Science.gov

Sample records for early glandular epithelial

  1. GEOPHYSICS, ASTRONOMY AND ASTROPHYSICS: Second-harmonic generation as a DNA malignancy indicator of prostate glandular epithelial cells

    NASA Astrophysics Data System (ADS)

    Zhuang, Zheng-Fei; Liu, Han-Ping; Guo, Zhou-Yi; Zhuo, Shuang-Mu; Yu, Bi-Ying; Deng, Xiao-Yuan

    2010-04-01

    This paper first demonstrates second-harmonic generation (SHG) in the intact cell nucleus, which acts as an optical indicator of DNA malignancy in prostate glandular epithelial cells. Within a scanning region of 2.7 μm×2.7 μm in cell nuclei, SHG signals produced from benign prostatic hyperplasia (BPH) and prostate carcinoma (PC) tissues (mouse model C57BL/6) have been investigated. Statistical analyses (t test) of a total of 405 measurements (204 nuclei from BPH and 201 nuclei from PC) show that SHG signals from BPH and PC have a distinct difference (p < 0.05), suggesting a potential optical method of revealing very early malignancy in prostate glandular epithelial cells based upon induced biochemical and/or biophysical modifications in DNA.

  2. Mixed squamous cell and glandular papilloma of the lung resembling early adenocarcinoma: A case report

    PubMed Central

    Abe, Jiro; Ito, Shigemi; Takahashi, Satomi; Sato, Ikuro; Tanaka, Ryota; Sato, Taku; Okazaki, Toshimasa

    2016-01-01

    Introduction An extremely rare case of mixed squamous cell and glandular papilloma of the lung is reported. The correlation between the radiological and the pathological features as well as the clinical pitfall in making a diagnosis is discussed. Presentation of case An asymptomatic 68-year-old female with a cigarette smoking habit presented with a small nodule in her peripheral lung. A wedge resection was performed though it failed on-site diagnosis which was instead obtained following pathological scrutiny. The postsurgical course was excellent with no recurrence of disease. Discussion A small ground glass nodule gradually enlarged and transformed to a partially solid nodule a year and a half later. This transformation falsely made us suspect an early adenocarcinoma development. Eventually, the extremely rare subtype of pulmonary papilloma, with biphasic glandular and squamous cells, had been demonstrated to obstruct the peripheral bronchiole; and the adjoining alveoli had filled with a large volume of mucus. These pathological features seemed to have constituted the inner solid portion and the marginal ground glass portion respectively in the CT images, mimicking invasive lepidic adenocarcinoma. Conclusion Both pre- and intra-operative diagnoses are difficult mainly because of the rareness of the disease, however, mixed squamous cell and glandular papilloma may be considered in case the presence of primary adenocarcinoma is not validated. PMID:27141302

  3. Allele-specific recognition by LILRB3 and LILRA6 of a cytokeratin 8 - associated ligand on necrotic glandular epithelial cells

    PubMed Central

    López-Álvarez, María R.; Jahnke, Martin; Russell, Alasdair I.; Radjabova, Valeria; Trowsdale, Alice R.Z.; Trowsdale, John

    2016-01-01

    The LILRs are a family of receptors that regulate the activities of myelomonocytic cells. We found that specific allelic variants of two related members of the LILR family, LILRB3 and LILRA6, interact with a ligand exposed on necrotic glandular epithelial cells. The extracellular domains of LILRB3 and LILRA6 are very similar and their genes are highly polymorphic. A commonly occurring allele, LILRB3*12, displayed particularly strong binding of these necrotic cells and further screening of the products of LILRB3 alleles identified motifs that correlated with binding. Immunoprecipitation of the ligand from epithelial cell lysates using recombinant LILRB3*12, identified cytokeratins 8, 18 and 19. Purified proteins obtained from epithelial cell lysates, using anti-cytokeratin 8 antibodies, were able to activate LILRB3*12 reporter cells. Knock-down of cytokeratin 8 in epithelial cells abrogated expression of the LILRB3 ligand, while staining with recombinant LILRB3*12 showed co-localisation with cytokeratin 8 and 18 in permeabilised breast cancer cells. Necrosis is a common feature of tumours. The finding of a necrosis-associated ligand for these two receptors raises the possibility of a novel interaction that alters immune responses within the tumour microenvironment. Since LILRB3 and LILRA6 genes are highly polymorphic the interaction may influence an individual's immune response to tumours. PMID:26769854

  4. Establishment of a long-term three-dimensional primary culture of mouse glandular stomach epithelial cells within the stem cell niche

    SciTech Connect

    Katano, Takahito; Ootani, Akifumi; Mizoshita, Tsutomu; Tanida, Satoshi; Tsukamoto, Hironobu; Ozeki, Keiji; Ebi, Masahide; Mori, Yoshinori; Kataoka, Hiromi; Kamiya, Takeshi; Toda, Shuji; Joh, Takashi

    2013-03-22

    Highlights: ► We established a 3D culture system to allow long-term culture of stomach cells. ► In this culture system, gastric epithelial cells grew for about 3 months. ► The cultured cells differentiated into multi-units of the stomach. ► This culture method should be useful for elucidating the cause of gastric diseases. -- Abstract: Compared to the small intestine and colon, little is known about stem cells in the stomach because of a lack of specific stem cell markers and an in vitro system that allows long-term culture. Here we describe a long-term three-dimensional (3D) primary gastric culture system within the stem cell niche. Glandular stomach cells from neonatal mice cultured in collagen gel yielded expanding sphere-like structures for 3 months. The wall of the gastrospheres consisted of a highly polarized epithelial monolayer with an outer lining of myofibroblasts. The epithelial cells showed a tall columnar cell shape, basal round nuclei, and mucus-filled cytoplasm as well as expression of MUC5AC, indicating differentiation into gastric surface mucous cells. These cells demonstrated the features of fully differentiated gastric surface mucous cells such as microvilli, junctional complexes, and glycogen and secretory granules. Fewer than 1% of cultured epithelial cells differentiated into enteroendocrine cells. Active proliferation of the epithelial cells and many apoptotic cells in the inner lumen revealed the rapid cell turnover in gastrospheres in vitro. This method enables us to investigate the role of signaling between cell–cell and epithelial–mesenchymal interactions in an environment that is extremely similar to the in vivo environment.

  5. Binding sites for iodinated endothelin-1, endothelin-2 and endothelin-3 demonstrated on human uterine glandular epithelial cells by quantitative high-resolution autoradiography.

    PubMed

    Davenport, A P; Cameron, I T; Smith, S K; Brown, M J

    1991-04-01

    Quantitative in-vitro receptor autoradiography has been used to localize and compare the anatomical distribution of binding sites for iodinated endothelins (ET-1, ET-2 and ET-3) in human uterus. Binding sites for the three iodinated isoforms had a similar gross anatomical distribution. The density of binding sites was significantly higher in the endometrium compared with the myometrium and greatest at the endometrial-myometrial junction. In cross-competition experiments, unlabelled ET-1, ET-2, ET-3, sarafotoxin S6b and mouse vasoactive intestinal contractor (1 mumol/l) competed for the binding sites of all the iodinated peptides suggesting that ETs may bind to the same receptor. However, preproendothelin(110-130) (endothelin-like peptide) or preproendothelin(124-130) and other non-endothelin vasoactive peptides tested as a concentration of 1 mumol/l did not compete. Micro-autoradiography revealed that high densities of iodinated ET-1, ET-2 and ET-3 binding sites were localized to glandular epithelial cells and blood vessels with lower levels in the myometrium and vascular smooth muscle, suggesting that these potent vasoactive and proliferative agents could play a role in the control of menstruation. PMID:2030325

  6. Effects of steroid hormones on differentiated glandular epithelial and stromal cells in a three dimensional cell culture model of the canine endometrium

    PubMed Central

    2013-01-01

    Background Oestrogens and progesterone have a significant impact on the endometrium during the canine oestrous cycle. Their receptors mediate plasma steroid hormone levels and are expressed in several endometrial cell types. Altered steroid receptor expression patterns are involved in serious uterine diseases; however the mechanisms of hormone action during pathogenesis in these tissues remain unclear. The development of 3D culture systems of canine endometrial cells provides an opportunity for the effects of steroid hormones to be quantitatively assessed in a more in vivo-like setting. The present study aimed to determine the effects of the steroid hormones 17β-estradiol (E) and progesterone (P) on the expression of the oestrogen and progesterone receptors (ER and PR), and on proliferative activity, in a 3D co-culture system of canine uterine origin, comprising differentiated endometrial glands, and stromal cells (SCs). Results Morphology, differentiation, and apical-basolateral polarity of cultured glandular epithelial cells (GECs) were comparable to those in native uterine tissue as assessed by immunohistochemistry using differentiation markers (β-catenin, laminin), lectin histochemistry, and transmission electron microscopy. Supplementation of our 3D-culture system with E (at 15, 30 and 100 pg/mL) resulted in constant levels of ER expression in GECs, but reduced expression levels in SCs. PR expression was reduced in both GECs and SCs following treatment with E. 3 ng/mL P resulted in increased ER expression in GECs, but a decrease in SCs. PR expression in GECs increased in all P-treated groups, whereas PRs in SCs decreased with the lowest and highest doses, but increased with the middle dose of treatment. Proliferative activity, assessed by Ki67 staining, remained below 1% in all assays and cell types. Conclusions The present study demonstrates the applicability of our 3D organotypic canine endometrium-derived culture system for cellular-level studies. 3D

  7. Helicobacter pylori CagA Suppresses Apoptosis through Activation of AKT in a Nontransformed Epithelial Cell Model of Glandular Acini Formation

    PubMed Central

    Vallejo-Flores, Gabriela; Torres, Javier; Sandoval-Montes, Claudia; Arévalo-Romero, Haruki; Meza, Isaura; Camorlinga-Ponce, Margarita; Torres-Morales, Julián; Chávez-Rueda, Adriana Karina; Legorreta-Haquet, María Victoria; Fuentes-Pananá, Ezequiel M.

    2015-01-01

    H. pylori infection is the most important environmental risk to develop gastric cancer, mainly through its virulence factor CagA. In vitro models of CagA function have demonstrated a phosphoprotein activity targeting multiple cellular signaling pathways, while cagA transgenic mice develop carcinomas of the gastrointestinal tract, supporting oncogenic functions. However, it is still not completely clear how CagA alters cellular processes associated with carcinogenic events. In this study, we evaluated the capacity of H. pylori CagA positive and negative strains to alter nontransformed MCF-10A glandular acini formation. We found that CagA positive strains inhibited lumen formation arguing for an evasion of apoptosis activity of central acini cells. In agreement, CagA positive strains induced a cell survival activity that correlated with phosphorylation of AKT and of proapoptotic proteins BIM and BAD. Anoikis is a specific type of apoptosis characterized by AKT and BIM activation and it is the mechanism responsible for lumen formation of MCF-10A acini in vitro and mammary glands in vivo. Anoikis resistance is also a common mechanism of invading tumor cells. Our data support that CagA positive strains signaling function targets the AKT and BIM signaling pathway and this could contribute to its oncogenic activity through anoikis evasion. PMID:26557697

  8. Early development of multiple epithelial neoplasms in Netherton syndrome.

    PubMed

    Krasagakis, K; Ioannidou, D J; Stephanidou, M; Manios, A; Panayiotides, J G; Tosca, A D

    2003-01-01

    We report a case of Netherton syndrome manifested as congenital ichthyosiform erythroderma, trichorrhexis invaginata and atopy, who in early adulthood developed multiple, aggressive epithelial neoplasms in sun-exposed areas of the skin, in areas with papillomatous skin hyperplasia and at the left parotid region. The occurrence of cutaneous neoplasia has been reported in syndromes with congenital ichthyosis and suggests that the underlying genetic defects may cause the development of cancer in prone patients. PMID:12920370

  9. Fertility sparing surgery in early stage epithelial ovarian cancer

    PubMed Central

    Martinelli, Fabio; Lorusso, Domenica; Haeusler, Edward; Carcangiu, Marialuisa; Raspagliesi, Francesco

    2014-01-01

    Objective Fertility sparing surgery (FSS) is a strategy often considered in young patients with early epithelial ovarian cancer. We investigated the role and the outcomes of FSS in eEOC patients who underwent comprehensive surgery. Methods From January 2003 to January 2011, 24 patients underwent fertility sparing surgery. Eighteen were one-to-one matched and balanced for stage, histologic type and grading with a group of patients who underwent radical comprehensive staging (n=18). Demographics, surgical procedures, morbidities, pathologic findings, recurrence-rate, pregnancy-rate and correlations with disease-free survival were assessed. Results A total of 36 patients had a complete surgical staging including lymphadenectomy and were therefore analyzed. Seven patients experienced a recurrence: four (22%) in the fertility sparing surgery group and three (16%) in the control group (p=not significant). Sites of recurrence were: residual ovary (two), abdominal wall and peritoneal carcinomatosis in the fertility sparing surgery group; pelvic (two) and abdominal wall in the control group. Recurrences in the fertility sparing surgery group appeared earlier (mean, 10.3 months) than in radical comprehensive staging group (mean, 53.3 months) p<0.001. Disease-free survival were comparable between the two groups (p=0.422). No deaths were reported. All the patients in fertility sparing surgery group recovered a regular period. Thirteen out of 18 (72.2%) attempted to have a pregnancy. Five (38%) achieved a spontaneous pregnancy with a full term delivery. Conclusion Fertility sparing surgery in early epithelial ovarian cancer submitted to a comprehensive surgical staging could be considered safe with oncological results comparable to radical surgery group. PMID:25142621

