Immunoexpression of P63 and SOX2 in triple-negative breast cancers, Indonesia

PubMed Central

Kamarlis, Reno K; Lubis, Muhammad ND; Hernowo, Bethy S; Kar, Azmi S

2018-01-01

Background: Using immunohistochemical stains to target specific breast cancer markers has become indispensable for evaluation of small diagnostic tissue specimens, and therefore novel marker cocktails for specific breast cancers are required. This study was conducted to assess the immunoexpression of P63 and SOX2 in triple negative breast cancer (TNBC), and to evaluate the predictive diagnostic value of these markers for specific types of TNBC. Methods: Histological slides and paraffin blocks of TNBC cases were collected from Dr. Hasan Sadikin Hospital, Bandung, Indonesia from 5-years period (2011-2015). Each histological slide was subjected to immunohistochemical staining for P63 (nucleus and cytoplasm) and SOX2 (nucleus), with specific primer antibodies. Immunoexpression of P63 and SOX2 was evaluated using immunoreactivity scoring. Associations between P63 and SOX2 immunoexpression and TNBC types were assessed using Mann Whitney tests. In addition, the predictive diagnostic values of these markers were assessed. Results: Forty TNBC histological slides were included, and 23 (57.5%) were Basal-like type TNBC and 17 (42.5%) were Non basal-like type TNBC. Immunoexpression of P63 nucleus and SOX2 was not different between types of TNBC. However, immunoexpression of P63 in the cytoplasm in Basal-like type TNBC was significantly higher than in Non basal-like type TNBC ( p=0.021). Predictor diagnostic value analysis suggested that immunoexpression of P63 in cytoplasm had 56.5% sensitivity and 70.6% specificity for diagnosing Basal-like type TNBC, with area under curve of 0.64.    Conclusions: Immunoexpression of P63 in the cytoplasm has a relatively weak diagnostic value to discriminate Basal-like and Non basal-like types of TNBC. PMID:29527291

Estrogen modulates sexually dimorphic contextual fear extinction in rats through estrogen receptor beta.

PubMed

Chang, Yao-Ju; Yang, Chih-Hao; Liang, Ying-Ching; Yeh, Che-Ming; Huang, Chiung-Chun; Hsu, Kuei-Sen

2009-11-01

Females and males are different in brain and behavior. These sex differences occur early during development due to a combination of genetic and hormonal factors and continue throughout the lifespan. Previous studies revealed that male rats exhibited significantly higher levels of contextual fear memory than female rats. However, it remains unknown whether a sex difference exists in the contextual fear extinction. To address this issue, male, normally cycling female, and ovariectomized (OVX) female Sprague-Dawley rats were subjected to contextual fear conditioning and extinction trials. Here we report that although male rats exhibited higher levels of freezing than cycling female rats after contextual fear conditioning, female rats subjected to conditioning in the proestrus and estrus stage exhibited an enhancement of fear extinction than male rats. An estrogen receptor (ER) beta agonist diarylpropionitrile but not an ERalpha agonist propyl-pyrazole-triol administration also enhanced extinction of contextual fear in OVX female rats, suggesting that estrogen-mediated facilitation of extinction involves the activation of ERbeta. Intrahippocampal injection of estradiol or diarylpropionitrile before extinction training in OVX female rats remarkably reduced the levels of freezing response during extinction trials. In addition, the locomotion or anxiety state of female rats does not vary across the ovarian cycle. These results reveal a crucial role for estrogen in mediating sexually dimorphic contextual fear extinction, and that estrogen-mediated enhancement of fear extinction involves the activation of ERbeta.

Estrogen receptors in skeletal metabolism: lessons from genetically modified models of receptor function.

PubMed

McCauley, Laurie K; Tözüm, Tolga F; Rosol, Thomas J

2002-01-01

Estrogens have long been known to be important for skeletal homeostasis, but their precise mechanisms of action in bone are still unclear. Mice with targeted deletions of the estrogen receptors alpha (ERalpha) and beta (ERbeta) have been generated by two research groups and several studies performed characterizing the phenotype of ERalpha knockout (ERKOalpha), ERbeta knockout (ERKObeta), or double deletion of ERalpha and ERbeta (DERKO) mice. Initial studies reported a reduction in bone mineral density in male ERKOalpha mice. More extensive analyses have been puzzling, likely because of compensatory mechanisms in ERKO mice. Furthermore, the existence of a third ER continues to be a potential explanation for some actions of estrogen in bone. Other rodent models, including the testicular feminized mouse and rat, the aromatase knockout mouse, and a rat with a dominant negative ER mutation, have added information regarding estrogen's actions in bone. This review summarizes many reports characterizing available rodent models with genetic alterations relevant to estrogen action. The sum of these reports suggests that the ERbeta is not highly protective in bone because loss of its function results in minimal alterations in the skeleton. Furthermore, loss of both the ERalpha and the ERbeta does not account for loss of estrogen action in bone, because the impact of DERKO is seemingly not as great as the impact of gonadectomy on the skeleton. Finally, through studies of ERKO mice and other rodent models of altered sex steroid action, it appears that estrogen may be more protective in the skeleton than androgens.

Link between immunoexpression of hMLH1 and hMSH2 proteins and clinical-epidemiological aspects of actinic cheilitis*

PubMed Central

Sarmento, Dmitry José de Santana; Godoy, Gustavo Pina; Miguel, Márcia Cristina da Costa; da Silveira, Éricka Janine Dantas

2016-01-01

Background The studies found in the literature associate the immunoexpression of hMLH1 and hMSH2 proteins with histologic aspects, but do not correlate it with clinical and epidemiological data. Objective To evaluate the immunoexpression of hMLH1 and hMSH2 in actinic cheilitis, correlating it with clinical characteristics. Methods We analyzed 40 cases. Histological and immunohistochemical analyses were performed. The following clinical variables were evaluated: gender, age range, ethnicity, clinical aspect and occupational sunlight exposure. Statistical evaluation included the Student t-test, while the significance level was set at 5%. Results Greater immunoexpression of hMLH1 and hMSH2 was observed in females, individuals aged over 40, and mixed-race/black patients. Furthermore, the immunoexpression of these proteins was greater in actinic cheilitis with a white-colored appearance and in patients without occupational sunlight exposure. No statistical differences were observed for the variables studied. Conclusion This study uncovered variations of hMLH1 and hMSH2 protein expression upon evaluation of clinical aspects in actinic cheilitis. PMID:27579741

Link between immunoexpression of hMLH1 and hMSH2 proteins and clinical-epidemiological aspects of actinic cheilitis.

PubMed

Sarmento, Dmitry José de Santana; Godoy, Gustavo Pina; Miguel, Márcia Cristina da Costa; Silveira, Éricka Janine Dantas da

2016-01-01

The studies found in the literature associate the immunoexpression of hMLH1 and hMSH2 proteins with histologic aspects, but do not correlate it with clinical and epidemiological data. To evaluate the immunoexpression of hMLH1 and hMSH2 in actinic cheilitis, correlating it with clinical characteristics. We analyzed 40 cases. Histological and immunohistochemical analyses were performed. The following clinical variables were evaluated: gender, age range, ethnicity, clinical aspect and occupational sunlight exposure. Statistical evaluation included the Student t-test, while the significance level was set at 5%. Greater immunoexpression of hMLH1 and hMSH2 was observed in females, individuals aged over 40, and mixed-race/black patients. Furthermore, the immunoexpression of these proteins was greater in actinic cheilitis with a white-colored appearance and in patients without occupational sunlight exposure. No statistical differences were observed for the variables studied. This study uncovered variations of hMLH1 and hMSH2 protein expression upon evaluation of clinical aspects in actinic cheilitis.

Functional characterization of estrogen receptor subtypes, ER{alpha} and ER{beta}, mediating vitellogenin production in the liver of rainbow trout

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

Leanos-Castaneda, Olga; Kraak, Glen van der

2007-10-15

The estrogen-dependent process of vitellogenesis is a key function on oviparous fish reproduction and it has been widely used as an indicator of xenoestrogen exposure. The two estrogen receptor (ER) subtypes, ER{alpha} and ER{beta}, are often co-expressed in the liver of fish. The relative contribution of each ER subtype to modulate vitellogenin production by hepatocytes was studied using selected compounds known to preferentially interact with specific ER subtypes: propyl-pyrazole-triol (PPT) an ER{alpha} selective agonist, methyl-piperidino-pyrazole (MPP) an ER{alpha} selective antagonist, and diarylpropionitrile (DPN) an ER{beta} selective agonist. First, the relative binding affinity of the test compounds to estradiol for rainbowmore » trout hepatic nuclear ER was determined using a competitive ligand binding assay. All the test ligands achieved complete displacement of specific [{sup 3}H]-estradiol binding from the nuclear ER extract. This indicates that the test ligands have the potential to modify the ER function in the rainbow trout liver. Secondly, the ability of the test compounds to induce or inhibit vitellogenin production by primary cultures of rainbow trout hepatocytes was studied. Estradiol and DPN were the only compounds that induced a dose-dependent increase on vitellogenin synthesis. The lack of vitellogenin induction by PPT indicates that ER{alpha} could not have a role on this reproductive process whereas the ability of DPN to induce vitellogenin production supports the participation of ER{beta}. In addition, this hypothesis is reinforced by the results obtained from MPP plus estradiol. On one hand, the absence of suppressive activity of MPP in the estradiol-induced vitellogenin production does not support the participation of ER{alpha}. On the other hand, once blocked ER{alpha} with MPP, the only manifestation of agonist activity of estradiol would be achieved via ER{beta}. In conclusion, the present results indicate that vitellogenin production is mainly mediated through ER{beta}, implying, furthermore that compounds which only exhibit ER{alpha} selectivity are not detected by vitellogenin bioassay.« less

Screening for estrogen and androgen receptor activities in 200 pesticides by in vitro reporter gene assays using Chinese hamster ovary cells.

PubMed Central

Kojima, Hiroyuki; Katsura, Eiji; Takeuchi, Shinji; Niiyama, Kazuhito; Kobayashi, Kunihiko

2004-01-01

We tested 200 pesticides, including some of their isomers and metabolites, for agonism and antagonism to two human estrogen receptor (hER) subtypes, hERalpha and hERbeta, and a human androgen receptor (hAR) by highly sensitive transactivation assays using Chinese hamster ovary cells. The test compounds were classified into nine groups: organochlorines, diphenyl ethers, organophosphorus pesticides, pyrethroids, carbamates, acid amides, triazines, ureas, and others. These pesticides were tested at concentrations < 10-5 M. Of the 200 pesticides tested, 47 and 33 showed hER- and hERbeta-mediated estrogenic activities, respectively. Among them, 29 pesticides had both hERalpha and hERbeta agonistic activities, and the effects of the organochlorine insecticides beta-benzene hexachloride (BHC) and delta-BHC and the carbamate insecticide methiocarb were predominantly hERbeta rather than hERalpha agonistic. Weak antagonistic effects toward hERalpha and hERbeta were shown in five and two pesticides, respectively. On the other hand, none of tested pesticides showed hAR-mediated androgenic activity, but 66 of 200 pesticides exhibited inhibitory activity against the transcriptional activity induced by 5alpha-dihydrotestosterone. In particular, the antiandrogenic activities of two diphenyl ether herbicides, chlornitrofen and chlomethoxyfen, were higher than those of vinclozolin and p,p -dichlorodiphenyl dichloroethylene, known AR antagonists. The results of our ER and AR assays show that 34 pesticides possessed both estrogenic and antiandrogenic activities, indicating pleiotropic effects on hER and hAR. We also discussed chemical structures related to these activities. Taken together, our findings suggest that a variety of pesticides have estrogenic and/or antiandrogenic potential via ER and/or AR, and that numerous other manmade chemicals may also possess such estrogenic and antiandrogenic activities. PMID:15064155

Quantitative RT-PCR analysis of estrogen receptor gene expression in laser microdissected prostate cancer tissue.

PubMed

Walton, Thomas J; Li, Geng; McCulloch, Thomas A; Seth, Rashmi; Powe, Desmond G; Bishop, Michael C; Rees, Robert C

2009-06-01

Real-time quantitative RT-PCR analysis of laser microdissected tissue is considered the most accurate technique for determining tissue gene expression. The discovery of estrogen receptor beta (ERbeta) has focussed renewed interest on the role of estrogen receptors in prostate cancer, yet few studies have utilized the technique to analyze estrogen receptor gene expression in prostate cancer. Fresh tissue was obtained from 11 radical prostatectomy specimens and from 6 patients with benign prostate hyperplasia. Pure populations of benign and malignant prostate epithelium were laser microdissected, followed by RNA isolation and electrophoresis. Quantitative RT-PCR was performed using primers for androgen receptor (AR), estrogen receptor beta (ERbeta), estrogen receptor alpha (ERalpha), progesterone receptor (PGR) and prostate specific antigen (PSA), with normalization to two housekeeping genes. Differences in gene expression were analyzed using the Mann-Whitney U-test. Correlation coefficients were analyzed using Spearman's test. Significant positive correlations were seen when AR and AR-dependent PSA, and ERalpha and ERalpha-dependent PGR were compared, indicating a representative population of RNA transcripts. ERbeta gene expression was significantly over-expressed in the cancer group compared with benign controls (P < 0.01). In contrast, PGR expression was significantly down-regulated in the cancer group (P < 0.05). There were no significant differences in AR, ERalpha or PSA expression between the groups. This study represents the first to show an upregulation of ERbeta gene expression in laser microdissected prostate cancer specimens. In concert with recent studies the findings suggest differential production of ERbeta splice variants, which may play important roles in the genesis of prostate cancer. (c) 2009 Wiley-Liss, Inc.

Isolation of linoleic acid as an estrogenic compound from the fruits of Vitex agnus-castus L. (chaste-berry).

PubMed

Liu, J; Burdette, J E; Sun, Y; Deng, S; Schlecht, S M; Zheng, W; Nikolic, D; Mahady, G; van Breemen, R B; Fong, H H S; Pezzuto, J M; Bolton, J L; Farnsworth, N R

2004-01-01

A methanol extract of chaste-tree berry (Vitex agnus-castus L.) was tested for its ability to displace radiolabeled estradiol from the binding site of estrogen receptors alpha (ERalpha) and beta (ERbeta). The extract at 46 +/- 3 microg/ml displaced 50% of estradiol from ERalpha and 64 +/- 4 microg/ml from ERbeta. Treatment of the ER+ hormone-dependent T47D:A18 breast cancer cell line with the extract induced up-regulation of ERbeta mRNA. Progesterone receptor (PR) mRNA was upregulated in the Ishikawa endometrial cancer cell line. However, chaste-tree berry extract did not induce estrogen-dependent alkaline phosphatase (AP) activity in Ishikawa cells. Bioassay-guided isolation, utilizing ER binding as a monitor, resulted in the isolation of linoleic acid as one possible estrogenic component of the extract. The use of pulsed ultrafiltration liquid chromatography-mass spectrometry, which is an affinity-based screening technique, also identified linoleic acid as an ER ligand based on its selective affinity, molecular weight, and retention time. Linoleic acid also stimulated mRNA ERbeta expression in T47D:A18 cells, PR expression in Ishikawa cells, but not AP activity in Ishikawa cells. These data suggest that linoleic acid from the fruits of Vitex agnus-castus can bind to estrogen receptors and induce certain estrogen inducible genes.

CD44 and ALDH1 immunoexpression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma.

PubMed

Ortiz, Rafael Carneiro; Lopes, Nathália Martins; Amôr, Nadia Ghinelli; Ponce, José Burgos; Schmerling, Cláudia Kliemann; Lara, Vanessa Soares; Moyses, Raquel Ajub; Rodini, Camila Oliveira

2018-05-23

Tumour metastasis has been associated with cancer stem cells, a small population with stem-like cells properties, higher rate of migration and metastatic potential compared to cells from the tumour bulk. Our aim was to evaluate the immunoexpression of the putative cancer stem cell biomarkers ALDH1 and CD44 in primary tumour and corresponding metastatic lymph nodes. Tumour tissue specimens (n=50) and corresponding metastatic lymph nodes (n=25) were surgically obtained from 50 patients with oral squamous cell carcinoma and submitted to immunohistochemistry. CD44 and ALDH1 were semi-quantitatively scored according to the proportion and intensity of positive cells within the invasive front and metastatic lymph nodes as a whole. A combined score was obtained by multiplying both parameters and later dichotomized into a final score classified as low (≤ 2) or high (> 2) immunoexpression. ALDH1 and CD44 immunoexpression was detected in both tumour sites, although the means of ALDH1 (P = 0.0985) and CD44 (P = 0.4220) cells were higher in metastasis compared to primary tumours. ALDH1 high was positively associated (P = 0.0184) with angiolymphatic invasion, while CD44 high was positively associated (P = 0.0181) with metastasis (N+). At multivariate analysis, CD44 significantly increased the odds of lymph node metastasis, regardless of T stage (OR=8,24; 1,64-65,64, p=0,0088). CD44 immunoexpression was a significant predictor of lymph node metastasis, while ALDH1 high immunostaining was associated with angiolymphatic invasion. Altogether, it suggests that immunoexpression of CD44 and ALDH1 links the cancer stem cell phenotype with oral squamous cell carcinoma invasion and metastasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[The estrogenic effect of formononetin and its effect on the expression of rats' atrium estrogen receptors].

PubMed

Xing, Dian-Xia; Liu, Xian-Ling; Xue, Cun-Kuan; Huang, Qi; Liu, Zhi-Gao; Xiong, Liang

2010-09-01

To observe the estrogenic effect of formononetin and its effect on the expressions of atrial estrogen receptor subtypes alpha and beta (ERalpha and ERbeta). 50 femal rats were randomly divided into five groups: sham group, model group, nilestriol group, formononetin groups of low and high dose. Rats in sham group were cut a piece of fat before closing the abdomen, the others were ovariectomized. Vaginal exfoliated cell were observed from the fifth day to the tenth after operation to test if the model is successful. The sham and model group were given nomal saline in 10 mL/kg by gavage, the remaining three groups were given nilestriol 2.5 mg/(kg x w), low [20 mg/(kg x d) land high dose [100 mg/(kg x d)) of formononetin by gavage respectively. In the 8th week, vaginal exfoliated cell were observed, then decapitated the rats, removed the uterus, weighed and take wright staining microscopy. The relative expressions of ERalpha and ERbeta of right atrium were detected by RT-PCR. The vaginal cells exhibit a change of estrus after had been fed with high dose of formononetin after 8 weeks. Formononetin increase the uterus coefficient and the expression of atrial ERbeta (P < 0.01), but it dose not have any effect on the expression of ERalpha (P > 0.05). Formononetin have estrogenic effect in ovariectomized rats, and it can markedly upregulate the expression of rats' atrial ERbeta.

Importance of extranuclear estrogen receptor-alpha and membrane G protein-coupled estrogen receptor in pancreatic islet survival.

PubMed

Liu, Suhuan; Le May, Cedric; Wong, Winifred P S; Ward, Robert D; Clegg, Deborah J; Marcelli, Marco; Korach, Kenneth S; Mauvais-Jarvis, Franck

2009-10-01

We showed that 17beta-estradiol (E(2)) favors pancreatic beta-cell survival via the estrogen receptor-alpha (ERalpha) in mice. E(2) activates nuclear estrogen receptors via an estrogen response element (ERE). E(2) also activates nongenomic signals via an extranuclear form of ERalpha and the G protein-coupled estrogen receptor (GPER). We studied the contribution of estrogen receptors to islet survival. We used mice and islets deficient in estrogen receptor-alpha (alphaERKO(-/-)), estrogen receptor-beta (betaERKO(-/-)), estrogen receptor-alpha and estrogen receptor-beta (alphabetaERKO(-/-)), and GPER (GPERKO(-/-)); a mouse lacking ERalpha binding to the ERE; and human islets. These mice and islets were studied in combination with receptor-specific pharmacological probes. We show that ERalpha protection of islet survival is ERE independent and that E(2) favors islet survival through extranuclear and membrane estrogen receptor signaling. We show that ERbeta plays a minor cytoprotective role compared to ERalpha. Accordingly, betaERKO(-/-) mice are mildly predisposed to streptozotocin-induced islet apoptosis. However, combined elimination of ERalpha and ERbeta in mice does not synergize to provoke islet apoptosis. In alphabetaERKO(-/-) mice and their islets, E(2) partially prevents apoptosis suggesting that an alternative pathway compensates for ERalpha/ERbeta deficiency. We find that E(2) protection of islet survival is reproduced by a membrane-impermeant E(2) formulation and a selective GPER agonist. Accordingly, GPERKO(-/-) mice are susceptible to streptozotocin-induced insulin deficiency. E(2) protects beta-cell survival through ERalpha and ERbeta via ERE-independent, extra-nuclear mechanisms, as well as GPER-dependent mechanisms. The present study adds a novel dimension to estrogen biology in beta-cells and identifies GPER as a target to protect islet survival.

Characterization of protein--DNA interactions using surface plasmon resonance spectroscopy with various assay schemes.

PubMed

Teh, Huey Fang; Peh, Wendy Y X; Su, Xiaodi; Thomsen, Jane S

2007-02-27

Specific protein-DNA interactions play a central role in transcription and other biological processes. A comprehensive characterization of protein-DNA interactions should include information about binding affinity, kinetics, sequence specificity, and binding stoichiometry. In this study, we have used surface plasmon resonance spectroscopy (SPR) to study the interactions between human estrogen receptors (ER, alpha and beta subtypes) and estrogen response elements (ERE), with four assay schemes. First, we determined the sequence-dependent receptors' binding capacity by monitoring the binding of ER to various ERE sequences immobilized on a sensor surface (assay format denoted as the direct assay). Second, we screened the relative affinity of ER for various ERE sequences using a competition assay, in which the receptors bind to an ERE-immobilized surface in the presence of competitor ERE sequences. Third, we monitored the assembly of ER-ERE complexes on a SPR surface and thereafter the removal and/or dissociation of the ER (assay scheme denoted as the dissociation assay) to determine the binding stoichiometry. Last, a sandwich assay (ER binding to ERE followed by anti-ER recognition of a specific ER subtype) was performed in an effort to understand how ERalpha and ERbeta may associate and compete when binding to the DNA. With these assay schemes, we reaffirmed that (1) ERalpha is more sensitive than ERbeta to base pair change(s) in the consensus ERE, (2) ERalpha and ERbeta form a heterodimer when they bind to the consensus ERE, and (3) the binding stoichiometry of both ERalpha- and ERbeta-ERE complexes is dependent on salt concentration. With this study, we demonstrate the versatility of the SPR analysis. With the involvement of various assay arrangements, the SPR analysis can be further extended to more than kinetics and affinity study.

Interaction of polymorphisms in the genes encoding interleukin-6 and estrogen receptor beta on the susceptibility to Parkinson's disease.

PubMed

Håkansson, Anna; Westberg, Lars; Nilsson, Staffan; Buervenich, Silvia; Carmine, Andrea; Holmberg, Björn; Sydow, Olof; Olson, Lars; Johnels, Bo; Eriksson, Elias; Nissbrandt, Hans

2005-02-05

The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system and increased levels of IL-6 have been found in patients with Parkinson's disease (PD). It is known that estrogen inhibits the production of IL-6, via action on estrogen receptors, thereby pointing to an important influence of estrogen on IL-6. In a previous study, we reported an association between a G/A single nucleotide polymorphism (SNP) at position 1730 in the gene coding for estrogen receptor beta (ERbeta) and age of onset of PD. To investigate the influence of a G/C SNP at position 174 in the promoter of the IL-6 gene, and the possible interaction of this SNP and the ERbeta G-1730A SNP on the risk for PD, the G-174C SNP was genotyped, by pyrosequencing, in 258 patients with PD and 308 controls. A significantly elevated frequency of the GG genotype of the IL-6 SNP was found in the patient group and this was most obvious among patients with an early age of onset (

Lymphatic vascular endothelial hyaluronan receptor-1 immunoexpression in placenta of HIV infected pre-eclamptic women.

PubMed

Onyangunga, Onankoy A; Moodley, Jagidesa; Merhar, Vesselina; Ofusori, David A; Naicker, Thajasvarie

2016-09-01

Lymphangiogenesis is the formation of new vessels from pre-existing lymphatic vessels. Data on lymphangiogenesis in the placenta of HIV-infected pre-eclamptics are sparse and the findings are conflicting. The aim of this novel study was to evaluate LYVE-1 immunoexpression in the placenta of HIV infected normotensive versus pre-eclamptic women. Placental tissue was obtained from normotensive and pre-eclamptic women stratified according to their HIV status. The pre-eclamptic group was divided into early (<34 weeks) and late (>34 weeks) onset. Immunohistochemistry utilized mouse anti-human LYVE-1 antibody and was morphometrically evaluated. LYVE-1 immunostaining was localized within endothelium of the arterial supply and venous drainage of both conducting and exchange villi as well as within medial cells of arteries. LYVE-1 immunostained macrophage-like cells were observed within the fetal and maternal circulation. LYVE-1 immunoexpression was higher (p=0.0001) in HIV positive cohort, regardless of pregnancy and villous type. Irrespective of HIV status and pregnancy type, LYVE-1 immunoexpression was significantly elevated in the conducting compared to the exchange villi (p=0.01). LYVE-1 immunoexpression was higher in N and LOPE compared to EOPE groups for both conducting and exchange villi types respectively (p=0.0001 and p=0.006). There is a decrease of LYVE-1 expression in EOPE+ (conducting villi) and EOPE- (exchange villi) compared to N and LOPE subgroups. This study provides a novel insight into an up-regulation of LYVE-1 expression in the fetal circulation of conducting and exchange villi of HIV-infected pre-eclamptics. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Tumorigenesis of K-ras mutation in human endometrial carcinoma via upregulation of estrogen receptor.

PubMed

Tu, Zheng; Gui, Liming; Wang, Jianliu; Li, Xiaoping; Sun, Pengming; Wei, Lihui

2006-05-01

To investigate the tumorigenesis of mutant [12Asp]-K-ras in endometrial carcinoma and its relationship with ER. We constructed pcDI-[12Asp]K-ras4B by inserting full-length [12Asp]K-ras4B from human endometrial carcinoma Hec-1A cells, into pcDI vector. Cell proliferation of NIH3T3 after transfection with pcDI-[12Asp]K-ras4B was measured by MTT assay. The cell transformation was determined by colony formation and tumor nodule development. [12Asp]-K-ras4B-NIH3T3 cells were transfected with constitutively active pCMV-RafCAAX and dominant-negative pCMV-RafS621A. Cell growth was measured by MTT assay and [3H]thymidine incorporation. After transfected with pcDI-[12Asp]K-ras4B or pCMV-RafS621A, the cells were harvested for Western blot and reporter assay to determine the expression and transcriptional activity of ERalpha and ERbeta, respectively. [12Asp]-K-ras4B enhanced NIH3T3 cells proliferation after 48 h post-transfection (P < 0.05). More colonies were grown 10 days after incubating pcDI-[12Asp]-K-ras4B-NIH3T3 cells (13.48%) than pcDI-NIH3T3 (4.26%) or untreated NIH3T3 (2.33%). The pcDI-[12Asp]-K-ras4B-NIH3T3 cells injected to the nude mice Balb/C developed tumor nodules with poor-differentiated cells after 12 days. An increase of ERalpha and ERbeta was observed in pcDI-[12Asp]-K-ras4B-NIH3T3 cells. RafS621A downregulated ERalpha and ERbeta expression. Estrogen induced the ER transcriptional activity by 5-fold in pcDI-NIH3T3 cells, 13-fold in pcDI-[12Asp]K-ras4B-NIH3T3 and 19-fold in HEC-1A. RafS621A suppressed the ER transcriptional activity. K-ras mutation induces tumorigenesis in endometrium, and this malignant transformation involves Raf signaling pathway and ER.

The anti-oestrogen ICI 182,780, but not tamoxifen, inhibits the growth of MCF-7 breast cancer cells refractory to long-term oestrogen deprivation through down-regulation of oestrogen receptor and IGF signalling.

PubMed

Martin, L-A; Pancholi, S; Chan, C M W; Farmer, I; Kimberley, C; Dowsett, M; Johnston, S R D

2005-12-01

Long-term culture of MCF-7 wild-type (wt) cells in steroid-depleted medium (LTED) results in hypersensitivity to oestradiol (E2) coinciding with elevated levels of ERalpha and enhanced growth factor signalling. In this study, we aimed to compare the effects of the pure anti-oestrogen ICI 182,780 (ICI) with the competitive anti-oestrogen tamoxifen (TAM) on oestrogen and IGF signalling in these cells. Wt MCF-7 and LTED cells were treated with a log 7 concentration range of E2, TAM or ICI. Effects on cell growth, ERalpha transactivation, expression of ERalpha, ERbeta and components of the IGF pathway were measured with and without insulin. In the presence of insulin, growth of LTED cells was refractory to TAM but inhibited by ICI and E2. In the absence of insulin, LTED cells showed persistent hypersensitivity to E2, and remained inhibited by ICI but were largely unaffected by TAM. ICI but not TAM inhibited ER-mediated gene transcription and treatment with ICI resulted in a dose-dependent reduction in ERalpha levels whilst having no effect on ERbeta expression. IGF-I receptor and insulin receptor substrate 2 levels were increased in LTED versus the Wt MCF-7 cells, and ICI but not TAM reduced their expression in a dose-dependent fashion. Thus IGF signalling as well as ERalpha expression and function are enhanced during LTED. While the resultant cells are resistant to TAM, ICI down-regulates ERalpha, reducing IGF signalling and cell growth. These results support the use of ICI in women with ER-positive breast cancer who have relapsed on an aromatase inhibitor.

Androgen receptor repeat length polymorphism associated with male-to-female transsexualism.

PubMed

Hare, Lauren; Bernard, Pascal; Sánchez, Francisco J; Baird, Paul N; Vilain, Eric; Kennedy, Trudy; Harley, Vincent R

2009-01-01

There is a likely genetic component to transsexualism, and genes involved in sex steroidogenesis are good candidates. We explored the specific hypothesis that male-to-female transsexualism is associated with gene variants responsible for undermasculinization and/or feminization. Specifically, we assessed the role of disease-associated repeat length polymorphisms in the androgen receptor (AR), estrogen receptor beta (ERbeta), and aromatase (CYP19) genes. Subject-control analysis included 112 male-to-female transsexuals and 258 non-transsexual males. Associations and interactions were investigated between CAG repeat length in the AR gene, CA repeat length in the ERbeta gene, and TTTA repeat length in the CYP19 gene and male-to-female transsexualism. A significant association was identified between transsexualism and the AR allele, with transsexuals having longer AR repeat lengths than non-transsexual male control subjects (p=.04). No associations for transsexualism were evident in repeat lengths for CYP19 or ERbeta genes. Individuals were then classified as short or long for each gene polymorphism on the basis of control median polymorphism lengths in order to further elucidate possible combined effects. No interaction associations between the three genes and transsexualism were identified. This study provides evidence that male gender identity might be partly mediated through the androgen receptor.

Immunoexpression of interleukin 17, transforming growth factor β1, and forkhead box P3 in periapical granulomas, radicular cysts, and residual radicular cysts.

PubMed

Andrade, Ana Luiza Dias Leite de; Nonaka, Cassiano Francisco Weege; Gordón-Núñez, Manuel Antonio; Freitas, Roseana de Almeida; Galvão, Hébel Cavalcanti

2013-08-01

Different cell types and cytokines have been identified as contributors to the formation of periapical lesions. In this perspective, this study aimed to evaluate the immunoexpression of interleukin (IL)-17, transforming growth factor (TGF)-β1, and the forkhead box P3 (FoxP3) in periapical lesions, correlating them with the type of lesion, the intensity of the inflammatory infiltrate, and the thickness of the cystic epithelial lining. Twenty periapical granulomas (PGs), 20 radicular cysts (RCs), and 20 residual radicular cysts (RRCs) were submitted to immunohistochemical analysis using anti-IL-17, anti-TGF-β1, and anti-FoxP3 antibodies. In comparison with PGs and RCs, RRCs exhibited a lower immunoexpression of IL-17 and TGF-β1 (P = .021 and P < .001, respectively). The number of FoxP3+ cells increased in this order: RRCs, RCs, and PGs (P < .001). In comparison with lesions with inflammatory infiltrates grades I and II, lesions with inflammatory infiltrate grade III exhibited a higher number of FoxP3+ cells (P = .002). Similarly, in comparison with lesions with inflammatory infiltrates grades II and III, lesions with inflammatory infiltrate grade I showed a tendency for a lower expression of IL-17 and TGF-β1 (P = .085 and P = .051, respectively). For all groups, there was a positive correlation between the immunoexpressions of IL-17 and TGF-β1 (P < .05). Positive correlations between the number of FoxP3+ cells and the immunoexpressions of IL-17 and TGF-β1 (P < .05) were found only in PGs. Th17 and Treg cells seem to interact at the site of injury, suggesting the involvement of proinflammatory and immunoregulatory cytokines in the pathogenesis of periapical lesions. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

[Immunoexpression of c-erbB-2 in intraductal proliferative lesions of the female breast].

PubMed

Oliveira, Agliberto Barbosa de; De Luca, Laurival Antônio; Carvalho, Grigna Teixeira; Arias, Victor Eduardo Arua; Carvalho, Lídia Raquel de; Assunção, Maria do Carmo

2004-01-01

Genetic modifications are related to genesis and development of cancer. Neoplasias in various organs express the c-erbB-2 oncogene. In intraductal proliferations of the breast it has been assessed as a risk factor for subsequent development of carcinoma. The c-erbB-2 immunoexpression in intraductal epithelial proliferations and the relationship with histopathological characteristics of ductal carcinoma in situ (DCIS) were evaluated. File material from 88 women, which were tissue samples formalin-fixed, paraffin-embedded blocks, was used. Of these 51 presented with DCIS and 37 with ductal hyperplasia without atypia. Ages of the women ranged from 35 to 76 years. All cases were reviewed and nuclear grade, presence of necrosis, preponderance of histological subtype and its extension were verified. Specimens were obtained for the c-erB-2 immunohistochemical study of 84 of the women in question. No expression of the oncogene was verified in the hyperplasias without atypias and in tissues adjacent to all tissue samples. Expression of c-erbB-2 was verified in 9 (19.1%) of the DCIS (p = 0.0001). Immunoexpression was not related to the extension of the lesions. The c-erbB-2 immunoexpression in DCIS was correlated to the histological subtype (p = 0.019), necrosis (p = 0.0066), nuclear grade (p = 0.0084) and Van Nuys Classification (p = 0.039). Expression of c-erbB-2 was significant in proliferative lesions with risk (DCIS) and was correlated to histopathological characteristics: high nuclear grade, presence of necrosis and comedy subtype. There was no expression in the hyperplasias without atypias and adjacent tissues.

E-cadherin regulators are differentially expressed in the epithelium and stroma of keratocystic odontogenic tumors.

PubMed

Porto, Lia Pontes Arruda; dos Santos, Jean Nunes; Ramalho, Luciana Maria Pedreira; Figueiredo, Andreia Leal; Carneiro Júnior, Bráulio; Gurgel, Clarissa Araújo; Paiva, Katiúcia Batista Silva; Xavier, Flávia Caló Aquino

2016-04-01

The epithelial-mesenchymal transition (EMT) is the process where cells lose their epithelial features and acquire properties of typical mesenchymal cells. The dissociation of tumor cells due to changes in cell-cell adhesion is one of the key principles of tumor invasion and EMT. Thus, the knowledge of the molecular features of EMT in keratocyst odontogenic tumor (KOT) can provide useful markers to aid in the diagnosis and prognosis and perhaps contribute to an alternative therapeutic approach as it shows an aggressive clinical behavior and high recurrence rates. This study aimed to evaluate the EMT in KOT by the immunoexpression of E-cadherin, N-cadherin, Snail, and Slug and comparing to radicular cysts and dental follicles. Thirty-two KOTs, 15 radicular cysts, and 08 dental follicles were used for immunohistochemistry, evaluating the extent, intensity, labeling pattern, cellular compartment in the epithelium and stroma, and the presence of inflammation. E-cadherin was preserved in most cases of keratocystic odontogenic tumor. N-cadherin was increased in the tumor epithelium, a result that was positively correlated with the heterogeneous and nuclear immunoexpression of Slug in the epithelium; Slug also correlated with high Snail immunoexpression. N-cadherin was positively correlated with Slug in the stroma of keratocystic odontogenic tumors. The high immunoexpression of Snail and nuclear Slug in keratocystic odontogenic tumors suggests these proteins as transcription factors without necessarily participating in 'cadherin switching'. However, the knowledge of their induction of the epithelial-mesenchymal transition in odontogenic tumors is still limited. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

TWIST and p-Akt immunoexpression in normal oral epithelium oral dysplasia and in oral squamous cell carcinoma

PubMed Central

Yamamoto, Fernanda-Paula; Corrêa Pontes, Flávia-Sirotheau; Cury, Sérgio-Elias; Fonseca, Felipe-Paiva; Rebelo-Pontes, Hélder; Pinto-Júnior, Décio-dos Santos

2012-01-01

Objectives: The aim of this study was to evaluate the immunoexpression of TWIST and p-Akt proteins in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC), correlating their expressions with the histological features of the lesions. Study design: Immunohistochemical studies were carried out on 10 normal oral epithelium, 30 OL and 20 OSCC formalin-fixed, paraffin-embedded tissue samples. Immunoperoxidase reactions for TWIST and p-Akt proteins were applied on the specimens and the positivity of the reactions was calculated for 1000 epithelial cells. Results: Kruskal-Wallis and Dunn’s post tests revealed a significant difference in TWIST and p-Akt immunoexpression among normal oral mucosa, OL and OSCC. In addition, a significant positive correlation was found between TWIST and p-Akt expressions according to the Pearson’s correlation test. Conclusions: The results obtained in the current study suggest that TWIST and p-Akt may participate of the multi-step process of oral carcinogenesis since its early stages. Key words: Oral cancer, oral leukoplakia, dysplasia, immunohistochemistry. PMID:21743395

Identification of human antibody fragment clones specific for tetanus toxoid in a bacteriophage. lambda. immunoexpression library

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

Mullinax, R.L.; Gross, E.A.; Amberg, J.R.

1990-10-01

The authors have applied a molecular biology approach to the identification of human monoclonal antibodies. Human peripheral blood lymphocyte mRNA was converted to cDNA and a select subset was amplified by the polymerase chain reaction. These products, containing coding sequences for numerous immunoglobulin heavy- and {kappa} light-chain variable and constant region domains, were inserted into modified bacteriophase {lambda} expression vectors and introduced into Escherichia coli by infection to yield a combinatorial immunoexpression library. Clones with binding activity to tetanus toxoid were identified by filter hybridization with radiolabeled antigen and appeared at a frequency of 0.2{percent} in the library. These humanmore » antigen binding fragments, consisting of a heavy-chain fragment covalently linked to a light chain, displayed high affinity of binding to tetanus toxoid with equilibrium constants in the nanomolar range but did not cross-react with other proteins tested. They estimate that this human immunoexpression library contains 20,000 clones with high affinity and specificity to our chosen antigen.« less

Immunoexpression of vascular endothelial growth factor in periapical granulomas, radicular cysts, and residual radicular cysts.

PubMed

Nonaka, Cassiano Francisco Weege; Maia, Alexandre Pinto; Nascimento, George João Ferreira do; de Almeida Freitas, Roseana; Batista de Souza, Lélia; Galvão, Hébel Cavalcanti

2008-12-01

Our aim was to assess and compare the immunoexpression of vascular endothelial growth factor (VEGF) in periapical granulomas (PGs), radicular cysts (RCs), and residual radicular cysts (RRCs), relating it to the angiogenic index and the intensity of the inflammatory infiltrate. Twenty PGs, 20 RCs, and 10 RRCs were evaluated by immunohistochemistry using anti-VEGF antibody. Angiogenic index was determined by microvessel count (MVC) using anti-von Willebrand factor antibody. The PGs and RCs showed higher expression of VEGF than the RRCs. Lesions presenting few inflammatory infiltrate revealed the lowest immunoexpression of VEGF (P < .05). Irrespective of the intensity of the inflammatory infiltrate, most of the RCs and RRCs showed moderate to strong epithelial expression of VEGF. Lesions showing dense inflammatory infiltrate presented higher MVC indices (P < .05). VEGF expression and MVC did not reveal a significant correlation (P > .05). VEGF is present in periapical inflammatory lesions but at a lower level in RRCs. The expression of this proangiogenic factor is closely related to the intensity of the inflammatory infiltrate in these lesions.

Immunoexpression of GLUT-1 and angiogenic index in pleomorphic adenomas, adenoid cystic carcinomas, and mucoepidermoid carcinomas of the salivary glands.

PubMed

de Souza, Lélia Batista; de Oliveira, Lucileide Castro; Nonaka, Cassiano Francisco Weege; Lopes, Maria Luiza Diniz de Sousa; Pinto, Leão Pereira; Queiroz, Lélia Maria Guedes

2017-06-01

This study aimed to evaluate and compare the immunoexpression of glucose transporter-1 (GLUT-1) and angiogenic index between pleomorphic adenomas (PAs), adenoid cystic carcinomas (ACCs), and mucoepidermoid carcinomas (MECs) of the salivary glands, and establish associations with the respective subtype/histological grade. Twenty PAs, 20 ACCs, and 10 MECs were submitted to morphological and immunohistochemical analysis. GLUT-1 expression was semi-quantitatively evaluated and angiogenic index was assessed by microvessel counts using anti-CD34 antibody. Higher GLUT-1 immunoexpression was observed in the MECs compared to PAs and ACCs (p = 0.022). Mean number of microvessels was 66.5 in MECs, 40.4 in PAs, and 21.2 in ACCs (p < 0.001). GLUT-1 expression and angiogenic index showed no significant correlation in the tumors studied. Results suggest that differences in biological behavior of the studied tumors are related to GLUT-1. Benign and malignant salivary gland tumors differ in the angiogenic index; however, angiogenesis may be independent of the tumor cell's metabolic demand.

Deregulation of PAX2 expression in renal cell tumours: mechanisms and potential use in differential diagnosis

PubMed Central

Patrício, Patrícia; Ramalho-Carvalho, João; Costa-Pinheiro, Pedro; Almeida, Mafalda; Barros-Silva, João Diogo; Vieira, Joana; Dias, Paula Cristina; Lobo, Francisco; Oliveira, Jorge; Teixeira, Manuel R; Henrique, Rui; Jeronimo, Carmen

2013-01-01

Expression of PAX2 (Paired-box 2) is suppressed through promoter methylation at the later stages of embryonic development, but eventually reactivated during carcinogenesis. Pax-2 is commonly expressed in the most prevalent renal cell tumour (RCT) subtypes—clear cell RCC (ccRCC), papillary RCC (pRCC) and oncocytoma—but not in chromophobe RCC (chrRCC), which frequently displays chromosome 10 loss (to which PAX2 is mapped). Herein, we assessed the epigenetic and/or genetic alterations affecting PAX2 expression in RCTs and evaluated its potential as biomarker. We tested 120 RCTs (30 of each main subtype) and four normal kidney tissues. Pax-2 expression was assessed by immunohistochemistry and PAX2 mRNA expression levels were determined by quantitative RT-PCR. PAX2 promoter methylation status was assessed by methylation-specific PCR and bisulfite sequencing. Chromosome 10 and PAX2 copy number alterations were determined by FISH. Pax-2 immunoexpression was significantly lower in chrRCC compared to other RCT subtypes. Using a 10% immunoexpression cut-off, Pax-2 immunoreactivity discriminated chrRCC from oncocytoma with 67% sensitivity and 90% specificity. PAX2 mRNA expression was significantly lower in chrRCC, compared to ccRCC, pRCC and oncocytoma, and transcript levels correlated with immunoexpression. Whereas no promoter methylation was found in RCTs or normal kidney, 69% of chrRCC displayed chromosome 10 monosomy, correlating with Pax-2 immunoexpression. We concluded that Pax-2 expression might be used as an ancillary tool to discriminate chrRCC from oncocytomas with overlapping morphological features. The biological rationale lies on the causal relation between Pax-2 expression and chromosome 10 monosomy, but not PAX2 promoter methylation, in chrRCC. PMID:23890189

Canine gastric carcinoma: immunohistochemical expression of cell cycle proteins (p53, p21, and p16) and heat shock proteins (Hsp27 and Hsp70).

PubMed

Carrasco, V; Canfrán, S; Rodríguez-Franco, F; Benito, A; Sáinz, A; Rodríguez-Bertos, A

2011-01-01

Immunohistochemical staining for cell cycle proteins and heat shock proteins was performed on 17 canine gastric carcinomas. The immunoexpression of p53, p21, p16, Hsp27, and Hsp70 was investigated. A study was conducted to determine the histological type and parameters related to tumor malignancy. Possible associations and trends were assessed between the immunoexpression of each protein and tumor type as well as specific parameters of malignancy. High intratumor frequency of cellular p53 immunostaining was observed (61.96% average), but lower frequencies of p21 and p16 expression were present (34.65% and 10.41%, respectively). The p53 overexpression was associated with tumor infiltration (P = .0258). Expression of p21 was lower in undifferentiated carcinomas, and the loss of expression was associated with histopathological parameters characteristic of a poor prognosis such as lymphatic vessel invasion (P = .0258). The lack of p16 immunoreactivity was related to histopathological characteristics of malignancy such as the presence of evident and multiple nucleoli (P = .0475). In contrast, deep tumor infiltration was observed in those carcinomas with a high p16 index (P = .0475). Hsp70 appeared to be overexpressed in all gastric neoplasms included in this study. This is in contrast to Hsp27, because a group of tumors showed complete lack of Hsp27 immunoexpression, whereas the others displayed extensive Hsp27 immunostaining. The differences in Hsp27 did not correlate with any of the histopathological parameters, but Hsp27 immunoexpression was higher in the undifferentiated carcinoma. No significant differences in the expression of the proteins were found in canine gastric carcinomas according to their histological type. These findings may be useful for establishing a prognosis for canine gastric carcinoma.

Immunoexpression of cleaved caspase-3 shows lower apoptotic area indices in lip carcinomas than in intraoral cancer.

PubMed

Leite, Ana Flávia Schueler de Assumpção; Bernardo, Vagner Gonçalves; Buexm, Luisa Aguirre; Fonseca, Eliene Carvalho da; Silva, Licínio Esmeraldo da; Barroso, Danielle Resende Camisasca; Lourenço, Simone de Queiroz Chaves

2016-01-01

This study aimed to evaluate apoptosis by assessing cleaved caspase-3 immunoexpression in hyperplastic, potentially malignant disorder (PMD), and malignant tumors in intraoral and lower lip sites. A retrospective study using paraffin blocks with tissues from patients with inflammatory fibrous hyperplasia (IFH), actinic cheilitis, oral leukoplakia, lower lip and intraoral squamous cell carcinoma (SCC) was performed. The tissues were evaluated by immunohistochemical analysis with anti-cleaved caspase-3 antibody. Apoptotic area index was then correlated with lesion type. From 120 lesions assessed, 55 (46%) were cleaved caspase-3-positive. The SCC samples (n=40) had the highest apoptotic area indices (n=35; 87.5%). Significant differences were detected between SCCs and PMDs (p=0.0003), as well as SCCs and IFHs (p=0.001), regarding caspase-3 immunopositivity. Carcinomas of the lower lip had lower apoptotic area indices than intraoral cancer (p=0.0015). Cleaved caspase-3 immunoexpression showed differences in oral SCCs and PMDs and demonstrated a distinct role of apoptosis in carcinogenesis of intraoral and lower lip cancer. In future, the expression of cleaved caspase-3 with other target molecules in oral cancer may be helpful in delineating the prognosis and treatment of these tumors.

Columnar cell lesions and pseudoangiomatous hyperplasia like stroma: is there an epithelial-stromal interaction?

PubMed

Recavarren, Rosemary A; Chivukula, Mamatha; Carter, Gloria; Dabbs, David J

2009-10-10

The significance of association between cancer and its microenvironment has been increasingly recognized. It has been shown in animal models that interaction between neoplastic epithelial cells and adjacent stroma can modulate tumor behavior. Carcinoma associated stromal cells can transform normal epithelial cells into neoplastic cells. In breast, columnar cell lesions are non-obligate precursors of low grade ductal carcinoma in situ. Columnar cell lesions can be seen intimately associated with PASH-like-stroma, a lesion we termed as CCPLS. Our aim is to investigate epithelial-stromal interactions in CCPLS and compare them to PASH without columnar cell lesions in breast core needle biopsies. Normal terminal duct lobular unit (TDLU) epithelium was seen in association with columnar cell lesions as well as PASH. Eight (8) cases of each category were examined by a panel of immunostains: CD117 (C-kit), CD34, CD105, bFGF, AR, ER-beta, MIB-1. We observed a markedly decreased expression of c-kit in columnar cell lesions compared to TDLU-epithelium. CD105 showed a quantitative increase in activated vessels in CCPLS compared to PASH. A subset of CCPLS and PASH were androgen receptor positive. A strong nuclear positivity for ER-beta is observed in the epithelium and stroma of all CCPLS cases. We conclude that (1) activated blood vessels predominate in CCPLS; (2) A molecular alteration is signified by c-kit loss in columnar cell lesions; (3) ER-beta and androgen receptor positivity indicate CCPLS are hormonally responsive lesions. Our study suggests an intimate vascular and hormone dependent epithelial-stromal interaction exists in CCPLS lesions.

Expression of estrogen receptors alpha and beta in the corpus luteum and uterus from non-pregnant and pregnant llamas.

PubMed

Powell, Susan A; Smith, Bradford B; Timm, Karen I; Menino, Alfred R

2007-08-01

Because estrogen may be involved in maternal recognition of pregnancy and embryonic migration in llamas, expression of estrogen receptor subtypes alpha (ERalpha) and beta (ERbeta) was evaluated in corpus luteum (CL), endometrium, and uterus using relative RT-PCR. Tissues were recovered from sterile-mated (SM) and pregnant (PG) females during Days 7-11 and 7-13 (Day 0 = day of mating), respectively, and follicular phase and juvenile females. Luteal expression of ERalpha and beta was similar (P > 0.10) in SM and PG females and within Days 7-11, however, expression of ERalpha in ovarian tissue from follicular phase females was greater (P < 0.05) than Days 7 and 9 CL. Uterus expressed less ERalpha and beta compared to endometrium (P = 0.07 and P < 0.01, respectively). Expression of ERalpha was greater (P < 0.05) in Day 7 and follicular phase uteri than Days 9 and 11, Day 13 PG and juvenile uteri. Uterine ERbeta expression was greater (P = 0.09) in PG versus SM females and in mated compared to follicular phase females (P < 0.05). Endometrial expression of ERalpha and beta did not differ (P > 0.10) between SM and PG females or by day. The presence of luteal ER during this period may mean a role for estradiol in maternal recognition of pregnancy. Observed increases in uterine ER expression with no changes in endometrium suggest expression increased in myometrium and/or perimetrium. Upregulation of myometrial ERbeta in PG females may be involved in supporting uterine migration of the embryo.

Variations in maternal care alter corticosterone and 17beta-estradiol levels, estrous cycle and folliculogenesis and stimulate the expression of estrogen receptors alpha and beta in the ovaries of UCh rats

PubMed Central

2011-01-01

Background Variations in maternal care are associated with neonatal stress, hormonal disturbances and reproductive injuries during adulthood. However, the effects of these variations on sex hormones and steroid receptors during ovary development remain undetermined. This study aimed to investigate whether variations in maternal care are able to influence the hormonal profile, follicular dynamics and expression of AR, ER-alpha and ER-beta in the ovaries of UCh rat offspring. Methods Twenty-four adult UCh rats, aged 120 days, were randomly divided into two groups (UChA and UChB) and mated. Maternal care was assessed from birth (day 0) to the 10th postnatal day (PND). In adulthood, twenty adult female rats (UChA and UChB offspring; n = 10/group), aged 120 days, were euthanized by decapitation during the morning estrus. Results UChA females (providing high maternal care) more frequently displayed the behaviors of carrying pups, as well as licking/grooming and arched back nursing cares. Also, mothers providing high care had elevated corticosterone levels. Additionally, offspring receiving low maternal care showed the highest estrous cycle duration, increased corticosterone and 17beta-estradiol levels, overexpression of receptors ER-alpha and ER-beta, increased numbers of primordial, antral and mature follicles and accentuated granulosa cell proliferation. Conclusions Our study suggests that low maternal care alters corticosterone and 17beta-estradiol levels, disrupting the estrous cycle and folliculogenesis and differentially regulating the expression of ER-alpha and ER-beta in the ovaries of adult rats. PMID:22192617

The immunoexpression of p53 and Snail in endometrioid endometrial carcinomas.

PubMed

Dragomirescu, Mihaela; Stepan, Alex Emilian; Mărgăritescu, Claudiu; Simionescu, Cristiana Eugenia

2018-01-01

Endometrial cancer is one of the most common tumors in women worldwide. P53 has a well-known function as tumor suppressor, but it can also regulate the tissues metabolism, differentiation and development. Snail is a zinc-finger transcription factor, involved in the cell differentiation and survival. We analyzed the immunoexpression of p53 and Snail in 55 cases of endometrioid endometrial carcinoma (EEC), in relation with the histopathological prognosis parameters and tumoral compartments, respectively intratumoral and advancing edge areas. For both markers, we found a statistically significant association with histological grade, in relation with tumoral compartments. P53 and Snail can be used in developing EEC targeted treatment.

Homeobox A7 stimulates breast cancer cell proliferation by up-regulating estrogen receptor-alpha

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

Zhang, Yu; Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4; Cheng, Jung-Chien

2013-11-01

Highlights: •HOXA7 regulates MCF7 cell proliferation. •HOXA7 up-regulates ERα expression. •HOXA7 mediates estrogen-induced MCF7 cell proliferation. -- Abstract: Breast cancer is the most common hormone-dependent malignancy in women. Homeobox (HOX) transcription factors regulate many cellular functions, including cell migration, proliferation and differentiation. The aberrant expression of HOX genes has been reported to be associated with human reproductive cancers. Estradiol (E2) and its nuclear receptors, estrogen receptor (ER)-alpha and ER-beta, are known to play critical roles in the regulation of breast cancer cell growth. However, an understanding of the potential relationship between HOXA7 and ER in breast cancer cells is limited.more » In this study, our results demonstrate that knockdown of HOXA7 in MCF7 cells significantly decreased cell proliferation and ERα expression. In addition, HOXA7 knockdown attenuated E2-induced cell proliferation as well as progesterone receptor (PR) expression. The stimulatory effects of E2 on cell proliferation and PR expression were abolished by co-treatment with ICI 182780, a selective ERα antagonist. In contrast, overexpression of HOXA7 significantly stimulated cell proliferation and ERα expression. Moreover, E2-induced cell proliferation, as well as PR expression, was enhanced by the overexpression of HOXA7. Neither knockdown nor overexpression of HOXA7 affected the ER-beta levels. Our results demonstrate a novel mechanistic role for HOXA7 in modulating breast cancer cell proliferation via regulation of ERα expression. This finding contributes to our understanding of the role HOXA7 plays in regulating the proliferation of ER-positive cancer cells.« less

Immunoexpression of cleaved caspase-3 shows lower apoptotic area indices in lip carcinomas than in intraoral cancer

PubMed Central

LEITE, Ana Flávia Schueler de Assumpção; BERNARDO, Vagner Gonçalves; BUEXM, Luisa Aguirre; da FONSECA, Eliene Carvalho; da SILVA, Licínio Esmeraldo; BARROSO, Danielle Resende Camisasca; LOURENÇO, Simone de Queiroz Chaves

2016-01-01

ABSTRACT Objective This study aimed to evaluate apoptosis by assessing cleaved caspase-3 immunoexpression in hyperplastic, potentially malignant disorder (PMD), and malignant tumors in intraoral and lower lip sites. Material and Methods A retrospective study using paraffin blocks with tissues from patients with inflammatory fibrous hyperplasia (IFH), actinic cheilitis, oral leukoplakia, lower lip and intraoral squamous cell carcinoma (SCC) was performed. The tissues were evaluated by immunohistochemical analysis with anti-cleaved caspase-3 antibody. Apoptotic area index was then correlated with lesion type. Results From 120 lesions assessed, 55 (46%) were cleaved caspase-3-positive. The SCC samples (n=40) had the highest apoptotic area indices (n=35; 87.5%). Significant differences were detected between SCCs and PMDs (p=0.0003), as well as SCCs and IFHs (p=0.001), regarding caspase-3 immunopositivity. Carcinomas of the lower lip had lower apoptotic area indices than intraoral cancer (p=0.0015). Conclusions Cleaved caspase-3 immunoexpression showed differences in oral SCCs and PMDs and demonstrated a distinct role of apoptosis in carcinogenesis of intraoral and lower lip cancer. In future, the expression of cleaved caspase-3 with other target molecules in oral cancer may be helpful in delineating the prognosis and treatment of these tumors. PMID:27556207

Deregulation of PAX2 expression in renal cell tumours: mechanisms and potential use in differential diagnosis.

PubMed

Patrício, Patrícia; Ramalho-Carvalho, João; Costa-Pinheiro, Pedro; Almeida, Mafalda; Barros-Silva, João Diogo; Vieira, Joana; Dias, Paula Cristina; Lobo, Francisco; Oliveira, Jorge; Teixeira, Manuel R; Henrique, Rui; Jeronimo, Carmen

2013-08-01

Expression of PAX2 (Paired-box 2) is suppressed through promoter methylation at the later stages of embryonic development, but eventually reactivated during carcinogenesis. Pax-2 is commonly expressed in the most prevalent renal cell tumour (RCT) subtypes-clear cell RCC (ccRCC), papillary RCC (pRCC) and oncocytoma--but not in chromophobe RCC (chrRCC), which frequently displays chromosome 10 loss (to which PAX2 is mapped). Herein, we assessed the epigenetic and/or genetic alterations affecting PAX2 expression in RCTs and evaluated its potential as biomarker. We tested 120 RCTs (30 of each main subtype) and four normal kidney tissues. Pax-2 expression was assessed by immunohistochemistry and PAX2 mRNA expression levels were determined by quantitative RT-PCR. PAX2 promoter methylation status was assessed by methylation-specific PCR and bisulfite sequencing. Chromosome 10 and PAX2 copy number alterations were determined by FISH. Pax-2 immunoexpression was significantly lower in chrRCC compared to other RCT subtypes. Using a 10% immunoexpression cut-off, Pax-2 immunoreactivity discriminated chrRCC from oncocytoma with 67% sensitivity and 90% specificity. PAX2 mRNA expression was significantly lower in chrRCC, compared to ccRCC, pRCC and oncocytoma, and transcript levels correlated with immunoexpression. Whereas no promoter methylation was found in RCTs or normal kidney, 69% of chrRCC displayed chromosome 10 monosomy, correlating with Pax-2 immunoexpression. We concluded that Pax-2 expression might be used as an ancillary tool to discriminate chrRCC from oncocytomas with overlapping morphological features. The biological rationale lies on the causal relation between Pax-2 expression and chromosome 10 monosomy, but not PAX2 promoter methylation, in chrRCC. © 2013 The Authors. Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Human MutL homolog 1 immunoexpression in oral leukoplakia and oral squamous cell carcinoma: A prospective study in Indian population

PubMed Central

Chaudhari, Narendra T; Tupkari, Jagdish V; Joy, Tabita; Ahire, Manisha S

2016-01-01

Background: Mammalian mismatch repair system is responsible for maintaining genomic stability during repeated duplications, and human MutL homolog 1 (hMLH1) protein constitutes an important part of it. Various isolated studies have reported the altered expression of hMLH1 in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC). Research is lacking in the quantitative estimation and comparison of hMLH1 expression in OL and OSCC. Aims: To evaluate, quantify and compare hMLH1 immunoexpression in normal oral mucosa, OL and OSCC. Settings and Design: Thirty patients of OL and thirty patients of OSCC formed the study group and thirty patients were included in the control group (normal oral mucosa). Formalin-fixed paraffin wax blocks were prepared from the tissue samples. Materials and Methods: Immunohistochemistry for hMLH1 was performed, and the total number of positive cells was counted in high-power fields, and based on that percentage positivity of hMLH1 was calculated in all the cases. Statistical Analysis: Kruskal–Wallis and t-test were used. P < 0.05 was considered to be statistically significant. Results: The mean hMLH1 value in control group, leukoplakia and OSCC was 78.26, 54.33 and 40.97 respectively. hMLH1 immunoexpression showed decreasing indexes from control group to leukoplakia and then further to OSCC. hMLH1 expression was significantly lower in OSCC as compared to leukoplakia. There was no significant correlation of mean hMLH1 expression between different clinical and histopathological stages of leukoplakia and OSCC. Conclusions: hMLH1 immunoexpression was inversely related to the degree of dysplasia. These findings suggest that there is a progressive decrease in hMLH1 expression from control to leukoplakia and further to OSCC. Thus, it can be concluded that hMLH1 can be used as a reliable biomarker for malignant transformation. PMID:27721611

Steroid signaling system responds differently to temperature and hormone manipulation in the red-eared slider turtle (Trachemys scripta elegans), a reptile with temperature-dependent sex determination.

PubMed

Ramsey, M; Crews, D

2007-01-01

Many reptiles, including the red-eared slider turtle (Trachemys scripta elegans), exhibit temperature-dependent sex determination (TSD). Temperature determines gonadal sex during the middle of embryogenesis, or the temperature-sensitive period (TSP), when gonadal sex is labile to both temperature and hormones--particularly estrogen. The biological actions of steroid hormones are mediated by their receptors as defined here as the classic transcriptional regulation of target genes. To elucidate estrogen action during sex determination, we examined estrogen receptor alpha (Esr1, hereafter referred to as ERalpha), estrogen receptor beta (Esr2, hereafter referred to as ERbeta), and androgen receptor (Ar, hereafter referred to as AR) expression in slider turtle gonads before, during and after the TSP, as well as following sex reversal via temperature or steroid hormone manipulation. ERalpha and AR levels spike at the female-producing temperature while ovarian sex is determined, but none of the receptors exhibited sexually dimorphic localization within the gonad prior to morphological differentiation. All three receptors respond differentially to sex-reversing treatments. When shifted to female-producing temperatures, embryos maintain ERalpha and AR expression while ERbeta is reduced. When shifted to male-producing temperatures, medullary expression of all three receptors is reduced. Feminization via estradiol (E(2)) treatment at a male-producing temperature profoundly changed the expression patterns for all three receptors. ERalpha and ERbeta redirected to the cortex in E(2)-created ovaries, while AR medullary expression was transiently reduced. Although warmer incubation temperature and estrogen result in the same endpoint (ovarian development), our results indicate different steroid signaling patterns between temperature- and estrogen-induced feminization. 2007 S. Karger AG, Basel

Virtual and biomolecular screening converge on a selective agonist for GPR30.

PubMed

Bologa, Cristian G; Revankar, Chetana M; Young, Susan M; Edwards, Bruce S; Arterburn, Jeffrey B; Kiselyov, Alexander S; Parker, Matthew A; Tkachenko, Sergey E; Savchuck, Nikolay P; Sklar, Larry A; Oprea, Tudor I; Prossnitz, Eric R

2006-04-01

Estrogen is a hormone critical in the development, normal physiology and pathophysiology of numerous human tissues. The effects of estrogen have traditionally been solely ascribed to estrogen receptor alpha (ERalpha) and more recently ERbeta, members of the soluble, nuclear ligand-activated family of transcription factors. We have recently shown that the seven-transmembrane G protein-coupled receptor GPR30 binds estrogen with high affinity and resides in the endoplasmic reticulum, where it activates multiple intracellular signaling pathways. To differentiate between the functions of ERalpha or ERbeta and GPR30, we used a combination of virtual and biomolecular screening to isolate compounds that selectively bind to GPR30. Here we describe the identification of the first GPR30-specific agonist, G-1 (1), capable of activating GPR30 in a complex environment of classical and new estrogen receptors. The development of compounds specific to estrogen receptor family members provides the opportunity to increase our understanding of these receptors and their contribution to estrogen biology.

M30 expression demonstrates apoptotic cells, correlates with in situ end-labeling, and is associated with Ki-67 expression in large intestinal neoplasms.

PubMed

Carr, N J

2000-12-01

The monoclonal antibody M30 recognizes a neoepitope of cytokeratin 18 produced during apoptosis. It is reactive in formalin-fixed, paraffin-embedded tissue and has great potential in the study of apoptosis in clinical and experimental material. To compare the results of M30 immunoexpression with a more established technique of demonstrating apoptosis in tissue sections, in situ end-labeling. A secondary objective was to compare the results with immunoexpression of the proliferation-associated antigen Ki-67. Retrospective analysis of adenomas and adenocarcinomas of the large intestine. Immunohistochemistry for M30 and Ki-67, and in situ end-labeling. Formalin-fixed, paraffin-embedded tissue was used. The number of cells positive for M30, Ki-67, and in situ end-labeling, expressed as a proportion of the total number of cells counted. A strong positive correlation was found between in situ end-labeling and expression of M30, although the counts were widely scattered around the regression line. Counts of Ki-67 were strongly correlated with both M30 expression and in situ end-labeling. Immunoexpression of M30 was generally easier to interpret than in situ end-labeling, and the procedures for M30 immunohistochemistry were technically less exacting. These findings support the application of M30 immunoreactivity in the study of apoptosis.

Nuclear factor κB and cyclooxygenase-2 immunoexpression in oral dysplasia and oral squamous cell carcinoma.

PubMed

Pontes, Hélder Antônio Rebelo; Pontes, Flávia Sirotheau Corrêa; Fonseca, Felipe Paiva; de Carvalho, Pedro Luiz; Pereira, Erika Martins; de Abreu, Michelle Carvalho; de Freitas Silva, Brunno Santos; dos Santos Pinto, Décio

2013-02-01

Oral leukoplakia is the main potentially malignant oral lesion, and oral squamous cell carcinoma accounts for more than 95% of all malignant neoplasms in the oral cavity. Therefore, the aim of this study was to verify the immunoexpression of nuclear factor κB (NF-κB) and cyclooxygenase-2 (COX-2) proteins in dysplastic oral lesions and oral squamous cell carcinoma. Immunohistochemical reactions were performed on 6 inflammatory fibrous hyperplasia, 28 oral leukoplakia, and 15 oral squamous cell carcinoma paraffin-embedded samples. Immunoperoxidase reaction for NF-κB and COX-2 was applied on the specimens, and the positivity of the reactions was calculated for 1000 epithelial cells. Using the analysis of variance and the Tukey post hoc statistical analyses, a significantly increased immunoexpression for NF-κB was observed when oral squamous cell carcinoma samples were compared with the other groups studied. However, using the Kruskal-Wallis and the Dunn post hoc tests, a statistically significant result for COX-2 expression was obtained only when the moderate dysplasia group was compared with the inflammatory fibrous hyperplasia group. Nuclear factor κB may participate in the malignant phenotype acquisition process of the oral squamous cell carcinoma in its late stages, whereas COX-2 may be involved in the early stages of oral carcinogenesis process. Copyright © 2013 Elsevier Inc. All rights reserved.

The antidepressant-like effect of Ocimum basilicum in an animal model of depression.

PubMed

Ali, S S; Abd El Wahab, M G; Ayuob, N N; Suliaman, M

2017-01-01

We investigated the efficacy of Ocimum basilicum (OB) essential oils for treating depression related behavioral, biochemical and histopathological changes caused by exposure to chronic unpredictable mild stress (CUMS) in mice and to explore the mechanism underlying the pathology. Male albino mice were divided into four groups: controls; CUMS; CUMS plus fluoxetine, the antidepressant administered for pharmacological validation of OB; and CUMS plus OB. Behavioral tests included the forced swim test (FST), elevated plus-maze (EPM) and the open field test (OFT); these tests were performed at the end of the experiment. We assessed serum corticosterone level, protein, gene and immunoexpression of brain-derived neurotropic factor (BDNF) and glucocorticoid receptors (GRs) as well as immunoexpression of glial fibrillary acidic protein (GFAP), Ki67, caspase-3 in the hippocampus. CUMS caused depression in the mice as evidenced by prolonged immobility in the FST, prolonged time spent in the open arms during the EPM test and reduction of open field activity in the OFT. OB ameliorated the CUMS induced depressive status. OB significantly reduced the corticosterone level and up-regulated protein and gene expressions of BDNF and GR. OB reduced CUMS induced hippocampal neuron atrophy and apoptosis, and increased the number of the astrocytes and new nerve cells. OB significantly increased GFAP-positive cells as well as BDNF and GR immunoexpression in the hippocampus.

DNA damage, p53, Ki-67 and COX-2 expression in rat tongue cells exposed to nandrolone decanoate.

PubMed

Pozzi, Renan; Fernandes, Kelly Rosseti; Foot Gomes de Moura, Carolina; Ferrari, Raquel Agnelli Mesquita; Fernandes, Kristianne Porta Santos; Chaves, Marcelo Donizeti; Renno, Ana Claudia Muniz; Ribeiro, Daniel Araki

2013-05-01

The objective of this article was to evaluate the impact potential of nandrolone decanoate on DNA damage, cellular regulatory proteins and cyclooxygenase (COX)-2 in oral mucosa cells of Wistar rats. A total of 40 rats were distributed into four groups. Two experimental groups were treated with nandrolone decanoate, at 5 mg/kg doses, subcutaneously, three times a week in two periods: 15 and 30 days. The remaining groups received only 0.9% saline subcutaneously, three times a week. To evaluate genetic damage, nandrolone decanoate at 15 mg/kg dose was exposed to 24 h. In the histopathological analysis, no remarkable morphological changes were observed in tongue tissue in all groups. Significant increase in immunoexpression of Ki-67, p53, COX-2 proteins was detected in the groups treated with nandrolone decanoate during 15 and 30 days, when compared to their respective controls. A positive correlation between immunoexpression of p53 and COX-2 protein was detected following nandrolone decanoate exposure. DNA damage was induced by nandrolone decanoate in oral mucosa cells at 15 mg/kg dose. Our results suggest that nandrolone decanoate was able to alter the expression of cell cycle-related proteins, as well as to induce genetic damage and COX-2 immunoexpression in tongue cells of Wistar rats.

HOMOLOGY MODELING OF THE ESTROGEN RECEPTOR SUBTYPE BETA (ER-BETA) AND CALCULATION OF LIGAND BINDING AFFINITIES. (R826133)

EPA Science Inventory

Abstract

Estrogen is a steroid hormone playing critical roles in physiological processes such as sexual differentiation and development, female and male reproductive processes, and bone health. Numerous natural and synthetic environmental compounds have been shown capa...

Gene Environment Interactions in Women With Breast and Secondary Lung Cancer

DTIC Science & Technology

2006-07-01

primary and metastatic tumors with emphasis on period of occurrence of metastases and survival. J.Surg.Oncol., 69, 137-146. 94. Koda ,M., Sulkowski...S., Kanczuga- Koda ,L., Surmacz,E., and Sulkowska,M. (2004) Expression of ERalpha, ERbeta and Ki-67 in primary tumors and lymph node metastases in

GPR30: a novel therapeutic target in estrogen-related disease.

PubMed

Prossnitz, Eric R; Sklar, Larry A; Oprea, Tudor I; Arterburn, Jeffrey B

2008-03-01

Estrogen is a crucial hormone in human physiology that regulates a multitude of biological processes. It is also an important target in many diseases such as cancer and skeletal, neurological and immunological conditions. The actions of estrogen have traditionally been ascribed to one of two closely related classical nuclear hormone receptors, ERalpha and ERbeta, which are best characterized for regulating gene expression. Recent studies have revealed the contribution of a novel estrogen receptor GPR30, which belongs to the family of seven-transmembrane G-protein-coupled receptors, to many of the rapid biological responses to estrogen. Many drugs, such as tamoxifen and fulvestrant, which seem to selectively inhibit the activities of the classical estrogen receptors, are in widespread clinical use. However, recent results indicate that these same drugs activate multiple cellular-signaling pathways via GPR30. Unraveling the pharmacological profiles and specificities of ERalpha, ERbeta and GPR30 will be vital for understanding not only the physiological roles of each receptor but also for the development of the next generation of receptor-specific drugs.

Early onset of puberty and early ovarian failure in CYP7B1 knockout mice.

PubMed

Omoto, Yoko; Lathe, Richard; Warner, Margaret; Gustafsson, Jan-Ake

2005-02-22

CYP7B1 is the enzyme responsible for hydroxylation and termination of the estrogenic actions of the androgen metabolite, 5alpha-androstane-3beta, 17beta-diol (3betaAdiol). 3betaAdiol is estrogenic in ERalpha or ERbeta positive cells only if they do not express CYP7B1. In this study we show that female CYP7B1(-/-) mice experience early onset of growth of the uterus and mammary glands and commence estrus cycles 2 days earlier than their wild-type littermates. Adult mammary glands and uteri appear to be under continuous estrogenic stimulation. We conclude that, by cell-specific regulation of the estrogenicity of 3betaAdiol, CYP7B1 performs two major tasks: (i) it allows 3betaAdiol to have growth inhibitory effects through ERbeta and (ii) it permits estradiol-specific activation of estrogen receptors by protection of certain cells from the estrogenic effects of 3betaAdiol. When CYP7B1 is inactivated, 3betaAdiol activates estrogen receptors indiscriminately, and the overall effect is prolonged and inappropriate exposure to estrogen.

β-catenin as a prognostic factor for prostate cancer (PCa)

PubMed Central

Nowicki, Andrzej; Duda-Szymańska, Joanna

2012-01-01

Introduction The prostate cancer is difficult to predict, and treatment failure is associated with local infiltration, as well as distant metastases. Adhesion and migration abilities to of cancer cells play a major role in formation of metastasis. The participation of β-catenin in pathogene-sis of many types of cancer and benign processes has been an important discovery of recent years. Material and methods The studied material was obtained by transrectal, sextant core biopsy from 102 patients hospitalized in Department of Urology, Regional Hospital in Kalisz (2001-2004). The aim of our study was to determine the predictive value of β-catenin immunoexpression in prostate cancer, to analyze the prognostic aspect of some histopathological features and finally to assess the relationship between β-catenin immunoreactivity and the microscopic image of the tumor. Relationships between the investigated variables were analyzed using the Chi2 test of compatibility. We used the Kaplan-Meier curves to assess survival differences between groups of patients. Finally we established which of the studied factors significantly affect the patient outcome, using the method of Cox proportional hazard regression. Results In prostate cancer in comparison with the normal epithelium, both the location and the strength of β-catenin immunoexpression are impaired. Conclusions Our results indicate that the presence of disorders in β-catenin immunoexpression in prostate cancer cells indicates a high risk of death due to tumor progression and makes it imperative for immediate treatment procedures. PMID:24578946

γ-amino butyric acid (GABA) level as an overall survival risk factor in breast cancer.

PubMed

Brzozowska, Anna; Burdan, Franciszek; Duma, Dariusz; Solski, Janusz; Mazurkiewicz, Maria

2017-09-21

The γ-amino butyric acid (GABA) plays important role in the proliferation and migration of cancer cells. The aim of the study was to evaluate the level of GABA in breast cancer, in relation to clinical and epidemiological data. The study was conducted on 89 patients with breast cancer in stage I-II. GABA level was assessed using spectrofluorometric method in tumour homogenates. Immunoexpression of E-cadherin was evaluated histologically on paraffin fixed specimens. Overall and disease-free survival was assessed for a 15-year interval period. Median overall survival was significantly longer (127.2 months) in patients with a high level of GABA (>89.3 μg/1), compared with a group with a low level of the amino acid (106.4 months). Disease-free survival was insignificantly different - 99 and 109 months, respectively. A significantly longer overall survival (131.2 months) was seen among patients with a high level of GABA and positive E-cadherin immunoexpression, compared with a group characterized by a low level of GABA and lack of E-cadherin immunorectivity (98.1 months). The co-existence of negative immunoexpression of E-cadherin and low GABA concentration resulted in a six-fold increase in the risk of death (HR=6.03). GABA has a significant prognostic value in breast cancer. Co-existence of a low level of GABA and loss of E-cadherin immune-expression seems to be a new, independent, and negative prognostic marker of the neoplasm.

Glial Fibrillary Acidic Protein (GFAP) as a Mesenchymal marker of Early Hepatic Stellate Cells Activation in Liver Fibrosis in Chronic Hepatitis C Infection

PubMed Central

Hassan, Sobia; Syed, Serajuddaula; Kehar, Shahnaz Imdad

2014-01-01

Objective: This study aims to determine expression of Glial Fibrillary Acidic Protein and of Alpha Smooth Muscle Actin (α-SMA) in hepatic stellate cells of CHC cases and their association with stage of fibrosis. Methods: The study was conducted at Ziauddin University, Clifton Campus during the year 2010-2012. Sixty Chronic Hepatitis C cases were immmunostained using anti α-SMA antibody and anti-GFAP antibody. Semi quantitative scoring in pericentral, periportal and perisinusoidal area of each case was done to assess immunoexpression of each marker. Results : Immunoexpression of GFAP showed significant association with α-SMA. GFAP expression was inversely correlated with progression of fibrosis. Conclusion : GFAP could represent a useful marker for early hepatic stellate cells activation. Follow up biopsies showing decline in GFAP levels may help identify the target group requiring aggressive therapy. PMID:25225520

Immunohistochemical expression of protein 53, murine double minute 2, B-cell lymphoma 2, and proliferating cell nuclear antigen in odontogenic cysts and keratocystic odontogenic tumor.

PubMed

Galvão, Hebel Cavalcanti; Gordón-Núñez, Manuel Antonio; de Amorim, Rivadavio Fernandes Batista; Freitas, Roseana de Almeida; de Souza, Lelia Batista

2013-01-01

Even though odontogenic cysts share a similar histogenesis, they show different growth and differentiation profile due to differences in the proliferative cellular activity. We perform an immunohistochemical assessment of protein 53 (p53), proliferating cell nuclear antigen (PCNA), B-cell lymphoma 2 (bcl-2), and murine double minute 2 (MDM2) expression in odontogenic cysts and keratocystic odontogenic tumor analyzing their correlation with the biological behavior of these lesions. By the streptavidin-biotin-peroxidase method with antibodies against p53, PCNA, bcl-2, and MDM2 proteins, 11 radicular cysts, 11 dentigerous cysts, and 11 keratocystic odontogenic tumor were analyzed. The non-parametric Mann-Whitney U-test and Kruskall-Wallis test (P ≤ 0.05) were used to analyze the data. Immunopositivity for PCNA was observed in all cases appraised, predominantly in the suprabasal layer of keratocystic odontogenic tumor epithelial lining (SD ± 19.44), but no significant differences were found among the groups of lesions. Bcl-2 immunoexpression was observed especially in the basal layer of keratocystic odontogenic tumor. PCNA LI was significantly higher than bcl-2 LI in keratocystic odontogenic tumor. MDM2 and p53 immunoexpression were not detected in the lesions studied. Among the evaluated lesions, the keratocystic odontogenic tumor showed different immunoexpression of the proliferation and apoptosis markers. The results of this study suggest that the keratocystic odontogenic tumor presents distinct biological behavior of the odontogenic cysts, as for the processes of proliferation, apoptosis, and differentiation, reinforcing the information in favor of the neoplastic nature of this lesion.

Expression of cyclooxygenase-2 in the endometrium of gilts with different stages of endometritis.

PubMed

Roongsitthichai, Atthaporn; Srisuwatanasagul, Sayamon; Koonjaenak, Seri; Tummaruk, Padet

2011-11-01

The present study determined the association among the expression of COX-2, stages of endometritis, and types and number of local immune cells infiltrating into the gilts' endometrium. The uterine tissues from 24 Landrace x Yorkshire gilts identified as acute endometritis (n = 7), chronic endometritis (n = 7), and normal endometrium (n = 10) were included. The tissues were prepared for both histological and immunohistochemical investigations. The immunoexpression of COX-2 in every layer of the gilts' endometria was appraised by avidin-biotin-peroxidase complex method via image analysis; and was reported as percentage of positive area and staining index. The results revealed that the immunoexpression of COX-2 was found only in the surface epithelial layer. The gilts with acute endometritis possessed higher both percentage of positive area (68.99% versus 4.50% and 3.43%, P < 0.001) and staining index (1.13 versus 0.05 and 0.04, P < 0.001) than those with chronic endometritis and normal endometrium, respectively. Positive correlations between the number of surface epithelial neutrophils and percentage of COX-2 positive area (r = 0.47, P = 0.022), as well as mean staining index (r = 0.44, P = 0.032) were observed. In conclusion, the immunoexpression of COX-2 was found strongest in the gilts with acute endometritis, meanwhile it was not different between those with chronic endometritis and normal endometrium. This suggested that the expression of COX-2 might be dependent not only on the infiltration of local immune cells in the endometrium, but also on the duration of exposure with inflammatory agents.

Synthesis of 3-alkyl naphthalenes as novel estrogen receptor ligands

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

Fang, Jing; Akwabi-Ameyaw, Adwoa; Britton, Jonathan E.

2009-06-24

A series of estrogen receptor ligands based on a 3-alkyl naphthalene scaffold was synthesized using an intramolecular enolate-alkyne cycloaromatization as the key step. Several of these compounds bearing a C6-OH group were shown to be high affinity ligands. All compounds had similar ER{alpha} and ER{beta} binding affinity ranging from micromolar to low nanomolar.

Role of estrogen receptors alpha, beta and GPER1/GPR30 in pancreatic beta-cells.

PubMed

Nadal, Angel; Alonso-Magdalena, Paloma; Soriano, Sergi; Ripoll, Cristina; Fuentes, Esther; Quesada, Ivan; Ropero, Ana Belen

2011-01-01

Estrogen receptors (ER) are emerging as important molecules involved in the adaptation of beta-cells to insulin resistance. The onset of type 2 diabetes is marked by insulin secretory dysfunction and decreased beta-cell mass. During pregnancy, puberty and obesity there is increased metabolic demand and insulin resistance is developed. This metabolic state increases the demand on beta-cells to augment insulin biosynthesis and release. In this respect, ERalpha is directly implicated in the E2-regulation of insulin content and secretion, while ERbeta is in the E2-potentiation of glucose-induced insulin release. Both receptors develop their actions within the physiological range of E2. In addition, the G protein-coupled estrogen receptor (GPER1/GPR30) seems to be implicated in the E2-regulation of stimulus-secretion coupling in the three cell types of the islet. The increased demand of insulin production for long time may lead to beta-cell stress and apoptosis. ERalpha, ERbeta and GPER1/GPR30 are involved in preventing beta-cell apoptosis, impeding the loss of critical beta-cell mass. Therefore, estrogen receptors may play an essential role in the adaptation of the pancreas to insulin resistant periods.

Aromatase and estrogen receptors in male reproduction.

PubMed

Carreau, Serge; Delalande, Christelle; Silandre, Dorothée; Bourguiba, Sonia; Lambard, Sophie

2006-02-26

Aromatase is a terminal enzyme which transforms irreversibly androgens into estrogens and it is present in the endoplasmic reticulum of numerous tissues. We have demonstrated that mature rat germ cells express a functional aromatase with a production of estrogens equivalent to that of Leydig cells. In humans in addition to Leydig cells, we have shown the presence of aromatase in ejaculated spermatozoa and in immature germ cells. In most tissues, high affinity estrogen receptors, ERalpha and/or ERbeta, mediate the role of estrogens. Indeed, in human spermatozoa, we have successfully amplified ERbeta mRNA but the protein was not detectable. Using ERalpha antibody we have detected two proteins in human immature germ cells: one at the expected size 66 kDa and another at 46 kDa likely corresponding to the ERalpha isoform lacking exon 1. In spermatozoa only the 46 kDa isoform was present, and we suggest that it may be located on the membrane. In addition, in men genetically deficient in aromatase, it is reported that alterations of spermatogenesis occur both in terms of the number and motility of spermatozoa. All together, these observations suggest that endogenous estrogens are important in male reproduction.

Study of the relationship between mononuclear inflammatory infiltrate and Ki-67 and basement membrane and extracellular matrix protein expression in radicular cysts.

PubMed

Mourão, R V C; Júnior, E C Pinheiro; Barros Silva, P G; Turatti, E; Mota, M R L; Alves, A P N N

2016-05-01

To evaluate the relationship between mononuclear inflammatory infiltrate and the expression of a proliferative immunomarker (Ki-67) as well as to evaluate basement membrane and extracellular matrix proteins (laminin and collagen type IV) in radicular cysts and dentigerous cysts (DC). Immunohistochemical analyses were performed in heavily inflamed radicular cysts (HIRC), slightly inflamed radicular cysts (SIRC) and DC (n = 20) using Ki-67 (Dako(®) , 1 : 50), anticollagen type IV (DBS(®) , 1 : 40) and antilaminin (DBS(®) , 1 : 20). The data were analysed using anova/Tukey's test (Ki-67) and Kruskal-Wallis/Dunn's test (collagen type IV and laminin) (P < 0.05). The immunoexpression of Ki-67 was significantly greater in the SIRC group compared with the HIRC and DC (P = 0.0040). Likewise, the immunoexpression of collagen type IV in the basement membrane of the SIRC group was significantly more continuous (P = 0.0475) than in the HIRC group. DC had significantly less collagen type IV in extracellular matrix immunoexpression than HIRC and SIRC (P = 0.0246). Laminin was absent in the basement membrane in the SIRC and DC groups, and the extracellular matrix of the HIRC was weak and punctate. The presence of inflammatory factors in the radicular cyst wall modified the expression of proliferation factors in the epithelial lining and the expression of collagen type IV and laminin in the basement membrane, but did not modify extracellular matrix behaviour in radicular cysts. © 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.

M2 macrophages and inflammatory cells in oral lesions of chronic paracoccidioidomycosis.

PubMed

de Carli, Marina Lara; Miyazawa, Marta; Nonogaki, Suely; Shirata, Neuza Kasumi; Oliveira, Denise Tostes; Pereira, Alessandro Antônio Costa; Hanemann, João Adolfo Costa

2016-02-01

Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by Paracoccidioides brasiliensis (Pb) and associated with deficient cellular immune response, which is modulated by inflammatory cells, mainly macrophages, and cytokines. Recently, the comprehension of the macrophage polarization mediated by Th1 and Th2 cytokines has contributed to elucidate the immune response that takes part in some diseases. Thus, the aim of this study was to assess the presence of Th1- and Th2-immune response and also Pb counting in oral lesions of chronic PCM. Forty-eight cases of chronic PCM oral lesions were included. All cases were classified as loose or dense granulomas. S100 protein, IL-1β, IL-6, TNF-α, CD163 and CD68 immunoexpressions, and Pb localization were evaluated. The fungi present in the tissue were quantified by anti-Pb antibody. Most patients were white men with mean age of 47 years old and showed higher incidence of multiple lesions. Loose granulomas were predominant and exhibited a great amount of M2 macrophages, which were visualized with anti-CD163 antibody. The expression for CD163 and CD68 was similar (P = 0.05), highlighting the predominance of M2 macrophages in PCM. IL-1β, IL-6, and TNF-α immunoexpression did not significantly change with CD163, CD68, and S100 protein. The number of fungi was significantly higher in cases with intense IL-1β immunoexpression (P = 0.003). M2-activated macrophages were the majority among inflammatory cells in chronic PCM, characterizing the action of a Th2-immune response. Nevertheless, Th1 cytokines were also found; mainly IL-1β, which was associated with fungi counting in oral lesions. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Immunoexpression of tryptase-positive mast cells in periapical granulomas and radicular cysts.

