptosis. Altogether, these results suggested that HPV16 E5 specifically down-regulates miR196a upon infection of the human cervix and initiates the transformation of normal cervix cells to cervical carcinoma. PMID:25563170

  7. A case report of prostate cancer metastasis to the stomach resembling undifferentiated-type early gastric cancer.

    PubMed

    Inagaki, Chiaki; Suzuki, Takuto; Kitagawa, Yoshiyasu; Hara, Taro; Yamaguchi, Taketo

    2017-08-07

    Occurrence of metastatic cancer to the stomach is rare, particularly in patients with prostate cancer. Gastric metastasis generally presents as a solitary and submucosal lesion with a central depression. We describe a case of gastric metastasis arising from prostate cancer, which is almost indistinguishable from the undifferentiated-type gastric cancer. A definitive diagnosis was not made until endoscopic resection. On performing both conventional and magnifying endoscopies, the lesion appeared to be slightly depressed and discolored area and it could not be distinguished from undifferentiated early gastric cancer. Biopsy from the lesion was negative for immunohistochemical staining of prostate-specific antigen, a sensitive and specific marker for prostate cancer. Thus, false initial diagnosis of an early primary gastric cancer was made and endoscopic submucosal dissection was performed. Pathological findings from the resected specimen aroused suspicion of a metastatic lesion. Consequently, immunostaining was performed. The lesion was positive for prostate-specific acid phosphatase and negative for prostate-specific antigen, cytokeratin 7, and cytokeratin 20. Accordingly, the final diagnosis was a metastatic gastric lesion originating from prostate cancer. In this patient, the definitive diagnosis as a metastatic lesion was difficult due to its unusual endoscopic appearance and the negative stain for prostate-specific antigen. We postulate that both of these are consequences of hormonal therapy against prostate cancer.

  8. Effect of bleaching on sound enamel and with early artificial caries lesions using confocal laser microscopy.

    PubMed

    Berger, Sandrine Bittencourt; Pavan, Sabrina; Dos Santos, Paulo Henrique; Giannini, Marcelo; Bedran-Russo, Ana Karina B

    2012-01-01

    The aim of this study was to evaluate effect of bleaching agents on sound enamel (SE) and enamel with early artificial caries lesions (CL) using confocal laser scanning microscopy (CLSM). Eighty blocks (4 x 5 x 5 mm) of bovine enamel were used and half of them were submitted to a pH cycling model to induce CL. Eight experimental groups were obtained from the treatments and mineralization level of the enamel (SE or CL) (n=10). SE groups: G1 - unbleached (control); G2 - 4% hydrogen peroxide (4 HP); G3 - 4 HP containing 0.05% Ca (Ca); G4 - 7.5% hydrogen peroxide (7.5 HP) containing amorphous calcium phosphate (ACP). CL groups: G5 - unbleached; G6 - 4 HP; G7 - 4 HP containing Ca; G8 - 7.5 HP ACP. G2, G3, G6, G7 were treated with the bleaching agents for 8 h/day during 14 days, while G4 and G8 were exposed to the bleaching agents for 30 min twice a day during 14 days. The enamel blocks were stained with 0.1 mM rhodamine B solution and the demineralization was quantified using fluorescence intensity detected by CLSM. Data were analyzed using ANOVA and Fisher's tests (α=0.05). For the SE groups, the bleaching treatments increased significantly the demineralization area when compared with the unbleached group. In the CL groups, no statistically significant difference was observed (p>0.05).The addition of ACP or Ca in the composition of the whitening products did not overcome the effects caused by bleaching treatments on SE and neither was able to promote remineralization of CL.

  9. Endoscopic submucosal dissection for early Barrett's neoplasia.

    PubMed

    Barret, Maximilien; Cao, Dalhia Thao; Beuvon, Frédéric; Leblanc, Sarah; Terris, Benoit; Camus, Marine; Coriat, Romain; Chaussade, Stanislas; Prat, Frédéric

    2016-04-01

    The possible benefit of endoscopic submucosal dissection (ESD) for early neoplasia arising in Barrett's esophagus remains controversial. We aimed to assess the efficacy and safety of ESD for the treatment of early Barrett's neoplasia. All consecutive patients undergoing ESD for the resection of a visible lesion in a Barrett's esophagus, either suspicious of submucosal infiltration or exceeding 10 mm in size, between February 2012 and January 2015 were prospectively included. The primary endpoint was the rate of curative resection of carcinoma, defined as histologically complete resection of adenocarcinomas without poor histoprognostic factors. Thirty-five patients (36 lesions) with a mean age of 66.2 ± 12 years, a mean ASA score of 2.1 ± 0.7, and a mean C4M6 Barrett's segment were included. The mean procedure time was 191 ± 79 mn, and the mean size of the resected specimen was 51.3 ± 23 mm. En bloc resection rate was 89%. Lesions were 12 ± 15 mm in size, and 81% (29/36) were invasive adenocarcinomas, six of which with submucosal invasion. Although R0 resection of carcinoma was 72.4%, the curative resection rate was 66% (19/29). After a mean follow-up of 12.9 ± 9 months, 16 (45.7%) patients had required additional treatment, among whom nine underwent surgical resection, and seven further endoscopic treatments. Metachronous lesions or recurrence of cancer developed during the follow-up period in 17.2% of the patients. The overall complication rate was 16.7%, including 8.3% perforations, all conservatively managed, and no bleeding. The 30-day mortality was 0%. In this early experience, ESD yielded a moderate curative resection rate in Barrett's neoplasia. At present, improvements are needed if ESD is to replace piecemeal endoscopic mucosal resection in the management of Barrett's neoplasia.

  10. Early osteoarthritis of the knee.

    PubMed

    Madry, Henning; Kon, Elizaveta; Condello, Vincenzo; Peretti, Giuseppe M; Steinwachs, Matthias; Seil, Romain; Berruto, Massimo; Engebretsen, Lars; Filardo, Giuseppe; Angele, Peter

    2016-06-01

    There is an increasing awareness on the importance in identifying early phases of the degenerative processes in knee osteoarthritis (OA), the crucial period of the disease when there might still be the possibility to initiate treatments preventing its progression. Early OA may show a diffuse and ill-defined involvement, but also originate in the cartilage surrounding a focal lesion, thus necessitating a separate assessment of these two entities. Early OA can be considered to include a maximal involvement of 50 % of the cartilage thickness based on the macroscopic ICRS classification, reflecting an OARSI grade 4. The purpose of this paper was to provide an updated review of the current status of the diagnosis and definition of early knee OA, including the clinical, radiographical, histological, MRI, and arthroscopic definitions and biomarkers. Based on current evidence, practical classification criteria are presented. As new insights and technologies become available, they will further evolve to better define and treat early knee OA.

  11. Is the morphology and activity of the occlusal carious lesion related to the lesion progression stage?

    PubMed

    Neves, Aline Almeida; Vargas, Daniel Otero Amaral; Santos, Thais Maria Pires; Lopes, Ricardo Tadeu; Sousa, Frederico Barbosa

    2016-12-01

    To investigate the relationship between degree of dentin demineralization with both lesion activity and morphology of the occlusal carious cavity. Occlusal sites (n=138) were identified by visual examination (Nyvad's scores 0-6) in 67 extracted teeth which were scanned in a high energy micro-CT. After 3D reconstruction, each stack was resliced in the mesio-distal direction and tooth mineral density (MD) was measured along a path from enamel to the deepest part of dentin in the slice showing the most severe carious involvement. Each site was classified in "open" or "closed" (if cavitated) depending on the morphology of the surrounding enamel walls as measured using micro-CT and as active or inactive in enamel or dentin by a clinical scoring system. Lesions showing dentin cavitation presented higher demineralization degree compared to non-cavitated, or enamel cavitated lesions. Inactive lesions presented lower demineralization degree compared to active lesions, although with a low effect size. According to the morphological aspect of the carious cavity, open enamel lesions showed lower dentin demineralization degree than closed lesion environments. Active lesions showed higher dentin demineralization degree than inactive ones, while lesions showing closed cavitation resulted in higher dentin demineralization degree only for enamel lesions. Including those parameters in treatment decisions may help to improve prognosis and increase effectiveness of the caries diagnostic systems in the clinical setting. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Early-Life Stress Is Associated with Gender-Based Vulnerability to Epileptogenesis in Rat Pups

    PubMed Central

    Desgent, Sébastien; Duss, Sandra; Sanon, Nathalie T.; Lema, Pablo; Lévesque, Maxime; Hébert, David; Rébillard, Rose-Marie; Bibeau, Karine; Brochu, Michèle; Carmant, Lionel

    2012-01-01

    During development, the risk of developing mesial temporal lobe epilepsy (MTLE) increases when the developing brain is exposed to more than one insult in early life. Early life insults include abnormalities of cortical development, hypoxic-ischemic injury and prolonged febrile seizures. To study epileptogenesis, we have developed a two-hit model of MTLE characterized by two early-life insults: a freeze lesion-induced cortical malformation at post-natal day 1 (P1), and a prolonged hyperthermic seizure (HS) at P10. As early life stressors lead to sexual dimorphism in both acute response and long-term outcome, we hypothesized that our model could lead to gender-based differences in acute stress response and long-term risk of developing MTLE. Male and female pups underwent a freeze-lesion induced cortical microgyrus at P1 and were exposed to HS at P10. Animals were monitored by video-EEG from P90 to P120. Pre and post-procedure plasma corticosterone levels were used to measure stress response at P1 and P10. To confirm the role of sex steroids, androgenized female pups received daily testosterone injections to the mother pre-natally and post-natally for nine days while undergoing both insults. We demonstrated that after both insults females did not develop MTLE while all males did. This correlated with a rise in corticosterone levels at P1 following the lesion in males only. Interestingly, all androgenized females showed a similar rise in corticosterone at P1, and also developed MTLE. Moreover, we found that the cortical lesion significantly decreased the latency to generalized convulsion during hyperthermia at P10 in both genders. The cortical dysplasia volumes at adulthood were also similar between male and female individuals. Our data demonstrate sexual dimorphism in long-term vulnerability to develop epilepsy in the lesion + hyperthermia animal model of MTLE and suggest that the response to early-life stress at P1 contributes significantly to epileptogenesis in a

  13. Early Dynamic 68Ga-DOTA-D-Phe1-Tyr3-Octreotide PET/CT in Patients With Hepatic Metastases of Neuroendocrine Tumors.

    PubMed

    Sänger, Philipp Wilhelm; Freesmeyer, Martin

    2016-06-01

    Whole-body PET with Ga-DOTA-D-Phe-Tyr-octreotide (Ga-DOTATOC) and contrast-enhanced CT (ceCT) are considered a standard for the staging of neuroendocrine tumors (NETs). This study sought to verify whether early dynamic (ed) Ga-DOTATOC PET/CT can reliably detect liver metastases of NETs (hypervascular, nonhypervascular; positive or negative for somatostatin receptors) and to verify if the receptor positivity has a significant impact on the detection of tumor hypervascularization. Twenty-seven patients with NET were studied by ceCT and standard whole-body PET according to established Ga-DOTATOC protocols. In addition, edPET data were obtained by continuous scanning during the first 300 seconds after bolus injections of the radiotracer. Early dynamic PET required an additional low-dose, native CT image of the liver for the purpose of attenuation correction. Time-activity and time-contrast curves were obtained, the latter being calculated by the difference between tumor and reference regions. Early dynamic PET/CT proved comparable with ceCT in readily identifying hypervascular lesions, irrespective of the receptor status, with activities rising within 16 to 40 seconds. Early dynamic PET/CT also readily identified nonhypervascular, receptor-positive lesions. Positive image contrasts were obtained for hypervascular, receptor-positive lesions, whereas early negative contrasts were obtained for nonhypervascular, receptor-negative lesions. The high image contrast of hypervascular NET metastases in early arterial phases suggests that edPET/CT can become a useful alternative in patients with contraindications to ceCT. The high density of somatostatin receptors did not seem to interfere with the detection of the lesion's hypervascularization.