  10. Early epithelial signaling center governs tooth budding morphogenesis.

    PubMed

    Ahtiainen, Laura; Uski, Isa; Thesleff, Irma; Mikkola, Marja L

    2016-09-12

    During organogenesis, cell fate specification and patterning are regulated by signaling centers, specialized clusters of morphogen-expressing cells. In many organs, initiation of development is marked by bud formation, but the cellular mechanisms involved are ill defined. Here, we use the mouse incisor tooth as a model to study budding morphogenesis. We show that a group of nonproliferative epithelial cells emerges in the early tooth primordium and identify these cells as a signaling center. Confocal live imaging of tissue explants revealed that although these cells reorganize dynamically, they do not reenter the cell cycle or contribute to the growing tooth bud. Instead, budding is driven by proliferation of the neighboring cells. We demonstrate that the activity of the ectodysplasin/Edar/nuclear factor κB pathway is restricted to the signaling center, and its inactivation leads to fewer quiescent cells and a smaller bud. These data functionally link the signaling center size to organ size and imply that the early signaling center is a prerequisite for budding morphogenesis. PMID:27621364

  11. Early Trypanosoma cruzi Infection Reprograms Human Epithelial Cells

    PubMed Central

    Chiribao, María Laura; Libisch, Gabriela; Parodi-Talice, Adriana; Robello, Carlos

    2014-01-01

    Trypanosoma cruzi, the causative agent of Chagas disease, has the peculiarity, when compared with other intracellular parasites, that it is able to invade almost any type of cell. This property makes Chagas a complex parasitic disease in terms of prophylaxis and therapeutics. The identification of key host cellular factors that play a role in the T. cruzi invasion is important for the understanding of disease pathogenesis. In Chagas disease, most of the focus is on the response of macrophages and cardiomyocytes, since they are responsible for host defenses and cardiac lesions, respectively. In the present work, we studied the early response to infection of T. cruzi in human epithelial cells, which constitute the first barrier for establishment of infection. These studies identified up to 1700 significantly altered genes regulated by the immediate infection. The global analysis indicates that cells are literally reprogrammed by T. cruzi, which affects cellular stress responses (neutrophil chemotaxis, DNA damage response), a great number of transcription factors (including the majority of NFκB family members), and host metabolism (cholesterol, fatty acids, and phospholipids). These results raise the possibility that early host cell reprogramming is exploited by the parasite to establish the initial infection and posterior systemic dissemination. PMID:24812617

  12. Early inflammatory response in epithelial ovarian tumor cyst fluids.

    PubMed

    Kristjánsdóttir, Björg; Partheen, Karolina; Fung, Eric T; Yip, Christine; Levan, Kristina; Sundfeldt, Karin

    2014-10-01

    Mortality rates for epithelial ovarian cancer (EOC) are high, mainly due to late-stage diagnosis. The identification of biomarkers for this cancer could contribute to earlier diagnosis and increased survival rates. Given that chronic inflammation plays a central role in cancer initiation and progression, we selected and tested 15 cancer-related cytokines and growth factors in 38 ovarian cyst fluid samples. We used ovarian cyst fluid since it is found in proximity to the pathology and mined it for inflammatory biomarkers suitable for early detection of EOC. Immunoprecipitation and high-throughput sample fractionation were obtained by using tandem antibody libraries bead and mass spectrometry. Two proteins, monocyte chemoattractant protein-1 (MCP-1/CCL2) and interleucin-8 (IL-8/CXCL8), were significantly (P < 0.0001) higher in the malignant (n = 16) versus benign (n = 22) tumor cysts. Validation of MCP-1, IL-8, and growth-regulated protein-α (GROα/CXCL1) was performed with ELISA in benign, borderline, and malignant cyst fluids (n = 256) and corresponding serum (n = 256). CA125 was measured in serum from all patients and used in the algorithms performed. MCP-1, IL-8, and GROα are proinflammatory cytokines and promoters of tumor growth. From 5- to 100-fold higher concentrations of MCP-1, IL-8 and GROα were detected in the cyst fluids compared to the serum. Significant (P < 0.001) cytokine response was already established in borderline cyst fluids and stage I EOC. In serum a significant (P < 0.01) increase of IL-8 and GROα was found, but not until stage I and stage III EOC, respectively. These findings confirm that early events in tumorigenesis can be analyzed and detected in the tumor environment and we conclude that ovarian cyst fluid is a promising source in the search for new biomarkers for early ovarian tumors. PMID:24947406

  13. Chlamydia muridarum Induction of Glandular Duct Dilation in Mice

    PubMed Central

    Sun, Xin; Yang, Zhangsheng; Zhang, Hongbo; Dai, Jin; Chen, Jianlin; Tang, Lingli; Rippentrop, Sheena; Xue, Min

    2015-01-01

    Although Chlamydia-induced hydrosalpinx in women and mice has been used as a surrogate marker for tubal infertility, the medical relevance of nontubal pathologies, such as uterine horn dilation, developed in mice following chlamydial infection remains unclear. We now report that the uterine horn dilation correlates with glandular duct dilation detected microscopically following Chlamydia muridarum infection. The dilated glandular ducts pushed the uterine horn lumen to closure or dilation and even broke through the myometrium to develop extrusion outside the uterine horn. The severity scores of uterine horn dilation observed macroscopically correlated well with the number of cross sections of the dilated glandular ducts counted under microscopy. Chlamydial infection was detected in the glandular epithelial cells, potentially leading to inflammation and dilation of the glandular ducts. Direct delivery of C. muridarum into the mouse uterus increased both uterine horn/glandular duct dilation and hydrosalpinx. However, the chlamydial plasmid, which is essential for the induction of hydrosalpinx, was not required for the induction of uterine horn/glandular duct dilation. Screening 12 strains of mice for uterine horn dilation following C. muridarum infection revealed that B10.D2, C57BL/10J, and C57BL/6J mice were most susceptible, followed by BALB/cJ and A/J mice. Deficiency in host genes involved in immune responses failed to significantly alter the C. muridarum induction of uterine horn dilation. Nevertheless, the chlamydial induction of uterine horn/glandular duct dilation may be used to evaluate plasmid-independent pathogenicity of Chlamydia in susceptible mice. PMID:25824829

  14. Use of Plasma Metabolomics to Identify Diagnostic Biomarkers for Early Stage Epithelial Ovarian Cancer

    PubMed Central

    Fan, Lijun; Yin, Mingzhu; Ke, Chaofu; Ge, Tingting; Zhang, Guangming; Zhang, Wang; Zhou, Xiaohua; Lou, Ge; Li, Kang

    2016-01-01

    The early detection of ovarian carcinoma is difficult due to the absence of recognizable physical symptoms and a lack of sensitive screening methods. The currently available biomarkers (such as CA125 and HE4) are insufficiently reliable to distinguish early stage (I/II) epithelial ovarian cancer (EOC) patients from normal individuals because they possess a relatively poor sensitivity and specificity. To evaluate the application of metabolomics to biomarker discovery in the early stages of epithelial ovarian cancer (EOC), plasma samples from 21 early stage EOC patients and 31 healthy controls were analyzed with ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-Tof/MS) in conjunction with multivariate statistical analysis. Eighteen metabolites, including lysophospholipids, 2-piperidone and MG (18:2), were found to be disturbed in early stage EOC with satisfactory diagnostic accuracy (AUC=0.920). These biomarkers were specifically validated in the EOC nude mouse model, and five of the biomarkers (lysophospholipids, adrenoyl ethanolamide et al.) were highly suspected of being associated with EOC because they were differentially expressed with the same tendency in the EOC nude mice versus normal controls. In conclusion, the selected metabolic biomarkers have considerable utility and significant potential for diagnosing early ovarian cancer and investigating its underlying mechanisms. PMID:27390602

  15. Early Epithelial Restitution by Nonsteroidal Anti-Inflammatory Drug-Activated Gene 1 Counteracts Intestinal Ulcerative Injuries.

    PubMed

    Choi, Hye Jin; Do, Kee Hun; Park, Jae-Hong; Kim, Juil; Yu, Mira; Park, Seong-Hwan; Moon, Yuseok

    2016-08-15

    In response to ulcerative mucosal injuries, intestinal epithelial restitution is a critical event in the early defense against harmful attacks by luminal Ags. Based on the assumption that epithelial NAG-1 is an endogenous regulator of ulcerative stress-induced injuries, the expression and functions of NAG-1 were investigated. Genetic ablation of NAG-1 decreased survival of mice with dextran sodium sulfate-induced intestinal ulcer and histologically delayed the epithelial restitution, confirming early protective roles of NAG-1 in ulcerative insults. Moreover, enhanced expression of NAG-1 during the wound-healing process was associated with epithelial cell migration and spreading. In response to ulcerative injury, RhoA GTPase, a cytoskeleton modulator, mediated epithelial restitution via enhanced motility. RhoA expression was prominently elevated in the restituting epithelia cells around the insulted wound bed and was attenuated by NAG-1 deficiency. Pharmacological intervention with RhoA thus attenuated NAG-1-mediated epithelial cell migration during epithelial restitution. Taken together, epithelial restitution was promoted by enhanced NAG-1 expression and subsequent enterocyte locomotion during the early wound-healing process, suggesting clinical usefulness of NAG-1 as a novel endogenous muco-protective factor or an indicator of therapeutic efficacy against the ulcerative gastrointestinal diseases, including inflammatory bowel disease. PMID:27421482

  16. Mean glandular dose in a breast screening programme

    SciTech Connect

    Galvan, H. A.; Perez-Badillo, M. P.; Villasenor, Y.

    2012-10-23

    Breast density has an important role in early detection of breast cancer, because has been reported the strong association between breast density and invasive breast cancer risk. Mammography is the gold standard to early detection of breast cancer, despite of this require ionizing radiation that may increase radio-induced cancer risk. This maybe limited with a quality control programme of mammographic units, with the main goal of achieving high quality images with low radiation dose. International Atomic Energy Agency (IAEA) published in 2011 the {sup Q}uality assurance programme for digital mammography{sup ,} where glandular tissue quantity is an important parameter to compute mean glandular dose (MGD), which is necessary to reduce its associated risk. In this work we show the first results in our country applying this protocol and studying breast density in a small group. MGD complies with national and IAEA dose limits.

  17. Mean glandular dose in a breast screening programme

    NASA Astrophysics Data System (ADS)

    Galván, H. A.; Pérez-Badillo, M. P.; Villaseñor, Y.

    2012-10-01

    Breast density has an important role in early detection of breast cancer, because has been reported the strong association between breast density and invasive breast cancer risk. Mammography is the gold standard to early detection of breast cancer, despite of this require ionizing radiation that may increase radio-induced cancer risk. This maybe limited with a quality control programme of mammographic units, with the main goal of achieving high quality images with low radiation dose. International Atomic Energy Agency (IAEA) published in 2011 the "Quality assurance programme for digital mammography", where glandular tissue quantity is an important parameter to compute mean glandular dose (MGD), which is necessary to reduce its associated risk. In this work we show the first results in our country applying this protocol and studying breast density in a small group. MGD complies with national and IAEA dose limits.

  18. [Effects some drugs of re-epithelialization in the early postoperative period after photorefraction keratectomy].

    PubMed

    Kurenkov, V V; Smirennaia, E V; Polunin, G S; Makarov, I A

    1999-01-01

    Terms of re-epithelialization, severity of the painful syndrome, intensity of corneal "crepe" (opacity) are assessed in myopic patients treated by maxitrol, eubetal, colbiocin ointments and maxitrol eyedrops in the early postoperative period after photorefraction keratectomy. The crepe intensity was assessed routinely according to a clinical score: 0) transparent cornea, 1) trace crepe; 2) moderate crepe; and 3) intensive crepe. Biomicroscopy on day 4 after photorefraction keratectomy showed complete epithelialization in 91.7% patients after colbiocin ointment, in 91.% after maxitrol eyedrops, 87% after eubetal ointment, and 82.6% after maxitrol ointment. The least corneal opacity (0 and 0-1) was observed after eubetal ointment and maxitrol eyedrops. The mean score for pain was virtually the same in all groups; in the colbiocin ointment group more patients complained of pain for more than 24 h in comparison with other groups. PMID:10665290

  19. Helminth co-infection in Helicobacter pylori infected INS-GAS mice attenuates gastric premalignant lesions of epithelial dysplasia and glandular atrophy and preserves colonization resistance of the stomach to lower bowel microbiota

    PubMed Central

    Whary, Mark T.; Muthupalani, Sureshkumar; Ge, Zhongming; Feng, Yan; Lofgren, Jennifer; Shi, Hai Ning; Taylor, Nancy S.; Correa, Pelayo; Versalovic, James; Wang, Timothy C.; Fox, James G.