PubMed

Costa Neto, H; de Andrade, A L D L; Gordón-Núñez, M A; Freitas, R de A; Galvão, H C

2015-08-01

To evaluate and compare the immunoexpression of tryptase in samples of periapical granulomas (PGs) and radicular cysts (RCs) correlating it with the type of lesion, localization, intensity of the inflammatory infiltrate and thickness of the cystic epithelial lining, in order to gain insight into the phlogistic role of these cells in the lesions studied. Twenty-five PGs and twenty-five RCs obtained from human teeth without endodontic treatment were submitted to morphological and immunohistochemical analysis using anti-tryptase antibody. Mast cells were identified and counted in three regions: intra-epithelial, central/superficial and deep portions. The data were analysed using the Mann-Whitney U-test (P < 0.05). In comparison with RCs, PGs exhibited higher immunoexpression of tryptase-positive mast cells located in both central/superficial and deep regions (P < 0.001 and P < 0.001, respectively). When considering the total number of mast cells and disregarding the location, the number of tryptase-positive mast cells increased gradually from RCs to PGs (P < 0.001). Lesions with inflammatory infiltrate grade III had greater number of tryptase-positive mast cells located in both central/superficial and deep regions than lesions with inflammatory infiltrates grade II (P = 0.045 and P = 0.025). When the location was ignored, the lesions with inflammatory infiltrate grade III also exhibited higher immunostaining of tryptase-positive mast cells (P = 0.01). Tryptase-positive mast cells were present in chronic periapical lesions in a larger number in periapical granulomas than in radicular cysts, in both central/superficial and deep regions. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Metalloproteinases 2 and 9 Immunoexpression in Periapical Lesions from Primary Endodontic Infection: Possible Relationship with the Histopathological Diagnosis and the Presence of Pain.

PubMed

Pereira Faustino, Isabel Schausltz; Azevedo, Rebeca Souza; Takahama, Ademar

2016-04-01

The aim of this study was to evaluate the possible associations among the histopathological diagnosis, the inflammatory infiltrate profile, the presence of pain, and the immunoexpression of matrix metalloproteinases MMP-2 and MMP-9 in periapical lesions from primary endodontic infection. Fifty-one primary periapical lesions obtained from extracted teeth were selected for this study. Patients were previously evaluated for the presence of pain and sinus tract related to the tooth to be extracted. Tissues were processed for microscopic examination and MMP-2 and MMP-9 immunoexpression. Microscopically, samples were classified as periapical granulomas or periapical cysts and the inflammatory infiltrate as chronic or mixed. The percentage of immunopositive cells for MMP-2 and MMP-9 of each case was performed based on 10 consecutive microscopic fields. The Student t or chi-square tests were used in the statistical analysis. Of the total, 28 cases were classified as periapical granulomas (54.90%) and 23 cases as periapical cysts (45.10%). Seventeen patients (33.33%) reported pain associated with the extracted tooth, with 12 cases of periapical granulomas (70.58%) and 5 cases of periapical cysts (29.42%). All cases showed immunopositivity for MMP-2 and MMP-9 in a high percentage of cells, mainly in the cytoplasm of the leukocytes. MMP-2 was expressed more in periapical granulomas than periapical cysts (P < .05) and in symptomatic cases (P < .05). According to the results, we may conclude that MMP-2 and MMP-9 are highly expressed in periapical lesions from a primary endodontic infection. Moreover, we may suggest MMP-2 is expressed more in periapical granuloma and in cases associated with pain. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Profile of NF-κBp(65/NFκBp50) among prostate specific antigen sera levels in prostatic pathologies.

PubMed

Bouraoui, Y; Ben Jemaa, A; Rodriguez, G; Ben Rais, N; Fraile, B; Paniagua, R; Sellemi, S; Royuela, M; Oueslati, R

2012-10-01

The aim of this work was to characterise the immunoexpression of NF-κB (p50/p65) in human prostatic pathologies and to study its profiles of activation among sera prostate specific antigen antigen (PSA) according the three groups: 0-4ng/mL, 4-20ng/mL and >20ng/mL. Twenty-four men with benign prostate hyperplasia (BPH); 19 men with prostate cancer (PC) and five men with normal prostates (NP). Immunohistochemical and western blot analysis was performed. Serum levels of PSA were assayed by immulite autoanalyser. In BPH and PC samples, immunoexpressions were observed for NF-κBp65 and NF-κBp50; while in NP samples, only were detected NF-κBp50. PC samples showed immunoreactions to NF-κBp65 and NF-κBp50 more intense (respectively 24.18±0.67 and 28.23±2.01) than that observed in BPH samples (respectively18.46±2.04 and 18.66±1.59) with special localisation in the nucleus. Different profiles of NF-κBp65 immunoexpressions were observed and BPH patients with sera PSA levels between 0-4ng/mL presented a significant weak percentage compared to BPH patients with sera PSA levels between 4-20ng/mL and >20ng/mL. No immunoreactions to NF-κBp65 were observed in PC patients with sera PSA levels between 4-20ng/mL. The sensibility of both NF-κB and PSA to inflammation allowed confirming the relationship between these two molecules and its involvement in prostatic diseases progression (inflammatory and neoplasic). Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Phenotypic Intratumoral Heterogeneity of Endometrial Carcinomas.

PubMed

Silva, Cátia; Pires-Luís, Ana S; Rocha, Eduardo; Bartosch, Carla; Lopes, José M

2018-03-01

Intratumoral heterogeneity has been shown to play an important role in diagnostic accuracy, development of treatment resistance, and prognosis of cancer patients. Recent studies have proposed quantitative measurement of phenotypic intratumoral heterogeneity, but no study is yet available in endometrial carcinomas. In our study we evaluated the phenotypic intratumoral heterogeneity of a consecutive series of 10 endometrial carcinomas using measures of dispersion and diversity. Morphometric architectural (%tumor cells, %solid tumor, %differentiated tumor, and %lumens) and nuclear [volume-weighted mean nuclear volume ((Equation is included in full-text article.))] parameters, as well as estrogen receptor, progesterone receptor, p53, vimentin, and beta-catenin immunoexpression (H-score) were digitally analyzed in 20 microscopic fields per carcinoma. Quantitative measures of intratumoral heterogeneity included coefficient of variation (CV) and relative quadratic entropy (rQE). In each endometrial carcinoma there was slight variation of architecture from field to field, resulting in globally low levels of heterogeneity measures (mean CV %tumor cells: 0.10, %solid tumor: 0.73, %differentiated tumor: 0.19, %lumens: 0.61 and mean rQE %tumor cells: 18.5, %solid tumor: 20.3, %differentiated tumor: 25.6, %lumens: 21.8). Nuclear intratumoral heterogeneity was also globally low (mean (Equation is included in full-text article.)CV: 0.23 and rQE: 27.3), but significantly higher than the heterogeneity of architectural parameters within most carcinomas. In general, there was low to moderate variability of immunoexpression markers within each carcinoma, but estrogen receptor (mean CV: 0.56 and rQE: 46.2) and progesterone receptor (mean CV: 0.60 and rQE: 39.3) displayed the highest values of heterogeneity measures. Intratumoral heterogeneity of immunoexpression was significantly higher than that observed for morphometric parameters. In conclusion, our study indicates that endometrial carcinomas present a variable but predominantly low degree of phenotypic intratumoral heterogeneity.

Ocular squamous cell carcinoma in Holstein cows from the South of Brazil

PubMed Central

Fornazari, Gabrielle A.; Kravetz, Juliana; Kiupel, Matti; Sledge, Dodd; Filho, Ivan Roque De Barros; Montiani-Ferreira, Fabiano

2017-01-01

Aim: The aim of this study was to investigate 10 cases of bovine ocular squamous cell carcinoma (OSCC) diagnosed in Holstein or Holstein-crosses cows. Materials and Methods: The investigation was performed exclusively in OSCC cases diagnosed in the State of Paraná and Santa Catarina. A combination of two previously existing histopathological classifications systems was used. The tissue samples were tested for immunoexpression of p53 and p16 and polymerase chain reaction (PCR) for bovine herpesvirus and papillomavirus. Results: A positive correlation between number of mitotic figures and tissue invasion was found. Anaplasia parameters did not correlate well with tumor invasion of deeper tissues and mitotic counts. Six of 10 OSCC cases were in animals with heavily pigmented eyes. Immunoexpression of p53 and p16 was observed in 3 cases each. Bovine herpesvirus and papillomavirus were not detected by PCR. Conclusions: Our results indicate that OSCC occurrence is most likely multifactorial with genetic, phenotypic, and environmental influences contributing to the pathogenesis of the disease. PMID:29391681

Determination of the Role of Estrogen Receptors and Estrogen Regulated Genes in B Cell Autoreactivity

DTIC Science & Technology

2011-07-01

Betty Diamond – DOD FINAL REPORT 9 Figure 3: (A) expression of estrogen receptors ERalpha( Esr1 ) and ERbeta (Esr2) in splenic B cells and (B...Urinary 16 OH-Estradiol metabolite in BALB/c and C57BL6 mice. Esr1 0 0.05 0.1 0.15 0.2 Transit. Mature Transit. Mature Transit. Mature Transit. mature P E2

Testing ER-Beta Agonist Synergy with B7-H1 and mTOR Inhibitors as Novel and Effective Treatments for Ovarian Cancer

DTIC Science & Technology

2016-08-01

requirements 6 Appendices None INTRODUCTION Ovarian cancer (OC) is the fifth leading cause of cancer death in US women and is the top gynecologic cancer...killer. The ACS estimates ~21,980 new OC cases and ~14,270 deaths in the US in 2014. Most patients fail front-line therapy and will die of their

Dilation of epicardial coronary arteries by the G protein-coupled estrogen receptor agonists G-1 and ICI 182,780.

PubMed

Meyer, Matthias R; Baretella, Oliver; Prossnitz, Eric R; Barton, Matthias

2010-01-01

Endogenous estrogens protect from coronary artery disease in premenopausal women, but the mechanisms involved are only partly understood. This study investigated whether activation of the novel G protein-coupled estrogen receptor (GPER, formerly known as GPR30) affects coronary artery tone, and whether this is affected by concomitant blockade of estrogen receptors (ER) alpha and beta. Rings of epicardial porcine coronary arteries suspended in organ chambers were precontracted with prostaglandin F(2)alpha, and direct effects of G-1 (GPER agonist) and ICI 182,780 (GPER agonist and ERalpha/ERbeta antagonist) were determined. In addition, indirect effects on contractility to endothelin-1 and serotonin (a vasoconstrictor released from aggregating platelets during acute myocardial infarction) were assessed. ICI 182,780 and G-1 caused acute dilation of coronary arteries to a comparable degree (p < 0.05 vs. solvent control). Both GPER agonists attenuated contractions to endothelin-1 (p < 0.05 vs. ethanol), but not to serotonin (n.s.). In summary, these findings provide evidence for direct and indirect coronary artery dilator effects of GPER independent of ERalpha and ERbeta, and are the first demonstration of arterial vasodilation in response to ICI 182,780. Copyright 2010 S. Karger AG, Basel.

Determination of the Role of Estrogen Receptors and Estrogen Regulated Genes in B cell Autoreactivity. Addendum

DTIC Science & Technology

2012-07-01

Betty Diamond – DOD FINAL REPORT 9 Figure 3: (A) expression of estrogen receptors ERalpha( Esr1 ) and ERbeta (Esr2) in splenic B cells and (B)Urinary...16 OH-Estradiol metabolite in BALB/c and C57BL6 mice. Esr1 0 0.05 0.1 0.15 0.2 Transit. Mature Transit. Mature Transit. Mature Transit. mature P E2 P

The environmental chemical tributyltin chloride (TBT) shows both estrogenic and adipogenic activities in mice which might depend on the exposure dose

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

Penza, M.; Jeremic, M.; Marrazzo, E.

2011-08-15

Exposure during early development to chemicals with hormonal action may be associated with weight gain during adulthood because of altered body homeostasis. It is known that organotins affect adipose mass when exposure occurs during fetal development, although no knowledge of effects are available for exposures after birth. Here we show that the environmental organotin tributyltin chloride (TBT) exerts adipogenic action when peripubertal and sexually mature mice are exposed to the chemical. The duration and extent of these effects depend on the sex and on the dose of the compound, and the effects are relevant at doses close to the estimatedmore » human intake (0.5 {mu}g/kg). At higher doses (50-500 {mu}g/kg), TBT also activated estrogen receptors (ERs) in adipose cells in vitro and in vivo, based on results from acute and longitudinal studies in ERE/luciferase reporter mice. In 3T3-L1 cells (which have no ERs), transiently transfected with the ERE-dependent reporter plus or minus ER{alpha} or ER{beta}, TBT (in a dose range of 1-100 nM) directly targets each ER subtype in a receptor-specific manner through a direct mechanism mediated by ER{alpha} in undifferentiated preadipocytic cells and by ER{beta} in differentiating adipocytes. The ER antagonist ICI-182,780 inhibits this effect. In summary, the results of this work suggest that TBT is adipogenic at all ages and in both sexes and that it might be an ER activator in fat cells. These findings might help to resolve the apparent paradox of an adipogenic chemical being also an estrogen receptor activator by showing that the two apparently opposite actions are separated by the different doses to which the organism is exposed. - Research Highlights: > The environmental organotin tributyltin chloride shows dose-dependent estrogenic and adipogenic activities in mice. > The duration and extent of these effects depend on the sex and the dose of the compound. > The estrogenic and adipogenic effects of TBT occur at doses closed to the estimated human intake. > TBT activates the estrogen receptors (ER{alpha} and ER{beta}) in 3T3-L1 cells at nM concentrations.« less

Modulation of vitellogenin synthesis through estrogen receptor beta-1 in goldfish (Carassius auratus) juveniles exposed to 17-{beta} estradiol and nonylphenol

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

Soverchia, L.; Ruggeri, B.; Palermo, F.

2005-12-15

Many synthetic chemicals, termed xenoestrogens, have been shown to interact as agonists with the estrogen receptor (ER) to elicit biological responses similar to those of natural hormones. To date, the regulation of vitellogenesis in oviparous vertebrates has been widely used for evaluation of estrogenic effects. Therefore, Carassius auratus juveniles were chosen as a fish model for studying the effects of estradiol-17{beta} and different concentrations (10{sup -6} and 10{sup -7} M) of 4-nonylphenol (4-NP) on the expression of liver ER{beta}-1 subtype; plasma vitellogenin and sex steroids (androgens and estradiol-17{beta}) were also evaluated together with the bioaccumulation process, through mass-spectrometry. C. auratusmore » is a species widespread in the aquatic environment and, on the toxicological point of view, can be considered a good 'sentinel' species. Juveniles of goldfish were maintained in tanks with only tap water or water with different concentrations (10{sup -6} and 10{sup -7} M) of 4-nonylphenol (4-NP), or 10{sup -7} M of estradiol-17{beta}. After 3 weeks of treatment, animals were anesthetized within 5 min after capture, and blood was immediately collected into heparinized syringes by cardiac puncture and stored at -70 deg. C; the gonads were fixed, then frozen and stored at -70 deg. C; the whole fish, liver, and muscle tissues were harvested and immediately stored at -70 deg. C for molecular biology experiments and bioaccumulation measurements. The estrogenic effects of 4-NP were evidenced by the presence of plasma vitellogenin in juveniles exposed both to estradiol-17{beta} and the two doses of 4-NP; moreover, exposure to 4-NP also increased aromatization of androgens, as suggested by decreasing androgens and increasing estradiol-17{beta} plasma levels. The changes of these parameters were in agreement with the increasing transcriptional rate of ER{beta}-1 mRNA in the liver, demonstrating that both estradiol-17{beta} and 4-NP modulate the vitellogenin rate through interaction with the ER{beta}-1 subtype. The present study also suggests that 4-NP at the concentration of 10{sup -6} M bioaccumulates in the liver.« less

Differential neonatal imprinting and regulation by estrogen of estrogen receptor subtypes alpha and beta and of the truncated estrogen receptor product (TERP-1) mRNA expression in the male rat pituitary.

PubMed

Tena-Sempere, M; Barreiro, M L; González, L C; Pinilla, L; Aguilar, E

2001-11-01

Two distinct nuclear estrogen receptors (ERs) have been identified, the classical one, renamed ERalpha, and the more recently cloned ERbeta. In a variety of tissues, gene expression of both receptor subtypes results in the generation of multiple transcripts encoding the full-length as well as several alternately spliced isoforms. In the rat pituitary, a truncated, tissue-specific variant of ERalpha, called TERP-1, has been identified and found able to modulate ERalpha and ERbeta activity. So far, its pattern of expression and hormonal regulation have been mostly studied in females. The present study was designed to analyze the pattern of expression of TERP-1 mRNA in the male rat pituitary at different stages of postnatal development, and to evaluate the impact of neonatal imprinting and estrogen treatment upon TERP-1 expression in the male pituitary. Assessment of TERP-1 mRNA levels by semi-quantitative RT-PCR, using a variant-specific primer pair, revealed that TERP-1 is also expressed in the male rat pituitary. Relative mRNA expression levels changed markedly during postnatal development, with moderate expression of the TERP-1 transcript at birth, barely detectable levels during the infantile-prepubertal period, and maximal values in adulthood. Expression of TERP-1 was sensitive to neonatal estrogen exposure, which resulted in a significant, persistent increase in mRNA levels from the infantile period until puberty. This phenomenon was not mimicked by neonatal blockade of endogenous GnRH. In addition, estrogen was able to acutely up-regulate pituitary TERP-1 mRNA expression levels in prepubertal (30-day-old) and adult (75-day-old) males. Interestingly, neonatal imprinting as well as acute estrogen treatment resulted in opposite effects on TERP-1 and full-length ERalpha and ERbeta transcripts, the latter being decreased under both conditions. In conclusion, our data indicate that TERP-1 mRNA is expressed in a developmentally regulated manner in the male rat pituitary, and is affected by neonatal estrogen imprinting and acute estrogen treatment. Regulation of TERP-1 expression by neonatal or acute estrogen treatment may thus represent an additional tuning mechanism for estrogen actions in the male rat pituitary. Copyright 2001 S. Karger AG, Basel

A critical review of fundamental controversies in the field of GPR30 research.

PubMed

Langer, Gernot; Bader, Benjamin; Meoli, Luca; Isensee, Jörg; Delbeck, Martina; Noppinger, Patricia Ruiz; Otto, Christiane

2010-01-01

The female sex hormone estradiol plays an important role in reproduction, mammary gland development, bone turnover, metabolism, and cardiovascular function. The effects of estradiol are mediated by two classical nuclear receptors, estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta). In 2005, G-protein-coupled receptor 30 (GPR30) was claimed to act as a non-classical estrogen receptor that was also activated by the ERalpha and ERbeta antagonists tamoxifen and fulvestrant (ICI 182780). Despite many conflicting results regarding the potential role of GPR30 as an estrogen receptor, the official nomenclature was changed to GPER (G-protein-coupled estrogen receptor). This review revisits the inconsistencies that still exist in the literature and focuses on selected publications that basically address the following two questions: what is the evidence for and against the hypothesis that GPR30 acts as an estrogen receptor? What is the potential in vivo role of GPR30? Thus, in the first part we focus on conflicting results from in vitro studies analysing the subcellular localization of GPR30, its ability to bind (or not to bind) estradiol and to signal (or not to signal) in response to estradiol. In the second part, we discuss the strengths and limitations of four available GPR30 mouse models. We elucidate the potential impact of different targeting strategies on phenotypic diversity. Copyright 2010 Elsevier Inc. All rights reserved.

Testing ER-Beta Agonist Synergy with B7-H1 and mTOR Inhibitors as Novel and Effective Treatments for Ovarian Cancer

DTIC Science & Technology

2016-08-01

other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a...RESPONSIBLE PERSON USAMRMC a. REPORT Unclassified b. ABSTRACT Unclassified c. THIS PAGE Unclassified Unclassified 19b. TELEPHONE...alter tumor growth when given 7 days after tumor challenge. When we added αB7-H1 to LY, we got a borderline significant improvement in survival in

Effect of low-level laser therapy (660 nm) on the healing of second-degree skin burns in rats.

PubMed

Renno, Ana Claudia Muniz; Iwama, Angela May; Shima, Patricia; Fernandes, Kelly Rossetti; Carvalho, Juliana Gonçalves; De Oliveira, Poliani; Ribeiro, Daniel Araki

2011-10-01

The aim of this study was to investigate the effects of 660 nm laser on the healing of burn wounds made on the backs of rats. Thirty-two Wistar male rats were used. The animals were randomly distributed into 2 groups of 16 animals each: control group (burned rats without treatment) and laser-treated group (burned rats treated with laser therapy). Each group was divided into two different subgroups, euthanized in different periods (subgroup A: 7 days post-surgery and subgroup B: 14 days post-surgery). Histopathological analysis revealed a significant decrease in the necrotic area in the laser-treated group compared to the controls at days 7 and 14 post-injury. COX-2 positive cells were found in a strong pattern in the group submitted to laser therapy after 7 days. Regarding VEGF immunomarker, a significant VEGF immunoexpression was detected in the laser-exposed group after 14 days when compared to the negative control group. Taken together, our results demonstrate that laser therapy is able to promote skin repair of burned rats as a result of decreasing necrotic area and an up-regulation of COX-2 and VEGF immunoexpression.

Correlation between cell cycle proteins and hMSH2 in actinic cheilitis and lip cancer.

PubMed

Lopes, Maria Luiza Diniz de Sousa; de Oliveira, Denise Hélen Imaculada Pereira; Sarmento, Dmitry José de Santana; Queiroz, Lélia Maria Guedes; Miguel, Márcia Cristina da Costa; da Silveira, Éricka Janine Dantas

2016-04-01

This study aims to evaluate and verify the relationship between the immunoexpression of hMSH2, p53 and p21 in actinic cheilitis (AC) and lower lip squamous cell carcinoma (SCC) cases. Forty AC and 40 SCC cases were submitted to immunoperoxidase method and quantitatively analyzed. Expression was compared by Mann-Whitney test, Student t test or one-way ANOVA. To correlate the variables, Pearson's correlation coefficient was calculated. The expression of p53 and p21 showed no significant differences between histopathological grades of AC or lower lip SCC (p > 0.05). Immunoexpression of p53 was higher in SCC than in AC (p < 0.001), while p21 expression was more observed in AC when compared to SCC group (p = 0.006). The AC group revealed an inverse correlation between p53 and hMSH2 expression (r = -0.30, p = 0.006). Alterations in p53 and p21 expression suggest that these proteins are involved in lower lip carcinogenesis. Moreover, p53 and hMSH2 seem to be interrelated in early events of this process.

Sex steroid-related genes and male-to-female transsexualism.

PubMed

Henningsson, Susanne; Westberg, Lars; Nilsson, Staffan; Lundström, Bengt; Ekselius, Lisa; Bodlund, Owe; Lindström, Eva; Hellstrand, Monika; Rosmond, Roland; Eriksson, Elias; Landén, Mikael

2005-08-01

Transsexualism is characterised by lifelong discomfort with the assigned sex and a strong identification with the opposite sex. The cause of transsexualism is unknown, but it has been suggested that an aberration in the early sexual differentiation of various brain structures may be involved. Animal experiments have revealed that the sexual differentiation of the brain is mainly due to an influence of testosterone, acting both via androgen receptors (ARs) and--after aromatase-catalyzed conversion to estradiol--via estrogen receptors (ERs). The present study examined the possible importance of three polymorphisms and their pairwise interactions for the development of male-to-female transsexualism: a CAG repeat sequence in the first exon of the AR gene, a tetra nucleotide repeat polymorphism in intron 4 of the aromatase gene, and a CA repeat polymorphism in intron 5 of the ERbeta gene. Subjects were 29 Caucasian male-to-female transsexuals and 229 healthy male controls. Transsexuals differed from controls with respect to the mean length of the ERbeta repeat polymorphism, but not with respect to the length of the other two studied polymorphisms. However, binary logistic regression analysis revealed significant partial effects for all three polymorphisms, as well as for the interaction between the AR and aromatase gene polymorphisms, on the risk of developing transsexualism. Given the small number of transsexuals in the study, the results should be interpreted with the utmost caution. Further study of the putative role of these and other sex steroid-related genes for the development of transsexualism may, however, be worthwhile.

Low-level laser irradiation promotes the proliferation and maturation of keratinocytes during epithelial wound repair

PubMed Central

Sperandio, Felipe F.; Simões, Alyne; Corrêa, Luciana; Aranha, Ana Cecília C.; Giudice, Fernanda S.; Hamblin, Michael R.; Sousa, Suzana C.O.M.

2015-01-01

Low-level laser therapy (LLLT) has been extensively employed to improve epithelial wound healing, though the exact response of epithelium maturation and stratification after LLLT is unknown. Thus, this study aimed to assess the in vitro growth and differentiation of keratinocytes (KCs) and in vivo wound healing response when treated with LLLT. Human KCs (HaCaT cells) showed an enhanced proliferation with all the employed laser energy densities (3, 6 and 12 J/cm2, 660nm, 100mW), together with an increased expression of Cyclin D1. Moreover, the immunoexpression of proteins related to epithelial proliferation and maturation (p63, CK10, CK14) all indicated a faster maturation of the migrating KCs in the LLLT-treated wounds. In that way, an improved epithelial healing was promoted by LLLT with the employed parameters; this improvement was confirmed by changes in the expression of several proteins related to epithelial proliferation and maturation. PMID:25411997

Analysis of hepatocyte growth factor immunostaining in the placenta of HIV-infected normotensive versus preeclamptic pregnant women.

PubMed

Cele, S B; Odun-Ayo, F; Onyangunga, O A; Moodley, J; Naicker, T

2018-08-01

Hepatocyte Growth Factor (HGF) plays a role in the migration and morphogenesis of different cell types and tissues. Preeclampsia (PE) is associated with deficient trophoblast invasion and placental insufficiency; hence HGF production is expected to be compromised. This study therefore aimed to immunolocalize and morphometrically analyse placental HGF in normotensive versus PE pregnancies stratified by HIV status and gestational age. Normotensive (N; n = 40) and preeclamptic (PE; n = 80) women were stratified by HIV status (HIV- and HIV+), and gestational age i.e. early onset of PE (EOPE; <34 weeks) and late onset of PE (LOPE; ≥34 weeks). Placental tissues were stained using conventional immunohistochemistry, performed using mouse anti-human HGF antibody. Morphometric image analysis was performed using Zeiss Axio-Vision software. HGF was immuno-localized within the syncytiotrophoblast, cytotrophoblast, endothelial and fibroblast-like cell populations of both conducting and exchange villi. Based on pregnancy type, HGF immunoexpression within the conducting villi was significantly different between Nvs EOPE (p = 0.0372) and EOPE vs LOPE (p = 0.0006). Within the exchange villi, no significant difference of HGF immunostaining was noted between N vs EOPE and N vs LOPE. A down-regulation of HGF immuno-expression was observed in LOPE compared to other groups within both villi types, albeit non-significant. Based on HIV status, no significant difference in HGF immuno-expression was demonstrated between HIV- vs HIV + within the exchange and conducting villi. However, the expression of HGF in HIV- group was elevated in both villi types. Across the groups, a significant difference was found between N+ vs EOPE- (p  = 0.0207), EOPE+ vs LOPE- (p = 0.0036) and EOPE- vs LOPE- (p = 0.0016) of the conducting villi while no significant difference was found within the exchange villi. This novel study demonstrates that HGF was two-fold higher in conducting compared to exchange villi irrespective of the pregnancy type. HIV infection does not influence HGF expression within the conducting and exchange villi. The HGF/c-MET receptor complex may modulate the ligand expression within the placenta. Copyright © 2018 Elsevier B.V. All rights reserved.

Mechanisms of spinal motoneurons survival in rats under simulated hypogravity on earth

NASA Astrophysics Data System (ADS)

Islamov, R. R.; Mishagina, E. A.; Tyapkina, O. V.; Shajmardanova, G. F.; Eremeev, A. A.; Kozlovskaya, I. B.; Nikolskij, E. E.; Grigorjev, A. I.

2011-05-01

It was previously shown that different cell types in vivo and in vitro may die via apoptosis under weightlessness conditions in space as well as in simulated hypogravity on the Earth. We assessed survivability of spinal motoneurons of rats after 35-day antiorthostatic hind limb suspension. Following weight bearing, unloading the total protein content in lumbar spinal cord is dropped by 21%. The electrophysiological studies of m. gastrocnemius revealed an elevated motoneurons' reflex excitability and conduction disturbances in the sciatic nerve axons. The number of myelinated fibers in the ventral root of experimental animals was insignificantly increased by 35-day of antiorthostatic hind limb suspension, although the retrograde axonal transport was significantly decreased during the first week of simulated hypogravity. The results of the immunohistochemical assay with antibodies against proapoptotic protein caspase 9 and cytotoxicity marker neuron specific nitric oxide synthase (nNOS) and the TUNEL staining did not reveal any signs of apoptosis in motoneurons of suspended and control animals. To examine the possible adaptation mechanisms activated in motoneurons in response to simulated hypogravity we investigated immunoexpression of Hsp25 and Hsp70 in lumbar spinal cord of the rats after 35-day antiorthostatic hind limb suspension. Comparative analysis of the immunohistochemical reaction with anti-Hsp25 antibodies revealed differential staining of motoneurons in intact and experimental animals. The density of immunoprecipitate with anti-Hsp25 antibodies was substantially higher in motoneurons of the 35-day suspended than control rats and the more intensive precipitate in this reaction was observed in motoneuron neuritis. Quantitative analysis of Hsp25 expression demonstrated an increase in the Hsp25 level by 95% in experimental rats compared to the control. The immunoexpression of Hsp70 found no qualitative and quantitative differences in control and experimental lumbar spinal cords. Taken together our results show that (1) rat motoneurons survived after 35-day antiorthostatic hind limb suspension and the changes in neurons had a mostly functional character, and (2) the increased immunoexpression of Hsp25 can be considered as the anti-apoptotic factor.

A selective estrogen receptor modulator for the treatment of hot flushes.

PubMed

Wallace, Owen B; Lauwers, Kenneth S; Dodge, Jeffrey A; May, Scott A; Calvin, Joel R; Hinklin, Ronald; Bryant, Henry U; Shetler, Pamela K; Adrian, Mary D; Geiser, Andrew G; Sato, Masahiko; Burris, Thomas P

2006-02-09

A selective estrogen receptor modulator (SERM) for the potential treatment of hot flushes is described. (R)-(+)-7,9-difluoro-5-[4-(2-piperidin-1-ylethoxy)phenyl]-5H-6-oxachrysen-2-ol, LSN2120310, potently binds ERalpha and ERbeta and is an antagonist in MCF-7 breast adenocarcinoma and Ishikawa uterine cancer cell lines. The compound is a potent estrogen antagonist in the rat uterus. In ovariectomized rats, the compound lowers cholesterol, maintains bone mineral density, and is efficacious in a morphine dependent rat model of hot flush efficacy.

Immunoexpression of Th17-related cytokines in oral lichen planus.

PubMed

Monteiro, Bárbara Vanessa de Brito; Pereira, Joabe Dos Santos; Nonaka, Cassiano F W; Godoy, Gustavo P; da Silveira, Éricka J D; Miguel, Márcia Cristina da Costa

2015-07-01

A recently described lineage of lymphocytes, Th17 cells, has been associated with inflammatory and autoimmune diseases. The aim of this article was to assess the immunoexpression of cytokines related to this lineage, interleukin-17 (IL-17) and IL-23 and in reticular and erosive oral lichen planus (OLP). The sample included 41 cases of OLP (23 reticular and 18 erosive) and 10 cases of inflammatory fibrous hyperplasia (IFH). Lymphocytes exhibiting cytoplasmic immunostaining were counted. Epithelial immunostaining was also evaluated. There was no statistical differences in the number of IL-17 and IL-23 lymphocytes between the OLP (55.40 and 48.40, respectively) and IFH (39.30 and 44.40, respectively). A significantly higher number of IL-23 lymphocytes was found in erosive OLP group (63.80) when compared with reticular (41.40) and IFH lesions (44.40) (P=0.019). Furthermore, epithelial immunopositivity for IL-17 and IL-23 was higher in OLP lesions than in IFH (P=0.012 and P=0.011, respectively). A significantly higher number of IL-23 lymphocytes in erosive OLP and the strong epithelial immunopositivity for IL-23 and IL-17 in OLP group could suggest an important participation of TCD4 Th17 response in this disorder.

The Immunoexpression of Glucocorticoid Receptors in Breast Carcinomas, Lactational Change, and Normal Breast Epithelium and Its Possible Role in Mammary Carcinogenesis

PubMed Central

Wazir, Javed Fayyaz; Brahmi, Urmil Prabha; Fakhro, Abdul Rahman

2017-01-01

The role of estrogen and progesterone receptors in breast cancer biology is well established. In contrast, other steroid hormones are less well studied. Glucocorticoids (GCs) are known to play a role in mammary development and differentiation; thus, it is of interest to attempt to delineate their immunoexpression across a spectrum of mammary epithelia. Aim. To delineate the distribution pattern of glucocorticoid receptors (GRs) in malignant versus nonmalignant epithelium with particular emphasis on lactational epithelium. Materials and Methods. Immunohistochemistry (IHC) for GRs was performed on archival formalin-fixed paraffin-embedded tissue blocks of 96 cases comprising 52 invasive carcinomas, 21 cases with lactational change, and 23 cases showing normal mammary tissue histology. Results. Results reveal an overexpression of GRs in mammary malignant epithelium as compared to both normal and lactational groups individually and combined. GR overexpression is significantly more pronounced in HER-2-negative cancers. Discussion. This is the first study to compare GR expression in human lactating epithelium versus malignant and normal epithelium. The article discusses the literature related to the pathobiology of GCs in the breast with special emphasis on breast cancer. Conclusion. The lactational epithelium did not show overexpression of GR, while GR was overexpressed in mammary NST (ductal) carcinoma, particularly HER-2-negative cancers. PMID:29348941

Grape juice concentrate modulates p16 expression in high fat diet-induced liver steatosis in Wistar rats.

PubMed

Ferreira, Andressa Orlandeli; Gollücke, Andréa Pittelli Boiago; Noguti, Juliana; da Silva, Victor Hugo Pereira; Yamamura, Elsa Tiemi Hojo; Ribeiro, Daniel Araki

2012-04-01

The goal of this study was to investigate whether subchronic treatment with grape juice concentrate is able to protect the liver from high fat diet injury in rats. The effects of grape juice concentrate treatment on histopathological changes, and immunohistochemistry for p53, p16 and p21 were evaluated. Male Wistar rats (n = 18) were distributed into three groups: group 1: negative control; group 2: cholesterol at 1% (w/w) in their diet, treated during 5 weeks; and group 3: cholesterol at 1% in their chow during 5 weeks, and grape juice concentrate at 222 mg per day in their drinking-water in the last week only. The results pointed out that treatment with grape juice concentrate did not show remarkable differences regarding liver tissue in the cholesterol-exposed group when compared to group 2. However, grape juice concentrate was able to modulate p16 immunoexpression when compared to high fat diet group. p53 and p21 did not show any significant statistical differences among groups. Taken together, our results suggest that subchronic grape juice concentrate administration was able to modulate cell cycle control by downregulation of p16 immunoexpression in high fat diet-induced liver steatosis in rats.

Characterization of an ICII82, 780-Induced, Estrogen Receptor (ER)-beta Mediated Apoptotic Pathway in Prostate Cancer Cells and Establishment of (ER)-beta-Regulated Electrophile-Processing Phase II Enzyme Downregulation as a Promotional Factor in Human Prostatic Carcinogenesis

DTIC Science & Technology

2001-05-01

absent in higher-grade cancers. ERP3 expression reappeared in metastatic prostatic carcinomas . The results were also compared to ERMo and androgen...metastatic prostatic carcinomas in bone and lymph nodes. The results were compared to ERax and androgen receptor expressions in those samples. Taken... carcinomas of the peripheral zone were in contrast strongly positive for the 13 receptor whereas its expression in grade 415 cancers was negligible to

The role of oestrogens in the adaptation of islets to insulin resistance.

PubMed

Nadal, Angel; Alonso-Magdalena, Paloma; Soriano, Sergi; Ropero, Ana B; Quesada, Ivan

2009-11-01

Pregnancy is characterized by peripheral insulin resistance, which is developed in parallel with a plasma increase of maternal hormones; these include prolactin, placental lactogens, progesterone and oestradiol among others. Maternal insulin resistance is counteracted by the adaptation of the islets of Langerhans to the higher insulin demand. If this adjustment is not produced, gestational diabetes may be developed. The adaptation process of islets is characterized by an increase of insulin biosynthesis, an enhanced glucose-stimulated insulin secretion (GSIS) and an increase of beta-cell mass. It is not completely understood why, in some individuals, beta-cell mass and function fail to adapt to the metabolic demands of pregnancy, yet a disruption of the beta-cell response to maternal hormones may play a key part. The role of the maternal hormone 17beta-oestradiol (E2) in this adaptation process has been largely unknown. However, in recent years, it has been demonstrated that E2 acts directly on beta-cells to increase insulin biosynthesis and to enhance GSIS through different molecular mechanisms. E2 does not increase beta-cell proliferation but it is involved in beta-cell survival. Classical oestrogen receptors ERalpha and ERbeta, as well as the G protein-coupled oestrogen receptor (GPER) seem to be involved in these adaptation changes. In addition, as the main production of E2 in post-menopausal women comes from the adipose tissue, E2 may act as a messenger between adipocytes and islets in obesity.

Low-level laser therapy induces an upregulation of collagen gene expression during the initial process of bone healing: a microarray analysis

NASA Astrophysics Data System (ADS)

Tim, Carla Roberta; Bossini, Paulo Sérgio; Kido, Hueliton Wilian; Malavazi, Iran; von Zeska Kress, Marcia Regina; Carazzolle, Marcelo Falsarella; Rennó, Ana Cláudia; Parizotto, Nivaldo Antonio

2016-08-01

This study investigates the histological modifications produced by low level laser therapy (LLLT) on the first day of bone repair, as well as evaluates the LLLT effects on collagen expression on the site of a fracture. Twenty Wistar rats were distributed into a control group (CG) and a laser group (LG). Laser irradiation of Ga-Al-As laser 830 nm, 30 mW, 94 s, 2.8 J was performed in five sessions. Animals were euthanized on day 5 postsurgery. Histopathological analysis showed that LLLT was able to increase deposition of granulation tissue and newly formed bone at the site of the injury. In addition, picrosirius analysis showed that collagen fiber organization in the LG was enhanced compared to CG. Microarray analysis demonstrated that LLLT produced an upregulation type I collagen (COL-I). Immunohistochemical analysis revealed that the subjects that were treated presented a higher immunoexpression of COL-I. Our findings indicated that LLLT improves bone healing by producing a significant increase in the expression of collagen genes.

Expression of CD44 and CD29 by PEComa cells suggests their possible origin of mesenchymal stem cells.

PubMed

Liu, Ruixue; Jia, Wei; Zou, Hong; Wang, Xinhua; Ren, Yan; Zhao, Jin; Wang, Lianghai; Li, Man; Qi, Yan; Shen, Yaoyuan; Liang, Weihua; Jiang, Jinfang; Sun, Zhenzhu; Pang, Lijuan; Li, Feng

2015-01-01

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. The perivascular epithelioid cell (PEC) co-expresses melanocytic and muscle markers. Since no normal counterpart to the PEC has ever been identified in any normal tissue, the cell origin of these tumors is still uncertain. Although, several hypotheses have recently been advanced to explain the histogenesis of PEComa, it remains unclear. The aim of this study was to discuss whether differential expression of stem cell-associated proteins could be used to aid in determining the histogenesis of PEComa. For this purpose, we detected the immunoexpression of 5 kinds of stem cell markers on PEComas, including CD29, CD44, CD133, ALDH1, and nestin. In addition to observed histopathologic morphology, we also performed PEComa relevant clinical diagnostic markers (HMB-45, SMA, melan-A, Desmin, Ki-67, S-100 and TFE3) to identify whether they belonged to PEComas. Our study included 13 PEComa samples, and we obtained positive immunoexpression results as follows: CD29 (13/13), CD44 (8/13), ALDH1 (10/13), nestin (1/13), and CD133 (0/13). Since CD44 and CD29 are surface proteins associated with MSCs, these results suggest that PEComa might arise from MSCs. However, whether MSCs are the origin of PEComa needs to be further explored in the future.

The efficacy of Aesculus hippocastanum seeds on diabetic nephropathy in a streptozotocin-induced diabetic rat model.

PubMed

Elmas, Onur; Erbas, Oytun; Yigitturk, Gurkan

2016-10-01

Cytokines, such as transforming growth factor (TGF)-ß1, and increased oxidative stress are considered to be responsible for the development of diabetic nephropathy. We hypothesized that Aesculus hippocastanum (AH) seeds may have preventive effects on oxidative stress and TGF-β-related diabetic nephropathy in streptozotocin (STZ)-induced diabetic nephropathy in rats. Twenty-one male Sprague-Dawley albino rats were divided into three groups (n=7). Except for the control group, they all had diabetic nephropathy induced by an intraperitoneal injection of STZ. While the diabetes group did not receive any medication, the diabetes+AH group was given the medication for 4 weeks. After the experiment, analyses were performed to evaluate the glomerular area, severity of sclerosis, and fibronectin immunoexpression, as well as levels of malondialdehyde (MDA), TGF-β, blood urea nitrogen (BUN), blood glucose, creatinine, and proteinuria. It was found that glomerular area, severity of sclerosis, fibronectin immunoexpression, and levels of MDA, TGF-β, BUN, creatinine, and proteinuria were decreased in the diabetes+AH group. It is known that diabetic nephropathy is induced, to a large extent, by hyperglycemia. In the present study, AH extract ameliorated diabetic nephropathy without decrease in blood glucose levels. In the study, AH seeds showed beneficial effects on the functional properties of the kidney and microscopic improvements in diabetic nephropathy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Immunoexpression of intermediate filaments and morphological changes in the liver and bile duct of rats infected with Fasciola hepatica.

PubMed

Kolodziejczyk, L; Laszczyńska, M; Masiuk, M; Grabowska, M; Skrzydlewska, E

2015-01-01

We investigated the immunoexpression of the intermediate filament proteins, cytokeratin and desmin, and the morphological changes in the liver of rats during experimental fasciolosis at 4, 7 and 10 weeks post-infection. Rats were infected with 30 Fasciola hepatica metacercariae. Paraffin sections of the liver were stained using H & E, PAS and azan stains. Immunohistochemical reactions were performed using antibodies against cytokeratin and desmin. The experimental F. hepatica infection led to fibrosis and cirrhosis of the liver, and to inflammation of the common bile ducts. The expression of cytokeratin was increased in the epithelial cells of both the liver bile ductules at 4, 7 and 10 weeks post-infection and in the common bile ducts at 7 and 10 weeks post-infection compared to uninfected rats; expression in the common bile ducts was more intense. The myofibroblasts of the liver and smooth myocytes of the interlobular bile ducts and common bile ducts, showed a slight increase in desmin expression compared to the uninfected rats. The increased expression of cytokeratins in the hyperplastic rat common bile duct epithelium during the biliary phase of fasciolosis at 7 and 10 weeks post-infection may be explained by mechanical irritation by the parasite and an inflammatory reaction in the bile duct epithelium and in periductal fibrous tissue.

Comparison of immunoexpression of 2 antibodies for estrogen receptors (1D5 and 6F11) in breast carcinomas using different antigen retrieval and detection methods.

PubMed

Vassallo, J; Pinto, G A; Alvarenga, J M; Zeferino, L C; Chagas, C A; Metze, K

2004-06-01

The importance of in situ immunodetection of hormone receptors for therapy planning and prognostic evaluation in patients with breast carcinoma is well established. Sensitive detection methods are of utmost importance, especially in poorly fixed tissues, which are not uncommon in routine pathologic practice. The purpose of the present study is to compare immunoexpression of estrogen receptors in 20 cases of invasive ductal carcinoma using two antibodies, 1D5 and 6F11, and to verify the effect of different antigen retrieval solutions and detection systems. Immunoperoxidase was performed on paraffin sections using 1D5 and 6F11 as primary antibodies. Heat-induced antigen retrieval was performed using citrate buffer (pH 6.0) or Tris-EDTA buffer (pH 8.9). Detection was achieved using the following systems: EnVision, EnVision Plus, and labeled streptavidin-biotin peroxidase complex. Reaction was semiquantified from 0 to 4. There were no differences between the two markers, 1D5 and 6F11, except when 6F11 was used with EnVision and citrate buffer, in which case weaker reactivity was observed. Only in this combination (6F11/EnVision) was EDTA buffer significantly better than citrate. Labeled streptavidin-biotin peroxidase complex presented the best results, followed by EnVision Plus.

Influence of surgical decompression on the expression of inflammatory and tissue repair biomarkers in periapical cysts.

PubMed

Rodrigues, Janderson Teixeira; Dos Santos Antunes, Henrique; Armada, Luciana; Pires, Fábio Ramôa

2017-12-01

The biologic effects of surgical decompression on the epithelium and connective tissues of periapical cysts are not fully understood. The aim of this study was to evaluate the expression of tissue repair and inflammatory biomarkers in periapical cysts before and after surgical decompression. Nine specimens of periapical cysts treated with decompression before undergoing complete enucleation were immunohistochemically analyzed to investigate the expression of interleukin-1β, tumor necrosis factor-α, transforming growth factor-β1, matrix metalloproteinase-9, Ki-67, and epidermal growth factor receptor. Expression of the biomarkers was classified as positive, focal, or negative. Ki-67 immunoexpression was calculated as a cell proliferation index. The expression of the biomarkers was compared in the specimens from decompression and from the final surgical procedure. Computed tomography demonstrated that volume was reduced in all cysts after decompression. There were no differences in the immunoexpression of the proinflammatory and tissue repair biomarkers when comparing the specimens obtained before and after the decompression. Surgical decompression was efficient in reducing the volume of periapical cysts before complete enucleation. When comparing the specimens obtained from surgical decompression and from complete surgical removal, the immunohistochemical analysis did not show a decrease in proinflammatory biomarkers; neither did it show an increase in tissue repair biomarkers. Copyright © 2017 Elsevier Inc. All rights reserved.

EVALUATION OF P53, E-CADHERIN, COX-2, AND EGFR PROTEIN IMUNNOEXPRESSION ON PROGNOSTIC OF RESECTED GALLBLADDER CARCINOMA

PubMed Central

PAIS-COSTA, Sergio Renato; FARAH, José Francisco de Matos; ARTIGIANI-NETO, Ricardo; MARTINS, Sandro José; GOLDENBERG, Alberto

2014-01-01

Background Gallbladder carcinoma presents a dismal prognosis. Choice treatment is surgical resection that is associated a high levels of both morbidity and mortality. Best knowledgement of prognostic factors may result a better selection of patients either for surgical or multimodal treatment. Aim To evaluate tecidual immunoexpression of P53, E-cadherin, Cox-2, and EGFR proteins and to correlate these findings with resected gallbladder adenocarcinoma survival. Methods Clinical, laboratorial, surgical, and anatomopathological reports of a series of gallbladder adenocarcinoma patients were collected by individualized questionary. Total sample was 42 patients. Median of age was 72 years (35-87). There were seven men and 35 women. Lesion distribuition in according TNM state was the following: T1 (n=2), T2 (n=5), T3 (n=31), T4 (n=4). Twenty-three patients underwent radical resection (R0), while 19 palliative surgery (R1-R2). A block of tissue microarray with neoplasic tissue of each patient was confected. It was performed evaluation of P53, E-Caderine, COX-2, and EGFR proteins imunoexpression. These findings were correlated with overall survival. Results Five-year survival was 28%. The median of global survival was eight months. Only immunoexpression of EGFR protein was considered independent variable at multivariated analysis. Conclusion Final prognosis was influenced by over-expression of EGFR protein in tumoral tissue. PMID:25004291

Dietary isoflavones act on bone marrow osteoprogenitor cells and stimulate ovary development before influencing bone mass in pre-pubertal piglets.

PubMed

De Wilde, Anne; Maria Rassi, Claudia; Cournot, Giulia; Colin, Colette; Lacroix, Herminie C; Chaumaz, Gilles; Coxam, Veronique; Bennetau-Pelissero, Catherine; Pointillart, Alain; Lieberherr, Michele

2007-07-01

Food containing soybeans provide isoflavone phytoestrogens that can preserve bone mass in postmenopausal women, and prevent bone loss in ovariectomized rats. But their effects on bone remain unclear, particularly on bone formation during growth. Two groups of eight pre-pubertal piglets were fed a basal or an isoflavone-enriched (S800) diet for 6 weeks. The S800 diet contained 800 mg SoyLifetrade mark/kg, providing 2.8 mg isoflavones/kg body weight/day. Several bones were collected and tested for bone strength and density. Bone marrow was collected from humeri together with blood samples and genital tracts. The plasma concentrations of isoflavones were increased in the pigs fed S800, but growth rate, body weight, plasma bone markers, bone mineral density, and strength were all unaffected. In contrast, cultured stromal cells from S800 pigs had more alkaline phosphatase-rich cells and mineralized nodules, secreted more osteocalcin, osteoprotegerin and RANK-L, synthesized more osteoprotegerin, and RANK-L. Cultured mononucleated nonadherent bone marrow cells from S800 pigs developed fewer tartrate-resistant acid phosphatase mononucleated cells (osteoclast progenitors) when cultured with 1,25(OH)(2)D(3), and resorbed a smaller area of dentine slices. Freshly isolated bone marrow osteoclast progenitors from S800 pigs had more caspase-3 cleavage activity, and synthesized less RANK. Both osteoclast and osteoblast progenitors had ERalpha and ERbeta, whose syntheses were stimulated by the S800 diet. The S800 piglets had heavier ovaries with more follicles, but their uterus weight was unaffected. We conclude that dietary isoflavones have no detectable effect on the bone mass of growing female piglets, but act on bone marrow osteoprogenitors via ERs--mainly ERbeta, and stimulate ovary development.

Steroid receptor profiling of vinclozolin and its primary metabolites.

PubMed

Molina-Molina, José-Manuel; Hillenweck, Anne; Jouanin, Isabelle; Zalko, Daniel; Cravedi, Jean-Pierre; Fernández, Mariana-Fátima; Pillon, Arnaud; Nicolas, Jean-Claude; Olea, Nicolás; Balaguer, Patrick

2006-10-01

Several pesticides and fungicides commonly used to control agricultural and indoor pests are highly suspected to display endocrine-disrupting effects in animals and humans. Endocrine disruption is mainly caused by the interference of chemicals at the level of steroid receptors: it is now well known that many of these chemicals can display estrogenic effects and/or anti-androgenic effects, but much less is known about the interaction of these compounds with other steroid receptors. Vinclozolin, a dicarboximide fungicide, like its primary metabolites 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), is known to bind androgen receptor (AR). Although vinclozolin and its metabolites were characterized as anti-androgens, relatively little is known about their effects on the function of the progesterone (PR), glucocorticoid (GR), mineralocorticoid (MR) or estrogen receptors (ERalpha and ERbeta). Objectives of the study were to determine the ability of vinclozolin and its two primary metabolites to activate AR, PR, GR, MR and ER. For this purpose, we used reporter cell lines bearing luciferase gene under the control of wild type or chimeric Gal4 fusion AR, PR, GR, MR or ERs. We confirmed that all three were antagonists for AR, whereas only M2 was found a partial agonist. Interestingly, M2 was also a PR, GR and MR antagonist (MR>PR>GR) while vinclozolin was an MR and PR antagonist. Vinclozolin, M1 and M2 were agonists for both ERs with a lower affinity for ERbeta. Although the potencies of the fungicide and its metabolites are low when compared to natural ligands, their ability to act via more than one mechanism and the potential for additive or synergistic effect must be taken into consideration in the risk assessment process.

Stimulating the GPR30 estrogen receptor with a novel tamoxifen analogue activates SF-1 and promotes endometrial cell proliferation.

PubMed

Lin, Benjamin C; Suzawa, Miyuki; Blind, Raymond D; Tobias, Sandra C; Bulun, Serdar E; Scanlan, Thomas S; Ingraham, Holly A

2009-07-01

Estrogens and selective estrogen receptor (ER) modulators such as tamoxifen are known to increase uterine cell proliferation. Mounting evidence suggests that estrogen signaling is mediated not only by ERalpha and ERbeta nuclear receptors, but also by GPR30 (GPER), a seven transmembrane (7TM) receptor. Here, we report that primary human endometriotic H-38 cells express high levels of GPR30 with no detectable ERalpha or ERbeta. Using a novel tamoxifen analogue, STX, which activates GPR30 but not ERs, significant stimulation of the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways was observed in H-38 cells and in Ishikawa endometrial cancer cells expressing GPR30; a similar effect was observed in JEG3 choriocarcinoma cells. STX treatment also increased cellular pools of phosphatidylinositol (3,4,5) triphosphate, a proposed ligand for the nuclear hormone receptor SF-1 (NR5A1). Consistent with these findings, STX, tamoxifen, and the phytoestrogen genistein were able to increase SF-1 transcription, promote Ishikawa cell proliferation, and induce the SF-1 target gene aromatase in a GPR30-dependent manner. Our findings suggest a novel signaling paradigm that is initiated by estrogen activation of the 7TM receptor GPR30, with signal transduction cascades (PI3K and MAPK) converging on nuclear hormone receptors (SF-1/LRH-1) to modulate their transcriptional output. We propose that this novel GPR30/SF-1 pathway increases local concentrations of estrogen, and together with classic ER signaling, mediate the proliferative effects of synthetic estrogens such as tamoxifen, in promoting endometriosis and endometrial cancers.

Estrogen signaling is not required for prostatic bud patterning or for its disruption by 2,3,7,8-tetrachlorodibenzo-p-dioxin

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

Allgeier, Sarah Hicks; Vezina, Chad M.; Lin, T.-M.

2009-08-15

Estrogens play an important role in prostatic development, health, and disease. While estrogen signaling is essential for normal postnatal prostate development, little is known about its prenatal role in control animals. We tested the hypothesis that estrogen signaling is needed for normal male prostatic bud patterning. Budding patterns were examined by scanning electron microscopy of urogenital sinus epithelium from wild-type mice, mice lacking estrogen receptor (ER){alpha}, ER{beta}, or both, and wild-type mice exposed to the antiestrogen ICI 182,780. Budding phenotypes did not detectably differ among any of these groups, strongly suggesting that estrogen signaling is not needed to establish themore » prototypical prostatic budding pattern seen in control males. This finding contributes to our understanding of the effects of low-level estrogen exposure on early prostate development. In utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can greatly alter the pattern in which prostatic buds form and reduce their number. For several reasons, including a prior observation that inhibitory effects of TCDD on prostatic budding in rats depend heavily on the sex of adjacent fetuses, we tested the hypothesis that estrogen signaling is needed for TCDD to disrupt prostatic budding. However, budding did not detectably differ among wild-type mice, or mice lacking ER{alpha}, ER{beta}, or both, that were exposed prenatally to TCDD (5 {mu}g/kg on embryonic day 13.5). Nor did ICI 182,780 detectably affect the response to TCDD. These results strongly suggest that estrogen signaling is not needed for TCDD to inhibit prostatic epithelial budding.« less

Rapid activation of ERK1/2 and AKT in human breast cancer cells by cadmium

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

Liu Zhiwei; Yu Xinyuan; Shaikh, Zahir A.

2008-05-01

Cadmium (Cd), an endocrine disruptor, can induce a variety of signaling events including the activation of ERK1/2 and AKT. In this study, the involvement of estrogen receptors (ER) in these events was evaluated in three human breast caner cell lines, MCF-7, MDA-MB-231, and SK-BR-3. The Cd-induced signal activation patterns in the three cell lines mimicked those exhibited in response to 17{beta}-estradiol. Specifically, treatment of MCF-7 cells, that express ER{alpha}, ER{beta} and GPR30, to 0.5-10 {mu}M Cd for only 2.5 min resulted in transient phosphorylation of ERK1/2. Cd also triggered a gradual increase and sustained activation of AKT during the 60more » min treatment period. In SK-BR-3 cells, that express only GPR30, Cd also caused a transient activation of ERK1/2, but not of AKT. In contrast, in MDA-MB-231 cells, that express only ER{beta}, Cd was unable to cause rapid activation of either ERK1/2 or AKT. A transient phosphorylation of ER{alpha} was also observed within 2.5 min of Cd exposure in the MCF-7 cells. While the estrogen receptor antagonist, ICI 182,780, did not prevent the effect of Cd on these signals, specific siRNA against hER{alpha} significantly reduced Cd-induced activation of ERK1/2 and completely blocked the activation of AKT. It is concluded that Cd, like estradiol, can cause rapid activation of ERK1/2 and AKT and that these signaling events are mediated by possible interaction with membrane ER{alpha} and GPR30, but not ER{beta}.« less

Decursin and decursinol angelate inhibit estrogen-stimulated and estrogen-independent growth and survival of breast cancer cells.

PubMed

Jiang, Cheng; Guo, Junming; Wang, Zhe; Xiao, Bingxiu; Lee, Hyo-Jung; Lee, Eun-Ok; Kim, Sung-Hoon; Lu, Junxuan

2007-01-01

Estrogen and estrogen receptor (ER)-mediated signaling are crucial for the etiology and progression of human breast cancer. Attenuating ER activities by natural products is a promising strategy to decrease breast cancer risk. We recently discovered that the pyranocoumarin compound decursin and its isomer decursinol angelate (DA) have potent novel antiandrogen receptor signaling activities. Because the ER and the androgen receptor belong to the steroid receptor superfamily, we examined whether these compounds affected ER expression and signaling in breast cancer cells. We treated estrogen-dependent MCF-7 and estrogen-independent MDA MB-231 human breast cancer cells with decursin and DA, and examined cell growth, apoptosis, and ERalpha and ERbeta expression in both cell lines - and, in particular, estrogen-stimulated signaling in the MCF-7 cells. We compared these compounds with decursinol to determine their structure-activity relationship. Decursin and DA exerted growth inhibitory effects on MCF-7 cells through G1 arrest and caspase-mediated apoptosis. These compounds decreased ERalpha in MCF-7 cells at both mRNA and protein levels, and suppressed estrogen-stimulated genes. Decursin and the pure antiestrogen Faslodex exerted an additive growth inhibitory effect on MCF-7 cells. In MDA MB-231 cells, these compounds induced cell-cycle arrests in the G1 and G2 phases as well as inducing apoptosis, accompanied by an increased expression of ERbeta. In contrast, decursinol, which lacks the side chain of decursin and DA, did not have these cellular and molecular activities at comparable concentrations. The side chain of decursin and DA is crucial for their anti-ER signaling and breast cancer growth inhibitory activities. These data provide mechanistic rationales for validating the chemopreventive and therapeutic efficacy of decursin and its derivatives in preclinical animal models of breast cancer.

Reproductive factors, hormone use, estrogen receptor expression and risk of non small-cell lung cancer in women.

PubMed

Schwartz, Ann G; Wenzlaff, Angela S; Prysak, Geoffrey M; Murphy, Valerie; Cote, Michele L; Brooks, Sam C; Skafar, Debra F; Lonardo, Fulvio

2007-12-20

Estrogen receptor (ER) expression in lung tumors suggests that estrogens may play a role in the development of lung cancer. We evaluated the role of hormone-related factors in determining risk of non-small-cell lung cancer (NSCLC) in women. We also evaluated whether risk factors were differentially associated with cytoplasmic ER-alpha and/or nuclear ER-beta expression-defined NSCLC in postmenopausal women. Population-based participants included women aged 18 to 74 years diagnosed with NSCLC in metropolitan Detroit between November 1, 2001 and October 31, 2005. Population-based controls were identified through random digit dialing, matched to patient cases on race and 5-year age group. Interview data were analyzed for 488 patient cases (241 with tumor ER results) and 498 controls. Increased duration of hormone replacement therapy (HRT) use in quartiles was associated with decreased risk of NSCLC in postmenopausal women (odds ratio = 0.88; 95% CI, 0.78 to 1.00; P = .04), adjusting for age, race, pack-years, education, family history of lung cancer, current body mass index, years exposed to second-hand smoke in the workplace, and obstructive lung disease history. Among postmenopausal women, ever using HRT, increasing HRT duration of use in quartiles, and increasing quartiles of estrogen use were significant predictors of reduced risk of NSCLC characterized as ER-alpha and/or ER-beta positive. None of the hormone-related variables were associated with nuclear ER-alpha- or ER-beta-negative NSCLC. These findings suggest that postmenopausal hormone exposures are associated with reduced risk of ER-alpha- and ER-beta-expressing NSCLC. Understanding tumor characteristics may direct development of targeted treatment for this disease.

MF-101, an estrogen receptor beta agonist for the treatment of vasomotor symptoms in peri- and postmenopausal women.

PubMed

Stovall, Dale W; Pinkerton, Joann V

2009-04-01

During peri- and postmenopausal stages, the majority of women experience moderate-to-severe vasomotor symptoms, such as hot flashes and night sweats, that interfere with sleep and reduce quality of life. Estrogen alone or in combination with a progestagen has been the standard therapy for such vasomotor symptoms; however, this therapeutic regimen is associated with severe side effects, such as breast cancer or cardiovascular events. To provide a better treatment option for menopausal women, Bionovo Inc is developing the estrogen receptor (ER)beta-selective agonist MF-101. Selective ER agonists can stimulate either ERalpha or ERbeta and induce tissue-specific estrogen-like effects, thus providing a safer alternative to conventional hormone therapy. MF-101 is derived from 22 herbs that are traditionally used in Chinese medicine for the treatment of menopausal symptoms. MF-101 did not promote the growth of breast cancer cells or stimulate uterine growth in preclinical studies and, in a phase II trial, was demonstrated to be safe and more effective in reducing the frequency and severity of hot flashes in postmenopausal women compared with placebo. To confirm the safety and efficacy of MF-101, larger phase III trials were planned for 2009. Although MF-101 appears to be a promising therapeutic, the herbal composition of the drug may be a disadvantage, because of the increased risk of causing allergic reactions in the general population. Studies with the MF-101-isolated active compounds liquiritigen and chalcone demonstrated selectivity for ERbeta, with no induction of proliferative events. If these isolates were demonstrated to be as effective and safe in clinical trials as preliminary data suggest regarding MF-101, these compounds could change the way clinicians treat menopause-associated symptoms.

ERalpha and ERbeta expression and transcriptional activity are differentially regulated by HDAC inhibitors

PubMed Central

Duong, Vanessa; Licznar, Anne; Margueron, Raphaël; Boulle, Nathalie; Busson, Muriel; Lacroix, Matthieu; Katzenellenbogen, Benita S.; Cavaillès, Vincent; Lazennec, Gwendal

2006-01-01

The proliferative action of ERα largely accounts for the carcinogenic activity of estrogens. By contrast, recent data show that ERβ displays tumor-suppressor properties, thus supporting the interest to identify compounds which could increase its activity. Here, we show that histone deacetylase inhibitors (HDI) up-regulated ERβ protein levels, whereas it decreased ERα expression. Part of this regulation took place at the mRNA level through a mechanism independent of de novo protein synthesis. In addition, we found that, in various cancer cells, the treatment with different HDI enhanced the ligand-dependent activity of ERβ more strongly than that of ERα. On the other hand, in MDA-MB231 and HeLa cells, the expression of ERs modified the transcriptional response to HDI. The use of deletion mutants of both receptors demonstrated that AF1 domain of the receptors was required. Finally, we show that ERβ expression led to a dramatic increased in the antiproliferative activity of HDI, which correlated with a modification of the transcription of genes involved in cell cycle control by HDI. Altogether, these data demonstrate that the interference of ERβ and HDAC on the control of transcription and cell proliferation constitute a promising approach for cancer therapy. PMID:16158045

Biological role of pituitary estrogen receptors ERalpha and ERbeta on progesterone receptor expression and action and on gonadotropin and prolactin secretion in the rat.

PubMed

Sánchez-Criado, José E; Martín De Las Mulas, Juana; Bellido, Carmina; Tena-Sempere, Manuel; Aguilar, Rafaela; Blanco, Alfonso

2004-01-01

Estrogen (E) is a key regulator of the synthesis and secretion of pituitary reproductive hormones [luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL)]. Until recently, it was thought that all biological actions of E at the pituitary were manifested through a single E receptor (R). The pituitary, like many other reproductive tissues, expresses two isoforms of ER, alpha and beta, both activated by E. The relative contribution of alpha and beta forms in E regulatory actions is largely unknown. To this end, 2-week-old ovariectomized (OVX) rats were injected over 3 days with 25 microg estradiol benzoate (EB), 1.5 mg of propylpyrazole triol (PPT), a selective ERalpha agonist, 1.5 mg of the selective ERbeta agonist diarylpropionitrile (DPN) or a combination of PPT and DPN. Controls were injected with 0.2 ml oil. At 10:00 h on the day after treatment, trunk blood was collected to determine serum concentration of LH, FSH and PRL, and pituitaries were processed for RT-PCR analysis of total (A+B) progesterone receptor (PR) mRNA, immunocytochemistry of PR and incubation. Pituitaries from each of the five groups were incubated in DMEM, with or without 20 nM of the antiprogestin at the receptor ZK299, for 3 h with: 10(-8)M 17beta-estradiol, 10(-6)M PPT, 10(-6)M DPN, PPT+DPN or medium alone, respectively, to determine LH, FSH and PRL secretion, and, when challenged with two pulses of 15 min 1 h apart of 10(-8)M gonadotropin-releasing hormone (GnRH) (GnRH self-priming). EB, PPT and PPT+DPN treatments increased PR mRNA and the number and intensity of nuclei immunoreactive (IR) for PR in gonadotropes, and reduced the number of gonadectomy cells. Like E, PPT alone or in combination with DPN stimulated PRL secretion, increased basal and GnRH-stimulated LH and FSH secretion and induced GnRH self-priming in the absence of ZK299 in the incubation medium. DPN alone had only a significant E-like effect on gonadectomy cells and IR-PR, but not on GnRH self-priming. In addition, while DPN lacked an agonistic action on peripheral tissue and serum pituitary reproductive hormones concentration, EB, PPT and PPT+DPN induced similar uterine ballooning and vaginal cornification, and increased and decreased, respectively, serum concentrations of PRL and gonadotropins. Overall, these results indicate that most of these E actions on the pituitary are exerted through the ERalpha isoform. The finding that activation of ERbeta with its selective DPN agonist had an estrogenic effect on IR-PR nuclei, but not on GnRH self-priming, a characteristic ERalpha-mediated effect of E, suggests that the biological action of E at the pituitary may involve both isoforms of ER.

Immunoexpression of PPAR-γ and osteocalcin proteins for bone repair of critical-size defects treated with fragmented autogenous abdominal adipose tissue graft.

PubMed

Deliberador, Tatiana Miranda; Giovanini, Allan Fernando; Lopes, Tertuliano Ricardo; Zielak, João César; Moro, Alexandre; Baratto Filho, Flares; Santos, Felipe Rychuv; Storrer, Carmen L Mueller

2014-01-01

Immunoexpression of PPAR-γ and osteocalcin proteins was evaluated for bone repair of critical-size defects (CSDs), created in rat calvaria (n=42) and treated with fragmented abdominal autogenous adipose tissue graft. Three groups (n=14) were formed: C (control - blood clot), AB (autogenous bone) and AT (fragmented adipose tissue). The groups were divided into subgroups (n=7) for euthanasia at 30 and 90 days. Histological and immunohistochemical analyses were performed. Data were subjected to descriptive statistics (mode). A complete bone closure was observed in Group AB 90 days after surgery. In Group C, repair was achieved by the formation of collagen fiber bundles oriented parallel to the wound surface at both post-surgery periods. In Group AT the type of healing was characterized by dense connective tissue containing collagen fiber bundles arranged amidst the remaining adipose tissue, with rare heterotopic bone formation associated with fibrosis and different types of tissue necrosis. Immunostaining of PPAR-γ was not observed in any specimen from Groups C and AB. In Group AT, the immunostaining of PPAR-γ was more evident 30 days after surgery. Immunostaining of osteocalcin was present in all groups and at both postoperative periods. The fragmented autogenous abdominal adipose tissue graft did not favor the repair of critical-size bone defects created surgically in rat calvaria as evidenced by the positive immunostaining of PPAR-γ protein and the negative immunostaining of osteocalcin in the osteoblast-like cells and bone matrix.

Expression of CD44 and CD29 by PEComa cells suggests their possible origin of mesenchymal stem cells

PubMed Central

Liu, Ruixue; Jia, Wei; Zou, Hong; Wang, Xinhua; Ren, Yan; Zhao, Jin; Wang, Lianghai; Li, Man; Qi, Yan; Shen, Yaoyuan; Liang, Weihua; Jiang, Jinfang; Sun, Zhenzhu; Pang, Lijuan; Li, Feng

2015-01-01

Background: Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. The perivascular epithelioid cell (PEC) co-expresses melanocytic and muscle markers. Since no normal counterpart to the PEC has ever been identified in any normal tissue, the cell origin of these tumors is still uncertain. Although, several hypotheses have recently been advanced to explain the histogenesis of PEComa, it remains unclear. Methods: The aim of this study was to discuss whether differential expression of stem cell-associated proteins could be used to aid in determining the histogenesis of PEComa. For this purpose, we detected the immunoexpression of 5 kinds of stem cell markers on PEComas, including CD29, CD44, CD133, ALDH1, and nestin. In addition to observed histopathologic morphology, we also performed PEComa relevant clinical diagnostic markers (HMB-45, SMA, melan-A, Desmin, Ki-67, S-100 and TFE3) to identify whether they belonged to PEComas. Results: Our study included 13 PEComa samples, and we obtained positive immunoexpression results as follows: CD29 (13/13), CD44 (8/13), ALDH1 (10/13), nestin (1/13), and CD133 (0/13). Conclusions: Since CD44 and CD29 are surface proteins associated with MSCs, these results suggest that PEComa might arise from MSCs. However, whether MSCs are the origin of PEComa needs to be further explored in the future. PMID:26722497

Low-level laser irradiation promotes the proliferation and maturation of keratinocytes during epithelial wound repair.

PubMed

Sperandio, Felipe F; Simões, Alyne; Corrêa, Luciana; Aranha, Ana Cecília C; Giudice, Fernanda S; Hamblin, Michael R; Sousa, Suzana C O M

2015-10-01

Low-level laser therapy (LLLT) has been extensively employed to improve epithelial wound healing, though the exact response of epithelium maturation and stratification after LLLT is unknown. Thus, this study aimed to assess the in vitro growth and differentiation of keratinocytes (KCs) and in vivo wound healing response when treated with LLLT. Human KCs (HaCaT cells) showed an enhanced proliferation with all the employed laser energy densities (3, 6 and 12 J/cm(2) , 660 nm, 100 mW), together with an increased expression of Cyclin D1. Moreover, the immunoexpression of proteins related to epithelial proliferation and maturation (p63, CK10, CK14) all indicated a faster maturation of the migrating KCs in the LLLT-treated wounds. In that way, an improved epithelial healing was promoted by LLLT with the employed parameters; this improvement was confirmed by changes in the expression of several proteins related to epithelial proliferation and maturation. Immunofluorescent expression of cytokeratin 10 (red) and Cyclin D1 (green) in (A) Control keratinocytes and (B) Low-level laser irradiated cells. Blue color illustrates the nuclei of the cells (DAPI staining). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Estrogen receptor alpha in obesity and diabetes].

PubMed

Cahua-Pablo, José Ángel; Flores-Alfaro, Eugenia; Cruz, Miguel

2016-01-01

Estradiol (E2) is an important hormone in reproductive physiology, cardiovascular, skeletal and in the central nervous system (CNS). In human and rodents, E2 and its receptors are involved in the control of energy and glucose metabolism in health and metabolic diseases. The estrogen receptor (ER) belongs to the superfamily of nuclear receptors (NR), which are transcription factors that regulate gene expression. Three ER, ER-alpha, ER-beta and the G protein-coupled ER (GPER; also called GPR30) in tissues are involved in glucose and lipid homeostasis. Also, it may have important implications for risk factors associated with metabolic syndrome (MS), insulin resistance (IR), obesity and type 2 diabetes (T2D).

Survivin and NAIP in Human Benign Prostatic Hyperplasia: Protective Role of the Association of Serenoa repens, Lycopene and Selenium from the Randomized Clinical Study.

PubMed

Morgia, Giuseppe; Micali, Antonio; Rinaldi, Mariagrazia; Irrera, Natasha; Marini, Herbert; Puzzolo, Domenico; Pisani, Antonina; Privitera, Salvatore; Russo, Giorgio I; Cimino, Sebastiano; Ieni, Antonio; Trichilo, Vincenzo; Altavilla, Domenica; Squadrito, Francesco; Minutoli, Letteria

2017-03-22

Benign prostatic hyperplasia (BPH) treatment includes the apoptosis machinery modulation through the direct inhibition of caspase cascade. We previously demonstrated that Serenoa repens (Ser) with lycopene (Ly) and selenium (Se) reawakened apoptosis by reducing survivin and neuronal apoptosis inhibitory protein (NAIP) levels in rats. The aim of this study was to evaluate the effectiveness of Ser-Se-Ly association on survivin and NAIP expression in BPH patients. Ninety patients with lower urinary tract symptoms (LUTS) due to clinical BPH were included in this randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to receive placebo (Group BPH + placebo, n = 45) or Ser-Se-Ly association (Group BPH + Ser-Se-Ly; n = 45) for 3 months. At time 0, all patients underwent prostatic biopsies. After 3 months of treatment, they underwent prostatic re-biopsy and specimens were collected for molecular, morphological, and immunohistochemical analysis. After 3 months, survivin and NAIP were significantly decreased, while caspase-3 was significantly increased in BPH patients treated with Ser-Se-Ly when compared with the other group. In BPH patients treated with Ser-Se-Ly for 3 months, the glandular epithelium was formed by a single layer of cuboidal cells. PSA showed high immunoexpression in all BPH patients and a focal positivity in Ser-Se-Ly treated patients after 3 months. Evident prostate specific membrane antigen (PSMA) immunoexpression was shown in all BPH patients, while no positivity was present after Ser-Se-Ly administration. Ser-Se-Ly proved to be effective in promoting apoptosis in BPH patients.

Medulloblastoma, WNT-activated/SHH-activated: clinical impact of molecular analysis and histogenetic evaluation.

PubMed

Cambruzzi, Eduardo

2018-05-01

Medulloblastoma (MDB) is a small cell poorly differentiated embryonal tumor of the cerebellum, which more frequently compromises children. Overall prognosis is favorable, but dependent of stage, histopathological pattern and molecular group. Approximately 30% of the affected patients will die from the disease. WHO 2016 Classification of Tumors of the Central Nervous System (CNS) has been classified MDB into four principal groups: WNT-activated MDB, SHH-activated MDB, group 3 MDB, and group 4 MDB. WNT-activated MDB is associated to monosomy 6, CTNNB1, DDX3X and TP53 mutations, beta-catenin nuclear immunoexpression, and a better prognosis than SHH-activated MDB. WNT-activated tumors account approximately for 10% of cases of MDBs, and are thought to arise from cells in the dorsal brain stem/lower rhombic lip progenitor cells. SHH-activated MDB more frequently arises in the lateral hemispheres of the cerebellum, and clinical outcome in this group is variable. TP53-mutant SHHactivated MDB usually shows the large cell/anaplastic pattern, and can be related to MYCN amplification, GLI2 amplification and 17p loss. TP53-wildtype SHH-activated MDB is more commonly of desmoplastic/nodular morphology, and can be related to PTCH1 deletion and 10q loss. Gene expression and methylation profiling is the gold standard for defining molecular groups of MDB. In immunohistochemistry assays, anti-GAB1 antibody expression is positive in tumors showing SHH pathway activation or PTCH mutation, while positive immunoexpression for YAP1 antibody can be only found in WNT-activated and SHH-activated MDB.

MUC-1 expression in pleomorphic adenomas using two human milk fat globule protein membrane antibodies (HMFG-1 and HMFG-2)

PubMed Central

PONCE-BRAVO, Santa; LEDESMA-MONTES, Constantino; GARCÉS-ORTÍZ, Maricela

2015-01-01

Pleomorphic adenoma (PA) is the most common salivary gland tumor and its microscopic features and histogenesis are a matter of debate. Human milk fat globule protein membrane (HMFG) monoclonal antibodies (MoAbs) comprise a set of antibodies against the mucin 1 (MUC-1) protein detected in several salivary gland tumors. Objective The aim of this study was to assess the immunoexpression of the PA neoplastic cells to MUC-1 protein using HMFG-1 and HMFG-2 MoAbs, contrasting these results with those from normal salivary gland tissue. Material and Methods Immunohistochemical detection of MUC-1 protein using HMFG-1 and HMFG-2 MoAbs was made in 5 mm thick, paraffin embedded slides, and the avidin-biotin method was used. Results Positivity to HMFG-1 and HMFG-2 MoAbs was found in ductal, squamous metaplastic and neoplastic myoepithelial cells, keratin pearls and intraductal mucous material. Two kinds of myoepithelial cells were identified: classic myoepithelial cells around ducts were negative to both MoAbs, and modified myoepithelial cells were positive to both MoAbs. This last cellular group of the analyzed tumors showed similar MUC-1 immunoexpression to ductal epithelial cells using both HMFG antibodies. Intraductal mucous secretion was also HMFG-1 and HMFG-2 positive. Conclusions Our results showed there are two kinds of myoepithelial cells in PA. The first cellular group is represented by the different kinds of neoplastic myoepithelial cells and is HMFG-positive. The second one is HMFG-negative and represented by the neoplastic myoepithelial cells located around the ducts. PMID:26221920

Effects of topical phenytoin on nasal wound healing after mechanical trauma: An experimental study.

PubMed

Şimşek, Gökçe; Ciftci, Osman; Karadag, Neşe; Karatas, Erkan; Kizilay, Ahmet

2014-12-01

Impaired postoperative wound healing is the second most common morbidity after synechia formation in endoscopic sinus surgery. The aim of this experimental study was to investigate the potential effects of topical phenytoin on wound healing after nasal mucosal trauma in rats. An experimental study at the Inonu University Faculty of Medicine. Twenty-four rats were randomized into three groups: 1) phenytoin group (n = 8), 2) control group (n = 8), and 3) vehicle group (n = 8). After damaging the right nasal cavity, in the phenytoin group, 1% topical phenytoin cream was applied for 7 days. The rats in the control group did not receive any treatment. The vehicle group was treated with daily topical cold cream for 1 week. The rats were sacrificed at the end, and the nasal cavities were excised. Tissue edema and inflammatory cell infiltration were compared among the groups. Additionally, proliferating cell nuclear antigen (PCNA) and cluster of differentiation 31 (CD31) immunoexpression levels were evaluated. Furthermore, in biochemical analysis, the tissue levels of vascular endothelial growth factor and (EGF) of the groups were investigated. In the phenytoin group, tissue edema and inflammatory cell infiltration were significantly decreased, and PCNA and CD31 immunoexpression levels were more prominent (P < .001) and the tissue EGF levels were significantly higher (P < .01). Topical phenytoin treatment may alter the nasal wound healing after mechanical trauma. The potential beneficial effects of topical phenytoin on nasal mucosa should be investigated by further experimental and human trials. NA. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Co-Expression and Co-Localization of Cartilage Glycoproteins CHI3L1 and Lubricin in Osteoarthritic Cartilage: Morphological, Immunohistochemical and Gene Expression Profiles

PubMed Central

Szychlinska, Marta Anna; Trovato, Francesca Maria; Di Rosa, Michelino; Malaguarnera, Lucia; Puzzo, Lidia; Leonardi, Rosy; Castrogiovanni, Paola; Musumeci, Giuseppe

2016-01-01

Osteoarthritis is the most common human arthritis characterized by degeneration of articular cartilage. Several studies reported that levels of human cartilage glycoprotein chitinase 3-like-1 (CHI3L1) are known as a potential marker for the activation of chondrocytes and the progression of Osteoarthritis (OA), whereas lubricin appears to be chondroprotective. The aim of this study was to investigate the co-expression and co-localization of CHI3L1 and lubricin in normal and osteoarthritic rat articular cartilage to correlate their modified expression to a specific grade of OA. Samples of normal and osteoarthritic rat articular cartilage were analyzed by the Kellgren–Lawrence OA severity scores, the Kraus’ modified Mankin score and the Histopathology Osteoarthritis Research Society International (OARSI) system for histomorphometric evaluations, and through CHI3L1 and lubricin gene expression, immunohistochemistry and double immuno-staining analysis. The immunoexpression and the mRNA levels of lubricin increased in normal cartilage and decreased in OA cartilage (normal vs. OA, p < 0.01). By contrast, the immunoexpression and the mRNA levels of CHI3L1 increased in OA cartilage and decreased in normal cartilage (normal vs. OA, p < 0.01). Our findings are consistent with reports suggesting that these two glycoproteins are functionally associated with the development of OA and in particular with grade 2/3 of OA, suggesting that in the future they could be helpful to stage the severity and progression of the disease. PMID:26978347

Immunoexpression of EGFR and EMMPRIN in a series of cases of head and neck squamous cell carcinoma.

PubMed

de Andrade, Ana Luiza Dias Leite; Ferreira, Stefânia Jeronimo; Ferreira, Sonia Maria Soares; Ribeiro, Camila Maria Beder; Freitas, Roseana de Almeida; Galvão, Hébel Cavalcanti

2015-10-01

The epidermal growth factor receptor (EGFR) and the extracellular matrix metalloproteinase inducer (EMMPRIN) have been identified as oncologically important targets. This study aimed to evaluate the immunoexpression of EGFR and EMMPRIN in a series of cases of head and neck squamous cell carcinoma (HNSCC). Forty-five cases of HNSCC were selected for this study and evaluated with anti-EGFR and anti-EMMPRIN antibodies. The percentage of positive cells was determined assessing to the following categories: score 1 (staining in 0-50% of cells), score 2 (staining in 51-75% of cells), and score 3 (staining in >75% of cells). Immunostaining intensity was graded according to the following parameters: score 1 (absent/weak expression) and score 2 (strong expression). For EGFR, a predominance of high median scores was observed in cases of both histological grades of malignancy and in different clinical stages (p>0.05). For EMMPRIN, a statistically significant difference was observed between the histological grades of malignancy (p=0.030). Regarding the immunostaining intensity of EMMPRIN, it was observed a predominance of score 1 in cases with stages I/II, whereas most cases with stages III/IV presented score 2 (p=0.032). Considering the anatomical location, most cases of buccal floor presented higher median score of EMMPRIN in comparison with the other sites (p=0.015). These findings suggest that both proteins are potential targets for cancer therapy and EMMPRIN can be used as a prognostic marker of a more aggressive biological behavior in patients with HNSCC. Copyright © 2015 Elsevier GmbH. All rights reserved.

p16 protein is upregulated in a stepwise fashion in colorectal adenoma and colorectal carcinoma.

PubMed

Al-Ahwal, Mahmoud; Gomaa, Wafaey; Emam, Eman; Qari, Yousif; Buhmeida, Abdelbaset; Radwi, Salman; Al-Maghrabi, Basim; Al-Qahtani, Mohammad; Al-Maghrabi, Jaudah

2016-11-01

p16 is tumor suppressor gene acting as a cell cycle regulator. The present study was conducted to compare p16 expression in normal, dysplastic, and malignant colonic mucosae, and to explore its relation to clinicopathological variables and follow-up data in colorectal carcinoma (CRC). Tissue microarrays were performed from 25 normal colonic mucosae, 41 colonic adenomas, and 191 CRC, with corresponding 50 nodal metastases. Immunohistochemistry was performed using anti-p16 antibody, sections were scored, and statistical analysis was performed. K-ras mutation detection was also performed. Immunoexpression of p16 was significantly higher in CRC than in adenomas (P = 0.033) and normal colonic mucosa (P = 0.005). There was no statistically significant difference between p16 expression in CRC and nodal metastasis. There was no significant association between p16 immunoexpression in CRC and all clinicopathological data and survival probability. K-ras mutations were detected in 34% of CRC. However, there was no correlation between K-ras status and p16 expression (P = 0.325). Absence of p16 expression is correlated to a benign course of CRC adenomas. p16 has a key role in CRC progression and can be used as a marker for colorectal adenoma. On the other hand, it has no role as a predictive and/or prognostic factor in CRC. Further extended studies are required to explore the role of p16 as indicator of premalignant lesions in the colon and to test its relation with CRC histological grade, as well as to test its value as a new therapeutic target.

Depot differences in steroid receptor expression in adipose tissue: possible role of the local steroid milieu.

PubMed

Rodriguez-Cuenca, S; Monjo, M; Proenza, A M; Roca, P

2005-01-01

Sex hormones play an important role in adipose tissue metabolism by activating specific receptors that alter several steps of the lipolytic and lipogenic signal cascade in depot- and sex-dependent manners. However, studies focusing on steroid receptor status in adipose tissue are scarce. In the present study, we analyzed steroid content [testosterone (T), 17beta-estradiol (17beta-E2), and progesterone (P4)] and steroid receptor mRNA levels in different rat adipose tissue depots. As expected, T levels were higher in males than in females (P = 0.031), whereas the reverse trend was observed for P4 (P < 0.001). It is noteworthy that 17beta-E2 adipose tissue levels were higher in inguinal than in the rest of adipose tissues for both sexes, where no sex differences in 17beta-E2 tissue levels were noted (P = 0.010 for retroperitoneal, P = 0.005 for gonadal, P = 0.018 for mesenteric). Regarding steroid receptor levels, androgen (AR) and estrogen receptor (ER)alpha and ERbeta densities were more clearly dependent on adipose depot location than on sex, with visceral depots showing overall higher mRNA densities than their subcutaneous counterparts. Besides, expression of ERalpha predominated over ERbeta expression, and progesterone receptor (PR-B form and PR-A+B form) mRNAs were identically expressed regardless of anatomic depot and sex. In vitro studies in 3T3-L1 cells showed that 17beta-E2 increased ERalpha (P = 0.001) and AR expression (P = 0.001), indicating that estrogen can alter estrogenic and androgenic signaling in adipose tissue. The results highlighted in this study demonstrate important depot-dependent differences in the sensitivity of adipose tissues to sex hormones between visceral and subcutaneous depots that could be related to metabolic situations observed in response to sex hormones.

Inter-laboratory quality control for hormone-dependent gene expression in human breast tumors using real-time reverse transcription-polymerase chain reaction.