  14. Lesion detection in ultra-wide field retinal images for diabetic retinopathy diagnosis

    NASA Astrophysics Data System (ADS)

    Levenkova, Anastasia; Sowmya, Arcot; Kalloniatis, Michael; Ly, Angelica; Ho, Arthur

    2018-02-01

    Diabetic retinopathy (DR) leads to irreversible vision loss. Diagnosis and staging of DR is usually based on the presence, number, location and type of retinal lesions. Ultra-wide field (UWF) digital scanning laser technology provides an opportunity for computer-aided DR lesion detection. High-resolution UWF images (3078×2702 pixels) may allow detection of more clinically relevant retinopathy in comparison with conventional retinal images as UWF imaging covers a 200° retinal area, versus 45° by conventional cameras. Current approaches to DR diagnosis that analyze 7-field Early Treatment Diabetic Retinopathy Study (ETDRS) retinal images provide similar results to UWF imaging. However, in 40% of cases, more retinopathy was found outside the 7- field ETDRS fields by UWF and in 10% of cases, retinopathy was reclassified as more severe. The reason is that UWF images examine both the central retina and more peripheral regions. We propose an algorithm for automatic detection and classification of DR lesions such as cotton wool spots, exudates, microaneurysms and haemorrhages in UWF images. The algorithm uses convolutional neural network (CNN) as a feature extractor and classifies the feature vectors extracted from colour-composite UWF images using a support vector machine (SVM). The main contribution includes detection of four types of DR lesions in the peripheral retina for diagnostic purposes. The evaluation dataset contains 146 UWF images. The proposed method for detection of DR lesion subtypes in UWF images using two scenarios for transfer learning achieved AUC ≈ 80%. Data was split at the patient level to validate the proposed algorithm.

  15. Breast cancer risk accumulation starts early – Prevention must also

    PubMed Central

    Colditz, Graham A; Bohlke, Kari; Berkey, Catherine S.

    2014-01-01

    Purpose Nearly 1 in 4 breast cancers is diagnosed before the age of 50, and many early-stage premalignant lesions are present but not yet diagnosed. Therefore, we review evidence to support the strategy that breast cancer prevention efforts must begin early in life. Methods Literature review Results Exposures during childhood and adolescence affect a woman’s long-term risk of breast cancer, but have received far less research attention than exposures that occur later in life. Breast tissue undergoes rapid cellular proliferation between menarche and first full-term pregnancy, and risk accumulates rapidly until the terminal differentiation that accompanies first pregnancy. Evidence on childhood diet and growth in height, and adolescent alcohol intake, among other adolescent factors are related to breast cancer risk and risk of premalignant proliferative benign lesions. Conclusion Breast cancer prevention efforts will have the greatest effect when initiated at an early age and continued over a lifetime. Gaps in knowledge are identified and deserve increase attention to inform prevention. PMID:24820413

  16. Limitations on the developing preterm brain: impact of periventricular white matter lesions on brain connectivity and cognition.

    PubMed

    Pavlova, Marina A; Krägeloh-Mann, Ingeborg

    2013-04-01

    Brain lesions to the white matter in peritrigonal regions, periventricular leukomalacia, in children who were born prematurely represent an important model for studying limitations on brain development. The lesional pattern is of early origin and bilateral, that constrains the compensatory potential of the brain. We suggest that (i) topography and severity of periventricular lesions may have a long-term predictive value for cognitive and social capabilities in preterm birth survivors; and (ii) periventricular lesions may impact cognitive and social functions by affecting brain connectivity, and thereby, the dissociable neural networks underpinning these functions. A further pathway to explore is the relationship between cerebral palsy and cognitive outcome. Restrictions caused by motor disability may affect active exploration of surrounding and social participation that may in turn differentially impinge on cognitive development and social cognition. As an outline for future research, we underscore sex differences, as the sex of a preterm newborn may shape the mechanisms by which the developing brain is affected.

  17. Functional outcomes following lesions in visual cortex: Implications for plasticity of high-level vision.

    PubMed

    Liu, Tina T; Behrmann, Marlene

    2017-10-01

    Understanding the nature and extent of neural plasticity in humans remains a key challenge for neuroscience. Importantly, however, a precise characterization of plasticity and its underlying mechanism has the potential to enable new approaches for enhancing reorganization of cortical function. Investigations of the impairment and subsequent recovery of cognitive and perceptual functions following early-onset cortical lesions in humans provide a unique opportunity to elucidate how the brain changes, adapts, and reorganizes. Specifically, here, we focus on restitution of visual function, and we review the findings on plasticity and re-organization of the ventral occipital temporal cortex (VOTC) in published reports of 46 patients with a lesion to or resection of the visual cortex early in life. Findings reveal that a lesion to the VOTC results in a deficit that affects the visual recognition of more than one category of stimuli (faces, objects and words). In addition, the majority of pediatric patients show limited recovery over time, especially those in whom deficits in low-level vision also persist. Last, given that neither the equipotentiality nor the modularity view on plasticity was clearly supported, we suggest some intermediate possibilities in which some plasticity may be evident but that this might depend on the area that was affected, its maturational trajectory as well as its structural and functional connectivity constraints. Finally, we offer suggestions for future research that can elucidate plasticity further. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Foot pad dermatitis develops at an early age in commercial turkeys.

    PubMed

    Mayne, R K; Hocking, P M; Else, R W

    2006-02-01

    1. A field experiment was conducted to identify the macroscopic and histological changes associated with the development of foot pad dermatitis (FPD) in growing turkeys. Two affected and two unaffected turkeys were sampled weekly from 1 to 8 and at 10 and 21 weeks of age. 2. At one week old, birds with external signs of FPD (surface skin discolouration) showed abnormal cellular changes of the foot pad integument. As the flock aged the reactions intensified, with one sample exhibiting a fully developed macroscopic lesion at 3 weeks. 3. Major pathological changes had occurred by 6 weeks and all turkeys with external signs of lesions had fully developed microscopic inflammatory cellular lesions. From 6 weeks of age onwards lesions were increasingly numerous and became more overtly necrotic. 4. Externally normal foot pads showed microscopic evidence of lesions after the turkeys reached 4 weeks. 5. We conclude that FPD lesions become severe over a short period of time and at a very early age.

  19. Neural networks supporting audiovisual integration for speech: A large-scale lesion study.

    PubMed

    Hickok, Gregory; Rogalsky, Corianne; Matchin, William; Basilakos, Alexandra; Cai, Julia; Pillay, Sara; Ferrill, Michelle; Mickelsen, Soren; Anderson, Steven W; Love, Tracy; Binder, Jeffrey; Fridriksson, Julius

    2018-06-01

    Auditory and visual speech information are often strongly integrated resulting in perceptual enhancements for audiovisual (AV) speech over audio alone and sometimes yielding compelling illusory fusion percepts when AV cues are mismatched, the McGurk-MacDonald effect. Previous research has identified three candidate regions thought to be critical for AV speech integration: the posterior superior temporal sulcus (STS), early auditory cortex, and the posterior inferior frontal gyrus. We assess the causal involvement of these regions (and others) in the first large-scale (N = 100) lesion-based study of AV speech integration. Two primary findings emerged. First, behavioral performance and lesion maps for AV enhancement and illusory fusion measures indicate that classic metrics of AV speech integration are not necessarily measuring the same process. Second, lesions involving superior temporal auditory, lateral occipital visual, and multisensory zones in the STS are the most disruptive to AV speech integration. Further, when AV speech integration fails, the nature of the failure-auditory vs visual capture-can be predicted from the location of the lesions. These findings show that AV speech processing is supported by unimodal auditory and visual cortices as well as multimodal regions such as the STS at their boundary. Motor related frontal regions do not appear to play a role in AV speech integration. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Sydenham chorea: clinical, EEG, MRI and SPECT findings in the early stage of the disease.

    PubMed

    Heye, N; Jergas, M; Hötzinger, H; Farahati, J; Pöhlau, D; Przuntek, H

    1993-02-01

    An 18-year-old man suffered from acute Sydenham chorea appearing coincidently with beta-haemolytic streptococcal throat infection. Imaging techniques documented lesions of basal ganglia and substantia nigra. In the early course of the disease vascular lesions may be important pathogenetic mechanisms of this acquired movement disorder.

  1. Fluorescence spectroscopy and imaging for noninvasive diagnostics: applications to early cancer detection in the lung

    NASA Astrophysics Data System (ADS)

    Mycek, Mary-Ann; Urayama, Paul; Zhong, Wei; Sloboda, Roger D.; Dragnev, Konstantin H.; Dmitrovsky, Ethan

    2003-10-01

    Tissue fluorescence spectroscopy and imaging are being investigated as potential methods for non-invasive detection of pre-neoplastic change in the lung and other organ systems. A substantial contribution to tissue fluorescence is known to arise from endogenous cellular fluorophores. Using steady-state and time-resolved fluorescence spectroscopy and imaging, we characterized the endogenous fluorescence properties of immortalized and carcinogen-transformed human bronchial epithelial cells. Non-invasive sensing of endogenous molecular biomarkers associated with human bronchial pre-neoplasia will be discussed.

  2. Assessment of natural enamel lesions with optical coherence tomography in comparison with microfocus x-ray computed tomography.