    2014-01-01

    Higher prevalence of helminth infections in H. pylori infected children was suggested to potentially lower the life-time risk for gastric adenocarcinoma. In rodent models, helminth co-infection does not reduce Helicobacter-induced inflammation but delays progression of pre-malignant gastric lesions. Because gastric cancer in INS-GAS mice is promoted by intestinal microflora, the impact of Heligmosomoides polygyrus co-infection on H. pylori-associated gastric lesions and microflora were evaluated. Male INS-GAS mice co-infected with H. pylori and H. polygyrus for 5 months were assessed for gastrointestinal lesions, inflammation-related mRNA expression, FoxP3+ cells, epithelial proliferation, and gastric colonization with H. pylori and Altered Schaedler Flora. Despite similar gastric inflammation and high levels of proinflammatory mRNA, helminth co-infection increased FoxP3+ cells in the corpus and reduced H. pylori-associated gastric atrophy (p<0.04), dysplasia (p<0.02) and prevented H. pylori-induced changes in the gastric flora (p<0.05). This is the first evidence of helminth infection reducing H. pylori-induced gastric lesions while inhibiting changes in gastric flora, consistent with prior observations that gastric colonization with enteric microbiota accelerated gastric lesions in INS-GAS mice. Identifying how helminths reduce gastric premalignant lesions and impact bacterial colonization of the H. pylori infected stomach could lead to new treatment strategies to inhibit progression from chronic gastritis to cancer in humans. PMID:24513446

  20. Metabolic history impacts mammary tumor epithelial hierarchy and early drug response in mice.

    PubMed

    Montales, Maria Theresa E; Melnyk, Stepan B; Liu, Shi J; Simmen, Frank A; Liu, Y Lucy; Simmen, Rosalia C M

    2016-09-01

    The emerging links between breast cancer and metabolic dysfunctions brought forth by the obesity pandemic predict a disproportionate early disease onset in successive generations. Moreover, sensitivity to chemotherapeutic agents may be influenced by the patient's metabolic status that affects the disease outcome. Maternal metabolic stress as a determinant of drug response in progeny is not well defined. Here, we evaluated mammary tumor response to doxorubicin in female mouse mammary tumor virus-Wnt1 transgenic offspring exposed to a metabolically compromised environment imposed by maternal high-fat diet. Control progeny were from dams consuming diets with regular fat content. Maternal high-fat diet exposure increased tumor incidence and reduced tumor latency but did not affect tumor volume response to doxorubicin, compared with control diet exposure. However, doxorubicin-treated tumors from high-fat-diet-exposed offspring demonstrated higher proliferation status (Ki-67), mammary stem cell-associated gene expression (Notch1, Aldh1) and basal stem cell-like (CD29(hi)CD24(+)) epithelial subpopulation frequencies, than tumors from control diet progeny. Notably, all epithelial subpopulations (CD29(hi)CD24(+), CD29(lo)CD24(+), CD29(hi)CD24(+)Thy1(+)) in tumors from high-fat-diet-exposed offspring were refractory to doxorubicin. Further, sera from high-fat-diet-exposed offspring promoted sphere formation of mouse mammary tumor epithelial cells and of human MCF7 cells. Untargeted metabolomics analyses identified higher levels of kynurenine and 2-hydroxyglutarate in plasma of high-fat diet than control diet offspring. Kynurenine/doxorubicin co-treatment of MCF7 cells enhanced the ability to form mammosphere and decreased apoptosis, relative to doxorubicin-only-treated cells. Maternal metabolic dysfunctions during pregnancy and lactation may be targeted to reduce breast cancer risk and improve early drug response in progeny, and may inform clinical management of disease

  1. Inducible nitric oxide synthase mediates early epithelial repair of porcine ileum.

    PubMed

    Gookin, Jody L; Rhoads, J Marc; Argenzio, Robert A

    2002-07-01

    Reports conflict regarding the effect of nitric oxide (NO) on intestinal epithelium. In chronic injury, NO appears detrimental by combining with reactive oxygen to form potent-free radicals. In contrast, inhibition of NO synthesis after acute injury exacerbates damage and inflammation. Recent studies have disclosed constitutive expression of inducible NO synthase (iNOS) by normal intestinal epithelia, yet little attention has been given to the role of iNOS in acute epithelial repair. We studied the local effects of iNOS on early epithelial repair of porcine ileal mucosa injured by deoxycholate within Ussing chambers. iNOS was constitutively expressed by the villous epithelium, and after deoxycholate injury, iNOS was expressed by injured and detaching enterocytes. Selective inhibition of iNOS abolished increases in NO synthesis and villous reepithelialization after injury. Exogenous L-arginine rescued baseline reepithelialization from NOS inhibitors but was only capable of stimulating additional repair in the presence of serum. These results demonstrate that iNOS-derived NO is a key mediator of early villous reepithelialization following acute mucosal injury. PMID:12065303

  2. Early events in skin appendage formation: induction of epithelial placodes and condensation of dermal mesenchyme.

    PubMed

    Widelitz, R B; Chuong, C M

    1999-12-01

    The formation of skin appendages represents a morphogenetic process through which a homogeneous system is converted into a patterned system. We have pursued molecules involved in the early placode induction and mesenchymal condensation stages of this process. We found that intracellular and extracellular signaling molecules collaborate to position the location of feather primordia and initiate mesenchymal condensations mediated by adhesion molecules. During the inductive stage, cells interact in a fashion best described by a reaction-diffusion mechanism. Thus in early feather morphogenesis, low level adhesion molecules drive cell interactions. The interactions were modulated by extracellular signaling molecules, which eventually increase the level of signaling molecules at sites of feather initiation and subsequently the level of adhesion molecules (Jiang et al, 1999a). These physico-chemical events lead to the formation of dermal condensations and epithelial placodes at sites of feather primordia, thus achieving the earliest and most fundamental events of skin appendage formation: induction. PMID:10674386

  3. Host cell autophagy modulates early stages of adenovirus infections in airway epithelial cells.

    PubMed

    Zeng, Xuehuo; Carlin, Cathleen R

    2013-02-01

    Human adenoviruses typically cause mild infections in the upper or lower respiratory tract, gastrointestinal tract, or ocular epithelium. However, adenoviruses may be life-threatening in patients with impaired immunity and some serotypes cause epidemic outbreaks. Attachment to host cell receptors activates cell signaling and virus uptake by endocytosis. At present, it is unclear how vital cellular homeostatic mechanisms affect these early steps in the adenovirus life cycle. Autophagy is a lysosomal degradation pathway for recycling intracellular components that is upregulated during periods of cell stress. Autophagic cargo is sequestered in double-membrane structures called autophagosomes that fuse with endosomes to form amphisomes which then deliver their content to lysosomes. Autophagy is an important adaptive response in airway epithelial cells targeted by many common adenovirus serotypes. Using two established tissue culture models, we demonstrate here that adaptive autophagy enhances expression of the early region 1 adenovirus protein, induction of mitogen-activated protein kinase signaling, and production of new viral progeny in airway epithelial cells infected with adenovirus type 2. We have also discovered that adenovirus infections are tightly regulated by endosome maturation, a process characterized by abrupt exchange of Rab5 and Rab7 GTPases, associated with early and late endosomes, respectively. Moreover, endosome maturation appears to control a pool of early endosomes capable of fusing with autophagosomes which enhance adenovirus infection. Many viruses have evolved mechanisms to induce autophagy in order to aid their own replication. Our studies reveal a novel role for host cell autophagy that could have a significant impact on the outcome of respiratory infections. PMID:23236070

  4. Transformation of the genital epithelial tract occurs early in California sea lion development

    PubMed Central

    Barragán-Vargas, Cecilia; Montano-Frías, Jorge; Ávila Rosales, Germán; Godínez-Reyes, Carlos R.; Acevedo-Whitehouse, Karina

    2016-01-01

    An unusually high prevalence of metastatic urogenital carcinoma has been observed in free-ranging California sea lions stranded off the coast of California in the past two decades. No cases have been reported for sea lions in the relatively unpolluted Gulf of California. We investigated occurrence of genital epithelial transformation in 60 sea lions (n=57 pups and 3 adult females) from the Gulf of California and examined whether infection by a viral pathogen previously found to be associated with urogenital carcinoma accounted for such alterations. We also explored the contribution of MHC class II gene expression on transformation. Cellular alterations, such as squamous cell atypia (ASC), atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions were observed in 42% of the pups and in 67% of the adult females. Normal genital epithelium was more common in male than female pups. ASC was five times more likely to occur in older pups. Epithelial alterations were unrelated to infection by the potentially oncogenic otarine type I gammaherpesvirus (OtHV-1), but ASCUS was more common in pups with marked and severe inflammation. Expression of MHC class II DRB loci (Zaca DRB-D) by peripheral antigen-presenting leucocytes showed a slightly ‘protective’ effect for ASC. We propose that transformation of the California sea lion genital epithelium is relatively common in young animals, increases with age and is probably the result of infection by an unidentified pathogen. Expression of a specific MHC class II gene, suggestive of presentation of specific antigenic peptides to immune effectors, appears to lower the risk of transformation. Our study provides the first evidence that epithelial transformation of the California sea lion genital tract is relatively common, even from an early age, and raises questions regarding differences in sea lion cancer-detection and -repair success between geographical regions. PMID:27069641

  5. Transformation of the genital epithelial tract occurs early in California sea lion development.

    PubMed

    Barragán-Vargas, Cecilia; Montano-Frías, Jorge; Ávila Rosales, Germán; Godínez-Reyes, Carlos R; Acevedo-Whitehouse, Karina

    2016-03-01

    An unusually high prevalence of metastatic urogenital carcinoma has been observed in free-ranging California sea lions stranded off the coast of California in the past two decades. No cases have been reported for sea lions in the relatively unpolluted Gulf of California. We investigated occurrence of genital epithelial transformation in 60 sea lions (n=57 pups and 3 adult females) from the Gulf of California and examined whether infection by a viral pathogen previously found to be associated with urogenital carcinoma accounted for such alterations. We also explored the contribution of MHC class II gene expression on transformation. Cellular alterations, such as squamous cell atypia (ASC), atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions were observed in 42% of the pups and in 67% of the adult females. Normal genital epithelium was more common in male than female pups. ASC was five times more likely to occur in older pups. Epithelial alterations were unrelated to infection by the potentially oncogenic otarine type I gammaherpesvirus (OtHV-1), but ASCUS was more common in pups with marked and severe inflammation. Expression of MHC class II DRB loci (Zaca DRB-D) by peripheral antigen-presenting leucocytes showed a slightly 'protective' effect for ASC. We propose that transformation of the California sea lion genital epithelium is relatively common in young animals, increases with age and is probably the result of infection by an unidentified pathogen. Expression of a specific MHC class II gene, suggestive of presentation of specific antigenic peptides to immune effectors, appears to lower the risk of transformation. Our study provides the first evidence that epithelial transformation of the California sea lion genital tract is relatively common, even from an early age, and raises questions regarding differences in sea lion cancer-detection and -repair success between geographical regions. PMID:27069641

  6. Medical treatment of early stage and rare histological variants of epithelial ovarian cancer.

    PubMed

    Cont, Nicoletta Tomasi; Ferrero, Annamaria; Peccatori, Fedro Alessandro; D'Alonzo, Marta; Codacci-Pisanelli, Giovanni; Colombo, Nicoletta; Biglia, Nicoletta

    2015-01-01

    Epithelial ovarian cancer is often considered a single pathological entity, but increasing evidence suggests that it is rather a group of different neoplasms, each with unique pathological characteristics, molecular features, and clinical behaviours. This heterogeneity accounts for the different sensitivity to antineoplastic drugs and makes the treatment of ovarian tumours a challenge. For early-stage disease, as well as for heavily pre-treated patients with recurrent ovarian cancer, the benefit of chemotherapy remains uncertain. Clear-cell, mucinous, low-grade serous, and endometrioid carcinomas show different molecular characteristics, which require different therapeutic approaches. In the era of personalised cancer medicine, understanding the pathogenesis and the genetic background of each subtype of epithelial ovarian tumour may lead to a tailored therapy, maximising the benefits of specific treatments and possibly reducing the side effects. Furthermore, personal factors, such as the patient's performance status, should be taken into account in the management of ovarian cancer, with the aim of safeguarding the patients' quality of life. PMID:26557882

  7. Medical treatment of early stage and rare histological variants of epithelial ovarian cancer

    PubMed Central

    Cont, Nicoletta Tomasi; Ferrero, Annamaria; Peccatori, Fedro Alessandro; D’Alonzo, Marta; Codacci-Pisanelli, Giovanni; Colombo, Nicoletta; Biglia, Nicoletta

    2015-01-01

    Epithelial ovarian cancer is often considered a single pathological entity, but increasing evidence suggests that it is rather a group of different neoplasms, each with unique pathological characteristics, molecular features, and clinical behaviours. This heterogeneity accounts for the different sensitivity to antineoplastic drugs and makes the treatment of ovarian tumours a challenge. For early-stage disease, as well as for heavily pre-treated patients with recurrent ovarian cancer, the benefit of chemotherapy remains uncertain. Clear-cell, mucinous, low-grade serous, and endometrioid carcinomas show different molecular characteristics, which require different therapeutic approaches. In the era of personalised cancer medicine, understanding the pathogenesis and the genetic background of each subtype of epithelial ovarian tumour may lead to a tailored therapy, maximising the benefits of specific treatments and possibly reducing the side effects. Furthermore, personal factors, such as the patient’s performance status, should be taken into account in the management of ovarian cancer, with the aim of safeguarding the patients’ quality of life. PMID:26557882