PubMed

de Cremoux, P; Bieche, I; Tran-Perennou, C; Vignaud, S; Boudou, E; Asselain, B; Lidereau, R; Magdelénat, H; Becette, V; Sigal-Zafrani, B; Spyratos, F

2004-09-01

Quantitative reverse transcription-polymerase chain reaction (RT-PCR) used to detect minor changes in specific mRNA concentrations may be associated with poor reproducibility. Stringent quality control is therefore essential at each step of the protocol, including the PCR procedure. We performed inter-laboratory quality control of quantitative PCR between two independent laboratories, using in-house RT-PCR assays on a series of hormone-related target genes in a retrospective consecutive series of 79 breast tumors. Total RNA was reverse transcribed in a single center. Calibration curves were performed for five target genes (estrogen receptor (ER)alpha, ERbeta, progesterone receptor (PR), CYP19 (aromatase) and Ki 67) and for two reference genes (human acidic ribosomal phosphoprotein PO (RPLPO) and TATA box-binding protein (TBP)). Amplification efficiencies of the calibrator were determined for each run and used to calculate mRNA expression. Correlation coefficients were evaluated for each target and each reference gene. A good correlation was observed for all target and reference genes in both centers using their own protocols and kits (P < 0.0001). The correlation coefficients ranged from 0.90 to 0.98 for the various target genes in the two centers. A good correlation was observed between the level of expression of the ERalpha and the PR transcripts (P < 0.001). A weak inverse correlation was observed in both centers between ERalpha and ERbeta levels, but only when TBP was the reference gene. No other correlation was observed with other parameters. Real-time PCR assays allow convenient quantification of target mRNA transcripts and quantification of target-derived nucleic acids in clinical specimens. This study addresses the importance of inter-laboratory quality controls for the use of a panel of real-time PCR assays devoted to clinical samples and protocols and to ensure their appropriate accuracy. This can also facilitate exchanges and multicenter comparison of data.

Immunoexpression of p16 in uterine leiomyomas with infarct-type necrosis: an analysis of 35 cases.

PubMed

Ip, Philip P; Lim, Diana; Cheung, Annie N Y; Oliva, Esther

2017-11-01

Uterine leiomyosarcomas frequently show p16 immunoexpression. However, p16 may also be expressed in some benign leiomyoma variants such as leiomyomas with bizarre nuclei and cellular leiomyomas, limiting its utility as a biomarker to distinguish between benign and malignant neoplasms. We investigated p16 expression in leiomyomas with infarct-type necrosis, tumours which may sometimes be misinterpreted as smooth muscle tumours of uncertain malignant potential or even leiomyosarcoma on conventional light microscopy. p16 immunostaining was performed on 35 leiomyomas with infarct-type necrosis and the staining pattern was analysed. Staining was classified as absent, scattered/isolated, <33-, 33-66- or >66%-positive cells, and was assessed in the areas immediately surrounding and distant from the infarct. The median age of patients was 44 years. Seventeen had hormonal/non-hormonal drugs and three were pregnant. The median tumour size was 7.25 cm. The mean mitotic count was 0.9/10 high-power fields. Only one tumour had multifocal mild nuclear atypia. Positive p16 was noted in 34 of 35 (97.2%) tumours. It was typically patchy, and was concentrated in areas immediately surrounding the necrosis. Distant from the necrosis, p16 positivity was seen predominantly in scattered/isolated cells. One tumour without any worrisome microscopic features showed diffuse p16 positivity throughout. Median follow-up was 55 months, and none of the patients experienced any recurrence. p16 expression in benign uterine smooth muscle tumours with infarct-type necrosis is common. The staining is particularly concentrated adjacent to areas of necrosis. It is important to be aware of this potential pitfall when interpreting p16 expression. © 2017 John Wiley & Sons Ltd.

Differences in uterine immunoexpression of PR, ERα and OTR when comparing prostaglandin- to progestagen-based protocols for ovine estrus synchronization.

PubMed

Ruiz-González, I; Sánchez, M A; García-Palencia, P; Sánchez, B; García-Fernández, R A; González-Bulnes, A; Flores, J M

2012-07-01

The aim of this work was to compare PR, ERα and OTR uterine expression between days 9 and 21 of pregnancy in ewes whose estrus had been synchronized with two different protocols. Sixty-four adult Manchega ewes were synchronized with either conventional progestagens (P) or prostaglandin analogues (PG), and mated. Uterine samples were obtained from pregnant animals (group P, n=24; group PG, n=25) on days 9 post coitus (pc), 13pc, 15pc, 17pc and 21pc. Immunohistochemical detection of progesterone receptor (PR), estrogen receptor-α (ERα) and oxytocin receptor (OTR) was assessed in different uterine cell compartments including luminal and glandular epithelium, stroma and myometrium. Interaction day × treatment was obtained when assessing PR expression in the caruncular stroma (P=0.027) and myometrium (P=0.000), as well as for ERα in the superficial stroma (P=0.05). Significant "day post coitus" effect was found regarding to PR (P<0.01, with the exception of the superficial stroma, deep stroma and myometrium), ERα (P<0.01), and OTR (P<0.05, except in the deep compartments). No significant "treatment" effect was found for PR, ERα or OTR protein immunoexpression. This study supports the implication of PR, ERα and OTR within days 9-21 of the ovine pregnancy. Moreover, different expression pattern of PR and ERα proteins has been found between treatments in various compartments studied. Collectively, these results indicate that PR, ERα and OTR expression during early pregnancy is similar between ewes treated with either progestagens or prostaglandin analogues-based protocols for estrus synchronization. Copyright © 2012 Elsevier B.V. All rights reserved.

Performance of Lynch syndrome predictive models in quantifying the likelihood of germline mutations in patients with abnormal MLH1 immunoexpression.

PubMed

Cabreira, Verónica; Pinto, Carla; Pinheiro, Manuela; Lopes, Paula; Peixoto, Ana; Santos, Catarina; Veiga, Isabel; Rocha, Patrícia; Pinto, Pedro; Henrique, Rui; Teixeira, Manuel R

2017-01-01

Lynch syndrome (LS) accounts for up to 4 % of all colorectal cancers (CRC). Detection of a pathogenic germline mutation in one of the mismatch repair genes is the definitive criterion for LS diagnosis, but it is time-consuming and expensive. Immunohistochemistry is the most sensitive prescreening test and its predictive value is very high for loss of expression of MSH2, MSH6, and (isolated) PMS2, but not for MLH1. We evaluated if LS predictive models have a role to improve the molecular testing algorithm in this specific setting by studying 38 individuals referred for molecular testing and who were subsequently shown to have loss of MLH1 immunoexpression in their tumors. For each proband we calculated a risk score, which represents the probability that the patient with CRC carries a pathogenic MLH1 germline mutation, using the PREMM 1,2,6 and MMRpro predictive models. Of the 38 individuals, 18.4 % had a pathogenic MLH1 germline mutation. MMRpro performed better for the purpose of this study, presenting a AUC of 0.83 (95 % CI 0.67-0.9; P < 0.001) compared with a AUC of 0.68 (95 % CI 0.51-0.82, P = 0.09) for PREMM 1,2,6 . Considering a threshold of 5 %, MMRpro would eliminate unnecessary germline mutation analysis in a significant proportion of cases while keeping very high sensitivity. We conclude that MMRpro is useful to correctly predict who should be screened for a germline MLH1 gene mutation and propose an algorithm to improve the cost-effectiveness of LS diagnosis.

Immunohistochemical study of integrin α₅β₁, fibronectin, and Bcl-2 in normal oral mucosa, inflammatory fibroepithelial hyperplasia, oral epithelial dysplasia, and oral squamous cell carcinoma.

PubMed

Núñez, Manuel Antonio Gordón; de Matos, Felipe Rodrigues; Freitas, Roseana de Almeida; Galvão, Hébel Cavalcanti

2013-07-01

The objective of this study was to compare the immunoexpression of integrin α₅β₁, fibronectin, and the Bcl-2 protein in normal oral mucosa (NOM), inflammatory fibroepithelial hyperplasia (IFH), oral epithelial dysplasia (OED), and oral squamous cell carcinoma (OSCC). Eleven cases of NOM, 16 IFH, 20 OED, and 27 OSCC were selected for analysis of the immunoexpression of integrin α₅β₁, fibronectin, and bcl-2 protein. There was an association between the intensity and location of the integrin α₅β₁ expression, especially in the OSCC, that 48.1% of cases showed weak immunoreactivity and 40.7% in the suprabasal layer (P < 0.05). There was an association between the pattern and distribution of fibronectin expression in basement membrane, where 90% of NOM showed a pattern of linear continuous and 80% of OED exhibited focal distribution (P < 0.05). The fibronectin expression in connective tissue was predominantly intense with an association of staining pattern among the different specimens, where 37% of OSCC showed a reticular pattern (P < 0.05). There was an association of bcl-2 protein among the types of specimens, especially in IFH and OSCC, where 100% of the cases exhibited scores 1 of staining (P < 0.05). Within this context, the interaction of integrin α₅β₁ with its main ligand in the extracellular matrix, fibronectin, is suggested to influence the survival of tumor cells and to favor their proliferation by modulating apoptosis through the upregulation of antiapoptotic proteins or the suppression of apoptotic mediators.

Sex steroid receptors and apoptosis-related proteins are differentially expressed in polycystic ovaries of adult dogs.

PubMed

Chuffa, Luiz Gustavo de Almeida; Lupi Júnior, Luiz Antonio; da Maia Lima, Alfredo Feio

2016-02-01

In Polycystic Ovaries (PCOs), the dynamics of sex hormone receptors and follicle-related apoptotic signaling remain unknown. In this study, we investigated the expression of androgen receptors (AR), estrogen receptors (ERα and ERβ), and apoptosis-related molecules (BAX, active caspase-3, Bcl-2 and Survivin) on different follicular stages of PCOs in adult dogs. Clinical evidences of high estradiol and testosterone levels, persistent estrus and vaginal discharge were observed. Inhibin B immunolabeling was increased in primary and 2 to 5-mm follicles, and a marked epithelial hyperplasia was common in the ovarian surface. Ovarian epithelia and primary follicles showed low expression of AR, ERα, and ERβ, whereas a moderate immunoexpression of AR was found in theca cells of secondary follicles and cysts. In PCOs, growing follicles displayed ERα expression, and secondary follicles exhibited higher ERβ expression. In addition, while few ERα-positive cells were found in the cysts, ERβ was moderately expressed in growing follicles and cysts. BAX was upregulated in the ovarian epithelium, primary follicles, and in the wall of follicular cysts. Active caspase-3 was significantly downregulated in the epithelium, primary follicles, and follicular cysts, whereas growing follicles had a strong immunoexpression in the granulosa cells. Bcl-2 and survivin were increased in the epithelium and primary follicles, and only survivin was upregulated in secondary and growing follicles. While Bcl-2 had a diffuse immunexpression in the follicular cysts, survivin was overexpressed by these cells. We concluded that sex steroid receptors and apoptotic proteins are differentially expressed in the follicles of adult dogs with PCOs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Role of HIF-1α and CASPASE-3 in cystogenesis of odontogenic cysts and tumors.

PubMed

da Costa, Natacha M M; de Siqueira, Adriane S; Ribeiro, André L R; da Silva Kataoka, Maria S; Jaeger, Ruy G; de Alves-Júnior, Sérgio M; Smith, Andrew M; de Jesus Viana Pinheiro, João

2018-01-01

Odontogenic cysts and tumors are the most relevant lesions that affect the gnathic bones. These lesions have in common the formation of cystic areas and this common feature may suggest involvement of similar mechanisms. The hypoxia inducible factor 1 alpha (HIF-1α), a responsive protein to hypoxia and caspase-3, an irreversible apoptosis marker, may contribute to cyst formation. Thus, this study aimed to investigate the immunoexpression of these proteins in odontogenic cysts and tumors. Twenty cases of ameloblastoma, keratocystic odontogenic tumor (KOT) (n = 20), radicular cyst (RC) (n = 18), dentigerous cyst (DC) (n = 11), calcifying cystic odontogenic tumor (n = 8), and dental follicle (DF) (n = 10) were used to investigate HIF-1α and caspase-3 expression in sequential serial cuts by immunohistochemistry. HIF-1α was overexpressed in RC, DC, and ameloblastoma when compared with DF. The basal and sometimes the lower suprabasal layer showed no or very low expression in DC, KOT, and ameloblastoma, the last also showing strong expression in solid epithelial areas and initial cystic formation regions. Caspase-3 was found to be overexpressed in all lesions, with the highest expression in odontogenic cysts compared to tumors. HIF-1α and caspase-3 were localized in similar areas of the same lesions, especially in the epithelium surrounding cystic formations. This study showed distinct immunoexpression of HIF-1α and caspase-3 in odontogenic cyst and tumors, with higher expression observed in odontogenic cysts. These findings suggest a possible correlation between hypoxia, apoptosis, and cystogenesis, leading to understand the mechanisms responsible to cystic formation in odontogenic lesions.

Histopathological, Molecular, and Genetic Profile of Hereditary Diffuse Gastric Cancer: Current Knowledge and Challenges for the Future.

PubMed

van der Post, Rachel S; Gullo, Irene; Oliveira, Carla; Tang, Laura H; Grabsch, Heike I; O'Donovan, Maria; Fitzgerald, Rebecca C; van Krieken, Han; Carneiro, Fátima

Familial clustering is seen in 10 % of gastric cancer cases and approximately 1-3 % of gastric cancer arises in the setting of hereditary diffuse gastric cancer (HDGC). In families with HDGC, gastric cancer presents at young age. HDGC is predominantly caused by germline mutations in CDH1 and in a minority by mutations in other genes, including CTNNA1. Early stage HDGC is characterized by a few, up to dozens of intramucosal foci of signet ring cell carcinoma and its precursor lesions. These include in situ signet ring cell carcinoma and pagetoid spread of signet ring cells. Advanced HDGC presents as poorly cohesive/diffuse type carcinoma, normally with very few typical signet ring cells, and has a poor prognosis. Currently, it is unknown which factors drive the progression towards aggressive disease, but it is clear that most intramucosal lesions will not have such progression.Immunohistochemical profile of early and advanced HDGC is often characterized by abnormal E-cadherin immunoexpression, including absent or reduced membranous expression, as well as "dotted" or cytoplasmic expression. However, membranous expression of E-cadherin does not exclude HDGC. Intramucosal HDGC (pT1a) presents with an "indolent" phenotype, characterized by typical signet ring cells without immunoexpression of Ki-67 and p53, while advanced carcinomas (pT > 1) display an "aggressive" phenotype with pleomorphic cells, that are immunoreactive for Ki-67 and p53. These features show that the IHC profile is different between intramucosal and more advanced HDGC, providing evidence of phenotypic heterogeneity, and may help to define predictive biomarkers of progression from indolent to aggressive, widely invasive carcinomas.

[Immunoexpression and clinical significance of interleukin-21 and receptor activator of nuclear factor κB ligand in human periapical granulomas and radicular cysts].

PubMed

Hu, Juhua; Li, Qian; Wang, Yanqing; Li, Song

2015-06-01

This study aimed to detect the immunoexpression of interleukin-21 (IL-21) and receptor activator. of nuclear factor KB ligand (RANKL) in periapical granulomas (PGs) and radicular cysts (RCs). The interaction of IL-21 with RANKL and its role in periapical pathogenesis were also speculated. A total of 32 PGs and 23 RCs were selected as experimental samples. Lesion size and occurrence of tenderness were recorded. Up to 10 healthy gingival tissues were collected as normal control samples. All tissues were subjected to immunohistocheincal analysis with anti-human IL-21 and RANKL polyclonal antibodies. The correlations of IL-21 with RANKL, lesion size, and the occurrence of tenderness of the PGs and RCs were evaluated. IL-21-positive cells were detected in all periapical lesion tissues but not in normal tissues. In the cyst group and granuloma group, the corresponding expression levels of IL-21 were 59.92±6.57 and 36.80± 6.81, whereas those of RANKL were 68.81±18.59 and 36.12±14.87, respectively. Moreover, t-test revealed a significantly higher expression of IL-21 and RANKL in RCs than in PGs (P<0.05). IL-21 and RANKL were positively correlated in both PGs and RCs (P<0.05). Furthermore, IL-21 was correlated with lesion size (P<0.05). This study demonstrated that IL-21 is potentially involved in the pathogenesis of apical periodontitis lesions. A role in the exacerbation of chronic inflammation, as well as in bone resorption, is suspected. Further studies are required to elucidate the specific functions of IL-21 in periradicular inflammatory processes.

Foetal exposure to Panax ginseng extract reverts the effects of prenatal dexamethasone in the synthesis of testosterone by Leydig cells of the adult rat.

PubMed

Wanderley, Maria I; Saraiva, Karina L A; César Vieira, Juliany S B; Peixoto, Christina A; Udrisar, Daniel P

2013-06-01

The aim of this study was to examine the effect of maternal exposure to Panax ginseng extract (GE) on the prenatal dexamethasone (DEXA)-induced increase in testosterone production by isolated Leydig cells in adult rats. Pregnant rats were treated with (i) GE (200 mg/kg) or vehicle on days 10-21; (ii) DEXA (100 μg/kg) or vehicle on days 14-21; or (iii) a combination of GE plus DEXA at the same doses and with the same regimen. Testosterone production was induced either by the activator of protein kinase A (dbcAMP) or substrates of steroidogenesis [22(R)-hydroxycholesterol (22(R)-OH-C)] and pregnenolone. The capacity of rat Leydig cells exposed to DEXA to synthesize testosterone induced by dbcAMP, 22(R)-OH-C or pregnenolone was increased in comparison with the control group. Combined exposure to DEXA + GE prevented the effect of DEXA on the responsiveness of Leydig cells to all inductors of testosterone synthesis, whereas GE alone did not modify the response to inductors. No modifications in testosterone production were observed under basal conditions. StAR immunoexpression in Leydig cells was not modified by prenatal exposure to DEXA, GE or DEXA + GE. P450scc and glucocorticoid receptor immunoexpression was higher in offspring exposed to DEXA in comparison with the control group. This increased expression was prevented by combined treatment with DEXA + GE. The present findings demonstrate that GE is capable of reversing the effect of DEXA on testosterone synthesis by rat Leydig cells. © 2013 The Authors. International Journal of Experimental Pathology © 2013 International Journal of Experimental Pathology.

Association of matrix metalloproteinase inducer (EMMPRIN) with the expression of matrix metalloproteinases-1, -2 and -9 during periapical lesion development.

PubMed

Sousa, Natália Guimarães Kalatzis; Cardoso, Cristina Ribeiro de Barros; Silva, João Satana da; Kuga, Milton Carlos; Tanomaru-Filho, Mário; Faria, Gisele

2014-09-01

To evaluate the expression of matrix metalloproteinase inducer (EMMPRIN) and its correlation with the expression of matrix metalloproteinases (MMPs)-1, -2 and -9 during the development of periapical lesion in mice. Periapical lesions were induced in the lower first molars of mice and after 7, 14, 21 and 42 days the mandibles were removed. The periapical lesions were measured by micro-computed tomography. The expression of EMMPRIN, MMPs-1, -2, and -9 genes were determined by real-time RT-PCR. The location and expression of EMMPRIN and MMPs were evaluated by immunohistochemistry. At 14 days, the periapical lesion area was higher than at 7 days. At 21 and 42 days no statistically significant bone loss was observed in comparison to 14 days. The control group showed discrete and occasional EMMPRIM, MMP-1, -2 and -9 immunostaining in the periodontal ligament fibroblasts. At 7, 14, 21 and 42 days intense immunoexpression was observed for EMMPRIN, MMPs-1, -2 and -9 in the region adjacent to the apical foramen. The EMMPRIN immunoexpression was higher at 7, 14, 21 and 42 days compared with the control. There was a positive correlation between gene expression of EMMPRIN and MMPs in the active phase of periapical lesion development. There is a high expression of EMMPRIM mainly by the inflammatory infiltrate in the region adjacent to the apical foramen during periapical lesion development. Furthermore, the positive correlation with MMP-1, -2, and -9 during the first days after periapical lesion induction indicates that EMMPRIM may be involved in the active phase of periapical lesions development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cellular and Hormonal Disruption of Fetal Testis Development in Sheep Reared on Pasture Treated with Sewage Sludge

PubMed Central

Paul, Catriona; Rhind, Stewart M.; Kyle, Carol E.; Scott, Hayley; McKinnell, Chris; Sharpe, Richard M.

2005-01-01

The purpose of this study was to evaluate whether experimental exposure of pregnant sheep to a mixture of environmental chemicals added to pasture as sewage sludge (n = 9 treated animals) exerted effects on fetal testis development or function; application of sewage sludge was undertaken so as to maximize exposure of the ewes to its contents. Control ewes (n = 9) were reared on pasture treated with an equivalent amount of inorganic nitrogenous fertilizer. Treatment had no effect on body weight of ewes, but it reduced body weight by 12–15% in male (n = 12) and female (n = 8) fetuses on gestation day 110. In treated male fetuses (n = 11), testis weight was significantly reduced (32%), as were the numbers of Sertoli cells (34% reduction), Leydig cells (37% reduction), and gonocytes (44% reduction), compared with control fetuses (n = 8). Fetal blood levels of testosterone and inhibin A were also reduced (36% and 38%, respectively) in treated compared with control fetuses, whereas blood levels of luteinizing hormone and follicle-stimulating hormone were unchanged. Based on immunoexpression of anti-Müllerian hormone, cytochrome P450 side chain cleavage enzyme, and Leydig cell cytoplasmic volume, we conclude that the hormone changes in treated male fetuses probably result from the reduction in somatic cell numbers. This reduction could result from fetal growth restriction in male fetuses and/or from the lowered testosterone action; reduced immunoexpression of α-smooth muscle actin in peritubular cells and of androgen receptor in testes of treated animals supports the latter possibility. These findings indicate that exposure of the developing male sheep fetus to real-world mixtures of environmental chemicals can result in major attenuation of testicular development and hormonal function, which may have consequences in adulthood. PMID:16263515

Expression of the G protein-coupled estrogen receptor (GPER) in endometriosis: a tissue microarray study.

PubMed

Samartzis, Nicolas; Samartzis, Eleftherios P; Noske, Aurelia; Fedier, André; Dedes, Konstantin J; Caduff, Rosmarie; Fink, Daniel; Imesch, Patrick

2012-04-20

The G protein-coupled estrogen receptor (GPER) is thought to be involved in non-genomic estrogen responses as well as processes such as cell proliferation and migration. In this study, we analyzed GPER expression patterns from endometriosis samples and normal endometrial tissue samples and compared these expression profiles to those of the classical sex hormone receptors. A tissue microarray, which included 74 samples from different types of endometriosis (27 ovarian, 19 peritoneal and 28 deep-infiltrating) and 30 samples from normal endometrial tissue, was used to compare the expression levels of the GPER, estrogen receptor (ER)-alpha, ER-beta and progesterone receptor (PR). The immunoreactive score (IRS) was calculated separately for epithelium and stroma as the product of the staining intensity and the percentage of positive cells. The expression levels of the hormonal receptors were dichotomized into low (IRS < 6) and high (IRS > = 6) expression groups. The mean epithelial IRS (+/- standard deviation, range) of cytoplasmic GPER expression was 1.2 (+/- 1.7, 0-4) in normal endometrium and 5.1 (+/- 3.5, 0-12) in endometriosis (p < 0.001), of nuclear GPER 6.4 (+/- 2.6, 0-12) and 6.8 (+/- 2.9, 2-12; p = 0.71), of ER-alpha 10.6 (+/- 2.4, 3-12) and 9.8 (+/- 3.0, 2-12; p = 0.26), of ER-beta 2.4 (+/- 2.2; 0-8) and 5.6 (+/- 2.6; 0-10; p < 0.001), and of PR 11.5 (+/- 1.7; 3-12) and 8.1 (+/- 4.5; 0-12; p < 0.001), respectively. The mean stromal IRS of nuclear GPER expression was 7.7 (+/- 3.0; 2-12) in endometrium and 10.8 (+/- 1.7; 6-12) in endometriosis (p < 0.001), of ER-alpha 8.7 (+/- 3.1; 2-12) and 10.6 (+/- 2.4; 2-12; p = 0.001), of ER-beta 1.8 (+/- 2.0; 0-8) and 5.4 (+/- 2.5; 0-10; p < 0.001), and of PR 11.7 (+/- 0.9; 8-12) and 10.9 (+/- 2.0; 3-12; p = 0.044), respectively. Cytoplasmic GPER expression was not detectable in the stroma of endometrium and endometriosis. The observed frequency of high epithelial cytoplasmic GPER expression levels was 50% (n = 30/60) in the endometriosis and none (0/30) in the normal endometrium samples (p < 0.001). High epithelial cytoplasmic GPER expression levels were more frequent in endometriomas (14/20, 70%; p = 0.01), as compared to peritoneal (9/18, 50%) or deep-infiltrating endometriotic lesions (7/22, 31.8%). The frequency of high stromal nuclear GPER expression levels was 100% (n = 74/74) in endometriosis and 76.7% (n = 23/30) in normal endometrium (p < 0.001). The frequency of high epithelial nuclear GPER expression levels did not differ between endometriosis and normal endometrium. The present data indicate a unique GPER expression pattern in endometriosis, especially in endometriomas as compared to the normal endometrium. The overexpression of GPER in endometriotic lesions suggests a potential role for GPER in the hormonal regulation of endometriosis, which should be taken into consideration for future hormonal treatment strategies.

Regulation of Thyroid Hormone-, Oestrogen- and Androgen-Related Genes by Triiodothyronine in the Brain of Silurana tropicalis

PubMed Central

Duarte-Guterman, Paula; Trudeau, Vance L

2010-01-01

Amphibian metamorphosis is an excellent example of hormone-dependent control of development. Thyroid hormones (THs) regulate almost all aspects of metamorphosis, including brain development and larval neuroendocrine function. Sex steroids are also important for early brain function, although little is known about interactions between the two hormonal systems. In the present study, we established brain developmental profiles for thyroid hormone receptors (tralpha and trbeta), deiodinases (dio1, dio2 and dio3), aromatase (cyp19) mRNA and activity, oestrogen receptors (eralpha and erbeta), androgen receptor (ar) and 5α-reductases (srd5alpha1 and srd5alpha2) mRNA during Silurana (Xenopus) tropicalis metamorphosis. Real-time reverse transcriptase-polymerase chain reaction analyses revealed that all of the genes were expressed in the brain and for most of the genes expression increased during development, with the exception of dio2, srd5alpha1 and srd5alpha2. The ability of premetamorphic tadpoles to respond to exogenous THs was used to investigate the regulation of TH- and sex steroid-related genes in the brain during development. Exposure of premetamorphic tadpoles to triiodothyronine (T3; 0, 0.5, 5 and 50 nm) for 48 h resulted in concentration-dependent increases in trbeta, dio2, dio3, eralpha and erbeta. Expression of srd5alpha2 showed large increases (six- to 7.5-fold) for all three concentrations of T3. No changes were detected in dio1, ar and cyp19 transcript levels; however, cyp19 activity increased significantly at 50 nm T3. The results obtained suggest that expression of TH-related genes and er during development could be regulated by rising levels of THs, as previously documented in Lithobates (Rana) pipiens. The positive regulation of srd5alpha by T3 in the brain suggests that endogenous TH levels help maintain or control the rate at which srd5alpha mRNA levels decrease as metamorphosis progresses. Finally, we have identified sex steroid-related genes that are responsive to T3, providing additional evidence of crosstalk between THs and sex steroids in the tadpole brain. PMID:20626568

GPR30: a seven-transmembrane-spanning estrogen receptor that triggers EGF release.

PubMed

Filardo, Edward J; Thomas, Peter

2005-10-01

Heterotrimeric G proteins and seven-transmembrane-spanning (7TM) receptors are implicated in rapid estrogen signaling. The orphan 7TM receptor GPR30 is linked to estrogen-mediated activation of adenylyl cyclase, release of epidermal growth factor (EGF)-related ligands, and specific estrogen binding. GPR30 acts independently of estrogen receptors, ERalpha and ERbeta, and probably functions as a heptahelical ER. 7TM receptors elicit signals that stimulate second messengers, and convey intracellular signals via EGF receptors. Identification of GPR30 as a Gs-coupled 7TM receptor that triggers release of heparin-binding EGF establishes its role in cell signaling cascades initiated by estrogens, and explains their capacity to activate second messengers and promote EGF-like effects. Thus, estrogen can signal by the same mechanism as various other hormones, through a specific 7TM receptor.

Bisphenol-A rapidly promotes dynamic changes in hippocampal dendritic morphology through estrogen receptor-mediated pathway by concomitant phosphorylation of NMDA receptor subunit NR2B

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

Xu Xiaohong, E-mail: xuxh63@zjnu.cn; Ye Yinping; Li Tao

Bisphenol-A (BPA) is known to be a potent endocrine disrupter. Evidence is emerging that estrogen exerts a rapid influence on hippocampal synaptic plasticity and the dendritic spine density, which requires activation of NMDA receptors. In the present study, we investigated the effects of BPA (ranging from 1 to 1000 nM), focusing on the rapid dynamic changes in dendritic filopodia and the expressions of estrogen receptor (ER) {beta} and NMDA receptor, as well as the phosphorylation of NMDA receptor subunit NR2B in the cultured hippocampal neurons. A specific ER antagonist ICI 182,780 was used to examine the potential involvement of ERs.more » The results demonstrated that exposure to BPA (ranging from 10 to 1000 nM) for 30 min rapidly enhanced the motility and the density of dendritic filopodia in the cultured hippocampal neurons, as well as the phosphorylation of NR2B (pNR2B), though the expressions of NMDA receptor subunits NR1, NR2B, and ER{beta} were not changed. The antagonist of ERs completely inhibited the BPA-induced increases in the filopodial motility and the number of filopodia extending from dendrites. The increased pNR2B induced by BPA (100 nM) was also completely eliminated. Furthermore, BPA attenuated the effects of 17{beta}-estradiol (17{beta}-E{sub 2}) on the dendritic filopodia outgrowth and the expression of pNR2B when BPA was co-treated with 17{beta}-E{sub 2}. The present results suggest that BPA, like 17{beta}-E{sub 2}, rapidly results in the enhanced motility and density of dendritic filopodia in the cultured hippocampal neurons with the concomitant activation of NMDA receptor subunit NR2B via an ER-mediated signaling pathway. Meanwhile, BPA suppressed the enhancement effects of 17{beta}-E{sub 2} when it coexists with 17{beta}-E{sub 2}. These results provided important evidence suggesting the neurotoxicity of the low levels of BPA during the early postnatal development of the brain.« less

Fertility in a high-altitude environment is compromised by luteal dysfunction: the relative roles of hypoxia and oxidative stress

PubMed Central

2013-01-01

Background At high altitudes, hypoxia, oxidative stress or both compromise sheep fertility. In the present work, we tested the relative effect of short- or long-term exposure to high altitude hypobaric hypoxia and oxidative stress on corpora luteal structure and function. Methods The growth dynamics of the corpora lutea during the estrous cycle were studied daily by ultrasonography in cycling sheep that were either native or naïve to high-altitude conditions and that were supplemented or not supplemented with antioxidant vitamins. Arterial and venous blood samples were simultaneously drawn for determination of gases and oxidative stress biomarkers and progesterone measurement. On day five after ovulation in the next cycle, the ovaries were removed for immunodetection of luteal HIF-1alpha and VEGF and IGF-I and to detect IGF-II gene expression. Results The results showed that both short- and long-term exposure to high-altitude conditions decreased luteal growth and IGF-I and IGF-II gene expression but increased HIF-1 alpha and VEGF immunoexpression. The level of plasma progesterone was also increased at a high altitude, although an association with increased corpus luteum vascularization was only found in sheep native to a high-altitude location. Administration of antioxidant vitamins resulted in a limited effect, which was restricted to decreased expression of oxidative stress biomarkers and luteal HIF-1alpha and VEGF immunoexpression. Conclusions Exposure of the sheep to high-altitude hypobaric hypoxia for short or long time periods affects the development and function of the corpus luteum. Moreover, the observed association of oxidative stress with hypoxia and the absence of any significant effect of antioxidant vitamins on most anatomical and functional corpus luteum traits suggests that the effects of high altitude on this ovarian structure are mainly mediated by hypoxia. Thus, these findings may help explain the decrease in sheep fertility at a high altitude. PMID:23521851

Strong association of insulin-like growth factor 1 receptor expression with histologic grade, subtype, and HPV status in penile squamous cell carcinomas: a tissue microarray study of 112 cases.

PubMed

Faraj, Sheila F; Gonzalez-Roibon, Nilda; Munari, Enrico; Sharma, Rajni; Burnett, Arthur L; Cubilla, Antonio L; Netto, George J; Chaux, Alcides

2017-06-01

Insulin-like growth factor-1 receptor (IGF1R) plays a key role in cell growth and transformation. It is overexpressed in several solid tumors. This study evaluates IGF1R immunoexpression in penile squamous cell carcinoma (SCC). Four tissue microarrays were built from formalin-fixed, paraffin-embedded blocks of 112 penile SCC from Paraguay. Membranous IGF1R expression was evaluated by immunohistochemistry using two different approaches. An H-score was calculated in each spot (stain intensity by extent), and a median score per tumor was obtained. The second approach consisted of a score similar to the scoring system that was used for evaluating HER2 immunoexpression. For each case, the highest category obtained at any spot was used for statistical analyses. IGF1R expression was compared by histologic subtype, grade, and human papillomavirus (HPV) status. Median H-score was 22.5. The distribution of IGF1R expression by HER2 approach was as follows: 0 in 33.0% cases, 1+ in 46.4%, 2+ in 14.3%, and 3+ in 6.2%. IGF1R H-scores were associated with basaloid and warty/basaloid subtypes (p = 0.0026) and higher grade (p = 0.00052). Although weaker when using the HER2 approach, the association of IGF1R expression with subtype (p = 0.015) and grade (p = 0.015) remained significant. Furthermore, there was an association between IGF1R expression by HER2 approach and HPV status (p = 0.012). IGF1R was expressed in about two thirds of penile SCC cases, showing a strong positive association with histologic grade, subtype, and HPV status. Considering that grade is a predictor of outcome IGF1R expression may have prognostic relevance and could point to a potential role for IGF1R inhibitors in treating penile SCC.

Fertility in a high-altitude environment is compromised by luteal dysfunction: the relative roles of hypoxia and oxidative stress.

PubMed

Parraguez, Víctor H; Urquieta, Bessie; Pérez, Laura; Castellaro, Giorgio; De los Reyes, Mónica; Torres-Rovira, Laura; Aguado-Martínez, Adriana; Astiz, Susana; González-Bulnes, Antonio

2013-03-23

At high altitudes, hypoxia, oxidative stress or both compromise sheep fertility. In the present work, we tested the relative effect of short- or long-term exposure to high altitude hypobaric hypoxia and oxidative stress on corpora luteal structure and function. The growth dynamics of the corpora lutea during the estrous cycle were studied daily by ultrasonography in cycling sheep that were either native or naïve to high-altitude conditions and that were supplemented or not supplemented with antioxidant vitamins. Arterial and venous blood samples were simultaneously drawn for determination of gases and oxidative stress biomarkers and progesterone measurement. On day five after ovulation in the next cycle, the ovaries were removed for immunodetection of luteal HIF-1alpha and VEGF and IGF-I and to detect IGF-II gene expression. The results showed that both short- and long-term exposure to high-altitude conditions decreased luteal growth and IGF-I and IGF-II gene expression but increased HIF-1 alpha and VEGF immunoexpression. The level of plasma progesterone was also increased at a high altitude, although an association with increased corpus luteum vascularization was only found in sheep native to a high-altitude location. Administration of antioxidant vitamins resulted in a limited effect, which was restricted to decreased expression of oxidative stress biomarkers and luteal HIF-1alpha and VEGF immunoexpression. Exposure of the sheep to high-altitude hypobaric hypoxia for short or long time periods affects the development and function of the corpus luteum. Moreover, the observed association of oxidative stress with hypoxia and the absence of any significant effect of antioxidant vitamins on most anatomical and functional corpus luteum traits suggests that the effects of high altitude on this ovarian structure are mainly mediated by hypoxia. Thus, these findings may help explain the decrease in sheep fertility at a high altitude.

Interactions between glioma and pregnancy: insight from a 52-case multicenter series.

PubMed

Peeters, Sophie; Pagès, Mélanie; Gauchotte, Guillaume; Miquel, Catherine; Cartalat-Carel, Stéphanie; Guillamo, Jean-Sébastien; Capelle, Laurent; Delattre, Jean-Yves; Beauchesne, Patrick; Debouverie, Marc; Fontaine, Denys; Jouanneau, Emmanuel; Stecken, Jean; Menei, Philippe; De Witte, Olivier; Colin, Philippe; Frappaz, Didier; Lesimple, Thierry; Bauchet, Luc; Lopes, Manuel; Bozec, Laurence; Moyal, Elisabeth; Deroulers, Christophe; Varlet, Pascale; Zanello, Marc; Chretien, Fabrice; Oppenheim, Catherine; Duffau, Hugues; Taillandier, Luc; Pallud, Johan

2018-01-01

OBJECTIVE The goal of this study was to provide insight into the influence of gliomas on gestational outcomes, the impact of pregnancy on gliomas, and the identification of patients at risk. METHODS In this multiinstitutional retrospective study, the authors identified 52 pregnancies in 50 women diagnosed with a glioma. RESULTS For gliomas known prior to pregnancy (n = 24), we found the following: 1) An increase in the quantified imaging growth rates occurred during pregnancy in 87% of cases. 2) Clinical deterioration occurred in 38% of cases, with seizures alone resolving after delivery in 57.2% of cases. 3) Oncological treatments were immediately performed after delivery in 25% of cases. For gliomas diagnosed during pregnancy (n = 28), we demonstrated the following: 1) The tumor was discovered during the second and third trimesters in 29% and 54% of cases, respectively, with seizures being the presenting symptom in 68% of cases. 2) The quantified imaging growth rates did not significantly decrease after delivery and before oncological treatment. 3) Clinical deterioration resolved after delivery in 21.4% of cases. 4) Oncological treatments were immediately performed after delivery in 70% of cases. Gliomas with a high grade of malignancy, negative immunoexpression of alpha-internexin, or positive immunoexpression for p53 were more likely to be associated with tumor progression during pregnancy. Deliveries were all uneventful (cesarean section in 54.5% of cases and vaginal delivery in 45.5%), and the infants were developmentally normal. CONCLUSIONS When a woman harboring a glioma envisions a pregnancy, or when a glioma is discovered in a pregnant patient, the authors suggest informing her and her partner that pregnancy may impact the evolution of the glioma clinically and radiologically. They strongly advise a multidisciplinary approach to management. ■ CLASSIFICATION OF EVIDENCE Type of question: association; study design: case series; evidence: Class IV.

Reduction of spermatogenesis in mice after tributyltin administration.

PubMed

Chen, Yufang; Zuo, Zhenghong; Chen, Shuzhen; Yan, Feihuang; Chen, Yixin; Yang, Zengming; Wang, Chonggang

2008-09-29

Organotin compounds, such as tributyltin (TBT) used as an antifouling biocide, can induce masculinization in female mollusks. However, few studies addressing the effect of TBT on spermatogenesis in mammalian have been reported. This study was conducted to investigate the effects of TBT at low doses (0.5, 5, and 50 microg/kg, respectively) on spermatogenesis in mice as exposed from puberty and gave insight into the mechanism. After exposure for 30 days, the gonadosomatic index (GSI) was significantly decreased. The testosterone levels in the testes were not altered and the 17beta-estradiol levels were significantly decreased in a dose-dependent manner, spermatogenesis of the testis was significantly inhibited. Estrogen receptor (ER-alpha and ER-beta) levels in testes of the mice exposed to TBT were decreased in a dose-dependent manner. The results suggest that ER play an important role in TBT-mediated inhibition of spermatogenesis.

Diosgenin promotes oligodendrocyte progenitor cell differentiation through estrogen receptor-mediated ERK1/2 activation to accelerate remyelination.

PubMed

Xiao, Lin; Guo, Dazhi; Hu, Chun; Shen, Weiran; Shan, Lei; Li, Cui; Liu, Xiuyun; Yang, Wenjing; Zhang, Weidong; He, Cheng

2012-07-01

Differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes is a prerequisite for remyelination after demyelination, and impairment of this process is suggested to be a major reason for remyelination failure. Diosgenin, a plant-derived steroid, has been implicated for therapeutic use in many diseases, but little is known about its effect on the central nervous system. In this study, using a purified rat OPC culture model, we show that diosgenin significantly and specifically promotes OPC differentiation without affecting the viability, proliferation, or migration of OPC. Interestingly, the effect of diosgenin can be blocked by estrogen receptor (ER) antagonist ICI 182780 but not by glucocorticoid and progesterone receptor antagonist RU38486, nor by mineralocorticoid receptor antagonist spirolactone. Moreover, it is revealed that both ER-alpha and ER-beta are expressed in OPC, and diosgenin can activate the extracellular signal-regulated kinase 1/2 (ERK1/2) in OPC via ER. The pro-differentiation effect of diosgenin can also be obstructed by the ERK inhibitor PD98059. Furthermore, in the cuprizone-induced demyelination model, it is demonstrated that diosgenin administration significantly accelerates/enhances remyelination as detected by Luxol fast blue stain, MBP immunohistochemistry and real time RT-PCR. Diosgenin also increases the number of mature oligodendrocytes in the corpus callosum while it does not affect the number of OPCs. Taking together, our results suggest that diosgenin promotes the differentiation of OPC into mature oligodendrocyte through an ER-mediated ERK1/2 activation pathway to accelerate remyelination, which implicates a novel therapeutic usage of this steroidal natural product in demyelinating diseases such as multiple sclerosis (MS). Copyright © 2012 Wiley Periodicals, Inc.

Immunohistochemical panel to characterize canine prostate carcinomas according to aberrant p63 expression.

PubMed

Fonseca-Alves, Carlos Eduardo; Kobayashi, Priscila Emiko; Rivera Calderón, Luis Gabriel; Felisbino, Sérgio Luis; Rinaldi, Jaqueline de Carvalho; Drigo, Sandra Aparecida; Rogatto, Silvia Regina; Laufer-Amorim, Renée

2018-01-01

An unusual variant of prostate adenocarcinoma (PC) expressing nuclear p63 in secretory cells instead of the typical basal expression has been reported in men. Nevertheless, the biological behavior and clinical significance of this phenomenon is unknown. In dogs, this unusual PC subtype has not been described. In this study, p63 immunoexpression was investigated in 90 canine PCs and 20 normal prostate tissues (NT). The p63 expression pattern in luminal or basal cells was confirmed in a selected group of 26 PCs and 20 NT by immunohistochemistry and/or Western blotting assays. Eleven canine PC samples aberrantly expressing p63 (p63+) in secretory cells were compared with 15 p63 negative (p63-) cases in the context of several molecular markers (high molecular weight cytokeratin-HMWC, CK8/18, CK5, AR, PSA, chromogranin, NKX3.1, PTEN, AKT and C-MYC). P63+ samples were positive for CK5, HMWC and CK8/18 and negative for PSA, NKX3.1, PTEN and chromogranin. Five p63+ PCs were negative for AR, and the remaining six samples had low AR expression. In contrast, p63- PC showed AR and PSA positive expression in all 15 samples. Only five p63- PCs were positive for CK5. Both p63+ and p63- PC samples showed higher cytoplasmic AKT expression and nuclear C-MYC staining in comparison with normal tissues. Metastatic (N = 12) and non-metastatic (N = 14) PCs showed similar immunoexpression for all markers tested. In contrast to human PC, canine PC aberrantly expressing p63 showed higher expression levels of HMWC and CK5 and lower levels of NKX3.1. Canine p63+ PC is a very rare PC group showing a distinct phenotype compared to typical canine PC, including AR and PSA negative expression. Although in a limited number of cases, p63 expression was not associated with metastasis in canine PC, and cytoplasmic p63 expression was observed in animals with shorter survival time, similar to human PC cases.

Expression of pERK and pAKT in human astrocytomas: correlation with IDH1-R132H presence, vascular endothelial growth factor, microvascular characteristics and clinical outcome.

PubMed

Saetta, Angelica A; Levidou, Georgia; El-Habr, Elias A; Panayotidis, Ioannis; Samaras, Vassilis; Thymara, Irene; Sakellariou, Stratigoula; Boviatsis, Efstathios; Patsouris, Efstratios; Korkolopoulou, Penelope

2011-06-01

Although pERK and pAKT are reportedly activated in various neoplasms, little information is available about their significance in astrocytomas. Paraffin-embedded tissue from 82 patients with diffuse infiltrating astrocytomas (grades II to IV) was investigated for the association of pERK and pAKT activation with clinicopathological features, vascular endothelial growth factor (VEGF), isocitrate dehydrogenase 1 and microvascular parameters. Nuclear pERK labelling index (LI) increased with increasing cytoplasmic pERK LI and nuclear and cytoplasmic pAKT LI (p = 0.0019, p = 0.0260 and p = 0.0012, respectively). Accordingly, cytoplasmic pERK increased with increasing levels of nuclear (p = 0.0001) and marginally with cytoplasmic pAKT LI (p = 0.0526). Nuclear and cytoplasmic pERK LI and nuclear pAKT LI were positively correlated with tumour histological grade (p = 0.0040, p = 0.0238 for pERK and p = 0.0004 for pAKT, respectively). VEGF expression was correlated with nuclear pERK (p = 0.0099) and nuclear pAKT LI (p = 0.0002). Interestingly, pERK cytoplasmic LI increased with microvessel calibre (p = 0.0287), whereas pAKT nuclear LI was marginally related to microvessel density (p = 0.0685). The presence of IDH1-R132H was related only to histological grade and lower microvessel calibre. Multivariate survival analysis in the entire cohort selected cytoplasmic pAKT LI (p = 0.045), histological grade, microvessel calibre (p = 0.028), patients' age, gender and surgical excision as independent predictors of survival. Moreover, in glioblastomas, pERK nuclear LI emerged as a favourable prognosticator in the presence of IDH1-R132H. pERK and pAKT in astrocytomas are interrelated and associated with tumour grade and angiogenesis. Moreover, the importance of cytoplasmic pAKT immunoexpression in patients' prognosis and nuclear pERK immunoexpression in glioblastomas is confirmed.

A novel carborane analog, BE360, with a carbon-containing polyhedral boron-cluster is a new selective estrogen receptor modulator for bone

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

Hirata, Michiko; Inada, Masaki; Matsumoto, Chiho

Carboranes are a class of carbon-containing polyhedral boron-cluster compounds with globular geometry and hydrophobic surface that interact with hormone receptors. Estrogen deficiency results in marked bone loss due to increased osteoclastic bone resorption in females, but estrogen replacement therapy is not generally used for postmenopausal osteoporosis due to the risk of uterine cancer. We synthesized a novel carborane compound BE360 to clarify its anti-osteoporosis activity. BE360 showed a high binding affinity to estrogen receptors (ER), ER{alpha} and ER{beta}. In ovariectomized (OVX) mice, femoral bone volume was markedly reduced and BE360 dose-dependently restored bone loss in OVX mice. However, BE360 didmore » not exhibit any estrogenic activity in the uterus. BE360 also restored bone loss in orchidectomized mice without androgenic action in the sex organs. Therefore, BE360 is a novel selective estrogen receptor modulator (SERM) that may offer a new therapy option for osteoporosis.« less

Expression of mucins in the mucosal surface of small intestines in 1 week-old pigs.

PubMed

Kim, Chung Hyun; Oh, Yeonsu; Ha, Yooncheol; Ahn, Qwein; Kim, Sung-Hoon; Cho, Kyung-Dong; Lee, Bog-Hieu; Chae, Chanhee

2010-02-01

The aim of this study was to determine the immunoexpression of mucins in jejunal and ileal villous epithelium using six antibodies against MUC1, MUC2, MUC4 MUC5AC, MUC5B and MUC6. The immunohistochemical score for MUC1 has significantly intense staining compared with MUC2 (P=0.008) and the immunohistochemical socre for MUC4 and MUC 6 has significantly intense staining compared with MUC2 (P=0.032) in ileal villous surface. The immunohistochemical score for MUC4 (P=0.008), MUC5AC (P=0.016) and MUC6 (P=0.016) in ileal villous surface has significantly intense staining compared with ileal cryptic surface. The results of this study demonstrated that six mucins gave distinctly different expression patterns throughout the 1 week-old porcine small intestinal tract.

Effect of different doses of monosodium glutamate on the thyroid follicular cells of adult male albino rats: a histological study

PubMed Central

Khalaf, Hanaa A; Arafat, Eetmad A

2015-01-01

Monosodium glutamate (MSG) is a major flavor enhancer used as a food additive. The present study investigates the effects of different doses of MSG on the morphometric and histological changes of the thyroid gland. 28 male albino rats were used. The rats were divided into four groups: group I control, group II, III and IV treated with MSG (0.25 g/kg, 3 g/kg, 6 g/kg daily for one month) respectively. The thyroid glands were dissected out and prepared for light and electron microscopic examination. Light microscopic examination of thyroid gland of group II revealed increase in follicular epithelial height. Groups III & IV showed decrease in the follicular diameter and irregularity in the shape of some follicles with discontinuity of basement membrane. Follicular hyperplasia was detected in some follicles with appearance of multiple pyknotic nuclei in follicular and interfollicular cells and multiple exfoliated cells in the colloid. In addition, areas of loss of follicular pattern were appeared in group IV. Immunohistochemical examination of BCL2 immunoexpression of the thyroid glands of groups III & IV reveals weak positive reaction in the follicular cells cytoplasm. Ultrathin sections examination of groups III & IV revealed follicular cells with irregular hyperchromatic nuclei, marked dilatation of rER and increased lysosomes with areas of short or lost apical microvilli. In addition, vacuolation of mitochondria was detected in group IV. The results displayed that MSG even at low doses is capable of producing alterations in the body weights and thyroid tissue function and histology. PMID:26884820

Microcystic adnexal carcinoma with sebaceous differentiation: Three cases.

PubMed

Fernandez-Flores, Angel; Llamas-Velasco, Mar; Saus, Carles; Patel, Anisha; Rutten, Arno

2018-04-01

Microcystic adnexal carcinoma (MAC) is a low-grade malignant tumor of the skin. Histologically, this tumor shows a biphasic pattern, with cords and nests of basaloid cells, as well as keratin horn cysts. This biphasic histological appearance has been interpreted by some authors as a sign of double eccrine and folliculosebaceous-apocrine differentiation, whereas some other authors defend a solely eccrine differentiation. In this context, sebaceous differentiation in MAC would support the first option. However, there are only 3 cases of MAC with sebaceous differentiation in the literature, and all of them were reported before adipophilin was available, which in the appropriate context (eg, testing clear cells for sebaceous vs eccrine differentiation) is very useful. In this study, we present 3 cases of MAC with focal sebaceous differentiation confirmed by immunoexpression of adipophilin in the sebaceous foci. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Loss of Endothelial Barrier Antigen Immunoreactivity in Rat Retinal Microvessels is Correlated with Clostridium perfringens Type D Epsilon Toxin-induced Damage to the Blood-Retinal Barrier.

PubMed

Mander, K A; Finnie, J W

2018-01-01

Clostridium perfringens type D epsilon toxin (ETX) is a potent neurotoxin producing a severe, and often fatal, neurological disorder in ruminant livestock. Microvascular damage appears to be the fundamental action of ETX in the brain and, recently, similar vascular injury, with subsequent severe vasogenic oedema, has been reported in the retina of rats given ETX. Endothelial barrier antigen (EBA) is a useful marker of an intact blood-brain barrier in rats and it has been shown that loss of EBA immunoreactivity is correlated with ETX-induced cerebral microvascular damage in this species. This paper reports, for the first time, that loss of EBA immunoexpression also occurs in rat retinal microvessels exposed to ETX, the marked reduction in EBA immunopositivity acting as a useful marker for blood-retinal barrier breakdown produced by this neurotoxin. Copyright © 2017 Elsevier Ltd. All rights reserved.

Median nerve trauma in a rat model of work-related musculoskeletal disorder.

PubMed

Clark, Brian D; Barr, Ann E; Safadi, Fayez F; Beitman, Lisa; Al-Shatti, Talal; Amin, Mamta; Gaughan, John P; Barbe, Mary F

2003-07-01

Anatomical and physiological changes were evaluated in the median nerves of rats trained to perform repetitive reaching. Motor degradation was evident after 4 weeks. ED1-immunoreactive macrophages were seen in the transcarpal region of the median nerve of both forelimbs by 5-6 weeks. Fibrosis, characterized by increased immunoexpression of collagen type I by 8 weeks and connective tissue growth factor by 12 weeks, was evident. The conduction velocity (NCV) within the carpal tunnel showed a modest but significant decline after 9-12 weeks. The lowest NCV values were found in animals that refused to participate in the task for the full time available. Thus, both anatomical and physiological signs of progressive tissue damage were present in this model. These results, together with other recent findings indicate that work-related carpal tunnel syndrome develops through mechanisms that include injury, inflammation, fibrosis and subsequent nerve compression.

Immunophenotype of nipple adenoma in a male patient.

PubMed

Fernandez-Flores, Angel; Suarez-Peñaranda, Jose-Manuel

2011-03-01

Adenoma of the nipple is rare in men. It must be distinguished from a breast carcinoma and from Paget disease. In this sense, immunohistochemistry can be of some help. In women, for instance, immunoexpression of c-erbB-2 favors a diagnosis of Paget disease, according to some studies. Nevertheless, we have not found any studies on HER2/neu status, estrogen receptors, or progesterone receptors in nipple adenoma of male patients. We present a case of an adenoma of the nipple in a 21-year-old man in which we carried out a wide immunohistochemical study. The lesion did not express estrogen receptors, progesterone receptors, or androgen receptors. The HercepTest was negative. Smooth muscle Actin and p63 were remarked in the basal layer of the tumoral tubules, supporting the benignancy of the lesion. This case of adenoma of the nipple in a male shows an immunophenotype that is similar to the ones reported in female patients.

Immunohistochemical study of motoneurons in lumbar spinal cord of c57black/6 mice after 30-days space flight

NASA Astrophysics Data System (ADS)

Tyapkina, Oksana; Islamov, Rustem; Nurullin, Leniz; Petrov, Konstantin.; Rezvyakov, Pavel; Nikolsky, Evgeny

To investigate mechanisms of hypogravity motor syndrome development the immunoexpression of heat shock proteins (Hsp27 and Hsp70), proteins of synaptic transmission (Synaptophysin and PSD95) and neuroprotective proteins (VEGF and Flt-1) in motoneurons of lumbar spinal cord in c57black/6 control mice (n=2) and after 30-days space flight (n=2) was studied. For a quantitative assessment of target proteins level in motoneurons frozen cross sections of lumbar spinal cord were underwent to immunohistochemical staining. Primary antibodies against VEGF, Flt-1, Hsp27 and Hsp70 (SantaCruz Biotechnology, inc. USA), against Synaptophysin and PSD95 (Abcam plc, UK) were visualized by streptavidin-biotin method. Images of spinal cords were received using OlympusBX51WI microscope with AxioCamMRm camera (CarlZeiss, Germany) and the AxioVisionRel. 4.6.3 software (CarlZeiss, Germany). The digitized data were analyzed using ImageJ 1.43 software (NIH, the USA). Quantitively, protein level in motoneurons was estimated by the density of immunoprecipitation. Results of research have not revealed any reliable changes in the immunnoexpression of vascular endothelial growth factor (VEGF) and its Flt-1 receptor in motoneurons of lumbar spinal cord in control and in mice after 30-day space flight. Studying of heat shock proteins, such as Hsp27 and Hsp70, revealed the decrease in level of these proteins immunoexpression in motoneurons of mice from flight group by 15% and 10%, respectively. Some decrease in level of immunnoexpression of presynaptic membrane proteins (synaptophysin, by 21%) and proteins of postsynaptic area (PSD95, by 55%) was observed after space flight. The data obtained testify to possible changes in a functional state (synaptic activity and stress resistance) of motoneurons of lumbar spinal cord in mice after space flight. Thus, we obtained new data on involvement of motoneurons innervating skeletal muscles in development of hypogravity motor syndrome. Research was supported by grants of: BION-M1, program of the President of the Russian Federation (Science School) no. No. 5584.214.4 (NEE), RFFR No.11-04-00602 (NEE), Program No.7 of Presidium of RAS (NEE), RFFR No.13-04-00310 (IRR), RFFR No.12-04-01414 (NLF).

[Regulation of [12Asp]K-ras4B on transcriptional activity of estrogen receptor in endometrial carcinoma HEC-1A cell lines].

PubMed

Gui, Li-ming; Wei, Li-hui; Xu, Ming-xu; Wang, Jian-liu; Zhong, Ying-cheng; Li, Xiao-ping; Tu, Zheng; Sun, Peng-ming; Ma, Da-long

2004-01-01

To investigate the effect of mutant-type [(12)Asp]K-ras4B gene on the expression of estrogen receptor (ER) alpha and beta and their transcriptional activity as a transcription factor in endometrial carcinoma HEC-1A cell line. (1) Effect of [(12)Asp]K-ras4B on the expression of ER alpha and beta were determined using Western blot assay. (2) Eukaryotic expression plasmid pGL3-luciferase-ERE containing luciferase report gene and estrogen receptor element (ERE) was constructed, and co-transfected into NIH3T3 and HEC-1A cell lines with pEGFP-N1 to examine the effect of [(12)Asp]K-ras4B on ER transcription that is regulated by estradiol. In addition, they were transfected into pSV5-HER0 (containing full length wide type ERalpha cDNA) and pCMV-rafS621A (inhibiting raf kinase) plasmids to test the effect of [(12)Asp]K-ras4B/raf signal pathway on transcriptional activity of ER proteins. (1) Protein level of ERs expressed in pcDI transfected control cells was low while it was increased for 3.6-fold (97 +/- 25, 349 +/- 67, P < 0.01) and 1.9-fold (128 +/- 37, 349 +/- 30, P < 0.05) in ERalpha and ERbeta, respectively, in pcDI-[(12)Asp]K-ras4B NIH3T3 cells after transfection. (2) In pcDI-[(12)Asp]K-ras4B NIH3T3 cells, the ratios for ERalpha and and ERbeta levels before transfection of rafS621A plasmids to that after the transfection, were 2.4:1 (724 +/- 45, 310 +/- 46, P < 0.05) and 1.8:1 (493 +/- 20, 284 +/- 20, P < 0.01), respectively; In HEC-1A cells, these ratios were 2.1:1 (566 +/- 22, 279 +/- 30, P < 0.01) and 2.4:1 (405 +/- 33, 165 +/- 15, P < 0.01), respectively. (3) In low serum (2%) culture condition, estradiol (E(2)) stimulated luciferase activity with an increase of 13-fold (130 +/- 42, 1681 +/- 242, P < 0.01) in pcDI-[(12)Asp] K-ras4B NIH3T3 cells, 19-fold (141 +/- 39, 2644 +/- 331, P < 0.001) in HEC-1A cells, respectively, when compared with those in the absence of E(2). (4) In pSV5-HER0 transfected pcDI-[(12)Asp] K-ras4B NIH3T3 cells and HEC-1A cells, compared to the untransfected cells, the ER transcriptional activity in the transfected cells increased markedly. The luciferase activity was increased for 8-fold (1048 +/- 91, 8099 +/- 452, P < 0.01) and 6-fold (2148 +/- 259, 12,705 +/- 2670, P < 0.001), respectively. rafS621A mutant had suppressive effects on luciferase activities in HEC-1A cells and pcDI-[(12)Asp]K-ras4B NIH3T3 cells. The ratio of luciferase activities in pcDI-[(12)Asp]K-ras4B NIH3T3 and HEC-1A cells, before and after transfection was 7.8:1 (1184 +/- 168, 152 +/- 27, P < 0.05) and 6.4:1 (1949 +/- 212, 304 +/- 60, P < 0.01), respectively. (1) [(12)Asp]K-ras4B can enhance the expression of ERalpha and beta proteins. This may be correlated with [(12)Asp]K-ras4B/raf signaling pathway. (2) The effect of mutant-type [(12)Asp]K-ras4B gene on ERs transcriptional activity in HEC-1A cells appears to need E(2).

Tissue immunostaining for factor XIIIa in dermal dendrocytes of pityriasis alba skin lesions*

PubMed Central

Carneiro, Francisca Regina Oliveira; do Amaral, Gabriela Borborema; Mendes, Maiana Darwich; Quaresma, Juarez Antônio Simões

2014-01-01

BACKGROUND Pityriasis alba affects 1% of the world population and about 9.9% of the children in Brazil. However, its etiology remains uncertain. OBJECTIVE The objective of the present study was to evaluate the immunoexpression of factor XIIIa in dermal dendrocytes of skin lesions of pityriasis alba. METHOD Twenty patients with pityriasis alba and 20 patients with atopic dermatitis underwent biopsy. The dermal dendrocytes marked by factor XIIIa were counted by means of immunohistochemical analysis. RESULTS The mean amount of dermal dendrocytes found in the patients with pityriasis alba was 2, whereas in the patients with atopic dermatitis it was 4, with a statistically significant difference between them. A cutoff point of 3 cells/square inch was established to differentiate pityriasis alba from atopic dermatitis, with 80% sensibility and 90% specificity. CONCLUSION We believe that pityriasis alba and atopic dermatitis should be considered different clinical forms within the spectrum of atopic disease, in which sun radiation plays an important role by modulating the progression of the disease. PMID:24770500

CD138 Expression Is Observed in the Urothelial Epithelium and in Various Urothelial Carcinomas, and Cannot Be Evidence for Plasmacytoid Urothelial Carcinoma.

PubMed

Goto, Keisuke

2016-10-01

CD138 (syndecan-1) immunoexpression has been reported to be specific for the plasmacytoid variant of urothelial carcinomas (UCs). The aim of this study was to examine the utility of CD138 immunohistochemistry for diagnosing the plasmacytoid variant of UCs. The extent and intensity of CD138 immunostaining were evaluated in 22 infiltrating UCs, 2 other infiltrating carcinomas, 15 noninvasive urothelial lesions, 3 other benign lesions, and perilesional normal tissues. CD138 immunostaining of the normal urothelial epithelium was universally diffuse and strong. In addition, all 42 cases of urinary tract lesions exhibited positive CD138 immunostaining; however, 1 of 3 plasmacytoid variants exhibited focal CD138 expression. The frequency of CD138 positivity in plasmacytoid variants may be relatively low, compared with that observed in the conventional types and other variants; thus, it is not appropriate to assume that CD138 expression in UCs is specific for plasmacytoid variants. © The Author(s) 2016.

Comparative immunoexpression of ICAM-1, TGF-β1 and ki-67 in periapical and residual cysts.

PubMed

Martins, R; Armada, L; Dos Santos, T-C; Pires, F-R

2017-01-01

This study compared the immunohistochemical expression of ki-67, transforming growth factor beta 1 (TGF-β1) and intercellular adhesion molecule-1 (ICAM-1) in inflammatory periapical cysts and residual cysts. The study sample was composed by 25 periapical cysts and 25 residual cysts and immunohistochemical reactions were carried out using antibodies directed against ICAM-1, TGF-β1 and ki-67. Clinical, radiological, gross, histological and immunohistochemical data were tabulated for descriptive and comparative analysis using the SPSS software and differences were considered statistically significant when p<0.05%. There were no differences between the expression of ICAM-1 (p=0.239) and TGF-β1 (p=0.258) when comparing both groups. Ki-67 labeling index was higher in residual cysts compared to periapical cysts (p=0.017). Results from the present study suggest that some specific inflammatory stimuli on residual cysts would modulate their mechanisms of etiopathogenesis, growing and repair.

GLUT-1 immunoexpression in oral epithelial dysplasia, oral squamous cell carcinoma, and verrucous carcinoma.

PubMed

Angadi, Vidya C; Angadi, Punnya V

2015-06-01

Glucose transporters, such as GLUT-1, mediate the important mechanisms involved in cellular glucose influx, allowing cells to proliferate and survive. The significance of GLUT-1 expression in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) has been less explored, and no study has investigated it in relation to verrucous carcinoma (VC). We evaluated 30 cases each of OED, OSCC, and VC, graded further on the basis of their differentiation, immunohistochemically for GLUT-1 expression, along with 10 specimens of normal oral mucosa (NOM) as controls. In OSCC, GLUT-1 expression increased with the degree of dysplasia and increasing grade (P < 0.001). The expression in VC was predominantly membranous and intense, resembling well differentiated OSCC. This increase of GLUT-1 expression in OSCC along with the degree of dysplasia and the histologic grade reflects the expanding glycolytic response to hypoxia. This is the first study to have revealed prominent GLUT-1 expression in VC, highlighting its inherent metabolic capacity.

Soy consumption and histopathologic markers in breast tissue using tissue microarrays.

PubMed

Maskarinec, Gertraud; Erber, Eva; Verheus, Martijn; Hernandez, Brenda Y; Killeen, Jeffrey; Cashin, Suzanne; Cline, J Mark

2009-01-01

This study examined the relation of soy intake with hormonal and proliferation markers in benign and malignant breast tissue using tissue microarrays (TMAs). TMAs with up to 4 malignant and 4 benign tissue samples for 268 breast cancer cases were constructed. Soy intake in early life and in adulthood was assessed by questionnaire. The TMAs were stained for estrogen receptor (ER) alpha, ERbeta, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2/neu), proliferating cell nuclear antigen (PCNA), and Ki-67 using standard immunohistochemical methods. Logistic regression was applied for statistical analysis. A higher percentage of women showed positive marker expression in malignant than in benign tissue. With one exception, HER2/neu, no significant associations between soy intake and pathologic markers were observed. Early life soy intake was associated with lower HER2/neu and PCNA staining of malignant tissue. In benign tissue, early life soy intake showed higher ER and PR expression, but no difference in proliferation markers. The results of this investigation provide some assurance that soy intake does not adversely affect markers of proliferation. TMAs were shown to be a useful tool for epidemiologic research.

Long-term potentiation in the rat medial vestibular nuclei depends on locally synthesized 17beta-estradiol.

PubMed

Grassi, Silvarosa; Frondaroli, Adele; Dieni, Cristina; Scarduzio, Mariangela; Pettorossi, Vito E

2009-08-26

In male rat brainstem slices, we investigated the involvement of locally synthesized 17beta-estradiol (E(2)) in the induction in the medial vestibular nucleus (MVN) of long-term potentiation (LTP) by high-frequency stimulation (HFS) of the primary vestibular afferents. We demonstrated that the blockade of aromatase by letrozole or of E(2) receptors (ERalpha and ERbeta) by ICI 182,780 prevented the HFS-induced LTP of the N1 wave of the evoked field potential (FP) without affecting baseline responses. Only prolonged afferent activation could induce low LTP. In contrast, HFS applied under a combined blockade of GABA(A) receptors and aromatase or ERs was still able to induce LTP, but it was significantly lower and slower. These findings demonstrate that E(2) does not have a tonic influence on the activity of the MVN neurons and provide the first evidence of the crucial role played by local synthesis of E(2) in inducing LTP. We suggest that the synthesis of E(2) occurs after aromatase activation during HFS and facilitates the development of vestibular synaptic plasticity by influencing glutamate and GABA transmission.

Up-regulation of the alligator CYP3A77 gene by toxaphene and dexamethasone and its short term effect on plasma testosterone concentrations.

PubMed

Gunderson, M P; Kohno, S; Blumberg, B; Iguchi, T; Guillette, L J

2006-06-30

In this study we describe an alligator hepatic CYP3A gene, CYP3A77, which is inducible by dexamethasone and toxaphene. CYP3A plays a broad role in biotransforming both exogenous compounds and endogenous hormones such as testosterone and estradiol. Alligators collected from sites in Florida that are contaminated with organochlorine compounds exhibit differences in sex steroid concentrations. Many organochlorine compounds induce CYP3A expression in other vertebrates; hence, CYP3A induction by organochlorine contaminants could increase biotransformation and clearance of sex steroids by CYP3A and provide a plausible mechanism for the lowering of endogenous sex steroid concentrations in alligator plasma. We used real time PCR to examine whether known and suspected CYP3A inducers (dexamethasone, metyrapone, rifampicin, and toxaphene) up-regulate steady state levels of hepatic CYP3A77 transcript to determine if induction patterns in female juvenile alligators are similar to those reported in other vertebrates and whether toxaphene, an organochlorine compound found in high concentrations in Lake Apopka alligators, induces this gene. Estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), androgen receptor (AR), glucocorticoid receptor (GR), progesterone receptor (PR), and steroid-xenobiotic receptor (SXR) transcripts were also measured to determine whether any of these nuclear receptors are also regulated by these compounds in alligators. Dexamethasone (4.2-fold) and toxaphene (3.5-fold) significantly induced CYP3A77 gene transcript, whereas rifampicin (2.8-fold) and metyrapone (2.1-fold) up-regulated ERbeta after 24h. None of the compounds significantly up-regulated AR, ERalpha, GR, PR, or SXR over this time period. Plasma testosterone (T) did not change significantly after 24h in alligators from any of the treatment groups. Dexamethasone treated animals exhibited a strong relationship between the 24h plasma T concentrations and CYP3A77 (R(2)=0.9, positive) and SXR (R(2)=0.77, negative) transcripts, which suggests that the expression of these genes is related to plasma T in alligators. In light of our findings, we hypothesized that higher steady state CYP3A77 (and possibly SXR) gene expression would be observed in alligators collected from Lake Apopka, a polluted lake containing organochlorine compounds known to induce CYP3A isoforms in other taxa. Therefore, we measured basal levels of CYP3A77 and SXR gene transcripts in wild juvenile alligators collected from Orange Lake (reference lake), Lake Woodruff (reference lake), and Lake Apopka (contaminated lake). We found that no differences existed in CYP3A77 or SXR gene expression among animals from the lakes sampled suggesting that exposure to organochlorine compounds at concentrations present in Lake Apopka does not lead to variation in the expression of these genes, although capture stress could be interfering with these results since the glucocorticoid dexamethasone induces CYP3A77 transcript in alligators.

Grape Juice Concentrate Protects Rat Liver Against Cadmium Intoxication: Histopathology, Cytochrome C and Metalloproteinases Expression.

PubMed

de Moura, C F G; Ribeiro, F A P; Handan, B A; Aguiar, O; Oshima, C T F; Ribeiro, D A

2016-07-01

The aim of this study was to investigate if grape juice concentrate is able to protect rat liver against cadmium toxicity. For this purpose, histopathological analysis, cytochrome C expression and immunoexpresssion of metalloproteinases (MMP) 2 and 9 were investigated. A total of 15 Wistar rats weighing 250 g on the average, and 8 weeks age were distributed into 3 groups (n=5), as follows: Control group (non-treated group, CTRL); Cadmium group (Cd) and grape juice concentrate group (Cd+GJ). Histopathological analysis revealed that liver from animals treated with grape juice concentrate improved tissue degeneration induced by cadmium intoxication. Animals intoxicated with cadmium and treated with grape juice concentrate showed higher cytochrome C gene expression in liver cells. No significant statistically differences (p>0.05) were found to MMP 2 and 9 immunoexpression between groups. Taken together, our results demonstrate that grape juice concentrate is able to prevent tissue degeneration in rat liver as a result of increasing apoptosis. © Georg Thieme Verlag KG Stuttgart · New York.

Comparative study of β-catenin and CD44 immunoexpression in oral lichen planus and squamous cell carcinoma.

PubMed

Zargaran, Massoumeh; Baghaei, Fahimeh; Moghimbeigi, Abbas

2018-04-24

Dysfunction of adhesion molecules is believed to play an early and important role in developing cancer. Accordingly, this study aims to compare beta-catenin (β-catenin) and CD44 expression in oral lichen planus (OLP) as a condition with malignant potential and oral squamous cell carcinoma (OSCC). β-Catenin and CD44 expression were evaluated in 15 patients with epithelial hyperplasia (group A), 20 OLP (group B), and 20 OSCC (group C) by immunohistochemistry. Quantitative and semi-quantitative evaluations revealed β-catenin, and CD44 membranous expression had significant differences among the three groups. Expression of these markers in the OSCC group decreased significantly compared to that of the OLP. Also, nuclear/cytoplasmic expression of β-catenin was significantly different among the three groups, considering that nuclear expression was not observed in any of the epithelial hyperplasia and OLP samples. According to the findings of this study, β-catenin and CD44 can differentiate between behavior of OLP and OSCC, while the precancerous nature of OLP and malignant transformation potential of it are not suggested. © 2018 The International Society of Dermatology.

The role of estrogens for male bone health.

PubMed

Ohlsson, Claes; Vandenput, Liesbeth

2009-06-01

Sex steroids are important for the growth and maintenance of both the female and the male skeleton. However, the relative contribution of androgens versus estrogens in the regulation of the male skeleton is unclear. Experiments using mice with inactivated sex steroid receptors demonstrated that both activation of the estrogen receptor (ER)alpha and activation of the androgen receptor result in a stimulatory effect on both the cortical and trabecular bone mass in males. ERbeta is of no importance for the skeleton in male mice while it modulates the ERalpha-action on bone in female mice. Previous in vitro studies suggest that the membrane G protein-coupled receptor GPR30 also might be a functional ER. Our in vivo analyses of GPR30-inactivated mice revealed no function of GPR30 for estrogen-mediated effects on bone mass but it is required for normal regulation of the growth plate and estrogen-mediated insulin-secretion. Recent clinical evidence suggests that a threshold exists for estrogen effects on bone in men: rates of bone loss and fracture risk seem to be the highest in men with estradiol levels below this threshold. Taken together, even though these findings do not exclude an important role for testosterone in male skeletal homeostasis, it is now well-established that estrogens are important regulators of bone health in men.

Oxytocin, vasopressin and estrogen receptor gene expression in relation to social recognition in female mice

PubMed Central

Clipperton-Allen, Amy E.; Lee, Anna W.; Reyes, Anny; Devidze, Nino; Phan, Anna; Pfaff, Donald W.; Choleris, Elena

2012-01-01

Inter- and intra-species differences in social behavior and recognition-related hormones and receptors suggest that different distribution and/or expression patterns may relate to social recognition. We used qRT-PCR to investigate naturally occurring differences in expression of estrogen receptor-alpha (ERα), ER-beta (ERβ), progesterone receptor (PR), oxytocin (OT) and receptor, and vasopressin (AVP) and receptors in proestrous female mice. Following four 5 min exposures to the same two conspecifics, one was replaced with a novel mouse in the final trial (T5). Gene expression was examined in mice showing high (85–100%) and low (40–60%) social recognition scores (i.e., preferential novel mouse investigation in T5) in eight socially-relevant brain regions. Results supported OT and AVP involvement in social recognition, and suggest that in the medial preoptic area, increased OT and AVP mRNA, together with ERα and ERβ gene activation, relate to improved social recognition. Initial social investigation correlated with ERs, PR and OTR in the dorsolateral septum, suggesting that these receptors may modulate social interest without affecting social recognition. Finally, increased lateral amygdala gene activation in the LR mice may be associated with general learning impairments, while decreased lateral amygdala activity may indicate more efficient cognitive mechanisms in the HR mice. PMID:22079582

Effect of glucagon-like peptide-1 analogue; Exendin-4, on cognitive functions in type 2 diabetes mellitus; possible modulation of brain derived neurotrophic factor and brain Visfatin.

PubMed

Abdelwahed, O M; Tork, O M; Gamal El Din, M M; Rashed, L; Zickri, M

2018-05-01

Brain derived neurotrophic factor (BDNF) is one of the most essential neurotrophic factors in the brain. BDNF is involved in learning, memory and locomotion suggesting it as a target in type 2 diabetes mellitus (T2DM) associated cognitive changes. Visfatin; an adipokine discovered to be expressed in the brain; was found to have multiple effects including its participation in keeping energy supply to the cell and is consequentially involved in cell survival. Its role in cognitive functions in T2DM was not studied before. Recent studies point to the possible neuro-protective mechanisms of glucagon-like peptide 1 analogue: Exendin-4 (Ex-4) in many cognitive disorders, but whether BDNF or Visfatin are involved or not in its neuro-protective mechanisms; is still unknown. to study the changes in cognitive functions in T2DM, either not treated or treated with Glucagon-like peptide 1 (GLP-1) analogue: Ex-4, and to identify the possible underlying mechanisms of these changes and whether BDNF and brain Visfatin are involved. A total of 36 adult male wistar albino rats were divided into 4 groups; Control, Exendin-4 control, Diabetic and Exendin-4 treated groups. At the end of the study, Y-maze and open field tests were done the day before scarification to assess spatial working memory and locomotion, respectively. Fasting glucose and insulin, lipid profile and tumor necrosis factor- alpha (TNF-α) were measured in the serum. Homeostasis model assessment insulin resistance was calculated. In the brain tissue, malondialdehyde (MDA) level, gene expression and protein levels of BDNF and Visfatin, area of degenerated neurons, area of glial cells and area % of synaptophysin immunoexpression were assessed. Compared with the control, the untreated diabetic rats showed insulin resistance, dyslipidemia and elevation of serum TNF-α. The brain tissue showed down-regulation of BDNF gene expression and reduction of its protein level, up-regulation of Visfatin gene expression and elevation of its protein level, increase in MDA, area of degenerated neurons and area of glial cells and reduction in area % of synaptophysin immunoexpression. These changes were paralleled with significant deterioration in spatial working memory and locomotion. Treatment of diabetic rats with Ex-4 reversed all these changes. T2DM has a negative impact on cognitive functions through different pathological and subcellular mechanisms. The current study provides evidence for involvement of BDNF and brain Visfatin in T2DM- associated cognitive dysfunction. BDNF and brain Visfatin were also found to contribute to the neuro-protective effect of Ex-4 via modulation of inflammation, oxidative stress, neuro-degeneration and synaptic function. Copyright © 2018 Elsevier Inc. All rights reserved.

Neutrophils in Oral Paracoccidioidomycosis and the Involvement of Nrf2

PubMed Central

Araújo, Vera Cavalcanti; Demasi, Ana Paula Dias; Soares, Andresa Borges; Passador-Santos, Fabrício; Napimoga, Marcelo Henrique; Martinez, Elizabeth Ferreira; Freitas, Nadir Severina; Araújo, Ney Soares

2013-01-01

Neutrophils have been implicated in granuloma formation in several infectious diseases, in addition to their main phagocytic and pathogen destruction role. It has been demonstrated that Nrf2 regulates antioxidant protection in neutrophils, attenuating inflammation without compromising the hosts bacterial defense. In this study, we analyzed the presence of neutrophils in Paracoccidioides brasiliensis mycosis (PCM), as well as the immunoexpression of Nrf2. Thirty-nine cases of oral PCM were classified according to quantity of fungi and to the presence of loose or well-organized granulomas and microabscesses. An Nrf2 antibody was used for immunohistochemical analysis. The results showed that neutrophils are present in microabscesses and loose granulomas, but were absent in structured granulomas. A greater quantity of fungi was shown in cases with only loose granulomas when compared to loose and well organized granulomas. Nrf2 was observed in the nuclei of neutrophils of loose granulomas and abscesses, with its expression in loose granulomas maintained despite the additional presence of well organized granulomas in the same specimen. This study suggests that neutrophils participate in P. brasiliensis granuloma formation and that Nrf2 has a possible role in neutrophil survival, via modulation of the inflammatory response. PMID:24204715

Oral Paracoccidioidomycosis Granulomas are Predominantly Populated by CD163+ Multinucleated Giant Cells.

PubMed

do Prado Gomes Pedreira, Renato; de Carli, Marina Lara; Beijo, Luiz Alberto; Nonogaki, Suely; Pereira, Alessandro Antônio Costa; Junior, Noé Vital Ribeiro; Sperandio, Felipe Fornias; Hanemann, João Adolfo Costa

2016-10-01

Multinucleated giant cells (MGC) are considered to be a hallmark of granulomatous inflammation; thus, they may play an essential role in the host response against pathogens, particularly Paracoccidioides brasiliensis. This study characterizes the MGC found in oral paracoccidioidomycosis and assesses the correlation of MGC with the amount of fungi within oral tissues. Twenty-six cases were included. They were classified as loose or dense granulomas, and the total MGC, including foreign-body and Langhans giant cells, besides the total and intracellular fungi, were taken into consideration. CD163 immunoexpression was performed, and CD163+ multinucleated giant cells were also quantified. Dense granulomas revealed more foreign-body type and total giant cells than loose granulomas (P < 0.05). Total giant cells showed a positive linear correlation with the CD163+ cells (P = 0.003; r = 0.56) and intracellular fungi quantification (P = 0.045; r = 0.40). Oral paracoccidioidomycosis lesions contain MGC that mainly belong to a CD163+ phenotype, also showing both Langhans and foreign-body arrangements. Additionally, the higher the presence of MGC, the higher the amount of phagocytized fungi.

Neutrophils in oral paracoccidioidomycosis and the involvement of Nrf2.

PubMed

Araújo, Vera Cavalcanti; Demasi, Ana Paula Dias; Soares, Andresa Borges; Passador-Santos, Fabrício; Napimoga, Marcelo Henrique; Martinez, Elizabeth Ferreira; Freitas, Nadir Severina; Araújo, Ney Soares

2013-01-01

Neutrophils have been implicated in granuloma formation in several infectious diseases, in addition to their main phagocytic and pathogen destruction role. It has been demonstrated that Nrf2 regulates antioxidant protection in neutrophils, attenuating inflammation without compromising the hosts bacterial defense. In this study, we analyzed the presence of neutrophils in Paracoccidioides brasiliensis mycosis (PCM), as well as the immunoexpression of Nrf2. Thirty-nine cases of oral PCM were classified according to quantity of fungi and to the presence of loose or well-organized granulomas and microabscesses. An Nrf2 antibody was used for immunohistochemical analysis. The results showed that neutrophils are present in microabscesses and loose granulomas, but were absent in structured granulomas. A greater quantity of fungi was shown in cases with only loose granulomas when compared to loose and well organized granulomas. Nrf2 was observed in the nuclei of neutrophils of loose granulomas and abscesses, with its expression in loose granulomas maintained despite the additional presence of well organized granulomas in the same specimen. This study suggests that neutrophils participate in P. brasiliensis granuloma formation and that Nrf2 has a possible role in neutrophil survival, via modulation of the inflammatory response.

Glutathione S-transferase Pi expression in invasive breast cancer and its relation with the clinical outcome.

PubMed

Franco, R L; Schenka, N G M; Schenka, A A A; Rezende, L F; Gurgel, M S C

2012-01-01

Glutathione S-transferase (GST) is a cytosolic enzymatic system involved in cellular detoxifying process. In vitro studies have shown that the presence of this enzymatic system in breast carcinoma cells can accelerate the elimination of drugs commonly used in chemotherapy, thereby decreasing its efficacy. The aim of the present study was to evaluate the association between GST Pi expression by breast carcinoma cells and disease-free and overall survival. Ninety-five female patients with invasive breast carcinoma submitted to surgical treatment and adjuvant chemotherapy from January, 1995 to June, 1997 and followed until August, 2006 were evaluated. The expression of GST Pi in breast carcinoma cells, determined by immunohistochemistry, was correlated with several clinical and pathological parameters of prognostic significance. There were 36 (37.9%) GST Pi-positive cases. GST Pi immunoexpression was not significantly correlated with patient's age, histological tumor type, clinical stage, hormone receptor status and survival. On the other hand, GST Pi positivity showed a significant correlation with a lower histological grade/C-erb-B2 negative breast carcinoma phenotype. The findings suggest that GST Pi expression does not constitute a satisfactory prognostic factor in breast cancer.

Immunohistochemical expression of myofibroblasts, TGF-β1 and IFN-γ in oral fibrous lesions.

PubMed

Santos, Pedro Paulo de Andrade; Barroso, Keila Martha Amorim; Nonaka, Cassiano Francisco Weege; Pereira Pinto, Leão; Souza, Lélia Batista de

2018-05-29

Analyze the presence of myofibroblasts (MFBs) in oral fibrous lesions and investigate TGF-β1 and IFN-γ expression by immunohistochemistry during their differentiation. Twenty giant cell fibromas (GCFs), 20 fibromas (FIBs), and 20 fibrous hyperplasias (FHs) were selected. To evaluate the presence of MFBs, anti-α-SMA-immunoreactive cells were quantified in connective tissue. TGF-β1 and IFN-γ expressions were evaluated in epithelial and connective tissue by determining the percentage of immunoreactive cells. Higher MFBs concentrations were observed in GCFs (median of 20.00), followed by FHs (15.00) and FIBs (14.00) (P = 0.072). No significant correlation between TGF-β1 or IFN-γ immunoexpression and the number of MFBs in oral fibrous lesions was observed (P > 0.05). The higher density of MFBs found in GCFs, followed by FHs and FIBs, reaffirms the fibrogenic role of these cells, while the higher concentrations detected in GCFs, including evidence of giant MFBs, also suggest a role in the neoplastic behavior of these lesions. No correlation was observed between TGF-β1 and IFN-γ in the myofibroblastic transdifferentiation process of the analyzed lesions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Miki (Mitotic Kinetics Regulator) Immunoexpression in Normal Liver, Cirrhotic Areas and Hepatocellular Carcinomas: a Preliminary Study with Clinical Relevance.

PubMed

Fernández-Vega, Iván; Santos-Juanes, Jorge; Camacho-Urkaray, Emma; Lorente-Gea, Laura; García, Beatriz; Gutiérrez-Corres, Francisco Borja; Quirós, Luis M; Guerra-Merino, Isabel; Aguirre, José Javier

2018-02-12

Hepatocellular carcinoma (HCC) is the most common type of primary malignant tumor in the liver. One of the main features of cancer survival is the generalized loss of growth control exhibited by cancer cells, and Miki is a protein related to the immunoglobulin superfamily that plays an important role in mitosis. We aim to study protein expression levels of Miki in non-tumoral liver and 20 HCCs recruited from a Pathology Department. Clinical information was also obtained. A tissue microarray was performed, and immunohistochemical techniques applied to study protein expression levels of Miki. In normal liver, Miki was weakly expressed, showing nuclear staining in the hepatocytes. Cirrhotic areas and HCCs showed a variety of staining patterns. Most HCC samples showed positive expression, with three different staining patterns being discernible: nuclear, cytoplasmic and mixed. Statistical analysis showed a significant association between grade of differentiation, Ki-67 proliferative index, survival rates and staining patterns. This study has revealed the positive expression of Miki in normal liver, cirrhotic areas and HCCs. Three different staining patterns of Miki expression with clinical relevance were noted in HCCs.

Comparative immunoexpression of ICAM-1, TGF-β1 and ki-67 in periapical and residual cysts

PubMed Central

Armada, Luciana; dos Santos, Teresa-Cristina; Pires, Fabio-Ramoa

2017-01-01

Background This study compared the immunohistochemical expression of ki-67, transforming growth factor beta 1 (TGF-β1) and intercellular adhesion molecule-1 (ICAM-1) in inflammatory periapical cysts and residual cysts. Material and Methods The study sample was composed by 25 periapical cysts and 25 residual cysts and immunohistochemical reactions were carried out using antibodies directed against ICAM-1, TGF-β1 and ki-67. Clinical, radiological, gross, histological and immunohistochemical data were tabulated for descriptive and comparative analysis using the SPSS software and differences were considered statistically significant when p<0.05%. Results There were no differences between the expression of ICAM-1 (p=0.239) and TGF-β1 (p=0.258) when comparing both groups. Ki-67 labeling index was higher in residual cysts compared to periapical cysts (p=0.017). Conclusions Results from the present study suggest that some specific inflammatory stimuli on residual cysts would modulate their mechanisms of etiopathogenesis, growing and repair. Key words:Periapical cyst, radicular cyst, residual cyst, transforming growth factor beta 1 (TGF-β1), intercellular adhesion molecule 1 (ICAM-1), ki-67. PMID:27918735

Comparative Study of the Minichromosome Maintenance Proteins Complex (MCM 4/5/6) in Ameloblastoma and Unicystic Ameloblastoma.