    PubMed

    Espigares, Jorge; Sadr, Alireza; Hamba, Hidenori; Shimada, Yasushi; Otsuki, Masayuki; Tagami, Junji; Sumi, Yasunori

    2015-01-01

    A technology to characterize early enamel lesions is needed in dentistry. Optical coherence tomography (OCT) is a noninvasive method that provides high-resolution cross-sectional images. The aim of this study is to compare OCT with microfocus x-ray computed tomography ([Formula: see text]) for assessment of natural enamel lesions in vitro. Ten human teeth with visible white spot-like changes on the enamel smooth surface and no cavitation (ICDAS code 2) were subjected to imaging by μCT (SMX-100CT, Shimadzu) and 1300-nm swept-source OCT (Dental SS-OCT, Panasonic Health Care). In [Formula: see text], the lesions appeared as radiolucent dark areas, while in SS-OCT, they appeared as areas of increased signal intensity beneath the surface. An SS-OCT attenuation coefficient based on Beer-Lambert law could discriminate lesions from sound enamel. Lesion depth ranged from 175 to [Formula: see text] in SS-OCT. A correlation between [Formula: see text] and SS-OCT was found regarding lesion depth ([Formula: see text], [Formula: see text]) and also surface layer thickness ([Formula: see text], [Formula: see text]). The images obtained clinically in real time using the dental SS-OCT system are suitable for the assessment of natural subsurface lesions and their surface layer, providing comparable images to a laboratory high-resolution [Formula: see text] without the use of x-ray.

  3. Assessment of natural enamel lesions with optical coherence tomography in comparison with microfocus x-ray computed tomography

    PubMed Central

    Espigares, Jorge; Sadr, Alireza; Hamba, Hidenori; Shimada, Yasushi; Otsuki, Masayuki; Tagami, Junji; Sumi, Yasunori

    2015-01-01

    Abstract. A technology to characterize early enamel lesions is needed in dentistry. Optical coherence tomography (OCT) is a noninvasive method that provides high-resolution cross-sectional images. The aim of this study is to compare OCT with microfocus x-ray computed tomography (μCT) for assessment of natural enamel lesions in vitro. Ten human teeth with visible white spot-like changes on the enamel smooth surface and no cavitation (ICDAS code 2) were subjected to imaging by μCT (SMX-100CT, Shimadzu) and 1300-nm swept-source OCT (Dental SS-OCT, Panasonic Health Care). In μCT, the lesions appeared as radiolucent dark areas, while in SS-OCT, they appeared as areas of increased signal intensity beneath the surface. An SS-OCT attenuation coefficient based on Beer–Lambert law could discriminate lesions from sound enamel. Lesion depth ranged from 175 to 606  μm in SS-OCT. A correlation between μCT and SS-OCT was found regarding lesion depth (R=0.81, p<0.001) and also surface layer thickness (R=0.76, p<0.005). The images obtained clinically in real time using the dental SS-OCT system are suitable for the assessment of natural subsurface lesions and their surface layer, providing comparable images to a laboratory high-resolution μCT without the use of x-ray. PMID:26158079

  4. Characterization of Light Lesion Paradigms and Optical Coherence Tomography as Tools to Study Adult Retina Regeneration in Zebrafish

    PubMed Central

    Weber, Anke; Hochmann, Sarah; Cimalla, Peter; Gärtner, Maria; Kuscha, Veronika; Hans, Stefan; Geffarth, Michaela; Kaslin, Jan; Koch, Edmund; Brand, Michael

    2013-01-01

    Light-induced lesions are a powerful tool to study the amazing ability of photoreceptors to regenerate in the adult zebrafish retina. However, the specificity of the lesion towards photoreceptors or regional differences within the retina are still incompletely understood. We therefore characterized the process of degeneration and regeneration in an established paradigm, using intense white light from a fluorescence lamp on swimming fish (diffuse light lesion). We also designed a new light lesion paradigm where light is focused through a microscope onto the retina of an immobilized fish (focused light lesion). Focused light lesion has the advantage of creating a locally restricted area of damage, with the additional benefit of an untreated control eye in the same animal. In both paradigms, cell death is observed as an immediate early response, and proliferation is initiated around 2 days post lesion (dpl), peaking at 3 dpl. We furthermore find that two photoreceptor subtypes (UV and blue sensitive cones) are more susceptible towards intense white light than red/green double cones and rods. We also observed specific differences within light lesioned areas with respect to the process of photoreceptor degeneration: UV cone debris is removed later than any other type of photoreceptor in light lesions. Unspecific damage to retinal neurons occurs at the center of a focused light lesion territory, but not in the diffuse light lesion areas. We simulated the fish eye optical properties using software simulation, and show that the optical properties may explain the light lesion patterns that we observe. Furthermore, as a new tool to study retinal degeneration and regeneration in individual fish in vivo, we use spectral domain optical coherence tomography. Collectively, the light lesion and imaging assays described here represent powerful tools for studying degeneration and regeneration processes in the adult zebrafish retina. PMID:24303018

  5. Video comparator system for early detection of cutaneous malignant melanoma

    NASA Astrophysics Data System (ADS)

    Craine, Eric R.; Craine, Brian L.

    1992-05-01

    The recognized incidence of cutaneous malignant melanoma in the United States is now rising faster than any other cancer, increasing by 83% from 1980 to 1987. Recent revelations that depletion of the earth's ozone layer is accelerating at a more rapid rate than previously believed can only exacerbate current projections for the increased incidence of this deadly disease. Because there is no good treatment for metastatic melanoma even small cancers often prove fatal if not detected early. Melanoma allowed to invade the subcutaneous tissue is associated with a five-year survival rate of only 44%. Ironically, few cancers provide a greater opportunity for early discovery and cure. Cutaneous melanoma is not only located where it is readily observed, but typically undergoes a `radial growth' phase prior to metastasis. During this phase the net growth is superficial and circumferential, gradually increasing the area of the lesion and changing its coloration. Screening measures for the early detection of melanoma must concentrate on two primary tasks: (1) detection of lesion changes indicative of the radial growth stage of malignancy and (2) alerting the patient and physician to the existence of a new or changed lesion on the skin. To accomplish these goals we have experimented with the applicability of a microcomputer based video imaging system which stores an image archive of historical reference images for each patient. With the acquisition of new images of the patient, easily registered with the archival images through a technique we have developed we are able to perform a blink comparison of the image pairs. This technique appears to be far more effective than currently used techniques for detecting changed lesions on a comprehensive basis.

  6. A medical ontology for intelligent web-based skin lesions image retrieval.

    PubMed

    Maragoudakis, Manolis; Maglogiannis, Ilias

    2011-06-01

    Researchers have applied increasing efforts towards providing formal computational frameworks to consolidate the plethora of concepts and relations used in the medical domain. In the domain of skin related diseases, the variability of semantic features contained within digital skin images is a major barrier to the medical understanding of the symptoms and development of early skin cancers. The desideratum of making these standards machine-readable has led to their formalization in ontologies. In this work, in an attempt to enhance an existing Core Ontology for skin lesion images, hand-coded from image features, high quality images were analyzed by an autonomous ontology creation engine. We show that by exploiting agglomerative clustering methods with distance criteria upon the existing ontological structure, the original domain model could be enhanced with new instances, attributes and even relations, thus allowing for better classification and retrieval of skin lesion categories from the web.

  7. Retrospective analysis of nonendodontic periapical lesions misdiagnosed as endodontic apical periodontitis lesions in a population of Taiwanese patients.

    PubMed

    Huang, Hsun-Yu; Chen, Yuk-Kwan; Ko, Edward Cheng-Chuan; Chuang, Fu-Hsiung; Chen, Ping-Ho; Chen, Ching-Yi; Wang, Wen-Chen

    2017-07-01

    We aimed to evaluate nonendodontic periapical lesions clinically misdiagnosed as endodontic periapical pathoses in a population of Taiwanese patients. Cases (2000-2014) of histopathological diagnoses of nonendodontic periapical lesions were retrieved from all cases with a clinical diagnosis of radicular cyst, apical granuloma, or apical periodontitis in the institution. These cases were regarded as misdiagnosed nonendodontic periapical lesions, of which the types and frequencies, in addition to the demographic data, were determined. Four thousand and four specimens were clinically diagnosed as endodontically associated pathoses, of which 118 cases (2.95%) received a histopathological diagnosis of a nonendodontic pathologic entity, the most frequent lesion being keratocystic odontogenic tumor (KCOT, n = 38, 32.20%), followed by fibro-osseous lesion (n = 18, 15.25%), and dentigerous cyst (n = 13, 11.02%). Nine malignant lesions in the periapical area [squamous cell carcinoma (n = 7, 5.93%), adenoid cystic carcinoma (n = 1, 0.85%), and Langerhans cell histiocytosis (n = 1, 0.85%)] were also noted. A wide variety of histopathological diagnoses, including benign odontogenic and non-odontogenic cystic and tumorous lesions and infectious diseases, as well as malignant lesions, was noted in these 118 cases of nonendodontic periapical lesions. Squamous cell carcinoma was the most predominant malignancy of nonendodontic periapical lesions misdiagnosed as apical periodontitis lesions from imaging examination overlooking the clinical findings. The current data form a useful basis for clinicopathological investigation and educational teaching regarding nonendodontic periapical lesions misdiagnosed as endodontic apical periodontitis lesions.

  8. Early detection of response to radiation therapy in patients with brain malignancies using conventional and high b-value diffusion-weighted magnetic resonance imaging.

    PubMed

    Mardor, Yael; Pfeffer, Raphael; Spiegelmann, Roberto; Roth, Yiftach; Maier, Stephan E; Nissim, Ouzi; Berger, Raanan; Glicksman, Ami; Baram, Jacob; Orenstein, Arie; Cohen, Jack S; Tichler, Thomas

    2003-03-15

    To study the feasibility of using diffusion-weighted magnetic resonance imaging (DWMRI), which is sensitive to the diffusion of water molecules in tissues, for detection of early tumor response to radiation therapy; and to evaluate the additional information obtained from high DWMRI, which is more sensitive to low-mobility water molecules (such as intracellular or bound water), in increasing the sensitivity to response. Standard MRI and DWMRI were acquired before and at regular intervals after initiating radiation therapy for 10 malignant brain lesions in eight patients. One week posttherapy, three of six responding lesions showed an increase in the conventional DWMRI parameters. Another three responding lesions showed no change. Four nonresponding lesions showed a decrease or no change. The early change in the diffusion parameters was enhanced by using high DWMRI. When high DWMRI was used, all responding lesions showed increase in the diffusion parameter and all nonresponding lesions showed no change or decrease. Response was determined by standard MRI 7 weeks posttherapy. The changes in the diffusion parameters measured 1 week after initiating treatment were correlated with later tumor response or no response (P <.006). This correlation was increased to P <.0006 when high DWMRI was used. The significant correlation between changes in diffusion parameters 1 week after initiating treatment and later tumor response or no response suggests the feasibility of using DWMRI for early, noninvasive prediction of tumor response. The ability to predict response may enable early termination of treatment in nonresponding patients, prevent additional toxicity, and allow for early changes in treatment.