  8. Macropinosomes are Key Players in Early Shigella Invasion and Vacuolar Escape in Epithelial Cells

    PubMed Central

    Weiner, Allon; Chang, Yuen-Yan; Souque, Célia; Schmitt, Christine; Enninga, Jost

    2016-01-01

    Intracellular pathogens include all viruses, many bacteria and parasites capable of invading and surviving within host cells. Key to survival is the subversion of host cell pathways by the pathogen for the purpose of propagation and evading the immune system. The intracellular bacterium Shigella flexneri, the causative agent of bacillary dysentery, invades host cells in a vacuole that is subsequently ruptured to allow growth of the pathogen within the host cytoplasm. S. flexneri invasion has been classically described as a macropinocytosis-like process, however the underlying details and the role of macropinosomes in the intracellular bacterial lifestyle have remained elusive. We applied dynamic imaging and advanced large volume correlative light electron microscopy (CLEM) to study the highly transient events of S. flexneri’s early invasion into host epithelial cells and elucidate some of its fundamental features. First, we demonstrate a clear distinction between two compartments formed during the first step of invasion: the bacterial containing vacuole and surrounding macropinosomes, often considered identical. Next, we report a functional link between macropinosomes and the process of vacuolar rupture, demonstrating that rupture timing is dependent on the availability of macropinosomes as well as the activity of the small GTPase Rab11 recruited directly to macropinosomes. We go on to reveal that the bacterial containing vacuole and macropinosomes come into direct contact at the onset of vacuolar rupture. Finally, we demonstrate that S. flexneri does not subvert pre-existing host endocytic vesicles during the invasion steps leading to vacuolar rupture, and propose that macropinosomes are the major compartment involved in these events. These results provide the basis for a new model of the early steps of S. flexneri epithelial cell invasion, establishing a different view of the enigmatic process of cytoplasmic access by invasive bacterial pathogens. PMID:27182929

  9. Macropinosomes are Key Players in Early Shigella Invasion and Vacuolar Escape in Epithelial Cells.

    PubMed

    Weiner, Allon; Mellouk, Nora; Lopez-Montero, Noelia; Chang, Yuen-Yan; Souque, Célia; Schmitt, Christine; Enninga, Jost

    2016-05-01

    Intracellular pathogens include all viruses, many bacteria and parasites capable of invading and surviving within host cells. Key to survival is the subversion of host cell pathways by the pathogen for the purpose of propagation and evading the immune system. The intracellular bacterium Shigella flexneri, the causative agent of bacillary dysentery, invades host cells in a vacuole that is subsequently ruptured to allow growth of the pathogen within the host cytoplasm. S. flexneri invasion has been classically described as a macropinocytosis-like process, however the underlying details and the role of macropinosomes in the intracellular bacterial lifestyle have remained elusive. We applied dynamic imaging and advanced large volume correlative light electron microscopy (CLEM) to study the highly transient events of S. flexneri's early invasion into host epithelial cells and elucidate some of its fundamental features. First, we demonstrate a clear distinction between two compartments formed during the first step of invasion: the bacterial containing vacuole and surrounding macropinosomes, often considered identical. Next, we report a functional link between macropinosomes and the process of vacuolar rupture, demonstrating that rupture timing is dependent on the availability of macropinosomes as well as the activity of the small GTPase Rab11 recruited directly to macropinosomes. We go on to reveal that the bacterial containing vacuole and macropinosomes come into direct contact at the onset of vacuolar rupture. Finally, we demonstrate that S. flexneri does not subvert pre-existing host endocytic vesicles during the invasion steps leading to vacuolar rupture, and propose that macropinosomes are the major compartment involved in these events. These results provide the basis for a new model of the early steps of S. flexneri epithelial cell invasion, establishing a different view of the enigmatic process of cytoplasmic access by invasive bacterial pathogens. PMID:27182929

  10. A Rapid Method for Isolating Glandular Trichomes

    PubMed Central

    Yerger, Ellen H.; Grazzini, Richard A.; Hesk, David; Cox-Foster, Diana L.; Craig, Richard; Mumma, Ralph O.

    1992-01-01

    A physical method is described for the rapid isolation of plant trichomes, with emphasis on stalked glandular types. The technique involved breaking frozen trichomes with powdered dry ice and collection of glandular heads by sieving from larger tissue fragments. This method was applied to several plants that bear similar stalked trichomes: geranium (Pelargonium), potato (Solanum tuberosum), tomato (Lycopersicon esculentum), squash (Cucurbita pepo), and velvetleaf (Abutilon theophrasti). The tissue preparation was of sufficient quality without further purification for biochemical and molecular studies. The preparation maintained the biochemical integrity of the trichomes for active enzymes and usable nucleic acids. A large quantity of tissue can be harvested; for example, 351 milligrams dry weight of glandular trichomes were harvested from geranium pedicels in 12 hours. The utility of the technique was demonstrated by examining the fatty acid composition of tall glandular trichomes of geraniums, Pelargonium ×hortorum L.H. Bailey. These purified cells contained high concentrations of unusual ω5-unsaturated fatty acids, proportionally 23.4% of total fatty acids in the trichomes. When the trichomes were removed, the supporting tissue contained no ω5-fatty acids, thereby unequivocally localizing ω5-fatty acids to the trichomes. Because ω5-fatty acids are unique precursors for the biosynthesis of ω5-anacardic acids, we conclude that anacardic acid synthesis must occur in the glandular trichomes. ImagesFigure 1Figure 2 PMID:16668834

  11. Calcitriol inhibits bleomycin-induced early pulmonary inflammatory response and epithelial-mesenchymal transition in mice.

    PubMed

    Tan, Zhu-Xia; Chen, Yuan-Hua; Xu, Shen; Qin, Hou-Ying; Zhang, Cheng; Zhao, Hui; Xu, De-Xiang

    2016-01-01

    Early pulmonary inflammation and epithelial-mesenchymal transition (EMT) play important roles during lung fibrosis. Increasing evidence demonstrates that calcitriol, the active form of vitamin D3, has anti-inflammatory activities. The aim of this study was to investigate the effects of calcitriol on bleomycin (BLM)-induced early pulmonary inflammation and subsequent EMT. Mice were intratracheally injected with BLM (3.0mg/kg). In three calcitriol+BLM groups, mice were intraperitoneal (i.p.) injected with different doses of calcitriol (0.2, 1.0 or 5.0 μg/kg) daily, beginning at 48 h before BLM injection. Twenty-four hours, seven and fourteen days after BLM injection, pulmonary inflammation and EMT were evaluated. As expected, BLM-induced infiltration of inflammatory cells in the lungs was attenuated by calcitriol. BLM-induced pulmonary inflammatory cytokines were repressed by calcitriol. Moreover, BLM-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 was blocked by calcitriol. In addition, BLM-induced phosphorylation of pulmonary p38 MAPK and protein kinase B (Akt) was inhibited by calcitriol. Further analysis showed that BLM-induced α-smooth muscle actin (α-SMA), a marker for EMT in the lungs, was significantly attenuated by calcitriol. BLM-induced transforming growth factor-beta 1 (TGF-β1) up-regulation and Smad phosphorylation were attenuated by calcitriol. In conclusion, calcitriol inhibits BLM-induced early pulmonary inflammation and subsequent EMT. PMID:26520185

  12. Lung epithelial MyD88 drives early pulmonary clearance of Pseudomonas aeruginosa by a flagellin dependent mechanism.

    PubMed

    Anas, Adam A; van Lieshout, Miriam H P; Claushuis, Theodora A M; de Vos, Alex F; Florquin, Sandrine; de Boer, Onno J; Hou, Baidong; Van't Veer, Cornelis; van der Poll, Tom

    2016-08-01

    Pseudomonas aeruginosa is a flagellated pathogen frequently causing pneumonia in hospitalized patients and sufferers of chronic lung disease. Here we investigated the role of the common Toll-like receptor (TLR) adaptor myeloid differentiation factor (MyD)88 in myeloid vs. lung epithelial cells in clearance of P. aeruginosa from the airways. Mice deficient for MyD88 in lung epithelial cells (Sftpccre-MyD88-lox mice) or myeloid cells (LysMcre-MyD88-lox mice) and bone marrow chimeric mice deficient for TLR5 (the receptor recognizing Pseudomonas flagellin) in either parenchymal or hematopoietic cells were infected with P. aeruginosa via the airways. Sftpccre-MyD88-lox mice demonstrated a reduced influx of neutrophils into the bronchoalveolar space and an impaired early antibacterial defense after infection with P. aeruginosa, whereas the response of LysMcre-MyD88-lox mice did not differ from control mice. The immune-enhancing role of epithelial MyD88 was dependent on recognition of pathogen-derived flagellin by epithelial TLR5, as demonstrated by an unaltered clearance of mutant P. aeruginosa lacking flagellin from the lungs of Sftpccre-MyD88-lox mice and an impaired bacterial clearance in bone marrow chimeric mice lacking TLR5 in parenchymal cells. These data indicate that early clearance of P. aeruginosa from the airways is dependent on flagellin-TLR5-MyD88-dependent signaling in respiratory epithelial cells. PMID:27288486

  13. Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer

    PubMed Central

    Park, Jin-Young; Lee, Yoo-Young; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

    2016-01-01

    Objective Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. Methods We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. Results A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. Conclusion FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC. PMID:26768783

  14. Glandular differentiation in dedifferentiated chondrosarcoma: molecular evidence of a rare phenomenon.

    PubMed

    Jour, George; Liu, Yajuan; Ricciotti, Robert; Pritchard, Colin; Hoch, Benjamin L

    2015-09-01

    Epithelial glandular differentiation in dedifferentiated chondrosarcoma has not been described. Our patient was a 64-year-old man with a history of prostate cancer status post-radiation and hormonal therapy. On screening bone scan, he was found to have increased uptake in his right femoral shaft. Biopsy revealed intermediate-grade conventional chondrosarcoma. Subsequent femoral resection was remarkable for an intermediate-grade chondrosarcomatous component juxtaposed to an area composed of anastomosing nests and cords of malignant epithelial cells showing nuclear atypia and increased mitotic activity. A fibroblastic-appearing spindle cell population was intimately associated with the epithelial cells. The epithelial cells labeled with 34bE12, AE1/AE3, EMA, and Vimentin (both spindled and epithelial components) while being negative for prostate-specific antigen, prostate specific acid phosphatase, cytokeratin 20, thyroid transcription factor-1, and CDX2. The patient developed local recurrence 9 months after the initial resection but has had no metastatic disease and consistently undetectable prostate-specific antigen levels. Deep parallel sequencing of the dedifferentiated component showed a nonsynonymous mutation at exon 4 of IDH1 gene at codon R132 leading to a substitution of arginine, with serine confirming glandular differentiation in dedifferentiated chondrosarcoma. PMID:26198745

  15. Population Responses of Potato Leafhopper (Hemiptera: Cicadellidae) to Insecticide in Glandular-Haired and Non-glandular-Haired Alfalfa Cultivars.

    PubMed

    Sulc, R Mark; McCormick, John S; Hammond, Ronald B; Miller, David J

    2014-12-01

    Conflicting results have been reported on the ability of glandular-haired alfalfa (Medicago sativa L.) cultivars to reduce potato leafhopper, Empoasca fabae Harris, population abundance in field environments. We measured potato leafhopper adult and nymph abundance and yield responses in a cultivar selected for high potato leafhopper resistance ('54H91') and in a non-glandular-haired susceptible cultivar ('54V54') with and without insecticide treatment across 3 yr. Treatments included no insecticide and insecticide applied either early or late in each summer growth cycle. Date × cultivar × treatment interactions were found for potato leafhopper population abundance. In the absence of insecticides, total potato leafhopper abundance (adults + nymphs per sweep) was lower in 54H91 than in 54V54 on 85% of sampling dates; cultivar differences were especially evident as potato leafhopper abundance peaked. Insecticide treatment reduced potato leafhopper populations in both cultivars, but populations recovered and often exceeded the normal action threshold in both cultivars within 2-3 wk of insecticide application. Yield gain from early insecticide treatment of 54V54 was >400 kg/ha in 11 of 14 summer harvests, whereas in 54H91 the yield gain was <250 kg/ha in 10 of 14 summer harvests. We conclude that glandular-haired alfalfa cultivars with high levels of potato leafhopper resistance significantly suppress potato leafhopper adult and nymph abundance, reduce yield losses in the absence of insecticides, and have potential within an integrated pest management strategy to reduce insecticide use in alfalfa production systems. PMID:26470072

  16. Glandular object based tumor morphometry in H&E biopsy samples for prostate cancer prognosis

    NASA Astrophysics Data System (ADS)

    Fogarasi, Stephen I.; Khan, Faisal M.; Pang, Ho-Yuen H.; Mesa-Tejada, Ricardo; Donovan, Michael J.; Fernandez, Gerardo

    2011-03-01

    Morphological and architectural characteristics of primary prostate tissue compartments, such as epithelial nuclei (EN) and cytoplasm, provide critical information for cancer diagnosis, prognosis and therapeutic response prediction. The subjective and variable Gleason grade assessed by expert pathologists in Hematoxylin and Eosin (H&E) stained specimens has been the standard for prostate cancer diagnosis and prognosis. We propose a novel morphometric, glandular object-oriented image analysis approach for the robust quantification of H&E prostate biopsy images. We demonstrate the utility of features extracted through the proposed method in predicting disease progression post treatment in a multi-institution cohort of 1027 patients. The biopsy based features were univariately predictive for clinical response post therapy; with concordance indexes (CI) <= 0.4 or >= 0.6. In multivariate analysis, a glandular object feature quantifying tumor epithelial cells not directly associated with an intact tumor gland was selected in a model incorporating preoperative clinical data, protein biomarker and morphological imaging features. The model achieved a CI of 0.73 in validation, which was significantly higher than a CI of 0.69 for the standard multivariate model based solely on clinical features currently used in clinical practice. This work presents one of the first demonstrations of glandular object based morphological features in the H&E stained biopsy specimen to predict disease progression post primary treatment. Additionally, it is the largest scale study of the efficacy and robustness of the proposed features in prostate cancer prognosis.