PubMed

Apellániz, Delmira; Pereira-Prado, Vanesa; Sicco, Estefania; Vigil-Bastitta, Gabriela; González-González, Rogelio; Mosqueda-Taylor, Adalberto; Molina-Frechero, Nelly; Hernandez, Marcela; Sánchez-Romero, Celeste; Bologna-Molina, Ronell

2018-05-01

Solid/conventional ameloblastoma (AM) and unicystic ameloblastoma (UAM) are the most frequent benign epithelial odontogenic tumors located in the maxillary region, and their treatment usually consists of extensive surgical resection. Therefore, it is relevant to study molecular markers to better understand the biological behavior of these tumors. The aim of this study was to describe and compare the expression of proteins related to cellular proliferation: Ki-67 and MCM4-6 complex. An immunohistochemistry technique was performed, with antibodies against Ki-67, MCM4, MCM5, and MCM6, in 10 AM and 10 UAM tumors. The results were quantified using label index and analyzed statistically. AM and UAM had greater expression of MCM6, followed by MCM5, MCM4, and Ki-67 ( P < .05). Immunoexpression of Ki-67 and MCM5 was exclusively nuclear, whereas the expression of MCM4 and MCM6 was nuclear and cytoplasmic. The results suggest that MCM5 is a trustable cell proliferation marker with higher sensitivity compared with Ki-67 and may be useful to predict the biological behavior of AM and UAM. Despite this, further studies are necessary, including a correlation with clinical parameters to confirm these findings.

The novel estrogen receptor G-protein-coupled receptor 30 is expressed in human bone.

PubMed

Heino, Terhi J; Chagin, Andrei S; Sävendahl, Lars

2008-05-01

Estrogens have significant impact on bone mineral metabolism. Besides the classical estrogen receptors (ERalpha and ERbeta), a trans-membrane G-protein-coupled receptor (GPR30) has been demonstrated to mediate estrogenic effects. We aimed to study whether GPR30 is expressed in bone cells and if so, whether the level of expression is developmentally regulated. Metaphyseal bone biopsies were collected from the tibia in 14 boys and 6 girls, all at different stages of puberty. GPR30 protein expression was studied by immunohistochemistry in paraffin-embedded sections. GPR30-positive osteocytes and osteoblasts were quantified and linear regression analysis was applied. Cytoplasmic GPR30 expression was detected in osteoblasts, osteocytes, and osteoclasts. Osteocytes were more frequently positive for GPR30 than osteoblasts (58+/-4% vs 46+/-3% positive cells respectively, P<0.05). Detailed analysis demonstrated that GPR30 positivity declined during pubertal development in osteocytes (R=-0.56, P<0.01) but not in osteoblasts (R=-0.31, P>0.05). No sex difference was observed in the numbers of GPR30-positive osteoblasts or osteocytes. Furthermore, GPR30 expression did not correlate with chronological or bone age. In conclusion, the novel ER GPR30 is expressed in osteoblasts, osteocytes, and osteoclasts suggesting that non-genomic estrogen signaling via GPR30 may exist in bone. However, the functional role of GPR30 in bone tissue remains to be elucidated.

Estrogen induces rapid decrease in dendritic thorns of CA3 pyramidal neurons in adult male rat hippocampus

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

Tsurugizawa, Tomokazu; Core Research for Evolutional Science and Technology Project of Japan Science and Technology Agency, Graduate School of Arts and Sciences, University of Tokyo at Komaba, 3-8-1 Meguro, Tokyo 153; Mukai, Hideo

2005-12-02

Modulation of hippocampal synaptic plasticity by estrogen has been attracting much attention. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. Here we demonstrated the rapid effect of estradiol on the density of thorns of thorny excrescences, by imaging Lucifer Yellow-injected CA3 neurons in adult male rat hippocampal slices. The application of 1 nM estradiol induced rapid decrease in the density of thorns on pyramidal neurons within 2 h. The estradiol-mediated decrease in the density of thorns was blocked by CNQX (AMPA receptor antagonist) and PD98059 (MAP kinase inhibitor), but notmore » by MK-801 (NMDA receptor antagonist). ER{alpha} agonist PPT induced the same suppressive effect as that induced by estradiol on the density of thorns, but ER{beta} agonist DPN did not affect the density of thorns. Note that a 1 nM estradiol treatment did not affect the density of spines in the stratum radiatum and stratum oriens. A search for synaptic ER{alpha} was performed using purified RC-19 antibody. The localization of ER{alpha} (67 kDa) in the CA3 mossy fiber terminals and thorns was demonstrated using immunogold electron microscopy. These results imply that estradiol drives the signaling pathway including ER{alpha} and MAP kinase.« less

Oxytocin, vasopressin and estrogen receptor gene expression in relation to social recognition in female mice.

PubMed

Clipperton-Allen, Amy E; Lee, Anna W; Reyes, Anny; Devidze, Nino; Phan, Anna; Pfaff, Donald W; Choleris, Elena

2012-02-28

Inter- and intra-species differences in social behavior and recognition-related hormones and receptors suggest that different distribution and/or expression patterns may relate to social recognition. We used qRT-PCR to investigate naturally occurring differences in expression of estrogen receptor-alpha (ERα), ER-beta (ERβ), progesterone receptor (PR), oxytocin (OT) and receptor, and vasopressin (AVP) and receptors in proestrous female mice. Following four 5 min exposures to the same two conspecifics, one was replaced with a novel mouse in the final trial (T5). Gene expression was examined in mice showing high (85-100%) and low (40-60%) social recognition scores (i.e., preferential novel mouse investigation in T5) in eight socially-relevant brain regions. Results supported OT and AVP involvement in social recognition, and suggest that in the medial preoptic area, increased OT and AVP mRNA, together with ERα and ERβ gene activation, relate to improved social recognition. Initial social investigation correlated with ERs, PR and OTR in the dorsolateral septum, suggesting that these receptors may modulate social interest without affecting social recognition. Finally, increased lateral amygdala gene activation in the LR mice may be associated with general learning impairments, while decreased lateral amygdala activity may indicate more efficient cognitive mechanisms in the HR mice. Copyright © 2011 Elsevier Inc. All rights reserved.

Advanced glycation products' levels and mechanical properties of vaginal tissue in pregnancy.

PubMed

Weli, Homayemem K; Akhtar, Riaz; Chang, Zhuo; Li, Wen-Wu; Cooper, Jason; Yang, Ying

2017-07-01

Non-enzymatic glycation is closely associated with altered mechanical properties of connective tissue. Pregnancy, marked with high levels of female hormones, confers unique alteration to the mechanical properties of pelvic connective tissues in order to meet their physiological demands. However, there are few studies on glycation content and its influence on the mechanical properties of pelvic connective tissues during pregnancy. We hypothesise that the glycation content in pelvic tissues will change with a corresponding alteration in their mechanical properties, and that these changes are influenced by hormone levels. This study aims to investigate the correlation of vaginal tissue glycation content and mechanical property changes during pregnancy in association with the expression of a key pregnancy hormone (oestrogen) receptor, and an antioxidant enzyme, glyoxalase I. A rat vaginal tissue model (tissues from non-pregnant and E15-E18 (last trimester) pregnant rats) was used in this study. Mechanical characteristics of vaginal tissues were analysed by a ball-indentation technique while modulus and morphology of the collagen fibrils within the tissues were measured with atomic force microscopy. A glycation marker, pentosidine, was quantified by a high performance liquid chromatography. The expression of oestrogen receptor and glyoxalase I in the tissue was qualified by immunochemical staining. The glycosaminoglycan (GAG) concentration difference in the tissues were quantified by a biochemical assay. Pregnant rat vaginal tissue was characterised by significantly lower amounts of pentosidine, higher oestrogen receptor and glyoxalase I expression with larger creep, lower elastic modulus, larger fibril diameter and higher GAG content than their non-pregnant counterpart. There was a negative correlation between pentosidine and vaginal tissue creep. There was a reduction in vaginal tissue pentosidine in pregnancy with an associated increase in oestrogen receptor and glyoxalase I immunoexpression. Reduced glycation was associated with increased creeping of vaginal tissue. Oestrogen may therefore play a role in the increase of the vaginal wall's capacity to stretch through glyoxalase I up-regulation and subsequent glycation reduction. The new insight of the correlation of women's oestrogen level, glycation reaction and pelvic tissue mechanical property from this study may enhance our understanding of some pelvic organ diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Slug, Twist, and E-Cadherin as Immunohistochemical Biomarkers in Meningeal Tumors

PubMed Central

Nagaishi, Masaya; Nobusawa, Sumihito; Tanaka, Yuko; Ikota, Hayato; Yokoo, Hideaki; Nakazato, Yoichi

2012-01-01

The overexpression of Twist and Slug and subsequent down-regulation of E-cadherin facilitate the acquirement of invasive growth properties in cancer cells. It is unclear which of these molecules are expressed in mesenchymal tumors in the central nervous system. Here, we investigated 10 cases each of hemangiopericytoma, solitary fibrous tumor, meningothelial, fibrous, angiomatous, and atypical meningiomas, and 5 cases of anaplastic meningioma for Slug, Twist, E-cadherin, and N-cadherin immunoexpression. Nuclear Slug expression was observed in 9/10 (90%) hemangiopericytomas and 5/10 (50%) solitary fibrous tumors, but not in any meningiomas, except for 1 case. Similarly, nuclear Twist expression was more extensive in hemangiopericytomas and solitary fibrous tumors than meningiomas. In contrast to Slug and Twist, the positive expression of E-cadherin was observed in 39/45 (87%) meningiomas, but not in any hemangiopericytomas or solitary fibrous tumors (P<0.0001). The fraction of tumor cells expressing E-cadherin in meningeal tumors was negatively correlated to those of Twist (P = 0.004) and Slug (P<0.0001). The overexpression of Slug and Twist with down-regulation of E-cadherin was characteristic findings in hemangiopericytomas and solitary fibrous tumors, but not in meningiomas. The immunohistochemical profiles of the two tumor groups may be useful as diagnostic markers in cases that present a differential diagnosis challenge. PMID:23029385

MMP-1 and MMP-8 expression in giant-cell fibroma and inflammatory fibrous hyperplasia.

PubMed

de Oliveira, Henrique Climeck; Tschoeke, André; da Cruz, Gabriele Claudino; Noronha, Lúcia; de Moraes, Rafaela Scariot; Mesquita, Ricardo Alves; de Aguiar, Maria Cássia Ferreira; Caldeira, Patrícia Carlos; de Oliveira Ribas, Marina; Grégio, Ana Maria Trindade; Alanis, Luciana Reis Azevedo; Ignácio, Sérgio Aparecido; Dos Santos, Jean Nunes; de Lima, Antonio Adilson Soares; Johann, Aline Cristina Batista Rodrigues

2016-12-01

The aim of this study is to compare the immunoexpression of metalloproteinases 1 and 8 in giant-cell fibroma, inflammatory fibrous hyperplasia and normal mucosa. Twenty-two cases of giant-cell fibroma, inflammatory fibrous hyperplasia and oral mucosa (control) each were subjected to immunohistochemistry using anti-metalloproteinase-1 and anti-metalloproteinase-8 antibodies. Eight images of each case were captured and analysed through the a) application of a count grid to count the number of positive neutrophils, macrophages, lymphocytes, plasma cells, fibroblasts and blood vessels to obtain the percentage of staining and b) semi-automated segmentation quantifying the stained area in square micrometres. Statistical tests included ANOVA Two-way, Kruskal Wallis and Games-Howell, with a significance level of 5%. An increased percentage of metalloproteinase-1-immunopositive blood vessels were observed in giant-cell fibroma (26.6±22.4; p=0.02) and inflammatory fibrous hyperplasia (34.3±31.5; p=0.01) compared with the control group (19.6±9.2). No significant differences in inflammatory cells, fibroblasts and total area of metalloproteinase-1 and -8 were noted among the three groups. Metalloproteinase-1 apparently acts within the pathogenesis of giant-cell fibroma and inflammatory fibrous hyperplasia. Copyright © 2016 Elsevier GmbH. All rights reserved.

An Immunohistochemical Study on the Expression of Sex Steroid Receptors in Canine Mammary Tumors

PubMed Central

Port Louis, Leena Rajathy; Varshney, Khub Chandra; Nair, Madhavan Gopalakrishnan

2012-01-01

Steroid hormones are found to play a major role in the genesis and progression of mammary tumors. The aim of this study was to immunohistochemically detect the presence of estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and progesterone receptor (PR) and also to study the association between these markers in 29 cases of benign (11) and malignant (18) canine mammary tumors. ERα immunostaining was noticed in only one case of carcinosarcoma specifically in the nuclei of epithelial and a few myoepithelial cells. ERβ immunostaining was noticed in the nuclei and cytoplasm of epithelial cells and smooth muscles lining the blood vessels. Immunoexpression of ERβ was 82% in benign tumors and 78% in malignant tumors. PR immunostaining was expressed in the nuclei of epithelial cells in both benign and malignant tumors. Among the 15 PR+ cases, 6 (55%) were of benign type, and 9 (50%) were of malignant type. The most common group of hormone receptor was the ERα−/PR+/ERβ+ (46%) in benign tumors and ERα−/PR−/ERβ+ (38%) in malignant tumors. Although there was no significant association between ERα and PR with ERβ, the findings indicated that ERβ was consistently expressed in both benign and malignant tumors, irrespective of ERα and PR status. PMID:23738123

Immunoexpression of vascular endothelial growth factor in gingival mucosa with papilloma and condyloma acuminata.

PubMed

Scrieciu, Monica; MercuŢ, Veronica; Andrei, Oana Cella; Predescu, Anca Mihaela; Niculescu, Mihaela; Pisoschi, Cătălina Gabriela; BaniŢă, Ileana Monica

2015-01-01

The histological changes of the oral mucosa in contact with a metal alloy dentures is one of the current issues widely debated in the literature. To highlight the expression of vascular endothelial growth factor (VEGF) in human paraprosthetic gingival mucosa exposed to nickel and copper compounds using the immunohistochemical technique. The selected participants were wearers of fixed dentures made of nickel-based alloys and copper-based alloys. The gingival mucosa fragments were prelevated through excision after removing fixed denture and extraction one of its affected teeth. The gingival mucosa fragments were processed through the histological technique of paraffin inclusion. The paraffin-embedded tissue sections were usually stained with Hematoxylin-Eosin and processed by immunohistochemical technique with VEGF antibody. The gingival mucosa fragments from nickel-based alloys dentures wearers were diagnosed with papilloma and, also, gingival mucosa samples prelevated from copper-based alloys dentures wearers were diagnosed with condyloma acuminata. Immunohistochemical reaction for VEGF was different in the gingival mucosa fragments with papilloma compared with condyloma acuminata samples. In papillomatosis gingival mucosa fragments, VEGF was implicated in principal in vasodilatation and inflammation process, and secondary in angiogenesis. In gingival mucosa fragments with condyloma acuminata, the principal role of VEGF was in angiogenesis and secondary in inflammation.

Pleomorphic dermal sarcoma: a more aggressive neoplasm than previously estimated.

PubMed

Tardío, Juan C; Pinedo, Fernando; Aramburu, José A; Suárez-Massa, Dolores; Pampín, Ana; Requena, Luis; Santonja, Carlos

2016-02-01

Pleomorphic dermal sarcoma (PDS) is a rare neoplasm sharing pathological features with atypical fibroxanthoma, but adding tumor necrosis, invasion beyond superficial subcutis or vascular or perineural infiltration. Although its metastatic risk has been estimated to be less than 5%, its real outcome is presently uncertain because of its rarity and to the lack of homogeneous criteria used in reported cases. Retrospective clinicopathological study of 18 cases of PDS. The lesions presented as tumors or plaques (size: 7-70 mm) on the head of elderly patients (median: 81 years), without a gender predominance. Histopathologically, they consisted of spindle cells arranged in a fascicular pattern, containing pleomorphic epithelioid and giant multinucleated cells in varying proportions, and usually exhibiting numerous mitotic figures and infiltrative tumor margins. No immunoexpression for cytokeratins, S100 protein, desmin or CD34 was observed. Necrosis and venous invasion were found in three tumors each (17%). Follow-up was available in 15 cases (median: 33 months). Three patients (20%) had local recurrences, all with incomplete primary surgical resections. Three patients (20%) developed distant metastases in the skin, regional lymph nodes and/or lungs and died from the disease. Our data suggest that PDS may be a more aggressive neoplasm than previously estimated. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Stress associated proteins metallothionein, HO-1 and HSP 70 in human zero-hour biopsies of transplanted kidneys.

PubMed

August, Christian; Brockmann, Jens; Vowinkel, Thorsten; Wolters, Heiner; Dietl, Karl-Heinz; Levkau, Bodo; Heidenreich, Stefan; Lang, Detlef; Baba, Hideo A

2006-08-01

Light microscopic alterations reflecting both previous and preservation-induced changes in the donor organ are usually not very distinctive. The ischemia/reperfusion-associated injury depends primarily on the conditions of donor organ preservation. The present study examined human kidney biopsies with special attention paid to the molecular mechanisms of preservation-induced injury preceding reperfusion. Stress-associated proteins hemeoxygenase-1 (HO-1), heat shock protein 70 (HSP 70), and metallothionein (MT) were studied in human zero-hour biopsies of transplanted kidneys prior to reperfusion in 29 patients. Protein expression was evaluated by semiquantitative immunohistochemistry and Western blotting for HO-1 and HSP 70. These findings were correlated with terminal deoxynucleotidyltransferase-mediated 2'-deoxyuridine 5'-triphosphate-digoxigenin nick end labeling (TUNEL) staining and follow up. Compared to controls, MT and HSP 70 expression was significantly higher at zero hour. In contrast, HO-1 and the number of TUNEL-positive cells were not elevated. MT and HO-1 immunoexpression were inversely associated with graft function, and hence, were of prognostic relevance. MT and HSP 70 were sensitive to the duration of cold ischemia. MT and HO-1 are suitable indicators for tissue injury during ischemia and may serve as new predictive markers that need to be validated in further independent studies.

Clinical value of protein expression of kallikrein-related peptidase 7 (KLK7) in ovarian cancer.

PubMed

Dorn, Julia; Gkazepis, Apostolos; Kotzsch, Matthias; Kremer, Marcus; Propping, Corinna; Mayer, Katharina; Mengele, Karin; Diamandis, Eleftherios P; Kiechle, Marion; Magdolen, Viktor; Schmitt, Manfred

2014-01-01

Expression of the kallikrein-related peptidase 7 (KLK7) is dysregulated in ovarian cancer. We assessed KLK7 expression by ELISA and quantitative immunohistochemistry and analyzed its association with clinicopathological parameters and patients' outcome. KLK7 antigen concentrations were determined in tumor tissue extracts of 98 ovarian cancer patients by ELISA. For analysis of KLK7 immunoexpression in ovarian cancer tissue microarrays, a manual quantitative scoring system as well as a software tool for quantitative high-throughput automated image analysis was used. In immunohistochemical analyses, expression levels of KLK7 were not associated with patients' outcome. However, in multivariate analyses, KLK7 antigen levels in tumor tissue extracts were significantly associated with both overall and progression-free survival: ovarian cancer patients with high KLK7 levels had a significantly, 2-fold lower risk of death [hazard ratio (HR)=0.51, 95% confidence interval (CI)=0.29-0.90, p=0.019] or relapse [HR=0.47, 95% CI=0.25-0.91, p=0.024), as compared with patients who displayed low KLK7 levels. Our results indicate that - in contrast to earlier findings - high KLK7 antigen levels in tumor tissue extracts may be associated with a better prognosis of ovarian cancer patients.

Adrenal-kidney-gonad complex measurements may not predict gonad-specific changes in gene expression patterns during temperature-dependent sex determination in the red-eared slider turtle (Trachemys scripta elegans).

PubMed

Ramsey, Mary; Crews, David

2007-08-01

Many turtles, including the red-eared slider turtle (Trachemys scripta elegans) have temperature-dependent sex determination in which gonadal sex is determined by temperature during the middle third of incubation. The gonad develops as part of a heterogenous tissue complex that comprises the developing adrenal, kidney, and gonad (AKG complex). Owing to the difficulty in excising the gonad from the adjacent tissues, the AKG complex is often used as tissue source in assays examining gene expression in the developing gonad. However, the gonad is a relatively small component of the AKG, and gene expression in the adrenal-kidney (AK) compartment may interfere with the detection of gonad-specific changes in gene expression, particularly during early key phases of gonadal development and sex determination. In this study, we examine transcript levels as measured by quantitative real-time polymerase chain reaction for five genes important in slider turtle sex determination and differentiation (AR, ERalpha, ERbeta, aromatase, and Sf1) in AKG, AK, and isolated gonad tissues. In all cases, gonad-specific gene expression patterns were attenuated in AKG versus gonad tissue. All five genes were expressed in the AK in addition to the gonad at all stages/temperatures. Inclusion of the AK compartment masked important changes in gonadal gene expression. In addition, AK and gonad expression patterns are not additive, and gonadal gene expression cannot be predicted from intact AKG measurements. (c) 2007 Wiley-Liss, Inc.

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

Oh, Yohan; Chung, Kwang Chul, E-mail: kchung@yonsei.ac.kr

Highlights: Black-Right-Pointing-Pointer ZNF131 directly interacts with ER{alpha}. Black-Right-Pointing-Pointer The binding affinity of ZNF131 to ER{alpha} increases upon E2 stimulation. Black-Right-Pointing-Pointer ZNF131 inhibits ER{alpha}-mediated trans-activation by suppressing its homo-dimerization. Black-Right-Pointing-Pointer ZNF131 inhibits ER{alpha}-dimerization and E2-induced breast cancer cell proliferation. Black-Right-Pointing-Pointer ZNF131 inhibits estrogen signaling by acting as an ER{alpha}-co-repressor. -- Abstract: Steroid hormone estrogen elicits various physiological functions, many of which are mediated through two structurally and functionally distinct estrogen receptors, ER{alpha} and ER{beta}. The functional role of zinc finger protein 131 (ZNF131) is poorly understood, but it is assumed to possess transcriptional regulation activity due to the presence of amore » DNA binding motif. A few recent reports, including ours, revealed that ZNF131 acts as a negative regulator of ER{alpha} and that SUMO modification potentiates the negative effect of ZNF131 on estrogen signaling. However, its molecular mechanism for ER{alpha} inhibition has not been elucidated in detail. Here, we demonstrate that ZNF131 directly interacts with ER{alpha}, which consequently inhibits ER{alpha}-mediated trans-activation by suppressing its homo-dimerization. Moreover, we show that the C-terminal region of ZNF131 containing the SUMOylation site is necessary for its inhibition of estrogen signaling. Taken together, these data suggest that ZNF131 inhibits estrogen signaling by acting as an ER{alpha}-co-repressor.« less

Estrogenic activity of lambda-cyhalothrin in the MCF-7 human breast carcinoma cell line.

PubMed

Zhao, Meirong; Zhang, Ying; Liu, Weiping; Xu, Chao; Wang, Lumei; Gan, Jianying

2008-05-01

Synthetic pyrethroids are widely used in both agricultural and urban environments for insect control. Lambda-cyhalothrin (LCT) is one of the most common pyrethroids and is used mainly for controlling mosquitoes, fleas, cockroaches, flies, and ants around households. Previous studies have addressed the environmental behaviors and acute toxicities of LCT, but little is known about its chronic toxicity, such as estrogen-like activity. In the present study, the estrogenic potential of LCT was evaluated using the MCF-7 human breast carcinoma cell line. The in vitro E-screen assay showed that 10(-7) M LCT could significantly promote MCF-7 cell proliferation, with a relative proliferative effect ratio of 45%. The cell proliferation induced by LCT could be blocked completely, however, by the addition of 10(-9) M of the estrogen receptor (ER)-antagonist ICI 182,780. The semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) results showed that the Trefoil factor 1 (pS2) and progesterone receptor gene expression were up-regulated by 10(-7) M LCT for 2- and 1.5-fold, respectively. On the other hand, RT-PCR, Western blot analysis, and immunofluorescent assay demonstrated that LCT significantly repressed the mRNA and protein expression levels of ERalpha and ERbeta. These observations indicate that LCT possesses estrogenic properties and may function as a xenoestrogen, likely via a mechanism similar to that of 17beta-estradiol. The endocrine-disruption potential of LCT should be considered when assessing the safety of this compound in sensitive environmental compartments.

Synthetic estrogen derivatives demonstrate the functionality of intracellular GPR30.

PubMed

Revankar, Chetana M; Mitchell, Hugh D; Field, Angela S; Burai, Ritwik; Corona, Cesear; Ramesh, Chinnasamy; Sklar, Larry A; Arterburn, Jeffrey B; Prossnitz, Eric R

2007-08-17

Estrogen mediates its effects through multiple cellular receptors. In addition to the classical nuclear estrogen receptors (ERalpha and ERbeta), estrogen also signals through the seven-transmembrane G-protein-coupled receptor (GPCR) GPR30. Although estrogen is a cell-permeable ligand, it is often assumed that all GPCRs function solely as cell surface receptors. Our previous results showed that GPR30 appeared to be expressed predominantly in the endoplasmic reticulum. A critical question that arises is whether this localization represents the site of functional receptor. To address this question, we synthesized a collection of cell-permeable and cell-impermeable estrogen derivatives. We hypothesized that if functional GPR30 were expressed at the cell surface, both permeable and impermeable derivatives would show activity. However, if functional GPR30 were predominantly intracellular, like ERalpha, only the permeable ligands should show activity. Cell permeability was assessed using cells expressing ERalpha as a model intracellular estrogen-binding receptor. Our results reveal that despite exhibiting similar binding affinities for GPR30, only the cell-permeable ligands are capable of stimulating rapid calcium mobilization and phosphoinositide 3-kinase (PI3K) activation. We conclude that GPR30 expressed intracellularly is capable of initiating cellular signaling and that there is insufficient GPR30 expressed on the cell surface to initiate signaling in response to impermeable ligands in the cell lines examined. To our knowledge, this is the first definitive demonstration of a functional intracellular transmembrane estrogen receptor.

Synthesis of a beta-estradiol-biotin chimera that potently heterodimerizes estrogen receptor and streptavidin proteins in a yeast three-hybrid system.

PubMed

Hussey, Stephen L; Muddana, Smita S; Peterson, Blake R

2003-04-02

Small molecules that dimerize proteins in living cells provide powerful probes of biological processes and have potential as tools for the identification of protein targets of natural products. We synthesized 7-alpha-substituted derivatives of beta-estradiol tethered to the natural product biotin to regulate heterodimerization of estrogen receptor (ER) and streptavidin (SA) proteins expressed as components of a yeast three-hybrid system. Addition of an estradiol-biotin chimera bearing a 19-atom linker to yeast expressing DNA-bound ER-alpha or ER-beta LexA fusion proteins and wild-type SA protein fused to the B42 activation domain activated reporter gene expression by as much as 450-fold in vivo (10 muM ligand). Comparative analysis of lower affinity Y43A (biotin Kd approximately 100 pM) and W120A (biotin Kd approximately 100 nM) mutants of SA indicated that moderate affinity interactions can be readily detected with this system. Comparison of a 7-alpha-substituted estradiol-biotin chimera with a structurally similar dexamethasone-biotin chimera revealed that yeast expressing ER proteins can detect cognate ligands with up to 5-fold greater potency and 70-fold higher activity than yeast expressing analogous glucocorticoid receptor (GR) proteins. This approach may facilitate the identification of protein targets of biologically active small molecules screened against genetically encoded libraries of proteins expressed in yeast three-hybrid systems.

Partial and weak oestrogenicity of the red wine constituent resveratrol: consideration of its superagonist activity in MCF-7 cells and its suggested cardiovascular protective effects.

PubMed

Ashby, J; Tinwell, H; Pennie, W; Brooks, A N; Lefevre, P A; Beresford, N; Sumpter, J P

1999-01-01

It was recently reported that the red wine phytoestrogen resveratrol (RES) acts as a superagonist to oestrogen-responsive MCF-7 cells. This activity of RES was speculated to be relevant to the 'French paradox' in which moderate red wine consumption is reported to yield cardiovascular health benefits to humans. We report here that RES binds to oestrogen receptors (ER) isolated from rat uterus with an affinity approximately 5 orders of magnitude lower than does either the reference synthetic oestrogen diethylstilboestrol (DES) or oestradiol (E2). In comparison with E2 or DES, RES is only a weak and partial agonist in a yeast hER-alpha transcription assay and in cos-1 cell assays employing transient transfections of ER-alpha or ER-beta associated with two different ER-response elements. Resveratrol was also concluded to be inactive in immature rat uterotrophic assays conducted using three daily administrations of 0.03-120 mgkg(-1)/day(-1) RES (administered by either oral gavage or subcutaneous injection). These data weaken the suggestion that the oestrogenicity of RES may account for the reported cardiovascular protective effects of red wine consumption, and they raise questions regarding the extent to which oestrogenicity data derived for a chemical using MCF-7 cells (or any other single in vitro assay) can be used to predict the hormonal effects likely to occur in animals or humans.

Involvement of estrogen receptor alpha, beta and oxytocin in social discrimination: A detailed behavioral analysis with knockout female mice.

PubMed

Choleris, E; Ogawa, S; Kavaliers, M; Gustafsson, J-A; Korach, K S; Muglia, L J; Pfaff, D W

2006-10-01

Social recognition, processing, and retaining information about conspecific individuals is crucial for the development of normal social relationships. The neuropeptide oxytocin (OT) is necessary for social recognition in male and female mice, with its effects being modulated by estrogens in females. In previous studies, mice whose genes for the estrogen receptor-alpha (alpha-ERKO) and estrogen receptor-beta (beta-ERKO) as well as OTKO were knocked out failed to habituate to a repeatedly presented conspecific and to dishabituate when the familiar mouse is replaced by a novel animal (Choleris et al. 2003, Proc Natl Acad Sci USA 100, 6192-6197). However, a binary social discrimination assay, where animals are given a simultaneous choice between a familiar and a previously unknown individual, offers a more direct test of social recognition. Here, we used alpha-ERKO, beta-ERKO, and OTKO female mice in the binary social discrimination paradigm. Differently from their wild-type controls, when given a choice, the KO mice showed either reduced (beta-ERKO) or completely impaired (OTKO and alpha-ERKO) social discrimination. Detailed behavioral analyses indicate that all of the KO mice have reduced anxiety-related stretched approaches to the social stimulus with no overall impairment in horizontal and vertical activity, non-social investigation, and various other behaviors such as, self-grooming, digging, and inactivity. Therefore, the OT, ER-alpha, and ER-beta genes are necessary, to different degrees, for social discrimination and, thus, for the modulation of social behavior (e.g. aggression, affiliation).

Inhibition of in vitro growth and arrest in the G0/G1 phase of HCT8 line human colon cancer cells by kaempferide triglycoside from Dianthus caryophyllus.

PubMed

Martineti, Valentina; Tognarini, Isabella; Azzari, Chiara; Carbonell Sala, Silvia; Clematis, Francesca; Dolci, Marcello; Lanzotti, Virginia; Tonelli, Francesco; Brandi, Maria Luisa; Curir, Paolo

2010-09-01

The effects of phytoestrogens have been studied in the hypothalamic-pituitary-gonadal axis and in various non-gonadal targets. Epidemiologic and experimental evidence indicates a protective effect of phytoestrogens also in colorectal cancer. The mechanism through which estrogenic molecules control colorectal cancer tumorigenesis could possibly involve estrogen receptor beta, the predominantly expressed estrogen receptor subtype in colon mucosa.To validate this hypothesis, we therefore used an engineered human colon cancer cell line induced to overexpress estrogen receptor beta, beside its native cell line, expressing very low levels of ERbeta and not expressing ERalpha; as a phytoestrogenic molecule, we used kaempferide triglycoside, a glycosylated flavonol from a Dianthus caryophyllus cultivar. The inhibitory properties of this molecule toward vegetal cell growth have been previously demonstrated: however, no data on its activity on animal cell or information about the mechanism of this activity are available. Kaempferide triglycoside proved to inhibit the proliferation of native and estrogen receptor beta overexpressing colon cancer cells through a mechanism not mediated by ligand binding dependent estrogen receptor activation. It affected HCT8 cell cycle progression by increasing the G(0)/G(1) cell fraction and in estrogen receptor beta overexpressing cells increased two antioxidant enzymes. Interestingly, the biological effects of this kaempferide triglycoside were strengthened by the presence of high levels of estrogen receptor beta.Pleiotropic molecular effects of phytoestrogens may explain their protective activity against colorectal cancer and may represent an interesting area for future investigation with potential clinical applications. Copyright 2010 John Wiley & Sons, Ltd.

Effects of the antiestrogen fulvestrant (ICI 182,780) on gene expression of the rat efferent ductules.

PubMed

Yasuhara, Fabiana; Gomes, Gisele Renata Oliveira; Siu, Erica Rosanna; Suenaga, Cláudia Igushi; Maróstica, Elisabeth; Porto, Catarina Segreti; Lazari, Maria Fatima Magalhaes

2008-09-01

The efferent ductules express the highest amount of estrogen receptors ESR1 (ERalpha) and ESR2 (ERbeta) within the male reproductive tract. Treatment of rats with the antiestrogen fulvestrant (ICI 182,780) causes inhibition of fluid reabsorption in the efferent ductules, leading to seminiferous tubule atrophy and infertility. To provide a more comprehensive knowledge about the molecular targets for estrogen in the rat efferent ductules, we investigated the effects of ICI 182,780 treatment on gene expression using a microarray approach. Treatment with ICI 182,780 increased or reduced at least 2-fold the expression of 263 and 98 genes, respectively. Not surprisingly, several genes that encode ion channels and macromolecule transporters were affected. Interestingly, treatment with ICI 182,780 markedly altered the expression of genes related to extracellular matrix organization. Matrix metalloproteinase 7 (Mmp7), osteopontin (Spp1), and neuronal pentraxin 1 (Nptx1) were among the most altered genes in this category. Upregulation of Mmp7 and Spp1 and downregulation of Nptx1 were validated by Northern blot. Increase in Mmp7 expression was further confirmed by immunohistochemistry and probably accounted for the decrease in collagen content observed in the efferent ductules of ICI 182,780-treated animals. Downregulation of Nptx1 probably contributed to the extracellular matrix changes and decreased amyloid deposition in the efferent ductules of ICI 182,780-treated animals. Identification of new molecular targets for estrogen action may help elucidate the regulatory role of this hormone in the male reproductive tract.

Telocytes play a key role in prostate tissue organisation during the gland morphogenesis.

PubMed

Sanches, Bruno D A; Maldarine, Juliana S; Zani, Bruno C; Tamarindo, Guilherme H; Biancardi, Manoel F; Santos, Fernanda C A; Rahal, Paula; Góes, Rejane M; Felisbino, Sérgio L; Vilamaior, Patricia S L; Taboga, Sebastião R

2017-12-01

Telocytes are CD34-positive interstitial cells, known to exert several functions, one of which is a role in tissue organisation, previously demonstrated by telocytes in the myocardium. The existence of telocytes in the prostate has recently been reported, however, there is a lack of information regarding the function of these cells in prostate tissue, and information regarding the possible role of these cells in prostatic development. This study used immunofluorescence techniques in prostate tissue and prostatic telocytes in culture to determine the relationship between telocytes and prostate morphogenesis. Furthermore, immunofluorescent labelling of telocytes was performed on prostate tissue at different stages of early postnatal development. Initially, CD34-positive cells are found at the periphery of the developing alveoli, later in the same region, c-kit-positive cells and cells positive for both factors are verified and CD34-positive cells were predominantly observed in the interalveolar stroma and the region surrounding the periductal smooth muscle. Fluorescence assays also demonstrated that telocytes secrete TGF-β1 and are ER-Beta (ERβ) positive. The results suggest that telocytes play a changing role during development, initially supporting the differentiation of periductal and perialveolar smooth muscle, and later, producing dense networks that separate alveoli groups and form a barrier between the interalveolar region and periurethral smooth muscle. We conclude that telocytes play a relevant role in prostate tissue organisation during postnatal development. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Quantification of C4d deposition and hepatitis C virus RNA in tissue in cases of graft rejection and hepatitis C recurrence after liver transplantation

PubMed Central

Song, Alice Tung Wan; de Mello, Evandro Sobroza; Alves, Venâncio Avancini Ferreira; Cavalheiro, Norma de Paula; Melo, Carlos Eduardo; Bonazzi, Patricia Rodrigues; Tengan, Fatima Mitiko; Freire, Maristela Pinheiro; Barone, Antonio Alci; D'Albuquerque, Luiz Augusto Carneiro; Abdala, Edson

2015-01-01

Histology is the gold standard for diagnosing acute rejection and hepatitis C recurrence after liver transplantation. However, differential diagnosis between the two can be difficult. We evaluated the role of C4d staining and quantification of hepatitis C virus (HCV) RNA levels in liver tissue. This was a retrospective study of 98 liver biopsy samples divided into four groups by histological diagnosis: acute rejection in patients undergoing liver transplant for hepatitis C (RejHCV+), HCV recurrence in patients undergoing liver transplant for hepatitis C (HCVTx+), acute rejection in patients undergoing liver transplant for reasons other than hepatitis C and chronic hepatitis C not transplanted (HCVTx-). All samples were submitted for immunohistochemical staining for C4d and HCV RNA quantification. Immunoexpression of C4d was observed in the portal vessels and was highest in the HCVTx- group. There was no difference in C4d expression between the RejHCV+ and HCVTx+ groups. However, tissue HCV RNA levels were higher in the HCVTx+ group samples than in the RejHCV+ group samples. Additionally, there was a significant correlation between tissue and serum levels of HCV RNA. The quantification of HCV RNA in liver tissue might prove to be an efficient diagnostic test for the recurrence of HCV infection. PMID:25742264

Cimetidine-induced Leydig cell apoptosis and reduced EG-VEGF (PK-1) immunoexpression in rats: Evidence for the testicular vasculature atrophy.

PubMed

Beltrame, Flávia L; Cerri, Paulo S; Sasso-Cerri, Estela

2015-11-01

The antiulcer drug cimetidine has shown to cause changes in the testicular microvasculature of adult rats. Since Leydig cells (LCs) produce the pro-angiogenic factor, EG-VEGF (endocrine gland-derived vascular endothelial growth factor), also known as prokineticin 1 (PK-1), this study examined the effect that cimetidine might have on LCs in testes with damaged vasculature. Rats received intraperitoneal injections of 100mg/kg of cimetidine (cimetidine group) or saline vehicle (control group) for 50 days. Serum testosterone levels were measured by chemiluminescence immunoassay and testicular sections were subjected to TUNEL and immunohistochemical reactions for caspase-3, 17β-HSD6, CD163 (ED2 macrophage), PK-1 and androgen receptor (AR). LCs in the cimetidine group showed TUNEL and caspase-3 positive labeling and apoptotic ultrastructural features. Moreover, the presence of 17β-HSD6-positive inclusions inside macrophages and the reduced number of LCs, AR immunoreactivity and serum testosterone levels correlated with a decrease in either the number of PK-1-immunostained LCs or PK-1 immunoreactivity. Although it is not clear which cell type is the primary target of cimetidine in the testicular interstitial compartment, these findings support a direct link between cimetidine-induced testicular vascular atrophy and LCs damage. Copyright © 2015 Elsevier Inc. All rights reserved.

Matrix metalloproteinase expression and activity in trophoblast-decidual tissues at organogenesis in CF-1 mouse.

PubMed

Fontana, Vanina; Coll, Tamara A; Sobarzo, Cristian M A; Tito, Leticia Perez; Calvo, Juan Carlos; Cebral, Elisa

2012-10-01

During early placentation, matrix metalloproteinases (MMPs) play important roles in decidualization, trophoblast migration, invasion, angiogenesis, vascularization and extracellular matrix (ECM) remodeling of the endometrium. The aim of our study was to analyze the localization, distribution and differential expression of MMP-2 and -9 in the organogenic implantation site and to evaluate in vivo and in vitro decidual MMP-2 and -9 activities on day 10 of gestation in CF-1 mouse. Whole extracts for Western blotting of organogenic E10-decidua expressed MMP-2 and -9 isoforms. MMP-2 immunoreactivity was found in a granular and discrete pattern in ECM of mesometrial decidua (MD) near maternal blood vessels and slightly in non-decidualized endometrium (NDE). Immunoexpression of MMP-9 was also detected in NDE, in cytoplasm of decidual cells and ECM of vascular MD, in trophoblastic area and in growing antimesometrial deciduum. Gelatin zymography showed that MMP-9 activity was significantly lower in CM compared to the active form of direct (not cultured) and cultured decidua. The decidual active MMP-9 was significantly higher than the active MMP-2. These results show differential localization, protein expression and enzymatic activation of MMPs, suggesting specific roles for MMP-2 and MMP-9 in decidual and trophoblast tissues related to organogenic ECM remodeling and vascularization during early establishment of mouse placentation.

Topoisomerase IIα in Wilms' tumour: gene alterations and immunoexpression

PubMed Central

Tretiakova, M; Turkyilmaz, M; Grushko, T; Kocherginsky, M; Rubin, C; Teh, B; Yang, X J

2006-01-01

Background Topoisomerase IIα (topoIIα) is an essential enzyme gene in regulating DNA structure and cell proliferation and is encoded by the TOP2A . Using cDNA microarray analysis, TOP2A has been reported to be one of the top genes overexpressed in Wilms' tumour. Aim To evaluate the role of TopoIIα in Wilms' tumorigenesis and its prognostic value. Methods TOP2A gene copy numbers were determined using the fluorescence in situ hybridisation technique, and protein expression levels of TopoIIα by immunostaining in 39 samples of primary and 18 samples of metastatic Wilms' tumour. Results TOP2A gene amplification was detected only in anaplastic Wilms' tumours, and none of the Wilms' tumours showed deletion of the TOP2A gene. TopoIIα protein overexpression was detected in 97% of Wilms' tumours, and correlated strongly with proliferation, as measured by Ki‐67 (r = 0.85). The high TopoIIα expression was associated with the presence of vascular invasion, prominent apoptosis, metastases and adverse clinical outcomes (p<0.05). Conclusions Our findings suggest that TopoIIα overexpression in Wilms' tumours is caused by a change at the transcription level, except for anaplastic Wilms' tumours, in which gene amplification was present. High levels of TopoIIα protein are correlated with tumour aggressiveness. The assessment of TopoIIα expression in Wilms' tumour may have prognostic value. PMID:16556665

Septin 7 immunoexpression in papillary thyroid carcinoma: a preliminary study.

PubMed

Igci, Yusuf Ziya; Erkilic, Suna; Arslan, Ahmet

2014-07-01

Papillary thyroid carcinoma (PTC) is the most common type among thyroid cancers. The diagnosis of PTC may be challenging when follicular variant (FVPTC) of this disease is present due to the resemblance of nuclear properties of the classical type (CVPTC). However, making use of ancillary molecular markers in the diagnosis of PTC may help. In our study, we aimed to evaluate the SEPT7 protein expression in PTC. A total of 55 paraffin block tissue samples comprising encapsulated FVPTC (FVPTC(e), n=25), and CVPTC (n=15), and benign hyperfunctioning thyroid nodules (HypN, n=15) were used in this study. Nuclear, cytoplasmic, and overall (total) SEPT7 protein expression levels were determined by using immunohistochemistry. Nuclear, cytoplasmic, and overall SEPT7 expressions (p=0.02, p=0.001, p=0.002, respectively) were significantly lower in FVPTC(e) tissues when compared to HypN. In CVPTC group, nuclear expression was significantly lower (p=0.004) while overall and cytoplasmic expressions were not changed (p>0.05). In HypN group, highest nuclear (mean=2.73), cytoplasmic (mean=2.86), and overall (mean=2.86) expression scores were detected. Significantly lower SEPT7 expression in all expressional categories in FVPTC(e) group may be a sign of different molecular signature in this type of tissue. Copyright © 2014 Elsevier GmbH. All rights reserved.

Immunohistochemical expression of apoptosis-related biomarkers in normal tissues of camel (Camelus dromedarius): A survey in a desert-dwelling mammalian model.

PubMed

Osman, Abdel-Hamid K; Caceci, Thomas; Shintani, Mitchiko

2018-05-01

Programmed cell death is a fundamental event that takes place during organ development and plays an important role in cellular homeostasis. Since various body organs of the camel are under high ecological and physiological stress during food and water deprivation, desiccation, and the long exposure to solar radiation in these desert nomads, we aimed to examine the immunohistochemical expression of apoptosis-related biomarkers in some of its normal body organs to illustrate a basic track for further pathological investigation. Regarding apoptosis, the present study has revealed that the higher expression of cleaved caspase-9 (CC9) [initiator of the intrinsic pathway] and CC3 (effector caspase), and the scanty expression of CC8 (initiator of the extrinsic pathway), highlight the role of the caspase-dependent, intrinsic apoptotic pathway particularly in the intestines and lymphoid organs. The apoptosis- inducing factor (AIF)-immunoexpression was completely missing in the cell nuclei of the examined tissues, indicating the absence of the caspase-independent pathway. The nuclear overexpression of the phospho-histone H2AX (γ H2AX) and the occasional expression of single-stranded DNA, particularly among the CNS neurons, suggest an efficient, protective DNA-repair mechanism in such cells. Thus, despite efficient anti-apoptotic mechanisms intrinsic apoptotic pathways exists in brain, intestine and lymph organs of adult desert camels. Copyright © 2018 Elsevier GmbH. All rights reserved.

Intratumoral CD3+ T-Lymphocytes Immunoexpression and Its Association with c-Kit, Angiogenesis, and Overall Survival in Malignant Canine Mammary Tumors

PubMed Central

Carvalho, Maria Isabel; Pires, Isabel; Dias, Marlene; Prada, Justina; Gregório, Hugo; Lobo, Luis; Queiroga, Felisbina

2015-01-01

In this study 80 malignant CMT were submitted to immunohistochemical detection of CD3, c-kit, VEGF, and CD31, together with clinicopathological parameters of tumor aggressiveness. CD3+ T-cells and c-kit overexpression revealed a positive correlation with VEGF (r = 0.503, P < 0.0001; r = 0.284, P = 0.023 for CD3 and c-kit, resp.) and CD31 (r = 0.654, P < 0.0001; r = 0.365, P = 0.003 for CD3 and c-kit, resp.). A significant association (P = 0.039) and a positive correlation (r = 0.263, P = 0.039) between CD3 and c-kit were also observed. High CD3/VEGF, c-kit/VEGF, and CD3/c-kit tumors were associated with elevated grade of malignancy (P < 0.0001 for all groups), presence of intravascular emboli (P < 0.0001 for CD3/VEGF and CD3/c-kit; P = 0.002 for c-kit/VEGF), and presence of lymph node metastasis (P < 0.0001 for all groups). Tumors with high CD3/VEGF (P = 0.006), c-kit/VEGF (P < 0.0001), and CD3/c-kit (P = 0.002) were associated with poor prognosis. Interestingly high c-kit/VEGF tumors retained their significance by multivariate analysis arising as independent prognostic factor. PMID:26346272

Distribution of macrophages and plasma cells in apical periodontitis and their relationship with clinical and image data

PubMed Central

Azeredo, Stéphane V.; Brasil, Sabrina C.; Antunes, Henrique; Marques, Fábio V.; Pires, Fábio R.

2017-01-01

Background Macrophages and plasma cells play a key role in the regulation of innate and adaptive immunity. The aim of this study was to assess the presence of these cells in apical periodontitis and their distribution comparing with clinical and image data. Material and Methods Thirty-three lesions were selected and divided in two groups (17 periapical cysts and 16 periapical granulomas). Immunoreactions using anti-CD68 and anti-CD138 antibodies were carried out; image analysis was performed with an optical microscope and 5 high-power fields from each slide were evaluated leading to an average score of immunoexpression. This mean score was compared between the two groups and correlated with the clinical and image data. Results There was no statistically significant difference (p >0.05) for the mean average score of CD68+ macrophages and CD138+ plasma cells when comparing the two groups (cysts x granulomas) and the specimens included in each specific group. No statistically significant differences (p >0.05) were also observed when comparing the average scores with clinical and image data. Conclusions The presence of CD68+ macrophages and CD138+ plasma cells was similar in periapical cysts and granulomas and the presence of these cells did not correlate with clinical and image data from both groups. Key words:Macrophages, plasma cells, apical periodontitis, periapical granuloma, periapical cyst. PMID:29075406

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

Molina-Molina, Jose-Manuel; INSERM, U896, Montpellier, F-34298; Universite Montpellier1, Montpellier, F-34298

Benzophenone (BP) derivatives, BP1 (2,4-dihydroxybenzophenone), BP2 (2,2',4,4'-tetrahydroxybenzophenone), BP3 (2-hydroxy-4-methoxybenzophenone), and THB (2,4,4'-trihydroxybenzophenone) are UV-absorbing chemicals widely used in pharmaceutical, cosmetics, and industrial applications, such as topical sunscreens in lotions and hair sprays to protect skin and hair from UV irradiation. Studies on their endocrine disrupting properties have mostly focused on their interaction with human estrogen receptor alpha (hER{alpha}), and there has been no comprehensive analysis of their potency in a system allowing comparison between hER{alpha} and hER{beta} activities. The objective of this study was to provide a comprehensive ER activation profile of BP derivatives using ER from human and fishmore » origin in a battery of in vitro tests, i.e., competitive binding, reporter gene based assays, vitellogenin (Vtg) induction in isolated rainbow trout hepatocytes, and proliferation based assays. The ability to induce human androgen receptor (hAR)-mediated reporter gene expression was also examined. All BP derivatives tested except BP3 were full hER{alpha} and hER{beta} agonists (BP2 > THB > BP1) and displayed a stronger activation of hER{beta} compared with hER{alpha}, the opposite effect to that of estradiol (E{sub 2}). Unlike E{sub 2}, BPs were more active in rainbow trout ER{alpha} (rtER{alpha}) than in hER{alpha} assay. All four BP derivatives showed anti-androgenic activity (THB > BP2 > BP1 > BP3). Overall, the observed anti-androgenic potencies of BP derivatives, together with their proposed greater effect on ER{beta} versus ER{alpha} activation, support further investigation of their role as endocrine disrupters in humans and wildlife.« less

Red wine interferes with oestrogen signalling in rat hippocampus.

PubMed

Monteiro, Rosário; Faria, Ana; Mateus, Nuno; Calhau, Conceição; Azevedo, Isabel

2008-07-01

Oestrogens have neuroprotective properties, resulting in memory and learning preservation. Red wine (RW) has been linked to neuroprotection, but mechanisms are largely unknown. The aim of this work was to test the effect of RW or 13% ethanol solution consumption on the expression of aromatase and estrogen receptors (ER) in the rat hippocampus. Beverages were supplied to male Wistar rats and after 8 weeks of treatment animals were euthanised, hippocampus was removed, aromatase expression assessed by western blotting and aromatase and ER transcription determined by RT-PCR. The effects of treatments on hippocampal aromatase activity were also determined, as well as the effect of several red wine polyphenols in hippocampal homogenates from untreated animals. Aromatase transcription was increased by ethanol (to 158+/-7%) but only significantly by RW (to 180+/-9%). No difference was found in ERalpha expression among groups, whereas RW significantly decreased ERbeta expression (to 63+/-10%). Resveratrol, quercetin, myricetin and kaempferol had no effect on aromatase activity and catechin (300 microM), epicatechin (200 microM), procyanidin extract (200 mg/L) and fractioned procyanidins (FI and FII; 200 mg/L) significantly decreased aromatase activity. The contribution of procyanidins in wine to the effect observed in aromatase was investigated in animals treated for the same period with these compounds (200 mg/L), although no effect was seen in aromatase activity, mRNA or protein levels, meaning that this group of compounds had little contribution, if any, to the effects observed. Nevertheless, the increase in aromatase expression induced by RW may corroborate the neuroprotective ability attributed to this beverage. Alterations in the relative abundance of ER expression may also play an important role in the protection.

Flaxseed and pure secoisolariciresinol diglucoside, but not flaxseed hull, reduce human breast tumor growth (MCF-7) in athymic mice.

PubMed

Chen, Jianmin; Saggar, Jasdeep K; Corey, Paul; Thompson, Lilian U

2009-11-01

Previous studies have shown that dietary flaxseed (FS) can reduce the growth of established human breast tumors in athymic mice with low circulating estrogen concentrations. In this study, we determined the effect of FS compared with pure lignan at the level it is present in FS [secoisolariciresinol diglucoside (SDG)] and to the lignan-rich fraction [FS hull (FH)] on human breast tumor growth and their potential mechanisms of action. Ovariectomized, athymic mice, each with an implanted 17 beta-estradiol (E2) pellet (0.36 mg), were injected with human estrogen receptor (ER) positive breast cancer cells (MCF-7). When tumors were established, the E2 pellet was removed. Mice were fed either the control basal diet (BD), FS (100 g/kg diet), SDG (1 g/kg diet), or FH (18 g/kg diet) for 8 wk. Compared with the BD, FS and SDG significantly decreased the palpable tumor size, but effects of FS, SDG, and FH did not differ from one another. All treatments significantly inhibited cell proliferation, but only FS and SDG induced significantly higher apoptosis. Both FS and SDG significantly decreased mRNA expressions of Bcl2, cyclin D1, pS2, ERalpha, and ERbeta, epidermal growth factor receptor, and insulin-like growth factor receptor. FS also reduced human epidermal growth factor receptor 2 mRNA and SDG decreased phospho-specific mitogen-activated protein kinase expression. FH did not significantly reduce these biomarkers. In conclusion, pure SDG has a similar effect as FS in reducing tumor growth and in mechanisms of action, including downregulating ER- and growth factor-mediated cell signaling. The lesser effects of FH indicate a need for a higher dose to be more effective.

The clinical importance of the metabolite equol-a clue to the effectiveness of soy and its isoflavones.

PubMed

Setchell, Kenneth D R; Brown, Nadine M; Lydeking-Olsen, Eva

2002-12-01

Equol [7-hydroxy-3-(4'-hydroxyphenyl)-chroman] is a nonsteroidal estrogen of the isoflavone class. It is exclusively a product of intestinal bacterial metabolism of dietary isoflavones and it possesses estrogenic activity, having affinity for both estrogen receptors, ERalpha and ERbeta. Equol is superior to all other isoflavones in its antioxidant activity. It is the end product of the biotransformation of the phytoestrogen daidzein, one of the two main isoflavones found in abundance in soybeans and most soy foods. Once formed, it is relatively stable; however, equol is not produced in all healthy adults in response to dietary challenge with soy or daidzein. Several recent dietary intervention studies examining the health effects of soy isoflavones allude to the potential importance of equol by establishing that maximal clinical responses to soy protein diets are observed in people who are good "equol-producers." It is now apparent that there are two distinct subpopulations of people and that "bacterio-typing" individuals for their ability to make equol may hold the clue to the effectiveness of soy protein diets in the treatment or prevention of hormone-dependent conditions. In reviewing the history of equol, its biological properties, factors influencing its formation and clinical data, we propose a new paradigm. The clinical effectiveness of soy protein in cardiovascular, bone and menopausal health may be a function of the ability to biotransform soy isoflavones to the more potent estrogenic isoflavone, equol. The failure to distinguish those subjects who are "equol-producers" from "nonequol producers" in previous clinical studies could plausibly explain the variance in reported data on the health benefits of soy.

Coordinate regulation of estrogen-mediated fibronectin matrix assembly and epidermal growth factor receptor transactivation by the G protein-coupled receptor, GPR30.

PubMed

Quinn, Jeffrey A; Graeber, C Thomas; Frackelton, A Raymond; Kim, Minsoo; Schwarzbauer, Jean E; Filardo, Edward J

2009-07-01

Estrogen promotes changes in cytoskeletal architecture not easily attributed to the biological action of estrogen receptors, ERalpha and ERbeta. The Gs protein-coupled transmembrane receptor, GPR30, is linked to specific estrogen binding and rapid estrogen-mediated release of heparin-bound epidermal growth factor. Using marker rescue and dominant interfering mutant strategies, we show that estrogen action via GPR30 promotes fibronectin (FN) matrix assembly by human breast cancer cells. Stimulation with 17beta-estradiol or the ER antagonist, ICI 182, 780, results in the recruitment of FN-engaged integrin alpha5beta1 conformers to fibrillar adhesions and the synthesis of FN fibrils. Concurrent with this cellular response, GPR30 promotes the formation of Src-dependent, Shc-integrin alpha5beta1 complexes. Function-blocking antibodies directed against integrin alpha5beta1 or soluble Arg-Gly-Asp peptide fragments derived from FN specifically inhibited GPR30-mediated epidermal growth factor receptor transactivation. Estrogen-mediated FN matrix assembly and epidermal growth factor receptor transactivation were similarly disrupted in integrin beta1-deficient GE11 cells, whereas reintroduction of integrin beta1 into GE11 cells restored these responses. Mutant Shc (317Y/F) blocked GPR30-induced FN matrix assembly and tyrosyl phosphorylation of erbB1. Interestingly, relative to recombinant wild-type Shc, 317Y/F Shc was more readily retained in GPR30-induced integrin alpha5beta1 complexes, yet this mutant did not prevent endogenous Shc-integrin alpha5beta1 complex formation. Our results suggest that GPR30 coordinates estrogen-mediated FN matrix assembly and growth factor release in human breast cancer cells via a Shc-dependent signaling mechanism that activates integrin alpha5beta1.

Fascin expression in cholesteatoma: correlation with destruction of the ossicular chain and extent of disease.

PubMed

Binnetoglu, A; Sari, M; Baglam, T; Erbarut Seven, I; Yumusakhuylu, A C; Topuz, M F; Batman, C

2015-08-01

Fascin is an actin-bundling protein found in cell membrane protrusions and increases cell motility. The expression of fascin in epithelial neoplasms has been described only recently. No data are available concerning the role of this protein in invasive cholesteatoma. Thus, we investigated the expression of fascin in cholesteatoma tissue and the relationship between fascin expression and intraoperative evaluation of the destruction of the ossicular chain and extent of disease. Cholesteatoma specimens of 28 patients and external auditory canal (EAC) skin specimens of the same patients (as the control group) were collected from mastoidectomies. Immunohistochemical technique was used to investigate the fascin expression in all cholesteatoma tissues and EAC skin specimens. Immunohistochemical staining was assessed semiquantitatively based on the thickness of epithelium. SPSS software version 16.0 (SPSS Inc., Chicago, IL, USA) was performed to statistically analyse the relationships between fascin expression and intraoperative evaluation destruction of ossicular chain and extent of the disease. Immunohistochemically, there was no or very low fascin expression observed in normal epithelial cells of EAC skin, while expressed in cholesteatoma tissue. Also, fascin expression in cholesteatoma tissues was significantly correlated with destruction of ossicular chain and extent of the disease. Fascin expression is usually found in cholesteatoma epithelium and is correlated with destruction of the ossicular chain and extent of disease. Considering all of the correlations between the clinical and histopathological findings, 'fascin immunoexpression scoring' may be used for histological grading of cholesteatoma. © 2015 John Wiley & Sons Ltd.

Overexpression of Cyclooxygenase-2 and Transforming Growth Factor-Beta 1 is an Independent Predictor of Poor Virological Response to Interferon Therapy in Chronic HCV Genotype 4 Patients

PubMed Central

Gomaa, Wafaey M.; Ibrahim, Mohammed A.; Shatat, Mohamed E.

2014-01-01

Background/Aims: COX-2 and TGF-β1 are overexpressed in hepatitis C virus (HCV) infection and are related to hepatitis pathogenesis and hepatic fibrosis. The current study investigated the relationship between pretreatment COX-2 and TGF-β1 hepatic expression in HCV genotype 4 and the virological response to interferon therapy. Patients and Methods: Liver biopsies of 55 patients with HCV infection genotype 4 were selected together with 10 liver biopsies as control. The patients’ clinicopathological data were collected. Immunohistochemistry was done using anti-COX-2 and anti-TGF-β1 antibodies. Statistical tests were used to determine the association between both COX-2 and TGF-β1 expression in relation to clinicopathological parameters and response to interferon therapy. Results: COX-2 was upregulated especially in nonresponders and was an independent predictor of poor virological response. However, COX-2 showed no association with other clinicopathological features. TGF-β1 was upregulated and associated with nonresponders, histological activity, and fibrosis stage. There was no association between TGF-β1 and other clinicopathological features. There was an association between COX-2 and TGF-β1 immunoexpression. Conclusion: Overexpression of COX-2 and TGF-β1 is an independent predictor for poor outcome of interferon and ribavirin therapy and these might be useful markers for the response to treatment. Both molecules are associated together; however, their role during hepatitis treatment has to be clarified. PMID:24496160

The 2013 German-Russian BION-M1 Joint Flight Project: Skeletal Muscle and Neuromuscular Changes in Mice Housed for 30 Days in a Biosatellite on Orbit

NASA Astrophysics Data System (ADS)

Blottner, Dieter; Shenkman, Boris; Salanova, Michele

Exposure to microgravity results in various structural, biochemical and molecular changes of the skeletal neuromuscular system. The BION Joint Flight Proposal between the Charité Berlin Center of Space Medicine (www.zwmb.de) in Berlin, and the Institute of Biomedical Problem (IMBP) in Moscow, provided an exciting opportunity for a more detailed analysis of neuromuscular changes in mice (C57/bl6) exposed to real microgravity housed for 30 days in a BION M1 biosatellite on orbit. The mice from the BION flight group (n=5) were compared to three different on-ground control groups (Flight control, BION-ground and Vivarium, each n=5 mice). We started to analyse various skeletal muscles from the hind limbs or trunk. Apart from routine structural and biochemical analysis (fiber size and type distribution, slow/fastMyHC) we test the hypothesis for the presence of a microgravity-induced sarcolemma-cytosolic protein shift of nitric oxide synthase (NOS) and partial loss in neuromuscular synapse scaffold protein (Homer) immunoexpression known to be prone to disuse in mice or humans (hind limb unloading, bed rest) as previously shown (Sandonà D et al., PLoS One, 2012, Salanova M et al., FASEB J, 2011). National Sponsors: Federal Ministry of Economics and Technology (BMWi) via the German AeroSpace Board, DLR e.V., Bonn-Oberkassel, Germany (#50WB1121); Contract RAS-IMBP/Charité Berlin # Bion-M1/2013

Architectural patterns of p16 immunohistochemical expression associated with cancer immunity and prognosis of head and neck squamous cell carcinoma.

PubMed

Ryu, Hyang Joo; Kim, Eun Kyung; Heo, Su Jin; Cho, Byoung Chul; Kim, Hye Ryun; Yoon, Sun Och

2017-11-01

We evaluated the expression patterns of p16, which is used as a surrogate marker of HPV infection in head and neck squamous cell carcinoma (HNSCC), in regard to their biological and prognostic implications. p16 expression patterns and infiltrated immune cells were analyzed through immunohistochemistry of p16, CD3, CD8, PD-1, FOXP3, and CD163 on surgically resected HNSCCs (n = 393). Patterns of p16 immunoexpression were defined as STRONG (strong, diffuse expression in cytoplasm, and nucleus in >70% of tumor cells), MARGINAL (expression restricted to tumor margins), MOSAIC (ragged, discontinued expression), NUCLEAR (expression in nuclei only), and ABSENT (no expression). The STRONG pattern was more frequent in the oropharynx, and the MARGINAL pattern was noted only in the oral cavity. MOSAIC and NUCLEAR patterns were noted at variable sites. No two patterns of p16 expression showed the same immune cell composition of CD3+ T cells, CD8+ cytotoxic T cells, PD-1+ T cells, FOXP3+ regulatory T cells, and CD163+ macrophages. In overall and disease-free survival analyses, the STRONG pattern showed the most favorable prognosis, while the NUCLEAR pattern had the worst prognosis. HNSCC anatomical sites, tumor-related immune cell components, and patient outcomes were associated with p16 expression patterns. Each architectural pattern of p16 expression may be related to different biological and prognostic phenotypes. © 2017 APMIS. Published by John Wiley & Sons Ltd.

High androgen receptor immunoexpression in human "Sertoli cell only" testis.

PubMed

Loukil, L Hadjkacem; Boudawara, T Sellami; Ayadi, I; Bahloul, A; Jlidi, R; Ayadi, H; Keskes, L Ammar

2005-01-01

Our purpose was to evaluate cellular androgen receptor (AR) distribution and intensity of immunostaining in the human azoospermic testis. Thirty six biopsy specimens from azoospermic men were immunostained, using a monoclonal antibody of human AR. The localization and the intensity of AR immunostaining was evaluated in Sertoli Cell Only (SCO) testis (G1, n = 21), in spermatogenesis arrest testis (G2, n = 11) and in histologically normal testis (G3, n = 4). We found an AR immunostaining in Sertoli, peritubular myoid and Leydig cells, but not in germ cells. The intensity of the immunostaining varied substantially between biopsy specimens of different patients. Sertoli and Leydig cells AR immunostaining (score and intensity) in SCO group was higher than in the other groups. For Sertoli cells, the score means of AR immunoreactivity were 20 +/- 2.36, 10.18 +/- 1.0 and 1 +/- 1, for G1, G2 and G3 groups, respectively. For Leydig cells, the score means were 10.24 +/- 1.37, 6 +/- 0.71 and 0, for G1, G2 and G3 groups, respectively. We found significant differences between G1 and G2 (p = 0.0008), between G1 and G3 (p = 1.54 10-7) and G2 and G3 (p = 0.00032). These results suggest that in the testis AR is located exclusively in somatic cells and its expression is higher in SCO syndrome than in normal and in arrest spermatogenesis testes.

Immunohistochemical study of the neural development transcription factors (TTF1, ASCL1 and BRN2) in neuroendocrine prostate tumours.

PubMed

Rodríguez-Zarco, E; Vallejo-Benítez, A; Umbría-Jiménez, S; Pereira-Gallardo, S; Pabón-Carrasco, S; Azueta, A; González-Cámpora, R; Espinal, P S; García-Escudero, A

2017-10-01

Prostatic small-cell neuroendocrine carcinoma is an uncommon malignancy that constitutes 0.5-1% of all prostate malignancies. The median cancer-specific survival of patients with prostatic small-cell neuroendocrine carcinoma is 19 months, and 60.5% of the patients have metastatic disease. Neural development transcription factors are molecules involved in the organogenesis of the central nervous system and of neuroendocrine precursors of various tissues, including the suprarenal gland, thyroid glands, lungs and prostate. We present 3 cases of this uncommon condition, applying the new World Health Organisation criteria. We conducted studies through haematoxylin and eosin staining and analysed the expression of the neural development transcription factors achaete-scute homolog like 1, thyroid transcription factor 1 and the class III/IV POU transcription factors, as a new research line in the carcinogenesis of prostatic neuroendocrine tumours. In case 1, there was no TTF1 immunoexpression. Cases 2 and 3 had positive immunostaining for ASCL1, and Case 1 had negative immunostaining. BRN2 immunostaining was negative in case 1 and positive in cases 2 and 3. The World Health Organisation does not recognise any molecular or genetic marker with prognostic value. ASCL-1 is related to the NOTCH and WNT signalling pathways. ASCL-1, TTF1 and BRN2 could be used for early diagnosis and as prognostic factors and therapeutic targets. Copyright © 2017 AEU. All rights reserved.

Immunoexpression of HDAC1, HDAC2, and HAT1 in actinic cheilitis and lip squamous cell carcinoma.

PubMed

Chrun, E S; Modolo, F; Vieira, Dsc; Borges-Júnior, Áls; Castro, R G; Daniel, F I

2017-05-01

Acetylation and deacetylation are the most studied covalent histone modifications resulting in transcriptional regulation with histone deacetylases (HDAC) and histone acetyltransferases (HAT) as the main associated enzymes. These enzymes overexpression induces abnormal transcription of key genes that regulate important cellular functions, such as proliferation, cell cycle regulation, and apoptosis. Thus, the expression of different HATs and HDACs has been evaluated in various cancers. To investigate HDAC1, HDAC2 and HAT1 expression in lip squamous cell carcinoma (LSCC) and actinic cheilitis (AC) and to demonstrate their correlation with DNA metyltransferases (DNMTs). Thirty cases of lip squamous cell carcinoma (LSCC), thirty cases of actinic cheilitis (AC), and 28 cases of non-neoplastic epithelium as control were selected for immunohistochemical investigation. Nuclear HDAC2 immunopositivity was significantly higher in AC (75.07% ± 29.70) when compared with LSCC (51.06% ± 39.02). HDAC1 and HAT1 nuclear immunostaining were higher in AC, with no statistical significance. When comparing data with our previous study, we found a positive correlation between HDAC1 X DNMT1/DNMT3b, HDAC2 X DNMT3b, and HAT1 X DNMT1/DNMT3b for certain studied groups. This study showed higher levels of nuclear HDAC2 immunopositivity in AC, possibly indicating that this enzyme plays a key role in lip photocarcinogenesis early stages. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Immunohistochemical expression of DNA methyltransferases 1, 3a, and 3b in actinic cheilitis and lip squamous cell carcinomas.

PubMed

Daniel, Filipe I; Alves, Soraia R; Vieira, Daniella S C; Biz, Michelle T; Daniel, Inah W B S; Modolo, Filipe

2016-11-01

Epigenetic modifications, including DNA methylation of tumor suppressor genes carried out by DNA methyltransferases (DNMTs), are important events in carcinogenesis. Although there are studies concerning to its expression in several cancer types, DNMTs expression pattern is not known in photoinduced lip carcinogenesis. The aim of this study was to investigate the immunoexpression of DNMTs 1, 3a, and 3b in lip precancerous lesion (actinic cheilitis) and cancer. Thirty cases of actinic cheilitis (AC), thirty cases of lip squamous cell carcinoma (LSCC), and twenty cases of non-neoplastic tissue (NNT) were selected for immunohistochemical investigation of DNMTs 1, 3a, and 3b. Nuclear DNMT 1 immunoreactivity was significantly higher in the LSCC group (68.6%) compared with NNT (47%), and nuclear DNMT 3b was higher in LSCC (70.9%) than in NNT (37.9%) and in AC (44%). Only DNMT 3a showed both higher nuclear and cytoplasmic expression in AC (35.9% and 35.5%, respectively) than in NNT (4.4% and 16.1%, respectively) and LSCC (8.8% and 13.2%, respectively) (P < 0.05). The results suggested that DNMT 3a could play a key role in the methylation process of initial steps of UV carcinogenesis present in AC while DNMT 3b could be responsible for de novo methylation in already established lip cancer. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Altered expression of key cell cycle regulators in renal cell carcinoma associated with Xp11.2 translocation.

PubMed

Barroca, H; Castedo, S; Vieira, J; Teixeira, M; Müller-Höcker, J

2009-01-01

Renal cell carcinoma (RCC) is a rare tumor in the pediatric population. Recently, a phenotypically and genetically distinct kidney carcinoma, mainly prevalent in children and associated with an Xp11.2 translocation or TFE3 gene fusion, has been described. It has been advanced that in this subtype of RCC, there is an accumulation of cyclin D1, cyclin D3, and p21 ((wafl/cip1)). The aim of the present study was to figure out in two pediatric RCC recently diagnosed in our department (one clear cell-type RCC and one TFE3-positive RCC) whether those features are indeed specific of the latter tumor or occur in pediatric RCC irrespective of the tumor type. The following immunostains were performed in both cases: Ki67, p16(ink4a), p21 ((wafl/cip1)), p27(kip1), p53, p63, mdm2, cyclin D1, cyclin D3, TFE3, CD10, vimentin, E-cadherin, and RCC-antigen. We observed in the TFE3-positive carcinoma an intense immunoreaction for p21 ((wafl/cip1)), cyclin D1, and cyclin D3, without expression for p53, p16, p27(kip1), and mdm2, whereas the immunoexpression profile observed in the classic RCC was similar to that of clear cell, adult-type RCC. Our study confirms that TFE3-positive RCC exhibits a deregulation of the cell cycle apparently unrelated to the young age of the patients.

Treponema denticola chymotrypsin-like proteinase is present in early-stage mobile tongue squamous cell carcinoma and related to the clinicopathological features.

PubMed

Listyarifah, Dyah; Nieminen, Mikko T; Mäkinen, Laura K; Haglund, Caj; Grenier, Daniel; Häyry, Valtteri; Nordström, Dan; Hernandez, Marcela; Yucel-Lindberg, Tülay; Tervahartiala, Taina; Ainola, Mari; Sorsa, Timo; Hagström, Jaana

2018-05-10

Certain periodontopathogenic bacteria have been linked to cancers. Treponema denticola (Td) is associated with severe periodontitis. Chymotrypsin-like proteinase (CTLP), a major virulence factor of Td, can degrade various host proteins and peptides, and modulate inflammatory responses. However the role of Td in the tongue carcinogenesis remains unknown. This study aimed to investigate the presence of Td-CTLP in early-stage mobile tongue squamous cell carcinoma (MTSCC) and its relation to clinical and pathological characteristics. The immunopositivity of Td-CTLP was assessed in samples obtained from 60 MTSCC patients and associated with their clinicopathological data. Additionally, Td-CTLP expression was compared with immunoexpression of matrix metalloproteinases (MMP-8 and -9), toll-like receptors (TLR-2, -4, -7 and -9), c-Myc, Ki-67, Bmi-1, and Snail. Td-CTLP was present in 95% of MTSCC tumours of which many (40.4%) showed high immunopositivity. Td-CTLP positivity was significantly associated with invasion depth, tumour diameter, and the expression of TLR-7, TLR-9, and c-Myc. High Td-CTLP immunopositivity in patients under the age of 60 predicted early relapse. Our data indicate that Td and its CTLP are present in early-stage MTSCC carcinoma and may contribute to carcinogenesis, and therefore provide novel perspectives into intervention and therapeutic measures of MTSCC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

M2 macrophages coexist with a Th1-driven profile in periapical cysts.

PubMed

Ribeiro, C M; de Carli, M L; Nonogaki, S; Nogueira, D A; Pereira, A A C; Sperandio, F F; Hanemann, J A C

2018-02-01

To evaluate the participation of both Th1 and Th2 responses in periapical cysts by assessing the presence of M2 macrophages, as well as acute IL-1 β, TNF-α and IL-6 cytokines. Twenty-four cases of periapical cysts were selected. Immuno-expressions of IL-1 β, IL-6, TNF-α and CD163 were analysed in the cystic capsules in both superficial and deeper regions. Data were analysed with paired Wilcoxon test and Spearman correlation coefficient (P ≤ 0.05). There was a higher expression of IL-1β, IL-6, TNF-α and M2 macrophages in the superficial region (P < 0.001) of cystic capsules. All acute cytokines had significant positive correlations amongst them regardless of the cystic capsule region. Regarding CD163, positive correlations occurred only with TNF-α (P = 0.007; r = 0.537) and IL-6 (P = 0.018; r = 0.478) in the superficial regions of the cystic capsule. M2 macrophages participated actively in the inflammatory response of periapical cysts and correlated with the expression of certain acute Th1-related cytokines. This illustrates the coexistence of an acute and chronic Th2-driven immune response in these lesions. Although M2 macrophages favour the healing process, their presence is not sufficient for periapical cyst regression, once an acute active response has occurred due to an infectious stimuli. © 2017 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Comparative Expression of CD34, Intercellular Adhesion Molecule-1, and Podoplanin and the Presence of Mast Cells in Periapical Granulomas, Cysts, and Residual Cysts.

PubMed

Lopes, Cristiane Barbosa; Armada, Luciana; Pires, Fábio Ramôa

2018-07-01

The aim of the present study was to compare the immunoexpression of CD34, intercellular adhesion molecule-1 (ICAM-1), and podoplanin and the presence of mast cells with clinical, demographic, radiologic, and histologic features from periapical granulomas, periapical cysts, and residual cysts. Thirty-one lesions (5 granulomas, 15 periapical cysts, and 11 residual cysts) were selected. Histologic sections in silanized slides were used for the immunohistochemical reactions. The analysis of the images was performed by using an optical microscope, and data were analyzed with 5% significance (P < .05). Cysts presented atrophic and hyperplastic epithelium in 11 cases (35.5%) and 15 cases (48.8%), respectively (P > .05). The intensity of the inflammatory infiltrate was similar when comparing the 3 groups (P > .05). CD34 and podoplanin expression and the presence of mast cells were similar when comparing the 3 groups; ICAM-1 expression was more intense in granulomas than cysts (P < .05). There were no statistically significant differences associated with the expression of the evaluated markers according to the intensity of the inflammatory infiltrate. There were no differences in the expression of CD34 and podoplanin and in the presence of mast cells when the 3 groups were compared. ICAM-1 expression was more common in periapical granulomas. Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Nrf2-peroxiredoxin I axis in polymorphous adenocarcinoma is associated with low matrix metalloproteinase 2 level.

PubMed

Brod, J M; Demasi, Ana Paula Dias; Montalli, V A; Teixeira, L N; Furuse, C; Aguiar, M C; Soares, A B; Sperandio, M; Araujo, V C

2017-12-01

Polymorphous adenocarcinoma (PAC) is a malignant epithelial neoplasm that affects almost exclusively the minor salivary glands, generally described as having a relatively good prognosis. Aberrant nuclear factor erythroid 2 (NF-E2)-related factor (Nrf2) activation in tumor cells has been associated with induction of antioxidant enzymes, such as peroxiredoxin I (Prx I) and increased matrix metalloproteinase (MMP) expression. In this context, the aim of the present study was to evaluate the expression of Nrf2 and correlate it with Prx I and MMP-2 secretion in PAC. Thirty-one cases of PAC from oral biopsies were selected and immunohistochemically analyzed for Nrf2 and Prx I. MMP-2 quantification was performed on primary cell cultures derived from PAC. Oral squamous cell carcinoma (OSCC) cell cultures were used as control. A high immunoexpression of Nrf2 was observed in both the cytoplasm and the nucleus of neoplastic cells from PAC. Nuclear staining for Nrf2 suggested its activation in the majority of the PAC cells, which was confirmed by the high expression of its target gene, Prx I. Quantification of MMP-2 secretion showed lower levels in PAC cell cultures when compared to OSCC cell cultures (p < 0.05). In conclusion, although Nrf2 overexpression has been frequently associated with high-grade malignancies, such relationship is not infallible and, in fact, the opposite may occur in low-grade tumors, such as PAC of minor salivary glands.

Androgens regulate scarless repair of the endometrial "wound" in a mouse model of menstruation.

PubMed

Cousins, Fiona L; Kirkwood, Phoebe M; Murray, Alison A; Collins, Frances; Gibson, Douglas A; Saunders, Philippa T K

2016-08-01

The human endometrium undergoes regular cycles of synchronous tissue shedding (wounding) and repair that occur during menstruation before estrogen-dependent regeneration. Endometrial repair is normally both rapid and scarless. Androgens regulate cutaneous wound healing, but their role in endometrial repair is unknown. We used a murine model of simulated menses; mice were treated with a single dose of the nonaromatizable androgen dihydrotestosterone (DHT; 200 µg/mouse) to coincide with initiation of tissue breakdown. DHT altered the duration of vaginal bleeding and delayed restoration of the luminal epithelium. Analysis of uterine mRNAs 24 h after administration of DHT identified significant changes in metalloproteinases (Mmp3 and -9; P < 0.01), a snail family member (Snai3; P < 0.001), and osteopontin (Spp1; P < 0.001). Chromatin immunoprecipitation analysis identified putative androgen receptor (AR) binding sites in the proximal promoters of Mmp9, Snai3, and Spp1. Striking spatial and temporal changes in immunoexpression of matrix metalloproteinase (MMP) 3/9 and caspase 3 were detected after DHT treatment. These data represent a paradigm shift in our understanding of the role of androgens in endometrial repair and suggest that androgens may have direct impacts on endometrial tissue integrity. These studies provide evidence that the AR is a potential target for drug therapy to treat conditions associated with aberrant endometrial repair processes.-Cousins, F. L., Kirkwood, P. M., Murray, A. A., Collins, F., Gibson, D. A., Saunders, P. T. K. Androgens regulate scarless repair of the endometrial "wound" in a mouse model of menstruation. © The Author(s).

Cellular Profile and Expression of Immunologic Markers in Chronic Apical Periodontitis from HIV-infected Patients Undergoing Highly Active Antiretroviral Therapy.

PubMed

Gama, Túlio Gustavo Veiga; Pires, Fabio Ramoa; Armada, Luciana; Gonçalves, Lucio Souza

2016-06-01

This study tested the hypothesis that the inflammatory cell profile (CD3-, CD4-, CD8-, CD20-, and CD68-positive cells) and the expression of immunologic markers (tumor necrosis factor α, interferon-γ, interleukin-6, and interleukin-18) in chronic apical periodontitis are the same between non-HIV-infected patients and HIV-infected patients undergoing highly active antiretroviral therapy (HAART). Thirty-four surgically excised chronic apical periodontitis lesions were sampled from 34 patients (17 HIV-infected and 17 non-HIV-infected). The lesions were extracted from teeth with no previous endodontic treatment. All HIV-infected patients were undergoing HAART. The specimens were submitted to histopathologic and immunohistochemical analyses by using an optical microscope. Immunoexpression was graded into 2 levels, focal to weak and moderate to strong. The χ(2), Fisher exact, and Mann-Whitney tests were used to analyze all significant differences between groups. Periapical cysts represented 70.6% and 52.9% of the lesions in the HIV-infected and non-HIV-infected groups, respectively; however, no statistically significant difference was observed (P = .481). There were no statistically significant differences between groups for the inflammatory cell profile and for any of the immunologic markers (P > .05). There are no statistically significant differences of the cellular profile and expression of immunologic markers in chronic apical periodontitis between non-HIV-infected patients and HIV-infected patients undergoing HAART. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Pattern of galectins expression in actinic cheilitis with different risks of malignant transformation.

PubMed

Lopes, Maria Luiza Diniz de Sousa; Nonaka, Cassiano Francisco Weege; Queiroz, Lélia Maria Guedes; de Souza, Lélia Batista; Miguel, Márcia Cristina da Costa; da Silveira, Éricka Janine Dantas

2016-09-01

Actinic cheilitis (AC) is a chronic inflammatory lesion that in some situations can turn into squamous cell carcinoma of the lip. The molecular mechanisms involved in this process are not yet completely understood. This study aimed to investigate the expression pattern of galectins in actinic cheilitis according to the histopathological grading. Immunoexpression of galectin-1, galectin-3, galectin-7, and galectin-9 was semiquantitatively analyzed in 65 cases of actinic cheilitis graded as low risk (n = 40) or high risk (n = 25) of malignant transformation. Association between the location of the galectins in the cellular compartments and histopathological grading was analyzed. Galectin-1 was mainly observed in the cell cytoplasm, and was elevated (score 3) in 60% of cases, regardless of the histopathological grade (P > 0.05). Galectin-3 expression was higher in high-risk group than in the low-risk group (P < 0.05), with a predominant expression in the cytoplasm and nucleus of low-risk (67.5%), and only in the cytoplasm of high-risk cases (60%) (P < 0.05). Galectin-7 expression did not show significant differences between low-risk and high-risk groups (P > 0.05). With respect to galectin-9, 89.2% of cases were positive, showing decrease in median of scores as there was an increase in histological grade (P < 0.001), with predominant expression in the nucleus and cytoplasm. This study is the first indication of galectins involvement in the pathogenesis and morphologic progression of actinic cheilitis, particularly galectin-3 and galectin-9. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Expression of p40 (∆Np63) protein in meningiomas, an unexpected finding: immunohistochemical study and evaluation of its possible prognostic role.

PubMed

Guadagno, Elia; Del Basso De Caro, Marialaura; Pignatiello, Sara; Sciammarella, Concetta; Solari, Domenico; Cappabianca, Paolo; Maiuri, Francesco; Dones, Flavia

2016-09-01

According to the 2007 WHO (World Health Organization) Classification, meningiomas are divided into three grades of malignancy, with different recurrence rate, based exclusively on histopathological parameters. Loss/reduction of PgR (Progesterone Receptor) expression and increased Ki67 L.I. (Labeling Index) have been proven as possible prognostic factors able to predict the relapse of the disease. However, they sometimes result unreliable, especially when discordant. p40 is the short form of the p53 homologue gene p63, also named ∆Np63, and its antibody has recently been introduced as a highly specific diagnostic marker of the squamous cell carcinoma of the lung. Nevertheless its expression has been found in many other unconventional sites (e.g. placenta, urotheluim, etc). Herein we assessed the immuno-expression of p40 protein in a series of 72 meningiomas (35 grade I and 37 grade II) and analyzed its correlation with clinicopathological parameters, overall survival and recurrence free interval. We found that a high p40 score correlated with high histological grade, presence of recurrence, increased Ki67 L.I. and loss/reduction of PgR signal. Moreover, a higher expression of p40 was shown to be a significant prognostic factor for the development of recurrences and resulted a prognostic independent variable in multivariate analysis. Overall, for the first time, we investigated the expression of p40 protein in meningiomas and explored its usefulness as prognostic marker in addition to PgR and Ki67 L.I.

Color threshold and ratio of S100 beta, MAP5, NF68/200, GABA & GAD. I. Distribution in inner ear afferents

NASA Technical Reports Server (NTRS)

Fermin, C. D.; Martin, D. S.; Hara, H.

1997-01-01

Afferents of chick embryos (Gallus domesticus) VIIIth nerve were examined at E3, E6, E9, E13, El7, and hatching (NH) for anti-S100 beta, anti-MAP5, anti-GABA, anti-GAD and anti-NF68/200 stain. Different ages were processed together to determine if the distribution of these antibodies changed during synaptogenesis and myelination. Color thresholding showed that saturation of pixels changed for S100 beta only 5%, for NF68/200 10%, and for MAP5, 10%, between E9-NH. Color ratio of NF68/200 over MAP5 was 1.00 at E13 and 0.25 at E16 and NH. S100 beta, GABA and GAD were co-expressed on nerve endings at the edge of the maculae and center of the cristae, whereas hair cells in the center of the maculae expressed either S100 beta or GABA, but not both. S100 beta/NF68/200 shared antigenic sites on the chalices, but NF68/200 expression was higher than S100 beta in the chalices at hatching. MAP5 was expressed in more neurons than NF68/200 at E11, whereas NF68/200 was more abundant than MAP5 at hatching. The results suggest that: 1) the immunoexpression of these neuronal proteins is modulated concomitantly with the establishment of afferent synapses and myelination; 2) S100 beta may serve a neurotrophic function in the chalices where it is co-expressed with the neurotransmitter GABA and its synthesizing enzyme GAD.

Targeting the superoxide/nitric oxide ratio by L-arginine and SOD mimic in diabetic rat skin.