  9. Skin manifestations in sulfur mustard exposed victims with ophthalmologic complications: Association between early and late phase.

    PubMed

    Hejazi, Somayeh; Soroush, Mohammadreza; Moradi, Ahmad; Khalilazar, Sara; Mousavi, Batool; Firooz, Alireza; Younespour, Shima

    2016-01-01

    Sulfur mustard (SM) was used during the Iraq-Iran war (1980-1988). Exposed veterans continue to suffer from its ocular, skin, and respiratory complications. We aimed to evaluate associations between early (at the time of acute exposure) and decades later skin manifestations in individuals with severe ophthalmologic complications secondary to sulfur mustard exposure. One hundred forty-nine veterans with severe ocular injuries were evaluated for acute and chronic skin complications. Logistic regression models were used to examine the associations between early and late skin manifestations. Late skin complaints were observed in nearly all survivors who had early skin lesions (131 out of 137; 95.62%). Seven out of 12 patients (58.33%) who did not have early skin lesions ultimately developed late skin complications. There was a significant relationship between the presence of lesions at the time of exposure and developing late skin complaints (two-sided Fisher's exact test, OR = 15.59, p < 0.001). There was an association between having at least one early skin lesion and occurrence of late skin complications. Survivors with blisters at the time of chemical exposure were more likely to complain of itching (95% CI: 3.63-25.97, p < 0.001), burning (OR = 11.16; 95% CI: 2.97-41.89, p < 0.001), pigmentation changes (OR = 10.17; 95% CI: 2.54-40.75, p = 0.001), dryness (OR = 6.71, 95% CI: 1.22-37.01, p = 0.03) or cherry angioma (OR = 2.59; 95% CI:1.21-5.55, p = 0.01) during the late phase. Using multivariate logistic models, early blisters remained significantly associated with latent skin complaints. Of note, the genitalia and great flexure areas were the most involved anatomical sites for both early and late skin lesions in SM exposed survivors. According to this study, the presence of blisters at the time of exposure to SM is the most important predictor of developing dermatologic complications decades later in patients with severe ophthalmologic

  10. Associations between a Genetic Risk Score for Clinical CAD and Early Stage Lesions in the Coronary Artery and the Aorta.

    PubMed

    Salfati, Elias L; Herrington, David M; Assimes, Themistocles L

    2016-01-01

    The correlation between the extent of fatty streaks, more advanced atherosclerotic lesions, and community rates of coronary artery disease (CAD) is substantially higher for the coronary artery compared to the aorta. We sought to determine whether a genetic basis contributes to these differences. We conducted a cluster analysis of 6 subclinical atherosclerosis phenotypes documented in 564 white participants of the Pathobiological Determinants of Atherosclerosis in Youth study including the extent of fatty streaks and raised lesions in the coronary artery (CF and CR), thoracic aorta (TF and TR), and abdominal aorta (AF and AR) followed by a genetic association analysis of the same phenotypes. Our cluster analysis grouped all raised lesions and fatty streaks in the coronary into one cluster (CF, CR, TR, and AR) and the fatty streaks in the aorta into a second cluster (TF and AF). We found a genetic risk score of high-risk alleles at 57 susceptibility loci for CAD to be variably associated with the phenotypes in the first cluster (OR: 1.30 p = 0.009 for being in top quartile of degree of involvement of CF, 1.34 p = 0.005 for CR, 1.25: p = 0.11 for TR, and 1.19 p = 0.08 for AR) but not at all with the phenotypes in the second cluster (OR: 1.01, p = 0.95 for TF and 0.98, p = 0.82 for AF). The genetic determinants of fatty streaks in the aorta do not appear to overlap substantially with the genetic determinants of fatty streaks in the coronary as well as raised lesions in both the coronary and the aorta. These findings may explain why a larger fraction of fatty streaks in the aorta are less likely to progress to raised lesions compared to the coronary artery.

  11. Associations between a Genetic Risk Score for Clinical CAD and Early Stage Lesions in the Coronary Artery and the Aorta

    PubMed Central

    Herrington, David M.

    2016-01-01

    Objective The correlation between the extent of fatty streaks, more advanced atherosclerotic lesions, and community rates of coronary artery disease (CAD) is substantially higher for the coronary artery compared to the aorta. We sought to determine whether a genetic basis contributes to these differences. Approach and Results We conducted a cluster analysis of 6 subclinical atherosclerosis phenotypes documented in 564 white participants of the Pathobiological Determinants of Atherosclerosis in Youth study including the extent of fatty streaks and raised lesions in the coronary artery (CF and CR), thoracic aorta (TF and TR), and abdominal aorta (AF and AR) followed by a genetic association analysis of the same phenotypes. Our cluster analysis grouped all raised lesions and fatty streaks in the coronary into one cluster (CF, CR, TR, and AR) and the fatty streaks in the aorta into a second cluster (TF and AF). We found a genetic risk score of high-risk alleles at 57 susceptibility loci for CAD to be variably associated with the phenotypes in the first cluster (OR: 1.30 p = 0.009 for being in top quartile of degree of involvement of CF, 1.34 p = 0.005 for CR, 1.25: p = 0.11 for TR, and 1.19 p = 0.08 for AR) but not at all with the phenotypes in the second cluster (OR: 1.01, p = 0.95 for TF and 0.98, p = 0.82 for AF). Conclusions The genetic determinants of fatty streaks in the aorta do not appear to overlap substantially with the genetic determinants of fatty streaks in the coronary as well as raised lesions in both the coronary and the aorta. These findings may explain why a larger fraction of fatty streaks in the aorta are less likely to progress to raised lesions compared to the coronary artery. PMID:27861582

  12. Convergence Analysis of Micro-Lesions (CAML): An approach to mapping of diffuse lesions from carotid revascularization.

    PubMed

    Rosen, Allyson C; Soman, Salil; Bhat, Jyoti; Laird, Angela R; Stephens, Jeffrey; Eickhoff, Simon B; Fox, P Mickle; Long, Becky; Dinishak, David; Ortega, Mario; Lane, Barton; Wintermark, Max; Hitchner, Elizabeth; Zhou, Wei

    2018-01-01

    Carotid revascularization (endarterectomy, stenting) prevents stroke; however, procedure-related embolization is common and results in small brain lesions easily identified by diffusion weighted magnetic resonance imaging (DWI). A crucial barrier to understanding the clinical significance of these lesions has been the lack of a statistical approach to identify vulnerable brain areas. The problem is that the lesions are small, numerous, and non-overlapping. Here we address this problem with a new method, the Convergence Analysis of Micro-Lesions (CAML) technique, an extension of the Anatomic Likelihood Analysis (ALE). The method combines manual lesion tracing, constraints based on known lesion patterns, and convergence analysis to represent regions vulnerable to lesions as probabilistic brain atlases. Two studies were conducted over the course of 12 years in an active, vascular surgery clinic. An analysis in an initial group of 126 patients at 1.5 T MRI was cross-validated in a second group of 80 patients at 3T MRI. In CAML, lesions were manually defined and center points identified. Brains were aligned according to side of surgery since this factor powerfully determines lesion distribution. A convergence based analysis, was performed on each of these groups. Results indicated the most consistent region of vulnerability was in motor and premotor cortex regions. Smaller regions common to both groups included the dorsolateral prefrontal cortex and medial parietal regions. Vulnerability of motor cortex is consistent with previous work showing changes in hand dexterity associated with these procedures. The consistency of CAML also demonstrates the feasibility of this new approach to characterize small, diffuse, non-overlapping lesions in patients with multifocal pathologies.

  13. Assessment of Lymph Nodes and Prostate Status Using Early Dynamic Curves with (18)F-Choline PET/CT in Prostate Cancer.

    PubMed

    Mathieu, Cédric; Ferrer, Ludovic; Carlier, Thomas; Colombié, Mathilde; Rusu, Daniela; Kraeber-Bodéré, Françoise; Campion, Loic; Rousseau, Caroline

    2015-01-01

    Dynamic image acquisition with (18)F-Choline [fluorocholine (FCH)] PET/CT in prostate cancer is mostly used to overcome the bladder repletion, which could obstruct the loco-regional analysis. The aim of our study was to analyze early dynamic FCH acquisitions to define pelvic lymph node or prostate pathological status. Retrospective analysis was performed on 39 patients for initial staging (n = 18), or after initial treatment (n = 21). Patients underwent 10-min dynamic acquisitions centered on the pelvis, after injection of 3-4 MBq/kg of FCH. Whole-body images were acquired about 1 h after injection using a PET/CT GE Discovery LS (GE-LS) or Siemens Biograph mCT (mCT). Maximum and mean SUV according to time were measured on nodal and prostatic lesions. SUVmean was corrected for partial volume effect (PVEC) with suitable recovery coefficients. The status of each lesion was based on histological results or patient follow-up (>6 months). A Mann-Whitney test and ANOVA were used to compare mean and receiver operating characteristic (ROC) curve analysis. The median PSA was 8.46 ng/mL and the median Gleason score was 3 + 4. Ninety-two lesions (43 lymph nodes and 49 prostate lesions) were analyzed, including 63 malignant lesions. In early dynamic acquisitions, the maximum and mean SUV were significantly higher, respectively, on mCT and GE-LS, in malignant versus benign lesions (p < 0.001, p < 0.001). Mean SUV without PVEC, allowed better discrimination of benign from malignant lesions, in comparison with maximum and mean SUV (with PVEC), for both early and late acquisitions. For patients acquired on mCT, area under the ROC curve showed a trend to better sensitivity and specificity for early acquisitions, compared with late acquisitions (SUVmax AUC 0.92 versus 0.85, respectively). Assessment of lymph nodes and prostate pathological status with early dynamic imaging using PET/CT FCH allowed prostate cancer detection in situations where proof of

  14. Cancer Prevention: Obstacles, Challenges, and the Road Ahead

    PubMed Central

    Mukhtar, Hasan; Rock, Cheryl L.; Cuzick, Jack; Kensler, Thomas W.; Yang, Chung S.; Ramsey, Scott D.; Lippman, Scott M.; Alberts, David S.