  17. Secreting Glandular Trichomes: More than Just Hairs

    PubMed Central

    Wagner, George J.

    1991-01-01

    Secreting glandular plant trichome types which accumulate large quantities of metabolic products in the space between their gland cell walls and cuticle permit the plant to amass secretions in a compartment that is virtually outside the plant body. These structures not only accumulate and store what are often phytotoxic oils but they position these compounds as an apparent first line of defense at the surface of the plant. Recent advances in methods for isolation and study of trichome glands have allowed more precise analysis of gland cell metabolism and enzymology. Isolation of mutants with altered trichome phenotypes provides new systems for probing the genetic basis of trichome development. These advances and their continuation can pave the way for future attempts at modification of trichome secretion. The biochemical capability of glandular secreting trichomes and the potential for its future manipulation to exploit this external storage compartment is the focus of this review. PMID:16668241

  18. Glandular Odontogenic Cyst of the Anterior Mandible

    PubMed Central

    Raju, Srinivasa Pathapati; Reddy, Sridhar Padala; Ananthnag, Jakkula

    2015-01-01

    Context: Glandular odontogenic cyst (GOC) is a rare cyst occurring in the middle-age people with mandibular anterior as the common site of occurrence. Case Report: We report a case of massive GOC in a 65-year-old female with an emphasis on its clinical course, histological features, and treatment modalities. Conclusion: The aggressiveness and recurrences of GOC warrants clinicians for the careful examination, treatment, and long-term follow-up. PMID:25789251

  19. Inflammatory and glandular skin disease in pregnancy.

    PubMed

    Yang, Catherine S; Teeple, Mary; Muglia, Jennie; Robinson-Bostom, Leslie

    2016-01-01

    A switch from cell-mediated to humoral immunity (helper T 1 [Th1] to helper T 2 [Th2] shift) during gestation plays a key role in placental immune tolerance. As a result, skin diseases that are Th2 mediated often worsen, whereas skin diseases that are Th1 mediated often improve during gestation. Also, due to fluctuations in glandular activity, skin diseases involving sebaceous and eccrine glands may flare, whereas those involving apocrine glands may improve during pregnancy. Despite these trends, inflammatory and glandular skin diseases do not always follow the predicted pattern, and courses are often diverse. We review the gestational course of inflammatory skin diseases, such as atopic dermatitis (atopic eruption of pregnancy), psoriasis, impetigo herpetiformis, urticaria, erythema annulare centrifugum, pityriasis rosea, sarcoidosis, Sweet syndrome, and erythema nodosum, as well as glandular skin diseases, including acne vulgaris, acne rosacea, perioral dermatitis, hidradenitis suppurativa, Fox-Fordyce disease, hyperhidrosis, and miliaria. For each of these diseases, we discuss the pathogenesis, clinical presentation, and management with special consideration for maternal and fetal safety. PMID:27265071

  20. Early Mucosal Sensing of SIV Infection by Paneth Cells Induces IL-1β Production and Initiates Gut Epithelial Disruption

    PubMed Central

    Bourry, Olivier; Hu, William K.; Somrit, Monsicha; Sankaran-Walters, Sumathi; Gaulke, Chris A.; Fenton, Anne N.; Li, Jay A.; Crawford, Robert W.; Chuang, Frank; Tarara, Ross; Marco, Maria L.; Bäumler, Andreas J.; Cheng, Holland; Dandekar, Satya

    2014-01-01

    HIV causes rapid CD4+ T cell depletion in the gut mucosa, resulting in immune deficiency and defects in the intestinal epithelial barrier. Breakdown in gut barrier integrity is linked to chronic inflammation and disease progression. However, the early effects of HIV on the gut epithelium, prior to the CD4+ T cell depletion, are not known. Further, the impact of early viral infection on mucosal responses to pathogenic and commensal microbes has not been investigated. We utilized the SIV model of AIDS to assess the earliest host-virus interactions and mechanisms of inflammation and dysfunction in the gut, prior to CD4+ T cell depletion. An intestinal loop model was used to interrogate the effects of SIV infection on gut mucosal immune sensing and response to pathogens and commensal bacteria in vivo. At 2.5 days post-SIV infection, low viral loads were detected in peripheral blood and gut mucosa without CD4+ T cell loss. However, immunohistological analysis revealed the disruption of the gut epithelium manifested by decreased expression and mislocalization of tight junction proteins. Correlating with epithelial disruption was a significant induction of IL-1β expression by Paneth cells, which were in close proximity to SIV-infected cells in the intestinal crypts. The IL-1β response preceded the induction of the antiviral interferon response. Despite the disruption of the gut epithelium, no aberrant responses to pathogenic or commensal bacteria were observed. In fact, inoculation of commensal Lactobacillus plantarum in intestinal loops led to rapid anti-inflammatory response and epithelial tight junction repair in SIV infected macaques. Thus, intestinal Paneth cells are the earliest responders to viral infection and induce gut inflammation through IL-1β signaling. Reversal of the IL-1β induced gut epithelial damage by Lactobacillus plantarum suggests synergistic host-commensal interactions during early viral infection and identify these mechanisms as potential

  1. Chlamydia trachomatis Infection of Endocervical Epithelial Cells Enhances Early HIV Transmission Events

    PubMed Central

    Buckner, Lyndsey R.; Amedee, Angela M.; Albritton, Hannah L.; Kozlowski, Pamela A.; Lacour, Nedra; McGowin, Chris L.; Schust, Danny J.; Quayle, Alison J.

    2016-01-01

    Chlamydia trachomatis causes a predominantly asymptomatic, but generally inflammatory, genital infection that is associated with an increased risk for HIV acquisition. Endocervical epithelial cells provide the major niche for this obligate intracellular bacterium in women, and the endocervix is also a tissue in which HIV transmission can occur. The mechanism by which CT infection enhances HIV susceptibility at this site, however, is not well understood. Utilizing the A2EN immortalized endocervical epithelial cell line grown on cell culture inserts, we evaluated the direct role that CT-infected epithelial cells play in facilitating HIV transmission events. We determined that CT infection significantly enhanced the apical-to-basolateral migration of cell-associated, but not cell-free, HIVBaL, a CCR5-tropic strain of virus, across the endocervical epithelial barrier. We also established that basolateral supernatants from CT-infected A2EN cells significantly enhanced HIV replication in peripheral mononuclear cells and a CCR5+ T cell line. These results suggest that CT infection of endocervical epithelial cells could facilitate both HIV crossing the mucosal barrier and subsequent infection or replication in underlying target cells. Our studies provide a mechanism by which this common STI could potentially promote the establishment of founder virus populations and the maintenance of local HIV reservoirs in the endocervix. Development of an HIV/STI co-infection model also provides a tool to further explore the role of other sexually transmitted infections in enhancing HIV acquisition. PMID:26730599

  2. Immediate early responses of avian tracheal epithelial cells to infection with highly pathogenic avian invluenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic (HP) avian influenza viruses (AIV) present an ongoing threat to the world poultry industry. In order to develop new AIV control strategies it is necessary to understand the underlying mechanism of viral infection at mucosal respiratory sites. Chicken and duck tracheal epithelial ...

  3. Induction of glandular and non-glandular trichomes by damage in leaves of Madia sativa under contrasting water regimes

    NASA Astrophysics Data System (ADS)

    Gonzáles, Wilfredo L.; Negritto, María A.; Suárez, Lorena H.; Gianoli, Ernesto

    2008-01-01

    Plant traits may play multiple functional roles simultaneously. Leaf trichomes have been related to resistance against herbivores as well as to enhanced water economy in the plant. In a greenhouse study, we evaluated the interactive effect of damage (control vs. mechanical damage) and water availability (control vs. low watering) on the expression of glandular and non-glandular leaf trichomes in the annual Chilean tarweed Madia sativa (Asteraceae). We found that the overall trichome density increased both after damage and when plants were grown under water shortage. Interestingly, the type of trichome induced after damage varied with each water environment. While damage induced glandular trichomes only under control watering, non-glandular trichomes were induced by damage only under experimental drought. Results indicate that in M. sativa glandular trichomes are equally induced by drought or damage but there is no additive effect of these factors. In both cases glandular trichome density apparently reached a limit, which may be interpreted in terms of constraint or efficacy. On the other hand, the synergistic effect of damage and drought on non-glandular trichomes might suggest that, compared to glandular ones, these trichomes are less responsive to each stress factor separately. Thus, for plants to induce non-glandular trichomes they must be subjected to a degree of stress above a threshold that was not reached for each individual factor in our experimental setting. We did not detect a significant correlation between trichome types. Thus, the contrasting patterns observed likely reflect independent responses of trichomes to the evaluated factors.

  4. Thymomas with prominent glandular differentiation: a clinicopathologic and immunohistochemical study of 12 cases.

    PubMed

    Weissferdt, Annikka; Moran, Cesar A

    2013-08-01

    Twelve cases of thymomas with prominent glandular differentiation are presented. The patients were 7 men and 5 women aged between 45 and 68 years (average, 56.5 years). Clinically, the patients presented with nonspecific symptoms of chest pain, cough, and fatigue. None of the patients had a history of myasthenia gravis or other autoimmune syndrome. Thymectomy was performed in all patients. The tumor size ranged from 4 to 7 cm in greatest diameter. Macroscopically, the tumors were described as firm and light tan without areas of necrosis, hemorrhage, or cystic change. Histologically, 7 tumors were classified as spindle cell (World Health Organization type A), 2 as mixed spindle cell and conventional (A+B1), 2 as conventional (B1), and 1 as atypical thymoma (B3). In 4 cases, the tumors showed invasion into periadipose thymic tissue. All cases showed the typical growth patterns of their particular subtypes. In addition, a distinct glandular component was present in all cases showing mucinous differentiation in 4 of them. Immunohistochemical studies showed tumor cells positive for CAM5.2, cytokeratin 5/6, and Pax8 and negative for carcinoembryonic antigen, thyroid transcription factor 1, and epithelial membrane antigen. Calretinin showed focal weak staining in the nonmucinous glandular components in 3 cases. Follow-up information obtained in 8 patients showed that all were alive and well in a period ranging from 2 to 5 years. The possibility of a glandular component in thymomas should be kept in mind in the assessment of mediastinoscopic biopsies to avoid misdiagnosis for other neoplasms that may require different treatment modalities. PMID:23528863

  5. Expression of mitogen-activated protein kinase phosphatase-1 in the early phases of human epithelial carcinogenesis.

    PubMed Central

    Loda, M.; Capodieci, P.; Mishra, R.; Yao, H.; Corless, C.; Grigioni, W.; Wang, Y.; Magi-Galluzzi, C.; Stork, P. J.

    1996-01-01

    Many mitogens and human oncogenes activate extracellular regulated kinases (ERKs), which in turn convey proliferation signals. ERKs or mitogen-activated protein (MAP) kinases are inactivated in vitro by MAP kinase phosphatases (MKPs). The gene encoding one of these MKPs, MKP-1, is a serum-inducible gene and is transcriptionally activated by mitogenic signals in cultured cells. As MKP-1 has been shown to block DNA synthesis by inhibiting ERKs when expressed at elevated levels in cultured cells, it has been suggested that it may act as a tumor suppressor. MKP-1 mRNA and MAP kinase (ERK-1 and -2) protein expression was assessed in 164 human epithelial tumors of diverse tissue origin by in situ hybridization and immunohistochemistry. MKP-1 was overexpressed in the early phases of prostate, colon, and bladder carcinogenesis, with progressive loss of expression with higher histological grade and in metastases. In contrast, breast carcinomas showed significant MKP-1 expression even when poorly differentiated or in late stages of the disease. MKP-1, ERK-1, and ERK-2 were co-expressed in most tumors examined. In a subset of 15 tumors, ERK-1 enzymatic activity as well as structural alterations that might be responsible for loss of function of MKP-1 during tumor progression, were examined. ERK-1 enzymatic activity was found to be elevated despite MKP-1 overexpression. No loss of 5q35-ter (containing the MKP-1 locus) was detected by polymerase chain reaction in metastases compared with primary tumors. Finally, no mutations were found in the catalytic domain of MKP-1. These data indicate that MKP-1 is an early marker for a wide range of human epithelial tumors and suggest that MKP-1 does not behave as a tumor suppressor in epithelial tumors. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8909245

  6. Endoscopic submucosal dissection vs laparoscopic colorectal resection for early colorectal epithelial neoplasia

    PubMed Central

    Hon, Sophie SF; Ng, Simon SM; Wong, Tiffany CL; Chiu, Philip WY; Mak, Tony WC; Leung, WW; Lee, Janet FY

    2015-01-01

    AIM: To compare the short term outcome of endoscopic submucosal dissection (ESD) with that of laparoscopic colorectal resection (LC) for the treatment of early colorectal epithelial neoplasms that are not amenable to conventional endoscopic removal. METHODS: This was a retrospective cohort study. The clinical data of all consecutive patients who underwent ESD for endoscopically assessed benign lesions that were larger than 2 cm in diameter from 2009 to 2013 were collected. These patients were compared with a cohort of controls who underwent LC from 2005 to 2013. Lesions that were proven to be malignant by initial endoscopic biopsies were excluded. Mid and lower rectal lesions were not included because total mesorectal excision, which bears a more complicated postoperative course, is not indicated for lesions without histological proof of malignancy. Both ESD and LC were performed by the same surgical unit with a standardized technique. The patients were managed according to a standard protocol, and they were closely monitored for complications after the procedures. All hospital records were reviewed, and the following data were compared between the ESD and LC groups: patient demographics, size and location of the lesions, procedure time, short-term clinical outcomes and pathology results. RESULTS: From 2005 to 2013, 65 patients who underwent ESD and 55 patients who underwent LC were included in this study. The two groups were similar in terms of sex (P = 0.41) and American Society of Anesthesiologist class (P = 0.58), although patients in the ESD group were slightly older (68.6 ± 9.4 vs 64.6 ± 9.9, P = 0.03). ESD could be accomplished with a shorter procedure time (113 ± 66 min vs 153 ± 43 min, P < 0.01) for lesions of comparable size (3.0 ± 1.2 cm vs 3.4 ± 1.4 cm, P = 0.22) and location (colon/rectum: 59/6 vs colon/rectum: 52/3, P = 0.43). ESD appeared to be associated with a lower short-term complication rate, but the difference did not reach statistical

  7. Transmissible Plasmid Containing Salmonella enterica Heidelberg Isolates Modulate Cytokine Production During Early Stage of Interaction with Intestinal Epithelial Cells.