PubMed

Jankovic, Aleksandra; Ferreri, Carla; Filipovic, Milos; Ivanovic-Burmazovic, Ivana; Stancic, Ana; Otasevic, Vesna; Korac, Aleksandra; Buzadzic, Biljana; Korac, Bato

2016-11-01

Setting the correct ratio of superoxide anion (O 2 •- ) and nitric oxide ( • NO) radicals seems to be crucial in restoring disrupted redox signaling in diabetic skin and improvement of • NO physiological action for prevention and treatment of skin injuries in diabetes. In this study we examined the effects of L-arginine and manganese(II)-pentaazamacrocyclic superoxide dismutase (SOD) mimic - M40403 in diabetic rat skin. Following induction of diabetes by alloxan (blood glucose level ≥12 mMol l  -1 ) non-diabetic and diabetic male Mill Hill hybrid hooded rats were divided into three subgroups: (i) control, and receiving: (ii) L-arginine, (iii) M40403. Treatment of diabetic animals started after diabetes induction and lasted for 7 days. Compared to control, lower cutaneous immuno-expression of endothelial NO synthase (eNOS), heme oxygenase 1 (HO1), manganese SOD (MnSOD) and glutathione peroxidase (GSH-Px), in parallel with increased NFE2-related factor 2 (Nrf2) and nitrotyrosine levels characterized diabetic skin. L-arginine and M40403 treatments normalized alloxan-induced increase in nitrotyrosine. This was accompanied by the improvement/restitution of eNOS and HO1 or MnSOD and GSH-Px protein expression levels in diabetic skin following L-arginine, i.e. SOD mimic treatments, respectively. The results indicate that L-arginine and M40403 stabilize redox balance in diabetic skin and suggest the underlying molecular mechanisms. Restitution of skin redox balance by L-arginine and M40403 may represent an effective strategy to ameliorate therapy of diabetic skin.

Analysis of the PI3K-AKT-mTOR pathway in penile cancer: evaluation of a therapeutically targetable pathway.

PubMed

Adimonye, Anthony; Stankiewicz, Elzbieta; Kudahetti, Sakunthala; Trevisan, Giorgia; Tinwell, Brendan; Corbishley, Cathy; Lu, Yong-Jie; Watkin, Nick; Berney, Daniel

2018-03-23

To determine whether phosphatidylinositol-4,5-bisphosphate 3- kinase, catalytic subunit alpha (PIK3CA) copy number gain is common and could prove a useful marker for the activation status of the PI3K-AKT-mTOR pathway in penile squamous cell carcinoma (PSCC). Fresh frozen tissue and archival blocks were collected from 24 PSCC patients with 15 matched normal penile epithelium (NPE) tissue from St George's Hospital. PIK3CA mutational and copy number status (CNS) was assessed via Sanger sequencing and fluorescence in-situ hybridisation, respectively. PIK3CA RNA expression was quantified using TaqMan gene expression assay. HPV DNA was detected with INNO-LiPA assay. p-AKT and p-mTOR protein expression were assessed using western blot and immunohistochemistry. PIK3CA copy number gain was found in 11/23 (48%) patients, with mutations present in only 2/24 (8%) patients. In comparison to NPE, PSCC showed significantly lower PIK3CA RNA expression (p=0.0007), p-AKT (Ser473) nuclear immunoexpression (p=0.026) and protein expression of p-AKT (Thr308) (p=0.0247) and p-mTOR (Ser2448) (p=0.0041). No association was found between PIK3CA CNS and p-AKT and p-mTOR protein expression. Based on our results the PI3K-AKT-mTOR pathway is not a key driver in PSCC carcinogenesis and the therapeutic targeting of this pathway is unlikely to produce significant clinical benefit.

Prognostic roles of pathology markers immunoexpression and clinical parameters in Hepatoblastoma.

PubMed

Wu, Jia-Feng; Chang, Hsiu-Hao; Lu, Meng-Yao; Jou, Shiann-Tarng; Chang, Kai-Chi; Ni, Yen-Hsuan; Chang, Mei-Hwei

2017-08-29

Hepatoblastoma, a leading primary hepatic malignant tumor in children, is originated from primitive hepatic stem cells. We aimed to elucidate the relationships between the histological distribution of β-catenin and hepatic stem cell markers with the clinical outcomes of hepatoblastoma. Immunohistochemistry was applied to detect β-catenin and hepatic stem cell markers expression in 31 hepatoblastoma tumors. We analyzed the relationship between the stem cell markers and the clinical course of hepatoblastoma. Thirty-one hepatoblastoma patients were diagnosed at a mean age of 2.58 ± 3.78 years, and 7 (22.58%) died. A lack of anticipated decrease in alpha-fetal protein levels after neoadjuvant chemotherapy indicated a higher mortality rate. Nuclear β-catenin expression was significantly associated with membranous epithelial cell adhesion molecule (EpCAM) expression in hepatoblastoma tumor specimens. The co-expression of nuclear β-catenin and membranous EpCAM together with an age at diagnosis ≤1.25 years were predictive of an alpha-fetoprotein level < 1200 ng/mL after neoadjuvant chemotherapy (P < 0.05). An alpha-fetoprotein level < 1200 ng/mL after neoadjuvant chemotherapy and age at hepatoblastoma diagnosis ≤1.25 years are both predictors of better overall and native liver survival in hepatoblastoma patients. Presence of membranous EpCAM with nuclear β-catenin and younger diagnostic age of hepatoblastoma are predictive of serum alpha-fetoprotein levels drop after chemotherapy. Younger diagnostic age and lower alpha-fetoprotein levels after neoadjuvant chemotherapy and are predictive of better overall and native liver survival in hepatoblastoma patients.

Comparison of the effects of caudal pole hemi-meniscectomy and complete medial meniscectomy in the canine stifle joint.

PubMed

Johnson, K A; Francis, D J; Manley, P A; Chu, Q; Caterson, B

2004-08-01

To compare the effects of caudal pole hemi-meniscectomy (CPHM) and complete medial meniscectomy (MM), specifically with respect to development of secondary osteoarthritis, in the stifle joints of clinically normal dogs. 14 large-breed dogs. Unilateral CPHM (7 dogs) or MM (7) was performed, and the left stifle joints served as untreated control joints. Gait was assessed in all dogs before surgery and at 4, 8, 12, and 16 weeks postoperatively. After euthanasia, joints were evaluated grossly; Mankin cartilage scores, subchondral bone density assessment, and articular cartilage proteoglycan extraction and western blot analyses of 3B3(-) and 7D4 epitopes were performed. Weight distribution on control limbs exceeded that of treated limbs at 4 and 16 weeks after surgery in the CPHM group and at 4 and 8 weeks after surgery in the MM group; weight distribution was not significantly different between the 2 groups. After 16 weeks, incomplete meniscal regeneration and cartilage fibrillation on the medial aspect of the tibial plateau and medial femoral condyle were detected in treated joints in both groups. Mankin cartilage scores, subchondral bone density, and immunoexpression of 3B3(-) or 7D4 in articular cartilage in CPHM- or MM-treated joints were similar; 7D4 epitope concentration in synovial fluid was significantly greater in the MM-treated joints than in CPHM-treated joints. Overall severity of secondary osteoarthritis induced by CPHM and MM was similar. Investigation of 7D4 epitope concentration in synovial fluid suggested that CPHM was associated with less disruption of chondrocyte metabolism.

Cytokine profiling identifies an interaction of IL-6 and IL-1α to drive PSMA-PSA prostate clones.

PubMed

Jemaa, Awatef Ben; Bouraoui, Yosra; Rais, Nawfel Ben; Nouira, Yassine; Oueslati, Ridha

2016-12-01

Several PSMA-PSA prostate clones have been identified during prostate cancer progression; however, until now, their in situ inflammatory characteristics have remained unclear. We therefore investigated the interplay between proinflammatory cytokines and (PSMA,PSA) sub-groups. 27 benign prostate hyperplasia (BPH) and 18 prostate cancers (PC) were enrolled in this study. Immunohistochemical analysis was performed. Serum levels of PSA were assayed by Immulite autoanalyser. In BPH and PC patients with elevated serum PSA levels, IL-1α was the most proinflammatory cytokine expressed in (PSMA+,PSA-) subgroup. However, most samples of (PSMA+,PSA+) subgroup had positive immunoreaction to IL-6. In samples of PC with PSA serum levels of 4-20ng/mL or >20ng/mL, immunoreaction to TNF-α was seen only in (PSMA+,PSA+) subgroup. Interestingly, several combinations of proinflammatory cytokines (IL-6, IL-1α and TNF-α) showed that coexpression of tissue PSMA and PSA was concomitant with high immunoreactions to (IL-6+,TNF-α-), (IL-6+,IL-1α+) and (IL-1α+,TNFα-) in BPH and PC patients. (PSMA,PSA) subgroup lacking tissue PSA expression showed a high immunoexpression of the profile (IL-6+,TNF-α-). The combinations of (IL-6-, TNF-α-) and (IL-6-, IL-1α-) were absent in (PSMA+,PSA-) and (PSMA+,PSA+) BPH sub-groups. Collectively, these findings underscore the importance of TNF-α and highlight the interaction between IL-6 and IL-1α to generate an inflammatory microenvironment in driving (PSMA,PSA) prostate clones. Copyright © 2016 Elsevier GmbH. All rights reserved.

CD147 and MCT1-potential partners in bladder cancer aggressiveness and cisplatin resistance.

PubMed

Afonso, Julieta; Santos, Lúcio L; Miranda-Gonçalves, Vera; Morais, António; Amaro, Teresina; Longatto-Filho, Adhemar; Baltazar, Fátima

2015-11-01

The relapsing and progressive nature of bladder tumors, and the heterogeneity in the response to cisplatin-containing regimens, are the major concerns in the care of urothelial bladder carcinoma (UBC) patients. The metabolic adaptations that alter the tumor microenvironment and thus contribute to chemoresistance have been poorly explored in UBC setting. We found significant associations between the immunoexpressions of the microenvironment-related molecules CD147, monocarboxylate transporters (MCTs) 1 and 4, CD44 and CAIX in tumor tissue sections from 114 UBC patients. The presence of MCT1 and/or MCT4 expressions was significantly associated with unfavorable clinicopathological parameters. The incidence of CD147 positive staining significantly increased with advancing stage, grade and type of lesion, and occurrence of lymphovascular invasion. Similar associations were observed when considering the concurrent expression of CD147 and MCT1. This expression profile lowered significantly the 5-year disease-free and overall survival rates. Moreover, when selecting patients who received platinum-based chemotherapy, the prognosis was significantly worse for those with MCT1 and CD147 positive tumors. CD147 specific silencing by small interfering RNAs (siRNAs) in UBC cells was accompanied by a decrease in MCT1 and MCT4 expressions and, importantly, an increase in chemosensitivity to cisplatin. Our results provide novel insights for the involvement of CD147 and MCTs in bladder cancer progression and resistance to cisplatin-based chemotherapy. We consider that the possible cooperative role of CD147 and MCT1 in determining cisplatin resistance should be further explored as a potential theranostics biomarker. © 2014 Wiley Periodicals, Inc.

Interleukin-18 (IL-18) is equally expressed in inflammatory breast cancer and noninflammatory locally advanced breast cancer: A possible association with chemotherapy response.

PubMed

Aguiar, Marco Antonio Nasser; Wanderley, Carlos Wagner S; Nobre, Lívia Maria Soares; Alencar, Mateus Rolim Mendes; Saldanha, Maria do Perpétuo Socorro; Souza, Alceu Machado; Wong, Deysi Viviana Tenazoa; Barros, Paulo Goberlânio; Almeida, Paulo Roberto Carvalho; Lima-Júnior, Roberto Cesar Pereira; Ribeiro, Ronaldo Albuquerque

2018-04-01

Inflammatory breast cancer (IBC) is the most aggressive form of locally advanced breast cancer. The signs of inflammation such as hyperemia and hyperthermia might suggest the possible participation of inflammatory mediators. This study investigates stromal and tumor expression of nuclear factor-kappa B (NF-κB) and interleukin-18 (IL-18) in samples obtained from IBC and noninflammatory locally advanced breast cancer (LABC) and the influence of these markers on patients' prognosis. Demographic data, tumor molecular characteristics and overall survival in both groups were also assessed. Furthermore, in this study, we evaluated the expression of IL-18 and p50 nuclear fraction of NF-κB by immunohistochemistry in specimens from IBC and LABC (T4b). We observed that 24.6% of women were diagnosed with IBC up to age 40. In addition, the patients with IBC showed a lower overall survival when compared to LABC. In regard to molecular markers, ER + , C-erbB2 - or triple negative IBC patients showed a significantly reduced overall survival. In addition, a higher IL-18 immunostaining in stroma of IBC and LABC was observed in comparison with tumor cells, but stromal immunoexpression was similar between IBC and LABC. Besides, IL-18 positivity seemed be related with a better clinical response to neoadjuvant chemotherapy. However, NF-κB expression was identical in both groups. The IL-18 is present in tumor stroma of IBC and LABC and seems to be associated with the complete response to neoadjuvant chemotherapy. © 2017 John Wiley & Sons Australia, Ltd.

Immunohistochemical expression of galectin-3 is significantly associated with grade, stage and differentiation of endometrial carcinomas.

PubMed

Al-Maghrabi, Jaudah; Abdelrahman, Amer Shafie; Ghabrah, Tawfik; Butt, Nadeem Shafique; Al-Maghrabi, Basim; Khabaz, Mohamad Nidal

2017-04-01

This study describes galectin-3 immunohistochemical phenotype and its association with clinicopathological factors in the carcinoma of endometrium. Seventy one cases of endometrial carcinoma and 30 cases of benign and normal endometrium were employed for the detection of galectin-3 protein using tissue microarrays and immunohistochemistry staining. Thirty nine (55%) cases, including 54.2% of endometrioid adenocarcinomas and 55.5% serous carcinomas, were positively stained for galectin-3. Brown granular expression of this glycoprotein was detected in transformed epithelial cells of 36 cases including 28 cases with membranous and cytoplasmic staining and 8 cases with only cytoplasmic staining; nuclear expression was present in stromal cells of the remaining 3 cases. Twenty-four (80%) control cases showed granular cytoplasmic and membranous expression, and six control cases were negative. Tumor grade, stage and differentiation were significantly associated with galectin-3 immunoreactivity (p-values are 0.043, 0.016, and 0.044 respectively), cases with membranous and cytoplasmic staining is significantly associated with grade I and stage II, while cases with loss of staining are more frequent in grade II, III and poorly differentiated tumors. No significant association of galectin-3 staining was observed with age, diagnosis, recurrence and alive status. The current study supports the tumor suppression role of galectin-3 in endometrial carcinoma. Greater galectin-3 immunostaining has been found in control endometrial tissues compared to endometrial tumors. Loss or decreased galectin-3 immunoexpression gives a sign for poor prognoses in endometrial carcinoma patients. Copyright © 2017 Elsevier GmbH. All rights reserved.

Can Ocimum basilicum relieve chronic unpredictable mild stress-induced depression in mice?

PubMed

Ayuob, Nasra Naeim; Firgany, Alaa El-Din L; El-Mansy, Ahmed A; Ali, Soad

2017-10-01

Depression is one of the important world-wide health problems. This study aimed to assess the ameliorative effect of Ocimum basilicum (OB) essential oil on the behavioral, biochemical and histopathological changes resulted from exposure to chronic unpredictable mild stress (CUMS). It also aimed to investigate the underlying mechanism in an animal model of depression. Forty male Swiss albino mice were divided into four groups (n=10): control, CUMS (exposed to CUMS for 4weeks), CUMS plus fluoxetine, and CUMS plus OB. At the end of the experiment, behavioral changes, serum corticosterone level, protein and gene expressions of brain derived neurotropic factor (BDNF) and glucocorticoid receptors (GR) in the hippocampus was all assessed. Immunoexpression of surface makers of glial fibrillary acidic protein (GFAP), Ki67, Caspase-3, BDNF and GR in the hippocampus were estimated. Data were analyzed by using the statistical package for the social sciences (SPSS). OB alleviated both behavioral and biochemical changes recorded in mice after exposure to CUMS. It also reduced neuronal atrophy observed in the hippocampal region III cornu ammonis (CA3) and dentate gyrus and restored back astrocyte number. OB decreased apoptosis in both neurons and glial cells and increased neurogenesis in the dentate gyrus in a pattern comparable to that of fluoxetine. Increased BDNF and GR gene and protein expressions seems to be behind the antidepressant-like effect of OB. Ocimum basilicum ameliorates the changes induced after exposure to the chronic stress. Assessing Ocimum basilicum efficacy on human as antidepressant is recommended in further studies. Copyright © 2017. Published by Elsevier Inc.

Prognostic Factors and Expression of MDM2 in Patients with Primary Extremity Liposarcoma

PubMed Central

Júnior, Rosalvo Zósimo Bispo; de Camargo, Olavo Pires; de Oliveira, Cláudia Regina G. C. M.; Filippi, Renée Zon; Baptista, André Mathias; Caiero, Marcelo Tadeu

2008-01-01

OBJECTIVE The objective of this study was to investigate MDM2 (murine double minute 2) protein expression and evaluate its relationship with some anatomical and pathological aspects, aiming also to identify prognostic factors concerning local recurrence-free survival, metastasis-free survival and overall survival in patients with primary liposarcomas of the extremities. MATERIALS AND METHODS Of 50 patients with primary liposarcomas of the extremities admitted to a Reference Service, between 1968 and 2004, 25 were enrolled in the study, following eligibility and exclusion criteria. RESULTS The adverse factors that influenced the risk for local recurrence in the univariant analysis included male sex (P = 0.023), pleomorphic histological subtype (P = 0.027), and high histological grade (P = 0.007). Concerning metastasis-free survival, age less than 50 years (P = 0.040), male sex (P = 0.040), pleomorphic subtype (P < 0.001), and high histological grade (P = 0.003) had a worse prognosis. Adverse factors for overall survival were age under 50 years (P = 0.040), male sex (P = 0.040), pleomorphic subtype (P < 0.001), and high histological grade (P = 0.003). CONCLUSIONS There was no correlation between immunohistochemically observed MDM2 protein expressions and the anatomical and pathological variables studied. The immunohistochemical expression of MDM2 protein was not considered to have a prognostic value for any of the surviving patients in this study (local recurrence-free survival, metastasis-free survival, or overall survival). The immunoexpression of MDM2 protein was a frequent event in the different subtypes of liposarcomas. PMID:18438568

Expression of GLUT-1 in oral squamous cell carcinoma in tobacco and non-tobacco users

PubMed Central

Azad, Neha; Kumari Maurya, Malti; Kar, Meenakshi; Goel, Madhu Mati; Singh, Ajay Kumar; Sagar, Mala; Mehrotra, Divya; Kumar, Vijay

2016-01-01

Background GLUTs are a family of proteins that mediate glucose transport through the membrane, expressed in head and neck squamous cell carcinoma. GLUT-1 positivity in malignant cells indicates increased proliferative activity, energy requirements, aggressive behaviour and poor radiation response. Aim To observe the expression of GLUT-1 protein in oral squamous cell carcinoma in tobacco and non-tobacco users and to correlate the expression with histopathological grading and pathological staging. Methods 50 cases (25 tobacco and 25 non-tobacco) of oral squamous cell carcinoma, selected during period of August 2014 to July 2015. Histopathological grading, TNM and staging were done. Immunohistochemical staining was performed using standard protocol for paraffin embedded sections. Analysis was performed on SPSS software (Windows version 17.0). Results Significant association of GLUT-1 expression was found with history of tobacco (p < 0.001), Bryne's grade (p < 0.001), tumour size (p = 0.001), nodal metastasis (p = 0.022) and stage (p < 0.001). Higher GLUT-1 expression in stage II, stage III and stage IV was found as compared to stage I. GLUT-1 immunoexpression also shows progressive switch from membranous to cytoplasmic to combined location correlating with histopathologic grade and pTNM stage. Conclusion GLUT-1 expression correlates significantly with histological grade and pTNM staging of oral squamous cell carcinoma. It also significantly correlates with tobacco addiction. Thus, GLUT-1 expression may serve as a biomarker for patients of oral squamous cell carcinoma. PMID:26937365

Mating changes the subcellular distribution and the functionality of estrogen receptors in the rat oviduct.

PubMed

Orihuela, Pedro A; Zuñiga, Lidia M; Rios, Mariana; Parada-Bustamante, Alexis; Sierralta, Walter D; Velásquez, Luis A; Croxatto, Horacio B

2009-11-30

Mating changes the mode of action of 17beta-estradiol (E2) to accelerate oviductal egg transport from a nongenomic to a genomic mode, although in both pathways estrogen receptors (ER) are required. This change was designated as intracellular path shifting (IPS). Herein, we examined the subcellular distribution of ESR1 and ESR2 (formerly known as ER-alpha and ER-beta) in oviductal epithelial cells of rats on day 1 of cycle (C1) or pregnancy (P1) using immunoelectron microscopy for ESR1 and ESR2. The effect of mating on intraoviductal ESR1 or ESR2 signaling was then explored comparing the expression of E2-target genes c-fos, brain creatine kinase (Ckb) and calbindin 9 kDa (s100g) in rats on C1 or P1 treated with selective agonists for ESR1 (PPT) or ESR2 (DPN). The effect of ER agonists on egg transport was also evaluated on C1 or P1 rats. Receptor immunoreactivity was associated with the nucleus, cytoplasm and plasma membrane of the epithelial cells. Mating affected the subcellular distribution of both receptors as well as the response to E2. In C1 and P1 rats, PPT increased Ckb while both agonists increased c-fos. DPN increased Ckb and s100g only in C1 and P1 rats, respectively. PPT accelerated egg transport in both groups and DPN accelerated egg transport only in C1 rats. Estrogen receptors present a subcellular distribution compatible with E2 genomic and nongenomic signaling in the oviductal epithelial cells of C1 and P1 although IPS occurs independently of changes in the distribution of ESR1 and ESR2 in the oviductal epithelial cells. Mating affected intraoviductal ER-signaling and induced loss of functional involvement of ESR2 on E2-induced accelerated egg transport. These findings reveal a profound influence on the ER signaling pathways exerted by mating in the oviduct.

Expression of the IGF and the aromatase/estrogen receptor systems in human adrenal tissues from early infancy to late puberty: implications for the development of adrenarche.

PubMed

Belgorosky, Alicia; Baquedano, María Sonia; Guercio, Gabriela; Rivarola, Marco A

2009-03-01

Adrenarche is a process of postnatal sexual maturation occurring in higher primates, in which there is an increase in the secretion of adrenal androgens. It is the consequence of a process of postnatal organogenesis characterized by the development of a new zone in the adrenal cortex, the zona reticularis (ZR). The mechanism of this phenomenon remains poorly understood, suggesting that it might be a multifactorial event. A relationship between circulating IGF-I, insulin sensitivity, and adrenal androgens has been postulated. Boys and girls have different patterns of changes in insulin sensitivity at puberty, perhaps secondary to differences in the estrogen milieu. Estrogen effects may also play a role in premature adrenarche. Peripheral or local IGF-1 actions could regulate adrenal progenitor cell proliferation and migration. Since adrenal progenitor cells as well as IGF-I and the IGF-R1 are located in the outer zone of the adrenal cortex during childhood and adolescence, this peripheral cell layer, below the capsule, may contain undifferentiated progenitor cells. Therefore, the IGF-R1 signaling pathway might positively modulate the proliferation and migration of adrenal progenitor cell to stimulate the development of adrenal zones, including ZR. However, no evidence of a direct action of IGF-I on ZR was found. In addition, a role for estrogens in the ontogenesis of ZR is suggested by the presence of aromatase (CYP19) in the subcapsular zona glomerulosa and in the adrenal medulla. Estrogens produced locally could act on ZR by interacting with estrogen receptor beta (ERbeta), but not alpha, and membrane estrogen receptor GPR-30. An estradiol-induced increase in DHEA/cortisol ratio was indeed seen in cultures of adrenocortical cells from post-adrenarche adrenals. In summary, several lines of evidence point to the action of multiple factors, such as local adrenal maturational changes and peripheral metabolic signals, on postnatal human adrenal gland ZR formation.

The G protein-coupled receptor GPR30 inhibits proliferation of estrogen receptor-positive breast cancer cells.

PubMed

Ariazi, Eric A; Brailoiu, Eugen; Yerrum, Smitha; Shupp, Heather A; Slifker, Michael J; Cunliffe, Heather E; Black, Michael A; Donato, Anne L; Arterburn, Jeffrey B; Oprea, Tudor I; Prossnitz, Eric R; Dun, Nae J; Jordan, V Craig

2010-02-01

The G protein-coupled receptor GPR30 binds 17beta-estradiol (E(2)) yet differs from classic estrogen receptors (ERalpha and ERbeta). GPR30 can mediate E(2)-induced nongenomic signaling, but its role in ERalpha-positive breast cancer remains unclear. Gene expression microarray data from five cohorts comprising 1,250 breast carcinomas showed an association between increased GPR30 expression and ERalpha-positive status. We therefore examined GPR30 in estrogenic activities in ER-positive MCF-7 breast cancer cells using G-1 and diethylstilbestrol (DES), ligands that selectively activate GPR30 and ER, respectively, and small interfering RNAs. In expression studies, E(2) and DES, but not G-1, transiently downregulated both ER and GPR30, indicating that this was ER mediated. In Ca(2+) mobilization studies, GPR30, but not ERalpha, mediated E(2)-induced Ca(2+) responses because E(2), 4-hydroxytamoxifen (activates GPR30), and G-1, but not DES, elicited cytosolic Ca(2+) increases not only in MCF-7 cells but also in ER-negative SKBr3 cells. Additionally, in MCF-7 cells, GPR30 depletion blocked E(2)-induced and G-1-induced Ca(2+) mobilization, but ERalpha depletion did not. Interestingly, GPR30-coupled Ca(2+) responses were sustained and inositol triphosphate receptor mediated in ER-positive MCF-7 cells but transitory and ryanodine receptor mediated in ER-negative SKBr3 cells. Proliferation studies involving GPR30 depletion indicated that the role of GPR30 was to promote SKBr3 cell growth but reduce MCF-7 cell growth. Supporting this, G-1 profoundly inhibited MCF-7 cell growth, potentially via p53 and p21 induction. Further, flow cytometry showed that G-1 blocked MCF-7 cell cycle progression at the G(1) phase. Thus, GPR30 antagonizes growth of ERalpha-positive breast cancer and may represent a new target to combat this disease.

Dietary arginine supplementation affects microvascular development in the small intestine of early-weaned pigs.

PubMed

Zhan, Zhenfeng; Ou, Deyuan; Piao, Xiangshu; Kim, Sung Woo; Liu, Yanhong; Wang, Junjun

2008-07-01

This study was conducted to evaluate the effects of dietary arginine levels on microvascular development of the small intestine in early-weaned pigs. Twenty-four crossbred pigs (5.0 +/- 0.3 kg body weight) were individually housed and randomly allotted to 1 of 3 diets supplemented with 0, 0.7, and 1.2% L-arginine (8 pigs per group). Pigs consumed the diets ad libitum for 10 d. We collected blood samples on d 3, 6, and 10. On d 10, 6 pigs from each group were randomly selected and killed for tissue sample collection. Compared with control pigs, dietary supplementation with 0.7% L-arginine increased (P < 0.05) jejunal concentrations of nitrite and nitrate (stable oxidation products of nitric oxide), intestinal villus height, as well as plasma proline and arginine concentrations on d 6 and 10. Dietary supplementation with 0.7% L-arginine also increased (P < 0.05) immunoreactive expression of CD34 in duodenal submucosa, ileal mucosa and submucosa, and expression of vascular endothelial growth factor (VEGF) in duodenal submucosa, jejunal mucosa and submucosa, and ileal mucosa compared with the control and 1.2% L-arginine supplementation. Dietary supplementation with 1.2% L-arginine increased (P < 0.05) the concentration of jejunal endothelin-1 compared with the control pigs. Immunoexpression of VEGF in duodenal mucosa and plasma lysine concentrations on d 6 and 10 were lower (P < 0.05) in pigs supplemented with 1.2% L-arginine than in unsupplemented pigs. Collectively, these findings indicate that the effects of L-arginine on microvascular development are beneficial at lower levels but have adverse effects at higher intakes. Dietary supplementation with 0.7% L-arginine may be a useful method to improve microvascular development in the small intestine of early-weaned pigs.

MDM2 is an important prognostic and predictive factor for platin-pemetrexed therapy in malignant pleural mesotheliomas and deregulation of P14/ARF (encoded by CDKN2A) seems to contribute to an MDM2-driven inactivation of P53.

PubMed

Walter, R F H; Mairinger, F D; Ting, S; Vollbrecht, C; Mairinger, T; Theegarten, D; Christoph, D C; Schmid, K W; Wohlschlaeger, J

2015-03-03

Malignant pleural mesothelioma (MPM) is a highly aggressive tumour that is first-line treated with a combination of cisplatin and pemetrexed. Until now, predictive and prognostic biomarkers are lacking, making it a non-tailored therapy regimen with unknown outcome. P53 is frequently inactivated in MPM, but mutations are extremely rare. MDM2 and P14/ARF are upstream regulators of P53 that may contribute to P53 inactivation. A total of 72 MPM patients were investigated. MDM2 immunoexpression was assessed in 65 patients. MDM2 and P14/ARF mRNA expression was analysed in 48 patients of the overall collective. The expression results were correlated to overall survival (OS) and progression-free survival (PFS). OS and PFS correlated highly significantly with MDM2 mRNA and protein expression, showing a dismal prognosis for patients with elevated MDM2 expression (for OS: Score (logrank) test: P⩽0.002, and for PFS: Score (logrank) test; P<0.007). MDM2 was identified as robust prognostic and predictive biomarker for MPM on the mRNA and protein level. P14/ARF mRNA expression reached no statistical significance, but Kaplan-Meier curves distinguished patients with low P14/ARF expression and hence shorter survival from patients with higher expression and prolonged survival. MDM2 is a prognostic and predictive marker for a platin-pemetrexed therapy of patients with MPMs. Downregulation of P14/ARF expression seems to contribute to MDM2-overexpression-mediated P53 inactivation in MPM patients.

Primordial odontogenic tumor: An immunohistochemical profile

PubMed Central

Bologna-Molina, Ronell; Mikami, Toshinari; Pereira-Prado, Vanesa; Pires, Fabio-Ramoa; Carlos-Bregni, Roman

2017-01-01

Background Primordial Odontogenic Tumor (POT) is a recently described odontogenic tumor characterized by a variably cellular loose fibrous tissue with areas similar to the dental papilla, covered by cuboidal to columnar epithelium that resembles the internal epithelium of the enamel organ, surrounded at least partly by a delicate fibrous capsule. The purpose of this study was to investigate the possible histogenesis and biological behavior of this rare tumor by means of a wide immunohistochemical analysis of its epithelial and mesenchymal components. Material and Methods The immunoexpression of twenty-three different antibodies were evaluated in four cases of POT. Results The epithelial cells that cover the periphery of the tumor showed immunopositivity for Cytokeratins 14 and 19, while Amelogenin, Glut-1, MOC-31, Caveolin-1. Galectin-3, PITX2, p53, Bax, Bcl-2, Survivin and PTEN were variably expressed in focal areas. The mesenchymal component of the tumor was positive for Vimentin, Syndecan-1, PITX2, Endoglin (CD105), CD 34, Cyclin D1, Bax, Bcl-2, Survivin and p53. PTEN and CD 90 showed a moderate positivity. BRAF V600E and Calretinin were negative in all samples. Cell proliferation markers (Ki-67, MCM-7) were expressed in <5% of the tumor cells. Conclusions According to these immunohistochemical findings, we may conclude that POT is a benign odontogenic tumor in which there is both epithelial and mesenchymal activity during its histogenesis, as there is expression of certain components in particular zones in both tissues that suggests this tumor develops during the immature (primordial) stage of tooth development, leading to its inclusion within the group of benign mixed epithelial and mesenchymal odontogenic tumours in the current World Health Organization classification of these lesions. Key words:Immunohistochemistry, jaw tumors, odontogenic, primordial. PMID:28390134

Endometrial Polyps and Benign Endometrial Hyperplasia Present Increased Prevalence of DNA Fragmentation Factors 40 and 45 (DFF40 and DFF45) Together With the Antiapoptotic B-Cell Lymphoma (Bcl-2) Protein Compared With Normal Human Endometria.

PubMed

Banas, Tomasz; Pitynski, Kazimierz; Mikos, Marcin; Cielecka-Kuszyk, Joanna

2017-09-13

DNA fragmentation factor 40 (DFF40) is a key executor of apoptosis. It localizes to the nucleus together with DNA fragmentation factor 45 (DFF45), which acts as a DFF40 inhibitor and chaperone. B-cell lymphoma (Bcl-2) protein is a proven antiapoptotic factor present in the cytoplasm. In this study, we aimed to investigate DFF40, DFF45, and Bcl-2 immunoexpression in endometrial polyps (EPs) and benign endometrial hyperplasia (BEH) tissue compared with that in normal proliferative endometrium (NPE) and normal secretory endometrium (NSE) as well as normal post menopausal endometrium (NAE). This study used archived samples from 65 and 62 cases of EPs and BEH, respectively. The control group consisted of 52 NPE, 54 NSE, and 54 NAE specimens. Immunohistochemistry was used to detect DFF40, DFF45, and Bcl-2. DFF40, DFF45, and Bcl-2 were more highly expressed in the glandular layer of EPs and BEH compared with the stroma, and this was not influenced by menopausal status. Both glandular and stromal expression of DFF40, DFF45, and Bcl-2 were significantly higher in EPs compared with NPE, NSE, and NAE. Glandular BEH tissue showed significantly higher DFF40, DFF45, and Bcl-2 expression than in NPE, NSE, and NAE. No differences in the glandular expression of DFF40, DFF45, and Bcl-2 were observed between EP and BEH tissues, while Bcl-2 stromal expression in BEH was significantly lower than in EPs. Glandular, menopause-independent DFF40, DFF45, and Bcl-2 overexpression may play an important role in the pathogenesis of EPs and BEH.

The prognostic value of Ki-67 expression in penile squamous cell carcinoma.

PubMed

Stankiewicz, Elzbieta; Ng, Mansum; Cuzick, Jack; Mesher, David; Watkin, Nick; Lam, Wayne; Corbishley, Cathy; Berney, Daniel M

2012-06-01

To determine whether Ki-67 immunoexpression in penile squamous cell carcinoma (PSCC) has a prognostic value and correlates with lymph node metastasis, human papillomavirus (HPV) infection and patient survival. 148 formalin-fixed paraffin-embedded PSCC samples were tissue-microarrayed, including 97 usual-type SCCs, 17 basaloid, 15 pure verrucous carcinomas, 2 warty and 17 mixed-type tumours. All samples were immunostained for Ki-67 protein. HPV DNA was detected with INNO-LiPA assay. Follow-up data were available for 134 patients. Ki-67 was strongly expressed in 57/148 (38.5%) of PSCCs. Different cancer subtypes showed significant difference in Ki-67 expression (p<0.0001) with highest positivity in basaloid, 16/17 (94%), followed by usual type, 38/97 (39%) and lack of Ki-67 positive cases within verrucous tumours, 0/15. Ki-67 positively correlated with high-risk HPV (p<0.0001) and showed good specificity (84%) but low sensitivity (61%) for high-risk HPV detection. Ki-67 protein strongly positively correlated with tumour grade (p<0.0001) but not with stage (p=0.2193), or lymph node status (p=0.7366). Ki-67 showed no prognostic value for cancer-specific survival (HR=1.00, 95%, CI 0.99 to 1.02, p=0.54) or overall survival (HR=1.00, 95%, CI 0.99 to 1.02, p=0.45). High tumour stage, lymph node metastasis, high tumour grade and age at diagnosis were all independent prognostic factors for cancer-specific survival and overall survival. Ki-67 is only a moderate surrogate marker for HPV infection in PSCC. It does not show prognostic value for cancer-specific survival and overall survival in PSCC.

Immunoexpression of tumour necrosis factor-α, interleukin-1α and interleukin-10 on odontogenic cysts and tumours.

PubMed

Sá, M C; de Matos, F R; Conceição, T S; Leitão, A C G H; Freitas, R A

2017-05-01

To analyse the immunoreactivity of IL-1α, TNF-α and IL-10 in odontogenic cysts and tumours and to investigate possible associations with established biological behaviours of these different lesions. Immunohistochemical expression of anti-IL-1α, anti-TNF-α and anti-IL-10 antibodies was assessed on epithelium and mesenchyme of 20 radicular cysts (RCs), 20 residual cysts (RECs), 20 dentigerous cysts (DCs), 18 solid ameloblastomas (SAs), 20 keratocystic odontogenic tumours (KCOTs) and 15 dental follicles (DFs). Comparative analysis of data was performed using the nonparametric Wilcoxon signed-rank test and Kruskal-Wallis's test. Significantly greater expression of IL-1α in the epithelium was noted in RC, KCOT and SA (P = 0.01), whilst IL-10 and TNF-α was in the epithelium of RC, DC and KCOT (P < 0.01). In the mesenchyme, significantly greater immunopositivity was observed for IL-1α, IL-10 and TNF-α in KCOT, DC and RC (P < 0.01). In epithelial and mesenchymal tissues, there were a significant number of cases of RC and DC with IL-1α < IL-10 ratio (P < 0.01), whilst SA and KCOT showed IL-1α > IL-10 (P < 0.01). There was a significantly greater percentage of DF, DC and KCOT with TNF-α > IL10 ratio (P < 0.01). These results suggest involvement of the proteins in the pathogenesis of odontogenic cysts and tumours, with emphasis on the highest immunoreactivity of osteolysis stimulating factors in tumours with aggressive biological behaviour, such as SA and KCOT. © 2016 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Aberrant expression of interleukin-22 and its targeting microRNAs in oral lichen planus: a preliminary study.

PubMed

Shen, Zhengyu; Du, Guanhuan; Zhou, Zengtong; Liu, Wei; Shi, Linjun; Xu, Hui

2016-08-01

Oral lichen planus (OLP) is a T cell-mediated autoimmune disease involving oral mucosa. Interleukin-22 (IL-22) as the signature cytokine of T helper 22 cells is increasingly recognized as a key regulator in various autoimmune diseases. Our previous study reported that IL-22 immunoexpression in OLP was significantly increased compared with the normal controls. The objective of this preliminary study was to compare the IL-22 expression levels in oral biopsies from patients with OLP (n = 50) against normal oral mucosa (n = 19) using RT-qPCR and Western blot, identify the potential targeting miRNAs of IL-22, and examine the miRNA expression levels in OLP. Interleukin-22 expression level in OLP was significantly increased compared with the normal controls. The Dual-Luciferase reporter assay system in human embryonic kidney 293 (HEK293) cells demonstrated that miR-562 and miR-203 were the target miRNAs of IL-22, which was consistent with predictions from bioinformatics software analyses. Interestingly, miR-562 expression in OLP was significantly decreased, but miR-203 expression in OLP was significantly increased compared with the normal controls. This preliminary study for the first time reported that aberrant expression levels of miR-562 and miR-203 were associated with high expression of IL-22 and demonstrated the target relationship between miRNAs and IL-22 in HEK293 cells. Our data indicated that IL-22 and its targeting miRNAs contribute to the pathogenesis of OLP. Further studies are required to investigate the regulatory pathways of IL-22 and miR-562 and miR-203 in OLP. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chondroitin sulfate and glucosamine sulfate associated to photobiomodulation prevents degenerative morphological changes in an experimental model of osteoarthritis in rats.

PubMed

Sanches, Marcella; Assis, Lívia; Criniti, Cyntia; Fernandes, Danilo; Tim, Carla; Renno, Ana Claudia Muniz

2018-04-01

The aim of this study was to compare the effects of combined treatment with chondroitin sulfate and glucosamine sulfate (CS/Gl) and photobiomodulation (PBM) on the degenerative process related to osteoarthritis (OA) in the articular cartilage in rats. Forty male Wistar rats were randomly divided into four groups: OA control group (CG); OA animals submitted to PBM treatment (PBM); OA animals submitted to CS/Gl treatment (CS/Gl); OA submitted to CS/GS associated with PBM treatments (GS/Gl + PBM). The CS/Gl started 48 h after the surgery, and they were performed for 29 consecutive days. Moreover, PBM was performed after the CS/Gl administration on the left joint. Morphological characteristics and immunoexpression of interleukin 10 (IL-10) and 1 beta (IL-1β) and collagen type II (Col II) of the articular cartilage were evaluated. The results showed that all treated groups (CS/Gl and PBM) presented attenuation signs of degenerative process (measured by histopathological analysis) and lower density chondrocytes [PBM (p = 0.0017); CS/Gl (p = 0.0153) and CS/Gl + PBM (p = 0.002)]. Additionally, CS/Gl [associated (p = 0.0089) or not with PBM (p = 0.0059)] showed significative lower values for OARSI grade evaluation. Furthermore, CS/GS + PBM decreased IL-1β protein expression (p = 0.0359) and increased IL-10 (p = 0.028) and Col II imunoexpression (p = 0.0204) compared to CG. This study showed that CS/Gl associated with PBM was effective in modulating inflammatory process and preventing the articular tissue degradation in the knees OA rats.

In utero betamethasone affects 3β-hydroxysteroid dehydrogenase and inhibin-α immunoexpression during testis development.

PubMed

Pedrana, G; Viotti, H; Lombide, P; Sanguinetti, G; Pino, C; Cavestany, D; Sloboda, D M; Martin, G B

2016-08-01

Prenatal glucocorticoids, commonly used in women at risk of preterm delivery, can predispose the newborn to disease in later life. Since male reproductive function is likely to reflect testis development during fetal life, we studied the effects of prenatal glucocorticoids on two key intra-testicular factors that play roles in cellular proliferation and differentiation, 3β-hydroxysteroid dehydrogenase (3β-HSD) and inhibin-α. Pregnant sheep (n=42) were treated with betamethasone (0.5 mg/kg) or saline (control) at 104, 111 and 118 days of gestation (DG). Testicular tissue was sampled from fetuses at 121 and 132DG, and from lambs at 45 and 90 postnatal days (PD). Within the betamethasone treated group, 3β-HSD immunostaining area was greater at 121DG than at 90PD (P=0.04), but the intensity of immunostaining was higher at 90PD than at 121DG (P=0.04), 132DG (P=0.04) and 45PD (P=0.03). Control animals showed no changes in 3β-HSD area or intensity of immunostaining. No significant differences were observed between treated and control animals in immunostaining area, but immunostaining was more intense in the treated group than in the control group at 90PD (P=0.03). For inhibin-α, the proportion of immunostaining area declined in treated offspring from 121DG to 45PD, in contrast to control values, but recovered fully by 90PD, concomitantly with the onset of spermatogenesis. In conclusion, prenatal betamethasone increased the postnatal testicular expression of inhibin-α but reduced the expression of 3β-HSD. These effects could compromise androgen-mediated testicular development and therefore adult capacity for spermatogenesis.

Immunohistochemical evaluation of proliferation, apoptosis and steroidogenic enzymes in the ovary of rats with polycystic ovary.

PubMed

Lombardi, Leonardo Augusto; Simões, Ricardo Santos; Maganhin, Carla Cristina; Baracat, Maria Cândida Pinheiro; Silva-Sasso, Gisela Rodrigues; Florencio-Silva, Rinaldo; Soares, José Maria; Baracat, Edmund Chada

2014-07-01

to evaluate the immunohistochemical expression of proliferative, apoptotic and steroidogenic enzyme markers in the ovaries of rats with polycystic ovary syndrome (PCOS). twenty rats were divided into two groups: GCtrl - estrous phase, and PCOS - with polycystic ovaries. The GCtrl animals were subjected to a lighting period from 7 am to 7 pm, while the animals with PCOS group remained with continuous lighting for 60 days. Subsequently, the animals were anesthetized, the ovaries were removed and fixed in 10% formaldehyde, prior to paraffin embedding. Sections were stained using H.E. or subjected to immunohistochemical methods for the detection of Ki-67, cleaved caspase-3, CYP11A1, CYP17A1 and CYP19A1. The results were analyzed using Student's t-test (p < 0,05). morphological results showed evidence of interstitial cells originating from the inner theca cells of degenerating ovarian cysts in PCOS. Immunoexpression of Ki-67 was higher in the granulosa cells in GCtrl, and the theca interna cells in PCOS, while cleaved caspase-3 was higher in granulosa cells of ovarian cysts from PCOS and in the theca interna cells of GCtrl. Immunoreactivity of CYP11A1 in the theca interna, granulosa and interstitial cells was similar between the two groups, while CYP17A1 and CYP19A1 were higher in the granulosa and interstitial cells in the PCOS group. the results indicate that the interstitial cells are derived from the theca interna and that enzymatic changes occur in the theca interna and interstitial cells in ovaries of rats with PCOS, responsible for the high levels of androgens and estradiol.

Medulloblastoma: histopathologic and molecular markers of anaplasia and biologic behavior.

PubMed

Min, Hye Sook; Lee, You Jeong; Park, Kyeongmee; Cho, Byung-Kyu; Park, Sung-Hye

2006-07-01

Large cell/anaplastic (LC/A) medulloblastoma (MB) is a recently recognized variant of medulloblastoma known to be associated with an advanced stage and a poor prognosis. Although Eberhart et al. suggested histopathologic grading of medulloblastoma in 2002, no consensus has been reached in terms of determining the criteria of an LC/A variant, and its biological behavior continues to be the subject of debate. We retrospectively analyzed 74 cases (range 0.25-15 years) of MB clinicopathologically using the criteria established by Eberhart et al. The LC/A variant was identified in 16 cases (22% of MB cases), five of which showed a poor outcome. Most LC/A variant cases revealed synaptophysin immunoexpression (75%), but no epidermal growth factor receptor (EGFR) expression. Expression of synaptophysin, NeuN, GFAP, p53, c-erbB2, and EGFR did not differ in LC/A and non-LC/A variants. Seven of the 74 cases of medulloblastoma showed erbB2 amplification by FISH, four of which were LC/A variants. N-myc amplification was observed in only one LC/A variant, but no c-myc amplification was found. In patients younger than 10 years, the LC/A variant showed a significantly poorer outcome than the non-LC/A variant (P = 0.02), while no difference was found in older patients. Multivariate analysis revealed only metastasis on MRI and p53 expression, but not anaplasia as unfavorable prognostic factors. Our study suggests that prognostic implications of anaplasia in medulloblastoma are uncertain, and that the reproducibility of the histopathologic criteria of the LC/A variant should be reassessed before they can be applied in practical use.

Immunohistochemical expression of matrix metalloproteinase-1, matrix metalloproteinase-2 and matrix metalloproteinase-9, myofibroblasts and Ki-67 in actinic cheilitis and lip squamous cell carcinoma.

PubMed

Bianco, Bianca C; Scotti, Fernanda M; Vieira, Daniella S C; Biz, Michelle T; Castro, Renata G; Modolo, Filipe

2015-10-01

Matrix metalloproteinases (MMPs), myofibroblasts (MFs) and epithelial proliferation have key roles in neoplastic progression. In this study immunoexpression of MMP-1, MMP-2 and MMP-9, presence of MFs and the epithelial proliferation index were investigated in actinic cheilitis (AC), lip squamous cell carcinoma (LSCC) and mucocele (MUC). Thirty cases of AC, thirty cases of LSCC and twenty cases of MUC were selected for immunohistochemical investigation of the proteins MMP-1, MMP-2, MMP-9, α-smooth muscle actin (α-SMA) and Ki-67. The MMP-1 expression in the epithelial component was higher in the AC than the MUC and LSCC. In the connective tissue, the expression was higher in the LSCC. MMP-2 showed lower epithelial and stromal immunostaining in the LSCC when compared to the AC and MUC. The epithelial staining for MMP-9 was higher in the AC when compared to the LSCC. However, in the connective tissue, the expression was lower in the AC compared to other lesions. The cell proliferation rate was increased in proportion to the severity of dysplasia in the AC, while in the LSCC it was higher in well-differentiated lesions compared to moderately differentiated. There were no statistically significant differences in number of MFs present in the lesions studied. The results suggest that MMPs could affect the biological behaviour of ACs and LSCCs inasmuch as they could participate in the development and progression from premalignant lesions to malignant lesions. © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.

Prognostic relevance of autophagy-related markers LC3, p62/sequestosome 1, Beclin-1 and ULK1 in colorectal cancer patients with respect to KRAS mutational status.

PubMed

Schmitz, Klaus Juergen; Ademi, Ceflije; Bertram, Stefanie; Schmid, Kurt Werner; Baba, Hideo Andreas

2016-07-22

Autophagy is a cellular pathway that regulates transportation of cytoplasmic macromolecules and organelles to lysosomes for degradation. Autophagy is involved in both tumorigenesis and tumour suppression. Here we investigated the potential prognostic value of the autophagy-related proteins Beclin-1, p62, LC3 and uncoordinated (UNC) 51-like kinase 1 (ULK1) in a cohort of colorectal cancer (CRC) specimens. In this study, we analysed the immunoexpression of the autophagy-related proteins p62, LC3, Beclin-1 and ULK1 in 127 CRC patients with known KRAS mutational status and detailed clinical follow-up. Survival analysis of p62 staining showed a significant correlation of cytoplasmic (not nuclear) p62 expression with a favourable tumour-specific overall survival (OS). The prognostic power of cytoplasmic p62 was found in the KRAS-mutated subgroup but was lost in the KRAS wildtype subgroup. Survival analysis of Beclin-1 staining did not show an association with OS in the complete cohort. LC3 overexpression demonstrated a slight, though not significant, association with decreased OS. Upon stratifying cases by KRAS mutational status, nuclear (not cytoplasmic) Beclin-1 staining was associated with a significantly decreased OS in the KRAS-mutated subgroup but not in the KRAS wildtype CRCs. In addition, LC3 overexpression was significantly associated with decreased OS in the KRAS-mutated CRC subgroup. ULK1 expression was not correlated to survival. Immunohistochemical analyses of LC3, p62 and Beclin-1 may constitute promising novel prognostic markers in CRC, especially in KRAS-mutated CRCs. This strategy might help in identifying high-risk patients who would benefit from autophagy-related anticancer drugs.

Pathogenesis of Pancreatitis in Chickens after Experimental Infection with 9a5b Newcastle Disease Virus Mutant Isolate.

PubMed

El-Bahrawy, A; Zaid, A; Sunden, Y; Sakurai, M; Ito, H; Ito, T; Morita, T

2015-11-01

The aim of this study was to investigate the effect of Newcastle disease virus (NDV) on the chicken pancreas. A virulent 9a5b mutant NDV isolate was inoculated intranasally into 32-day-old specific pathogen-free white Leghorn chickens. The pancreas was examined grossly and fixed for histopathological, immunohistochemical and electron microscopical investigations. Inflammatory changes were observed in the peripancreatic tissue at the early stage of infection (12 h post infection) and became more prevalent towards the end of the experiment. Multifocal areas of necrotizing inflammation were detected in the exocrine portion of the pancreas by 5 days post infection (dpi) and became more severe at 10 dpi. The endocrine islets were generally preserved, but slight degenerative changes were observed at 10 dpi. Immunohistochemically, NDV-nucleoprotein (NDV-NP) signals were detected in the peripancreatic tissues (associated with macrophages and other lymphoid cells) by 1 dpi. In the exocrine portion of the pancreas, NDV-NP signals were detected at 5 dpi and increased in intensity and distribution by 10 dpi. NDV particles were confirmed in the cytoplasm of exocrine acinar cells by transmission electron microscopy. CD3-positive cells were observed in the peripancreatic tissues earlier than in the pancreatic tissue. Moreover, in comparison with control chickens, insulin immunoexpression was unchanged, except on the last day of the experiment, when it was slightly reduced. The 9a5b NDV infection induced an inflammatory reaction and viral replication in the peripancreatic tissues earlier than in the pancreatic tissue. Furthermore, necrosis affected mainly the exocrine portion of the pancreas, while the endocrine portion was generally unaffected. Copyright © 2015 Elsevier Ltd. All rights reserved.

Imaging growth and isocitrate dehydrogenase 1 mutation are independent predictors for diffuse low-grade gliomas

PubMed Central

Gozé, Catherine; Blonski, Marie; Le Maistre, Guillaume; Bauchet, Luc; Dezamis, Edouard; Page, Philippe; Varlet, Pascale; Capelle, Laurent; Devaux, Bertrand; Taillandier, Luc; Duffau, Hugues; Pallud, Johan

2014-01-01

Background We explored whether spontaneous imaging tumor growth (estimated by the velocity of diametric expansion) and isocitrate dehydrogenase 1 (IDH1) mutation (estimated by IDH1 immunoexpression) were independent predictors of long-term outcomes of diffuse low-grade gliomas in adults. Methods One hundred thirty-one adult patients with newly diagnosed supratentorial diffuse low-grade gliomas were retrospectively studied. Results Isocitrate dehydrogenase 1 mutations were present in 107 patients. The mean spontaneous velocity of diametric expansion was 5.40 ± 5.46 mm/y. During follow-up (mean, 70 ± 54.7 mo), 56 patients presented a malignant transformation and 23 died. The median malignant progression-free survival and the overall survival were significantly longer in cases of slow velocity of diametric expansion (149 and 198 mo, respectively) than in cases of fast velocity of diametric expansion (46 and 82 mo; P < .001 and P < .001, respectively) and in cases with IDH1 mutation (100 and 198 mo, respectively) than in cases without IDH1 mutation (72 mo and not reached; P = .028 and P = .001, respectively). In multivariate analyses, spontaneous velocity of diametric expansion and IDH1 mutation were independent prognostic factors for malignant progression-free survival (P < .001; hazard ratio, 4.23; 95% CI, 1.81–9.40 and P = .019; hazard ratio, 2.39; 95% CI, 1.19–4.66, respectively) and for overall survival (P < .001; hazard ratio, 26.3; 95% CI, 5.42–185.2 and P = .007; hazard ratio, 17.89; 95% CI, 2.15–200.1, respectively). Conclusions The spontaneous velocity of diametric expansion and IDH1 mutation status are 2 independent prognostic values that should be obtained at the beginning of the management of diffuse low-grade gliomas in adults. PMID:24847087

Impact of an Energy Drink on the Structure of Stomach and Pancreas of Albino Rat: Can Omega-3 Provide a Protection?

PubMed

Ayuob, Nasra; ElBeshbeishy, Rana

2016-01-01

A controversy developed between the benefits of energy drinks (EDs) versus the possible health threats since its revolution. Lack of information was a call to assess the effect of chronic consumption of Power Horse (PH) as one of the EDs, on the structure of pancreas and fundic mucosa of stomach in rats, and possible protective role of Omega-3. Thirty two adult male albino rats were divided equally into 4 groups; control received group which only received a standard diet, Omega-3 group, PH group which given PH and PH plus Omega-3 group received both PH plus Omega-3 for 4 weeks. Biochemical assessment of blood glucose, serum insulin, gastrin, tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthetase (iNOS) was performed. The antioxidant activity and histopathological examination of both pancreatic tissue and fundic mucosa of stomach were assessed. Administration of PH significantly increased serum insulin and glucose levels while it significantly reduced serum gastrin level compared to control. PH also caused oxidants/antioxidants imbalance in both pancreas and fundic mucosa. The latter revealed degenerative changes and increased apoptosis which was evident by increased caspase-3 immunoexpression. Pancreas exhibited signs of β-cells overstimulation. Fundic mucosa showed reduced number of parietal cells, gastrin hormone expression compared to control group. Omega-3 administration could alleviate, to some extent, these changes. It significantly decreased TNF-α, iNOS and reduced glutathione (GSH) as well as significantly increasing superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities compared to the group which received PH alone. Power Horse intake significantly injures islet cells, pancreatic acini as well as the glandular cells of the fundic mucosa. Omega-3 decreases these detrimental effects mostly through its antioxidant and anti-inflammatory action.

[Solitary fibrous tumors and hemangiopericytomas of the meninges: Immunophenotype and histoprognosis in a series of 17 cases].

PubMed

Savary, Caroline; Rousselet, Marie-Christine; Michalak, Sophie; Fournier, Henri-Dominique; Taris, Michaël; Loussouarn, Delphine; Rousseau, Audrey

2016-08-01

The 2007 World Health Organization (WHO) classification of tumors of the central nervous system distinguishes meningeal hemangiopericytomas (HPC) from solitary fibrous tumors (TFS). In the WHO classification of tumors of soft tissue and bone, those neoplasms are no longer separate entities since the discovery in 2013 of a common oncogenic event, i.e. the NAB2-STAT6 gene fusion. A shared histopronostic grading system, called "Marseille grading system", was recently proposed, based on hypercellularity, mitotic count and necrosis. We evaluated the immunophenotype and histoprognosis in a retrospective cohort of intracranial HPC and TFS. Fifteen initial tumors and 2 recurrences were evaluated by immunohistochemistry for STAT6, CD34, EMA, progesterone receptors and Ki67. The pronostic value of the WHO and the Marseille grading systems was tested on 12 patients with clinical follow-up. Initial tumors were 11 HPC and 4 SFT. STAT6 and CD34 were expressed in 16/17 tumors, EMA and progesterone receptors in 2 and 5 cases, respectively. The Ki67 labelling index was 6.25% in HPC and 3% in SFT. Half of the tumors recurred between 2 years and 9 years after initial diagnosis (mean time 5 years). No statistical difference in the risk of recurrence was associated with either grade (WHO or Marseille), in this small cohort. The diagnosis of HPC and TFS is facilitated by the almost constant immuno-expression of STAT6, and this justifies their common classification. The high rate of recurrence implies a very long-term follow-up because the current grading systems do not accurately predict the individual risk. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Study of the participation of MMP-7, EMMPRIN and cyclophilin A in the pathogenesis of periodontal disease.

PubMed

de Oliveira Nóbrega, Fernando José; de Oliveira, Denise Hélen Imaculada Pereira; Vasconcelos, Rodrigo Gadelha; Nonaka, Cassiano Francisco Weege; Queiroz, Lélia Maria Guedes

2016-12-01

Periodontal disease is an infectious disease resulting from the immunoinflammatory response of the host to microorganisms present in the dental biofilm which causes tissue destruction. The objective of this study was to evaluate the immunohistochemical expression of matrix metalloproteinase 7 (MMP-7), extracellular matrix metalloproteinase inducer (EMMPRIN) and cyclophilin A (CypA) in periodontal disease. Gingival tissue samples were divided as follows: clinically healthy gingiva (n=32), biofilm-induced gingivitis (n=28), and chronic periodontitis (n=30). Histological sections of 3μm were submitted to immunoperoxidase method and undergone quantitative analysis. The results were analyzed statistically by the Mann-Whitney and Spearman correlation tests, with the level of significance set at 0.05 (α=0.05). Immunopositivity for MMP-7, EMMPRIN and CypA differed significantly between the three groups, with higher percentages of staining in chronic periodontitis specimens, followed by chronic gingivitis and healthy gingiva specimens (p<0.05). Immunoexpression of CypA and MMP-7 was higher in the intense inflammatory infiltrate observed mainly in cases of periodontitis (p<0.05). CypA expression was positively correlated with MMP-7 (r=0.831; p<0.001) and EMMPRIN (r=0.289; p=0.006). In addition, there was a significant positive correlation between probing depth and expression of MMP-7 (r=0.726; p<0.001), EMMPRIN (r=0.345; p=0.001), and CypA (r=0.803; p<0.001). These results suggest that MMP-7, EMMPRIN and CypA are associated with the pathogenesis and progression of periodontal disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clusterin immunoexpression is associated with early stage endometrial carcinomas.

PubMed

Al-Maghrabi, Jaudah Ahmed; Butt, Nadeem Shafique; Anfinan, Nisrin; Sait, Khalid; Sait, Hesham; Bajouh, Osama; Khabaz, Mohamad Nidal

2016-05-01

Clusterin has anti-apoptotic, regeneration and migration stimulating effects on tumor cells. This study investigates the relation between clusterin expression and the clinicopathological parameters in endometrial carcinomas. Seventy one cases of previously diagnosed endometrial carcinoma (including 59 endometrioid adenocarcinoma, 9 serous adenocarcinoma, 1 clear cell adenocarcinoma, and 2 malignant mixed Mullerian tumor) and 30 tissue samples of non-cancerous endometrium (including 16 proliferative endometrium, 10 secretory endometrium and 4 endometrial polyps) were employed for clusterin detection using tissue microarrays and immunostaining. A total number of 23 (32.4%) cases were positive for clusterin immunostaining. Brown granular cytoplasmic expression of clusterin was detected in 33.9% of endometrioid adenocarcinomas, 22.2% papillary serous endometrial carcinomas. Three (10%) control cases showed granular cytoplasmic expression. Positive clusterin immunostaining was found more frequent in well differentiated and stage I endometrial carcinomas, showing significant statistical association (p-value=0.036 and p-value=0.002 respectively). Significant difference in clusterin expression was observed between tumor cases and control group (P-Value=0.019), i.e., endometrial carcinoma cases are more than four times likely to show positive clusterin immunostaining (odds ratio 4.313 with 95% confidence interval 1.184-15.701). This study did not find relation between clusterin expression and disease recurrence, survival or any of the other clinicopathological parameters in endometrial tumors. The results of our study confirms the diagnostic values of clusterin in supporting the diagnosis of endometrioid carcinoma. When clusterin is expressed in endometrial tumors, it is associated with lower stage. The correlation of clusterin with tumor stage suggests involvement of this molecule in endometrial tumor progression. Copyright © 2016 Elsevier GmbH. All rights reserved.

Replication protein A in nonearly ovarian adenocarcinomas: correlation with MCM-2, MCM-5, Ki-67 index and prognostic significance.

PubMed

Levidou, Georgia; Ventouri, Kiriaki; Nonni, Afroditi; Gakiopoulou, Hariklia; Bamias, Aristotle; Sotiropoulou, Maria; Papaspirou, Irene; Dimopoulos, Meletios A; Patsouris, Efstratios; Korkolopoulou, Penelope

2012-07-01

Replication protein A (RPA) is an ssDNA-binding protein required for the initiation of DNA replication and the stabilization of ssDNA. Collaboration with several molecules, that is, the MCM2-7 complex, has been suggested to be imperative for its multifaceted role. In this study, we investigated the immunohistochemical expression of the RPA2 subunit in correlation with the MCM-2 and MCM-5 and Ki67 index, and assessed its prognostic significance in 76 patients with nonearly ovarian adenocarcinomas, the majority of whom had a serous histotype. RPA2 protein expression was observed in all cases, whereas the staining intensity varied from weak to strong. RPA2 expression was correlated with the tumor stage in the entire cohort and in serous tumors (P=0.0053 in both relationships). Moreover, RPA2 immunoexpression was positively correlated with MCM-2 (P=0.0001) and MCM-5 (P<0.0001) expression, but was unrelated to the Ki67 index (P>0.10). In multivariate survival analysis, RPA2 expression emerged as an independent predictor of adverse outcome (P<0.0001) along with tumor histologic grade. RPA2 remained an independent predictor of survival (P=0.002) even after adjustment for MCM-2 and MCM-5 expression and when analysis was restricted to serous carcinomas (P=0.004). Our results further support the interrelation of RPA2 protein with MCM-2 and MCM-5 in OCs. Moreover, RPA2 protein may play an important role in ovarian tumorigenesis, and may serve as a useful independent molecular marker for stratifying patients with OC in terms of prognosis.

Assessment of Bax and Bcl-2 Immunoexpression in Patients with Oral Lichen Planus and Oral Squamous Cell Carcinoma

PubMed Central

Nafarzadeh, Shima; Jafari, Sina; Bijani, Ali

2013-01-01

Lichen planus (LP) is a chronic inflammatory disease of probable immune-based etiology. The pathogenesis of LP is unclear, but apoptotic changes in epidermal (epithelial) cells have been reported. Destruction of the basal cell layer is observed and many changes in cell proliferation, cell repair and cell death occur in the injured mucosal epithelium. The aim of this study was to evaluate and compare the expression of bax and bcl-2 in oral lichen planus (OLP), well differentiated oral squamous cell carcinoma (WOSCC) and normal mucosa. Sixty one paraffin-embedded biopsy including 11 cases of WOSCC, 30 cases of OLP (n=15 erosive OLP [OLP-E], n=15 reticular OLP [OLP-R]) and 20 normal mucosa were entered in our research. We used immunohistochemistry staining method for assessing bax and bcl-2 expression in epithelial layers. The percentage of stained cells was estimated in 5 randomized microscopic fields and classified as (-): 0%, (+) :< 10%, (++): 10-25%, (+++): 26-50%, (++++): > 50% positive cells. The data were analyzed with Mann-Whitney, Chi Square, and Kruskal-Wallis tests. Significant differences in bax expression were observed among OLP, WOSCC compared to normal mucosa (P=0.008). No significant difference in bax expression between OLP-E and OLP-R compared to WOSCC was seen (P>0.05). Bcl-2 was negative for all OLP and normal mucosa samples, and weak positivity was observed in WOSCC samples. According to the findings of our study, it may be possible to correlate the difference of bax and bcl-2 expression levels among the mentioned lesions to the malignant potential of OLP. PMID:24551804

Stromal Expression of Fibroblast Activation Protein Alpha (FAP) Predicts Platinum Resistance and Shorter Recurrence in patients with Epithelial Ovarian Cancer.

PubMed

Mhawech-Fauceglia, Paulette; Yan, Li; Sharifian, Maryam; Ren, Xing; Liu, Song; Kim, Grace; Gayther, Simon A; Pejovic, Tanja; Lawrenson, Kate

2015-04-01

The microenvironment plays an important role in tumorigenesis. Fibroblast activation protein alpha (FAP) is overexpressed by fibroblasts present in the microenvironment of many tumors. High FAP expression is a negative prognostic factor in several malignancies, but this has not been investigated in epithelial ovarian cancer (EOC). The aim of this study is to define the value of FAP in EOC. Immunohistochemical staining using an anti-FAP antibody was performed on 338 EOC tissues. mRNA levels in cancer cell lines and FAP silencing using siRNA was also done. FAP immunoexpression by tumor stroma was a significant predictive factor for platinum resistance (p = 0.0154). In survival analysis of days to recurrence, FAP stoma (+) was associated with shorter recurrence than those with FAP (-) stroma (p = 0.0247). In 21.8 % of tumors, FAP protein was expressed by the tumor epithelium, and FAP mRNA was more highly expressed in tumors (n = 489) than in normal tissues (n = 8) (p = 3.88 × 10(-4)). In vitro, addition of FAP to EOC cells induced a 10-12 % increase in cell viability both in the presence and absence of cisplatin. Conversely, siRNA silencing of FAP resulted in ~10 % reduction in EOC cell proliferation. We have shown that FAP expression in EOC is associated with poorer clinical outcomes. FAP may have novel cell-autonomous effects suggesting that targeting FAP could have pleiotropic anti-tumor effects, and anti-FAP therapy could be a highly effective novel treatment for EOC, especially in cisplatinum-resistant cases.

Secondary mutation in a coding mononucleotide tract in MSH6 causes loss of immunoexpression of MSH6 in colorectal carcinomas with MLH1/PMS2 deficiency.

PubMed

Shia, Jinru; Zhang, Liying; Shike, Moshe; Guo, Min; Stadler, Zsofia; Xiong, Xiaoling; Tang, Laura H; Vakiani, Efsevia; Katabi, Nora; Wang, Hangjun; Bacares, Ruben; Ruggeri, Jeanine; Boland, C Richard; Ladanyi, Marc; Klimstra, David S

2013-01-01

Immunohistochemical staining for DNA mismatch repair proteins may be affected by various biological and technical factors. Staining variations that could potentially lead to erroneous interpretations have been recognized. A recently recognized staining variation is the significant reduction of staining for MSH6 in some colorectal carcinomas. The frequency and specific characteristics of this aberrant MSH6 staining pattern, however, have not been well analyzed. In this study of 420 colorectal carcinoma samples obtained from patients fulfilling the Revised Bethesda Guidelines, we detected 9 tumors (2%) showing extremely limited staining for MSH6 with positive staining present in <5% of the tumor cells. Our analyses showed that these tumors belonged to two distinct categories: (1) MLH1 and/or PMS2 protein-deficient carcinomas (n=5, including 1 with a pathogenic mutation in PMS2); and (2) MLH1, PMS2 and MSH2 normal but with chemotherapy or chemoradiation therapy before surgery (n=4). To test our hypothesis that somatic mutation in the coding region microsatellite of the MSH6 gene might be a potential underlying mechanism for such limited MSH6 staining, we evaluated frameshift mutation in a (C)(8) tract in exon 5 of the MSH6 gene in seven tumors that had sufficient DNA for analysis, and detected mutation in four; all four tumors belonged to the MLH1/PMS2-deficient group. In conclusion, our data outline the main scenarios where significant reduction of MSH6 staining is more likely to occur in colorectal carcinoma, and suggest that somatic mutations of the coding region microsatellites of the MSH6 gene is an underlying mechanism for this staining phenomenon in MLH1/PMS2-deficient carcinomas.

The effect of low-dose experimental zearalenone intoxication on the immunoexpression of estrogen receptors in the ovaries of pre-pubertal bitches.

PubMed

Gajecka, M

2012-01-01

Zearalenone is an estrogenic mycotoxin that often contaminates plant material used in the production of feeds for companion animals. Small daily doses of ingested zearalenone--a competitive substrate modulating the activity of enzymes participating in estrogen biosynthesis at the pre-receptor level--can induce subclinical symptoms of hyperestrogenism in bitches. The objective of this study was to determine the effects of low zearalenone doses on the presence of estrogen receptors in the ovaries of pre-pubertal Beagle bitches. The bitches were divided into three groups of 10 animals each: experimental group I--50 microg zearalenone/kg body weight administered once daily per os; experimental group II--75 microg zearalenone/kg body weight administered once daily per os; control group--placebo containing no ZEN administered per os. The animals were ovariorectomized at the end of the experiment, at 112 days of age. Estrogen receptors were detected in ovarian specimens by immunohistochemical methods. The results revealed an absence of estrogen receptors alpha in all groups. In both experimental groups a decrease in the positive response of estrogen receptors beta in specified structures of ovaries was observed. Very low alpha-zearalenol levels probably attested to the slowing down (hypostimulation) of the biotransformation process. Overall, zearalenone intoxication led to hyperestrogenism during a specific developmental stage of pre-pubertal bitches. As regards hormesis, the threshold dose of zearalenone (adaptive capability) was exceeded in the ovaries of experimental group II animals. The results obtained in both experimental groups suggest that long-term exposure to low-dose zearalenone intoxication decreased the degree of estrogen receptors beta staining in particular structures of ovaries in the experimental bitches, which initiated epigenetic modification mechanisms that inhibited ovarian development.

Mating changes the subcellular distribution and the functionality of estrogen receptors in the rat oviduct

PubMed Central

2009-01-01

Background Mating changes the mode of action of 17beta-estradiol (E2) to accelerate oviductal egg transport from a nongenomic to a genomic mode, although in both pathways estrogen receptors (ER) are required. This change was designated as intracellular path shifting (IPS). Methods Herein, we examined the subcellular distribution of ESR1 and ESR2 (formerly known as ER-alpha and ER-beta) in oviductal epithelial cells of rats on day 1 of cycle (C1) or pregnancy (P1) using immunoelectron microscopy for ESR1 and ESR2. The effect of mating on intraoviductal ESR1 or ESR2 signaling was then explored comparing the expression of E2-target genes c-fos, brain creatine kinase (Ckb) and calbindin 9 kDa (s100g) in rats on C1 or P1 treated with selective agonists for ESR1 (PPT) or ESR2 (DPN). The effect of ER agonists on egg transport was also evaluated on C1 or P1 rats. Results Receptor immunoreactivity was associated with the nucleus, cytoplasm and plasma membrane of the epithelial cells. Mating affected the subcellular distribution of both receptors as well as the response to E2. In C1 and P1 rats, PPT increased Ckb while both agonists increased c-fos. DPN increased Ckb and s100g only in C1 and P1 rats, respectively. PPT accelerated egg transport in both groups and DPN accelerated egg transport only in C1 rats. Conclusion Estrogen receptors present a subcellular distribution compatible with E2 genomic and nongenomic signaling in the oviductal epithelial cells of C1 and P1 although IPS occurs independently of changes in the distribution of ESR1 and ESR2 in the oviductal epithelial cells. Mating affected intraoviductal ER-signaling and induced loss of functional involvement of ESR2 on E2-induced accelerated egg transport. These findings reveal a profound influence on the ER signaling pathways exerted by mating in the oviduct. PMID:19948032

Tamoxifen induces the expression of maspin through estrogen receptor-alpha.

PubMed

Liu, Zesheng; Shi, Heidi Y; Nawaz, Zafar; Zhang, Ming

2004-06-08

Maspin (mammary serine protease inhibitor) is a tumor suppressor gene that plays an important role in inhibiting tumor growth, invasion and metastasis. Maspin expression is down regulated at transcription level in primary and metastatic breast tumor cells. Previous studies on hormonal regulation of maspin prompt us to test whether an estrogen antagonist tamoxifen (TAM) can exert its anti-tumor function by up regulating maspin gene expression. For this purpose, we first tested whether maspin promoter could be activated in normal and several breast tumor cells. We then carried out a series of promoter analysis in which estrogen receptors and TAM were reconstituted in an in vitro cell culture system. Here we report our new finding that tumor suppresser gene maspin is one of the TAM target genes. TAM induces a maspin/luciferase reporter in cell culture and this induction requires the presence of (estrogen receptor alpha) ERalpha but not estrogen receptor-beta (ERbeta). Maspin promoter deletion and mutation analysis showed that the cis element(s) within a region between -90and+87 bp but not the HRE site (-272 bp) was involved in TAM induction of maspin expression. TAM bound ERalpha may directly control maspin gene expression through the interaction with cofactor (s). Analysis using several ERalpha mutants showed that the N-terminal A/B motif (AF-1) was critical for maspin basal level transcription activation. An ERalpha mutant with point mutations at DNA binding domain abolished estrogen induction of an ERE-luciferase reporter but was still active in activating maspin promoter by TAM. LBD-AF2 domain was required for ERalpha-dependent TAM induction. Deletion of LBD-AF2 or a point mutation in the ERalpha LBD-AF2 region (LBDmtL539A) completely abolished the activation of maspin promoter, suggesting that TAM induction of maspin involves the recruitment of cofactor(s) by ERalpha to the maspin promoter region. This finding indicates that one of the pathways for cancer prevention and tumor inhibition by TAM is mediated through the activation of tumor suppressor gene maspin in breast cancer.

Effects of ICI 182780 on estrogen receptor expression, fluid absorption and sperm motility in the epididymis of the bonnet monkey

PubMed Central

Shayu, Deshpande; Kesava, Chenna CS; Soundarajan, Rama; Rao, A Jagannadha

2005-01-01

Background The importance of estrogen in regulation of fluid absorption and sperm maturation in the rodent epididymis has been established from studies on estrogen receptor-alpha knockout mice. However, functional studies on the role of estrogen in primate epididymis have been few. The main objective of this study was therefore to extend these observations and systematically analyze the presence and function of estrogen receptors in modulating the function of the primate epididymis, using the bonnet monkey (Macaca radiata) as a model system. Methods A steroidal estrogen receptor (ER) antagonist, ICI 182780 (ICI), was administered to adult male bonnet monkeys via mini-osmotic pumps for a duration of 30 to 180 days. The expression of key estrogen-regulated genes (ER-alpha, Na-K ATPase alpha-1 and Aquaporin-1) was examined at specific time points. Further, the effect of ICI in modulating fluid reabsorption in efferent ductules was monitored, and critical sperm-maturation parameters were also analyzed. Results Our studies in the bonnet monkey revealed that both ER-alpha and ER-beta were expressed in all the three regions of the epididymis. We observed an increase in ER-alpha mRNA and protein in the caput of ICI-treated monkeys. Steady state mRNA levels of the water-channel protein, Aquaporin-1, was significantly lower in the caput of ICI-treated monkeys compared to controls, whereas the mRNA levels of Na-K ATPase alpha-1 remained unchanged. In vitro incubation of efferent ductules with ICI resulted in two-fold increase in tubular diameter, indicating affected fluid reabsorption capacity. Furthermore, sperm from ICI-treated monkeys were immotile. Conclusion Taken together, our results point to an integral role for estrogen in modulating the functions of the bonnet monkey epididymis. This study also demonstrates possible differences in the epididymal physiology of rodents and non-human primates, and thus underscores the significance of reports such as these, that examine the physiology of non-human primates (as opposed to rodents), in an attempt to understand similar events in the human. PMID:15743524

Effects of ICI 182780 on estrogen receptor expression, fluid absorption and sperm motility in the epididymis of the bonnet monkey.

PubMed

Shayu, Deshpande; ChennaKesava, C S; Soundarajan, Rama; Rao, A Jagannadha

2005-03-02

The importance of estrogen in regulation of fluid absorption and sperm maturation in the rodent epididymis has been established from studies on estrogen receptor-alpha knockout mice. However, functional studies on the role of estrogen in primate epididymis have been few. The main objective of this study was therefore to extend these observations and systematically analyze the presence and function of estrogen receptors in modulating the function of the primate epididymis, using the bonnet monkey (Macaca radiata) as a model system. A steroidal estrogen receptor (ER) antagonist, ICI 182780 (ICI), was administered to adult male bonnet monkeys via mini-osmotic pumps for a duration of 30 to 180 days. The expression of key estrogen-regulated genes (ER-alpha, Na-K ATPase alpha-1 and Aquaporin-1) was examined at specific time points. Further, the effect of ICI in modulating fluid reabsorption in efferent ductules was monitored, and critical sperm-maturation parameters were also analyzed. Our studies in the bonnet monkey revealed that both ER-alpha and ER-beta were expressed in all the three regions of the epididymis. We observed an increase in ER-alpha mRNA and protein in the caput of ICI-treated monkeys. Steady state mRNA levels of the water-channel protein, Aquaporin-1, was significantly lower in the caput of ICI-treated monkeys compared to controls, whereas the mRNA levels of Na-K ATPase alpha-1 remained unchanged. In vitro incubation of efferent ductules with ICI resulted in two-fold increase in tubular diameter, indicating affected fluid reabsorption capacity. Furthermore, sperm from ICI-treated monkeys were immotile. Taken together, our results point to an integral role for estrogen in modulating the functions of the bonnet monkey epididymis. This study also demonstrates possible differences in the epididymal physiology of rodents and non-human primates, and thus underscores the significance of reports such as these, that examine the physiology of non-human primates (as opposed to rodents), in an attempt to understand similar events in the human.

Effects of tributyltin (TBT) on in vitro hormonal and biotransformation responses in Atlantic salmon (Salmo salar).

PubMed

Mortensen, Anne S; Arukwe, Augustine

2009-01-01

The mechanisms by which the biocide tributyltin (TBT) and its metabolites affect the hormonal and xenobiotic biotransformation pathways in aquatic species are not well understood. In this study hepatocytes isolated from salmon were used to evaluate the mechanistical effects of TBT on fish hormonal and xenobiotic biotransformation pathways. Cells were exposed to 0.01, 0.1, 1, or 5 microM TBT and samples were collected at 0, 12, 24, or 48 h following exposure. Gene expression patterns were evaluated using quantitative polymerase chain reaction (PCR), and cytochrome P-450 (CYP)-mediated enzyme activities were evaluated by ethoxyresorufin, benzyloxyresorufin, and pentoxyresorufin O-deethylase (EROD, BROD, and PROD, respectively) activity assays. Generally, exposure of hepatocytes to 1 microM (at 48 h) and 5 microM TBT (at 12, 24, and 48 h) consistently produced reductions in all mRNA species investigated. TBT produced significant decreases of vitellogen (Vtg) expression at 48 h and modified the expression patterns of estrogen receptors (ERalpha and ERbeta) and androgen receptor-beta (ARbeta) that were dependent on time and TBT concentration. In the xenobiotic biotransformation pathway, TBT produced differential expression patterns that were dependent on exposure time and concentration for all salmonid AhR2 isoforms (AhR2alpha, AhR2beta, AhR2delta, and AhR2gamma). For CYP1A1, CYP3A, AhRR, and Arnt mRNA, TBT produced exposure- and time-specific modulations. Catalytic CYP activities showed that BROD activity increased in an apparent concentration-specific manner in cells exposed to TBT for 12 h. Interestingly, EROD activity showed a TBT concentration-dependent increase at 24 h and PROD at 12 and 48 h of exposure. In general our data show that TBT differentially modulated hormonal and biotransformation responses in the salmon in vitro system. The apparent and consistent decrease of the studied responses with time in 1 and 5 microM exposed hepatocytes suggest a possible transcription inhibitory effect of TBT.

Secretome profiling of oral squamous cell carcinoma-associated fibroblasts reveals organization and disassembly of extracellular matrix and collagen metabolic process signatures.

PubMed

Bagordakis, Elizabete; Sawazaki-Calone, Iris; Macedo, Carolina Carneiro Soares; Carnielli, Carolina M; de Oliveira, Carine Ervolino; Rodrigues, Priscila Campioni; Rangel, Ana Lucia C A; Dos Santos, Jean Nunes; Risteli, Juha; Graner, Edgard; Salo, Tuula; Paes Leme, Adriana Franco; Coletta, Ricardo D

2016-07-01

An important role has been attributed to cancer-associated fibroblasts (CAFs) in the tumorigenesis of oral squamous cell carcinoma (OSCC), the most common tumor of the oral cavity. Previous studies demonstrated that CAF-secreted molecules promote the proliferation and invasion of OSCC cells, inducing a more aggressive phenotype. In this study, we searched for differences in the secretome of CAFs and normal oral fibroblasts (NOF) using mass spectrometry-based proteomics and biological network analysis. Comparison of the secretome profiles revealed that upregulated proteins involved mainly in extracellular matrix organization and disassembly and collagen metabolism. Among the upregulated proteins were fibronectin type III domain-containing 1 (FNDC1), serpin peptidase inhibitor type 1 (SERPINE1), and stanniocalcin 2 (STC2), the upregulation of which was validated by quantitative PCR and ELISA in an independent set of CAF cell lines. The transition of transforming growth factor beta 1 (TGF-β1)-mediating NOFs into CAFs was accompanied by significant upregulation of FNDC1, SERPINE1, and STC2, confirming the participation of these proteins in the CAF-derived secretome. Type I collagen, the main constituent of the connective tissue, was also associated with several upregulated biological processes. The immunoexpression of type I collagen N-terminal propeptide (PINP) was significantly correlated in vivo with CAFs in the tumor front and was associated with significantly shortened survival of OSCC patients. Presence of CAFs in the tumor stroma was also an independent prognostic factor for OSCC disease-free survival. These results demonstrate the value of secretome profiling for evaluating the role of CAFs in the tumor microenvironment and identify potential novel therapeutic targets such as FNDC1, SERPINE1, and STC2. Furthermore, type I collagen expression by CAFs, represented by PINP levels, may be a prognostic marker of OSCC outcome.

Epithelial-type and neural-type cadherin expression in malignant noncarcinomatous neoplasms with epithelioid features that involve the soft tissues.

PubMed

Laskin, William B; Miettinen, Markku

2002-04-01

Transmembrane adhesion molecules, epithelial-type cadherin (ECAD) and neural-type cadherin (NCAD), help in regulating transformations between epithelial and mesenchymal cells in the developing embryo and in maintaining the epithelioid phenotype. Consequently, the presence of epithelioid cells in certain malignant noncarcinomatous neoplasms raises speculation that the expression of ECAD and NCAD in these neoplasms may have diagnostic significance. To investigate the utility of ECAD and NCAD immunoexpression in distinguishing malignant (noncarcinomatous) neoplasms with epithelioid features that involve the soft tissues. Membranous immunoreactivity of anti-ECAD and anti-NCAD was evaluated on archived cases selected from the files of the Armed Forces Institute of Pathology. Epithelial-type cadherin was found in biphasic synovial sarcoma (35 of 35 cases), malignant melanoma (13/21), monophasic fibrous synovial sarcoma (13/26), clear cell sarcoma (4/9), poorly differentiated synovial sarcoma (3/13), diffuse mesothelioma (4/20), malignant epithelioid peripheral nerve sheath tumor (1/6), and epithelioid sarcoma (5/62). Neural-type cadherin was observed in chordoma (11/11), biphasic synovial sarcoma (30/35), diffuse mesothelioma (14/20), malignant melanoma (14/25), epithelioid sarcoma (24/63), epithelioid angiosarcoma (1/4), poorly differentiated synovial sarcoma (2/13), clear cell sarcoma (1/10), and monophasic fibrous synovial sarcoma (1/26). Eighteen cases of primary cutaneous squamous cell carcinomas all tested positive for ECAD, whereas NCAD was focally observed in 5 cases. No expression of either molecule was observed in cases of epithelioid hemangioendothelioma (n = 9), alveolar soft part sarcoma (n = 8), and extraskeletal myxoid chondrosarcoma (n = 7). Epithelial-type and neural-type cadherins are found in a variety of noncarcinomatous neoplasms with epithelioid features that involve the soft tissues and can be utilized, in association with other immunomarkers, in distinguishing chordoma (100% NCAD) from extraskeletal myxoid chondrosarcoma and conventional chondrosarcoma of bone (0% NCAD), squamous cell carcinoma (100% ECAD) from epithelioid sarcoma (8% ECAD), and biphasic synovial sarcoma (100% ECAD) from diffuse mesothelioma (20% ECAD).

Dual effect of silymarin on experimental non-alcoholic steatohepatitis induced by irinotecan.

PubMed

Marcolino Assis-Júnior, Eudmar; Melo, Anielle Torres; Pereira, Venúcia Bruna Magalhães; Wong, Deysi Viviana Tenazoa; Sousa, Nathalia Ribeiro Pinho; Oliveira, Christiane Mendes Gonçalves; Malveira, Lara Raissa Cavalcante; Moreira, Leonardo Silva; Souza, Marcellus Henrique Loiola Ponte; Almeida, Paulo Roberto Carvalho; Lima-Júnior, Roberto César Pereira

2017-07-15

Irinotecan-based regimens are commonly used for treatment of colorectal cancer, which is limited by mucositis and non-alcoholic steatohepatitis (NASH). Silymarin (SIL) prevents fatty liver disease in the clinical setting and in models of liver damage induced chemically. This study investigated the possible effect of SIL on irinotecan (IRI)-induced NASH. Swiss female mice were injected with saline (SAL 5ml/kg i.p.), IRI (50mg/kg i.p.), SIL (150mg/kg p.o.) or IRI (50mg/kg i.p.)+(SIL 1.5, 15 or 150mg/kg p.o.) thrice/week/7weeks. On the seventh week, blood samples were collected for transaminases assay and livers were collected for histopathology, measurement of the total lipids, malondyadehyde (MDA), non-protein sulfhydryl groups (NPSH), cytokines (IL-1β, IL 6 and IL-10), 3-nitrotyrosine (N-Tyr) and toll-like receptor 4 (TLR4) immunoexpression, quantification of NF-kB, α-smooth muscle actin (α-SMA), and Escherichia coli 16S rRNA gene (RRS) expression. IRI increased liver transaminases, neutrophil infiltration, lipid accumulation, MDA, IL-1β and IL-6 levels, N-Tyr and TLR4 immunostaining, NF-kB, α-SMA expression and RRS versus the SAL group (p<0.05). Additionally, SIL (1.5mg/kg) improved these parameters (p<0.05), except neutrophil infiltration and RSS versus the IRI group. Furthermore, the SIL (15mg/kg) only improved the inflammatory parameters, the expression of α-SMA and RRS versus the IRI group (p<0.05). The higher dose of SIL (150mg/kg) was even more deleterious than the intermediate dose. Therefore, silymarin showed a dual effect on liver damage induced by IRI. Hepatoprotection seems to involve the inhibition of oxidative stress and protein nitrosylation, preventing activation of hepatic fibrosis mechanisms. Copyright © 2017 Elsevier Inc. All rights reserved.