    2016-01-01

    Approaches to reduce the global burden of cancer include two major strategies: screening and early detection and active preventive intervention. The latter is the topic of this Commentary and spans a broad range of activities. The genetic heterogeneity and complexity of advanced cancers strongly support the rationale for early interruption of the carcinogenic process and an enhanced focus on prevention as a priority strategy to reduce the burden of cancer; however, the focus of cancer prevention management should be on individuals at high risk and on primary localized disease in which screening and detection should also play a vital role. The timing and dose of (chemo-)preventive intervention also affects response. The intervention may be ineffective if the target population is very high risk or already presenting with preneoplastic lesions with cellular changes that cannot be reversed. The field needs to move beyond general concepts of carcinogenesis to targeted organ site prevention approaches in patients at high risk, as is currently being done for breast and colorectal cancers. Establishing the benefit of new cancer preventive interventions will take years and possibly decades, depending on the outcome being evaluated. We also propose that comparative effectiveness research designs and the value of information obtained from large-scale prevention studies are necessary in order for preventive interventions to become a routine part of cancer management. PMID:26547931

  15. Transient widespread cortical and splenial lesions in acute encephalitis/encephalopathy associated with primary Epstein-Barr virus infection.

    PubMed

    Zhang, Shuo; Feng, Juan; Shi, Yifang

    2016-01-01

    Infection with Epstein-Barr virus (EBV) is very common and usually occurs in childhood or early adulthood. Encephalitis/encephalopathy is an uncommon but serious neurological complication of EBV. A case of EBV-associated encephalitis/encephalopathy with involvement of reversible widespread cortical and splenial lesions is presented herein. An 8-year-old Chinese girl who presented with fever and headache, followed by seizures and drowsiness, was admitted to the hospital. Magnetic resonance imaging revealed high signal intensities on diffusion-weighted imaging in widespread cortical and splenial lesions. The clinical and laboratory examination results together with the unusual radiology findings suggested acute encephalitis/encephalopathy due to primary EBV infection. After methylprednisolone pulse therapy together with ganciclovir, the patient made a full recovery without any brain lesions. The hallmark clinical-radiological features of this patient included severe encephalitis/encephalopathy at onset, the prompt and complete recovery, and rapidly reversible widespread involvement of the cortex and splenium. Patients with EBV encephalitis/encephalopathy who have multiple lesions, even with the widespread involvement of cortex and splenium of the corpus callosum, may have a favorable outcome with complete disappearance of all brain lesions. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Identification of lesion images from gastrointestinal endoscope based on feature extraction of combinational methods with and without learning process.

    PubMed

    Liu, Ding-Yun; Gan, Tao; Rao, Ni-Ni; Xing, Yao-Wen; Zheng, Jie; Li, Sang; Luo, Cheng-Si; Zhou, Zhong-Jun; Wan, Yong-Li

    2016-08-01

    The gastrointestinal endoscopy in this study refers to conventional gastroscopy and wireless capsule endoscopy (WCE). Both of these techniques produce a large number of images in each diagnosis. The lesion detection done by hand from the images above is time consuming and inaccurate. This study designed a new computer-aided method to detect lesion images. We initially designed an algorithm named joint diagonalisation principal component analysis (JDPCA), in which there are no approximation, iteration or inverting procedures. Thus, JDPCA has a low computational complexity and is suitable for dimension reduction of the gastrointestinal endoscopic images. Then, a novel image feature extraction method was established through combining the algorithm of machine learning based on JDPCA and conventional feature extraction algorithm without learning. Finally, a new computer-aided method is proposed to identify the gastrointestinal endoscopic images containing lesions. The clinical data of gastroscopic images and WCE images containing the lesions of early upper digestive tract cancer and small intestinal bleeding, which consist of 1330 images from 291 patients totally, were used to confirm the validation of the proposed method. The experimental results shows that, for the detection of early oesophageal cancer images, early gastric cancer images and small intestinal bleeding images, the mean values of accuracy of the proposed method were 90.75%, 90.75% and 94.34%, with the standard deviations (SDs) of 0.0426, 0.0334 and 0.0235, respectively. The areas under the curves (AUCs) were 0.9471, 0.9532 and 0.9776, with the SDs of 0.0296, 0.0285 and 0.0172, respectively. Compared with the traditional related methods, our method showed a better performance. It may therefore provide worthwhile guidance for improving the efficiency and accuracy of gastrointestinal disease diagnosis and is a good prospect for clinical application. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Management of Lesion Nematodes and Potato Early Dying with Rotation Crops

    PubMed Central

    LaMondia, J.A.

    2006-01-01

    Soil-incorporated rotation/green manure crops were evaluated for management of potato early dying caused by Verticillium dahliae and Pratylenchus penetrans. After two years of rotation/green manure and a subsequent potato crop, P. penetrans numbers were less after ‘Saia’ oat/‘Polynema’ marigold, ‘Triple S’ sorghum-sudangrass, or ‘Garry’ oat than ‘Superior’ potato or ‘Humus’ rapeseed. The area under the disease progress curve (AUDPC) for early dying was lowest after Saia oat/marigold, and tuber yields were greater than continuous potato after all crops except sorghum-sudangrass. Saia oat/marigold crops resulted in the greatest tuber yields. After one year of rotation/green manure, a marigold crop increased tuber yields and reduced AUDPC and P. penetrans. In the second potato crop after a single year of rotation, plots previously planted to marigolds had reduced P. penetrans densities and AUDPC and increased tuber yield. Rapeseed supported more P. penetrans than potato, but had greater yields. After two years of rotation/green manure crops and a subsequent potato crop, continuous potato had the highest AUDPC and lowest tuber weight. Rotation with Saia oats (2 yr) and Rudbeckia hirta (1 yr) reduced P. penetrans and increased tuber yields. AUDPC was lowest after R. hirta. Two years of sorghum-sudangrass did not affect P. penetrans, tuber yield or AUDPC. These results demonstrate that P. penetrans may be reduced by one or two years of rotation to non-host or antagonistic plants such as Saia oat, Polynema marigold, or R. hirta and that nematode control may reduce the severity of potato early dying. PMID:19259461

  18. Preoperative endoscopic titanium clip placement facilitates intraoperative localization of early-stage esophageal cancer or severe dysplasia.

    PubMed

    Tan, Lei; Feng, Juan; Zhao, Qin; Chen, Ping; Yang, Guotao

    2017-08-02

    Accurate intraoperative localization of esophageal lesions is essential for successful surgical resection. We tested whether preoperative endoscopic placement of titanium clips could facilitate intraoperative localization of early-stage esophageal cancer or severe dysplasia. A prospective randomized clinical trial was performed between May 2012 and July 2014. All enrolled patients received preoperative endoscopy and esophageal endoscopic ultrasound, as well as pathological study on the biopsy specimen, to confirm early stage esophageal cancer or severe dysplasia. One day before the surgical operation, patients in the experimental group received the preoperative endoscopic titanium labeling of esophageal lesions. Then, during the surgical operation, palpitation of titanium clips was used to localize the lesions in these patients. In patients in the control group, palpitation of nodules or esophageal wall mucosal thickening, together with the consideration of the results from preoperative endoscopic and ultrasound studies, was applied to estimate the location of the esophageal lesions. Study outcomes included the proportions of patients having successful intraoperative pre-resection lesion localization, post-esophagectomy lesion visualization, negative upper surgical margin, change of surgical approaches, and positive postoperative pathological diagnosis. A total of 27 patients were enrolled into the study, with 14 in the experimental group and 13 in the control group. Compared to the patients in the control group, a higher proportion of patients in the experimental group had statistically significant successful intraoperative esophageal lesion localization (100 versus 15.3% in the experimental versus control group). Preoperative endoscopic titanium clip placement could facilitate intraoperative localization of early-stage esophageal cancer or severe dysplasia. Current study was registered in Chinese Clinical Trial Registry and World Health Organization International

  19. Lesions of the Broad Ligament: A Review.

    PubMed

    Heller, Debra S

    2015-01-01

    The differential diagnosis of lesions arising in the broad ligament is quite large. Many of these lesions can be clinically interpreted before surgery as adnexal or uterine neoplasms. Although some lesions are similar to those arising in other müllerian sites, there are unique lesions as well. The lesions are uncommon and may prove challenging to clinicians. The purpose was to review the scope of lesions affecting the broad ligament. A literature review was conducted. A Medline search was performed using the terms broad ligament, mesosalpinx, and mesovarium. A review of the scope of broad ligament lesions is presented to assist in developing a differential diagnosis if a patient with such a lesion is encountered. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.

  20. Meat processing and colon carcinogenesis: cooked, nitrite-treated, and oxidized high-heme cured meat promotes mucin-depleted foci in rats.

    PubMed

    Santarelli, Raphaëlle L; Vendeuvre, Jean-Luc; Naud, Nathalie; Taché, Sylviane; Guéraud, Françoise; Viau, Michelle; Genot, Claude; Corpet, Denis E; Pierre, Fabrice H F

    2010-07-01

    Processed meat intake is associated with colorectal cancer risk, but no experimental study supports the epidemiologic evidence. To study the effect of meat processing on carcinogenesis promotion, we first did a 14-day study with 16 models of cured meat. Studied factors, in a 2 x 2 x 2 x 2 design, were muscle color (a proxy for heme level), processing temperature, added nitrite, and packaging. Fischer 344 rats were fed these 16 diets, and we evaluated fecal and urinary fat oxidation and cytotoxicity, three biomarkers of heme-induced carcinogenesis promotion. A principal component analysis allowed for selection of four cured meats for inclusion into a promotion study. These selected diets were given for 100 days to rats pretreated with 1,2-dimethylhydrazine. Colons were scored for preneoplastic lesions: aberrant crypt foci (ACF) and mucin-depleted foci (MDF). Cured meat diets significantly increased the number of ACF/colon compared with a no-meat control diet (P = 0.002). Only the cooked nitrite-treated and oxidized high-heme meat significantly increased the fecal level of apparent total N-nitroso compounds (ATNC) and the number of MDF per colon compared with the no-meat control diet (P < 0.05). This nitrite-treated and oxidized cured meat specifically increased the MDF number compared with similar nonnitrite-treated meat (P = 0.03) and with similar nonoxidized meat (P = 0.004). Thus, a model cured meat, similar to ham stored aerobically, increased the number of preneoplastic lesions, which suggests colon carcinogenesis promotion. Nitrite treatment and oxidation increased this promoting effect, which was linked with increased fecal ATNC level. This study could lead to process modifications to make nonpromoting processed meat. 2010 AACR.