    PubMed

    Gokulan, Kuppan; Khare, Sangeeta; Williams, Katherine; Foley, Steven L

    2016-08-01

    The variation in cytokine production during bacterial invasion of human intestinal epithelial cells (IECs) is a contributing factor for progression of the infection. A few Salmonella enterica Heidelberg strains isolated from poultry products harbor transmissible plasmids (TPs), including those that encode a type-IV secretion system. Earlier, we showed that these TPs are responsible for increased virulence during infection. This study examines the potential role of these TPs in cytokine production in IECs. This study showed that S. Heidelberg strains containing TPs (we refer as virulent strains) caused decreased interleukin (IL)-10 production in IECs after 1 h infection. The virulent strains induced a high level of tumor necrosis factor-α production under identical conditions. The virulent strains of S. Heidelberg also altered the production of IL-2, IL-17, and granulocyte macrophage colony-stimulating factor compared to an avirulent strain. As a part of infection, bacteria cross the epithelial barrier and encounter intestinal macrophages. Hence, we examined the cytotoxic mechanism of strains of S. Heidelberg in macrophages. Scanning electron microscopy showed cell necrosis occurs during the early stage of infection. In conclusion, virulent S. Heidelberg strains were able to modify the host cytokine profile during the early stages of infection and also caused necrosis in macrophages. PMID:27082282

  8. CYR61 and TAZ Upregulation and Focal Epithelial to Mesenchymal Transition May Be Early Predictors of Barrett's Esophagus Malignant Progression.

    PubMed

    Cardoso, Joana; Mesquita, Marta; Dias Pereira, António; Bettencourt-Dias, Mónica; Chaves, Paula; Pereira-Leal, José B

    2016-01-01

    Barrett's esophagus is the major risk factor for esophageal adenocarcinoma. It has a low but non-neglectable risk, high surveillance costs and no reliable risk stratification markers. We sought to identify early biomarkers, predictive of Barrett's malignant progression, using a meta-analysis approach on gene expression data. This in silico strategy was followed by experimental validation in a cohort of patients with extended follow up from the Instituto Português de Oncologia de Lisboa de Francisco Gentil EPE (Portugal). Bioinformatics and systems biology approaches singled out two candidate predictive markers for Barrett's progression, CYR61 and TAZ. Although previously implicated in other malignancies and in epithelial-to-mesenchymal transition phenotypes, our experimental validation shows for the first time that CYR61 and TAZ have the potential to be predictive biomarkers for cancer progression. Experimental validation by reverse transcriptase quantitative PCR and immunohistochemistry confirmed the up-regulation of both genes in Barrett's samples associated with high-grade dysplasia/adenocarcinoma. In our cohort CYR61 and TAZ up-regulation ranged from one to ten years prior to progression to adenocarcinoma in Barrett's esophagus index samples. Finally, we found that CYR61 and TAZ over-expression is correlated with early focal signs of epithelial to mesenchymal transition. Our results highlight both CYR61 and TAZ genes as potential predictive biomarkers for stratification of the risk for development of adenocarcinoma and suggest a potential mechanistic route for Barrett's esophagus neoplastic progression. PMID:27583562

  9. Inhibition of hypoxia inducible factor-1α downregulates the expression of epithelial to mesenchymal transition early marker proteins without undermining cell survival in hypoxic lens epithelial cells

    PubMed Central

    Neelam, Sudha; Brooks, Morgan M.

    2015-01-01

    Purpose The purpose of this study was to identify potential therapeutic strategies to slow down or prevent the expression of early-onset epithelial to mesenchymal transition (EMT) marker proteins (fibronectin and alpha smooth muscle actin, α-SMA) without sacrificing the synthesis and accumulation of the prosurvival protein vascular endothelial growth factor (VEGF) in cultured virally transformed human lens epithelial (HLE) cells. Methods HLE-B3 cells, maintained in a continuous hypoxic environment (1% oxygen), were treated with SB216763, a specific inhibitor of glycogen synthase kinase-3β (GSK-3β) catalytic activity. Western blot analysis was employed to detect the cytoplasmic and nuclear levels of β-catenin, as well as the total lysate content of fibronectin and α-SMA. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of VEGF in cell culture medium. A hypoxia-inducible factor-1α (HIF-1α) translation inhibitor and an HIF-2α translation inhibitor were independently employed to evaluate the effect of hypoxia inducible factor inhibition on EMT marker protein and VEGF expression. XAV932 was used to assess the suppression of nuclear β-catenin and its downstream effect on EMT marker proteins and VEGF expression. Results SB216763-treated HLE-B3 cells caused marked inhibition of GSK-3β activity prompting a significant increase in the translocation of cytoplasmic β-catenin to the nucleus. The enhancement of nuclear β-catenin looked as if it positively correlated with a significant increase in the basal expression of VEGF as well as increased expression of fibronectin and α-SMA. In conjunction with SB216763, coadministration of an HIF-1α translation inhibitor, but not an HIF-2α translation inhibitor, markedly suppressed the expression of fibronectin and α-SMA without affecting VEGF levels. Treatment with XAV932 significantly reduced the level of nuclear β-catenin, but the levels of neither the EMT marker proteins nor VEGF were changed

  10. Glandular odontogenic cyst: A diagnostic dilemma.

    PubMed

    Shah, Amisha A; Sangle, Amit; Bussari, Smita; Koshy, Ajit V

    2016-01-01

    Glandular odontogenic cyst (GOC) is a rare and uncommon jaw bone cyst of odontogenic origin described in 1987 by Gardener et al. as a distinct entity. It is a cyst having an unpredictable, potentially aggressive behavior, and has the propensity to grow in large size with relatively high recurrence rate. It poses a diagnostic challenge as it can be clinically and histopathologically confused with lateral periodontal cyst, botryoid odontogenic cyst, radicular and residual cysts with mucous metaplasia, and low-grade mucoepidermoid carcinoma. The present case report describes GOC in both male and female patients with intra-oral swelling following extraction of 36 and 46, respectively. Careful histopathological examination is needed to diagnose GOC, and a careful long-term follow-up is advocated. PMID:27134453

  11. Glandular odontogenic cyst: A diagnostic dilemma

    PubMed Central

    Shah, Amisha A.; Sangle, Amit; Bussari, Smita; Koshy, Ajit V.

    2016-01-01

    Glandular odontogenic cyst (GOC) is a rare and uncommon jaw bone cyst of odontogenic origin described in 1987 by Gardener et al. as a distinct entity. It is a cyst having an unpredictable, potentially aggressive behavior, and has the propensity to grow in large size with relatively high recurrence rate. It poses a diagnostic challenge as it can be clinically and histopathologically confused with lateral periodontal cyst, botryoid odontogenic cyst, radicular and residual cysts with mucous metaplasia, and low-grade mucoepidermoid carcinoma. The present case report describes GOC in both male and female patients with intra-oral swelling following extraction of 36 and 46, respectively. Careful histopathological examination is needed to diagnose GOC, and a careful long-term follow-up is advocated. PMID:27134453

  12. Glandular odontogenic cyst: A case report

    PubMed Central

    Karjodkar, Freny R.; Yadav, Archana; Sansare, Kaustubh; Sontakke, Subodh

    2014-01-01

    Glandular odontogenic cysts (GOCs) are rare intrabony solitary or multiloculated cysts of odontogenic origin. The importance of GOCs lies in the fact that they exhibit a propensity for recurrence similar to keratocystic odontogenic tumors and that they may be confused microscopically with central mucoepidermoid carcinoma. Thus, the oral and maxillofacial radiologists play an important role in definitive diagnosis of GOC based on distinctive cases; though they are rare. In large part, this is due to the GOC's complex and frequently non-specific histopathology. This report describes a case of GOC occurrence in the posterior mandibular ramus region in a 17-year-old female, which is a rare combination of site, age, and gender for occurrence. PMID:24701462

  13. Increase in proliferation and apoptosis of gastric epithelial cells early in the natural history of Helicobacter pylori infection.

    PubMed Central

    Jones, N. L.; Shannon, P. T.; Cutz, E.; Yeger, H.; Sherman, P. M.

    1997-01-01

    Childhood acquisition of Helicobacter pylori is a critical risk factor for gastric cancer. Since tumorigenesis involves deregulation of proliferation and apoptosis, we examined gastric epithelial cell proliferation and apoptosis in H. pylori-infected children. Apoptosis and proliferation of gastric antral epithelial cells in biopsy specimens from patients with H. pylori-induced gastritis, secondary gastritis, and noninflamed controls were compared. p53 protein expression was examined immunohistochemically. Apoptotic cells were identified in the surface epithelium in each group. The apoptotic index was higher in specimens from patients with H. pylori gastritis (120 +/- 10) than secondary gastritis (50 +/- 10) and noninflamed controls (40 +/- 10, analysis of variance P < 0.005). Apoptosis decreased following H. pylori eradication and resolution of gastritis (P < 0.02). An expanded proliferative compartment was identified in H. pylori-induced gastritis (32.4 +/- 3.5; proliferative labeling index +/- SE) compared with secondary gastritis (18.9 +/- 2.8) and noninflamed controls (13.7 +/- 3.1, analysis of variance P < 0.01). The accelerated cell turnover was associated with p53 overexpression (analysis of variance P < 0.005). Accumulation of p53 was not associated with expression of the cyclin-dependent kinase inhibitor p21. The occurrence of altered cell turnover early in the natural history of chronic infection provides an explanation for the increased risk of gastric cancer development associated with childhood acquisition of infection. Images Figure 1 Figure 4 Figure 6 Figure 8 PMID:9403720

  14. Glycomics Laboratory for the Early Detection of Epithelial Ovarian Cancer | Division of Cancer Prevention

    Cancer.gov

    DESCRIPTION (provided by applicant): Ovarian cancer is a silent killer with few early symptoms and advanced disease present at the time of diagnosis. This cancer is the most lethal of all gynecologic malignancies with over 20,000 new cases diagnosed each year. The 5 year survival rates for ovarian cancer dramatically improve when the disease is diagnosed at an early stage. |

  15. Early soy exposure via maternal diet regulates rat mammary epithelial differentiation by paracrine signaling from stromal adipocytes.