Glycogen metabolism in brain and neurons - astrocytes metabolic cooperation can be altered by pre- and neonatal lead (Pb) exposure.

PubMed

Baranowska-Bosiacka, Irena; Falkowska, Anna; Gutowska, Izabela; Gąssowska, Magdalena; Kolasa-Wołosiuk, Agnieszka; Tarnowski, Maciej; Chibowska, Karina; Goschorska, Marta; Lubkowska, Anna; Chlubek, Dariusz

2017-09-01

Lead (Pb) is an environmental neurotoxin which particularly affects the developing brain but the molecular mechanism of its neurotoxicity still needs clarification. The aim of this paper was to examine whether pre- and neonatal exposure to Pb (concentration of Pb in rat offspring blood below the "threshold level") may affect the brain's energy metabolism in neurons and astrocytes via the amount of available glycogen. We investigated the glycogen concentration in the brain, as well as the expression of the key enzymes involved in glycogen metabolism in brain: glycogen synthase 1 (Gys1), glycogen phosphorylase (PYGM, an isoform active in astrocytes; and PYGB, an isoform active in neurons) and phosphorylase kinase β (PHKB). Moreover, the expression of connexin 43 (Cx43) was evaluated to analyze whether Pb poisoning during the early phase of life may affect the neuron-astrocytes' metabolic cooperation. This work shows for the first time that exposure to Pb in early life can impair brain energy metabolism by reducing the amount of glycogen and decreasing the rate of its metabolism. This reduction in brain glycogen level was accompanied by a decrease in Gys1 expression. We noted a reduction in the immunoreactivity and the gene expression of both PYGB and PYGM isoform, as well as an increase in the expression of PHKB in Pb-treated rats. Moreover, exposure to Pb induced decrease in connexin 43 immunoexpression in all the brain structures analyzed, both in astrocytes as well as in neurons. Our data suggests that exposure to Pb in the pre- and neonatal periods results in a decrease in the level of brain glycogen and a reduction in the rate of its metabolism, thereby reducing glucose availability, which as a further consequence may lead to the impairment of brain energy metabolism and the metabolic cooperation between neurons and astrocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

Immuno- and gene expression analysis of EGFR and Nestin during mice skin development.

PubMed

Falodah, Fawaz Adnan; Al-Karim, Saleh

2016-06-01

Skin stem cell populations reside in the adult hair follicle, sebaceous gland, dermis and epidermis. However, the origin of most of the stem cell populations found in the adult epidermis is still unknown. Far more unknown is the embryonic origin of other stem cells that populate the other layers of this tissue. The main objectives of the present study were to identify the precise anatomical localization of stem cells in mice during skin developing; and to determine the expression levels by using immuno- and gene expression analysis. In this comparative cross sectional study, six ages been chosen and divided into: embryonic days (E12.5, E14.5 and E19.5) and litter days (L7, L14 and L19). Skin were removed from the back side and processed to assess both immuno- and gene-expression of EGFR and Nestin surface antigen markers. Data of the different studied age groups was compared using the SPSS software. EGFR was mainly expressed in the outer root sheath (ORS), in basal and, to a lesser extent, in suprabasal keratinocytes and tend to lie where the dermis comes closest to the skin surface, while Nestin expressed throughout the dermis in the early embryo, but it is subsequently restricted to the follicular connective tissue sheaths later in development and to hair follicles after birth. Immunoexpression analysis showed a strong EGFR expression in all group ages except E12.5 which recorded as moderate, while Nestin showed strong expression level for all embryonic stages, while in the litters it was moderate. The qRT-PCR results were consistent with those of the immunohistochemical study. The Pearson correlation analyze present a correlation between the cases of study with age (p≤0.01), which indicated to the effect of age to mice development. EGFR and Nestin showed to have vital role during mice development, and considered to be suitable markers for the study of skin stem cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immunohistochemical study of Ki67, CD34 and p53 expression in human tooth buds.

PubMed

Muica Nagy-Bota, Monica Cristina; Pap, Zsuzsanna; Denes, Lóránd; Ghizdavăţ, Alexandru; Brînzaniuc, Klara; Lup Coşarcă, Adina Simona; Chibelean Cireş-Mărginean, Manuela; Păcurar, Mariana; Pávai, Zoltán

2014-01-01

Establishment of Ki67, p53 and CD34 expression in human tooth buds of different stages of odontogenetic development. Tissue samples containing tooth buds were removed from the incisor areas of human fetuses in different stages of development (weeks 9-10, 12-13, 13-16, 21-24), and from the canine and molar areas of 21-24 weeks fetuses. The tissue fragments were fixed using formalin and were processed using common histological techniques with paraffin embedding. Immunostaining for Ki67, p53 and CD34 has been performed using the dextran method and moist heat antigen retrieval (except for CD34). The resulting slides were photographed and quantitatively evaluated. Ki67 immunoexpression decreases with advancement of the developmental stage of the tooth bud: in the inner enamel epithelium, between weeks 9 and 16 (IEE), in the preameloblasts (PB) between weeks 13 and 16, in the ameloblasts (AB) between weeks 21 and 24; outer enamel epithelium (OEE); stratum intermedium (SI); in the dental papilla: between weeks 9 and 10 in the dental papilla (DP), between weeks 13 and 16 in the outer layer of the dental papilla (DP1) and in the central layer of the dental papilla (DP2). Likewise, we noted Ki67 expression in the odontoblast layer (O) and pulp (P), between weeks 21 and 24. Concerning CD34 expression, we observed a decrease from weeks 9-10 until weeks 13-16, followed by an increase until weeks 21-24 of intrauterine life. From weeks 9-10, we observed a constant decrease of expression until weeks 13-16, followed by an increase during weeks 21-24. All Ki67, p53 and CD34 have been identified in the tooth bud. Ki67 expression gradually decreases with the embryonic development of the tooth, while p53 and CD34 expression decreases from weeks 9-10 to weeks 13-16 of intrauterine life, followed by an increase until weeks 21-24.

Detection of lymphovascular invasion by D2-40 (podoplanin) immunoexpression in endometrial cancer.

PubMed

Weber, Sarah K; Sauerwald, Axel; Pölcher, Martin; Braun, Michael; Debald, Manuel; Serce, Nuran Bektas; Kuhn, Walther; Brunagel-Walgenbach, Giesela; Rudlowski, Christian

2012-10-01

Lymph node involvement is a major feature in tumor spread of endometrial cancer and predicts prognosis. Therefore, evaluation of lymph vessel invasion (LVI) in tumor tissue as a predictor for lymph node metastasis is of great importance. Immunostaining of D2-40 (podoplanin), a specific marker for lymphatic endothelial cells, might be able to increase the detection rate of LVI compared with conventional hematoxylin-eosin (H-E) staining. The aim of this retrospective study was to analyze the eligibility of D2-40-based LVI evaluation for the prediction of lymph node metastases and patients' outcome. Immunohistochemical staining with D2-40 monoclonal antibodies was performed on paraffin-embedded tissue sections of 182 patients with primary endometrioid adenocarcinoma treated in 1 gynecologic cancer center. Tumors were screened for the presence of LVI. Correlations with clinicopathological features and clinical outcome were assessed. Immunostaining of D2-40 significantly increased the frequency LVI detection compared with conventional H-E staining. Lymph vessel invasion was identified by D2-40 in 53 (29.1%) of 182 tumors compared with 34 (18.3%) of 182 carcinomas by routine H-E staining (P = 0.001). D2-40 LVI was detectable in 81.0% (17/21) of nodal-positive tumors and significantly predicted lymph node metastasis (P = 0.001). Furthermore, D2-40 LVI was an independent prognostic factor for patients overall survival considering tumor stage, lymph node involvement, and tumor differentiation (P < 0.01). D2-40-negative tumors confined to the inner half of the myometrium showed an excellent outcome (5-year overall survival, 97.8%). D2-40-based LVI assessment improves the histopathological detection of lymphovascular invasion in endometrial cancer. Furthermore, LVI is of prognostic value and predicts lymph node metastasis. D2-40 LVI detection might help to select endometrial cancer patients who will benefit from a lymphadenectomy.

Analysis of HER2 status in breast carcinoma by fully automated HER2 fluorescence in situ hybridization (FISH): comparison of two immunohistochemical tests and manual FISH.

PubMed

Yoon, Nara; Do, In-Gu; Cho, Eun Yoon

2014-09-01

Easy and accurate HER2 testing is essential when considering the prognostic and predictive significance of HER2 in breast cancer. The use of a fully automated, quantitative FISH assay would be helpful to detect HER2 amplification in breast cancer tissue specimens with reduced inter-laboratory variability. We compared the concordance of HER2 status as assessed by an automated FISH staining system to manual FISH testing. Using 60 formalin-fixed paraffin-embedded breast carcinoma specimens, we assessed HER2 immunoexpression with two antibodies (DAKO HercepTest and CB11). In addition, HER2 status was evaluated with automated FISH using the Leica FISH System for BOND and a manual FISH using the Abbott PathVysion DNA Probe Kit. All but one specimen were successfully stained using both FISH methods. When the data were divided into two groups according to HER2/CEP17 ratio, positive and negative, the results from both the automated and manual FISH techniques were identical for all 59 evaluable specimens. The HER2 and CEP17 copy numbers and HER2/CEP17 ratio showed great agreement between both FISH methods. The automated FISH technique was interpretable with signal intensity similar to those of the manual FISH technique. In contrast with manual FISH, the automated FISH technique showed well-preserved architecture due to low membrane digestion. HER2 immunohistochemistry and FISH results showed substantial significant agreement (κ = 1.0, p < 0.001). HER2 status can be reliably determined using a fully automated HER2 FISH system with high concordance to the well-established manual FISH method. Because of stable signal intensity and high staining quality, the automated FISH technique may be more appropriate than manual FISH for routine applications. © 2013 APMIS. Published by John Wiley & Sons Ltd.

Investigation of c-KIT and Ki67 expression in normal, preneoplastic and neoplastic canine prostate.

PubMed

Fonseca-Alves, Carlos Eduardo; Kobayashi, Priscilla Emiko; Palmieri, Chiara; Laufer-Amorim, Renée

2017-12-06

c-KIT expression has been related to bone metastasis in human prostate cancer, but whether c-KIT expression can be similarly classified in canine prostatic tissue is unknown. This study assessed c-KIT and Ki67 expression in canine prostate cancer (PC). c-KIT gene and protein expression and Ki67 expression were evaluated in forty-four canine prostatic tissues by immunohistochemistry, RT-qPCR and western blot. Additionally, we have investigated c-KIT protein expression by immunoblotting in two primary canine prostate cancer cell lines. Eleven normal prostates, 12 proliferative inflammatory atrophy (PIA) prostates, 18 PC, 3 metastatic lesions and two prostate cancer cell cultures (PC1 and PC2) were analysed. The prostatic tissue exhibited varying degrees of membranous, cytoplasmic or membranous/cytoplasmic c-KIT staining. Four normal prostates, 4 PIA and 5 prostatic carcinomas showed positive c-KIT expression. No c-KIT immunoexpression was observed in metastases. Canine prostate cancer and PIA samples contained a higher number of Ki67-positive cells compared to normal samples. The median relative quantification (RQ) for c-KIT expression in normal, PIA and prostate cancer and metastatic samples were 0.6 (0.1-2.5), 0.7 (0.09-2.1), 0.7 (0.09-5.1) and 0.1 (0.07-0.6), respectively. A positive correlation between the number of Ki67-positive cells and c-KIT transcript levels was observed in prostate cancer samples. In the cell line, PC1 was negative for c-KIT protein expression, while PC2 was weakly positive. The present study identified a strong correlation between c-KIT expression and proliferative index, suggesting that c-KIT may influence cell proliferation. Therefore, c-KIT heterogeneous protein expression among the samples (five positive and thirteen negative prostate cancer samples) indicates a personalized approach for canine prostate cancer.

Immunohistochemical Analysis of Galectins-1, -3, and -7 in Periapical Granulomas, Radicular Cysts, and Residual Radicular Cysts.

PubMed

Brito, Lívia Natália Sales; de Lemos Almeida, Maria Manuela Rodrigues; de Souza, Lélia Batista; Alves, Pollianna Muniz; Nonaka, Cassiano Francisco Weege; Godoy, Gustavo Pina

2018-05-01

Galectins play important roles in immunoinflammatory responses, but their participation in the development of periapical lesions remains unclear. This study aimed to evaluate the expressions of galectins-1, -3, and -7 in periapical lesions, correlating them with the intensity of the inflammatory infiltrate and the pattern of the cystic epithelium. Twenty periapical granulomas (PGs), 20 radicular cysts (RCs), and 20 residual radicular cysts (RRCs) were submitted to immunohistochemistry using anti-galectin-1, -3, and -7 antibodies. The percentage of immunopositive cells in epithelial and connective tissues was determined. In connective tissue, PGs exhibited higher cytoplasmic/membrane expression of galectins-1 and -7 than RCs and RRCs (P < .05). There was higher nuclear expression of galectin-1 in PGs compared with RCs and RRCs (P < .05). The expression of galectins-1 and -7 in connective tissue was higher in lesions with grade III inflammation (P < .05). No significant differences in galectin-3 immunoexpression were observed for any of the parameters evaluated (P > .05). In the epithelial component, a higher nuclear expression of galectin-7 was detected in RRCs (P < .05), and a higher cytoplasmic/membrane expression of this protein was found in cysts with hyperplastic epithelium (P < .05). Positive correlations were observed between the nuclear and cytoplasmic/membrane expression of galectin-1 in connective tissue (P < .05) as well as between the nuclear and cytoplasmic/membrane expression of galectin-7 in epithelial tissue of cysts (P < .05). Galectins-1 and -7 may play important roles in the pathogenesis of PGs, RCs, and RRCs. On the other hand, the present results suggest only a minor involvement of galectin-3 in the development of these lesions. Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

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.

Upregulation of estrogen receptor expression in the uterus of ovariectomized B6C3F1 mice and Ishikawa cells treated with bromoethane

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

Aoyama, Hiroaki; Couse, John F.; Hewitt, Sylvia C.

2005-12-15

In a 2-year NTP bioassay, Bromoethane (BE) was found to induce endometrial neoplasms in the uterus of B6C3F1 mice [; ]. In women, hormonal influences, such as 'unopposed' estrogenic stimulus, have been implicated as important etiologic factors in uterine cancer. BE, however, does not affect the serum concentrations of sex hormones in female B6C3F1 mice [] and the mechanism of BE-induced uterine carcinogenesis still remains unclear. In the present study, we examined the estrogenic effects of BE on the uterus of ovariectomized B6C3F1 mice and on Ishikawa cells. Groups of 6 mice were given daily s.c. injections of 0, 100,more » 500 or 1000 mg BE/kg for 3 consecutive days. Mice treated with 17{beta}-estradiol served as positive controls. Mice were necropsied 24 h after the final injection, and uteri were weighed and examined histologically and immunohistochemically along with the vagina. Changes observed in the estrogen-treated mice included increased uterine weights, edema and inflammation of the endometrium, increased epithelial layers of the uterine and vaginal lumens and keratinization of the vaginal epithelium. In the BE-treated mice, no such changes occurred; however, immunohistochemical staining of the uterus revealed a significant increase in immunoexpression of the estrogen receptor alpha (ER{alpha}) in the two higher dose groups. Analysis of mRNA also showed slightly increased uterine ER{alpha} expression in these groups. Upregulated expression of ER{alpha} was confirmed in BE-treated Ishikawa cells, in which Western blotting analyses identified an intense signal at approximately 66 kDa, which is consistent with ER{alpha}. These data suggest that upregulated expression of ER{alpha} may be important in the induction of endometrial neoplasms in BE-treated mice.« less

Modulation of xenobiotic biotransformation system and hormonal responses in Atlantic salmon (Salmo salar) after exposure to tributyltin (TBT).

PubMed

Mortensen, Anne Skjetne; Arukwe, Augustine

2007-04-01

Multiple biological effects of tributyltin (TBT) on juvenile salmon have been investigated. Fish were exposed for 7 days to waterborne TBT at nominal concentrations of 50 and 250 microg/L dissolved in dimethyl sulfoxide (DMSO). Hepatic samples were analyzed for gene expression patterns in the hormonal and xenobiotic biotransformation pathways using validated real-time PCR method. Immunochemical and several cytochrome P450 (CYP)-mediated enzyme activity (ethoxyresorufin: EROD, benzyloxyresorufin: BROD, methoxyresorufin: MROD and pentoxyresorufin: PROD) assays were analyzed. Our data show that TBT produced concentration-specific decrease of estrogen receptor-alpha (ERalpha), vitellogenin (Vtg), zona radiata protein (Zr-protein) and increase of estrogen receptor-beta (ERbeta) and androgen receptor-beta (ARbeta) in the hormonal pathway. In the xenobiotic biotransformation pathway, TBT produced apparent increase and decrease at respective low and high concentration, on aryl hydrocarbon receptor-alpha (AhRalpha), AhR nuclear translocator (ARNT) and AhR repressor (AhRR) mRNA. The expression of CYP1A1 and GST showed a TBT concentration-dependent decrease. The AhRbeta, CYP3A and uridine diphosphoglucuronosyl transferase (UGT) mRNA expressions were significantly induced after exposure to TBT. Immunochemical analysis of CYP3A and CYP1A1 protein levels confirmed the TBT effects observed at the transcriptional levels. The effect of TBT on the biotransformation enzyme gene expressions partially co-related but did not directly parallel enzyme activity levels for EROD, BROD, MROD and PROD. In general, these findings confirm previous reports on the endocrine effects of TBT, in addition to effects on hepatic CYP1A isoenzyme at the transcriptional level that transcends to protein and enzymatic levels. The induced expression patterns of CYP3A and UGT mRNA after TBT exposure, suggest the involvement of CYP3A and UGT in TBT metabolism in fish. The effect of TBT on CYP3A is proposed to represent another hormonal effect of TBT not previously reported in any fish or lower vertebrate. The proposed androgenic effect is supported by the observation that TBT also induced ARbeta mRNA expression in a concentration-specific manner. To our knowledge, this is the first study that has simultaneously studied multiple responses after exposure to TBT in fish.

Prognostic scores after surgical treatment for cervical intraepithelial neoplasia: a proposed model and possible implications for post-operative follow-up.

PubMed

Andrade, Carlos E M C; Scapulatempo-Neto, Cristovam; Longatto-Filho, Adhemar; Vieira, Marcelo A; Tsunoda, Audrey T; Da Silva, Ismael D C G; Fregnani, José Humberto T G

2014-09-01

To develop a prognostic model for women who underwent surgical treatment for cervical intraepithelial neoplasia. Cohort study. Patient inclusion and follow-up occurred retrospectively and prospectively. Barretos Cancer Hospital, Barretos, São Paulo, Brazil. Women (n = 242) diagnosed with cervical intraepithelial neoplasia who were submitted to conization. Immediately prior to surgical treatment, a cervical cytology sample was collected from each individual included in the study by endocervical brushing and stored in a preservative solution with methanol. A human papilloma virus-DNA test was conducted using an aliquot of the endocervical brushings. The surgical specimens were subjected to immunohistochemical analysis of p16 (immunohistochemical analysis 4a) protein expression. Two-year disease-free survival rates calculated for each study variable. Identified variables in the multivariate Cox model were used for elaboration of prognostic scores. Variables associated with outcome included age (p = 0.033), tobacco use (p < 0.001), final histopathological diagnosis (p = 0.007), surgical margins (p < 0.001), high-risk human papilloma virus status (p = 0.008), human papilloma virus-16 status (p < 0.001) and immunoexpression of p16 in the cytoplasm (p = 0.049). By the Cox model, independent risk factors for disease recurrence/persistence were: tobacco use (hazard risk = 3.0; 95% confidence interval 1.6-5.6), positive surgical margins (hazard risk = 3.2; 95% confidence interval 1.6-6.1), human papilloma virus-16 (hazard risk = 3.3; 95% confidence interval 1.6-6.9) and age over 45 years (hazard risk = 2.7; 95% confidence interval 1.1-6.6). Establishment of a prognostic score can represent a valuable tool for determining the risk of cervical intraepithelial neoplasia recurrence after conization. The use of clinical (age and tobacco use), pathological (surgical margins) and molecular (human papilloma virus-16 genotyping) factors can facilitate more appropriate patient follow up according to risk stratification. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Ghrelin and obestatin in thyroid gland - immunohistochemical expression in nodular goiter, papillary and medullary cancer.

PubMed

Gurgul, Edyta; Kasprzak, Aldona; Blaszczyk, Agata; Biczysko, Maciej; Surdyk-Zasada, Joanna; Seraszek-Jaros, Agnieszka; Ruchala, Marek

2015-01-01

Previous studies analyzing ghrelin and obestatin expression in thyroid gland tissue are not unanimous and are mostly related to ghrelin. The role of ghrelin and obestatin in the thyroid gland appears very interesting due to their probable involvement in cell proliferation. Furthermore, since the thyroid gland is associated with the maintenance of energy balance, the relationship between ghrelin, obestatin and thyroid function is worthy of consideration. The aim of the study was to assess ghrelin and obestatin immunocytochemical expression in nodular goiter (NG), papillary cancer (PTC) and medullary cancer (MTC). Analyzed samples included 9 cases of NG, 8 cases of PTC and 11 cases of MTC. The analysis of ghrelin and obestatin expression was performed by use of the immunohistochemical (IHC) EnVision system and evaluated with filter HSV software (quantitative morphometric analysis). Quantitative ghrelin expression in MTC cells was higher than in NG (p = 0.013) and correlated negatively with the size of the tumor (r= -0.829, p < 0.05). We did not observe any differences in ghrelin expression neither between MTC and PTC nor between NG and PTC. Obestatin immunoexpression pattern in all analyzed specimens was irregular and poorly accented. The strongest immunoreactivity for obestatin was demonstrated in NG. In MTC obestatin expression was significantly weaker than in NG and PTC (p < 0.05 in both cases). In NG the intensity of obestatin immunostaining was significantly higher than that of ghrelin (p = 0.03). Conversely, ghrelin expression in MTC was definitely more evident than obestatin immunoreactivity (p < 0.01). There was no statistically significant difference between ghrelin and obestatin expression in PTC. No correlations were detected between reciprocal tissue expressions of ghrelin and obestatin in the analyzed specimens of NG, PTC or MTC. The differences between ghrelin expression in NG and MTC suggest that ghrelin may be involved in thyroid cell proliferation. The differences between ghrelin and obestatin immunoreactivity in benign and malignant thyroid tumors could support the theory of alternative transcription of the preproghrelin gene and independent production of ghrelin and obestatin.

Incorporation of p-53 mutation status and Ki-67 proliferating index in classifying Her2-neu positive gastric adenocarcinoma.

PubMed

Ahmed, Ayesha; Al-Tamimi, Dalal M

2018-12-01

Her2-neu overexpression has a pathogenetic, therapeutic and a controversial prognostic role in gastric cancer. p-53 mutation status and Ki-67 proliferation index are established prognostic markers in many tumors. In this study we evaluated p-53 and Ki-67 in relation to Her2-neu positive and negative gastric adenocarcinoma (GA). This cross-sectional study was carried out at King Fahd Hospital of Imam Abdulrahman bin Faisal University. Fifty cases of GA were retrieved from pathology archives. Clinico-pathological parameters were evaluated. Immunohistochemical protein analysis for Her2-neu, Ki-67 and p-53 was carried out. Fluorescent in situ hybridization (FISH) analysis was done for Her2-neu positive cases showing 2+ immunoexpression. Frequency of Ki-67 and p-53 positivity in Her2-neu positive cases was calculated and compared with those in Her2-neu negative cases. Correlation of clinicopatological parameters with Her2 positive and negative cases, p-53 mutation status and Ki-67 proliferation index was carried out. Her2-neu overexpression was present in 12% (n = 6) cases. A high Ki-67 was seen predominantly in Her2-neu positive cases (83%, n = 5). Her2-neu negative cases (n = 44) showed moderate (31.88%, n = 14) to low (34%, n = 15) Ki-67. Diffuse p-53 positivity was seen predominantly in Her2-neu positive cases (33.33%, n = 2). Focal p-53 was seen mainly in Her2-neu negative cases 56.8% (n = 25). Negative p-53 was seen to be independent of Her2-neu status. Her2-neu positivity is strongly associated with diffuse p-53 mutation status and high Ki-67 proliferation. Her 2-neu negative status is associated with focal p-53 positivity and low to moderate Ki-67 proliferation index. Such stratifications in prognostic markers could not only be predictive in patient's prognostics but could also form a basis of molecular classification of gastric cancer.

Comparative histological and immunohistochemical study of ameloblastomas and ameloblastic carcinomas

PubMed Central

Mosqueda-Taylor, Adalberto; Carlos-Bregni, Román; Pires, Fabio-Ramoa; Delgado-Azañero, Wilson; Neves-Silva, Rodrigo; Aldape-Barrios, Beatriz; Paes-de Almeida, Oslei

2017-01-01

Background This study aimed to compare the histological and immunohistochemical characteristics of ameloblastomas (AM) and ameloblastic carcinomas (AC). Material and Methods Fifteen cases of AM and 9 AC were submitted to hematoxilin and eosin (H&E) and immunohistochemical analysis with the following antibodies: cytokeratins 5,7,8,14 and 19, Ki-67, p53, p63 and the cellular adhesion molecules CD138 (Syndecan-1), E-cadherin and β-catenin. The mean score of the expression of Ki-67 and p53 labelling index (LIs) were compared between the groups using the t test. A value of p<0.05 was considered to be statistically significant. Results All cases were positive for CKs 5, 14 and 19, but negative for CKs 7 and 8. CKs 5 and 19 were positive mainly in the central regions of the ameloblastic islands, while the expression in AC was variable in intensity and localization. CK14 was also variably expressed in both AM and AC. Ki-67 (P=.001) and p53 (P=.004) immunoexpression was higher in AC. All cases were positive for p63, but values were higher in AC. CD138 was mainly expressed in peripheral cells of AM, with a weak positivity in the central areas, while it was positive in most areas of ACs, except in less differentiated regions, where expression was decreased or lost. E-cadherin and β-catenin were weakly positive in both AM and AC. Conclusions These results shows that Ki-67, p53 and p63 expression was higher in AC as compared to AM, suggesting that these markers can be useful when considering diagnosis of malignancy, and perhaps could play a role in malignant transformation of AM. Pattern of expression of CKs 5 and 19 in AC were different to those found in AM, suggesting genetic alterations of these proteins in malignant cells. It was confirmed that CK19 is a good marker for benign odontogenic tumors, such as AM, but it is variably expressed in malignant cases. Key words:Ameloblastoma, ameloblastic carcinoma, immunohistochemistry, odontogenic tumors. PMID:28390135

Determination of BRAF V600E (VE1) protein expression and BRAF gene mutation status in codon 600 in borderline and low-grade ovarian cancers.

PubMed

Sadlecki, Pawel; Walentowicz, Pawel; Bodnar, Magdalena; Marszalek, Andrzej; Grabiec, Marek; Walentowicz-Sadlecka, Malgorzata

2017-05-01

Epithelial ovarian tumors are a group of morphologically and genetically heterogeneous neoplasms. Based on differences in clinical phenotype and genetic background, ovarian neoplasms are classified as low-grade and high-grade tumor. Borderline ovarian tumors represent approximately 10%-20% of all epithelial ovarian masses. Various histological subtypes of ovarian malignancies differ in terms of their risk factor profiles, precursor lesions, clinical course, patterns of spread, molecular genetics, response to conventional chemotherapy, and prognosis. The most frequent genetic aberrations found in low-grade serous ovarian carcinomas and serous borderline tumors, as well as in mucinous cancers, are mutations in BRAF and KRAS genes. The most commonly observed BRAF mutation is substitution of glutamic acid for valine in codon 600 (V600E) in exon 15. The primary aim of this study was to determine whether fully integrated, real-time polymerase chain reaction-based Idylla™ system may be useful in determination of BRAF gene mutation status in codon 600 in patients with borderline ovarian tumors and low-grade ovarian carcinomas. The study included tissue specimens from 42 patients with histopathologically verified ovarian masses, who were operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz (Poland). Based on histopathological examination of surgical specimens, 35 lesions were classified as low-grade ovarian carcinomas, and 7 as borderline ovarian tumors. Specimens with expression of BRAF V600E (VE1) protein were tested for mutations in codon 600 of the BRAF gene, using an automated molecular diagnostics platform Idylla™. Cytoplasmic immunoexpression of BRAF V600E (VE1) protein was found in three specimens: serous superficial papilloma, serous papillary cystadenoma of borderline malignancy, and partially proliferative serous cystadenoma. All specimens with the expression of BRAF V600E (VE1) protein were tested positively for BRAF V600E/E2/D mutation. No statistically significant relationship (p > 0.05) was found between the presence of BRAF V600E mutation and the probability of 5-year survival. BRAF mutation testing with a rapid, fully integrated molecular diagnostics system Idylla™ may be also a powerful prognostic tool in subjects with newly diagnosed serous borderline tumors, identifying a subset of patients who are unlikely to progress.

Cyclin D1 is significantly associated with stage of tumor and predicts poor survival in endometrial carcinoma patients.

PubMed

Khabaz, Mohamad Nidal; Abdelrahman, Amer Shafie; Butt, Nadeem Shafique; Al-Maghrabi, Basim; Al-Maghrabi, Jaudah

2017-10-01

Cyclin D1 overexpression has been described to have oncogenic role and association with diagnosis, prognosis and survival in various tumors. This study will describe the immunohistochemical phenotype of cyclin D1, and investigate the correlation between these patterns of expression and clinicopathological parameters of endometrial carcinomas, to conclude the clinical relevance of cyclin D1 expression in the evolution of endometrial neoplasms. This study employed 101 endometrial tissue samples which include 71 endometrial carcinomas and thirty normal and benign endometrium cases. All these tissue samples were used in the assembly of tissue microarrays which have been utilized afterward in immunohistochemistry staining to detect cyclin D1 expression. Forty (56.3%) cases of endometrial carcinomas showed brown nuclear expression of cyclin D1 including 36 (61%) cases of endometrioid carcinomas, and 3 (33.3%) cases of serous carcinomas. Twenty three (76.6%) cases of control group demonstrated nuclear expression. High score cyclin D1 immunohistochemical staining has been significantly linked with patient age (P=0.0001). Large proportion of high score cyclin D1 immunohistochemical staining was observed in females who are <40years of age while high proportions of negative staining were observed in older age groups. Histologic type of tissue was also significantly related to cyclin D1 immunohistochemical staining (P-value=0.0001), high staining is more common in normal proliferative and secretory endometrium while serous carcinoma is more prevalent with negative staining. Stage of tumor was significantly associated with cyclin D1 immunohistochemical staining (P-value=0.029), proportion of stage III and IV are higher in negative cyclin D1 immunostaining. Significantly higher proportion of high score cyclin D1 immunostaining is observed in controls while higher proportion of negative cyclin D1 immunostaining is observed among carcinoma cases (P-value=0.0001). No significant associations between cyclin D1 immunohistochemical staining and grade, recurrence and alive status were observed. Significant different survival distributions were observed (P-value=0.011) and poor survival behavior was correlated with negative cyclin D1 immunohistochemical staining. In conclusion, greater frequency of cyclin D1 expression was revealed in normal endometrial tissues in comparison with carcinomas. The distribution pattern of cyclin D1 immunoexpression suggests poor prognoses in endometrial carcinoma patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Expression of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and topoisomerase IIα) in borderline ovarian tumors: Correlation with clinicopathological features.

PubMed

Ciepliński, Klaudiusz; Jóźwik, Maciej; Semczuk-Sikora, Anna; Gogacz, Marek; Lewkowicz, Dorota; Ignatov, Atanas; Semczuk, Andrzej

2018-02-01

The expression of p53 has been studied not only in primary human ovarian carcinomas, but also in borderline ovarian tumors, however, the results were discordant. Expression patterns of proteins involved in cell proliferation and apoptosis have been investigated in various human neoplasms, including female genital tract neoplasms. The aim of this investigation was to assess the staining pattern and immunolocalization of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and topoisomerase IIα) in borderline ovarian tumors (BOTs). The study group consisted of 42 women who underwent pelvic surgery between 2006-2015. The median patients' age was 46 years. The immunoperoxidase technique was employed using antibodies against p53, Ki-67, MCM3, PCNA, and topoisomerase IIα. For p53, nuclear expression was observed in BOTs, however, cytoplasmatic immunoreactivity was also detected. Altogether, 25 (60%) tumors demonstrated positive p53 immunostaining, including overexpression found in 6 (14%). There were no significant differences in p53 expression between subgroups of clinicopathological variables. Immunoexpression of Ki-67, MCM3, PCNA, and topoisomerase IIα was nuclear. Ki-67 expression was positive in 12 (29%) cases and there was a trend towards a relationship between patients' age and Ki-67 staining (P=0.08). Interestingly, a significantly higher Ki-67 expression was found in tumors of ≥10 cm in diameter compared to smaller tumors (P=0.008). MCM3 expression was detected in 38 (90%) tumors, and PCNA expression in 28 (67%), yet none of clinicopathological factors was related to them. Topoisomerase IIα expression was present in 14 (33%) cases and, interestingly, its significantly higher expression was observed in BOTs of ≥10 cm in diameter compared to smaller tumors (P=0.008). Moreover, Spearman's correlation revealed highly significant positive associations between Ki-67 and topoisomerase IIα (R=0.403, P=0.008) and Ki-67 and MCM3 (R=0.469, P=0.001). We report a high positive immunostaining rate for p53, suggesting a role of TP53 alterations in the development of BOTs in humans. The new finding of higher topoisomerase IIα immunostaining positivity in BOTs of ≥10 cm may be clinically relevant and requires further studies on larger patient groups.

Minimizing the cancer-promotional activity of cox-2 as a central strategy in cancer prevention.

PubMed

McCarty, Mark F

2012-01-01

A recent meta-analysis examining long-term mortality in subjects who participated in controlled studies evaluating the impact of daily aspirin on vascular risk, has concluded that aspirin confers substantial protection from cancer mortality. Remarkably, low-dose aspirin was as effective as higher-dose regimens; hence this protection may be achievable with minimal risk. There is reason to believe that this protection stems primarily from inhibition of cox-2 in pre-neoplastic lesions. Since safe aspirin regimens can only achieve a partial and transitory inhibition of cox-2, it may be feasible to complement the cancer-protective benefit of aspirin with other measures which decrease cox-2 expression or which limit the bioactivity of cox-2-derived PGE2. Oxidative stress boosts cox-2 expression by up-regulating activation of NF-kappaB and MAP kinases; NADPH oxidase activation may thus promote carcinogenesis by increasing cox-2 expression while also amplifying oxidant-mediated mutagenesis. A prospective cohort study has observed that relatively elevated serum bilirubin levels are associated with a marked reduction in subsequent cancer mortality; this may reflect bilirubin's physiological role as a potent inhibitor of NADPH oxidase. It may be feasible to mimic this protective effect by supplementing with spirulina, a rich source of a phycobilin which shares bilirubin's ability to inhibit NADPH oxidase. Ancillary antioxidant measures - phase 2 inducing phytochemicals, melatonin, N-acetylcysteine, and astaxanthin - may also aid cox-2 down-regulation. The cancer protection often associated with high-normal vitamin D status may be attributable, in part, to the ability of the activated vitamin D receptor to decrease cox-2 expression while promoting PGE2 catabolism and suppressing the expression of PGE2 receptors. Diets with a relatively low ratio of omega-6 to long-chain omega-3 fats may achieve cancer protection by antagonizing the production and bioactivity of PGE2. Growth factors such as IGF-I increase cox-2 expression by several complementary mechanisms; hence, decreased cox-2 activity may play a role in the remarkably low mortality from "Western" cancers enjoyed by Third World cultures in which systemic growth factor activity was minimized by quasi-vegan diets complemented by leanness and excellent muscle insulin sensitivity. Practical strategies for achieving a modest degree of calorie restriction may also have potential for down-regulating cox-2 expression while decreasing cancer risk. Soy isoflavones, linked to reduced cancer risk in Asian epidemiology, may suppress cox-2 induction by activating ERbeta. In aggregate, these considerations suggest that a comprehensive lifestyle strategy targeting cox-2 expression and bioactivity may have tremendous potential for cancer prevention. Copyright © 2011 Elsevier Ltd. All rights reserved.

Immunohistochemical evidence for an endocrine/paracrine role for ghrelin in the reproductive tissues of sheep

PubMed Central

Miller, David W; Harrison, Joanne L; Brown, Yvonne A; Doyle, Una; Lindsay, Alanna; Adam, Clare L; Lea, Richard G

2005-01-01

Background The gut hormone, ghrelin, is involved in the neuroendocrine and metabolic responses to hunger. In monogastric species, circulating ghrelin levels show clear meal-related and body weight-related changes. The pattern of secretion and its role in ruminant species is less clear. Ghrelin acts via growth hormone secretagogue receptors (GHSR-1a) to alter food intake, fat utilization, and cellular proliferation. There is also evidence that ghrelin is involved in reproductive function. In the present study we used immunohistochemistry to investigate the presence of ghrelin and GHSR-1a in sheep reproductive tissues. In addition, we examined whether ghrelin and GHSR-1a protein expression is developmentally regulated in the adult and fetal ovine testis, and whether there is an association with markers of cellular proliferation, i.e. stem cell factor (SCF) and proliferating cell nuclear antigen (PCNA). Methods Antibodies raised against ghrelin and its functional receptor, GHSR-type 1a, were used in standard immunohistochemical protocols on various reproductive tissues collected from adult and fetal sheep. GHSR-1a mRNA presence was also confirmed by in situ hybridisation. SCF and PCNA immunoexpression was investigated in fetal testicular samples. Adult and fetal testicular immunostaining for ghrelin, GHSR-1a, SCF and PCNA was analysed using computer-aided image analysis. Image analysis data were subjected to one-way ANOVA, with differences in immunostaining between time-points determined by Fisher's least significant difference. Results In adult sheep tissue, ghrelin and GHSR-1a immunostaining was detected in the stomach (abomasum), anterior pituitary gland, testis, ovary, and hypothalamic and hindbrain regions of the brain. In the adult testis, there was a significant effect of season (photoperiod) on the level of immunostaining for ghrelin (p < 0.01) and GHSR-1a (p < 0.05). In the fetal sheep testis, there was a significant effect of gestational age on the level of immunostaining for ghrelin (p < 0.001), GHSR-1a (p < 0.05), SCF (p < 0.05) and PCNA (p < 0.01). Conclusion Evidence is presented for the presence of ghrelin and its receptor in various reproductive tissues of the adult and fetal sheep. In addition, the data indicate that testicular expression of ghrelin and its receptor is physiologically regulated in the adult and developmentally regulated in the fetus. Therefore, the ghrelin ligand/receptor system may have a role (endocrine and/or paracrine) in the development (cellular proliferation) and function of the reproductive axis of the sheep. PMID:16259638

Derivation of cat embryonic stem-like cells from in vitro-produced blastocysts on homologous and heterologous feeder cells.

PubMed

Gómez, M C; Serrano, M A; Pope, C Earle; Jenkins, J A; Biancardi, M N; López, M; Dumas, C; Galiguis, J; Dresser, B L

2010-09-01

The domestic cat is a focal mammalian species that is used as a model for developing assisted reproductive technologies for preserving endangered cats and for studying human diseases. The generation of stable characterized cat embryonic stem cells (ESC) lines to use as donor nuclei may help to improve the efficiency of interspecies somatic cell nuclear transfer for preserving endangered cats and allow the creation of knockout cell lines to generate knockout cats for studying function of specific genes related to human diseases. It will also enable the possibility of producing gametes in vitro from ESC of endangered cats. In the present study, we report the generation of cat embryonic stem-like (cESL) cells from blastocysts derived entirely in vitro. We generated 32 cESL cell lines from 331 in vitro derived blastocysts from which inner cell masses were isolated by immunosurgery or by a mechanical method. Inhibition of cat dermal fibroblast (CDF) proliferation after exposure to mitomycin-C was both dose and time dependent, where doses of 30 to 40 microg/mL for 5 h were most efficient. These dosages were higher than that required to inhibit cell proliferation of mouse fetal fibroblasts (MFF; 10 microg/mL for 2.5 h). Mitomycin-C did not significantly increase necrosis of cells from either species, and had an anti-proliferative effect at concentrations below cytotoxicity. A clear species-specific relationship between feeder layers and derivation of cESL cell lines was observed, where higher numbers of cESL cell lines were generated on homologous cat feeder layers (n = 26) than from those derived on heterologous mouse feeder layers (n = 6). Three cESL cell lines generated from immunosurgery and cultured on CDF maintained self-renewal and were morphologically undifferentiated for nine and twelve passages (69-102 days). These lines showed a tightly packed dome shaped morphology, exhibited alkaline phosphatase activity and immuno-expression of the pluripotent marker OCT-4 and surface marker SSEA-1. Primary colonies at P0 to P3 and cat blastocysts expressed transcription factors OCT-4, NANOG and SOX-2 and the proto-oncogene C-MYC. However, expression was at levels significantly lower than in vitro produced blastocysts. During culture, cESL colonies spontaneously differentiated into fibroblasts, cardiomyocytes, and embryoid bodies. Development of techniques to prevent differentiation of cESL cells will be essential for maintaining defined cell lines. Copyright 2010 Elsevier Inc. All rights reserved.

Co-expression of COX-2 and 5-LO in primary glioblastoma is associated with poor prognosis.

PubMed

Wang, Xingfu; Chen, Yupeng; Zhang, Sheng; Zhang, Lifeng; Liu, Xueyong; Zhang, Li; Li, Xiaoling; Chen, Dayang

2015-11-01

Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) are important factors in tumorigenesis and malignant progression; however, studies of their roles in glioblastoma have produced conflicting results. To define the frequencies of COX-2 and 5-LO expression and their correlation with clinicopathological features and prognosis, tumor tissues from 76 cases of newly diagnosed primary ordinary glioblastoma were examined for COX-2 and 5-LO expression by immunohistochemistry. The expression levels of COX-2 and 5-LO and the relationships between the co-expression of COX-2/5-LO and patient age and gender, edema index (EI), Karnofsky Performance Scale and overall survival (OS) were analyzed. COX-2 and 5-LO were expressed in 73.7 % (56/76) and 92.1 % (70/76) of the samples, respectively. Among the clinicopathological characteristics, only age (>60 years) exhibited a significant association with the high expression of COX-2. No statistically significant correlations were found in the 5-LO cohort. A significant positive correlation was revealed between the COX-2 and 5-LO scores (r = 0.374; p = 0.001). The elevated co-expression of COX-2 and 5-LO was observed primarily in the patients over the age of 60 years. Patients with a high expression of COX-2 had a significantly shorter OS (p < 0.01), whereas the immunoexpression of 5-LO was not associated with the OS of patients with glioblastoma. Survival analysis indicated that simultaneous high levels of COX-2 and 5-LO expression were significantly correlated with poor OS and, conversely, that a low/low expression pattern of these two proteins was significantly associated with better OS (p < 0.05). Moreover, the Cox multivariable proportional hazard model showed that a high expression of COX-2, high co-expression of COX-2 and 5-LO, and a high Ki-67 index were significant predictors of shorter OS in primary glioblastoma, independent of age, gender, EI, 5-LO expression and p53 status. The hazard ratios for OS were 2.347 (95 % CI 1.30-4.25, p = 0.005), 1.900 (95 % CI 1.30-2.78, p = 0.001), and 2.210 (95 % CI 1.19-4.09, p = 0.011), respectively. These results suggest that COX-2 and 5-LO play roles in tumorigenesis and the progression of primary glioblastoma and that the co-expression pattern of COX-2/5-LO may be used as an independent prognostic factor in this disease.

[Relationship between the changes in ischemia/reperfusion cerebro-microvessel basement membrane injury and gelatinase system in senile rat].

PubMed

Li, Jian-sheng; Liu, Ke; Liu, Jing-xia; Wang, Ming-hang; Zhao, Yue-wu; Liu, Zheng-guo

2008-11-01

To study the relationship of cerebro-microvessel basement membrane injury and gelatinase system after cerebral ischemia/reperfusion (I/R) in aged rats. Cerebral I/R injury model was reproduced by intraluminal silk ligature thrombosis of the middle cerebral artery occlusion (MCAO). Rats were divided randomly into sham control and I/R groups in young rats [ischemia 3 hours (I 3 h) and reperfusion 6 hours (I/R 6 h), 12 hours (I/R 12 h), 24 hours (I/R 24 h), 3 days (I/R 3 d), 6 days (I/R 6 d)], and sham control group and I/R group in aged rats (I 3 h and I/R 6 h, I/R 12 h, I/R 24 h , I/R 3 d, I/R 6 d). The change in cerebro-cortex microvessel basement membrane structure, basement membrane type IV collagen (Col IV) and laminin (LN) contents, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) expression in every group were determined with immunohistochemical method and zymogram analysis. With the increase in age, Col IV and LN contents of the microvessel basement membrane were increased, and MMP-2 and MMP-9 expressions were stronger. With prolongation of I/R, the degradation of microvessel basement membrane components (Col IV and LN) was positively correlated with the duration of cerebral I/R. MMP-2 expression was increased gradually, and MMP-9 and TIMP-1 expression increased at the beginning and decreased subsequently. Col IV(I 3 h, I/R 6 h , I/R 12 h), LN (I 3 h, I/R 6-24 h), MMP-2 (I 3 h, I/R 6 h-6 d) and MMP-9 (I 3 h, I/R 6-24 h) expression level in aged rats with I/R injury were higher, and TIMP-1 (I/R 24 h) expression was lower than those in young rats (P<0.05 or P<0.01). In addition, changes in MMP-2 and MMP-9 contents as determined by zymogram analysis method coincided with their immunoexpression. With the increase of age, alteration in membrane components of cerebro-microvessel basement membrane in rats is related with MMPs and TIMP. Cerebro-microvessel basement membrane injury is more serious in aged rats than that of young rats. Changes in cerebro-microvessel basement membrane injury in aged rats is related with gelatinase system change.

Activation of estrogen receptor signaling by the dioxin-like aryl hydrocarbon receptor agonist, 3,3',4,4',5-Pentachlorobiphenyl (PCB126) in salmon in vitro system

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

Mortensen, Anne Skjetne; Arukwe, Augustine

2008-03-01

Available toxicological evidence indicates that environmental contaminants with strong affinity to the aryl hydrocarbon receptor (AhR) have anti-estrogenic properties in both mammalian and non-mammalian in vivo and in vitro studies. The primary objective of the present study was to investigate the interactions between the AhR and estrogen receptor (ER) in salmon in vitro system. Two separate experiments were performed and gene expression patterns were analyzed using real-time PCR, while protein analysis was done by immunoblotting. Firstly, salmon primary hepatocytes were exposed to the dioxin-like PCB126 at 1, 10 and 50 pM and ER agonist nonylphenol (NP) at 5 and 10more » {mu}M, singly or in combination. Our data showed increased levels of ER-mediated gene expression (vitellogenin: Vtg, zona radiata protein: Zr-protein, ER{alpha}, ER{beta} and vigilin) as well as increased cellular ER{alpha} protein levels after treatment with NP and PCB126, singly or in combination. PCB126 treatment alone produced, as expected, increased transcription of AhR nuclear translocator (Arnt), CYP1A1 and AhR repressor (AhRR) mRNA, and these responses were reduced in the presence of NP concentrations. PCB126 exposure alone did not produce significant effect on AhR2{alpha} mRNA but increased (at 1 and 50 pM) and decreased (at 10 pM) AhR2{beta} mRNA below control level. For AhR2{delta} and AhR2{gamma} isotypes, PCB126 (at 1 pM) produced significant decreases (total inhibition for AhR2{gamma}) of mRNA levels but was indifferent at 10 and 50 pM, compared to control. NP exposure alone produced concentration-dependent significant decrease of AhR2{beta} mRNA. In contrast, while 5 {mu}M NP produced an indifferent effect on AhR2{delta} and AhR2{gamma}, 10 {mu}M NP produced significant decrease (total inhibition for AhR2{gamma}) and the presence of NP produced apparent PCB126 concentration-specific modulation of all AhR isotypes. A second experiment was performed to evaluate the involvement of ER isoforms in PCB126 mediated estrogenicity. Here, cells were treated with the different concentrations of PCB126, alone or in combination with ICI182,780 (ICI) and sampled at 12, 24 and 48 h post-exposure. Our data showed that PCB126 produced a time- and concentration-specific increase of ER{alpha} and Vtg expressions and these responses were decreased in the presence of ICI. In general, these responses show a direct PCB126 induced transcriptional activation of ER{alpha} and estrogenic responses in the absence of ER agonists. Although not conclusive, our findings represent the first study showing the activation of estrogenic responses by a dioxin-like PCB in fish in vitro system and resemble the 'ER-hijacking' hypothesis that was recently proposed. Thus, the direct estrogenic actions of PCB126 observed in the present study add new insight on the mechanisms of ER-AhR cross-talk, prompting a new wave of discussion on whether AhR-mediated anti-estrogenicity is an exception rather than rule of action.« less

Eastern U.S. Infrared, Enhancement 4 - NOAA GOES Geostationary Satellite

Science.gov Websites

Enhancement 4 Eastern U.S. Infrared Enhancements IR Enhancement 1 Eastern U.S. Infrared Enhancement 1 IR Enhancement 2 Eastern U.S. Infrared Enhancement 2 IR Enhancement 3 Eastern U.S. Infrared Enhancement 3 IR large amount of water vapor. » Enhancement types In an infrared (IR) image cold clouds are high clouds

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.

Moral Enhancement

PubMed Central

Douglas, Thomas

2008-01-01

Opponents of biomedical enhancement often claim that, even if such enhancement would benefit the enhanced, it would harm others. But this objection looks unpersuasive when the enhancement in question is a moral enhancement — an enhancement that will expectably leave the enhanced person with morally better motives than she had previously. In this article I (1) describe one type of psychological alteration that would plausibly qualify as a moral enhancement, (2) argue that we will, in the medium-term future, probably be able to induce such alterations via biomedical intervention, and (3) defend future engagement in such moral enhancements against possible objections. My aim is to present this kind of moral enhancement as a counter-example to the view that biomedical enhancement is always morally impermissible. PMID:19132138

Enhancers and super-enhancers have an equivalent regulatory role in embryonic stem cells through regulation of single or multiple genes

PubMed Central

Moorthy, Sakthi D.; Davidson, Scott; Shchuka, Virlana M.; Singh, Gurdeep; Malek-Gilani, Nakisa; Langroudi, Lida; Martchenko, Alexandre; So, Vincent; Macpherson, Neil N.; Mitchell, Jennifer A.

2017-01-01

Transcriptional enhancers are critical for maintaining cell-type–specific gene expression and driving cell fate changes during development. Highly transcribed genes are often associated with a cluster of individual enhancers such as those found in locus control regions. Recently, these have been termed stretch enhancers or super-enhancers, which have been predicted to regulate critical cell identity genes. We employed a CRISPR/Cas9-mediated deletion approach to study the function of several enhancer clusters (ECs) and isolated enhancers in mouse embryonic stem (ES) cells. Our results reveal that the effect of deleting ECs, also classified as ES cell super-enhancers, is highly variable, resulting in target gene expression reductions ranging from 12% to as much as 92%. Partial deletions of these ECs which removed only one enhancer or a subcluster of enhancers revealed partially redundant control of the regulated gene by multiple enhancers within the larger cluster. Many highly transcribed genes in ES cells are not associated with a super-enhancer; furthermore, super-enhancer predictions ignore 81% of the potentially active regulatory elements predicted by cobinding of five or more pluripotency-associated transcription factors. Deletion of these additional enhancer regions revealed their robust regulatory role in gene transcription. In addition, select super-enhancers and enhancers were identified that regulated clusters of paralogous genes. We conclude that, whereas robust transcriptional output can be achieved by an isolated enhancer, clusters of enhancers acting on a common target gene act in a partially redundant manner to fine tune transcriptional output of their target genes. PMID:27895109

Understanding and managing enhancements: why fisheries scientists should care.

PubMed

Lorenzen, K

2014-12-01

Fisheries enhancements are a set of management approaches involving the use of aquaculture technologies to enhance or restore fisheries in natural ecosystems. Enhancements are widely used in inland and coastal fisheries, but have received limited attention from fisheries scientists. This paper sets out 10 reasons why fisheries scientists should care about understanding and managing enhancements. (1) Enhancements happen, driven mostly by resource users and managers rather than scientists. (2) Enhancements create complex fisheries systems that encompass and integrate everything fisheries stakeholders can practically manage. (3) Enhancements emerge in fisheries where the scope for technical and governance control is high, and they synergistically reinforce both. (4) Successful enhancements expand management options and achievable outcomes. (5) Many enhancements fail or do ecological harm but persist regardless. (6) Effective science engagement is crucial to developing beneficial enhancements and preventing harmful ones. (7) Good scientific guidance is available to aid development or reform of enhancements but is not widely applied. (8) Enhancement research advances, integrates and unifies the fisheries sciences. (9) Enhancements provide unique opportunities for learning about natural fish populations and fisheries. (10) Needs, opportunities and incentives for enhancements are bound to increase. © 2014 The Fisheries Society of the British Isles.

7SK-BAF axis controls pervasive transcription at enhancers

PubMed Central

Flynn, Ryan A.; Do, Brian T.; Rubin, Adam J.; Calo, Eliezer; Lee, Byron; Kuchelmeister, Hannes; Rale, Michael; Chu, Ci; Kool, Eric T.; Wysocka, Joanna; Khavari, Paul A.

2016-01-01

RNA functions at enhancers remain mysterious. Here we show that the 7SK small nuclear RNA (snRNA) inhibits enhancer transcription by modulating nucleosome position. 7SK occupies enhancers and super enhancers genome-wide in mouse and human cells, and 7SK is required to limit eRNA initiation and synthesis in a manner distinct from promoter pausing. Clustered elements at super enhancers uniquely require 7SK to prevent convergent transcription and DNA damage signaling. 7SK physically interacts with the BAF chromatin remodeling complex, recruit BAF to enhancers, and inhibits enhancer transcription by modulating chromatin structure. In turn, 7SK occupancy at enhancers coincides with Brd4 and is exquisitely sensitive to the bromodomain inhibitor JQ1. Thus, 7SK employs distinct mechanisms to counteract diverse consequences of pervasive transcription that distinguish super enhancers, enhancers, and promoters. PMID:26878240

Right ventricular involvement in cardiac sarcoidosis demonstrated with cardiac magnetic resonance

PubMed Central

van Geuns, Robert‐Jan; Ainslie, Gillian; Ector, Joris; Heidbuchel, Hein; Crijns, Harry J.G.M.

2017-01-01

Abstract Aims Cardiac involvement in sarcoidosis is reported in up to 30% of patients. Left ventricular involvement demonstrated by contrast‐enhanced cardiac magnetic resonance has been well validated. We sought to determine the prevalence and distribution of right ventricular late gadolinium enhancement in patients diagnosed with pulmonary sarcoidosis. Methods and results We prospectively evaluated 87 patients diagnosed with pulmonary sarcoidosis with contrast‐enhanced cardiac magnetic resonance for right ventricular involvement. Pulmonary artery pressures were non‐invasively evaluated with Doppler echocardiography. Patient characteristics were compared between the groups with and without right ventricular involvement, and right ventricular enhancement was correlated with pulmonary hypertension, ventricular mass, volume, and systolic function. Left ventricular late gadolinium enhancement was demonstrated in 30 patients (34%). Fourteen patients (16%) had right ventricular late gadolinium enhancement, with sole right ventricular enhancement in only two patients. The pattern of right ventricular enhancement consisted of right ventricular outflow tract enhancement in 1 patient, free wall enhancement in 8 patients, ventricular insertion point enhancement in 10 patients, and enhancement of the right side of the interventricular septum in 11 patients. Pulmonary arterial hypertension correlated with the presence of right ventricular enhancement (P < 0.001). Right ventricular enhancement correlated with systolic ventricular dysfunction (P < 0.001), hypertrophy (P = 0.001), and dilation (P < 0.001). Conclusions Right ventricular enhancement was present in 16% of patients diagnosed with pulmonary sarcoidosis and in 48% of patients with left ventricular enhancement. The presence of right ventricular enhancement correlated with pulmonary arterial hypertension, right ventricular systolic dysfunction, hypertrophy, and dilation. PMID:29154434

Effects of contour enhancement on low-vision preference and visual search.

PubMed

Satgunam, Premnandhini; Woods, Russell L; Luo, Gang; Bronstad, P Matthew; Reynolds, Zachary; Ramachandra, Chaithanya; Mel, Bartlett W; Peli, Eli

2012-09-01

To determine whether image enhancement improves visual search performance and whether enhanced images were also preferred by subjects with vision impairment. Subjects (n = 24) with vision impairment (vision: 20/52 to 20/240) completed visual search and preference tasks for 150 static images that were enhanced to increase object contours' visual saliency. Subjects were divided into two groups and were shown three enhancement levels. Original and medium enhancements were shown to both groups. High enhancement was shown to group 1, and low enhancement was shown to group 2. For search, subjects pointed to an object that matched a search target displayed at the top left of the screen. An "integrated search performance" measure (area under the curve of cumulative correct response rate over search time) quantified performance. For preference, subjects indicated the preferred side when viewing the same image with different enhancement levels on side-by-side high-definition televisions. Contour enhancement did not improve performance in the visual search task. Group 1 subjects significantly (p < 0.001) rejected the High enhancement, and showed no preference for medium enhancement over the original images. Group 2 subjects significantly preferred (p < 0.001) both the medium and the low enhancement levels over original. Contrast sensitivity was correlated with both preference and performance; subjects with worse contrast sensitivity performed worse in the search task (ρ = 0.77, p < 0.001) and preferred more enhancement (ρ = -0.47, p = 0.02). No correlation between visual search performance and enhancement preference was found. However, a small group of subjects (n = 6) in a narrow range of mid-contrast sensitivity performed better with the enhancement, and most (n = 5) also preferred the enhancement. Preferences for image enhancement can be dissociated from search performance in people with vision impairment. Further investigations are needed to study the relationships between preference and performance for a narrow range of mid-contrast sensitivity where a beneficial effect of enhancement may exist.

Improvement of absorption enhancing effects of n-dodecyl-beta-D-maltopyranoside by its colon-specific delivery using chitosan capsules.

PubMed

Fetih, Gihan; Lindberg, Sara; Itoh, Katsuhito; Okada, Naoki; Fujita, Takuya; Habib, Fawsia; Artersson, Per; Attia, Mohammed; Yamamoto, Akira

2005-04-11

In general, absorption enhancing effects of various absorption enhancers were greater in the large intestine than those in the small intestinal regions. Therefore, the effectiveness of absorption enhancers is expected to be remarkably observed, if these enhancers can be delivered to the large intestine with some poorly absorbable drugs after oral administration. In this study, therefore, we examined whether chitosan capsules were effective for the colon-specific delivery of a certain absorption enhancer and can improve the absorption enhancing action of the absorption enhancer after oral administration. 5(6)-Carboxyfluorescein (CF) was used as a model drug to investigate the site-dependent effectiveness of various absorption enhancers by an in situ closed loop method. Sodium glycocholate (NaGC), n-dodecyl-beta-d-maltopyranoside (LM), sodium salicylate (NaSal) and sodium caprate (NaCap) were used as models of absorption enhancers in this study. Overall, the absorption enhancing effects of these enhancers for intestinal absorption of CF were greater in the colon than those in the jejunum and the ileum. Especially, among these enhancers tested in this study, LM showed much greater absorption enhancing effect in the colon than in the jejunum and the ileum. Therefore, LM was selected as a model absorption enhancer to examine the effect of chitosan capsules on the absorption enhancing effect of LM. When CF and LM were orally administered to rats using chitosan capsules, the plasma concentration of CF was much higher than those in other dosage forms including solution and gelatin capsules. Therefore, chitosan capsules may be useful carriers for colon-specific delivery of LM, thereby increasing its absorption enhancing effect from the intestinal membranes.

Right ventricular involvement in cardiac sarcoidosis demonstrated with cardiac magnetic resonance.

PubMed

Smedema, Jan-Peter; van Geuns, Robert-Jan; Ainslie, Gillian; Ector, Joris; Heidbuchel, Hein; Crijns, Harry J G M

2017-11-01

Cardiac involvement in sarcoidosis is reported in up to 30% of patients. Left ventricular involvement demonstrated by contrast-enhanced cardiac magnetic resonance has been well validated. We sought to determine the prevalence and distribution of right ventricular late gadolinium enhancement in patients diagnosed with pulmonary sarcoidosis. We prospectively evaluated 87 patients diagnosed with pulmonary sarcoidosis with contrast-enhanced cardiac magnetic resonance for right ventricular involvement. Pulmonary artery pressures were non-invasively evaluated with Doppler echocardiography. Patient characteristics were compared between the groups with and without right ventricular involvement, and right ventricular enhancement was correlated with pulmonary hypertension, ventricular mass, volume, and systolic function. Left ventricular late gadolinium enhancement was demonstrated in 30 patients (34%). Fourteen patients (16%) had right ventricular late gadolinium enhancement, with sole right ventricular enhancement in only two patients. The pattern of right ventricular enhancement consisted of right ventricular outflow tract enhancement in 1 patient, free wall enhancement in 8 patients, ventricular insertion point enhancement in 10 patients, and enhancement of the right side of the interventricular septum in 11 patients. Pulmonary arterial hypertension correlated with the presence of right ventricular enhancement (P < 0.001). Right ventricular enhancement correlated with systolic ventricular dysfunction (P < 0.001), hypertrophy (P = 0.001), and dilation (P < 0.001). Right ventricular enhancement was present in 16% of patients diagnosed with pulmonary sarcoidosis and in 48% of patients with left ventricular enhancement. The presence of right ventricular enhancement correlated with pulmonary arterial hypertension, right ventricular systolic dysfunction, hypertrophy, and dilation. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Comparison of Oral Contrast-Enhanced Transabdominal Ultrasound Imaging With Transverse Contrast-Enhanced Computed Tomography in Preoperative Tumor Staging of Advanced Gastric Carcinoma.

PubMed

He, Xuemei; Sun, Jing; Huang, Xiaoling; Zeng, Chun; Ge, Yinggang; Zhang, Jun; Wu, Jingxian

2017-12-01

This study assessed the diagnostic performance of transabdominal oral contrast-enhanced ultrasound (US) imaging for preoperative tumor staging of advanced gastric carcinoma by comparing it with transverse contrast-enhanced computed tomography (CT). This retrospective study included 42 patients with advanced gastric cancer who underwent laparoscopy, radical surgery, or palliative surgery because of serious complications and had a body mass index of less than 25 kg/m 2 . A cereal-based oral contrast agent was used for transabdominal oral contrast-enhanced US. Retrospective analyses were conducted using preoperative tumor staging data acquired by either transabdominal oral contrast-enhanced US or transverse contrast-enhanced CT. Both contrast-enhanced US and contrast-enhanced CT examinations were reviewed by 2 experienced radiologists independently for preoperative tumor staging according to the seventh edition of the TNM classification. The accuracy, sensitivity, and specificity were calculated by comparing the results of contrast-enhanced US and contrast-enhanced CT with pathologic findings. The overall accuracies of the imaging modalities were compared by the McNemar test. No significant difference was noted in the overall accuracy of transabdominal oral contrast-enhanced US (86% [36 of 42]) and transverse contrast-enhanced CT (83% [35 of 42] P > .999). For stage T2 to T4 gastric cancer, the accuracies of transabdominal oral contrast-enhanced US were 88%, 86%, and 98%, respectively, and those of transverse contrast-enhanced CT were 93%, 83%, and 90%. The overall accuracy of transabdominal oral contrast-enhanced US was comparable with that of transverse contrast-enhanced CT for preoperative tumor staging of advanced gastric cancer. © 2017 by the American Institute of Ultrasound in Medicine.

Genome-Wide Prediction and Validation of Intergenic Enhancers in Arabidopsis Using Open Chromatin Signatures[OPEN

PubMed Central

Zhu, Bo; Zhang, Wenli; Jiang, Jiming

2015-01-01

Enhancers are important regulators of gene expression in eukaryotes. Enhancers function independently of their distance and orientation to the promoters of target genes. Thus, enhancers have been difficult to identify. Only a few enhancers, especially distant intergenic enhancers, have been identified in plants. We developed an enhancer prediction system based exclusively on the DNase I hypersensitive sites (DHSs) in the Arabidopsis thaliana genome. A set of 10,044 DHSs located in intergenic regions, which are away from any gene promoters, were predicted to be putative enhancers. We examined the functions of 14 predicted enhancers using the β-glucuronidase gene reporter. Ten of the 14 (71%) candidates were validated by the reporter assay. We also designed 10 constructs using intergenic sequences that are not associated with DHSs, and none of these constructs showed enhancer activities in reporter assays. In addition, the tissue specificity of the putative enhancers can be precisely predicted based on DNase I hypersensitivity data sets developed from different plant tissues. These results suggest that the open chromatin signature-based enhancer prediction system developed in Arabidopsis may serve as a universal system for enhancer identification in plants. PMID:26373455

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.

Hierarchy within the mammary STAT5-driven Wap super-enhancer.

PubMed

Shin, Ha Youn; Willi, Michaela; HyunYoo, Kyung; Zeng, Xianke; Wang, Chaochen; Metser, Gil; Hennighausen, Lothar

2016-08-01

Super-enhancers comprise dense transcription factor platforms highly enriched for active chromatin marks. A paucity of functional data led us to investigate the role of super-enhancers in the mammary gland, an organ characterized by exceptional gene regulatory dynamics during pregnancy. ChIP-seq analysis for the master regulator STAT5A, the glucocorticoid receptor, H3K27ac and MED1 identified 440 mammary-specific super-enhancers, half of which were associated with genes activated during pregnancy. We interrogated the Wap super-enhancer, generating mice carrying mutations in STAT5-binding sites within its constituent enhancers. Individually, the most distal site displayed the greatest enhancer activity. However, combinatorial mutation analysis showed that the 1,000-fold induction in gene expression during pregnancy relied on all enhancers. Disabling the binding sites of STAT5, NFIB and ELF5 in the proximal enhancer incapacitated the entire super-enhancer. Altogether, these data suggest a temporal and functional enhancer hierarchy. The identification of mammary-specific super-enhancers and the mechanistic exploration of the Wap locus provide insights into the regulation of cell-type-specific expression of hormone-sensing genes.

Smart Image Enhancement Process

NASA Technical Reports Server (NTRS)

Jobson, Daniel J. (Inventor); Rahman, Zia-ur (Inventor); Woodell, Glenn A. (Inventor)

2012-01-01

Contrast and lightness measures are used to first classify the image as being one of non-turbid and turbid. If turbid, the original image is enhanced to generate a first enhanced image. If non-turbid, the original image is classified in terms of a merged contrast/lightness score based on the contrast and lightness measures. The non-turbid image is enhanced to generate a second enhanced image when a poor contrast/lightness score is associated therewith. When the second enhanced image has a poor contrast/lightness score associated therewith, this image is enhanced to generate a third enhanced image. A sharpness measure is computed for one image that is selected from (i) the non-turbid image, (ii) the first enhanced image, (iii) the second enhanced image when a good contrast/lightness score is associated therewith, and (iv) the third enhanced image. If the selected image is not-sharp, it is sharpened to generate a sharpened image. The final image is selected from the selected image and the sharpened image.

Hierarchy within the mammary STAT5-driven Wap super-enhancer

PubMed Central

Zeng, Xianke; Wang, Chaochen; Metser, Gil; Hennighausen, Lothar

2016-01-01

Super-enhancers comprise of dense transcription factor platforms highly enriched for active chromatin marks. A paucity of functional data led us to investigate their role in the mammary gland, an organ characterized by exceptional gene regulatory dynamics during pregnancy. ChIP-Seq for the master regulator STAT5, the glucocorticoid receptor, H3K27ac and MED1, identified 440 mammary-specific super-enhancers, half of which were associated with genes activated during pregnancy. We interrogated the Wap super-enhancer, generating mice carrying mutations in STAT5 binding sites within its three constituent enhancers. Individually, only the most distal site displayed significant enhancer activity. However, combinatorial mutations showed that the 1,000-fold gene induction relied on all enhancers. Disabling the binding sites of STAT5, NFIB and ELF5 in the proximal enhancer incapacitated the entire super-enhancer, suggesting an enhancer hierarchy. The identification of mammary-specific super-enhancers and the mechanistic exploration of the Wap locus provide insight into the complexity of cell-specific and hormone-regulated genes. PMID:27376239

Effective blocking of the white enhancer requires cooperation between two main mechanisms suggested for the insulator function.

PubMed

Kyrchanova, Olga; Maksimenko, Oksana; Stakhov, Viacheslav; Ivlieva, Tatyana; Parshikov, Alexander; Studitsky, Vasily M; Georgiev, Pavel

2013-01-01

Chromatin insulators block the action of transcriptional enhancers when interposed between an enhancer and a promoter. In this study, we examined the role of chromatin loops formed by two unrelated insulators, gypsy and Fab-7, in their enhancer-blocking activity. To test for this activity, we selected the white reporter gene that is activated by the eye-specific enhancer. The results showed that one copy of the gypsy or Fab-7 insulator failed to block the eye enhancer in most of genomic sites, whereas a chromatin loop formed by two gypsy insulators flanking either the eye enhancer or the reporter completely blocked white stimulation by the enhancer. However, strong enhancer blocking was achieved due not only to chromatin loop formation but also to the direct interaction of the gypsy insulator with the eye enhancer, which was confirmed by the 3C assay. In particular, it was observed that Mod(mdg4)-67.2, a component of the gypsy insulator, interacted with the Zeste protein, which is critical for the eye enhancer-white promoter communication. These results suggest that efficient enhancer blocking depends on the combination of two factors: chromatin loop formation by paired insulators, which generates physical constraints for enhancer-promoter communication, and the direct interaction of proteins recruited to an insulator and to the enhancer-promoter pair.

A Systematic Survey and Characterization of Enhancers that Regulate Sox3 in Neuro-Sensory Development in Comparison with Sox2 Enhancers.

PubMed

Nishimura, Naoko; Kamimura, Yoshifumi; Ishida, Yoshiko; Takemoto, Tatsuya; Kondoh, Hisato; Uchikawa, Masanori

2012-11-22

Development of neural and sensory primordia at the early stages of embryogenesis depends on the activity of two B1 Sox transcription factors, Sox2 and Sox3. The embryonic expression patterns of the Sox2 and Sox3 genes are similar, yet they show gene-unique features. We screened for enhancers of the 231-kb genomic region encompassing Sox3 of chicken, and identified 13 new enhancers that showed activity in different domains of the neuro-sensory primordia. Combined with the three Sox3-proximal enhancers determined previously, at least 16 enhancers were involved in Sox3 regulation. Starting from the NP1 enhancer, more enhancers with different specificities are activated in sequence, resulting in complex overlapping patterns of enhancer activities. NP1 was activated in the caudal lateral epiblast adjacent to the posterior growing end of neural plate, and by the combined action of Wnt and Fgf signaling, similar to the Sox2 N1 enhancer involved in neural/mesodermal dichotomous cell lineage segregation. The Sox3 D5 enhancer and Sox2 N3 enhancer were also activated similarly in the diencephalon, optic vesicle and lens placode, suggesting analogies in their regulation. In general, however, the specificities of the enhancers were not identical between Sox3 and Sox2, including the cases of the NP1 and D5 enhancers.

Method for enhancing amidohydrolase activity of fatty acid amide hydrolase

DOEpatents

John, George; Nagarajan, Subbiah; Chapman, Kent; Faure, Lionel; Koulen, Peter

2016-10-25

A method for enhancing amidohydrolase activity of Fatty Acid Amide Hydrolase (FAAH) is disclosed. The method comprising administering a phenoxyacylethanolamide that causes the enhanced activity. The enhanced activity can have numerous effects on biological organisms including, for example, enhancing the growth of certain seedlings. The subject matter disclosed herein relates to enhancers of amidohydrolase activity.

Thinking across species--a critical bioethics approach to enhancement.

PubMed

Twine, Richard

2007-01-01

Drawing upon a concept of 'critical bioethics' [7] this paper takes a species-broad approach to the social and ethical aspects of enhancement. Critical Bioethics aims to foreground interdisciplinarity, socio-political dimensions, as well as reflexivity to what becomes bioethical subject matter. This paper focuses upon the latter component and uses the example of animal enhancement as a way to think about both enhancement generally, and bioethics. It constructs several arguments for including animal enhancement as a part of enhancement debates, and considers some connections between human and animal enhancement. The paper concludes in a plea for an 'enhancement' to our critical abilities to examine some of the underlying social, moral and ethical assumptions bound up in varied anticipated 'enhanced' futures.

A Common Molecular Motif Characterizes Extracellular Allosteric Enhancers of GPCR Aminergic Receptors and Suggests Enhancer Mechanism of Action

PubMed Central

Bernstein, Robert Root; Dillon, Patrick F

2014-01-01

Several classes of compounds that have no intrinsic activity on aminergic systems nonetheless enhance the potency of aminergic receptor ligands three-fold or more while significantly increasing their duration of activity, preventing tachyphylaxis and reversing fade. Enhancer compounds include ascorbic acid, ethylenediaminetetraacetic acid, cortico-steroids, opioid peptides, opiates and opiate antagonists. This paper provides the first review of aminergic enhancement, demonstrating that all enhancers have a common, inobvious molecular motif and work through a common mechanism that is manifested by three common characteristics. First, aminergic enhancers bind directly to the amines they enhance, suggesting that the common structural motif is reflected in common binding targets. Second, one common target is the first extracellular loop of aminergic receptors. Third, at least some enhancers are antiphosphodiesterases. These observations suggest that aminergic enhancers act on the extracellular surface of aminergic receptors to keep the receptor in its high affinity state, trapping the ligand inside the receptor. Enhancer binding produces allosteric modifications of the receptor structure that interfere with phosphorylation of the receptor, thereby inhibiting down-regulation of the receptor. The mechanism explains how enhancers potentiate aminergic activity and increase duration of activity and makes testable predictions about additional compounds that should act as aminergic enhancers. PMID:25174918

ChIP-seq Identification of Weakly Conserved Heart Enhancers

PubMed Central

Blow, Matthew J.; McCulley, David J.; Li, Zirong; Zhang, Tao; Akiyama, Jennifer A.; Holt, Amy; Plajzer-Frick, Ingrid; Shoukry, Malak; Wright, Crystal; Chen, Feng; Afzal, Veena; Bristow, James; Ren, Bing; Black, Brian L.; Rubin, Edward M.; Visel, Axel; Pennacchio, Len A.

2011-01-01

Accurate control of tissue-specific gene expression plays a pivotal role in heart development, but few cardiac transcriptional enhancers have thus far been identified. Extreme non-coding sequence conservation successfully predicts enhancers active in many tissues, but fails to identify substantial numbers of heart enhancers. Here we used ChIP-seq with the enhancer-associated protein p300 from mouse embryonic day 11.5 heart tissue to identify over three thousand candidate heart enhancers genome-wide. Compared to other tissues studied at this time-point, most candidate heart enhancers are less deeply conserved in vertebrate evolution. Nevertheless, the testing of 130 candidate regions in a transgenic mouse assay revealed that most of them reproducibly function as enhancers active in the heart, irrespective of their degree of evolutionary constraint. These results provide evidence for a large population of poorly conserved heart enhancers and suggest that the evolutionary constraint of embryonic enhancers can vary depending on tissue type. PMID:20729851

Cognitive Enhancement and Education

ERIC Educational Resources Information Center

Buchanan, Allen

2011-01-01

Cognitive enhancement--augmenting normal cognitive capacities--is not new. Literacy, numeracy, computers, and the practices of science are all cognitive enhancements. Science is now making new cognitive enhancements possible. Biomedical cognitive enhancements (BCEs) include the administration of drugs, implants of genetically engineered or…

Thermal Performance of Microencapsulated Phase Change Material Slurry

DTIC Science & Technology

2008-03-01

the enhanced tubing to account for the microfin enhancement size. Figure 4.2 suggests that a roughness factor value for an 8 mm enhanced tubing ...After taking into account the enhanced tubing additional surface area, it can be concluded that that the microfins or enhancements on the tubing ...39 4.2 Pressure drop of water with 8 mm enhanced tubing

Thermal Performance of Microencapsulated Phase Change Material Survey

DTIC Science & Technology

2008-03-01

the enhanced tubing to account for the microfin enhancement size. Figure 4.2 suggests that a roughness factor value for an 8 mm enhanced tubing ...After taking into account the enhanced tubing additional surface area, it can be concluded that that the microfins or enhancements on the tubing ...39 4.2 Pressure drop of water with 8 mm enhanced tubing

Metal-enhanced fluorescence exciplex emission.

PubMed

Zhang, Yongxia; Mali, Buddha L; Geddes, Chris D

2012-01-01

In this letter, we report the first observation of metal-enhanced exciplex fluorescence, observed from anthracene in the presence of diethylaniline. Anthracene in the presence of diethylaniline in close proximity to Silver Island Films (SIFs) shows enhanced monomer and exciplex emission as compared to a non-silvered control sample containing no silver nanoparticles. Our findings suggest two complementary methods for the enhancement: (i) surface plasmons can radiate coupled monomer and exciplex fluorescence efficiently, and (ii) enhanced absorption (enhanced electric near-field) further facilitates enhanced emission. Our exciplex studies help us to further understand the complex photophysics of the metal-enhanced fluorescence technology. Copyright © 2011 Elsevier B.V. All rights reserved.

Identification of activated enhancers and linked transcription factors in breast, prostate, and kidney tumors by tracing enhancer networks using epigenetic traits.

PubMed

Rhie, Suhn Kyong; Guo, Yu; Tak, Yu Gyoung; Yao, Lijing; Shen, Hui; Coetzee, Gerhard A; Laird, Peter W; Farnham, Peggy J

2016-01-01

Although technological advances now allow increased tumor profiling, a detailed understanding of the mechanisms leading to the development of different cancers remains elusive. Our approach toward understanding the molecular events that lead to cancer is to characterize changes in transcriptional regulatory networks between normal and tumor tissue. Because enhancer activity is thought to be critical in regulating cell fate decisions, we have focused our studies on distal regulatory elements and transcription factors that bind to these elements. Using DNA methylation data, we identified more than 25,000 enhancers that are differentially activated in breast, prostate, and kidney tumor tissues, as compared to normal tissues. We then developed an analytical approach called Tracing Enhancer Networks using Epigenetic Traits that correlates DNA methylation levels at enhancers with gene expression to identify more than 800,000 genome-wide links from enhancers to genes and from genes to enhancers. We found more than 1200 transcription factors to be involved in these tumor-specific enhancer networks. We further characterized several transcription factors linked to a large number of enhancers in each tumor type, including GATA3 in non-basal breast tumors, HOXC6 and DLX1 in prostate tumors, and ZNF395 in kidney tumors. We showed that HOXC6 and DLX1 are associated with different clusters of prostate tumor-specific enhancers and confer distinct transcriptomic changes upon knockdown in C42B prostate cancer cells. We also discovered de novo motifs enriched in enhancers linked to ZNF395 in kidney tumors. Our studies characterized tumor-specific enhancers and revealed key transcription factors involved in enhancer networks for specific tumor types and subgroups. Our findings, which include a large set of identified enhancers and transcription factors linked to those enhancers in breast, prostate, and kidney cancers, will facilitate understanding of enhancer networks and mechanisms leading to the development of these cancers.

Progress and challenges in bioinformatics approaches for enhancer identification

PubMed Central

Kleftogiannis, Dimitrios; Kalnis, Panos

2016-01-01

Enhancers are cis-acting DNA elements that play critical roles in distal regulation of gene expression. Identifying enhancers is an important step for understanding distinct gene expression programs that may reflect normal and pathogenic cellular conditions. Experimental identification of enhancers is constrained by the set of conditions used in the experiment. This requires multiple experiments to identify enhancers, as they can be active under specific cellular conditions but not in different cell types/tissues or cellular states. This has opened prospects for computational prediction methods that can be used for high-throughput identification of putative enhancers to complement experimental approaches. Potential functions and properties of predicted enhancers have been catalogued and summarized in several enhancer-oriented databases. Because the current methods for the computational prediction of enhancers produce significantly different enhancer predictions, it will be beneficial for the research community to have an overview of the strategies and solutions developed in this field. In this review, we focus on the identification and analysis of enhancers by bioinformatics approaches. First, we describe a general framework for computational identification of enhancers, present relevant data types and discuss possible computational solutions. Next, we cover over 30 existing computational enhancer identification methods that were developed since 2000. Our review highlights advantages, limitations and potentials, while suggesting pragmatic guidelines for development of more efficient computational enhancer prediction methods. Finally, we discuss challenges and open problems of this topic, which require further consideration. PMID:26634919

A saturation hypothesis to explain both enhanced and impaired learning with enhanced plasticity

PubMed Central

Nguyen-Vu, TD Barbara; Zhao, Grace Q; Lahiri, Subhaneil; Kimpo, Rhea R; Lee, Hanmi; Ganguli, Surya; Shatz, Carla J; Raymond, Jennifer L

2017-01-01

Across many studies, animals with enhanced synaptic plasticity exhibit either enhanced or impaired learning, raising a conceptual puzzle: how enhanced plasticity can yield opposite learning outcomes? Here, we show that the recent history of experience can determine whether mice with enhanced plasticity exhibit enhanced or impaired learning in response to the same training. Mice with enhanced cerebellar LTD, due to double knockout (DKO) of MHCI H2-Kb/H2-Db (KbDb−/−), exhibited oculomotor learning deficits. However, the same mice exhibited enhanced learning after appropriate pre-training. Theoretical analysis revealed that synapses with history-dependent learning rules could recapitulate the data, and suggested that saturation may be a key factor limiting the ability of enhanced plasticity to enhance learning. Optogenetic stimulation designed to saturate LTD produced the same impairment in WT as observed in DKO mice. Overall, our results suggest that the recent history of activity and the threshold for synaptic plasticity conspire to effect divergent learning outcomes. DOI: http://dx.doi.org/10.7554/eLife.20147.001 PMID:28234229

DNA Hypomethylation in Intragenic and Intergenic Enhancer Chromatin of Muscle-Specific Genes Usually Correlates with their Expression

PubMed Central

Ehrlich, Kenneth C.; Paterson, Heather L.; Lacey, Michelle; Ehrlich, Melanie

2016-01-01

Tissue-specific enhancers are critical for gene regulation. In this study, we help elucidate the contribution of muscle-associated differential DNA methylation to the enhancer activity of highly muscle-specific genes. By bioinformatic analysis of 44 muscle-associated genes, we show that preferential gene expression in skeletal muscle (SkM) correlates with SkM-specific intragenic and intergenic enhancer chromatin and overlapping foci of DNA hypomethylation. Some genes, e.g., CASQ1 and FBXO32, displayed broad regions of both SkM- and heart-specific enhancer chromatin but exhibited focal SkM-specific DNA hypomethylation. Half of the genes had SkM-specific super-enhancers. In contrast to simple enhancer/gene-expression correlations, a super-enhancer was associated with the myogenic MYOD1 gene in both SkM and myoblasts even though SkM has < 1 percent as much MYOD1 expression. Local chromatin differences in this super-enhancer probably contribute to the SkM/myoblast differential expression. Transfection assays confirmed the tissue-specificity of the 0.3-kb core enhancer within MYOD1’s super-enhancer and demonstrated its repression by methylation of its three CG dinucleotides. Our study suggests that DNA hypomethylation increases enhancer tissue-specificity and that SkM super-enhancers sometimes are poised for physiologically important, rapid up-regulation. PMID:28018137

Spatial enhancer clustering and regulation of enhancer-proximal genes by cohesin

PubMed Central

Ing-Simmons, Elizabeth; Seitan, Vlad C.; Faure, Andre J.; Flicek, Paul; Carroll, Thomas; Dekker, Job; Fisher, Amanda G.; Lenhard, Boris

2015-01-01

In addition to mediating sister chromatid cohesion during the cell cycle, the cohesin complex associates with CTCF and with active gene regulatory elements to form long-range interactions between its binding sites. Genome-wide chromosome conformation capture had shown that cohesin's main role in interphase genome organization is in mediating interactions within architectural chromosome compartments, rather than specifying compartments per se. However, it remains unclear how cohesin-mediated interactions contribute to the regulation of gene expression. We have found that the binding of CTCF and cohesin is highly enriched at enhancers and in particular at enhancer arrays or “super-enhancers” in mouse thymocytes. Using local and global chromosome conformation capture, we demonstrate that enhancer elements associate not just in linear sequence, but also in 3D, and that spatial enhancer clustering is facilitated by cohesin. The conditional deletion of cohesin from noncycling thymocytes preserved enhancer position, H3K27ac, H4K4me1, and enhancer transcription, but weakened interactions between enhancers. Interestingly, ∼50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements. We propose a model for cohesin-dependent gene regulation in which spatial clustering of enhancer elements acts as a unified mechanism for both enhancer-promoter “connections” and “insulation.” PMID:25677180

Development and validation of a predictor of insufficient enhancement during the hepatobiliary phase of Gd-EOB-DTPA-enhanced magnetic resonance imaging.

PubMed

Cui, Enming; Long, Wansheng; Luo, Liangping; Hu, Maoqing; Huang, Liebin; Chen, Xiangmeng

2017-10-01

Background Insufficient enhancement of liver parenchyma negatively affects diagnostic accuracy of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI). Currently, there is no reliable method for predicting insufficient enhancement during the hepatobiliary phase (HBP) in Gd-EOB-DTPA-enhanced MRI. Purpose To develop a predictor for insufficient enhancement of liver parenchyma during HBP in Gd-EOB-DTPA-enhanced MRI. Material and Methods In order to formulate a HBP enhancement test (HBP-ET), clinical factors associated with relative enhancement ratio (RER) of liver parenchyma were retrospectively determined from the datasets of 156 patients (Development group) who underwent Gd-EOB-DTPA-enhanced MRI between November 2012 and May 2015. The independent clinical factors were identified by Pearson's correlation and multiple stepwise regression analysis; the performance of HBP-ET was compared to Child-Pugh score (CPS), Model for End-stage Liver Disease score (MELD), and total bilirubin (TBIL) using receiver operating characteristic (ROC) curve analysis. The datasets of 52 patients (Validation group), which were examined between June 2015 and Oct 2015, were applied to validate the HBP-ET. Results Six biochemical parameters independently influenced RER and were used to develop HBP-ET. The mean HBP-ET score of patients with insufficient enhancement was significantly higher than that of patients with sufficient enhancement ( P < 0.001) in both the Development and Validation groups. HBP-ET (area under the curve [AUC] = 0.895) had better performance in predicting insufficient enhancement than CPS (AUC = 0.707), MELD (AUC = 0.798), and TBIL (AUC = 0.729). Conclusion The HBP-ET is more accurate than routine indicators in predicting insufficient enhancement during HBP, which is valuable to aid clinical decisions.

Estrogen suppresses melatonin-enhanced hyperactivation of hamster spermatozoa

PubMed Central

FUJINOKI, Masakatsu; TAKEI, Gen L.