  1. Establishment of a protocol for the gene expression analysis of laser microdissected rat kidney samples with affymetrix genechips

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stemmer, Kerstin; Ellinger-Ziegelbauer, Heidrun; Lotz, Kerstin

    2006-11-15

    Laser microdissection in conjunction with microarray technology allows selective isolation and analysis of specific cell populations, e.g., preneoplastic renal lesions. To date, only limited information is available on sample preparation and preservation techniques that result in both optimal histomorphological preservation of sections and high-quality RNA for microarray analysis. Furthermore, amplification of minute amounts of RNA from microdissected renal samples allowing analysis with genechips has only scantily been addressed to date. The objective of this study was therefore to establish a reliable and reproducible protocol for laser microdissection in conjunction with microarray technology using kidney tissue from Eker rats p.o. treatedmore » for 7 days and 6 months with 10 and 1 mg Aristolochic acid/kg bw, respectively. Kidney tissues were preserved in RNAlater or snap frozen. Cryosections were cut and stained with either H and E or cresyl violet for subsequent morphological and RNA quality assessment and laser microdissection. RNA quality was comparable in snap frozen and RNAlater-preserved samples, however, the histomorphological preservation of renal sections was much better following cryopreservation. Moreover, the different staining techniques in combination with sample processing time at room temperature can have an influence on RNA quality. Different RNA amplification protocols were shown to have an impact on gene expression profiles as demonstrated with Affymetrix Rat Genome 230{sub 2}.0 arrays. Considering all the parameters analyzed in this study, a protocol for RNA isolation from laser microdissected samples with subsequent Affymetrix chip hybridization was established that was also successfully applied to preneoplastic lesions laser microdissected from Aristolochic acid-treated rats.« less

  2. [Precancerous lesions of the uterine cervix in Pointe-Noire, Congo].

    PubMed

    Moukassa, D; N'Golet, A; Lingouala, L G; Eouani, M L; Samba, J B; Mambou, J V; Ompaligoli, S; Moukengue, L F; Taty-Pambou, E

    2007-02-01

    The purpose of this study was to determine the cytological profile and risk factors for intraepithelial precancerous lesions of the uterine cervix in an urban community of Pointe-Noire, an industrialized seaport located in the southeast region of Congo-Brazzaville. A transverse study was carried out over a period of 18 months (January 2003 to July 2004) in the Center for the Study of Human and Animal Diseases (CSHAD) at the General Adolphe Sie Hospital in Pointe-Noire. A total of 1347 files of women benefiting from cervico-vaginal smears were included in the study. Testing was undertaken either at the request of the patient (voluntary screening) or at the request of a health care provider (physician, midwife or nurse) in relation with various gynecological problems. The relative frequency of intraepithelial lesions was estimated to be 15.36% including 9.17% of low-grade intraepithelial lesions (Ig IEL) and 6.19% of high-grade intraepithelial lesions (hg IEL). The mean age of patients with hg IEL was 42.25 years (range, 12 to 17). Study of the interval between actual age at the time of sample collection and age of first sexual relations showed that women presenting IEL had an interval of at least 20 years. This interval probably corresponds to the time necessary for the interaction between human papillomavirus (HPV) and epithelial cells of the uterine cervix to induce intraepithelial lesions that lead to development of cancer of the uterine cervix. Comparative analysis of the number of sexual partners between the group of women with normal smears and the group with smears showing hg IEL indicated a clear predominance of the mean number of partners in the latter group, i.e., 2 +/- 1,2 versus 5 +/- 1,8 (p < 0.05). Most IEL were observed in multigestational women who accounted for 75.39% with a mean of 6.21 for hg IEL. This preliminary study provides a sound factual basis in terms of epidemiological data on these precancerous lesions of the uterine cervix in the

  3. A retrospective analysis of dermatological lesions in kidney transplant patients

    PubMed Central

    Castello, Michela; Gregorini, Marilena; Rampino, Teresa; Bosio, Francesca; Bedino, Giulia; Piotti, Giovanni; Soccio, Grazia; Esposito, Pasquale; Klersy, Catherine; Abelli, Massimo; Borroni, Giovanni; Canton, Antonio Dal

    2013-01-01

    ; 16 (9.29%) cutaneous xerosis, 15 (8.74%) dermatitis, while absence of cutaneous disease was evident only in 8 (4.37%) cases. An association between drug side effects and anti-rejection treatment (P≤0.01) and/or calcineurin-inhibitors (CNI) exposure (P≤0.01) was found. Longer exposure to immunosuppressive drugs (>60 months) was associated with pre-malignancy and malignancy lesions. Interpretation & conclusions: Cutaneous diseases are frequent in kidney transplanted patients. Continuous skin monitoring is necessary to make an early diagnosis and to start appropriate treatment. PMID:23852300

  4. Muscle sarcomere lesions and thrombosis after spaceflight and suspension unloading

    NASA Technical Reports Server (NTRS)

    Riley, D. A.; Ellis, S.; Giometti, C. S.; Hoh, J. F. Y.; Il'ina-Kakueva, E. I.; Oganov, V. S.; Slocum, G. R.; Bain, J. L. W.; Sedlak, F. R.

    1992-01-01

    Data obtained during Cosmos 2044 bisatellite mission are reviewed and found to be consistent with the results of previous rodent spaceflight experiments. Investigation was carried out of hindlimb muscles from flight rats killed as close to land as possible so that changes induced by spaceflight and early readaptation to weight bearing could be distinguished from the changes that resulted from the two-day postflight period during Cosmos 1887. Results presented pertain to muscle atrophy and fiber type changes, eccentric contraction-like lesions, microcirculatory changes and interstitial edema, and tissue damage.

  5. Voxel-based lesion-symptom mapping of stroke lesions underlying somatosensory deficits

    PubMed Central

    Meyer, Sarah; Kessner, Simon S.; Cheng, Bastian; Bönstrup, Marlene; Schulz, Robert; Hummel, Friedhelm C.; De Bruyn, Nele; Peeters, Andre; Van Pesch, Vincent; Duprez, Thierry; Sunaert, Stefan; Schrooten, Maarten; Feys, Hilde; Gerloff, Christian; Thomalla, Götz; Thijs, Vincent; Verheyden, Geert

    2015-01-01

    The aim of this study was to investigate the relationship between stroke lesion location and the resulting somatosensory deficit. We studied exteroceptive and proprioceptive somatosensory symptoms and stroke lesions in 38 patients with first-ever acute stroke. The Erasmus modified Nottingham Sensory Assessment was used to clinically evaluate somatosensory functioning in the arm and hand within the first week after stroke onset. Additionally, more objective measures such as the perceptual threshold of touch and somatosensory evoked potentials were recorded. Non-parametric voxel-based lesion-symptom mapping was performed to investigate lesion contribution to different somatosensory deficits in the upper limb. Additionally, structural connectivity of brain areas that demonstrated the strongest association with somatosensory symptoms was determined, using probabilistic fiber tracking based on diffusion tensor imaging data from a healthy age-matched sample. Voxels with a significant association to somatosensory deficits were clustered in two core brain regions: the central parietal white matter, also referred to as the sensory component of the superior thalamic radiation, and the parietal operculum close to the insular cortex, representing the secondary somatosensory cortex. Our objective recordings confirmed findings from clinical assessments. Probabilistic tracking connected the first region to thalamus, internal capsule, brain stem, postcentral gyrus, cerebellum, and frontal pathways, while the second region demonstrated structural connections to thalamus, insular and primary somatosensory cortex. This study reveals that stroke lesions in the sensory fibers of the superior thalamocortical radiation and the parietal operculum are significantly associated with multiple exteroceptive and proprioceptive deficits in the arm and hand. PMID:26900565

  6. Transcriptome Analysis Reveals Markers of Aberrantly Activated Innate Immunity in Vitiligo Lesional and Non-Lesional Skin

    PubMed Central

    Huang, Yuanshen; Wang, Yang; Yu, Jie; Gao, Min; Levings, Megan; Wei, Shencai; Zhang, Shengquan; Xu, Aie; Su, Mingwan; Dutz, Jan; Zhang, Xuejun; Zhou, Youwen

    2012-01-01

    Background Vitiligo is characterized by the death of melanocytes in the skin. This is associated with the presence of T cell infiltrates in the lesional borders. However, at present, there is no detailed and systematic characterization on whether additional cellular or molecular changes are present inside vitiligo lesions. Further, it is unknown if the normal appearing non-lesional skin of vitiligo patients is in fact normal. The purpose of this study is to systematically characterize the molecular and cellular characteristics of the lesional and non-lesional skin of vitiligo patients. Methods and Materials Paired lesional and non-lesional skin biopsies from twenty-three vitiligo patients and normal skin biopsies from sixteen healthy volunteers were obtained with informed consent. The following aspects were analyzed: (1) transcriptome changes present in vitiligo skin using DNA microarrays and qRT-PCR; (2) abnormal cellular infiltrates in vitiligo skin explant cultures using flow cytometry; and (3) distribution of the abnormal cellular infiltrates in vitiligo skin using immunofluorescence microscopy. Results Compared with normal skin, vitiligo lesional skin contained 17 genes (mostly melanocyte-specific genes) whose expression was decreased or absent. In contrast, the relative expression of 13 genes was up-regulated. The up-regulated genes point to aberrant activity of the innate immune system, especially natural killer cells in vitiligo. Strikingly, the markers of heightened innate immune responses were also found to be up-regulated in the non-lesional skin of vitiligo patients. Conclusions and Clinical Implications As the first systematic transcriptome characterization of the skin in vitiligo patients, this study revealed previously unknown molecular markers that strongly suggest aberrant innate immune activation in the microenvironment of vitiligo skin. Since these changes involve both lesional and non-lesional skin, our results suggest that therapies targeting

  7. Immunohistological Analysis of In Situ Expression of Mycobacterial Antigens in Skin Lesions of Leprosy Patients Across the Histopathological Spectrum

    PubMed Central

    Verhagen, Claudia; Faber, William; Klatser, Paul; Buffing, Anita; Naafs, Ben; Das, Pranab

    1999-01-01

    The presence of mycobacterial antigens in leprosy skin lesions was studied by immunohistological methods using monoclonal antibodies (MAbs) to Mycobacterium leprae-specific phenolic glycolipid I (PGL-I) and to cross-reactive mycobacterial antigens of 36 kd, 65 kd, and lipoarabinomannan (LAM). The staining patterns with MAb to 36 kd and 65 kd were heterogeneous and were also seen in the lesions of other skin diseases. The in situ staining of PGL-I and LAM was seen only in leprosy. Both antigens were abundantly present in infiltrating macrophages in the lesions of untreated multibacillary (MB) patients, whereas only PGL-I was occasionally seen in scattered macrophages in untreated paucibacillary lesions. During treatment, clearance of PGL-I from granulomas in MB lesions occurred before that of LAM, although the former persisted in scattered macrophages in some treated patients. This persistence of PGL-I in the lesions paralleled high serum anti-PGL-I antibody titers but was not indicative for the presence of viable bacilli in the lesions. Interestingly, we also observed a differential expression pattern of PGL-I and LAM in the lesions of MB patients with reactions during the course of the disease as compared with those without reactions. In conclusion, the in situ expression pattern of PGL-I and LAM in MB patients may assist in early diagnosis of reactions versus relapse. PMID:10362804