    PubMed

    Su, Ying; Shankar, Kartik; Simmen, Rosalia C M

    2009-05-01

    Diet-mediated changes in transcriptional programs that promote the early differentiation of the mammary gland may lead to reduced breast cancer risk. The disparity in adult breast cancer incidence between Asian women and Western counterparts is attributed partly to high soy food intake. Here, we conducted genome-wide profiling of mammary tissues of weanling rats exposed to soy protein isolate (SPI) or control casein (CAS) via maternal diet to evaluate the contribution of early exposure on mammary gene expression. Of the identified 18 up- and 39 downregulated genes with SPI relative to CAS, a subset was associated with lipid metabolic pathways, consistent with reduced mammary adipocyte size and suggesting stromal adipocyte-specific genomic changes. Female offspring of rats fed SPI tended to have fewer terminal end buds (P = 0.06) and had significantly lower body weight and abdominal fat mass. To demonstrate the functional consequence of SPI-mediated adipocyte metabolic changes on neighboring mammary epithelium, the expression of in vivo regulated genes in 3T3-L1 adipocytes treated with soy isoflavone genistein and effects of the resultant conditioned medium (CM) on the differentiation of HC11 mammary epithelial cells were evaluated by quantitative RT-PCR and/or Western immunoblots. In differentiated 3T3-L1, genistein decreased fatty acid synthase and stearoyl-CoA desaturase and increased hydroxysteroid 11-beta dehydrogenase 1 expression. CM from genistein-treated adipocytes had higher adiponectin levels and augmented prolactin-induced, glucocorticoid-regulated beta-casein levels. These findings suggest that soy-associated components, by targeting mammary adipocytes, alter paracrine signaling to enhance mammary epithelial differentiation, with important implications for the prevention of breast cancer associated with obesity and obesity-related diseases. PMID:19321580

  16. Identification of Plet-1 as a specific marker of early thymic epithelial progenitor cells.

    PubMed

    Depreter, Marianne G L; Blair, Natalie F; Gaskell, Terri L; Nowell, Craig S; Davern, Kathleen; Pagliocca, Adelina; Stenhouse, Frances H; Farley, Alison M; Fraser, Adrian; Vrana, Jan; Robertson, Kevin; Morahan, Grant; Tomlinson, Simon R; Blackburn, C Clare

    2008-01-22

    The thymus is essential for a functional immune system, because the thymic stroma uniquely supports T lymphocyte development. We have previously identified the epithelial progenitor population from which the thymus arises and demonstrated its ability to generate an organized functional thymus upon transplantation. These thymic epithelial progenitor cells (TEPC) are defined by surface determinants recognized by the mAbs MTS20 and MTS24, which were also recently shown to identify keratinocyte progenitor cells in the skin. However, the biochemical nature of the MTS20 and MTS24 determinants has remained unknown. Here we show, via expression profiling of fetal mouse TEPC and their differentiated progeny and subsequent analyses, that both MTS20 and MTS24 specifically bind an orphan protein of unknown function, Placenta-expressed transcript (Plet)-1. In the postgastrulation embryo, Plet-1 expression is highly restricted to the developing pharyngeal endoderm and mesonephros until day 11.5 of embryogenesis, consistent with the MTS20 and MTS24 staining pattern; both MTS20 and MTS24 specifically bind cell lines transfected with Plet-1; and antibodies to Plet-1 recapitulate MTS20/24 staining. In adult tissues, we demonstrate expression in a number of sites, including mammary and prostate epithelia and in the pancreas, where Plet-1 is specifically expressed by the major duct epithelium, providing a specific cell surface marker for this putative reservoir of pancreatic progenitor/stem cells. Plet-1 will thus provide an invaluable tool for genetic analysis of the lineage relationships and molecular mechanisms operating in the development, homeostasis, and injury in several organ/tissue systems. PMID:18195351

  17. Macrophage-derived LIF and IL1B regulate alpha(1,2)fucosyltransferase 2 (Fut2) expression in mouse uterine epithelial cells during early pregnancy.

    PubMed

    Jasper, Melinda J; Care, Alison S; Sullivan, Brad; Ingman, Wendy V; Aplin, John D; Robertson, Sarah A

    2011-01-01

    Macrophages accumulate within stromal tissue subjacent to the luminal epithelium in the mouse uterus during early pregnancy after seminal fluid exposure at coitus. To investigate their role in regulating epithelial cell expression of fucosylated structures required for embryo attachment and implantation, fucosyltransferase enzymes Fut1, Fut2 (Enzyme Commission number [EC] 2.4.1.69), and Fut4 (EC 2.4.1.214) and Muc1 and Muc4 mRNAs were quantified by quantitative real-time PCR in uterine epithelial cells after laser capture microdissection in situ or after epithelial cell coculture with macrophages or macrophage-secreted factors. When uterine macrophage recruitment was impaired by mating with seminal plasma-deficient males, epithelial cell Fut2 expression on Day 3.5 postcoitus (pc) was reduced compared to intact-mated controls. Epithelial cell Fut2 was upregulated in vitro by coculture with macrophages or macrophage-conditioned medium (MCM). Macrophage-derived cytokines LIF, IL1B, and IL12 replicated the effect of MCM on Fut2 mRNA expression, and MCM-stimulated expression was inhibited by anti-LIF and anti-IL1B neutralizing antibodies. The effects of acute macrophage depletion on fucosylated structures detected with lectins Ulex europaeus 1 (UEA-1) and Lotus tetragonolobus purpureas (LTP), or LewisX immunoreactivity, were quantified in vivo in Cd11b-dtr transgenic mice. Depletion of macrophages caused a 30% reduction in luminal epithelial UEA-1 staining and a 67% reduction in LewisX staining in uterine tissues of mice hormonally treated to mimic early pregnancy. Together, these data demonstrate that uterine epithelial Fut2 mRNA expression and terminal fucosylation of embryo attachment ligands is regulated in preparation for implantation by factors including LIF and IL1B secreted from macrophages recruited during the inflammatory response to insemination. PMID:20864644

  18. Dosimetric implications of age related glandular changes in screening mammography

    NASA Astrophysics Data System (ADS)

    Beckett, J. R.; Kotre, C. J.

    2000-03-01

    The UK National Health Service Breast Screening Programme is currently organized to routinely screen women between the ages of 50 and 64, with screening for older women available on request. The lower end of this age range closely matches the median age for the menopause (51 years), during which significant changes in the composition of the breast are known to occur. In order to quantify the dosimetric effect of these changes, radiographic factors and compressed breast thickness data for a cohort of 1258 women aged between 35 and 79 undergoing breast screening mammography have been used to derive estimates of breast glandularity and mean glandular dose (MGD), and examine their variation with age. The variation of mean radiographic exposure factors with age is also investigated. The presence of a significant number of age trial women within the cohort allowed an extended age range to be studied. Estimates of MGD including corrections for breast glandularity based on compressed breast thickness only, compressed breast thickness and age and for each individual woman are compared with the MGD based on the conventional assumption of a 50:50 adipose/glandular composition. It has been found that the use of the conventional 50:50 assumption leads to overestimates of MGD of up to 13% over the age range considered. By using compressed breast thickness to estimate breast glandularity, this error range can be reduced to 8%, whilst age and compressed breast thickness based glandularity estimates result in an error range of 1%.

  19. Epithelial stratification and placode invagination are separable functions in early morphogenesis of the molar tooth.

    PubMed

    Li, Jingjing; Chatzeli, Lemonia; Panousopoulou, Eleni; Tucker, Abigail S; Green, Jeremy B A

    2016-02-15

    Ectodermal organs, which include teeth, hair follicles, mammary ducts, and glands such as sweat, mucous and sebaceous glands, are initiated in development as placodes, which are epithelial thickenings that invaginate and bud into the underlying mesenchyme. These placodes are stratified into a basal and several suprabasal layers of cells. The mechanisms driving stratification and invagination are poorly understood. Using the mouse molar tooth as a model for ectodermal organ morphogenesis, we show here that vertical, stratifying cell divisions are enriched in the forming placode and that stratification is cell division dependent. Using inhibitor and gain-of-function experiments, we show that FGF signalling is necessary and sufficient for stratification but not invagination as such. We show that, instead, Shh signalling is necessary for, and promotes, invagination once suprabasal tissue is generated. Shh-dependent suprabasal cell shape suggests convergent migration and intercalation, potentially accounting for post-stratification placode invagination to bud stage. We present a model in which FGF generates suprabasal tissue by asymmetric cell division, while Shh triggers cell rearrangement in this tissue to drive invagination all the way to bud formation. PMID:26755699

  20. Epithelial stratification and placode invagination are separable functions in early morphogenesis of the molar tooth

    PubMed Central

    Li, Jingjing; Chatzeli, Lemonia; Panousopoulou, Eleni; Tucker, Abigail S.; Green, Jeremy B. A.

    2016-01-01

    Ectodermal organs, which include teeth, hair follicles, mammary ducts, and glands such as sweat, mucous and sebaceous glands, are initiated in development as placodes, which are epithelial thickenings that invaginate and bud into the underlying mesenchyme. These placodes are stratified into a basal and several suprabasal layers of cells. The mechanisms driving stratification and invagination are poorly understood. Using the mouse molar tooth as a model for ectodermal organ morphogenesis, we show here that vertical, stratifying cell divisions are enriched in the forming placode and that stratification is cell division dependent. Using inhibitor and gain-of-function experiments, we show that FGF signalling is necessary and sufficient for stratification but not invagination as such. We show that, instead, Shh signalling is necessary for, and promotes, invagination once suprabasal tissue is generated. Shh-dependent suprabasal cell shape suggests convergent migration and intercalation, potentially accounting for post-stratification placode invagination to bud stage. We present a model in which FGF generates suprabasal tissue by asymmetric cell division, while Shh triggers cell rearrangement in this tissue to drive invagination all the way to bud formation. PMID:26755699

  1. Loss of vitamin D receptor signaling from the mammary epithelium or adipose tissue alters pubertal glandular development

    PubMed Central

    Johnson, Abby L.; Zinser, Glendon M.

    2014-01-01

    Vitamin D3 receptor (VDR) signaling within the mammary gland regulates various postnatal stages of glandular development, including puberty, pregnancy, involution, and tumorigenesis. Previous studies have shown that vitamin D3 treatment induces cell-autonomous growth inhibition and differentiation of mammary epithelial cells in culture. Furthermore, mammary adipose tissue serves as a depot for vitamin D3 storage, and both epithelial cells and adipocytes are capable of bioactivating vitamin D3. Despite the pervasiveness of VDR in mammary tissue, individual contributions of epithelial cells and adipocytes, as well as the VDR-regulated cross-talk between these two cell types during pubertal mammary development, have yet to be investigated. To assess the cell-type specific effect of VDR signaling during pubertal mammary development, novel mouse models with mammary epithelial- or adipocyte-specific loss of VDR were generated. Interestingly, loss of VDR in either cellular compartment accelerated ductal morphogenesis with increased epithelial cell proliferation and decreased apoptosis within terminal end buds. Conversely, VDR signaling specifically in the mammary epithelium modulated hormone-induced alveolar growth, as ablation of VDR in this cell type resulted in precocious alveolar development. In examining cellular cross-talk ex vivo, we show that ligand-dependent VDR signaling in adipocytes significantly inhibits mammary epithelial cell growth in part through the vitamin D3-dependent production of the cytokine IL-6. Collectively, these studies delineate independent roles for vitamin D3-dependent VDR signaling in mammary adipocytes and epithelial cells in controlling pubertal mammary gland development. PMID:25139050

  2. Early events in the pathogenesis of chronic obstructive pulmonary disease. Smoking-induced reprogramming of airway epithelial basal progenitor cells.

    PubMed

    Shaykhiev, Renat; Crystal, Ronald G

    2014-12-01

    The airway epithelium is the primary site of the earliest pathologic changes induced by smoking, contributing to the development of chronic obstructive pulmonary disease (COPD). The normal human airway epithelium is composed of several major cell types, including differentiated ciliated and secretory cells, intermediate undifferentiated cells, and basal cells (BC). BC contain the stem/progenitor cell population responsible for maintenance of the normally differentiated airway epithelium. Although inflammatory and immune processes play a significant role in the pathogenesis of COPD, the earliest lesions include hyperplasia of the BC population, suggesting that the disease may start with this cell type. Apart from BC hyperplasia, smoking induces a number of COPD-relevant airway epithelial remodeling phenotypes that are likely initiated in the BC population, including mucous cell hyperplasia, squamous cell metaplasia, epithelial-mesenchymal transition, altered ciliated and nonmucous secretory cell differentiation, and suppression of junctional barrier integrity. Significant progress has been recently made in understanding the biology of human airway BC, including gene expression features, stem/progenitor, and other functions, including interaction with other airway cell types. Accumulating evidence suggests that human airway BC function as both sensors and cellular sources of various cytokines and growth factors relevant to smoking-associated airway injury, as well as the origin of various molecular and histological phenotypes relevant to the pathogenesis of COPD. In the context of these considerations, we suggest that early BC-specific smoking-induced molecular changes are critical to the pathogenesis of COPD, and these represent a candidate target for novel therapeutic approaches to prevent COPD progression in susceptible individuals. PMID:25525728

  3. Immediate early responses of avian tracheal epithelial cells to infection with highly pathogenic avian influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic (HP) avian influenza viruses (AIV) present an on going threat to the U.S. poultry industry. In order to develop new AIV control strategies it is necessary to understand the underlying mechanism of viral infection. Because the early events of AIV infection can occur on tracheal ep...