2015-01-01

Hamster sperm hyperactivation is enhanced by progesterone, and this progesterone-enhanced hyperactivation is suppressed by 17β-estradiol (17βE2) and γ-aminobutyric acid (GABA). Although it has been indicated that melatonin also enhances hyperactivation, it is unknown whether melatonin-enhanced hyperactivation is also suppressed by 17βE2 and GABA. In the present study, melatonin-enhanced hyperactivation was significantly suppressed by 17βE2 but not by GABA. Moreover, suppression of melatonin-enhanced hyperactivation by 17βE2 occurred through non-genomic regulation via the estrogen receptor (ER). These results suggest that enhancement of hyperactivation is regulated by melatonin and 17βE2 through non-genomic regulation. PMID:25959801

Enhancement: are ethicists excessively influenced by baseless speculations?

PubMed

Jones, D G

2006-12-01

Most commentators draw a sharp distinction between therapy and enhancement, applauding therapy and rejecting enhancement. Not only is this distinction unclear but enhancement is often seen in grandiose terms in which human beings are radically transformed. Such far-reaching visions are then used to reject current procedures such as pre-implantation genetic diagnosis. To overcome this highly problematic impasse, enhancement has been divided into three categories, ranging from the health-related enhancement of category 1, through the non-health-related enhancement of category 2, to the transhumanism or posthumanism of category 3. Arguably, most enhancements are of the category 1 variety, and hence closely related to treatment. Also, we are already enhanced, when compared with our forebears. It is only when we accept this and dispense with baseless speculation will we be in a position to conduct ethical discussions within a realistic framework.

A new method for enhancer prediction based on deep belief network.

PubMed

Bu, Hongda; Gan, Yanglan; Wang, Yang; Zhou, Shuigeng; Guan, Jihong

2017-10-16

Studies have shown that enhancers are significant regulatory elements to play crucial roles in gene expression regulation. Since enhancers are unrelated to the orientation and distance to their target genes, it is a challenging mission for scholars and researchers to accurately predicting distal enhancers. In the past years, with the high-throughout ChiP-seq technologies development, several computational techniques emerge to predict enhancers using epigenetic or genomic features. Nevertheless, the inconsistency of computational models across different cell-lines and the unsatisfactory prediction performance call for further research in this area. Here, we propose a new Deep Belief Network (DBN) based computational method for enhancer prediction, which is called EnhancerDBN. This method combines diverse features, composed of DNA sequence compositional features, DNA methylation and histone modifications. Our computational results indicate that 1) EnhancerDBN outperforms 13 existing methods in prediction, and 2) GC content and DNA methylation can serve as relevant features for enhancer prediction. Deep learning is effective in boosting the performance of enhancer prediction.

Naturalness preservation image contrast enhancement via histogram modification

NASA Astrophysics Data System (ADS)

Tian, Qi-Chong; Cohen, Laurent D.

2018-04-01

Contrast enhancement is a technique for enhancing image contrast to obtain better visual quality. Since many existing contrast enhancement algorithms usually produce over-enhanced results, the naturalness preservation is needed to be considered in the framework of image contrast enhancement. This paper proposes a naturalness preservation contrast enhancement method, which adopts the histogram matching to improve the contrast and uses the image quality assessment to automatically select the optimal target histogram. The contrast improvement and the naturalness preservation are both considered in the target histogram, so this method can avoid the over-enhancement problem. In the proposed method, the optimal target histogram is a weighted sum of the original histogram, the uniform histogram, and the Gaussian-shaped histogram. Then the structural metric and the statistical naturalness metric are used to determine the weights of corresponding histograms. At last, the contrast-enhanced image is obtained via matching the optimal target histogram. The experiments demonstrate the proposed method outperforms the compared histogram-based contrast enhancement algorithms.

Enhancer Activation Requires Trans-Recruitment of a Mega Transcription Factor Complex

PubMed Central

Liu, Zhijie; Merkurjev, Daria; Yang, Feng; Li, Wenbo; Oh, Soohwan; Friedman, Meyer J.; Song, Xiaoyuan; Zhang, Feng; Ma, Qi; Ohgi, Kenneth; Krones, Anna; Rosenfeld, Michael G.

2014-01-01

Summary Enhancers provide critical information directing cell-type specific transcriptional programs, regulated by binding of signal-dependent transcription factors and their associated cofactors. Here we report that the most strongly activated estrogen (E2)-responsive enhancers are characterized by trans-recruitment and in situ assembly of a large 1-2 MDa complex of diverse DNA-binding transcription factors by ERα at ERE-containing enhancers. We refer to enhancers recruiting these factors as mega transcription factor-bound in trans (MegaTrans) enhancers. The MegaTrans complex is a signature of the most potent functional enhancers and is required for activation of enhancer RNA transcription and recruitment of coactivators, including p300 and Med1. The MegaTrans complex functions, in part, by recruiting specific enzymatic machinery, exemplified by DNA-dependent protein kinase. Thus, MegaTrans-containing enhancers represent a cohort of functional enhancers that mediate a broad and important transcriptional program and provide a molecular explanation for transcription factor clustering and hotspots noted in the genome. PMID:25303530

Active and inactive enhancers co-operate to exert localized and long-range control of gene regulation

PubMed Central

Proudhon, Charlotte; Snetkova, Valentina; Raviram, Ramya; Lobry, Camille; Badri, Sana; Jiang, Tingting; Hao, Bingtao; Trimarchi, Thomas; Kluger, Yuval; Aifantis, Iannis; Bonneau, Richard; Skok, Jane A

2016-01-01

V(D)J recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR) loci in a lineage and stage specific manner. Unexpectedly we find that both active and inactive AgR enhancers co-operate to disseminate their effects in a localized and long-range manner. Here we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. We further establish that in T cells long-range contact and co-operation between the inactive Igk enhancer, MiEκ and the active Tcrb enhancer, Eβ, alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage and stage specific control. PMID:27239026

Contrast Enhancement Algorithm Based on Gap Adjustment for Histogram Equalization

PubMed Central

Chiu, Chung-Cheng; Ting, Chih-Chung

2016-01-01

Image enhancement methods have been widely used to improve the visual effects of images. Owing to its simplicity and effectiveness histogram equalization (HE) is one of the methods used for enhancing image contrast. However, HE may result in over-enhancement and feature loss problems that lead to unnatural look and loss of details in the processed images. Researchers have proposed various HE-based methods to solve the over-enhancement problem; however, they have largely ignored the feature loss problem. Therefore, a contrast enhancement algorithm based on gap adjustment for histogram equalization (CegaHE) is proposed. It refers to a visual contrast enhancement algorithm based on histogram equalization (VCEA), which generates visually pleasing enhanced images, and improves the enhancement effects of VCEA. CegaHE adjusts the gaps between two gray values based on the adjustment equation, which takes the properties of human visual perception into consideration, to solve the over-enhancement problem. Besides, it also alleviates the feature loss problem and further enhances the textures in the dark regions of the images to improve the quality of the processed images for human visual perception. Experimental results demonstrate that CegaHE is a reliable method for contrast enhancement and that it significantly outperforms VCEA and other methods. PMID:27338412

Moral Enhancement Meets Normative and Empirical Reality: Assessing the Practical Feasibility of Moral Enhancement Neurotechnologies.

PubMed

Dubljević, Veljko; Racine, Eric

2017-06-01

Moral enhancement refers to the possibility of making individuals and societies better from a moral standpoint. A fierce debate has emerged about the ethical aspects of moral enhancement, notably because steering moral enhancement in a particular direction involves choosing amongst a wide array of competing options, and these options entail deciding which moral theory or attributes of the moral agent would benefit from enhancement. Furthermore, the ability and effectiveness of different neurotechnologies to enhance morality have not been carefully examined. In this paper, we assess the practical feasibility of moral enhancement neurotechnologies. We reviewed the literature on neuroscience and cognitive science models of moral judgment and analyzed their implications for the specific target of intervention (cognition, volition or affect) in moral enhancement. We also reviewed and compared evidence on available neurotechnologies that could serve as tools of moral enhancement. We conclude that the predictions of rationalist, emotivist, and dual process models are at odds with evidence, while different intuitionist models of moral judgment are more likely to be aligned with it. Furthermore, the project of moral enhancement is not feasible in the near future as it rests on the use of neurointerventions, which have no moral enhancement effects or, worse, negative effects. © 2017 John Wiley & Sons Ltd.

BiRen: predicting enhancers with a deep-learning-based model using the DNA sequence alone.

PubMed

Yang, Bite; Liu, Feng; Ren, Chao; Ouyang, Zhangyi; Xie, Ziwei; Bo, Xiaochen; Shu, Wenjie

2017-07-01

Enhancer elements are noncoding stretches of DNA that play key roles in controlling gene expression programmes. Despite major efforts to develop accurate enhancer prediction methods, identifying enhancer sequences continues to be a challenge in the annotation of mammalian genomes. One of the major issues is the lack of large, sufficiently comprehensive and experimentally validated enhancers for humans or other species. Thus, the development of computational methods based on limited experimentally validated enhancers and deciphering the transcriptional regulatory code encoded in the enhancer sequences is urgent. We present a deep-learning-based hybrid architecture, BiRen, which predicts enhancers using the DNA sequence alone. Our results demonstrate that BiRen can learn common enhancer patterns directly from the DNA sequence and exhibits superior accuracy, robustness and generalizability in enhancer prediction relative to other state-of-the-art enhancer predictors based on sequence characteristics. Our BiRen will enable researchers to acquire a deeper understanding of the regulatory code of enhancer sequences. Our BiRen method can be freely accessed at https://github.com/wenjiegroup/BiRen . shuwj@bmi.ac.cn or boxc@bmi.ac.cn. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Comparison of Inner Ear Contrast Enhancement among Patients with Unilateral Inner Ear Symptoms in MR Images Obtained 10 Minutes and 4 Hours after Gadolinium Injection.

PubMed

Kim, T Y; Park, D W; Lee, Y J; Lee, J Y; Lee, S H; Chung, J H; Lee, S

2015-12-01

Recently 4-hour delayed-enhanced 3D-FLAIR MR imaging has been used in pathophysiologic analysis of the inner ear in many auditory diseases, including sudden sensorineural hearing loss, but comparison among different time points is not clear in patients with unilateral inner ear symptoms. We compared the signal-intensity ratios of the inner ears in patients with unilateral inner ear symptoms on 10-minute delayed-enhanced and 4-hour delayed-enhanced 3D-FLAIR MR images after IV gadolinium injection. The 10-minute delayed-enhanced and 4-hour delayed-enhanced 3D-FLAIR MR images were retrospectively analyzed. Signal-intensity ratios between the cerebellum and inner ear structures, such as the cochleae, vestibules, and vestibulocochlear nerve were assessed. Multiple comparisons were performed. Signal-intensity ratios of the affected cochleae, vestibules, and vestibulocochlear nerve were higher than those of unaffected sides in both 10-minute delayed-enhanced and 4-hour delayed-enhanced images. At the affected side, signal-intensity ratios of the vestibulocochlear nerve were higher in patients with nonsudden sensorineural hearing loss than in those with sudden sensorineural hearing loss on both 10-minute delayed-enhanced and 4-hour delayed-enhanced images. The signal-intensity ratios of some affected inner ear structures were higher than those of the unaffected sides in a group of 30 patients with sudden sensorineural hearing loss and 20 patients with nonsudden sensorineural hearing loss on 10-minute delayed-enhanced and 4-hour delayed-enhanced images. Signal-intensity ratios of the inner ear show statistically significant increases in many diseases, especially neuritis, in 10-minute delayed-enhanced and 4-hour delayed-enhanced images. The 4-hour delayed-enhanced images may be superior in neural inflammatory-dominant conditions, while 10-minute delayed-enhanced images may be superior in neural noninflammatory-dominant conditions. © 2015 by American Journal of Neuroradiology.

Method for enhancing amidohydrolase activity of fatty acid amide hydrolase

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

John, George; Nagarajan, Subbiah; Chapman, Kent

A method for enhancing amidohydrolase activity of Fatty Acid Amide Hydrolase (FAAH) is disclosed. The method comprising administering a phenoxyacyl-ethanolamide that causes the enhanced activity. The enhanced activity can have numerous effects on biological organisms including, for example, enhancing the growth of certain seedlings.

Comparative cardiopulmonary effects of particulate matter- and ozone-enhanced smog atmospheres in mice

EPA Science Inventory

This study was conducted to compare the cardiac effects of particulate matter (PM)-enhanced and ozone(O3)-enhanced smog atmospheres in mice. We hypothesized that O3-enhanced smog would cause greater cardiac dysfunction than PM-enhanced smog due to the higher concentrations of irr...

40 CFR 141.134 - Reporting and recordkeeping requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... byproduct precursors and enhanced coagulation or enhanced softening. Systems must report the information... quarterly for TOC under the requirements of § 141.132(d) and required to meet the enhanced coagulation or... compliance with the enhanced coagulation or enhanced softening percent removal requirements in § 141.135(b...

40 CFR 141.134 - Reporting and recordkeeping requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... byproduct precursors and enhanced coagulation or enhanced softening. Systems must report the information... quarterly for TOC under the requirements of § 141.132(d) and required to meet the enhanced coagulation or... compliance with the enhanced coagulation or enhanced softening percent removal requirements in § 141.135(b...

40 CFR 141.134 - Reporting and recordkeeping requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... byproduct precursors and enhanced coagulation or enhanced softening. Systems must report the information... quarterly for TOC under the requirements of § 141.132(d) and required to meet the enhanced coagulation or... compliance with the enhanced coagulation or enhanced softening percent removal requirements in § 141.135(b...

JPRS Report, Science & Technology, Japan, 4th International Conference on Langmuir-Blodgett Films

DTIC Science & Technology

1989-08-23

Toshiba-cho, Saiwai-ku, Kawasaki, 210 Japan Surface enhanced resonance Raman scattering (SERRS) from a Langmuir-Blodgett monolayer of 4’-n...4000 cm" . These results show that the spectra are affected by the enhancement due to resonance Raman scattering . The dependence of SERRS intensity...enhanced adsorption is one of the surface enhanced processes such as the surface enhanced Raman scattering (SERS) and the enhanced fluorescence. There

Enhancement and Civic Virtue

PubMed Central

Jefferson, Will; Douglas, Thomas; Kahane, Guy; Savulescu, Julian

2014-01-01

Opponents of biomedical enhancement frequently adopt what Allen Buchanan has called the Personal Goods Assumption. On this assumption, the benefits of biomedical enhancement will accrue primarily to those individuals who undergo enhancements, not to wider society. Buchanan has argued that biomedical enhancements might in fact have substantial social benefits by increasing productivity. We outline another way in which enhancements might benefit wider society: by augmenting civic virtue and thus improving the functioning of our political communities. We thus directly confront critics of biomedical enhancement who argue that it will lead to a loss of social cohesion and a breakdown in political life. PMID:24882886

Recurrent medulloblastoma: Frequency of tumor enhancement on Gd-DTPA MR imaging

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

Rollins, N.; Mendelsohn, D.; Mulne, A.

1990-05-01

Thirty-two children with medulloblastoma were evaluated postoperatively with conventional and gadolinium-enhanced MR imaging. Eleven patients had abnormal cranial MR studies; nine of these had recurrent tumor. In six patients recurrent tumor enhanced with Gd, while in the other three patients recurrent tumor did not enhance. The remaining two patients had areas of abnormal Gd enhancement that were caused by radiation-induced breakdown of the blood-brain barrier rather than by recurrent tumor. This study shows that not all recurrent medulloblastoma enhances and that the absence of Gd enhancement does not necessarily indicate the absence of recurrent tumor.

Recurrent medulloblastoma: Frequency of tumor enhancement on Gd-DTPA MR imaging

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

Rollins, N.; Mendelsohn, D.; Mulne, A.

1990-07-01

Thirty-two children with medulloblastoma were evaluated postoperatively with conventional and gadolinium-enhanced MR imaging. Eleven patients had abnormal cranial MR studies; nine of these had recurrent tumor. In six patients recurrent tumor enhanced with Gd, while in the other three patients recurrent tumor did not enhance. The remaining two patients had areas of abnormal Gd enhancement that were caused by radiation-induced breakdown of the blood-brain barrier rather than by recurrent tumor. This study shows that not all recurrent medulloblastoma enhances and that the absence of Gd enhancement does not necessarily indicate the absence of recurrent tumor.

Genetic enhancement in sport: just another form of doping?

PubMed

Mehlman, Maxwell J

2012-12-01

Patented genetic technologies such as the ACTN3 genetic test are adding a new dimension to the types of performance enhancement available to elite athletes. Organized sports organizations and governments are seeking to prevent athletes' use of biomedical enhancements. This paper discusses how these interdiction efforts will affect the use and availability of genetic technologies that can enhance athletic performance. The paper provides a working definition of enhancement, and in light of that definition and the concerns of the sports community, reviews genetic enhancement as a result of varied technologies, including, genetic testing to identify innate athletic ability, performance-enhancing drugs developed with genetic science and technology, pharmacogenetics, enhancement through reproductive technologies, somatic gene transfer, and germ line gene transfer.

Do cultures vary in self-enhancement? ERP, behavioral, and self-report evidence.

PubMed

Hampton, Ryan S; Varnum, Michael E W

2017-08-02

Psychologists have long debated whether self-enhancement is universal or varies across cultures. Extant studies using explicit and implicit measures have provided mixed results. In this study (N = 93; 35 European American, 58 Chinese: 28 tested in English, 30 tested in Mandarin), we measured self-enhancement covertly using an ERP paradigm. Self-enhancement was also assessed via self-report and reaction-time based measures. Americans showed strong evidence of self-enhancement across all measures, whereas this effect was absent or weaker among Chinese, who instead showed an other-enhancing bias across measures. Language did not affect self-enhancement tendencies among Chinese participants, with the exception of one self-report measure. Nor did the two cultural groups differ in enhancement for a close other. This is the first study to directly compare self-enhancement across cultural groups using ERPs and provides evidence that positive self-regard does indeed vary by culture.

Cognitive diversity and moral enhancement.

PubMed

Gyngell, Chris; Easteal, Simon

2015-01-01

One debate in contemporary bioethics centers on whether the development of cognitive enhancement technologies (CETs) will hasten the need for moral enhancement. In this article we provide a new argument in favor of pursuing these enhancement technologies together. The widespread availability of CETs will likely increase population-level cognitive diversity. Different people will choose to enhance different aspects of their cognition, and some won't enhance themselves at all. Although this has the potential to be beneficial for society, it could also result in harms as people become more different from one another. Aspects of our moral psychology make it difficult for people to cooperate and coordinate actions with those who are very different from themselves. These moral failings could be targeted by moral enhancement technologies, which may improve cooperation among individuals. Moral enhancement technologies will therefore help society maximize the benefits, and reduce the costs, associated with widespread access to cognitive enhancements.

Super-enhancer-mediated RNA processing revealed by integrative microRNA network analysis

PubMed Central

Suzuki, Hiroshi I.; Young, Richard A; Sharp, Phillip A

2017-01-01

Summary Super-enhancers are an emerging sub-class of regulatory regions controlling cell identity and disease genes. However, their biological function and impact on miRNA networks are unclear. Here we report that super-enhancers drive the biogenesis of master miRNAs crucial for cell identity by enhancing both transcription and Drosha/DGCR8-mediated primary miRNA (pri-miRNA) processing. Super-enhancers, together with broad H3K4me3 domains, shape a tissue-specific and evolutionarily conserved atlas of miRNA expression and function. CRISPR/Cas9 genomics revealed that super-enhancer constituents act cooperatively and facilitate Drosha/DGCR8 recruitment and pri-miRNA processing to boost cell-specific miRNA production. The BET-bromodomain inhibitor JQ1 preferentially inhibits super-enhancer-directed cotranscriptional pri-miRNA processing. Furthermore, super-enhancers are characterized by pervasive interaction with DGCR8/Drosha and DGCR8/Drosha-regulated mRNA stability control, suggesting unique RNA regulation at super-enhancers. Finally, super-enhancers mark multiple miRNAs associated with cancer hallmarks. This study presents principles underlying miRNA biology in health and disease and a unrecognized higher-order property of super-enhancers in RNA processing beyond transcription. PMID:28283057

Low enhancement on multiphase contrast-enhanced CT images: an independent predictor of the presence of high tumor grade of clear cell renal cell carcinoma.

PubMed

Zhu, Ye-Hua; Wang, Xun; Zhang, Jin; Chen, Yong-Hui; Kong, Wen; Huang, Yi-Ran

2014-09-01

The purpose of this study was to assess the relation between tumor enhancement on multiphase contrast-enhanced CT images and Fuhrman grade of clear cell renal cell carcinoma. A single-institution retrospective review was conducted on the records of 255 patients who underwent radical or partial nephrectomy and received a histologic diagnosis of clear cell renal cell carcinoma. Two radiologists recorded the radiographic features of each patient, including the attenuation value of the lesion, lesion size, calcification within the lesion, cystic versus solid appearance, and margin regularity. Parameters representing the extent of tumor enhancement were defined and calculated. The association between tumor enhancement and Fuhrman grade was analyzed, and multivariate analysis was performed to find independent predictors of high tumor grade. Significant differences existed in tumor enhancement among different Fuhrman grades (p < 0.001). High-grade tumors had significantly lower enhancement (p < 0.001). The enhancement parameter had a sensitivity of 0.84 and specificity of 0.93 in prediction of high tumor grade. In the multivariate analysis, more advanced age, irregular margin, and low tumor enhancement were the three independent predictors of high tumor grade. Tumor enhancement of clear cell renal cell carcinoma on multiphase contrast-enhanced CT images is associated with Fuhrman grade. Low tumor enhancement in the corticomedullary phase is an independent predictor of high tumor grade. This system may be helpful in clinical decision making about the care of patients treated by nonsurgical approaches.

Contrast-enhanced fluid-attenuated inversion recovery vs. contrast-enhanced spin echo T1-weighted brain imaging.

PubMed

Falzone, Cristian; Rossi, Federica; Calistri, Maurizio; Tranquillo, Massimo; Baroni, Massimo

2008-01-01

In humans, contrast-enhanced fluid-attenuated inversion recovery (FLAIR) imaging plays an important role in detecting brain disease. The aim of this study was to define the clinical utility of contrast-enhanced FLAIR imaging by comparing the results with those with contrast-enhanced spin echo T1-weighted images (SE T1WI) in animals with different brain disorders. Forty-one dogs and five cats with a clinical suspicion of brain disease and 30 normal animals (25 dogs and five cats) were evaluated using a 0.2 T permanent magnet. Before contrast medium injection, spin echo T1-weighted, SE T1WI, and FLAIR sequences were acquired in three planes. SE T1WI and FLAIR images were also acquired after gadolinium injection. Sensitivity in detecting the number, location, margin, and enhancement pattern and rate were evaluated. No lesions were found in a normal animal. In affected animals, 48 lesions in 34 patients were detected in contrast-enhanced SE T1WI whereas 81 lesions in 44 patients were detected in contrast-enhanced FLAIR images. There was no difference in the characteristics of the margins or enhancement pattern of the detected lesions. The objective enhancement rate, the mean value between lesion-to-white matter ratio and lesion-to-gray matter ratio, although representing an overlap of T1 and T2 effects and not pure contrast medium shortening of T1 relaxation, was better in contrast-enhanced FLAIR images. These results suggest a superiority of contrast-enhanced FLAIR images as compared with contrast-enhanced SE T1WI in detecting enhancing brain lesions.

Surface-enhanced Raman scattering from AgNP-graphene-AgNP sandwiched nanostructures

NASA Astrophysics Data System (ADS)

Wu, Jian; Xu, Yijun; Xu, Pengyu; Pan, Zhenghui; Chen, Sheng; Shen, Qishen; Zhan, Li; Zhang, Yuegang; Ni, Weihai

2015-10-01

We developed a facile approach toward hybrid AgNP-graphene-AgNP sandwiched structures using self-organized monolayered AgNPs from wet chemical synthesis for the optimized enhancement of the Raman response of monolayer graphene. We demonstrate that the Raman scattering of graphene can be enhanced 530 fold in the hybrid structure. The Raman enhancement is sensitively dependent on the hybrid structure, incident angle, and excitation wavelength. A systematic simulation is performed, which well explains the enhancement mechanism. Our study indicates that the enhancement resulted from the plasmonic coupling between the AgNPs on the opposite sides of graphene. Our approach towards ideal substrates offers great potential to produce a ``hot surface'' for enhancing the Raman response of two-dimensional materials.We developed a facile approach toward hybrid AgNP-graphene-AgNP sandwiched structures using self-organized monolayered AgNPs from wet chemical synthesis for the optimized enhancement of the Raman response of monolayer graphene. We demonstrate that the Raman scattering of graphene can be enhanced 530 fold in the hybrid structure. The Raman enhancement is sensitively dependent on the hybrid structure, incident angle, and excitation wavelength. A systematic simulation is performed, which well explains the enhancement mechanism. Our study indicates that the enhancement resulted from the plasmonic coupling between the AgNPs on the opposite sides of graphene. Our approach towards ideal substrates offers great potential to produce a ``hot surface'' for enhancing the Raman response of two-dimensional materials. Electronic supplementary information (ESI) available: Additional SEM images, electric field enhancement profiles, Raman scattering spectra, and structure-dependent peak ratios. See DOI: 10.1039/c5nr04500b

Niobium pentoxide: a promising surface-enhanced Raman scattering active semiconductor substrate

NASA Astrophysics Data System (ADS)

Shan, Yufeng; Zheng, Zhihui; Liu, Jianjun; Yang, Yong; Li, Zhiyuan; Huang, Zhengren; Jiang, Dongliang

2017-03-01

Surface-enhanced Raman scattering technique, as a powerful tool to identify the molecular species, has been severely restricted to the noble metals. The surface-enhanced Raman scattering substrates based on semiconductors would overcome the shortcomings of metal substrates and promote development of surface-enhanced Raman scattering technique in surface science, spectroscopy, and biomedicine studies. However, the detection sensitivity and enhancement effects of semiconductor substrates are suffering from their weak activities. In this work, a semiconductor based on Nb2O5 is reported as a new candidate for highly sensitive surface-enhanced Raman scattering detection of dye molecules. The largest enhancement factor value greater than 107 was observed with the laser excitation at 633 and 780 nm for methylene blue detection. As far as literature review shows, this is in the rank of the highest sensitivity among semiconductor materials; even comparable to the metal nanostructure substrates with "hot spots". The impressive surface-enhanced Raman scattering activities can be attributed to the chemical enhancement dominated by the photo-induced charge transfer, as well as the electromagnetic enhancement, which have been supported by the density-functional-theory and finite element method calculation results. The chemisorption of dye on Nb2O5 creates a new highest occupied molecular orbital and lowest unoccupied molecular orbital contributed by both fragments in the molecule-Nb2O5 system, which makes the charge transfer more feasible with longer excitation wavelength. In addition, the electromagnetic enhancement mechanism also accounts for two orders of magnitude enhancement in the overall enhancement factor value. This work has revealed Nb2O5 nanoparticles as a new semiconductor surface-enhanced Raman scattering substrate that is able to replace noble metals and shows great potentials applied in the fields of biology related.

Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease

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

Ounzain, Samir; Pezzuto, Iole; Micheletti, Rudi

We report here that the key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Throughmore » a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.« less

Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease

DOE PAGES

Ounzain, Samir; Pezzuto, Iole; Micheletti, Rudi; ...

2014-08-19

We report here that the key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Throughmore » a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.« less

iEnhancer-EL: Identifying enhancers and their strength with ensemble learning approach.

PubMed

Liu, Bin; Li, Kai; Huang, De-Shuang; Chou, Kuo-Chen

2018-06-07

Identification of enhancers and their strength is important because they play a critical role in controlling gene expression. Although some bioinformatics tools were developed, they are limited in discriminating enhancers from non-enhancers only. Recently, a two-layer predictor called "iEnhancer-2L" was developed that can be used to predict the enhancer's strength as well. However, its prediction quality needs further improvement to enhance the practical application value. A new predictor called "iEnhancer-EL" was proposed that contains two layer predictors: the first one (for identifying enhancers) is formed by fusing an array of six key individual classifiers, and the second one (for their strength) formed by fusing an array of ten key individual classifiers. All these key classifiers were selected from 171 elementary classifiers formed by SVM (Support Vector Machine) based on kmer, subsequence profile, and PseKNC (Pseudo K-tuple Nucleotide Composition), respectively. Rigorous cross-validations have indicated that the proposed predictor is remarkably superior to the existing state-of-the-art one in this area. A web server for the iEnhancer-EL has been established at http://bioinformatics.hitsz.edu.cn/iEnhancer-EL/, by which users can easily get their desired results without the need to go through the mathematical details. bliu@hit.edu.cn, dshuang@tongji.edu.cn or kcchou@gordonlifescience.org. Supplementary data are available at Bioinformatics online.

Adjacent DNA sequences modulate Sox9 transcriptional activation at paired Sox sites in three chondrocyte-specific enhancer elements

PubMed Central

Bridgewater, Laura C.; Walker, Marlan D.; Miller, Gwen C.; Ellison, Trevor A.; Holsinger, L. Daniel; Potter, Jennifer L.; Jackson, Todd L.; Chen, Reuben K.; Winkel, Vicki L.; Zhang, Zhaoping; McKinney, Sandra; de Crombrugghe, Benoit

2003-01-01

Expression of the type XI collagen gene Col11a2 is directed to cartilage by at least three chondrocyte-specific enhancer elements, two in the 5′ region and one in the first intron of the gene. The three enhancers each contain two heptameric sites with homology to the Sox protein-binding consensus sequence. The two sites are separated by 3 or 4 bp and arranged in opposite orientation to each other. Targeted mutational analyses of these three enhancers showed that in the intronic enhancer, as in the other two enhancers, both Sox sites in a pair are essential for enhancer activity. The transcription factor Sox9 binds as a dimer at the paired sites, and the introduction of insertion mutations between the sites demonstrated that physical interactions between the adjacently bound proteins are essential for enhancer activity. Additional mutational analyses demonstrated that although Sox9 binding at the paired Sox sites is necessary for enhancer activity, it alone is not sufficient. Adjacent DNA sequences in each enhancer are also required, and mutation of those sequences can eliminate enhancer activity without preventing Sox9 binding. The data suggest a new model in which adjacently bound proteins affect the DNA bend angle produced by Sox9, which in turn determines whether an active transcriptional enhancer complex is assembled. PMID:12595563

Nutrient Composition of Enhanced and Non-enhanced Boneless Skinless Chicken Breast Fillets Purchased from Retail

USDA-ARS?s Scientific Manuscript database

The objective of this study was to compare nutritional composition of raw enhanced (E) and non-enhanced (NE), boneless, skinless chicken breast fillets (pectoralis major), obtained from U.S. retail supermarkets. Fillets were either enhanced with a salt, phosphate, and water solution, or were non-en...

A Framework for Examining the Utility of Technology-Enhanced Items

ERIC Educational Resources Information Center

Russell, Michael

2016-01-01

Interest in and use of technology-enhanced items has increased over the past decade. Given the additional time required to administer many technology-enhanced items and the increased expense required to develop them, it is important for testing programs to consider the utility of technology-enhanced items. The Technology-Enhanced Item Utility…

Active and Inactive Enhancers Cooperate to Exert Localized and Long-Range Control of Gene Regulation.

PubMed

Proudhon, Charlotte; Snetkova, Valentina; Raviram, Ramya; Lobry, Camille; Badri, Sana; Jiang, Tingting; Hao, Bingtao; Trimarchi, Thomas; Kluger, Yuval; Aifantis, Iannis; Bonneau, Richard; Skok, Jane A

2016-06-07

V(D)J recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR) loci in a lineage- and stage-specific manner. Unexpectedly, we find that both active and inactive AgR enhancers cooperate to disseminate their effects in a localized and long-range manner. Here, we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. Furthermore, we establish that, in T cells, long-range contact and cooperation between the inactive Igk enhancer MiEκ and the active Tcrb enhancer Eβ alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage- and stage-specific control. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Enhancement factor in low-coherence enhanced backscattering and its applications for characterizing experimental skin carcinogenesis

NASA Astrophysics Data System (ADS)

Liu, Jingjing; Xu, Zhengbin; Song, Qinghai; Konger, Raymond L.; Kim, Young L.

2010-05-01

We experimentally study potential mechanisms by which the enhancement factor in low-coherence enhanced backscattering (LEBS) can probe subtle variations in radial intensity distribution in weakly scattering media. We use enhanced backscattering of light by implementing either (1) low spatial coherence illumination or (2) multiple spatially independent detections using a microlens array under spatially coherent illumination. We show that the enhancement factor in these configurations is a measure of the integrated intensity within the localized coherence or detection area, which can exhibit strong dependence on small perturbations in scattering properties. To further evaluate the utility of the LEBS enhancement factor, we use a well-established animal model of cutaneous two-stage chemical carcinogenesis. In this pilot study, we demonstrate that the LEBS enhancement factor can be substantially altered at a stage of preneoplasia. Our animal result supports the idea that early carcinogenesis can cause subtle alterations in the scattering properties that can be captured by the LEBS enhancement factor. Thus, the LEBS enhancement factor has the potential as an easily measurable biomarker in skin carcinogenesis.

Novel medical image enhancement algorithms

NASA Astrophysics Data System (ADS)

Agaian, Sos; McClendon, Stephen A.

2010-01-01

In this paper, we present two novel medical image enhancement algorithms. The first, a global image enhancement algorithm, utilizes an alpha-trimmed mean filter as its backbone to sharpen images. The second algorithm uses a cascaded unsharp masking technique to separate the high frequency components of an image in order for them to be enhanced using a modified adaptive contrast enhancement algorithm. Experimental results from enhancing electron microscopy, radiological, CT scan and MRI scan images, using the MATLAB environment, are then compared to the original images as well as other enhancement methods, such as histogram equalization and two forms of adaptive contrast enhancement. An image processing scheme for electron microscopy images of Purkinje cells will also be implemented and utilized as a comparison tool to evaluate the performance of our algorithm.

Clinical utility of three-dimensional contrast-enhanced ultrasound in the differentiation between noninvasive and invasive neoplasms of urinary bladder.

PubMed

Li, Qiu-yang; Tang, Jie; He, En-hui; Li, Yan-mi; Zhou, Yun; Zhang, Xu; Chen, Guangfu

2012-11-01

The purpose of this study was to evaluate the effectiveness of three-dimensional contrast-enhanced ultrasound in differentiating invasive and noninvasive neoplasms of urinary bladder. A total of 60 lesions in 60 consecutive patients with bladder tumors received three dimensional ultrasonography, low acoustic power contrast enhanced ultrasonography and low acoustic power three-dimensional contrast-enhanced ultrasound examination. The IU22 ultrasound scanner and a volume transducer were used and the ultrasound contrast agent was SonoVue. The contrast-specific sonographic imaging modes were PI (pulse inversion) and PM (power modulation). The three dimensional ultrasonography, contrast enhanced ultrasonography, and three-dimensional contrast-enhanced ultrasound images were independently reviewed by two readers who were not in the images acquisition. Images were analyzed off-site. A level of confidence in the diagnosis of tumor invasion of the muscle layer was assigned on a 5° scale. Receiver operating characteristic analysis was used to assess overall confidence in the diagnosis of muscle invasion by tumor. Kappa values were used to assess inter-readers agreement. Histologic diagnosis was obtained for all patients. Final pathologic staging revealed 44 noninvasive tumors and 16 invasive tumors. Three-dimensional contrast-enhanced ultrasound depicted all 16 muscle-invasive tumors. The diagnostic performance of three-dimensional contrast-enhanced ultrasound was better than those of three dimensional ultrasonography and contrast enhanced ultrasonography. The receiver operating characteristic curves were 0.976 and 0.967 for three-dimensional contrast-enhanced ultrasound, those for three dimensional ultrasonography were 0.881 and 0.869, those for contrast enhanced ultrasonography were 0.927 and 0.929. The kappa values in the three dimensional ultrasonography, contrast enhanced ultrasonography and three-dimensional contrast-enhanced ultrasound for inter-reader agreements were 0.717, 0.794 and 0.914. Three-dimensional contrast-enhanced ultrasound imaging, with contrast-enhanced spatial visualization is clinical useful for differentiating invasive and noninvasive neoplasms of urinary bladder objectively. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Digital enhancement of sub-quality bitemark photographs.

PubMed

Karazalus, C P; Palmbach, T T; Lee, H C

2001-07-01

Digital enhancement software was used to enhance bitemark photographs. This enhancement technique improved the resolution of the bitemark images. Lucis was the software program utilized in this study and case applications. First, this technique was applied on known bitemark images to evaluate the potential effectiveness of this digital enhancement method. Subsequently, Lucis was utilized on two separate unsolved cases involving enhancement of bitemark evidence. One case involved a severely beaten infant with a bitemark on the upper thigh. The second case involves a bitemark observed on the breast of a female sexual assault strangulation victim. In both cases, bitemark images were significantly improved after digital enhancement.

Use of a Drosophila Genome-Wide Conserved Sequence Database to Identify Functionally Related cis-Regulatory Enhancers

PubMed Central

Brody, Thomas; Yavatkar, Amarendra S; Kuzin, Alexander; Kundu, Mukta; Tyson, Leonard J; Ross, Jermaine; Lin, Tzu-Yang; Lee, Chi-Hon; Awasaki, Takeshi; Lee, Tzumin; Odenwald, Ward F

2012-01-01

Background: Phylogenetic footprinting has revealed that cis-regulatory enhancers consist of conserved DNA sequence clusters (CSCs). Currently, there is no systematic approach for enhancer discovery and analysis that takes full-advantage of the sequence information within enhancer CSCs. Results: We have generated a Drosophila genome-wide database of conserved DNA consisting of >100,000 CSCs derived from EvoPrints spanning over 90% of the genome. cis-Decoder database search and alignment algorithms enable the discovery of functionally related enhancers. The program first identifies conserved repeat elements within an input enhancer and then searches the database for CSCs that score highly against the input CSC. Scoring is based on shared repeats as well as uniquely shared matches, and includes measures of the balance of shared elements, a diagnostic that has proven to be useful in predicting cis-regulatory function. To demonstrate the utility of these tools, a temporally-restricted CNS neuroblast enhancer was used to identify other functionally related enhancers and analyze their structural organization. Conclusions: cis-Decoder reveals that co-regulating enhancers consist of combinations of overlapping shared sequence elements, providing insights into the mode of integration of multiple regulating transcription factors. The database and accompanying algorithms should prove useful in the discovery and analysis of enhancers involved in any developmental process. Developmental Dynamics 241:169–189, 2012. © 2011 Wiley Periodicals, Inc. Key findings A genome-wide catalog of Drosophila conserved DNA sequence clusters. cis-Decoder discovers functionally related enhancers. Functionally related enhancers share balanced sequence element copy numbers. Many enhancers function during multiple phases of development. PMID:22174086

Postoperative enhancement on breast MRI: Time course and pattern of changes.

PubMed

Mahoney, Mary C; Sharda, Radhika G

2018-04-23

Expected postoperative enhancement on breast MRI can appear similar to enhancement seen in recurrent or residual malignancy. Our aim was to assess the time course and patterns of enhancement at the surgical site, thereby helping to distinguish between benign and malignant postoperative enhancement. In 200 MRI scans performed in 153 patients after breast conservation treatment, 43 after surgical excision of atypia, and 4 patients after benign excisional biopsy were categorized by postoperative time interval. We defined 4 patterns of morphologic enhancement on MRI: cavity wall/seroma (Pattern I); thin linear (Pattern II); mass (Pattern III); and fat necrosis (Pattern IV). Of 200 MRI scans, 66 (33%) demonstrated enhancement at the surgical site. Enhancement typically decreased through the postoperative follow-up period. Enhancement was observed in 41% (28/68) of cases beyond the 18-month interval but was uncommon after 5 years. Pattern III enhancement was the morphologic pattern seen most commonly with malignancy (5/19 cases, 26%). When associated with delayed washout kinetics, it was even more strongly predictive of malignancy (4/5 cases, 80%). In patients with a history of excisional biopsy and no prior radiation treatment, the percentage of MRI scans showing enhancement was significantly lower than (21% vs 49% with P-value .0027) in patients who had undergone radiation. Enhancement at the surgical site occurred in one-third of cases up to 5 years after surgery, particularly in patients who underwent both radiation and surgery. Mass enhancement, particularly in conjunction with delayed washout kinetics, is most predictive of malignancy and should prompt biopsy or re-excision. © 2018 Wiley Periodicals, Inc.

Patterns of contrast enhancement in the brain and meninges.

PubMed

Smirniotopoulos, James G; Murphy, Frances M; Rushing, Elizabeth J; Rees, John H; Schroeder, Jason W

2007-01-01

Contrast material enhancement for cross-sectional imaging has been used since the mid 1970s for computed tomography and the mid 1980s for magnetic resonance imaging. Knowledge of the patterns and mechanisms of contrast enhancement facilitate radiologic differential diagnosis. Brain and spinal cord enhancement is related to both intravascular and extravascular contrast material. Extraaxial enhancing lesions include primary neoplasms (meningioma), granulomatous disease (sarcoid), and metastases (which often manifest as mass lesions). Linear pachymeningeal (dura-arachnoid) enhancement occurs after surgery and with spontaneous intracranial hypotension. Leptomeningeal (pia-arachnoid) enhancement is present in meningitis and meningoencephalitis. Superficial gyral enhancement is seen after reperfusion in cerebral ischemia, during the healing phase of cerebral infarction, and with encephalitis. Nodular subcortical lesions are typical for hematogenous dissemination and may be neoplastic (metastases) or infectious (septic emboli). Deeper lesions may form rings or affect the ventricular margins. Ring enhancement that is smooth and thin is typical of an organizing abscess, whereas thick irregular rings suggest a necrotic neoplasm. Some low-grade neoplasms are "fluid-secreting," and they may form heterogeneously enhancing lesions with an incomplete ring sign as well as the classic "cyst-with-nodule" morphology. Demyelinating lesions, including both classic multiple sclerosis and tumefactive demyelination, may also create an open ring or incomplete ring sign. Thick and irregular periventricular enhancement is typical for primary central nervous system lymphoma. Thin enhancement of the ventricular margin occurs with infectious ependymitis. Understanding the classic patterns of lesion enhancement--and the radiologic-pathologic mechanisms that produce them--can improve image assessment and differential diagnosis.

Sequential contrast-enhanced MR imaging of the penis.

PubMed

Kaneko, K; De Mouy, E H; Lee, B E

1994-04-01

To determine the enhancement patterns of the penis at magnetic resonance (MR) imaging. Sequential contrast material-enhanced MR images of the penis in a flaccid state were obtained in 16 volunteers (12 with normal penile function and four with erectile dysfunction). Subjects with normal erectile function showed gradual and centrifugal enhancement of the corpora cavernosa, while those with erectile dysfunction showed poor enhancement with abnormal progression. Sequential contrast-enhanced MR imaging provides additional morphologic information for the evaluation of erectile dysfunction.

Field-enhanced electrodes for additive-injection non-thermal plasma (NTP) processor

DOEpatents

Rosocha, Louis A [Los Alamos, NM; Ferreri, Vincent [Westminster, CO; Kim, Yongho [Los Alamos, NM

2009-04-21

The present invention comprises a field enhanced electrode package for use in a non-thermal plasma processor. The field enhanced electrode package includes a high voltage electrode and a field-enhancing electrode with a dielectric material layer disposed in-between the high voltage electrode and the field-enhancing electrode. The field-enhancing electrode features at least one raised section that includes at least one injection hole that allows plasma discharge streamers to occur primarily within an injected additive gas.

Image contrast enhancement using adjacent-blocks-based modification for local histogram equalization

NASA Astrophysics Data System (ADS)

Wang, Yang; Pan, Zhibin

2017-11-01

Infrared images usually have some non-ideal characteristics such as weak target-to-background contrast and strong noise. Because of these characteristics, it is necessary to apply the contrast enhancement algorithm to improve the visual quality of infrared images. Histogram equalization (HE) algorithm is a widely used contrast enhancement algorithm due to its effectiveness and simple implementation. But a drawback of HE algorithm is that the local contrast of an image cannot be equally enhanced. Local histogram equalization algorithms are proved to be the effective techniques for local image contrast enhancement. However, over-enhancement of noise and artifacts can be easily found in the local histogram equalization enhanced images. In this paper, a new contrast enhancement technique based on local histogram equalization algorithm is proposed to overcome the drawbacks mentioned above. The input images are segmented into three kinds of overlapped sub-blocks using the gradients of them. To overcome the over-enhancement effect, the histograms of these sub-blocks are then modified by adjacent sub-blocks. We pay more attention to improve the contrast of detail information while the brightness of the flat region in these sub-blocks is well preserved. It will be shown that the proposed algorithm outperforms other related algorithms by enhancing the local contrast without introducing over-enhancement effects and additional noise.

The local enhancement conundrum: in search of the adaptive value of a social learning mechanism.

PubMed

Arbilly, Michal; Laland, Kevin N

2014-02-01

Social learning mechanisms are widely thought to vary in their degree of complexity as well as in their prevalence in the natural world. While learning the properties of a stimulus that generalize to similar stimuli at other locations (stimulus enhancement) prima facie appears more useful to an animal than learning about a specific stimulus at a specific location (local enhancement), empirical evidence suggests that the latter is much more widespread in nature. Simulating populations engaged in a producer-scrounger game, we sought to deploy mathematical models to identify the adaptive benefits of reliance on local enhancement and/or stimulus enhancement, and the alternative conditions favoring their evolution. Surprisingly, we found that while stimulus enhancement readily evolves, local enhancement is advantageous only under highly restricted conditions: when generalization of information was made unreliable or when error in social learning was high. Our results generate a conundrum over how seemingly conflicting empirical and theoretical findings can be reconciled. Perhaps the prevalence of local enhancement in nature is due to stimulus enhancement costs independent of the learning task itself (e.g. predation risk), perhaps natural habitats are often characterized by unreliable yet highly rewarding payoffs, or perhaps local enhancement occurs less frequently, and stimulus enhancement more frequently, than widely believed. Copyright © 2013 Elsevier Inc. All rights reserved.

Enhancement of linear/nonlinear optical responses of molecular vibrations using metal nanoantennas

NASA Astrophysics Data System (ADS)

Morichika, Ikki; Kusa, Fumiya; Takegami, Akinobu; Ashihara, Satoshi

2017-04-01

Plasmonic enhancements of optical near-fields with metal nanostructures offer extensive potential for amplifying lightmatter interactions. We analytically formulate the enhancement of linear and nonlinear optical responses of molecular vibrations through resonant nanoantennas, based on a coupled-dipole model. We apply the formulae to evaluation of signal enhancement factors in the antenna-enhanced vibrational spectroscopy.

An atlas of active enhancers across human cell types and tissues

NASA Astrophysics Data System (ADS)

Andersson, Robin; Gebhard, Claudia; Miguel-Escalada, Irene; Hoof, Ilka; Bornholdt, Jette; Boyd, Mette; Chen, Yun; Zhao, Xiaobei; Schmidl, Christian; Suzuki, Takahiro; Ntini, Evgenia; Arner, Erik; Valen, Eivind; Li, Kang; Schwarzfischer, Lucia; Glatz, Dagmar; Raithel, Johanna; Lilje, Berit; Rapin, Nicolas; Bagger, Frederik Otzen; Jørgensen, Mette; Andersen, Peter Refsing; Bertin, Nicolas; Rackham, Owen; Burroughs, A. Maxwell; Baillie, J. Kenneth; Ishizu, Yuri; Shimizu, Yuri; Furuhata, Erina; Maeda, Shiori; Negishi, Yutaka; Mungall, Christopher J.; Meehan, Terrence F.; Lassmann, Timo; Itoh, Masayoshi; Kawaji, Hideya; Kondo, Naoto; Kawai, Jun; Lennartsson, Andreas; Daub, Carsten O.; Heutink, Peter; Hume, David A.; Jensen, Torben Heick; Suzuki, Harukazu; Hayashizaki, Yoshihide; Müller, Ferenc; Consortium, The Fantom; Forrest, Alistair R. R.; Carninci, Piero; Rehli, Michael; Sandelin, Albin

2014-03-01

Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. We show that enhancers share properties with CpG-poor messenger RNA promoters but produce bidirectional, exosome-sensitive, relatively short unspliced RNAs, the generation of which is strongly related to enhancer activity. The atlas is used to compare regulatory programs between different cells at unprecedented depth, to identify disease-associated regulatory single nucleotide polymorphisms, and to classify cell-type-specific and ubiquitous enhancers. We further explore the utility of enhancer redundancy, which explains gene expression strength rather than expression patterns. The online FANTOM5 enhancer atlas represents a unique resource for studies on cell-type-specific enhancers and gene regulation.

How does enhancing cognition affect human values? How does this translate into social responsibility?

PubMed

Cabrera, Laura Y

2015-01-01

The past decade has seen a rise in the use of different technologies aimed at enhancing cognition of normal healthy individuals. While values have been acknowledged to be an important aspect of cognitive enhancement practices, the discussion has predominantly focused on just a few values, such as safety, peer pressure, and authenticity. How are values, in a broader sense, affected by enhancing cognitive abilities? Is this dependent on the type of technology or intervention used to attain the enhancement, or does the cognitive domain targeted play a bigger role in how values are affected? Values are not only likely to be affected by cognitive enhancement practices; they also play a crucial role in defining the type of interventions that are likely to be undertaken. This paper explores the way values affect and are affected by enhancing cognitive abilities. Furthermore, it argues that knowledge of the interplay between values and cognitive enhancement makes a strong case for social responsibility around cognitive enhancement practices.

STATs shape the active enhancer landscape of T cell populations.

PubMed

Vahedi, Golnaz; Takahashi, Hayato; Nakayamada, Shingo; Sun, Hong-Wei; Sartorelli, Vittorio; Kanno, Yuka; O'Shea, John J

2012-11-21

Signaling pathways are intimately involved in cellular differentiation, allowing cells to respond to their environment by regulating gene expression. Although enhancers are recognized as key elements that regulate selective gene expression, the interplay between signaling pathways and actively used enhancer elements is not clear. Here, we use CD4(+) T cells as a model of differentiation, mapping the activity of cell-type-specific enhancer elements in T helper 1 (Th1) and Th2 cells. Our data establish that STAT proteins have a major impact on the activation of lineage-specific enhancers and the suppression of enhancers associated with alternative cell fates. Transcriptome analysis further supports a functional role for enhancers regulated by STATs. Importantly, expression of lineage-defining master regulators in STAT-deficient cells fails to fully recover the chromatin signature of STAT-dependent enhancers. Thus, these findings point to a critical role of STATs as environmental sensors in dynamically molding the specialized enhancer architecture of differentiating cells. Copyright © 2012 Elsevier Inc. All rights reserved.

STATs Shape the Active Enhancer Landscape of T Cell Populations

PubMed Central

Vahedi, Golnaz; Takahashi, Hayato; Nakayamada, Shingo; Sun, Hong-wei; Sartorelli, Vittorio; Kanno, Yuka; O’Shea, John J.

2012-01-01

SUMMARY Signaling pathways are intimately involved in cellular differentiation, allowing cells to respond to their environment by regulating gene expression. While enhancers are recognized as key elements that regulate selective gene expression, the interplay between signaling pathways and actively used enhancer elements is not clear. Here, we use CD4+ T cells as a model of differentiation, mapping the acquisition of cell-type-specific enhancer elements in T-helper 1 (Th1) and Th2 cells. Our data establish that STAT proteins have a major impact on the acquisition of lineage-specific enhancers and the suppression of enhancers associated with alternative cell fates. Transcriptome analysis further supports a functional role for enhancers regulated by STATs. Importantly, expression of lineage-defining master regulators in STAT-deficient cells fails to fully recover the chromatin signature of STAT-dependent enhancers. Thus, these findings point to a critical role of STATs as environmental sensors in dynamically molding the specialized enhancer architecture of differentiating cells. PMID:23178119

The Meaning-Enhancing Properties of Psychedelics and Their Mediator Role in Psychedelic Therapy, Spirituality, and Creativity.

PubMed

Hartogsohn, Ido

2018-01-01

Past research has demonstrated to the ability of psychedelics to enhance suggestibility, and pointed to their ability to amplify perception of meaning. This paper examines the existing evidence for the meaning-enhancing properties of psychedelics, and argues that the tendency of these agents to enhance the perception of significance offers valuable clues to explaining their reported ability to stimulate a variety of therapeutic processes, enhance creativity, and instigate mystical-type experiences. Building upon previous research, which suggested the potential role of psychedelic meaning-enhancement in enhancing placebo response, the paper explores the mechanisms by which the meaning-amplifying properties of psychedelics might also play a role in enhancing creativity, as well as in effecting mystical-type experiences. The wider social and public-health implications of this hypothesis are discussed, and suggestions are made as to the various ways in which scientific understanding of the meaning-enhancing properties of psychedelics might be advanced and utilized.

Shell-Isolated Tip-Enhanced Raman and Fluorescence Spectroscopy.

PubMed

Huang, Ya-Ping; Huang, Sheng-Chao; Wang, Xiang-Jie; Bodappa, Nataraju; Li, Chao-Yu; Yin, Hao; Su, Hai-Sheng; Meng, Meng; Zhang, Hua; Ren, Bin; Yang, Zhi-Lin; Zenobi, Renato; Tian, Zhong-Qun; Li, Jian-Feng

2018-06-18

Tip-enhanced Raman spectroscopy can provide molecular fingerprint information with ultrahigh spatial resolution, but the tip will be easily contaminated, thus leading to artifacts. It also remains a great challenge to establish tip-enhanced fluorescence because of the quenching resulting from the proximity of the metal tip. Herein, we report shell-isolated tip-enhanced Raman and fluorescence spectroscopies by employing ultrathin shell-isolated tips fabricated by atomic layer deposition. Such shell-isolated tips not only show outstanding electromagnetic field enhancement in TERS but also exclude interference by contaminants, thus greatly promoting applications in solution. Tip-enhanced fluorescence has also been achieved using these shell-isolated tips, with enhancement factors of up to 1.7×10 3 , consistent with theoretical simulations. Furthermore, tip-enhanced Raman and fluorescence signals are acquired simultaneously, and their relative intensities can be manipulated by changing the shell thickness. This work opens a new avenue for ultrahigh resolution surface analysis using plasmon-enhanced spectroscopies. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhanced Raman scattering in porous silicon grating.

PubMed

Wang, Jiajia; Jia, Zhenhong; Lv, Changwu

2018-03-19

The enhancement of Raman signal on monocrystalline silicon gratings with varying groove depths and on porous silicon grating were studied for a highly sensitive surface enhanced Raman scattering (SERS) response. In the experiment conducted, porous silicon gratings were fabricated. Silver nanoparticles (Ag NPs) were then deposited on the porous silicon grating to enhance the Raman signal of the detective objects. Results show that the enhancement of Raman signal on silicon grating improved when groove depth increased. The enhanced performance of Raman signal on porous silicon grating was also further improved. The Rhodamine SERS response based on Ag NPs/ porous silicon grating substrates was enhanced relative to the SERS response on Ag NPs/ porous silicon substrates. Ag NPs / porous silicon grating SERS substrate system achieved a highly sensitive SERS response due to the coupling of various Raman enhancement factors.

Functional analysis of limb enhancers in the developing fin

PubMed Central

Booker, Betty M.; Murphy, Karl K.

2013-01-01

Despite diverging ~365 million years ago, tetrapod limbs and pectoral fins express similar genes that could be regulated by shared regulatory elements. In this study, we set out to analyze the ability of enhancers to maintain tissue specificity in these two divergent structures. We tested 22 human sequences that were previously reported as mouse limb enhancers for their enhancer activity in zebrafish (Danio rerio). Using a zebrafish enhancer assay, we found that 10/22 (45 %) were positive for pectoral fin activity. Analysis of the various criteria that correlated with positive fin activity found that both spatial limb activity and evolutionary conservation are not good predictors of fin enhancer activity. These results suggest that zebrafish enhancer assays may be limited in detecting human limb enhancers, and this limitation does not improve by the use of limb spatial expression or evolutionary conservation. PMID:24068387

Identifying the association between contrast enhancement pattern, surgical resection, and prognosis in anaplastic glioma patients.

PubMed

Wang, Yinyan; Wang, Kai; Wang, Jiangfei; Li, Shaowu; Ma, Jun; Dai, Jianping; Jiang, Tao

2016-04-01

Contrast enhancement observable on magnetic resonance (MR) images reflects the destructive features of malignant gliomas. This study aimed to investigate the relationship between radiologic patterns of tumor enhancement, extent of resection, and prognosis in patients with anaplastic gliomas (AGs). Clinical data from 268 patients with histologically confirmed AGs were retrospectively analyzed. Contrast enhancement patterns were classified based on preoperative T1-contrast MR images. Univariate and multivariate analyses were performed to evaluate the prognostic value of MR enhancement patterns on progression-free survival (PFS) and overall survival (OS). The pattern of tumor contrast enhancement was associated with the extent of surgical resection in AGs. A gross total resection was more likely to be achieved for AGs with focal enhancement than those with diffuse (p = 0.001) or ring-like (p = 0.024) enhancement. Additionally, patients with focal-enhanced AGs had a significantly longer PFS and OS than those with diffuse (log-rank, p = 0.025 and p = 0.031, respectively) or ring-like (log-rank, p = 0.008 and p = 0.011, respectively) enhanced AGs. Furthermore, multivariate analysis identified the pattern of tumor enhancement as a significant predictor of PFS (p = 0.016, hazard ratio [HR] = 1.485) and OS (p = 0.030, HR = 1.446). Our results suggested that the contrast enhancement pattern on preoperative MR images was associated with the extent of resection and predictive of survival outcomes in AG patients.

Evolutionary constraint on Otx2 neuroectoderm enhancers-deep conservation from skate to mouse and unique divergence in teleost

PubMed Central

Kurokawa, Daisuke; Sakurai, Yusuke; Inoue, Ai; Nakayama, Rika; Takasaki, Nobuyoshi; Suda, Yoko; Miyake, Tsutomu; Amemiya, Chris T.; Aizawa, Shinichi

2006-01-01

Otx2 is a paired type homeobox gene that plays essential roles in each step and site of head development in vertebrates. In the mouse, Otx2 expression in the anterior neuroectoderm is regulated primarily by two distinct enhancers: anterior neuroectoderm (AN) and forebrain/midbrain (FM) enhancers at 92 kb and 75 kb 5′of the Otx2 locus, respectively. The AN enhancer has activity in the entire anterior neuroectoderm at headfold and early somite stages, whereas the FM enhancer is subsequently active in the future caudal forebrain and midbrain ectoderm. In tetrapods, both AN and FM enhancers are conserved, whereas the AN region is missing in teleosts, despite overt Otx2 expression in the anterior neuroectoderm. Here, we show that zebrafish and fugu FM regions drive expression not only in the forebrain and midbrain but also in the anterior neuroectoderm at headfold stage. The analysis of coelacanth and skate genomic Otx2 orthologues suggests that the utilization of the two enhancers, AN and FM, is an ancestral condition. In contrast, the AN enhancer has been specifically lost in the teleost lineage with a compensatory establishment of AN activity within the FM enhancer. Furthermore, the AN activity in the fish FM enhancer was established by recruiting upstream factors different from those that direct the tetrapod AN enhancer, yet zebrafish FM enhancer is active in both mouse and zebrafish anterior neuroectoderm at the headfold stage. PMID:17159156

Gd-EOB-DTPA-enhanced 3.0-Tesla MRI findings for the preoperative detection of focal liver lesions: Comparison with iodine-enhanced multi-detector computed tomography

NASA Astrophysics Data System (ADS)

Park, Hyong-Hu; Goo, Eun-Hoe; Im, In-Chul; Lee, Jae-Seung; Kim, Moon-Jib; Kwak, Byung-Joon; Chung, Woon-Kwan; Dong, Kyung-Rae

2012-12-01

The safety of gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic-acid (Gd-EOB-DTPA) has been confirmed, but more study is needed to assess the diagnostic accuracy of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) in patients with a hepatocellular carcinoma (HCC) for whom surgical treatment is considered or with a metastatic hepatoma. Research is also needed to examine the rate of detection of hepatic lesions compared to multi-detector computed tomography (MDCT), which is used most frequently to localize and characterize a HCC. Gd-EOB-DTPA-enhanced MRI and iodine-enhanced MDCT imaging were compared for the preoperative detection of focal liver lesions. The clinical usefulness of each method was examined. The current study enrolled 79 patients with focal liver lesions who preoperatively underwent MRI and MDCT. In these patients, there was less than one month between the two diagnostic modalities. Imaging data were taken before and after contrast enhancement in both methods. To evaluate the images, we analyzed the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR) in the lesions and the liver parenchyma. To compare the sensitivity of the two methods, we performed a quantitative analysis of the percentage signal intensity of the liver (PSIL) on a high resolution picture archiving and communication system (PACS) monitor (paired-samples t-test, p < 0.05). The enhancement was evaluated based on a consensus of four observers. The enhancement pattern and the morphological features during the arterial and the delayed phases were correlated between the Gd-EOB-DTPA-enhanced MRI findings and the iodine-enhanced MDCT by using an adjusted x2 test. The SNRs, CNRs, and PSIL all had a greater detection rate in Gd-EOB-DTPA enhanced MRI than in iodine-enhanced MDCT. Hepatocyte-selective uptake was observed 20 minutes after the injection in the focal nodular hyperplasia (FNH, 9/9), adenoma (9/10), and highly-differentiated HCC (grade G1, 27/30). Rim enhancement was detected in all metastases (30/30). During the arterial and the delayed phases, good overall agreement between the gadoxetic-acid-enhanced MR and CT was observed (x2 test, p < 0.05). For the preoperative detection of focal liver lesions, Gd-EOB-DTPA-enhanced MRI had a higher diagnostic value and higher detection rate than iodine-enhanced MDCT. The arterial and the delayed dynamic enhancement patterns, and the gadoxetic-acid-enhanced MR imaging can provide information on the possible degree of cellular differentiation of a HCC, adenoma or metastatic tumor.

Automatic image enhancement based on multi-scale image decomposition

NASA Astrophysics Data System (ADS)

Feng, Lu; Wu, Zhuangzhi; Pei, Luo; Long, Xiong

2014-01-01

In image processing and computational photography, automatic image enhancement is one of the long-range objectives. Recently the automatic image enhancement methods not only take account of the globe semantics, like correct color hue and brightness imbalances, but also the local content of the image, such as human face and sky of landscape. In this paper we describe a new scheme for automatic image enhancement that considers both global semantics and local content of image. Our automatic image enhancement method employs the multi-scale edge-aware image decomposition approach to detect the underexposure regions and enhance the detail of the salient content. The experiment results demonstrate the effectiveness of our approach compared to existing automatic enhancement methods.

Linear enhancement after radio-frequency ablation for hepatocellular carcinoma: is it a sign of recurrence?

PubMed

Takahashi, Masanori; Maruyama, Hitoshi; Shimada, Taro; Kamezaki, Hidehiro; Okabe, Shinichiro; Kanai, Fumihiko; Yoshikawa, Masaharu; Yokosuka, Osamu

2012-11-01

This prospective study was performed in 179 hepatocellular carcinoma (HCC) lesions treated by radio-frequency ablation (RFA) to explore the clinical outcome of "linear enhancement" on contrast-enhanced sonogram. Thirty-three lesions (18.4%) showed linear enhancement, a linear-shaped positive enhancement in the RFA-treated area. Seventeen of them were followed up with no treatment (remaining 16; dropout in eight, additional RFA in six and ineffective treatment in two) and three lesions (3/17, 17.6%) showed local tumor progression corresponding to linear enhancement at 7, 14, 19 months after RFA. Although there was no significant difference in local recurrence rate between the lesions with (3/17) and without linear enhancement (10/35), local tumor progression inside the ablation zone occurred only in the lesions with linear enhancement. In conclusion, linear enhancement inside the RFA-treated area should be followed up within 7 months because it has a risk of local tumor progression. Histology of linear enhancement and its influence on distant recurrence remain to be solved. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Transcription through enhancers suppresses their activity in Drosophila

PubMed Central

2013-01-01

Background Enhancer elements determine the level of target gene transcription in a tissue-specific manner, providing for individual patterns of gene expression in different cells. Knowledge of the mechanisms controlling enhancer action is crucial for understanding global regulation of transcription. In particular, enhancers are often localized within transcribed regions of the genome. A number of experiments suggest that transcription can have both positive and negative effects on regulatory elements. In this study, we performed direct tests for the effect of transcription on enhancer activity. Results Using a transgenic reporter system, we investigated the relationship between the presence of pass-through transcription and the activity of Drosophila enhancers controlling the expression of the white and yellow genes. The results show that transcription from different promoters affects the activity of enhancers, counteracting their ability to activate the target genes. As expected, the presence of a transcriptional terminator between the inhibiting promoter and the affected enhancer strongly reduces the suppression. Moreover, transcription leads to dislodging of the Zeste protein that is responsible for the enhancer-dependent regulation of the white gene, suggesting a 'transcription interference’ mechanism for this regulation. Conclusions Our findings suggest a role for pass-through transcription in negative regulation of enhancer activity. PMID:24279291

Characterization method for relative Raman enhancement for surface-enhanced Raman spectroscopy using gold nanoparticle dimer array

NASA Astrophysics Data System (ADS)

Sugano, Koji; Ikegami, Kohei; Isono, Yoshitada

2017-06-01

In this paper, a characterization method for Raman enhancement for highly sensitive and quantitative surface-enhanced Raman spectroscopy (SERS) is reported. A particle dimer shows a marked electromagnetic enhancement when the particle connection direction is matched to the polarization direction of incident light. In this study, dimers were arrayed by nanotrench-guided self-assembly for a marked total Raman enhancement. By measuring acetonedicarboxylic acid, the fabricated structures were characterized for SERS depending on the polarization angle against the particle connection direction. This indicates that the fabricated structures cause an effective SERS enhancement, which is dominated by the electromagnetic enhancement. Then, we measured 4,4‧-bipyridine, which is a pesticide material, for quantitative analysis. In advance, we evaluated the enhancement of the particle structure by the Raman measurement of acetonedicarboxylic acid. Finally, we compared the Raman intensities of acetonedicarboxylic acid and 4,4‧-bipyridine. Their intensities showed good correlation. The advantage of this method for previously evaluating the enhancement of the substrate was demonstrated. This developed SERS characterization method is expected to be applied to various quantitative trace analyses of molecules with high sensitivity.

Discovery of stimulation-responsive immune enhancers with CRISPR activation

PubMed Central

Simeonov, Dimitre R.; Gowen, Benjamin G.; Boontanrart, Mandy; Roth, Theodore L.; Gagnon, John D.; Mumbach, Maxwell R.; Satpathy, Ansuman T.; Lee, Youjin; Bray, Nicolas L.; Chan, Alice Y.; Lituiev, Dmytro S.; Nguyen, Michelle L.; Gate, Rachel E.; Subramaniam, Meena; Li, Zhongmei; Woo, Jonathan M.; Mitros, Therese; Ray, Graham J.; Curie, Gemma L.; Naddaf, Nicki; Chu, Julia S.; Ma, Hong; Boyer, Eric; Van Gool, Frederic; Huang, Hailiang; Liu, Ruize; Tobin, Victoria R.; Schumann, Kathrin; Daly, Mark J.; Farh, Kyle K; Ansel, K. Mark; Ye, Chun J.; Greenleaf, William J.; Anderson, Mark S.; Bluestone, Jeffrey A.; Chang, Howard Y.; Corn, Jacob E.; Marson, Alexander

2017-01-01

The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues1–3. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption4–6, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied. We hypothesized that recruitment of a strong transcriptional activator to an enhancer would be sufficient to drive target gene expression, even if that enhancer was not currently active in the assayed cells. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. We used tiled CRISPR activation (CRISPRa)7 to synthetically recruit a transcriptional activator to sites across large genomic regions (more than 100 kilobases) surrounding two key autoimmunity risk loci, CD69 and IL2RA. We identified several CRISPRa-responsive elements with chromatin features of stimulus-responsive enhancers, including an IL2RA enhancer that harbours an autoimmunity risk variant. Using engineered mouse models, we found that sequence perturbation of the disease-associated Il2ra enhancer did not entirely block Il2ra expression, but rather delayed the timing of gene activation in response to specific extracellular signals. Enhancer deletion skewed polarization of naive T cells towards a pro-inflammatory T helper (TH17) cell state and away from a regulatory T cell state. This integrated approach identifies functional enhancers and reveals how non-coding variation associated with human immune dysfunction alters context-specific gene programs. PMID:28854172

Discovery of stimulation-responsive immune enhancers with CRISPR activation.

PubMed

Simeonov, Dimitre R; Gowen, Benjamin G; Boontanrart, Mandy; Roth, Theodore L; Gagnon, John D; Mumbach, Maxwell R; Satpathy, Ansuman T; Lee, Youjin; Bray, Nicolas L; Chan, Alice Y; Lituiev, Dmytro S; Nguyen, Michelle L; Gate, Rachel E; Subramaniam, Meena; Li, Zhongmei; Woo, Jonathan M; Mitros, Therese; Ray, Graham J; Curie, Gemma L; Naddaf, Nicki; Chu, Julia S; Ma, Hong; Boyer, Eric; Van Gool, Frederic; Huang, Hailiang; Liu, Ruize; Tobin, Victoria R; Schumann, Kathrin; Daly, Mark J; Farh, Kyle K; Ansel, K Mark; Ye, Chun J; Greenleaf, William J; Anderson, Mark S; Bluestone, Jeffrey A; Chang, Howard Y; Corn, Jacob E; Marson, Alexander

2017-09-07

The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied. We hypothesized that recruitment of a strong transcriptional activator to an enhancer would be sufficient to drive target gene expression, even if that enhancer was not currently active in the assayed cells. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. We used tiled CRISPR activation (CRISPRa) to synthetically recruit a transcriptional activator to sites across large genomic regions (more than 100 kilobases) surrounding two key autoimmunity risk loci, CD69 and IL2RA. We identified several CRISPRa-responsive elements with chromatin features of stimulus-responsive enhancers, including an IL2RA enhancer that harbours an autoimmunity risk variant. Using engineered mouse models, we found that sequence perturbation of the disease-associated Il2ra enhancer did not entirely block Il2ra expression, but rather delayed the timing of gene activation in response to specific extracellular signals. Enhancer deletion skewed polarization of naive T cells towards a pro-inflammatory T helper (T H 17) cell state and away from a regulatory T cell state. This integrated approach identifies functional enhancers and reveals how non-coding variation associated with human immune dysfunction alters context-specific gene programs.

Discovery of stimulation-responsive immune enhancers with CRISPR activation

NASA Astrophysics Data System (ADS)

Simeonov, Dimitre R.; Gowen, Benjamin G.; Boontanrart, Mandy; Roth, Theodore L.; Gagnon, John D.; Mumbach, Maxwell R.; Satpathy, Ansuman T.; Lee, Youjin; Bray, Nicolas L.; Chan, Alice Y.; Lituiev, Dmytro S.; Nguyen, Michelle L.; Gate, Rachel E.; Subramaniam, Meena; Li, Zhongmei; Woo, Jonathan M.; Mitros, Therese; Ray, Graham J.; Curie, Gemma L.; Naddaf, Nicki; Chu, Julia S.; Ma, Hong; Boyer, Eric; van Gool, Frederic; Huang, Hailiang; Liu, Ruize; Tobin, Victoria R.; Schumann, Kathrin; Daly, Mark J.; Farh, Kyle K.; Ansel, K. Mark; Ye, Chun J.; Greenleaf, William J.; Anderson, Mark S.; Bluestone, Jeffrey A.; Chang, Howard Y.; Corn, Jacob E.; Marson, Alexander

2017-09-01

The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied. We hypothesized that recruitment of a strong transcriptional activator to an enhancer would be sufficient to drive target gene expression, even if that enhancer was not currently active in the assayed cells. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. We used tiled CRISPR activation (CRISPRa) to synthetically recruit a transcriptional activator to sites across large genomic regions (more than 100 kilobases) surrounding two key autoimmunity risk loci, CD69 and IL2RA. We identified several CRISPRa-responsive elements with chromatin features of stimulus-responsive enhancers, including an IL2RA enhancer that harbours an autoimmunity risk variant. Using engineered mouse models, we found that sequence perturbation of the disease-associated Il2ra enhancer did not entirely block Il2ra expression, but rather delayed the timing of gene activation in response to specific extracellular signals. Enhancer deletion skewed polarization of naive T cells towards a pro-inflammatory T helper (TH17) cell state and away from a regulatory T cell state. This integrated approach identifies functional enhancers and reveals how non-coding variation associated with human immune dysfunction alters context-specific gene programs.

Cognitive enhancement kept within contexts: neuroethics and informed public policy

PubMed Central

Shook, John R.; Galvagni, Lucia; Giordano, James

2014-01-01

Neurothics has far greater responsibilities than merely noting potential human enhancements arriving from novel brain-centered biotechnologies and tracking their implications for ethics and civic life. Neuroethics must utilize the best cognitive and neuroscientific knowledge to shape incisive discussions about what could possibly count as enhancement in the first place, and what should count as genuinely “cognitive” enhancement. Where cognitive processing and the mental life is concerned, the lived context of psychological performance is paramount. Starting with an enhancement to the mental abilities of an individual, only performances on real-world exercises can determine what has actually been cognitively improved. And what can concretely counts as some specific sort of cognitive improvement is largely determined by the classificatory frameworks of cultures, not brain scans or laboratory experiments. Additionally, where the public must ultimately evaluate and judge the worthiness of individual performance enhancements, we mustn’t presume that public approval towards enhancers will somehow automatically arrive without due regard to civic ideals such as the common good or social justice. In the absence of any nuanced appreciation for the control which performance contexts and public contexts exert over what “cognitive” enhancements could actually be, enthusiastic promoters of cognitive enhancement can all too easily depict safe and effective brain modifications as surely good for us and for society. These enthusiasts are not unaware of oft-heard observations about serious hurdles for reliable enhancement from neurophysiological modifications. Yet those observations are far more common than penetrating investigations into the implications to those hurdles for a sound public understanding of cognitive enhancement, and a wise policy review over cognitive enhancement. We offer some crucial recommendations for undertaking such investigations, so that cognitive enhancers that truly deserve public approval can be better identified. PMID:25538573

40 CFR 141.64 - Maximum contaminant levels for disinfection byproducts.

Code of Federal Regulations, 2012 CFR

2012-07-01

... trihalomethanes (TTHM) and Haloacetic acids (five) (HAA5) Enhanced coagulation or enhanced softening or GAC10... Haloacetic acids (five) (HAA5) Enhanced coagulation or enhanced softening, plus GAC10; or nanofiltration with...

40 CFR 141.64 - Maximum contaminant levels for disinfection byproducts.

Code of Federal Regulations, 2011 CFR

2011-07-01

... trihalomethanes (TTHM) and Haloacetic acids (five) (HAA5) Enhanced coagulation or enhanced softening or GAC10... Haloacetic acids (five) (HAA5) Enhanced coagulation or enhanced softening, plus GAC10; or nanofiltration with...

40 CFR 141.64 - Maximum contaminant levels for disinfection byproducts.

Code of Federal Regulations, 2013 CFR

2013-07-01

... trihalomethanes (TTHM) and Haloacetic acids (five) (HAA5) Enhanced coagulation or enhanced softening or GAC10... Haloacetic acids (five) (HAA5) Enhanced coagulation or enhanced softening, plus GAC10; or nanofiltration with...

40 CFR 141.64 - Maximum contaminant levels for disinfection byproducts.

Code of Federal Regulations, 2014 CFR

2014-07-01

... trihalomethanes (TTHM) and Haloacetic acids (five) (HAA5) Enhanced coagulation or enhanced softening or GAC10... Haloacetic acids (five) (HAA5) Enhanced coagulation or enhanced softening, plus GAC10; or nanofiltration with...

Metal-enhanced chemiluminescence from chromium, copper, nickel, and zinc nanodeposits: Evidence for a second enhancement mechanism in metal-enhanced fluorescence

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

Weisenberg, Micah; Zhang Yongxia; Geddes, Chris D.

Over the past decade metal-fluorophore interactions, metal-enhanced fluorescence, have attracted significant research attention, with the technology now becoming common place in life science applications. In this paper, we address the underlying mechanisms of metal-enhanced fluorescence (MEF) and experimentally show using chemiluminescence solutions that MEF is indeed underpinned by two complimentary mechanisms, consistent with the recent reports by Geddes and co-workers [Zhang et al., J. Phys. Chem. C 113, 12095 (2009)] and their enhanced fluorescence hypothesis.

How organizations can enhance the quality of life of their clients and assess their results: the concept of QOL enhancement.

PubMed

Reinders, Hans S; Schalock, Robert L

2014-07-01

This article presents the framework of a dynamic approach to quality of life (QOL) enhancement based on the conceptualization and measurement of individual-referenced quality of life. Sections of the article summarize the premises of QOL enhancement, provide the rationale for a dynamic approach to QOL enhancement, discuss six components of QOL enhancement, and discuss the parameters of an emerging theory of quality of life and the contributions such a theory would make to service delivery, policy development, and QOL-related research.

Intragenic Locus in Human PIWIL2 Gene Shares Promoter and Enhancer Functions.

PubMed

Skvortsova, Yulia V; Kondratieva, Sofia A; Zinovyeva, Marina V; Nikolaev, Lev G; Azhikina, Tatyana L; Gainetdinov, Ildar V

2016-01-01

Recently, more evidence supporting common nature of promoters and enhancers has been accumulated. In this work, we present data on chromatin modifications and non-polyadenylated transcription characteristic for enhancers as well as results of in vitro luciferase reporter assays suggesting that PIWIL2 alternative promoter in exon 7 also functions as an enhancer for gene PHYHIP located 60Kb upstream. This finding of an intragenic enhancer serving as a promoter for a shorter protein isoform implies broader impact on understanding enhancer-promoter networks in regulation of gene expression.

Surface-enhanced Raman scattering on tunable plasmonic nanoparticle substrates

PubMed Central

Jackson, J. B.; Halas, N. J.

2004-01-01

Au and Ag nanoshells are investigated as substrates for surface-enhanced Raman scattering (SERS). We find that SERS enhancements on nanoshell films are dramatically different from those observed on colloidal aggregates, specifically that the Raman enhancement follows the plasmon resonance of the individual nanoparticles. Comparative finite difference time domain calculations of fields at the surface of smooth and roughened nanoshells reveal that surface roughness contributes only slightly to the total enhancement. SERS enhancements as large as 2.5 × 1010 on Ag nanoshell films for the nonresonant molecule p-mercaptoaniline are measured. PMID:15608058

Journal Club: Comparison of assessment of preoperative pulmonary vasculature in patients with non-small cell lung cancer by non-contrast- and 4D contrast-enhanced 3-T MR angiography and contrast-enhanced 64-MDCT.

PubMed

Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Seki, Shinichiro; Sugimura, Kazuro

2014-03-01

The purpose of this article is to prospectively and directly compare the capabilities of non-contrast-enhanced MR angiography (MRA), 4D contrast-enhanced MRA, and contrast-enhanced MDCT for assessing pulmonary vasculature in patients with non-small cell lung cancer (NSCLC) before surgical treatment. A total of 77 consecutive patients (41 men and 36 women; mean age, 71 years) with pathologically proven and clinically assessed stage I NSCLC underwent thin-section contrast-enhanced MDCT, non-contrast-enhanced and contrast-enhanced MRA, and surgical treatment. The capability for anomaly assessment of the three methods was independently evaluated by two reviewers using a 5-point visual scoring system, and final assessment for each patient was made by consensus of the two readers. Interobserver agreement for pulmonary arterial and venous assessment was evaluated with the kappa statistic. Then, sensitivity, specificity, and accuracy for the detection of anomalies were directly compared among the three methods by use of the McNemar test. Interobserver agreement for pulmonary artery and vein assessment was substantial or almost perfect (κ=0.72-0.86). For pulmonary arterial and venous variation assessment, there were no significant differences in sensitivity, specificity, and accuracy among non-contrast-enhanced MRA (pulmonary arteries: sensitivity, 77.1%; specificity, 97.4%; accuracy, 87.7%; pulmonary veins: sensitivity, 50%; specificity, 98.5%; accuracy, 93.2%), 4D contrast-enhanced MRA (pulmonary arteries: sensitivity, 77.1%; specificity, 97.4%; accuracy, 87.7%; pulmonary veins: sensitivity, 62.5%; specificity, 100.0%; accuracy, 95.9%), and thin-section contrast-enhanced MDCT (pulmonary arteries: sensitivity, 91.4%; specificity, 89.5%; accuracy, 90.4%; pulmonary veins: sensitivity, 50%; specificity, 100.0%; accuracy, 95.9%) (p>0.05). Pulmonary vascular assessment of patients with NSCLC before surgical resection by non-contrast-enhanced MRA can be considered equivalent to that by 4D contrast-enhanced MRA and contrast-enhanced MDCT.

Distributive justice and cognitive enhancement in lower, normal intelligence.

PubMed

Dunlop, Mikael; Savulescu, Julian

2014-01-01

There exists a significant disparity within society between individuals in terms of intelligence. While intelligence varies naturally throughout society, the extent to which this impacts on the life opportunities it affords to each individual is greatly undervalued. Intelligence appears to have a prominent effect over a broad range of social and economic life outcomes. Many key determinants of well-being correlate highly with the results of IQ tests, and other measures of intelligence, and an IQ of 75 is generally accepted as the most important threshold in modern life. The ability to enhance our cognitive capacities offers an exciting opportunity to correct disabling natural variation and inequality in intelligence. Pharmaceutical cognitive enhancers, such as modafinil and methylphenidate, have been shown to have the capacity to enhance cognition in normal, healthy individuals. Perhaps of most relevance is the presence of an 'inverted U effect' for most pharmaceutical cognitive enhancers, whereby the degree of enhancement increases as intelligence levels deviate further below the mean. Although enhancement, including cognitive enhancement, has been much debated recently, we argue that there are egalitarian reasons to enhance individuals with low but normal intelligence. Under egalitarianism, cognitive enhancement has the potential to reduce opportunity inequality and contribute to relative income and welfare equality in the lower, normal intelligence subgroup. Cognitive enhancement use is justifiable under prioritarianism through various means of distribution; selective access to the lower, normal intelligence subgroup, universal access, or paradoxically through access primarily to the average and above average intelligence subgroups. Similarly, an aggregate increase in social well-being is achieved through similar means of distribution under utilitarianism. In addition, the use of cognitive enhancement within the lower, normal intelligence subgroup negates, or at the very least minimises, several common objections to cognitive enhancement. Subsequently, this paper demonstrates that there is a compelling case for cognitive enhancement use in individuals with lower, normal intelligence.

Effective Blocking of the White Enhancer Requires Cooperation between Two Main Mechanisms Suggested for the Insulator Function

PubMed Central

Stakhov, Viacheslav; Ivlieva, Tatyana; Parshikov, Alexander; Studitsky, Vasily M.; Georgiev, Pavel

2013-01-01

Chromatin insulators block the action of transcriptional enhancers when interposed between an enhancer and a promoter. In this study, we examined the role of chromatin loops formed by two unrelated insulators, gypsy and Fab-7, in their enhancer-blocking activity. To test for this activity, we selected the white reporter gene that is activated by the eye-specific enhancer. The results showed that one copy of the gypsy or Fab-7 insulator failed to block the eye enhancer in most of genomic sites, whereas a chromatin loop formed by two gypsy insulators flanking either the eye enhancer or the reporter completely blocked white stimulation by the enhancer. However, strong enhancer blocking was achieved due not only to chromatin loop formation but also to the direct interaction of the gypsy insulator with the eye enhancer, which was confirmed by the 3C assay. In particular, it was observed that Mod(mdg4)-67.2, a component of the gypsy insulator, interacted with the Zeste protein, which is critical for the eye enhancer–white promoter communication. These results suggest that efficient enhancer blocking depends on the combination of two factors: chromatin loop formation by paired insulators, which generates physical constraints for enhancer–promoter communication, and the direct interaction of proteins recruited to an insulator and to the enhancer–promoter pair. PMID:23861668

Limits to human enhancement: nature, disease, therapy or betterment?

PubMed

Hofmann, Bjørn

2017-10-10

New technologies facilitate the enhancement of a wide range of human dispositions, capacities, or abilities. While it is argued that we need to set limits to human enhancement, it is unclear where we should find resources to set such limits. Traditional routes for setting limits, such as referring to nature, the therapy-enhancement distinction, and the health-disease distinction, turn out to have some shortcomings. However, upon closer scrutiny the concept of enhancement is based on vague conceptions of what is to be enhanced. Explaining why it is better to become older, stronger, and more intelligent presupposes a clear conception of goodness, which is seldom provided. In particular, the qualitative better is frequently confused with the quantitative more. We may therefore not need "external" measures for setting its limits - they are available in the concept of enhancement itself. While there may be shortcomings in traditional sources of limit setting to human enhancement, such as nature, therapy, and disease, such approaches may not be necessary. The specification-of-betterment problem inherent in the conception of human enhancement itself provides means to restrict its unwarranted proliferation. We only need to demand clear, sustainable, obtainable goals for enhancement that are based on evidence, and not on lofty speculations, hypes, analogies, or weak associations. Human enhancements that specify what will become better, and provide adequate evidence, are good and should be pursued. Others should not be accepted.

75 FR 16719 - Agricultural Water Enhancement Program

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-02

... DEPARTMENT OF AGRICULTURE Commodity Credit Corporation Agricultural Water Enhancement Program... Energy Act of 2008 (2008 Act) established the Agricultural Water Enhancement Program (AWEP) by amending... to implement agricultural water enhancement activities on agricultural land for the purposes of...

HEDD: Human Enhancer Disease Database

PubMed Central

Wang, Zhen; Zhang, Quanwei; Zhang, Wen; Lin, Jhih-Rong; Cai, Ying; Mitra, Joydeep

2018-01-01

Abstract Enhancers, as specialized genomic cis-regulatory elements, activate transcription of their target genes and play an important role in pathogenesis of many human complex diseases. Despite recent systematic identification of them in the human genome, currently there is an urgent need for comprehensive annotation databases of human enhancers with a focus on their disease connections. In response, we built the Human Enhancer Disease Database (HEDD) to facilitate studies of enhancers and their potential roles in human complex diseases. HEDD currently provides comprehensive genomic information for ∼2.8 million human enhancers identified by ENCODE, FANTOM5 and RoadMap with disease association scores based on enhancer–gene and gene–disease connections. It also provides Web-based analytical tools to visualize enhancer networks and score enhancers given a set of selected genes in a specific gene network. HEDD is freely accessible at http://zdzlab.einstein.yu.edu/1/hedd.php. PMID:29077884

Gap-mode enhancement on MoS2 probed by functionalized tip-enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

Alajlan, Abdulrahman M.; Voronine, Dmitri V.; Sinyukov, Alexander M.; Zhang, Zhenrong; Sokolov, Alexei V.; Scully, Marlan O.

2016-09-01

Surface enhancement of molecular spectroscopic signals has been widely used for sensing and nanoscale imaging. Because of the weak electromagnetic enhancement of Raman signals on semiconductors, it is motivating but challenging to study the electromagnetic effect separately from the chemical effects. We report tip-enhanced Raman scattering measurements on Au and bulk MoS2 substrates using a metallic tip functionalized with copper phthalocyanine molecules and demonstrate similar gap-mode enhancement on both substrates. We compare the experimental results with theoretical calculations to confirm the gap-mode enhancement on MoS2 using a well-established electrostatic model. The functionalized tip approach allows for suppressing the background and is ideal for separating electromagnetic and chemical enhancement mechanisms on various substrates. Our results may find a wide range of applications in MoS2-based devices, sensors, and metal-free nanoscale bio-imaging.