  8. MALDI imaging mass spectrometry analysis-A new approach for protein mapping in multiple sclerosis brain lesions.

    PubMed

    Maccarrone, Giuseppina; Nischwitz, Sandra; Deininger, Sören-Oliver; Hornung, Joachim; König, Fatima Barbara; Stadelmann, Christine; Turck, Christoph W; Weber, Frank

    2017-03-15

    Multiple sclerosis is a disease of the central nervous system characterized by recurrent inflammatory demyelinating lesions in the early disease stage. Lesion formation and mechanisms leading to lesion remyelination are not fully understood. Matrix Assisted Laser Desorption Ionisation Mass Spectrometry imaging (MALDI-IMS) is a technology which analyses proteins and peptides in tissue, preserves their spatial localization, and generates molecular maps within the tissue section. In a pilot study we employed MALDI imaging mass spectrometry to profile and identify peptides and proteins expressed in normal-appearing white matter, grey matter and multiple sclerosis brain lesions with different extents of remyelination. The unsupervised clustering analysis of the mass spectra generated images which reflected the tissue section morphology in luxol fast blue stain and in myelin basic protein immunohistochemistry. Lesions with low remyelination extent were defined by compounds with molecular weight smaller than 5300Da, while more completely remyelinated lesions showed compounds with molecular weights greater than 15,200Da. An in-depth analysis of the mass spectra enabled the detection of cortical lesions which were not seen by routine luxol fast blue histology. An ion mass, mainly distributed at the rim of multiple sclerosis lesions, was identified by liquid chromatography and tandem mass spectrometry as thymosin beta-4, a protein known to be involved in cell migration and in restorative processes. The ion mass of thymosin beta-4 was profiled by MALDI imaging mass spectrometry in brain slides of 12 multiple sclerosis patients and validated by immunohistochemical analysis. In summary, our results demonstrate the ability of the MALDI-IMS technology to map proteins within the brain parenchyma and multiple sclerosis lesions and to identify potential markers involved in multiple sclerosis pathogenesis and/or remyelination. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Humanization of the mouse mammary gland by replacement of the luminal layer with genetically engineered preneoplastic human cells.

    PubMed

    Verbeke, Stephanie; Richard, Elodie; Monceau, Elodie; Schmidt, Xenia; Rousseau, Benoit; Velasco, Valerie; Bernard, David; Bonnefoi, Herve; MacGrogan, Gaetan; Iggo, Richard D

    2014-12-20

    The cell of origin for estrogen receptor α-positive (ERα+) breast cancer is probably a luminal stem cell in the terminal duct lobular units. To model these cells, we have used the murine myoepithelial layer in the mouse mammary ducts as a scaffold upon which to build a human luminal layer. To prevent squamous metaplasia, a common artifact in genetically-engineered breast cancer models, we sought to limit activation of the epidermal growth factor receptor (EGFR) during in vitro cell culture before grafting the cells. Human reduction mammoplasty cells were grown in vitro in WIT medium. Epidermal growth factor in the medium was replaced with amphiregulin and neuregulin to decrease activation of EGFR and increase activation of EGFR homologs 3 and 4 (ERBB3 and ERBB4). Lentiviral vectors were used to express oncogenic transgenes and fluorescent proteins. Human mammary epithelial cells were mixed with irradiated mouse fibroblasts and Matrigel, then injected through the nipple into the mammary ducts of immunodeficient mice. Engrafted cells were visualized by stereomicroscopy for fluorescent proteins and characterized by histology and immunohistochemistry. Growth of normal mammary epithelial cells in conditions favoring ERBB3/4 signaling prevented squamous metaplasia in vitro. Normal human cells were quickly lost after intraductal injection, but cells infected with lentiviruses expressing CCND1, MYC, TERT, BMI1 and a short-hairpin RNA targeting TP53 were able to engraft and progressively replace the luminal layer in the mouse mammary ducts, resulting in the formation of an extensive network of humanized ducts. Despite expressing multiple oncogenes, the human cells formed a morphologically normal luminal layer. Expression of a single additional oncogene, PIK3CA-H1047R, converted the cells into invasive cancer cells. The resulting tumors were ERα+, Ki67+ luminal B adenocarcinomas that were resistant to treatment with fulvestrant. Injection of preneoplastic human mammary

  10. Aging promotes neoplastic disease through effects on the tissue microenvironment.

    PubMed

    Marongiu, Fabio; Serra, Maria Paola; Doratiotto, Silvia; Sini, Marcella; Fanti, Maura; Cadoni, Erika; Serra, Monica; Laconi, Ezio

    2016-12-06

    A better understanding of the complex relationship between aging and cancer will provide important tools for the prevention and treatment of neoplasia. In these studies, the hypothesis was tested that aging may fuel carcinogenesis via alterations imposed in the tissue microenvironment. Preneoplastic hepatocytes isolated from liver nodules were orthotopically injected into either young or old syngeneic rats and their fate was followed over time using the dipeptidyl-peptidase type IV (DPPIV) system to track donor-derived-cells. At 3 months post-Tx, the mean size of donor-derived clusters was 11±3 cells in young vs. 42±8 in old recipients. At 8 months post-Tx, no visible lesion were detected in any of 21 young recipients, while 17/18 animals transplanted at old age displayed hepatic nodules, including 7 large tumors. All tumors expressed the DPPIV marker enzyme, indicating that they originated from transplanted cells. Expression of senescence-associated β-galactosidase was common in liver of 18-month old animals, while it was a rare finding in young controls. Finally, both mRNA and IL6 protein were found to be increased in the liver of aged rats compared to young controls. These results are interpreted to indicate that the microenvironment of the aged liver promotes the growth of pre-neoplastic hepatocytes.

  11. Pathology of serrated colorectal lesions.

    PubMed

    Bateman, Adrian C

    2014-10-01

    The concept of serrated colorectal neoplasia has become recognised as a key process in the development of colorectal cancer (CRC) and an important alternative pathway to malignancy compared with the long established ‘adenoma-carcinoma’ sequence. Increasing recognition of the morphological spectrum of serrated lesions has occurred in parallel with elucidation of the distinct molecular genetic characteristics of progression from normal mucosa, via the ‘serrated pathway’, to CRC. Some of these lesions can be difficult to identify at colonoscopy. Challenges for pathologists include the requirement for accurate recognition of the forms of serrated lesions that are associated with a significant risk of malignant progression and therefore the need for widely disseminated reproducible criteria for their diagnosis. Alongside this process, pathologists and endoscopists need to formulate clear guidelines for the management of patients with these lesions, particularly with respect to the optimal follow-up intervals. This review provides practical guidance for the recognition of these lesions by pathologists, a discussion of ‘serrated adenocarcinoma’ and an insight into the distinct molecular genetic alterations that are seen in this spectrum of lesions in comparison to those that characterise the classic ‘adenoma-carcinoma’ sequence.

  12. Three Cases of Intravascular Large B-Cell Lymphoma Detected in a Biopsy of Skin Lesions.

    PubMed

    Arai, Takashi; Kato, Yukihiko; Funaki, Maki; Shimamura, Sanae; Yokogawa, Naoto; Sugii, Syoji; Tsuboi, Ryoji

    2016-01-01

    Intravascular large B-cell lymphoma (IVL) is a rare subtype of extranodal malignant lymphoma. The proliferation of neoplastic B cells within small blood vessels causes eruptions and other symptoms in a variety of organs. The random skin biopsy is useful for diagnosing this condition in its early stages. In order to assess the diagnostic utility of this method, we examined 3 cases with the aim of comparing the occurrence of tumor cells in lesional and healthy-looking skin by performing a random skin biopsy of 32 separate sites. Our findings from the total of 32 biopsy specimens collected from the 3 cases indicated that 16 of the 17 sites on the lesional skin and 1 of the 15 sites on the healthy-looking skin were positive for neoplastic cells. This finding suggested that IVL cells occurred more frequently in the lesional skin than in the healthy-looking skin. © 2016 S. Karger AG, Basel.

  13. First International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions).

    PubMed

    Rageth, Christoph J; O'Flynn, Elizabeth Am; Comstock, Christopher; Kurtz, Claudia; Kubik, Rahel; Madjar, Helmut; Lepori, Domenico; Kampmann, Gert; Mundinger, Alexander; Baege, Astrid; Decker, Thomas; Hosch, Stefanie; Tausch, Christoph; Delaloye, Jean-François; Morris, Elisabeth; Varga, Zsuzsanna

    2016-09-01

    The purpose of this study is to obtain a consensus for the therapy of B3 lesions. The first International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions) including atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), classical lobular neoplasia (LN), papillary lesions (PL), benign phyllodes tumors (PT), and radial scars (RS) took place in January 2016 in Zurich, Switzerland organized by the International Breast Ultrasound School and the Swiss Minimally Invasive Breast Biopsy group-a subgroup of the Swiss Society of Senology. Consensus recommendations for the management and follow-up surveillance of these B3 lesions were developed and areas of research priorities were identified. The consensus recommendation for FEA, LN, PL, and RS diagnosed on core needle biopsy or vacuum-assisted biopsy (VAB) is to therapeutically excise the lesion seen on imaging by VAB and no longer by open surgery, with follow-up surveillance imaging for 5 years. The consensus recommendation for ADH and PT is, with some exceptions, therapeutic first-line open surgical excision. Minimally invasive management of selected B3 lesions with therapeutic VAB is acceptable as an alternative to first-line surgical excision.

  14. Morel-Lavallee lesion.

    PubMed

    Li, Hui; Zhang, Fangjie; Lei, Guanghua

    2014-01-01

    To review current knowledge of the Morel-Lavallee lesion (MLL) to help clinicians become familiar with this entity. Familiarization may decrease missed diagnoses and misdiagnoses. It could also help steer the clinician to the proper treatment choice. A search was performed via PubMed and EMBASE from 1966 to July 2013 using the following keywords: Morel-Lavallee lesion, closed degloving injury, concealed degloving injury, Morel-Lavallee effusion, Morel-Lavallee hematoma, posttraumatic pseudocyst, posttraumatic soft tissue cyst. Chinese and English language literatures relevant to the subject were collected. Their references were also reviewed. Morel-Lavallee lesion is a relatively rare condition involving a closed degloving injury. It is characterized by a filled cystic cavity created by separation of the subcutaneous tissue from the underlying fascia. Apart from the classic location over the region of the greater trochanter, MLLs have been described in other parts of the body. The natural history of MLL has not yet been established. The lesion may decrease in volume, remain stable, enlarge progressively or show a recurrent pattern. Diagnosis of MLL was often missed or delayed. Ultrasonography, computed tomography, and magnetic resonance imaging have great value in the diagnosis of MLL. Treatment of MLL has included compression, local aspiration, open debridement, and sclerodesis. No standard treatment has been established. A diagnosis of MLL should be suspected when a soft, fluctuant area of skin or chronic recurrent fluid collection is found in a region exposed to a previous shear injury. Clinicians and radiologists should be aware of both the acute and chronic appearances to make the correct diagnosis. Treatment decisions should base on association with fractures, the condition of the lesion, symptom and desire of the patient.