Loudness enhancement and decrement in four paradigms

NASA Technical Reports Server (NTRS)

Elmasian, R.; Galambos, R.; Bernheim, A., Jr.

1980-01-01

When one tone burst (the conditioner) preceeds another (the target) by 100 ms, target loudness is enhanced if the conditioner is more intense and decreased if it is less intense. We show here that similar loudness enhancements and decrements occur when the conditioner follows the target. In all instances, monaural loudness enhancements (in which the conditioner and target are delivered to the same ear) are greater than the dichotic enhancements (in which the conditioner is presented contralaterally), but the decrements, which are smaller than the enhancements, are similar in magnitude. Loudness enhancements and decrements are similar to sequential loudness effects and central tendency effects; the major difference is the relatively very large increases in loudness obtainable in loudness enhancement experiments. We outline a mechanism to account for these loudness phenomena and suggest that this mechanism is responsible for similar perceptual effects that occur in other stimulus dimensions and modalities.

Hotspots of aberrant enhancer activity punctuate the colorectal cancer epigenome

PubMed Central

Cohen, Andrea J.; Saiakhova, Alina; Corradin, Olivia; Luppino, Jennifer M.; Lovrenert, Katreya; Bartels, Cynthia F.; Morrow, James J.; Mack, Stephen C.; Dhillon, Gursimran; Beard, Lydia; Myeroff, Lois; Kalady, Matthew F.; Willis, Joseph; Bradner, James E.; Keri, Ruth A.; Berger, Nathan A.; Pruett-Miller, Shondra M.; Markowitz, Sanford D.; Scacheri, Peter C.

2017-01-01

In addition to mutations in genes, aberrant enhancer element activity at non-coding regions of the genome is a key driver of tumorigenesis. Here, we perform epigenomic enhancer profiling of a cohort of more than forty genetically diverse human colorectal cancer (CRC) specimens. Using normal colonic crypt epithelium as a comparator, we identify enhancers with recurrently gained or lost activity across CRC specimens. Of the enhancers highly recurrently activated in CRC, most are constituents of super enhancers, are occupied by AP-1 and cohesin complex members, and originate from primed chromatin. Many activate known oncogenes, and CRC growth can be mitigated through pharmacologic inhibition or genome editing of these loci. Nearly half of all GWAS CRC risk loci co-localize to recurrently activated enhancers. These findings indicate that the CRC epigenome is defined by highly recurrent epigenetic alterations at enhancers which activate a common, aberrant transcriptional programme critical for CRC growth and survival. PMID:28169291

TALE-mediated modulation of transcriptional enhancers in vivo.

PubMed

Crocker, Justin; Stern, David L

2013-08-01

We tested whether transcription activator-like effectors (TALEs) could mediate repression and activation of endogenous enhancers in the Drosophila genome. TALE repressors (TALERs) targeting each of the five even-skipped (eve) stripe enhancers generated repression specifically of the focal stripes. TALE activators (TALEAs) targeting the eve promoter or enhancers caused increased expression primarily in cells normally activated by the promoter or targeted enhancer, respectively. This effect supports the view that repression acts in a dominant fashion on transcriptional activators and that the activity state of an enhancer influences TALE binding or the ability of the VP16 domain to enhance transcription. In these assays, the Hairy repression domain did not exhibit previously described long-range transcriptional repression activity. The phenotypic effects of TALER and TALEA expression in larvae and adults are consistent with the observed modulations of eve expression. TALEs thus provide a novel tool for detection and functional modulation of transcriptional enhancers in their native genomic context.

Regulation of hepatitis B virus ENI enhancer activity by hepatocyte-enriched transcription factor HNF3.

PubMed

Chen, M; Hieng, S; Qian, X; Costa, R; Ou, J H

1994-11-15

Hepatitis B virus (HBV) ENI enhancer can activate the expression of HBV and non-HBV genes in a liver-specific manner. By performing the electrophoretic mobility-shift assays, we demonstrated that the three related, liver-enriched, transcription factors, HNF3 alpha, HNF3 beta, and HNF3 gamma could all bind to the 2c site of HBV ENI enhancer. Mutations introduced in the 2c site to abolish the binding by HNF3 reduced the enhancer activity approximately 15-fold. Moreover, expression of HNF3 antisense sequences to suppress the expression of HNF3 in Huh-7 hepatoma cells led to reduction of the ENI enhancer activity. These results indicate that HNF3 positively regulates the ENI enhancer activity and this regulation is most likely mediated through the 2c site. The requirement of HNF3 for the ENI enhancer activity could explain the liver specificity of this enhancer element.

Visibility enhancement of color images using Type-II fuzzy membership function

NASA Astrophysics Data System (ADS)

Singh, Harmandeep; Khehra, Baljit Singh

2018-04-01

Images taken in poor environmental conditions decrease the visibility and hidden information of digital images. Therefore, image enhancement techniques are necessary for improving the significant details of these images. An extensive review has shown that histogram-based enhancement techniques greatly suffer from over/under enhancement issues. Fuzzy-based enhancement techniques suffer from over/under saturated pixels problems. In this paper, a novel Type-II fuzzy-based image enhancement technique has been proposed for improving the visibility of images. The Type-II fuzzy logic can automatically extract the local atmospheric light and roughly eliminate the atmospheric veil in local detail enhancement. The proposed technique has been evaluated on 10 well-known weather degraded color images and is also compared with four well-known existing image enhancement techniques. The experimental results reveal that the proposed technique outperforms others regarding visible edge ratio, color gradients and number of saturated pixels.

How Organizations Can Enhance the Quality of Life of Their Clients and Assess Their Results: The Concept of QOL Enhancement

ERIC Educational Resources Information Center

Reinders, Hans S.; Schalock, Robert L.

2014-01-01

This article presents the framework of a dynamic approach to quality of life (QOL) enhancement based on the conceptualization and measurement of individual-referenced quality of life. Sections of the article summarize the premises of QOL enhancement, provide the rationale for a dynamic approach to QOL enhancement, discuss six components of QOL…

Land classification of south-central Iowa from computer enhanced images

NASA Technical Reports Server (NTRS)

Lucas, J. R. (Principal Investigator); Taranik, J. V.; Billingsley, F. C.

1976-01-01

The author has identified the following significant results. The Iowa Geological Survey developed its own capability for producing color products from digitally enhanced LANDSAT data. Research showed that efficient production of enhanced images required full utilization of both computer and photographic enhancement procedures. The 29 August 1972 photo-optically enhanced color composite was more easily interpreted for land classification purposes than standard color composites.

Promoting effects of chemical permeation enhancers on insulin permeation across TR146 cell model of buccal epithelium in vitro.

PubMed

Xue, Xiao-yan; Zhou, Ying; Chen, Ying-ying; Meng, Jing-ru; Jia, Min; Hou, Zheng; Bai, Hui; Mao, Xing-gang; Luo, Xiao-xing

2012-04-01

To find potential enhancers for facilitating the buccal delivery of insulin, a TR146 cell-culture model of buccal epithelium, cultured on commercially available insert plates, was used to evaluate the permeability-enhancing effects of several traditional and new types of chemical enhancers, including N-acetyl-L-cysteine (NAC), sodium deoxycholate (SDC), sodium nitroprusside (SNP), reduced glutathione (GSH), glutamine (Gln), chitosan (CS), L-arginine (Arg), 1-dodecylazacycloheptan-2-one (Azone), and soybean lecithin (SPC) (50 and 10 μg/mL respectively). Permeability studies were performed to determine the enhancing effects of these compounds on insulin permeation across the cell-culture model. The enhancing effects of the enhancers were assessed by calculating the apparent permeability coefficients and enhancement ratio. Cytotoxicity of the permeation enhancers at different concentrations was investigated by using the methylthiazolydiphenyl-tetrazolium bromide (MTT) assay. Results showed that 50 μg/mL of NAC, SDC, GSH, CS, Arg, Azone, SPC, SNP, and 10 μg/mL of SNP had a significant enhancing effect on promoting the transport of insulin across the TR146 cell model. MTT assays showed that 50 μg/mL of Gln, Azone, SDC, SNP, Arg, 10 μg/mL SDC, and Arg had obvious toxic effects on TR146 cells. Therefore, NAC, GSH, CS, SPC, and SNP appear to be safe, effective permeability enhancers that promote the transport of insulin across the TR146 cell-culture model of buccal epithelium and may be potential enhancers for buccal delivery of insulin with both low toxicity and high efficiency.

Contrast-enhanced spectral mammography: Impact of the qualitative morphology descriptors on the diagnosis of breast lesions.

PubMed

Mohamed Kamal, Rasha; Hussien Helal, Maha; Wessam, Rasha; Mahmoud Mansour, Sahar; Godda, Iman; Alieldin, Nelly

2015-06-01

To analyze the morphology and enhancement characteristics of breast lesions on contrast-enhanced spectral mammography (CESM) and to assess their impact on the differentiation between benign and malignant lesions. This ethics committee approved study included 168 consecutive patients with 211 breast lesions over 18 months. Lesions classified as non-enhancing and enhancing and then the latter group was subdivided into mass and non-mass. Mass lesions descriptors included: shape, margins, pattern and degree of internal enhancement. Non-mass lesions descriptors included: distribution, pattern and degree of internal enhancement. The impact of each descriptor on diagnosis individually assessed using Chi test and the validity compared in both benign and malignant lesions. The overall performance of CESM were also calculated. The study included 102 benign (48.3%) and 109 malignant (51.7%) lesions. Enhancement was encountered in 145/211 (68.7%) lesions. They further classified into enhancing mass (99/145, 68.3%) and non-mass lesions (46/145, 31.7%). Contrast uptake was significantly more frequent in malignant breast lesions (p value ≤ 0.001). Irregular mass lesions with intense and heterogeneous enhancement patterns correlated with a malignant pathology (p value ≤ 0.001). CESM showed an overall sensitivity of 88.99% and specificity of 83.33%. The positive and negative likelihood ratios were 5.34 and 0.13 respectively. The assessment of the morphology and enhancement characteristics of breast lesions on CESM enhances the performance of digital mammography in the differentiation between benign and malignant breast lesions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Dynamic Contrast-Enhanced Magnetic Resonance Imaging With Gadolinium Ethoxybenzyl Diethylenetriamine Pentaacetic Acid for Quantitative Assessment of Vascular Effects on Hepatocellular-Carcinoma Lesions Treated by Transarterial Chemoembolization or Radiofrequency Ablation.

PubMed

Ippolito, Davide; Trattenero, Chiara; Talei Franzesi, Cammillo; Casiraghi, Alessandra; Lombardi, Sophie; Vacirca, Francesco; Corso, Rocco; Sironi, Sandro

2016-01-01

The aim of this study was to investigate the role of dynamic contrast-enhanced magnetic resonance imaging (MRI) in evaluation of blood flow changes related to transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) procedures in patients with hepatocellular carcinoma (HCC) lesions. Fifty-four patients, with biopsy-proven HCC, who underwent TACE or RFA, were evaluated, 1 month after treatment, with upper abdominal MRI examination. Multiplanar T2-weighted, T1-weighted, and dynamic contrast-enhanced sequences were acquired. Dedicated perfusion software (T1 Perfusion Package, Viewforum; Philips Medical Systems, The Netherlands) was used to generate color permeability maps. After placing regions of interest in normal hepatic parenchyma, in successfully treated lesions, and in area of recurrence, the following perfusion parameters were calculated and statistically analyzed: relative arterial, venous, and late enhancement; maximum enhancement; maximum relative enhancement, and time to peak. Twenty-one of 54 patients had residual disease, and perfusion parameters values measured within tumor tissue were: relative arterial enhancement median, 42%; relative venous enhancement median, 69%; relative late enhancement median, 57.7%; maximum enhancement median, 749.6%; maximum relative enhancement median, 69%; time to peak median, 81.1 seconds. As for all the evaluated parameters, a significant difference (P < 0.05) was found between residual viable tumor tissue and effective treated lesions. Dynamic contrast-enhanced MRI represents a complementary noninvasive tool that may offer quantitative and qualitative information about HCC lesions treated with TACE and RFA.

Plant Enhancers: A Call for Discovery.

PubMed

Weber, Blaise; Zicola, Johan; Oka, Rurika; Stam, Maike

2016-11-01

Higher eukaryotes typically contain many different cell types, displaying different cellular functions that are influenced by biotic and abiotic cues. The different functions are characterized by specific gene expression patterns mediated by regulatory sequences such as transcriptional enhancers. Recent genome-wide approaches have identified thousands of enhancers in animals, reviving interest in enhancers in gene regulation. Although the regulatory roles of plant enhancers are as crucial as those in animals, genome-wide approaches have only very recently been applied to plants. Here we review characteristics of enhancers at the DNA and chromatin level in plants and other species, their similarities and differences, and techniques widely used for genome-wide discovery of enhancers in animal systems that can be implemented in plants. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pancultural self-enhancement.

PubMed

Sedikides, Constantine; Gaertner, Lowell; Toguchi, Yoshiyasu

2003-01-01

The culture movement challenged the universality of the self-enhancement motive by proposing that the motive is pervasive in individualistic cultures (the West) but absent in collectivistic cultures (the East). The present research posited that Westerners and Easterners use different tactics to achieve the same goal: positive self-regard. Study 1 tested participants from differing cultural backgrounds (the United States vs. Japan), and Study 2 tested participants of differing self-construals (independent vs. interdependent). Americans and independents self-enhanced on individualistic attributes, whereas Japanese and interdependents self-enhanced on collectivistic attributes. Independents regarded individualistic attributes, whereas interdependents regarded collectivistic attributes, as personally important. Attribute importance mediated self-enhancement. Regardless of cultural background or self-construal, people self-enhance on personally important dimensions. Self-enhancement is a universal human motive.

Can we apply the MRI BI-RADS lexicon morphology descriptors on contrast-enhanced spectral mammography?

PubMed

Kamal, Rasha M; Helal, Maha H; Mansour, Sahar M; Haggag, Marwa A; Nada, Omniya M; Farahat, Iman G; Alieldin, Nelly H

2016-07-12

To assess the feasibility of using the MRI breast imaging reporting and data system (BI-RADS) lexicon morphology descriptors to characterize enhancing breast lesions identified on contrast-enhanced spectral mammography (CESM). The study is a retrospective analysis of the morphology descriptors of 261 enhancing breast lesions identified on CESM in 239 patients. We presented the morphological categorization of the included lesions into focus, mass and non-mass. Further classifications included (1) the multiplicity for "focus" category, (2) the shape, margin and internal enhancement for "mass" category and (3) the distribution and internal enhancement for "non-mass" category. Each morphology descriptor was evaluated individually (irrespective of all other descriptors) by calculating its sensitivity, specificity, positive-predictive value (PPV) and negative-predictive value (NPV) and likelihood ratios (LRs). The study included 68/261 (26.1%) benign lesions and 193/261 (73.9%) malignant lesions. Intensely enhancing foci, whether single (7/12, 58.3%) or multiple (2/12, 16.7%), were malignant. Descriptors of "irregular"-shape (PPV: 92.4%) and "non-circumscribed" margin (odds ratio: 55.2, LR positive: 4.77; p-value: <0.001) were more compatible with malignancy. Internal mass enhancement patterns showed a very low specificity (58.0%) and NPV (40.0%). Non-mass enhancement (NME) was detected in 81/261 lesions. Asymmetrical NME in 81% (n = 52/81) lesions was malignant lesions and internal enhancement patterns indicative of malignancy were the heterogeneous and clumped ones. We can apply the MRI morphology descriptors to characterize lesions on CESM, but with few expectations. In many situations, irregular-shaped, non-circumscribed masses and NME with focal, ductal or segmental distribution and heterogeneous or clumped enhancement are the most suggestive descriptors of malignant pathologies. (1) The MRI BI-RADS lexicon morphology descriptors can be applied in the characterization of enhancing lesions on CESM with a few exceptions. (2) Multiple bilateral intensely enhancing foci should not be included under the normal background parenchymal enhancement unless they are proved to be benign by biopsy. (3) Mass lesion features that indicated malignancy were irregular-shaped, spiculated and irregular margins and heterogeneous internal enhancement patterns. The rim enhancement pattern should not be considered as a descriptor of malignant lesions unless CESM is coupled with an ultrasound examination.

Can we apply the MRI BI-RADS lexicon morphology descriptors on contrast-enhanced spectral mammography?

PubMed Central

Kamal, Rasha M; Helal, Maha H; Haggag, Marwa A; Nada, Omniya M; Farahat, Iman G; Alieldin, Nelly H

2016-01-01

Objective: To assess the feasibility of using the MRI breast imaging reporting and data system (BI-RADS) lexicon morphology descriptors to characterize enhancing breast lesions identified on contrast-enhanced spectral mammography (CESM). Methods: The study is a retrospective analysis of the morphology descriptors of 261 enhancing breast lesions identified on CESM in 239 patients. We presented the morphological categorization of the included lesions into focus, mass and non-mass. Further classifications included (1) the multiplicity for “focus” category, (2) the shape, margin and internal enhancement for “mass” category and (3) the distribution and internal enhancement for “non-mass” category. Each morphology descriptor was evaluated individually (irrespective of all other descriptors) by calculating its sensitivity, specificity, positive-predictive value (PPV) and negative-predictive value (NPV) and likelihood ratios (LRs). Results: The study included 68/261 (26.1%) benign lesions and 193/261 (73.9%) malignant lesions. Intensely enhancing foci, whether single (7/12, 58.3%) or multiple (2/12, 16.7%), were malignant. Descriptors of “irregular”-shape (PPV: 92.4%) and “non-circumscribed” margin (odds ratio: 55.2, LR positive: 4.77; p-value: <0.001) were more compatible with malignancy. Internal mass enhancement patterns showed a very low specificity (58.0%) and NPV (40.0%). Non-mass enhancement (NME) was detected in 81/261 lesions. Asymmetrical NME in 81% (n = 52/81) lesions was malignant lesions and internal enhancement patterns indicative of malignancy were the heterogeneous and clumped ones. Conclusion: We can apply the MRI morphology descriptors to characterize lesions on CESM, but with few expectations. In many situations, irregular-shaped, non-circumscribed masses and NME with focal, ductal or segmental distribution and heterogeneous or clumped enhancement are the most suggestive descriptors of malignant pathologies. Advances in knowledge: (1) The MRI BI-RADS lexicon morphology descriptors can be applied in the characterization of enhancing lesions on CESM with a few exceptions. (2) Multiple bilateral intensely enhancing foci should not be included under the normal background parenchymal enhancement unless they are proved to be benign by biopsy. (3) Mass lesion features that indicated malignancy were irregular-shaped, spiculated and irregular margins and heterogeneous internal enhancement patterns. The rim enhancement pattern should not be considered as a descriptor of malignant lesions unless CESM is coupled with an ultrasound examination. PMID:27327403

Enhancing Exposure Therapy for Anxiety Disorders, Obsessive Compulsive Disorder, and Posttraumatic Stress Disorder

PubMed Central

McGuire, Joseph F.; Lewin, Adam B.; Storch, Eric A.

2014-01-01

Translating findings from basic science, several compounds have been identified that may enhance therapeutic outcomes and/or expedite treatment gains when administered alongside exposure-based treatments. Four of these compounds (referred to as cognitive enhancers) have been evaluated in the context of randomized controlled trials for anxiety disorders (e.g., specific phobias, panic disorder, social anxiety disorder), obsessive compulsive disorder (OCD), and posttraumatic stress disorder (PTSD). These cognitive enhancers include D-cycloserine, yohimbine hydrochloride, glucocorticoids and cortisol, and brain derived neurotrophic factor. There is consistent evidence that cognitive enhancers can enhance therapeutic outcomes and/or expedite treatment gains across anxiety disorders, OCD, and PTSD. Emerging evidence has highlighted the importance of within-session fear habituation and between-session fear learning, which can either enhance fear extinction or reconsolidate of fear responses. Although findings from these trials are promising, there are several considerations that warrant further evaluation prior to wide-spread use of cognitive enhancers in exposure-based treatments. Consistent trial design and large sample sizes are important in future studies of cognitive enhancers. PMID:24972729

Information Propagation in Developmental Enhancers

NASA Astrophysics Data System (ADS)

Jena, Siddhartha; Levine, Michael

Rather than encoding information about protein sequence, certain lengths of noncoding DNA, called enhancers, interact with protein machinery such as transcription factors to precisely regulate gene expression. Enhancers have been studied extensively in the fruit fly Drosophila melanogaster, where they regulate the expression of developmental genes that establish the blueprint of the adult fly. It has been suggested that enhancer sequences possess a specific but unknown syntax with regards to the placement and strength of transcription factor binding sites. Moreover, studies in divergent fly species have shown that compensatory evolution allows for maintenance of enhancer functionality despite considerable variation in primary DNA sequence. Here, the possible role of enhancers as signal processing modules is studied as a way of explaining these two findings. We first demonstrate how this framework can be used to explain the fine-tuned spatiotemporal dynamics of gene expression. We then explore the evolutionary pressure on enhancer sequences and the resulting emergence of enhancers that are linked by compensatory mutations. This study provides a possible mechanism for the function of multiple enhancers linked to a single gene.

Expression of Terminal Effector Genes in Mammalian Neurons Is Maintained by a Dynamic Relay of Transient Enhancers.

PubMed

Rhee, Ho Sung; Closser, Michael; Guo, Yuchun; Bashkirova, Elizaveta V; Tan, G Christopher; Gifford, David K; Wichterle, Hynek

2016-12-21

Generic spinal motor neuron identity is established by cooperative binding of programming transcription factors (TFs), Isl1 and Lhx3, to motor-neuron-specific enhancers. How expression of effector genes is maintained following downregulation of programming TFs in maturing neurons remains unknown. High-resolution exonuclease (ChIP-exo) mapping revealed that the majority of enhancers established by programming TFs are rapidly deactivated following Lhx3 downregulation in stem-cell-derived hypaxial motor neurons. Isl1 is released from nascent motor neuron enhancers and recruited to new enhancers bound by clusters of Onecut1 in maturing neurons. Synthetic enhancer reporter assays revealed that Isl1 operates as an integrator factor, translating the density of Lhx3 or Onecut1 binding sites into transient enhancer activity. Importantly, independent Isl1/Lhx3- and Isl1/Onecut1-bound enhancers contribute to sustained expression of motor neuron effector genes, demonstrating that outwardly stable expression of terminal effector genes in postmitotic neurons is controlled by a dynamic relay of stage-specific enhancers. Copyright © 2016 Elsevier Inc. All rights reserved.

Transcriptional Dysregulation of MYC Reveals Common Enhancer-Docking Mechanism.

PubMed

Schuijers, Jurian; Manteiga, John Colonnese; Weintraub, Abraham Selby; Day, Daniel Sindt; Zamudio, Alicia Viridiana; Hnisz, Denes; Lee, Tong Ihn; Young, Richard Allen

2018-04-10

Transcriptional dysregulation of the MYC oncogene is among the most frequent events in aggressive tumor cells, and this is generally accomplished by acquisition of a super-enhancer somewhere within the 2.8 Mb TAD where MYC resides. We find that these diverse cancer-specific super-enhancers, differing in size and location, interact with the MYC gene through a common and conserved CTCF binding site located 2 kb upstream of the MYC promoter. Genetic perturbation of this enhancer-docking site in tumor cells reduces CTCF binding, super-enhancer interaction, MYC gene expression, and cell proliferation. CTCF binding is highly sensitive to DNA methylation, and this enhancer-docking site, which is hypomethylated in diverse cancers, can be inactivated through epigenetic editing with dCas9-DNMT. Similar enhancer-docking sites occur at other genes, including genes with prominent roles in multiple cancers, suggesting a mechanism by which tumor cell oncogenes can generally hijack enhancers. These results provide insights into mechanisms that allow a single target gene to be regulated by diverse enhancer elements in different cell types. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

enhancedGraphics: a Cytoscape app for enhanced node graphics

PubMed Central

Morris, John H.; Kuchinsky, Allan; Ferrin, Thomas E.; Pico, Alexander R.

2014-01-01

enhancedGraphics ( http://apps.cytoscape.org/apps/enhancedGraphics) is a Cytoscape app that implements a series of enhanced charts and graphics that may be added to Cytoscape nodes. It enables users and other app developers to create pie, line, bar, and circle plots that are driven by columns in the Cytoscape Node Table. Charts are drawn using vector graphics to allow full-resolution scaling. PMID:25285206

Considerations in Designing and Implementing Enhancements to COSTAR

PubMed Central

Piggins, Judith; McLatchey, John; Zielstorff, Rita; Barrett, Suzanne; Smith, Monica; Weidman-Dahl, Frances; Brown, Kibbe; Barnett, G. Octo

1982-01-01

The addition of enhancements to a COSTAR system can involve a significant investment of effort. This paper describes recent experience in implementing two major COSTAR enhancements, namely a patient-specific encounter form and an order entry and dispatch subsystem. A number of points to be considered in regard to planning and implementing such enhancements are raised, and the relative success of these two enhancements at one particular site is discussed.

Exploring the chemical enhancement for surface-enhanced Raman scattering with Au bowtie nanoantennas

PubMed Central

Fromm, David P.; Kinkhabwala, Anika; Schuck, P. James; Moerner, W. E.; Sundaramurthy, Arvind; Kino, Gordon S.

2006-01-01

Single metallic bowtie nanoantennas provide a controllable environment for surface-enhanced Raman scattering (SERS) of adsorbed molecules. Bowties have experimentally measured electromagnetic enhancements, enabling estimation of chemical enhancement for both the bulk and the few-molecule regime. Strong fluctuations of selected Raman lines imply that a small number of p-mercaptoaniline molecules on a single bowtie show chemical enhancement >107, much larger than previously believed, likely due to charge transfer between the Au surface and the molecule. This chemical sensitivity of SERS has significant implications for ultra-sensitive detection of single molecules. PMID:16483189

Enhancement of lymphocyte proliferation by mouse glandular kallikrein.

PubMed

Hu, Z Q; Murakami, K; Ikigai, H; Shimamura, T

1992-03-01

Mouse glandular kallikrein (mGK) strongly enhanced the spontaneous and mitogen-induced proliferation of lymphocytes. Both blast formation and 3H-TdR incorporation were dose-dependently enhanced at the same time many cells were killed. The enhancing activity was independent of EGF, because EGF-binding proteins (mGK-9 in mGK-6,9 mixture and mGK-13), renal kallikrein (mGK-6) and human kallikrein all displayed the same enhancement. A serine proteinase inhibitor, diisopropyl fluorophosphate, could block the enhancement by mGK. The new function suggests that mGK is important in the immune system as a regulatory molecule.

Color enhancement of landsat agricultural imagery: JPL LACIE image processing support task

NASA Technical Reports Server (NTRS)

Madura, D. P.; Soha, J. M.; Green, W. B.; Wherry, D. B.; Lewis, S. D.

1978-01-01

Color enhancement techniques were applied to LACIE LANDSAT segments to determine if such enhancement can assist analysis in crop identification. The procedure involved increasing the color range by removing correlation between components. First, a principal component transformation was performed, followed by contrast enhancement to equalize component variances, followed by an inverse transformation to restore familiar color relationships. Filtering was applied to lower order components to reduce color speckle in the enhanced products. Use of single acquisition and multiple acquisition statistics to control the enhancement were compared, and the effects of normalization investigated. Evaluation is left to LACIE personnel.

OBLIGING SURGEONS TO ENHANCE: NEGLIGENCE LIABILITY FOR UNCORRECTED FATIGUE AND PROBLEMS WITH PROVING CAUSATION.

PubMed

Goold, Imogen; Maslen, Hannah

2015-01-01

Increasing interest in the use of cognitive enhancing pharmaceuticals, such as modafinil, has led to considerable ethical debate about issues around authenticity, fairness and even whether there is a moral obligation to enhance. This latter question has raised questions as to whether there might be a legal obligation to enhance. We have argued elsewhere that the law will not oblige a professional to self-enhance. In this article, we explore a second reason why a claim of negligence for a failure to enhance would be unlikely to succeed: the problem of establishing causation. As the science on enhancers and what they are capable of currently stands, it would be almost invariably impossible to establish a causal link between failure to enhance to redress fatigue, and the harm that allegedly resulted. Even where a link between fatigue and harm can be established, it will be extremely difficult to show that taking an enhancer would have averted the harm. We focus on the most likely context in which such claims might arise--clinical negligence--and on the most efficacious enhancing drug currently available-modafinil. © The Author 2014. Published by Oxford University Press; all rights reserved. For Permissions, please email: journals.permissions@oup.com.

Raman Enhancement Effect on Thin GaSe Flake and Its Thickness Dependence

NASA Astrophysics Data System (ADS)

Quan, Lin; Song, Yuqing; Zhang, Guanghui; Wu, Yukun; Jin, Ke; Ding, Huaiyi; Pan, Nan; Luo, Yi; Wang, Xiaoping

Chemical enhancement is one of the important mechanisms in surface-enhanced Raman spectroscopy, however, its origin is still under debate. Two dimensional (2D) layered material is thought to be a strong candidate to investigate the chemical mechanism of Raman enhancement because it has flat surface, well defined structure and without the interference of electromagnetic enhancement. Herein we report the systematic studies of Raman enhancement effect on the gallium selenide (GaSe) flake by using copper phthalocyanine (CuPc) molecule as a probe. It is found that the Raman signal of CuPc on the monolayer GaSe can be significantly increased by one order of magnitude than that on the SiO2/Si substrate. Meanwhile, the enhancement effect is found to decrease with increasing the thickness of GaSe flake. The origin of the Raman enhancement is attributed to the chemical mechanism resulted from the charge transfer between the GaSe flake and the detected molecules. The supposition is further verified by the investigation of Raman enhancement effect of CuPc with different thicknesses on the GaSe flake. Our work will shed more light on the understanding of the chemical mechanism for Raman enhancement and expand more practical applications of GaSe.

Well-Loved Music Robustly Relieves Pain: A Randomized, Controlled Trial

PubMed Central

Hsieh, Christine; Kong, Jian; Kirsch, Irving; Edwards, Robert R.; Jensen, Karin B.; Kaptchuk, Ted J.; Gollub, Randy L.

2014-01-01

Music has pain-relieving effects, but its mechanisms remain unclear. We sought to verify previously studied analgesic components and further elucidate the underpinnings of music analgesia. Using a well-characterized conditioning-enhanced placebo model, we examined whether boosting expectations would enhance or interfere with analgesia from strongly preferred music. A two-session experiment was performed with 48 healthy, pain experiment-naïve participants. In a first cohort, 36 were randomized into 3 treatment groups, including music enhanced with positive expectancy, non-musical sound enhanced with positive expectancy, and no expectancy enhancement. A separate replication cohort of 12 participants received only expectancy-enhanced music following the main experiment to verify the results of expectancy-manipulation on music. Primary outcome measures included the change in subjective pain ratings to calibrated experimental noxious heat stimuli, as well as changes in treatment expectations. Without conditioning, expectations were strongly in favor of music compared to non-musical sound. While measured expectations were enhanced by conditioning, this failed to affect either music or sound analgesia significantly. Strongly preferred music on its own was as pain relieving as conditioning-enhanced strongly preferred music, and more analgesic than enhanced sound. Our results demonstrate the pain-relieving power of personal music even over enhanced expectations. Trial Information Clinicaltrials.gov NCT01835275. PMID:25211164

Edge enhancement improves disruptive camouflage by emphasising false edges and creating pictorial relief

PubMed Central

Egan, John; Sharman, Rebecca J.; Scott-Brown, Kenneth C.; Lovell, Paul George

2016-01-01

Disruptive colouration is a visual camouflage composed of false edges and boundaries. Many disruptively camouflaged animals feature enhanced edges; light patches are surrounded by a lighter outline and/or a dark patches are surrounded by a darker outline. This camouflage is particularly common in amphibians, reptiles and lepidopterans. We explored the role that this pattern has in creating effective camouflage. In a visual search task utilising an ultra-large display area mimicking search tasks that might be found in nature, edge enhanced disruptive camouflage increases crypsis, even on substrates that do not provide an obvious visual match. Specifically, edge enhanced camouflage is effective on backgrounds both with and without shadows; i.e. this is not solely due to background matching of the dark edge enhancement element with the shadows. Furthermore, when the dark component of the edge enhancement is omitted the camouflage still provided better crypsis than control patterns without edge enhancement. This kind of edge enhancement improved camouflage on all background types. Lastly, we show that edge enhancement can create a perception of multiple surfaces. We conclude that edge enhancement increases the effectiveness of disruptive camouflage through mechanisms that may include the improved disruption of the object outline by implying pictorial relief. PMID:27922058

Edge enhancement improves disruptive camouflage by emphasising false edges and creating pictorial relief.

PubMed

Egan, John; Sharman, Rebecca J; Scott-Brown, Kenneth C; Lovell, Paul George

2016-12-06

Disruptive colouration is a visual camouflage composed of false edges and boundaries. Many disruptively camouflaged animals feature enhanced edges; light patches are surrounded by a lighter outline and/or a dark patches are surrounded by a darker outline. This camouflage is particularly common in amphibians, reptiles and lepidopterans. We explored the role that this pattern has in creating effective camouflage. In a visual search task utilising an ultra-large display area mimicking search tasks that might be found in nature, edge enhanced disruptive camouflage increases crypsis, even on substrates that do not provide an obvious visual match. Specifically, edge enhanced camouflage is effective on backgrounds both with and without shadows; i.e. this is not solely due to background matching of the dark edge enhancement element with the shadows. Furthermore, when the dark component of the edge enhancement is omitted the camouflage still provided better crypsis than control patterns without edge enhancement. This kind of edge enhancement improved camouflage on all background types. Lastly, we show that edge enhancement can create a perception of multiple surfaces. We conclude that edge enhancement increases the effectiveness of disruptive camouflage through mechanisms that may include the improved disruption of the object outline by implying pictorial relief.

Far-side geometrical enhancement in surface-enhanced Raman scattering with Ag plasmonic films

NASA Astrophysics Data System (ADS)

Perera, M. Nilusha M. N.; Gibbs, W. E. Keith; Juodkazis, Saulius; Stoddart, Paul R.

2018-01-01

Surface-enhanced Raman scattering (SERS) is a surface sensitive technique where the large increase in scattering has primarily been attributed to electromagnetic and chemical enhancements. While smaller geometrical enhancements due to thin film interference and cavity resonances have also been reported, an additional enhancement in the SERS signal, referred to as the `far-side geometrical enhancement', occurs when the SERS substrate is excited through an underlying transparent dielectric substrate. Here the far-side geometrically-enhanced SERS signal has been explored experimentally in more detail. Thermally evaporated Ag plasmonic films functionalised with thiophenol were used to study the dependence of the geometrically-enhanced SERS signal on the excitation wavelength, supporting substrate material and excitation angle of incidence. The results were interpreted using a `geometrical enhancement factor' (GEF), defined as the ratio of far-side to near-side SERS signal intensity. The experimental results confirmed that the highest GEFs of 3.2-3.5× are seen closer to the localized surface plasmon resonance peak of the Ag metallic nanostructures. Interestingly, the GEF for Ag plasmonic films deposited on glass and sapphire were the same within the measurement errors, whereas increasing angle of incidence showed a decrease in the GEF. Given this improved understanding of the far-side geometrical SERS enhancement, the potential for further signal amplification and optimisation for practical sensing applications can now be considered, especially for SERS detection modes at the farend of optical fibre probes and through process windows.

An insight into the molecular mechanism of the temporary enhancement effect of isopulegol decanoate on the skin.

PubMed

Liu, Xiaochang; Liu, Meiying; Liu, Chao; Quan, Peng; Zhao, Yongshan; Fang, Liang

2017-08-30

Chemical enhancers are widely used to facilitate drug permeation in transdermal drug delivery system (TDDS) and the effect of chemical enhancers is desired to be temporary. Though temporary enhancement effect of chemical enhancers has been widely discussed, there is still a lack of knowledge about the molecular mechanism of temporary enhancement effect. Using the skin permeation of flurbiprofen as a probe, the temporary enhancement effect of isopulegol decanoate (ISO-10) was evaluated with in vitro permeation experiment and confocal laser scanning microscopy (CLSM). In addition, molecular mechanism of skin recovery was explored with skin retention of ISO-10, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), molecular dynamic (MD) simulation and transepidermal water loss (TEWL). Temporary enhancement effect of ISO-10 was observed by the permeation of flurbiprofen after the treatment of 180min. Furthermore, temporary enhancement effect of ISO-10 on the diffusion of intercellular lipid in the stratum cornuem (SC) was observed by ATR-FTIR, molecular dynamic (MD) simulation. The SC barrier function recovered with the existence of ISO-10 in the lipid bilayer as indicated by the retention study and TEWL. In conclusion, the lipid bilayer accepted the enhancer as a new component to form a new stable arrangement, resulted the recovery of the skin barrier function. This work processed a novel mechanism of the recovery of skin barrier function after the addition of chemical enhancers. Copyright © 2017 Elsevier B.V. All rights reserved.

75 FR 38863 - Tenth Meeting: Joint RTCA Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-06

... Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS) AGENCY...-79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS). SUMMARY: The FAA is issuing...: Enhanced Flight [[Page 38864

75 FR 18146 - Wetlands Reserve Enhancement Program

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-09

... DEPARTMENT OF AGRICULTURE Commodity Credit Corporation Wetlands Reserve Enhancement Program AGENCY... assistance will be made available in fiscal year (FY) 2010 for the Wetlands Reserve Enhancement Program (WREP... partners to help enhance conservation outcomes on wetlands and adjacent lands. WREP targets and leverages...

Information Tailoring Enhancements for Large-Scale Social Data

DTIC Science & Technology

2016-06-15

Intelligent Automation Incorporated Information Tailoring Enhancements for Large-Scale... Automation Incorporated Progress Report No. 3 Information Tailoring Enhancements for Large-Scale Social Data Submitted in accordance with...1 Work Performed within This Reporting Period .................................................... 2 1.1 Enhanced Named Entity Recognition (NER

The discovery and mechanism of sweet taste enhancers.

PubMed

Li, Xiaodong; Servant, Guy; Tachdjian, Catherine

2011-08-01

Excess sugar intake posts several health problems. Artificial sweeteners have been used for years to reduce dietary sugar content, but they are not ideal substitutes for sugar owing to their off-taste. A new strategy focused on allosteric modulation of the sweet taste receptor led to identification of sweet taste 'enhancers' for the first time. The enhancer molecules do not taste sweet, but greatly potentiate the sweet taste of sucrose and sucralose selectively. Following a similar mechanism as the natural umami taste enhancers, the sweet enhancer molecules cooperatively bind with the sweeteners to the Venus flytrap domain of the human sweet taste receptor and stabilize the active conformation. Now that the approach has proven successful, enhancers for other sweeteners and details of the molecular mechanism for the enhancement are being actively pursued.

[Ethical aspects of pharmacological cognition enhancement and the use of psychostimulants by children and young persons].

PubMed

Walcher-Andris, Elfriede

2006-03-01

Pharmacological cognition enhancement aims at an improvement of cognitive activity and performance in healthy people by means of appropriate drugs. Ethical implications of this kind of cognition enhancement stand in need of reflection. For a number of reasons, the distinction between treatment and enhancement is fuzzy with regard to Attention Deficit Hyperactivity Disorder (ADHD). In consideration of the growing number methylphenidate prescriptions, one question addressed in this article is whether or not psychostimulants are used not only for therapy but also for cognitive enhancement by children and young people. The possibility of a "grey zone" between treatment and enhancement seems to open the field for medicalization of social and pedagogical problems as well as for "hidden enhancement." In clinical practice, the use of stimulants is associated with certain ethical problems concerning diagnosis, treatment and prevention of ADHD. Some of these problems are associated with the possibility of cognition enhancement. In order to evaluate ethical problems of pharmacological cognition enhancement, short-term and long-term consequences of stimulant use need to be taken into account. This refers to the level of transmitter balance in the learning process, to the level of individual learning strategies as well as to the level of interaction. This raises the question (1) of how well adapted the means of enhancement are with regard to the end of a comprehensive education and socialization, and (2) whether there are justifiable limits to the standardization of behavior and knowledge. (3) Moreover, stipulating an autonomous decision as a minimum prerequisite for legitimate cognition enhancement seems inadequate in the case of children and young persons. Considering the evidence and the many open questions associated with pharmacological cognition enhancement for children and young persons, it is concluded that it is indeed a morally problematic technique.

Sex differences and the role of dopamine receptors in the reward-enhancing effects of nicotine and bupropion.

PubMed

Barrett, Scott T; Geary, Trevor N; Steiner, Amy N; Bevins, Rick A

2017-01-01

Nicotine and bupropion have been demonstrated to enhance the value of other reinforcers, and this may partially account for nicotine reward and dependence. Evidence suggests that the sexes differ in their sensitivity to the primary and secondary reinforcing effects of nicotine and nicotine-associated stimuli. Whether the sexes also differ in sensitivity to the reward-enhancing effects of nicotine (and bupropion) is yet unclear. The present study evaluated potential sex differences in the enhancement effects of nicotine and bupropion using a reinforcer demand approach. Furthermore, we sought to investigate the role that D1- and D2-type dopamine receptors play in the reward-enhancing effects of nicotine and bupropion. Demand for sensory reinforcement was assessed in male and female rats responding on a progression of fixed ratio schedules. The effects of nicotine and 10 or 20 mg/kg bupropion on reinforcer demand were assessed within subjects. Subsequently, the effects of SCH-23390 and eticlopride were assessed on the enhancing effects of nicotine and bupropion on progressive ratio responding. Nicotine and bupropion enhanced demand metrics of reinforcement value in both sexes. Females were more sensitive to the enhancement effects of bupropion assessed by reinforcer demand and progressive ratio performance. D2-like dopamine receptor antagonism by eticlopride attenuated the enhancement effects of bupropion, but not of nicotine. Nicotine and bupropion both enhance reinforcement value in both sexes, though females may be more sensitive to the reward-enhancing effects of bupropion. D2- and possibly D1-type receptors appear to be involved in the reward-enhancing effects of bupropion, but not necessarily nicotine.

Selling and Smooth-Talking: Effects of Interviewer Impression Management from a Signaling Perspective.

PubMed

Wilhelmy, Annika; Kleinmann, Martin; Melchers, Klaus G; Götz, Martin

2017-01-01

Prior research suggests that interviewers play an important role in representing their organization and in making the interview a pleasant experience for applicants. This study examined whether impression management used by interviewers (organization-enhancement and applicant-enhancement) is perceived by applicants, and how it influences applicants' attitudes, intentions, and emotions. Adopting a signaling perspective, this article argues that applicants' positive attitudes and intentions toward the organization increase if interviewers not only enhance the organization, but if the signals they sent (i.e., organization-enhancement) are actually received by the applicant. Similarly, applicants' positive emotions should increase if interviewers not only enhance the applicant, but if the signals they send (i.e., applicant-enhancement) are actually received by the applicant. A field study that involved video coding interviewers' impression management behavior during 153 selection interviews and pre- and post-interview applicant surveys showed that the signals sent by interviewers during the interview were received by applicants. In addition, applicants rated the organization's prestige and their own positive affect after the interview more positively when they perceived higher levels of organization-enhancement during the interview. Furthermore, applicants reported more positive affect and interview self-efficacy after the interview when they perceived higher levels of interviewer applicant-enhancement. We also found an indirect effect of interviewers' organization-enhancement on organizational prestige through applicants' perceptions of organization-enhancement as well as indirect effects of interviewers' applicant-enhancement on applicants' positive affect and interview self-efficacy through applicants' perceptions of applicant-enhancement. Our findings contribute to an integrated understanding of the effects of interviewer impression management and point out both risks and chances in selling and smooth-talking toward applicants.

Selling and Smooth-Talking: Effects of Interviewer Impression Management from a Signaling Perspective

PubMed Central

Wilhelmy, Annika; Kleinmann, Martin; Melchers, Klaus G.; Götz, Martin

2017-01-01

Prior research suggests that interviewers play an important role in representing their organization and in making the interview a pleasant experience for applicants. This study examined whether impression management used by interviewers (organization-enhancement and applicant-enhancement) is perceived by applicants, and how it influences applicants' attitudes, intentions, and emotions. Adopting a signaling perspective, this article argues that applicants' positive attitudes and intentions toward the organization increase if interviewers not only enhance the organization, but if the signals they sent (i.e., organization-enhancement) are actually received by the applicant. Similarly, applicants' positive emotions should increase if interviewers not only enhance the applicant, but if the signals they send (i.e., applicant-enhancement) are actually received by the applicant. A field study that involved video coding interviewers' impression management behavior during 153 selection interviews and pre- and post-interview applicant surveys showed that the signals sent by interviewers during the interview were received by applicants. In addition, applicants rated the organization's prestige and their own positive affect after the interview more positively when they perceived higher levels of organization-enhancement during the interview. Furthermore, applicants reported more positive affect and interview self-efficacy after the interview when they perceived higher levels of interviewer applicant-enhancement. We also found an indirect effect of interviewers' organization-enhancement on organizational prestige through applicants' perceptions of organization-enhancement as well as indirect effects of interviewers' applicant-enhancement on applicants' positive affect and interview self-efficacy through applicants' perceptions of applicant-enhancement. Our findings contribute to an integrated understanding of the effects of interviewer impression management and point out both risks and chances in selling and smooth-talking toward applicants. PMID:28611696

Results of vardenafil mediated power Doppler ultrasound, contrast enhanced ultrasound and systematic random biopsies to detect prostate cancer.

PubMed

Morelli, Girolamo; Pagni, Riccardo; Mariani, Chiara; Minervini, Riccardo; Morelli, Andrea; Gori, Francesco; Ferdeghini, Ezio Maria; Paterni, Marco; Mauro, Eva; Guidi, Elisa; Armillotta, Nicola; Canale, Domenico; Vitti, Paolo; Caramella, Davide; Minervini, Andrea

2011-06-01

We evaluated the ability of the phosphodiesterase-5 inhibitor vardenafil to increase prostate microcirculation during power Doppler ultrasound. We also evaluated the results of contrast and vardenafil enhanced targeted biopsies compared to those of standard 12-core random biopsies to detect cancer. Between May 2008 and January 2010, 150 consecutive patients with prostate specific antigen more than 4 ng/ml at first diagnosis with negative digital rectal examination and transrectal ultrasound, and no clinical history of prostatitis underwent contrast enhanced power Doppler ultrasound (bolus injection of 2.4 ml SonoVue® contrast agent), followed by vardenafil enhanced power Doppler ultrasound (1 hour after oral administration of vardenafil 20 mg). All patients underwent standard 12-core transrectal ultrasound guided random prostate biopsy plus 1 further sampling from each suspected hypervascular lesion detected by contrast and vardenafil enhanced power Doppler ultrasound. Prostate cancer was detected in 44 patients (29.3%). Contrast and vardenafil enhanced power Doppler ultrasound detected suspicious, contrast enhanced and vardenafil enhanced areas in 112 (74.6%) and 110 patients (73.3%), and was diagnostic for cancer in 32 (28.5%) and 42 (38%), respectively. Analysis of standard technique, and contrast and vardenafil enhanced power Doppler ultrasound findings by biopsy core showed significantly higher detection using vardenafil vs contrast enhanced power Doppler ultrasound and standard technique (41.2% vs 22.7% and 8.1%, p <0.005 and <0.001, respectively). The detection rate of standard plus contrast or vardenafil enhanced power Doppler ultrasound was 10% and 11.7% (p not significant). Vardenafil enhanced power Doppler ultrasound enables excellent visualization of the microvasculature associated with cancer and can improve the detection rate compared to contrast enhanced power Doppler ultrasound and the random technique. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Assessment of Gd-EOB-DTPA-enhanced MRI for HCC and dysplastic nodules and comparison of detection sensitivity versus MDCT.

PubMed

Inoue, Tatsuo; Kudo, Masatoshi; Komuta, Mina; Hayaishi, Sosuke; Ueda, Taisuke; Takita, Masahiro; Kitai, Satoshi; Hatanaka, Kinuyo; Yada, Norihisa; Hagiwara, Satoru; Chung, Hobyung; Sakurai, Toshiharu; Ueshima, Kazuomi; Sakamoto, Michiie; Maenishi, Osamu; Hyodo, Tomoko; Okada, Masahiro; Kumano, Seishi; Murakami, Takamichi

2012-09-01

We aimed to evaluate gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for the detection of hepatocellular carcinomas (HCCs) and dysplastic nodules (DNs) compared with dynamic multi-detector row computed tomography (MDCT), and to discriminate between HCCs and DNs. Eighty-six nodules diagnosed as HCC or DNs were retrospectively investigated. Gd-EOB-DTPA-enhanced MRI and dynamic MDCT were compared with respect to their diagnostic ability for hypervascular HCCs and detection sensitivity for hypovascular tumors. The ability of hepatobiliary images of Gd-EOB-DTPA-enhanced MRI to discriminate between these nodules was assessed. We also calculated the EOB enhancement ratio of the tumors. For hypervascular HCCs, the diagnostic ability of Gd-EOB-DTPA-enhanced MRI was significantly higher than that of MDCT for tumors less than 2 cm (p = 0.048). There was no difference in the detection of hypervascular HCCs between hepatobiliary phase images of Gd-EOB-DTPA-enhanced MRI (43/45: 96%) and dynamic MDCT (40/45: 89%), whereas the detection sensitivity of hypovascular tumors by Gd-EOB-DTPA-enhanced MRI was significantly higher than that by dynamic MDCT (39/41: 95% vs. 25/41: 61%, p = 0.001). EOB enhancement ratios were decreased in parallel with the degree of differentiation in DNs and HCCs, although there was no difference between DNs and hypovascular well-differentiated HCCs. The diagnostic ability of Gd-EOB-DTPA-enhanced MRI for hypervascular HCCs less than 2 cm was significantly higher than that of MDCT. For hypovascular tumors, the detection sensitivity of hepatobiliary phase images of Gd-EOB-DTPA-enhanced MRI was significantly higher than that of dynamic Gd-EOB-DTPA-enhanced MRI and dynamic MDCT. It was difficult to distinguish between DNs and hypovascular well-differentiated HCCs based on the EOB enhancement ratio.

Transcriptional enhancer from milk protein genes

DOEpatents

Casperson, Gerald F.; Schmidhauser, Christian T.; Bissell, Mina J.

1999-01-01

The invention relates to novel enhancer nucleotide sequences which stimulate transcription of heterologous DNA in cells in culture. The enhancers are derived from major milk protein genes by the process of deletion mapping and functional analysis. The invention also relates to expression vectors containing the novel enhancers.

Giant Suppression of Photobleaching for Single Molecule Detection via the Purcell Effect

DTIC Science & Technology

2013-11-18

the molecule dissipates energy to emit another photon (spontaneous emission, or fluorescence, with rate kf) or to heat (intrinsic nonradiative process...enhancement gives rise to both enhanced radiation and enhanced nonradiation (energy dissipation due to Ohmic losses). The enhancement of

7 CFR 1467.9 - Wetlands Reserve Enhancement Program.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 10 2011-01-01 2011-01-01 false Wetlands Reserve Enhancement Program. 1467.9 Section... CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS WETLANDS RESERVE PROGRAM § 1467.9 Wetlands Reserve Enhancement Program. (a) Wetlands Reserve Enhancement Program (WREP). (1) The...

Composite Materials with Magnetically Aligned Carbon Nanoparticles Having Enhanced Electrical Properties and Methods of Preparation

NASA Technical Reports Server (NTRS)

Peterson, G.P. (Bud) (Inventor); Hong, Haiping (Inventor); Salem, David R. (Inventor)

2016-01-01

Magnetically aligned carbon nanoparticle composites have enhanced electrical properties. The composites comprise carbon nanoparticles, a host material, magnetically sensitive nanoparticles and a surfactant. In addition to enhanced electrical properties, the composites can have enhanced mechanical and thermal properties.

Enhanced biogenic emissions of nitric oxide and nitrous oxide following surface biomass burning

Treesearch

Iris C. Anderson; Joel S. Levine; Mark A. Poth; Philip J. Riggan

1988-01-01

Recent measurements indicate significantly enhanced biogenic soil emissions of both nitric oxide (NO) and nitrous oxide (N2O) following surface burning. These enhanced fluxes persisted for at least 6 months following the burn. Simultaneous measurements indicate enhanced levels of...

NORMAL HUMAN VARIATION: REFOCUSSING THE ENHANCEMENT DEBATE

PubMed Central

Kahane, Guy; Savulescu, Julian

2015-01-01

This article draws attention to several common mistakes in thinking about biomedical enhancement, mistakes that are made even by some supporters of enhancement. We illustrate these mistakes by examining objections that John Harris has recently raised against the use of pharmacological interventions to directly modulate moral decision-making. We then apply these lessons to other influential figures in the debate about enhancement. One upshot of our argument is that many considerations presented as powerful objections to enhancement are really strong considerations in favour of biomedical enhancement, just in a different direction. Another upshot is that it is unfortunate that much of the current debate focuses on interventions that will radically transform normal human capacities. Such interventions are unlikely to be available in the near future, and may not even be feasible. But our argument shows that the enhancement project can still have a radical impact on human life even if biomedical enhancement operated entirely within the normal human range. PMID:23906367

An improved contrast enhancement algorithm for infrared images based on adaptive double plateaus histogram equalization

NASA Astrophysics Data System (ADS)

Li, Shuo; Jin, Weiqi; Li, Li; Li, Yiyang

2018-05-01

Infrared thermal images can reflect the thermal-radiation distribution of a particular scene. However, the contrast of the infrared images is usually low. Hence, it is generally necessary to enhance the contrast of infrared images in advance to facilitate subsequent recognition and analysis. Based on the adaptive double plateaus histogram equalization, this paper presents an improved contrast enhancement algorithm for infrared thermal images. In the proposed algorithm, the normalized coefficient of variation of the histogram, which characterizes the level of contrast enhancement, is introduced as feedback information to adjust the upper and lower plateau thresholds. The experiments on actual infrared images show that compared to the three typical contrast-enhancement algorithms, the proposed algorithm has better scene adaptability and yields better contrast-enhancement results for infrared images with more dark areas or a higher dynamic range. Hence, it has high application value in contrast enhancement, dynamic range compression, and digital detail enhancement for infrared thermal images.

Enhanced activation of the left hemisphere promotes normative decision making.

PubMed

Corser, Ryan; Jasper, John D

2014-01-01

Previous studies have reported that enhanced activation of the left cerebral hemisphere reduces risky-choice, attribute, and goal-framing effects relative to enhanced activation of the right cerebral hemisphere. The present study sought to extend these findings and show that enhanced activation of the left hemisphere also reduces violations of other normative principles, besides the invariance principle. Participants completed ratio bias (Experiment 1, N = 296) and base rate neglect problems (Experiment 2, N = 145) under normal (control) viewing or with the right or left hemisphere primarily activated by imposing a unidirectional gaze. In Experiment 1 we found that enhanced left hemispheric activation reduced the ratio bias relative to normal viewing and a group experiencing enhanced right hemispheric activation. In Experiment 2 enhanced left hemispheric activation resulted in using base rates more than normal viewing, but not significantly more than enhanced right hemispheric activation. Results suggest that hemispheric asymmetries can affect higher-order cognitive processes, such as decision-making biases. Possible theoretical accounts are discussed as well as implications for dual-process theories.

Competition Between Extinction and Enhancement in Surface Enhanced Raman Spectroscopy.

PubMed

van Dijk, Thomas; Sivapalan, Sean T; Devetter, Brent M; Yang, Timothy K; Schulmerich, Matthew V; Murphy, Catherine J; Bhargava, Rohit; Carney, P Scott

2013-04-04

Conjugated metallic nanoparticles are a promising means to achieve ultrasensitive and multiplexed sensing in intact three-dimensional samples, especially for biological applications, via surface enhanced Raman scattering (SERS). We show that enhancement and extinction are linked and compete in a collection of metallic nanoparticles. Counterintuitively, the Raman signal vanishes when nanoparticles are excited at their plasmon resonance, while increasing nanoparticle concentrations at off-resonance excitation sometimes leads to decreased signal. We develop an effective medium theory that explains both phenomena. Optimal choices of excitation wavelength, individual particle enhancement factor and concentrations are indicated. The same processes which give rise to enhancement also lead to increased extinction of both the illumination and the Raman scattered light. Nanoparticles attenuate the incident field (blue) and at the same time provide local enhancement for SERS. Likewise the radiation of the Raman-scattered field (green) is enhanced by the near-by sphere but extinguished by the rest of the spheres in the suspension on propagation.

Sleep Deprivation Impairs and Caffeine Enhances My Performance, but Not Always Our Performance.

PubMed

Faber, Nadira S; Häusser, Jan A; Kerr, Norbert L

2017-02-01

What effects do factors that impair or enhance performance in individuals have when these individuals act in groups? We provide a framework, called the GIE ("Effects of Grouping on Impairments and Enhancements") framework, for investigating this question. As prominent examples for individual-level impairments and enhancements, we discuss sleep deprivation and caffeine. Based on previous research, we derive hypotheses on how they influence performance in groups, specifically process gains and losses in motivation, individual capability, and coordination. We conclude that the effect an impairment or enhancement has on individual-level performance is not necessarily mirrored in group performance: grouping can help or hurt. We provide recommendations on how to estimate empirically the effects individual-level performance impairments and enhancements have in groups. By comparing sleep deprivation to stress and caffeine to pharmacological cognitive enhancement, we illustrate that we cannot readily generalize from group results on one impairment or enhancement to another, even if they have similar effects on individual-level performance.

A Geophysical Inversion Model Enhancement Technique Based on the Blind Deconvolution

NASA Astrophysics Data System (ADS)

Zuo, B.; Hu, X.; Li, H.

2011-12-01

A model-enhancement technique is proposed to enhance the geophysical inversion model edges and details without introducing any additional information. Firstly, the theoretic correctness of the proposed geophysical inversion model-enhancement technique is discussed. An inversion MRM (model resolution matrix) convolution approximating PSF (Point Spread Function) method is designed to demonstrate the correctness of the deconvolution model enhancement method. Then, a total-variation regularization blind deconvolution geophysical inversion model-enhancement algorithm is proposed. In previous research, Oldenburg et al. demonstrate the connection between the PSF and the geophysical inverse solution. Alumbaugh et al. propose that more information could be provided by the PSF if we return to the idea of it behaving as an averaging or low pass filter. We consider the PSF as a low pass filter to enhance the inversion model basis on the theory of the PSF convolution approximation. Both the 1D linear and the 2D magnetotelluric inversion examples are used to analyze the validity of the theory and the algorithm. To prove the proposed PSF convolution approximation theory, the 1D linear inversion problem is considered. It shows the ratio of convolution approximation error is only 0.15%. The 2D synthetic model enhancement experiment is presented. After the deconvolution enhancement, the edges of the conductive prism and the resistive host become sharper, and the enhancement result is closer to the actual model than the original inversion model according the numerical statistic analysis. Moreover, the artifacts in the inversion model are suppressed. The overall precision of model increases 75%. All of the experiments show that the structure details and the numerical precision of inversion model are significantly improved, especially in the anomalous region. The correlation coefficient between the enhanced inversion model and the actual model are shown in Fig. 1. The figure illustrates that more information and details structure of the actual model are enhanced through the proposed enhancement algorithm. Using the proposed enhancement method can help us gain a clearer insight into the results of the inversions and help make better informed decisions.

Temporal subtraction contrast-enhanced dedicated breast CT

NASA Astrophysics Data System (ADS)

Gazi, Peymon M.; Aminololama-Shakeri, Shadi; Yang, Kai; Boone, John M.

2016-09-01

The development of a framework of deformable image registration and segmentation for the purpose of temporal subtraction contrast-enhanced breast CT is described. An iterative histogram-based two-means clustering method was used for the segmentation. Dedicated breast CT images were segmented into background (air), adipose, fibroglandular and skin components. Fibroglandular tissue was classified as either normal or contrast-enhanced then divided into tiers for the purpose of categorizing degrees of contrast enhancement. A variant of the Demons deformable registration algorithm, intensity difference adaptive Demons (IDAD), was developed to correct for the large deformation forces that stemmed from contrast enhancement. In this application, the accuracy of the proposed method was evaluated in both mathematically-simulated and physically-acquired phantom images. Clinical usage and accuracy of the temporal subtraction framework was demonstrated using contrast-enhanced breast CT datasets from five patients. Registration performance was quantified using normalized cross correlation (NCC), symmetric uncertainty coefficient, normalized mutual information (NMI), mean square error (MSE) and target registration error (TRE). The proposed method outperformed conventional affine and other Demons variations in contrast enhanced breast CT image registration. In simulation studies, IDAD exhibited improvement in MSE (0-16%), NCC (0-6%), NMI (0-13%) and TRE (0-34%) compared to the conventional Demons approaches, depending on the size and intensity of the enhancing lesion. As lesion size and contrast enhancement levels increased, so did the improvement. The drop in the correlation between the pre- and post-contrast images for the largest enhancement levels in phantom studies is less than 1.2% (150 Hounsfield units). Registration error, measured by TRE, shows only submillimeter mismatches between the concordant anatomical target points in all patient studies. The algorithm was implemented using a parallel processing architecture resulting in rapid execution time for the iterative segmentation and intensity-adaptive registration techniques. Characterization of contrast-enhanced lesions is improved using temporal subtraction contrast-enhanced dedicated breast CT. Adaptation of Demons registration forces as a function of contrast-enhancement levels provided a means to accurately align breast tissue in pre- and post-contrast image acquisitions, improving subtraction results. Spatial subtraction of the aligned images yields useful diagnostic information with respect to enhanced lesion morphology and uptake.

Progress and prospects: gene therapy for performance and appearance enhancement.

PubMed

Kiuru, M; Crystal, R G

2008-03-01

While medical therapies aim at reversing, reducing or eliminating diseases, the goal of enhancements is to improve performance or appearance beyond normal levels. Distinction between the two interventions is not always clear as they often present as a continuum. Gene therapy typically aims at treating or preventing disease, but the technology can theoretically be employed for enhancement. Some of the gene therapy enhancement strategies include improving performance by increasing muscle mass, endurance, memory, and cognition and bettering appearance by controlling weight, height and hair growth. In addition to the technical challenges of making enhancement strategies safe and effective, genetic enhancement presents significant ethical/societal questions that must be addressed.

Internal quantum efficiency enhancement of GaInN/GaN quantum-well structures using Ag nanoparticles

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

Iida, Daisuke; Department of Photonics Engineering, Technical University of Denmark, 2800 Lyngby; Faculty of Science and Technology, Meijo University, 1-501 Shiogamaguchi Tempaku, 468-8502 Nagoya

2015-09-15

We report internal quantum efficiency enhancement of thin p-GaN green quantum-well structure using self-assembled Ag nanoparticles. Temperature dependent photoluminescence measurements are conducted to determine the internal quantum efficiency. The impact of excitation power density on the enhancement factor is investigated. We obtain an internal quantum efficiency enhancement by a factor of 2.3 at 756 W/cm{sup 2}, and a factor of 8.1 at 1 W/cm{sup 2}. A Purcell enhancement up to a factor of 26 is estimated by fitting the experimental results to a theoretical model for the efficiency enhancement factor.

Unraveling the Raman Enhancement Mechanism on 1T'-Phase ReS2 Nanosheets.

PubMed

Miao, Peng; Qin, Jing-Kai; Shen, Yunfeng; Su, Huimin; Dai, Junfeng; Song, Bo; Du, Yunchen; Sun, Mengtao; Zhang, Wei; Wang, Hsing-Lin; Xu, Cheng-Yan; Xu, Ping

2018-04-01

2D transition metal dichalcogenides materials are explored as potential surface-enhanced Raman spectroscopy substrates. Herein, a systematic study of the Raman enhancement mechanism on distorted 1T (1T') rhenium disulfide (ReS 2 ) nanosheets is demonstrated. Combined Raman and photoluminescence studies with the introduction of an Al 2 O 3 dielectric layer unambiguously reveal that Raman enhancement on ReS 2 materials is from a charge transfer process rather than from an energy transfer process, and Raman enhancement is inversely proportional while the photoluminescence quenching effect is proportional to the layer number (thickness) of ReS 2 nanosheets. On monolayer ReS 2 film, a strong resonance-enhanced Raman scattering effect dependent on the laser excitation energy is detected, and a detection limit as low as 10 -9 m can be reached from the studied dye molecules such as rhodamine 6G and methylene blue. Such a high enhancement factor achieved through enhanced charge interaction between target molecule and substrate suggests that with careful consideration of the layer-number-dependent feature and excitation-energy-related resonance effect, ReS 2 is a promising Raman enhancement platform for sensing applications. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The influence of shell thickness of Au@TiO2 core-shell nanoparticles on the plasmonic enhancement effect in dye-sensitized solar cells.

PubMed

Liu, Wei-Liang; Lin, Fan-Cheng; Yang, Yu-Chen; Huang, Chen-Hsien; Gwo, Shangjr; Huang, Michael H; Huang, Jer-Shing

2013-09-07

Plasmonic core-shell nanoparticles (PCSNPs) can function as nanoantennas and improve the efficiency of dye-sensitized solar cells (DSSCs). To achieve maximum enhancement, the morphology of PCSNPs needs to be optimized. Here we precisely control the morphology of Au@TiO2 PCSNPs and systematically study its influence on the plasmonic enhancement effect. The enhancement mechanism was found to vary with the thickness of the TiO2 shell. PCSNPs with a thinner shell mainly enhance the current, whereas particles with a thicker shell improve the voltage. While pronounced plasmonic enhancement was found in the near infrared regime, wavelength-independent enhancement in the visible range was observed and attributed to the plasmonic heating effect. Emission lifetime measurement confirms that N719 molecules neighboring nanoparticles with TiO2 shells exhibit a longer lifetime than those in contact with metal cores. Overall, PCSNPs with a 5 nm shell give the highest efficiency enhancement of 23%. Our work provides a new synthesis route for well-controlled Au@TiO2 core-shell nanoparticles and gains insight into the plasmonic enhancement in DSSCs.

Ghost image in enhanced self-heterodyne synthetic aperture imaging ladar

NASA Astrophysics Data System (ADS)

Zhang, Guo; Sun, Jianfeng; Zhou, Yu; Lu, Zhiyong; Li, Guangyuan; Xu, Mengmeng; Zhang, Bo; Lao, Chenzhe; He, Hongyu

2018-03-01

The enhanced self-heterodyne synthetic aperture imaging ladar (SAIL) self-heterodynes two polarization-orthogonal echo signals to eliminate the phase disturbance caused by atmospheric turbulence and mechanical trembling, uses heterodyne receiver instead of self-heterodyne receiver to improve signal-to-noise ratio. The principle and structure of the enhanced self-heterodyne SAIL are presented. The imaging process of enhanced self-heterodyne SAIL for distributed target is also analyzed. In enhanced self-heterodyne SAIL, the phases of two orthogonal-polarization beams are modulated by four cylindrical lenses in transmitter to improve resolutions in orthogonal direction and travel direction, which will generate ghost image. The generation process of ghost image in enhanced self-heterodyne SAIL is mathematically detailed, and a method of eliminating ghost image is also presented, which is significant for far-distance imaging. A number of experiments of enhanced self-heterodyne SAIL for distributed target are presented, these experimental results verify the theoretical analysis of enhanced self-heterodyne SAIL. The enhanced self-heterodyne SAIL has the capability to eliminate the influence from the atmospheric turbulence and mechanical trembling, has high advantage in detecting weak signals, and has promising application for far-distance ladar imaging.

7 CFR 457.172 - Coverage Enhancement Option.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Coverage Enhancement Option. 457.172 Section 457.172..., DEPARTMENT OF AGRICULTURE COMMON CROP INSURANCE REGULATIONS § 457.172 Coverage Enhancement Option. The Coverage Enhancement Option for the 2009 and succeeding crop years are as follows: FCIC policies: United...

33 CFR 157.430 - Enhanced survey requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Enhanced survey requirements. 157... § 157.430 Enhanced survey requirements. Beginning at each tank vessel's next regularly scheduled drydock... tank vessel owner or operator shall— (a) Implement an enhanced survey program that complies with the...

33 CFR 157.430 - Enhanced survey requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Enhanced survey requirements. 157... § 157.430 Enhanced survey requirements. Beginning at each tank vessel's next regularly scheduled drydock... tank vessel owner or operator shall— (a) Implement an enhanced survey program that complies with the...

33 CFR 157.430 - Enhanced survey requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Enhanced survey requirements. 157... § 157.430 Enhanced survey requirements. Beginning at each tank vessel's next regularly scheduled drydock... tank vessel owner or operator shall— (a) Implement an enhanced survey program that complies with the...

33 CFR 157.430 - Enhanced survey requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Enhanced survey requirements. 157... § 157.430 Enhanced survey requirements. Beginning at each tank vessel's next regularly scheduled drydock... tank vessel owner or operator shall— (a) Implement an enhanced survey program that complies with the...

33 CFR 157.430 - Enhanced survey requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Enhanced survey requirements. 157... § 157.430 Enhanced survey requirements. Beginning at each tank vessel's next regularly scheduled drydock... tank vessel owner or operator shall— (a) Implement an enhanced survey program that complies with the...

76 FR 31639 - Comment Request for Information Collection for Enhanced Transitional Jobs Demonstration, New...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-01

... DEPARTMENT OF LABOR Comment Request for Information Collection for Enhanced Transitional Jobs... soliciting comments concerning the collection of data to support the Enhanced Transitional Jobs Demonstration... for the Enhanced Transitional Jobs Demonstration grants, grantees agree to submit participant data and...

Enhancement of fluorescence using nanoplasmonic and photonic structures

NASA Astrophysics Data System (ADS)

Arya, Akash; Tagore, Amit K.; Dantham, Venkata R.

2018-05-01

Two different nanoplasmonic structures have been synthesized using wet-chemistry method and demonstrated the enhancement of fluorescence of dye molecules. The difficulties associated with the plasmonic enhancement of fluorescence are discussed and to overcome these, an efficient approach has been proposed to enhance the fluorescence of a few molecules with the help of a high quality factor photonic microstructure (whispering gallery mode microresonator). The fabrication details of microresonators and experimental arrangement for enhancing the fluorescence are reported here.

Antecedents, Consequences, and Mechanisms: On the Longitudinal Interplay Between Academic Self-Enhancement and Psychological Adjustment.

PubMed

Dufner, Michael; Reitz, Anne K; Zander, Lysann

2015-10-01

We investigated the reciprocal associations between academic self-enhancement and key indicators of intra- and interpersonal adjustment as well as the role of self-esteem as a mediator. This longitudinal study involved three assessments in a sample of 709 German children and adolescents (Mage  = 11.83; 54% female) over the course of one academic year. We assessed self-reported subjective well-being as an indicator of intrapersonal adjustment and peer-reported popularity as an indicator of interpersonal adjustment. We computed cross-lagged and longitudinal mediational analyses. Academic self-enhancement prospectively predicted high subsequent well-being and popularity. Vice versa, well-being and popularity prospectively predicted high subsequent levels of self-enhancement. High self-esteem mediated the longitudinal associations between self-enhancement and well-being in both directions, but not the links between self-enhancement and popularity. Self-enhancement and adjustment are bidirectionally linked: Self-enhancement entails intrapersonal and interpersonal benefits; at the same time, adjustment in both domains fosters self-enhancement. In terms of intrapersonal, but not interpersonal adjustment, self-esteem seems to serve as a linchpin, accounting for all longitudinal associations. Furthermore, we present evidence indicating that self-enhancement indicators that are based on difference scores (instead of residuals) are problematic and might have led to negatively biased results in the literature. © 2014 Wiley Periodicals, Inc.

SEA: a super-enhancer archive.

PubMed

Wei, Yanjun; Zhang, Shumei; Shang, Shipeng; Zhang, Bin; Li, Song; Wang, Xinyu; Wang, Fang; Su, Jianzhong; Wu, Qiong; Liu, Hongbo; Zhang, Yan

2016-01-04

Super-enhancers are large clusters of transcriptional enhancers regarded as having essential roles in driving the expression of genes that control cell identity during development and tumorigenesis. The construction of a genome-wide super-enhancer database is urgently needed to better understand super-enhancer-directed gene expression regulation for a given biology process. Here, we present a specifically designed web-accessible database, Super-Enhancer Archive (SEA, http://sea.edbc.org). SEA focuses on integrating super-enhancers in multiple species and annotating their potential roles in the regulation of cell identity gene expression. The current release of SEA incorporates 83 996 super-enhancers computationally or experimentally identified in 134 cell types/tissues/diseases, including human (75 439, three of which were experimentally identified), mouse (5879, five of which were experimentally identified), Drosophila melanogaster (1774) and Caenorhabditis elegans (904). To facilitate data extraction, SEA supports multiple search options, including species, genome location, gene name, cell type/tissue and super-enhancer name. The response provides detailed (epi)genetic information, incorporating cell type specificity, nearby genes, transcriptional factor binding sites, CRISPR/Cas9 target sites, evolutionary conservation, SNPs, H3K27ac, DNA methylation, gene expression and TF ChIP-seq data. Moreover, analytical tools and a genome browser were developed for users to explore super-enhancers and their roles in defining cell identity and disease processes in depth. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Optogenetic Stimulation of Prefrontal Glutamatergic Neurons Enhances Recognition Memory.

PubMed

Benn, Abigail; Barker, Gareth R I; Stuart, Sarah A; Roloff, Eva V L; Teschemacher, Anja G; Warburton, E Clea; Robinson, Emma S J

2016-05-04

Finding effective cognitive enhancers is a major health challenge; however, modulating glutamatergic neurotransmission has the potential to enhance performance in recognition memory tasks. Previous studies using glutamate receptor antagonists have revealed that the medial prefrontal cortex (mPFC) plays a central role in associative recognition memory. The present study investigates short-term recognition memory using optogenetics to target glutamatergic neurons within the rodent mPFC specifically. Selective stimulation of glutamatergic neurons during the online maintenance of information enhanced associative recognition memory in normal animals. This cognitive enhancing effect was replicated by local infusions of the AMPAkine CX516, but not CX546, which differ in their effects on EPSPs. This suggests that enhancing the amplitude, but not the duration, of excitatory synaptic currents improves memory performance. Increasing glutamate release through infusions of the mGluR7 presynaptic receptor antagonist MMPIP had no effect on performance. These results provide new mechanistic information that could guide the targeting of future cognitive enhancers. Our work suggests that improved associative-recognition memory can be achieved by enhancing endogenous glutamatergic neuronal activity selectively using an optogenetic approach. We build on these observations to recapitulate this effect using drug treatments that enhance the amplitude of EPSPs; however, drugs that alter the duration of the EPSP or increase glutamate release lack efficacy. This suggests that both neural and temporal specificity are needed to achieve cognitive enhancement. Copyright © 2016 Benn et al.

Liquefaction of Semen Generates and Later Degrades a Conserved Semenogelin Peptide That Enhances HIV Infection

PubMed Central

Liu, Haichuan; Usmani, Shariq M.; Neidleman, Jason; Müller, Janis A.; Avila-Herrera, Aram; Gawanbacht, Ali; Zirafi, Onofrio; Chu, Simon; Dong, Ming; Kumar, Senthil T.; Smith, James F.; Pollard, Katherine S.; Fändrich, Marcus; Kirchhoff, Frank; Münch, Jan; Witkowska, H. Ewa; Greene, Warner C.

2014-01-01

ABSTRACT Semen enhances HIV infection in vitro, but how long it retains this activity has not been carefully examined. Immediately postejaculation, semen exists as a semisolid coagulum, which then converts to a more liquid form in a process termed liquefaction. We demonstrate that early during liquefaction, semen exhibits maximal HIV-enhancing activity that gradually declines upon further incubation. The decline in HIV-enhancing activity parallels the degradation of peptide fragments derived from the semenogelins (SEMs), the major components of the coagulum that are cleaved in a site-specific and progressive manner upon initiation of liquefaction. Because amyloid fibrils generated from SEM fragments were recently demonstrated to enhance HIV infection, we set out to determine whether any of the liquefaction-generated SEM fragments associate with the presence of HIV-enhancing activity. We identify SEM1 from amino acids 86 to 107 [SEM1(86-107)] to be a short, cationic, amyloidogenic SEM peptide that is generated early in the process of liquefaction but that, conversely, is lost during prolonged liquefaction due to the activity of serine proteases. Synthetic SEM1(86-107) amyloids directly bind HIV-1 virions and are sufficient to enhance HIV infection of permissive cells. Furthermore, endogenous seminal levels of SEM1(86-107) correlate with donor-dependent variations in viral enhancement activity, and antibodies generated against SEM1(86-107) recognize endogenous amyloids in human semen. The amyloidogenic potential of SEM1(86-107) and its virus-enhancing properties are conserved among great apes, suggesting an evolutionarily conserved function. These studies identify SEM1(86-107) to be a key, HIV-enhancing amyloid species in human semen and underscore the dynamic nature of semen's HIV-enhancing activity. IMPORTANCE Semen, the most common vehicle for HIV transmission, enhances HIV infection in vitro, but how long it retains this activity has not been investigated. Semen naturally undergoes physiological changes over time, whereby it converts from a gel-like consistency to a more liquid form. This process, termed liquefaction, is characterized at the molecular level by site-specific and progressive cleavage of SEMs, the major components of the coagulum, by seminal proteases. We demonstrate that the HIV-enhancing activity of semen gradually decreases over the course of extended liquefaction and identify a naturally occurring semenogelin-derived fragment, SEM1(86-107), whose levels correlate with virus-enhancing activity over the course of liquefaction. SEM1(86-107) amyloids are naturally present in semen, and synthetic SEM1(86-107) fibrils bind virions and are sufficient to enhance HIV infection. Therefore, by characterizing dynamic changes in the HIV-enhancing activity of semen during extended liquefaction, we identified SEM1(86-107) to be a key virus-enhancing component of human semen. PMID:24741080

Numerical study of surface plasmon enhanced nonlinear absorption and refraction.

PubMed

Kohlgraf-Owens, Dana C; Kik, Pieter G

2008-07-07

Maxwell Garnett effective medium theory is used to study the influence of silver nanoparticle induced field enhancement on the nonlinear response of a Kerr-type nonlinear host. We show that the composite nonlinear absorption coefficient, beta(c), can be enhanced relative to the host nonlinear absorption coefficient near the surface plasmon resonance of silver nanoparticles. This enhancement is not due to a resonant enhancement of the host nonlinear absorption, but rather due to a phase shifted enhancement of the host nonlinear refractive response. The enhancement occurs at the expense of introducing linear absorption, alpha(c), which leads to an overall reduced figure of merit beta(c)/alpha(c) for nonlinear absorption. For thin (< 1 microm) composites, the use of surface plasmons is found to result in an increased nonlinear absorption response compared to that of the host material.

Complete penile corporeal septation: evaluation with contrast enhanced US.

PubMed

Bertolotto, Michele; Bucci, Stefano; Quaia, Emilio; Coss, Matteo; Liguori, Giovanni

2008-01-01

Complete penile corporeal septation is a rare malformation in which the corpora cavernosa are completely isolated. We describe a new method to reach the diagnosis of this malformation using contrast enhanced US. Two patients with complete penile corporeal septation underwent color Doppler and contrast enhanced US after bilateral cavernosal injection of 10 microg prostaglandin E1. Contrast enhanced US was performed using a contrast specific software (Contrast-Tuned imaging, EsaOte, Genoa, Italy) and a linear transducer designed to evaluate superficial structures. Microbubbles of SonoVue (Bracco, Milan, Italy) were injected in one corpus cavernosum. After cavernosal injection of microbubbles no adverse events were observed. Contrast enhanced US showed unilateral enhancement of the corpus cavernosum in which microbubbles were injected. Cavernosography confirmed unilateral corporeal opacification. Contrast enhanced US can be used effectively to diagnose complete penile corporeal septation.

Genetic dissection of the α-globin super-enhancer in vivo

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

Hay, Deborah; Hughes, Jim R.; Babbs, Christian

Many genes determining cell identity are regulated by clusters of Mediator-bound enhancer elements collectively referred to as super-enhancers. Furthermore, these super-enhancers have been proposed to manifest higher-order properties important in development and disease. Here we report a comprehensive functional dissection of one of the strongest putative super-enhancers in erythroid cells. By generating a series of mouse models, deleting each of the five regulatory elements of the α-globin super-enhancer individually and in informative combinations, we demonstrate that each constituent enhancer seems to act independently and in an additive fashion with respect to hematological phenotype, gene expression, chromatin structure and chromosome conformation,more » without clear evidence of synergistic or higher-order effects. This study highlights the importance of functional genetic analyses for the identification of new concepts in transcriptional regulation.« less

Genetic dissection of the α-globin super-enhancer in vivo

DOE PAGES

Hay, Deborah; Hughes, Jim R.; Babbs, Christian; ...

2016-07-04

Many genes determining cell identity are regulated by clusters of Mediator-bound enhancer elements collectively referred to as super-enhancers. Furthermore, these super-enhancers have been proposed to manifest higher-order properties important in development and disease. Here we report a comprehensive functional dissection of one of the strongest putative super-enhancers in erythroid cells. By generating a series of mouse models, deleting each of the five regulatory elements of the α-globin super-enhancer individually and in informative combinations, we demonstrate that each constituent enhancer seems to act independently and in an additive fashion with respect to hematological phenotype, gene expression, chromatin structure and chromosome conformation,more » without clear evidence of synergistic or higher-order effects. This study highlights the importance of functional genetic analyses for the identification of new concepts in transcriptional regulation.« less

Surface-enhanced Raman spectroscopy of double-shell hollow nanoparticles: electromagnetic and chemical enhancements.

PubMed

Mahmoud, Mahmoud A

2013-05-28

Enhancements of the Raman signal by the newly prepared gold-palladium and gold-platinum double-shell hollow nanoparticles were examined and compared with those using gold nanocages (AuNCs). The surface-enhanced Raman spectra (SERS) of thiophenol adsorbed on the surface of AuNCs assembled into a Langmuir-Blodgett monolayer were 10-fold stronger than AuNCs with an inner Pt or Pd shell. The chemical and electromagnetic enhancement mechanisms for these hollow nanoparticles were further proved by comparing the Raman enhancement of nitrothiophenol and nitrotoulene. Nitrothiophenol binds to the surface of the nanoparticles by covalent interaction, and Raman enhancement by both the two mechanisms is possible, while nitrotoulene does not form any chemical bond with the surface of the nanoparticles and hence no chemical enhancement is expected. Based on discrete dipole approximation (DDA) calculations and the experimental SERS results, AuNCs introduced a high electromagnetic enhancement, while the nanocages with inner Pt or Pd shell have a strong chemical enhancement. The optical measurements of the localized surface plasmon resonance (LSPR) of the nanocages with an outer Au shell and an inner Pt or Pd shell were found, experimentally and theoretically, to be broad compared with AuNCs. The possible reason could be due to the decrease of the coherence time of Au oscillated free electrons and fast damping of the plasmon energy. This agreed well with the fact that a Pt or Pd inner nanoshell decreases the electromagnetic field of the outer Au nanoshell while increasing the SERS chemical enhancement.

30 CFR 1206.265 - Value enhancement of marketable coal.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Value enhancement of marketable coal. 1206.265... INTERIOR Natural Resources Revenue PRODUCT VALUATION Federal Coal § 1206.265 Value enhancement of marketable coal. If, prior to use, sale, or other disposition, the lessee enhances the value of coal after...

76 FR 50199 - National Center To Enhance the Professional Development of School Personnel Who Share...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-12

... DEPARTMENT OF EDUCATION [CFDA No. 84.325F] National Center To Enhance the Professional Development... of project period and waiver for the National Center to Enhance the Professional Development of... waiver enables the currently funded National Center to Enhance the Professional Development of School...

77 FR 2342 - Seventeenth Meeting: RTCA Special Committee 213, Enhanced Flight Vision/Synthetic Vision Systems...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-17

... Committee 213, Enhanced Flight Vision/Synthetic Vision Systems (EFVS/SVS) AGENCY: Federal Aviation..., Enhanced Flight Vision/ Synthetic Vision Systems (EFVS/SVS). SUMMARY: The FAA is issuing this notice to advise the public of the seventeenth meeting of RTCA Special Committee 213, Enhanced Flight Vision...

Sedimentary and Enhanced Geothermal Systems | Geothermal Technologies |

Science.gov Websites

NREL Sedimentary and Enhanced Geothermal Systems Sedimentary and Enhanced Geothermal Systems To innovative technologies, such as sedimentary and enhanced geothermal systems (EGS). Photo of a geothermal power plant in Imperial California. Capabilities To advance EGS and sedimentary geothermal systems, NREL

44 CFR 201.5 - Enhanced State Mitigation Plans.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true Enhanced State Mitigation..., DEPARTMENT OF HOMELAND SECURITY DISASTER ASSISTANCE MITIGATION PLANNING § 201.5 Enhanced State Mitigation Plans. (a) A State with a FEMA approved Enhanced State Mitigation Plan at the time of a disaster...

Textual Enhancement of Input: Issues and Possibilities

ERIC Educational Resources Information Center

Han, ZhaoHong; Park, Eun Sung; Combs, Charles

2008-01-01

The input enhancement hypothesis proposed by Sharwood Smith (1991, 1993) has stimulated considerable research over the last 15 years. This article reviews the research on textual enhancement of input (TE), an area where the majority of input enhancement studies have aggregated. Methodological idiosyncrasies are the norm of this body of research.…

Enhanced Perceptual Functioning in Autism: An Update, and Eight Principles of Autistic Perception

ERIC Educational Resources Information Center

Mottron, Laurent; Dawson, Michelle; Soulieres, Isabelle; Hubert, Benedicte; Burack, Jake

2006-01-01

We propose an "Enhanced Perceptual Functioning" model encompassing the main differences between autistic and non-autistic social and non-social perceptual processing: locally oriented visual and auditory perception, enhanced low-level discrimination, use of a more posterior network in "complex" visual tasks, enhanced perception…

Multispectral histogram normalization contrast enhancement

NASA Technical Reports Server (NTRS)

Soha, J. M.; Schwartz, A. A.

1979-01-01

A multispectral histogram normalization or decorrelation enhancement which achieves effective color composites by removing interband correlation is described. The enhancement procedure employs either linear or nonlinear transformations to equalize principal component variances. An additional rotation to any set of orthogonal coordinates is thus possible, while full histogram utilization is maintained by avoiding the reintroduction of correlation. For the three-dimensional case, the enhancement procedure may be implemented with a lookup table. An application of the enhancement to Landsat multispectral scanning imagery is presented.

Anatomy of a new B-cell-specific enhancer.

PubMed Central

Koch, W; Benoist, C; Mathis, D

1989-01-01

The major histocompatibility complex class II molecules, like the immunoglobulins, are prominent B-lymphocyte markers. Herein, we describe a B-cell-specific enhancer associated with the murine class II gene, Ek alpha. This enhancer has a complex anatomy that suggests interactions between remotely spaced elements. Of particular interest is the finding that two CCAAT boxes spaced one kilobase apart are important for enhancer activity. Somewhat surprisingly, the E alpha and immunoglobulin enhancers seem to show little resemblance. Images PMID:2467189