  15. Endoscopic submucosal dissection for early Barrett’s neoplasia

    PubMed Central

    Barret, Maximilien; Cao, Dalhia Thao; Beuvon, Frédéric; Leblanc, Sarah; Terris, Benoit; Camus, Marine; Coriat, Romain; Chaussade, Stanislas

    2015-01-01

    Introduction The possible benefit of endoscopic submucosal dissection (ESD) for early neoplasia arising in Barrett’s esophagus remains controversial. We aimed to assess the efficacy and safety of ESD for the treatment of early Barrett’s neoplasia. Methods All consecutive patients undergoing ESD for the resection of a visible lesion in a Barrett’s esophagus, either suspicious of submucosal infiltration or exceeding 10 mm in size, between February 2012 and January 2015 were prospectively included. The primary endpoint was the rate of curative resection of carcinoma, defined as histologically complete resection of adenocarcinomas without poor histoprognostic factors. Results Thirty-five patients (36 lesions) with a mean age of 66.2 ± 12 years, a mean ASA score of 2.1 ± 0.7, and a mean C4M6 Barrett’s segment were included. The mean procedure time was 191 ± 79 mn, and the mean size of the resected specimen was 51.3 ± 23 mm. En bloc resection rate was 89%. Lesions were 12 ± 15 mm in size, and 81% (29/36) were invasive adenocarcinomas, six of which with submucosal invasion. Although R0 resection of carcinoma was 72.4%, the curative resection rate was 66% (19/29). After a mean follow-up of 12.9 ± 9 months, 16 (45.7%) patients had required additional treatment, among whom nine underwent surgical resection, and seven further endoscopic treatments. Metachronous lesions or recurrence of cancer developed during the follow-up period in 17.2% of the patients. The overall complication rate was 16.7%, including 8.3% perforations, all conservatively managed, and no bleeding. The 30-day mortality was 0%. Conclusion In this early experience, ESD yielded a moderate curative resection rate in Barrett’s neoplasia. At present, improvements are needed if ESD is to replace piecemeal endoscopic mucosal resection in the management of Barrett’s neoplasia. PMID:27087948

  16. Proteoglycan depletion and size reduction in lesions of early grade chondromalacia of the patella.

    PubMed

    Väätäinen, U; Häkkinen, T; Kiviranta, I; Jaroma, H; Inkinen, R; Tammi, M

    1995-10-01

    To determine the content and molecular size of proteoglycans (PGs) in patellar chondromalacia (CM) and control cartilages as a first step in investigating the role of matrix alterations in the pathogenesis of this disease. Chondromalacia tissue from 10 patients was removed with a surgical knife. Using identical techniques, apparently healthy cartilage of the same site was obtained from 10 age matched cadavers (mean age 31 years in both groups). Additional pathological cartilage was collected from 67 patients with grades II-IV CM (classified according to Outerbridge) using a motorised shaver under arthroscopic control. The shaved cartilage chips were collected with a dense net from the irrigation fluid of the shaver. The content of tissue PGs was determined by Safranin O precipitation or uronic acid content, and the molecular size by mobility on agarose gel electrophoresis. The mean PG content of the CM tissue samples with a knife was dramatically reduced, being only 15% of that in controls. The cartilage chips collected from shaving operations of grades II, III, and IV CM showed a decreasing PG content: 9%, 5%, and 1% of controls, respectively. Electrophoretic analysis of PGs extracted with guanidium chloride from the shaved tissue samples suggested a significantly reduced size of aggrecans in the mild (grade II) lesions. These data show that there is already a dramatic and progressive depletion of PGs in CM grade II lesions. This explains the softening of cartilage, a typical finding in the arthroscopic examination of CM. The PG size reduction observed in grade II implicates proteolytic attack as a factor in the pathogenesis of CM.

  17. Pigmented skin lesion detection using random forest and wavelet-based texture

    NASA Astrophysics Data System (ADS)

    Hu, Ping; Yang, Tie-jun

    2016-10-01

    The incidence of cutaneous malignant melanoma, a disease of worldwide distribution and is the deadliest form of skin cancer, has been rapidly increasing over the last few decades. Because advanced cutaneous melanoma is still incurable, early detection is an important step toward a reduction in mortality. Dermoscopy photographs are commonly used in melanoma diagnosis and can capture detailed features of a lesion. A great variability exists in the visual appearance of pigmented skin lesions. Therefore, in order to minimize the diagnostic errors that result from the difficulty and subjectivity of visual interpretation, an automatic detection approach is required. The objectives of this paper were to propose a hybrid method using random forest and Gabor wavelet transformation to accurately differentiate which part belong to lesion area and the other is not in a dermoscopy photographs and analyze segmentation accuracy. A random forest classifier consisting of a set of decision trees was used for classification. Gabor wavelets transformation are the mathematical model of visual cortical cells of mammalian brain and an image can be decomposed into multiple scales and multiple orientations by using it. The Gabor function has been recognized as a very useful tool in texture analysis, due to its optimal localization properties in both spatial and frequency domain. Texture features based on Gabor wavelets transformation are found by the Gabor filtered image. Experiment results indicate the following: (1) the proposed algorithm based on random forest outperformed the-state-of-the-art in pigmented skin lesions detection (2) and the inclusion of Gabor wavelet transformation based texture features improved segmentation accuracy significantly.

  18. Early pulmonary toxicity following lung stereotactic body radiation therapy delivered in consecutive daily fractions.

    PubMed

    Stauder, Michael C; Macdonald, O Kenneth; Olivier, Kenneth R; Call, Jason A; Lafata, Kyle; Mayo, Charles S; Miller, Robert C; Brown, Paul D; Bauer, Heather J; Garces, Yolanda I

    2011-05-01

    Identify the incidence of early pulmonary toxicity in a cohort of patients treated with lung stereotactic body radiation therapy (SBRT) on consecutive treatment days. A total of 88 lesions in 84 patients were treated with SBRT in consecutive daily fractions (Fx) for medically inoperable non-small cell lung cancer or metastasis. The incidence of pneumonitis was evaluated and graded according to the NCI CTCAE v3.0. With a median follow-up of 15.8 months (range 2.5-28.6), the median age at SBRT was 71.8 years (range 23.8-87.8). 47 lesions were centrally located and 41 were peripheral. Most central lesions were treated with 48Gy in 4 Fx, and most peripheral lesions with 54Gy in 3 Fx. The incidence of grade ≥ 2 pneumonitis was 12.5% in all patients treated, and 14.3% among the subset of patients treated with 54Gy in 3 Fx. A total of two grade 3 toxicities were seen as one grade 5 toxicity in a patient treated for recurrence after pneumonectomy. Treating both central and peripheral lung lesions with SBRT in consecutive daily fractions in this cohort was well tolerated and did not cause excessive early pulmonary toxicity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Stroke Lesions in a Large Upper Limb Rehabilitation Trial Cohort Rarely Match Lesions in Common Preclinical Models

    PubMed Central

    Edwardson, Matthew A.; Wang, Ximing; Liu, Brent; Ding, Li; Lane, Christianne J.; Park, Caron; Nelsen, Monica A.; Jones, Theresa A; Wolf, Steven L; Winstein, Carolee J; Dromerick, Alexander W.

    2017-01-01

    Background Stroke patients with mild-moderate upper extremity (UE) motor impairments and minimal sensory and cognitive deficits provide a useful model to study recovery and improve rehabilitation. Laboratory-based investigators use lesioning techniques for similar goals. Objective Determine whether stroke lesions in an UE rehabilitation trial cohort match lesions from the preclinical stroke recovery models used to drive translational research. Methods Clinical neuroimages from 297 participants enrolled in the Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) study were reviewed. Images were characterized based on lesion type (ischemic or hemorrhagic), volume, vascular territory, depth (cortical gray matter, cortical white matter, subcortical), old strokes, and leukoaraiosis. Lesions were compared with those of preclinical stroke models commonly used to study upper limb recovery. Results Among the ischemic stroke participants, median infarct volume was 1.8 mL, with most lesions confined to subcortical structures (61%) including the anterior choroidal artery territory (30%) and the pons (23%). Of ICARE participants, <1 % had lesions resembling proximal MCA or surface vessel occlusion models. Preclinical models of subcortical white matter injury best resembled the ICARE population (33%). Intracranial hemorrhage participants had small (median 12.5 mL) lesions that best matched the capsular hematoma preclinical model. Conclusions ICARE subjects are not representative of all stroke patients, but they represent a clinically and scientifically important subgroup. Compared to lesions in general stroke populations and widely-studied animal models of recovery, ICARE participants had smaller, more subcortically-based strokes. Improved preclinical-clinical translational efforts may require better alignment of lesions between preclinical and human stroke recovery models. PMID:28337932

  20. Correlating Cognitive Decline with White Matter Lesion and Brain Atrophy MRI Measurements in Alzheimer’s Disease

    PubMed Central

    Bilello, Michel; Doshi, Jimit; Nabavizadeh, S. Ali; Toledo, Jon B.; Erus, Guray; Xie, Sharon X.; Trojanowski, John Q.; Han, Xiaoyan; Davatzikos, Christos

    2015-01-01

    Background Vascular risk factors are increasingly recognized as risks factors for Alzheimer’s disease (AD) and early conversion from mild cognitive impairment (MCI) to dementia. While neuroimaging research in AD has focused on brain atrophy, metabolic function or amyloid deposition, little attention has been paid to the effect of cerebrovascular disease to cognitive decline. Objective To investigate the correlation of brain atrophy and white matter lesions with cognitive decline in AD, MCI, and control subjects. Methods Patients with AD and MCI, and healthy subjects were included in this study. Subjects had a baseline MRI scan, and baseline and follow-up neuropsychological battery (CERAD). Regional volumes were measured, and white matter lesion segmentation was performed. Correlations between rate of CERAD score decline and white matter lesion load and brain structure volume were evaluated. In addition, voxel-based correlations between baseline CERAD scores and atrophy and white matter lesion measures were computed. Results CERAD rate of decline was most significantly associated with lesion loads located in the fornices. Several temporal lobe ROI volumes were significantly associated with CERAD decline. Voxel-based analysis demonstrated strong correlation between baseline CERAD scores and atrophy measures in the anterior temporal lobes. Correlation of baseline CERAD scores with white matter lesion volumes achieved significance in multilobar subcortical white matter. Conclusion Both baseline and declines in CERAD scores correlate with white matter lesion load and gray matter atrophy. Results of this study highlight the dominant effect of volume loss, and underscore the importance of small vessel disease as a contributor to cognitive decline in the elderly. PMID:26402108