  4. Detachment-induced autophagy during anoikis and lumen formation in epithelial acini.

    PubMed

    Debnath, Jayanta

    2008-04-01

    The individual units (called acini) comprising glandular epithelium possess a hollow lumen that is filled in early epithelial cancers. While investigating the generation of this hollow lumen using an in vitro three-dimensional (3D) epithelial cell culture model, we observed extensive autophagy in dying cells during lumen formation, and thus, proposed that excessive self-eating may promote cell death in the lumen. However, we now reassess this hypothesis. Because cells in the lumen die due to extracellular matrix (ECM) deprivation (anoikis), we tested if autophagy is regulated by ECM detachment. We discovered that detachment strongly induces autophagy in epithelial cells, even when apoptosis is inhibited by Bcl-2 expression. RNAi-mediated depletion of autophagy-related (ATG) genes inhibits detachment-induced autophagy, resulting in increased apoptosis and reduced clonogenic recovery following anoikis. Similarly, during 3D morphogenesis, ATG-depletion enhances luminal apoptosis and fails to elicit long-term luminal survival and filling, even when combined with apoptotic inhibition. Thus, autophagy promotes epithelial cell survival during anoikis. These results broach the possibility that autophagy contributes to the survival of tumor cells lacking appropriate matrix contact, either during early carcinoma formation or in the later stages of dissemination and metastasis. PMID:18196957

  5. Early pregnancy sex steroids and maternal risk of epithelial ovarian cancer

    PubMed Central

    Schock, Helena; Surcel, Heljä-Marja; Zeleniuch-Jacquotte, Anne; Grankvist, Kjell; Lakso, Hans-Åke; Fortner, Renée Turzanski; Kaaks, Rudolf; Pukkala, Eero; Lehtinen, Matti; Toniolo, Paolo; Lundin, Eva

    2014-01-01

    Well-established associations between reproductive characteristics and epithelial ovarian cancer (EOC) support an involvement of sex steroid hormones in the etiology of EOC. Limited prior studies have evaluated circulating androgens and risk of EOC, and estrogens and progesterone have been investigated in only one prior study. Further, there is little data on potential heterogeneity in the association between circulating hormones and EOC by histologic subgroup. Therefore, we conducted a nested case-control study within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort to investigate the associations between circulating pre-diagnostic sex steroid concentrations with the histologic subtypes of EOC. We identified 1,052 EOC cases among cohort members diagnosed after recruitment (1975-2008) and before March 2011. Up to three controls were individually matched to each case (n=2,694). Testosterone, androstenedione, 17-hydroxyprogesterone (17-OHP), progesterone, estradiol, and sex hormone-binding globulin were measured in serum samples collected during the last pregnancy before EOC diagnosis. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals [CI]. Associations between hormones and EOC differed by tumor histology and invasiveness. Sex steroid concentrations were not associated with invasive serous tumors, however, doubling of testosterone and 17-OHP concentration was associated with ~40% increased risk of borderline serous tumors. A doubling of androgen concentrations was associated with a 50% risk increase for mucinous tumors. Risk of endometrioid tumors increased with higher estradiol concentrations (OR: 1.89 [1.20-2.98]). This large prospective study in pregnant women supports a role of sex steroid hormones in the etiology of EOC arising in the ovaries. PMID:25270324

  6. In Liddle Syndrome, Epithelial Sodium Channel Is Hyperactive Mainly in the Early Part of the Aldosterone-Sensitive Distal Nephron.

    PubMed

    Nesterov, Viatcheslav; Krueger, Bettina; Bertog, Marko; Dahlmann, Anke; Palmisano, Ralf; Korbmacher, Christoph

    2016-06-01

    The epithelial sodium channel (ENaC) is rate limiting for Na(+) absorption in the aldosterone-sensitive distal nephron comprising the late distal convoluted tubule (DCT2), the connecting tubule (CNT), and the entire collecting duct. Liddle syndrome (pseudohyperaldosteronism), a severe form of salt-sensitive hypertension, is caused by gain-of-function mutations of ENaC, but the precise tubular site of increased ENaC function is unknown. In the cortical collecting duct (CCD), ENaC is known to be regulated by aldosterone. In contrast, we recently reported aldosterone-independent ENaC regulation in the early part of the aldosterone-sensitive distal nephron. Here, we investigated ENaC function in the transition zone of DCT2/CNT or CNT/CCD microdissected from mice homozygous for Liddle syndrome mutation or from wild-type control mice. Whole-cell patch-clamp recordings were used to measure amiloride-sensitive ENaC currents in nephron fragments from mice maintained on different sodium diets to vary plasma aldosterone levels. Our data indicate that in mice with Liddle syndrome, the primary site of increased Na(+) reabsorption is the DCT2/CNT. In addition, increased aldosterone responsiveness of ENaC in CNT/CCD may contribute to salt-sensitive hypertension in Liddle syndrome. Single channel properties of ENaC were similar in Liddle syndrome mutation and wild-type mice, but ENaC expression at the apical membrane was increased in Liddle syndrome mutation when compared with wild-type mice, in particular, in animals maintained on a high salt diet. Our findings highlight the importance of ENaC function and regulation in the early part of the aldosterone-sensitive distal nephron for the maintenance of sodium balance and blood pressure control. PMID:27170740

  7. Genetics and biochemistry of collagen binding-triggered glandular differentiation in a human colon carcinoma cell line

    SciTech Connect

    Pignatelli, M.; Bodmer, W.F. )

    1988-08-01

    The authors have examined the interaction between collagen binding and epithelial differentiation by using a human colon carcinoma cell line (SW1222) that can differentiate structurally when grown in a three-dimensional collagen gel to form glandular structures. As much as 66% inhibition of glandular differentiation can be achieved by addition to the culture of a synthetic peptide containing the Arg-Gly-Asp-Thr (RGDT) sequence, which is a cell recognition site found in collagen. Arg-Gly-Asp-Thr also inhibited the cell attachment to collagen-coated plates. Chromosome 15 was found in all human-mouse hybrid clones that could differentiate in the collagen gel and bind collagen. Both binding to collagen and glandular differentiation of the hybrid cells were also inhibited by Arg-Gly-Asp-Thr as for the parent cell line SW1222. The ability of SW1222 cells to express the differentiated phenotype appears, therefore, to be determined by an Arg-Gly-Asp-directed collagen receptor on the cell surface that is controlled by a gene on chromosome 15.

  8. The nonvolatile metabolome of sunflower linear glandular trichomes.

    PubMed

    Spring, Otmar; Pfannstiel, Jens; Klaiber, Iris; Conrad, Jürgen; Beifuß, Uwe; Apel, Lysanne; Aschenbrenner, Anna-Katharina; Zipper, Reinhard

    2015-11-01

    Uniseriate linear glandular trichomes occur on stems, leaves and flowering parts of Helianthus species and related taxa. Their metabolic activity and biological function are still poorly understood. A phytochemical study documented the accumulation of bisabolene type sesquiterpenes and flavonoids as the major constituents of the non-volatile metabolome of linear glandular trichomes in the common sunflower, Helianthus annuus. Besides known sesquiterpenes of the glandulone, helibisabonol and heliannuol type, four previously undescribed sesquiterpenes named glandulone D, E, F and helibisabonol C were identified by spectroscopic analysis. In addition, four known nevadensin type flavonoids varying in O-methoxy substitutions were found. None of them has previously been reported from Helianthus annuus. PMID:26412774

  9. Tobacco NtLTP1, a glandular-specific lipid transfer protein, is required for lipid secretion from glandular trichomes.

    PubMed

    Choi, Yong Eui; Lim, Soon; Kim, Hyun-Jung; Han, Jung Yeon; Lee, Mi-Hyun; Yang, Yanyan; Kim, Ji-Ah; Kim, Yun-Soo

    2012-05-01

    Glandular trichomes are the phytochemical factories of plants, and they secrete a wide range of commercially important natural products such as lipids, terpenes and flavonoids. Herein, we report that the Nicotiana tabacum LTP1 (NtLTP1) gene, which is specifically expressed in long glandular trichomes, plays a role in lipid secretion from trichome heads. NtLTP1 mRNA is abundantly transcribed in trichomes, but NtLTP3, NtLTP4 and NtLTP5 are not. In situ hybridization revealed that NtLTP1 mRNAs accumulate specifically in long trichomes and not in short trichomes or epidermal cells. X-gluc staining of leaves from a transgenic plant expressing the NtLTP1 promoter fused to a GUS gene revealed that NtLTP1 protein accumulated preferentially on the tops of long glandular trichomes. GFP fluorescence from transgenic tobacco plants expressing an NtLTP1-GFP fusion protein was localized at the periphery of cells and in the excreted liquid droplets from the glandular trichome heads. In vitro assays using a fluorescent 2-p-toluidinonaphthalene-6-sulfonate probe indicated that recombinant NtLTP1 had lipid-binding activity. The overexpression of NtLTP1 in transgenic tobacco plants resulted in the increased secretion of trichome exudates, including epicuticular wax. In transgenic NtLTP1-RNAi lines, liquid secretion from trichomes was strongly reduced, but epicuticular wax secretion was not altered. Moreover, transgenic tobacco plants overexpressing NtLTP1 showed increased protection against aphids. Taken together, these data suggest that NtLTP1 is abundantly expressed in long glandular trichomes, and may play a role in lipid secretion from long glandular trichomes. PMID:22171964

  10. Glandular Trichomes and Essential Oil of Thymus quinquecostatus

    PubMed Central

    Jia, Ping; Liu, Hanzhu; Gao, Ting; Xin, Hua

    2013-01-01

    The distribution and types of glandular trichomes and essential oil chemistry of Thymus quinquecostatus were studied. The glandular trichomes are distributed on the surface of stem, leaf, rachis, calyx and corolla, except petiole, pistil and stamen. Three morphologically distinct types of glandular trichomes are described. Peltate trichomes, consisting of a basal cell, a stalk cell and a 12-celled head, are distributed on the stem, leaf, corolla and outer side of calyx. Capitate trichomes, consisting of a unicellular base, a 1–2-celled stalk and a unicellular head, are distributed more diffusely than peltate ones, existing on stem, leaf, rachis and calyx. Digitiform trichomes are just distributed on the outer side of corolla, consisting of 1 basal cell, 3 stalk cells and 1 head cell. All three types of glandular trichomes can secrete essential oil, and in small capitate trichomes of rachis, all peltate trichomes and digitiform trichomes, essential oil is stored in a large subcuticular space, released by cuticle rupture, whereas, in other capitate trichomes, essential oil crosses the thin cuticle. The essential oil of T. quinquecostatus is yellow, and its content is highest in the growth period. 68 constituents were identified in the essential oils. The main constituent is linalool. PMID:24250266

  11. Glandular Odontogenic Cyst of Mandible: A Rare Entity

    PubMed Central

    Mittal, Ankur; Kaur, Gursheen; Sood, Neena

    2015-01-01

    Glandular odontogenic cyst (GOC) is a rare developmental odontogenic cyst. It is a slow growing and asymptomatic swelling, usually affecting middle aged men and has tendency to reoccur. Here, we report a case of GOC in the anterior portion of mandible diagnosed by histopathology. PMID:26813085

  12. Glandular dose in breast computed tomography with synchrotron radiation.

    PubMed

    Mettivier, G; Fedon, C; Di Lillo, F; Longo, R; Sarno, A; Tromba, G; Russo, P

    2016-01-21

    The purpose of this work is to provide an evaluation of the mean glandular dose (MGD) for breast computed tomography (CT) with synchrotron radiation in an axial scanning configuration with a partial or total organ volume irradiation, for the in vivo program of breast CT ongoing at the ELETTRA facility (Trieste, Italy). A Geant4 Monte Carlo code was implemented, simulating the photon irradiation from a synchrotron radiation source in the energetic range from 8 to 50 keV with 1 keV intervals, to evaluate the MGD. The code was validated with literature data, in terms of mammographic normalized glandular dose coefficients (DgN) and with ad hoc experimental data, in terms of computed tomography dose index (CTDI). Simulated cylindrical phantoms of different sizes (diameter at phantom base 8, 10, 12, 14 or 16 cm, axial length 1.5 times the radius) and glandular fraction by weight (0%, 14.3%, 25%, 50%, 75% and 100%) were implemented into the code. The validation of the code shows an excellent agreement both with previously published work and in terms of DgN and CDTI measurements. The implemented simulations show a dependence of the glandular dose estimate on the vertical dimension of the irradiated zone when a partial organ irradiation was implemented. Specific normalized coefficients for calculating the MGD to the whole breast or to the single irradiated slice were reported. PMID:26683710

  13. Glandular dose in breast computed tomography with synchrotron radiation

    NASA Astrophysics Data System (ADS)

    Mettivier, G.; Fedon, C.; Di Lillo, F.; Longo, R.; Sarno, A.; Tromba, G.; Russo, P.

    2016-01-01

    The purpose of this work is to provide an evaluation of the mean glandular dose (MGD) for breast computed tomography (CT) with synchrotron radiation in an axial scanning configuration with a partial or total organ volume irradiation, for the in vivo program of breast CT ongoing at the ELETTRA facility (Trieste, Italy). A Geant4 Monte Carlo code was implemented, simulating the photon irradiation from a synchrotron radiation source in the energetic range from 8 to 50 keV with 1 keV intervals, to evaluate the MGD. The code was validated with literature data, in terms of mammographic normalized glandular dose coefficients (DgN) and with ad hoc experimental data, in terms of computed tomography dose index (CTDI). Simulated cylindrical phantoms of different sizes (diameter at phantom base 8, 10, 12, 14 or 16 cm, axial length 1.5 times the radius) and glandular fraction by weight (0%, 14.3%, 25%, 50%, 75% and 100%) were implemented into the code. The validation of the code shows an excellent agreement both with previously published work and in terms of DgN and CDTI measurements. The implemented simulations show a dependence of the glandular dose estimate on the vertical dimension of the irradiated zone when a partial organ irradiation was implemented. Specific normalized coefficients for calculating the MGD to the whole breast or to the single irradiated slice were reported.

  14. [The glandular odontogenic cyst--a rare entity].

    PubMed

    Brauer, H U; Manegold-Brauer, G

    2014-05-01

    In this short communication, the very rare glandular odontogenic cyst (GOC) is presented as an independent entity. The GOC is a jawbone cyst of the maxilla and mandible. The typical radiological and histopathological characteristics of the GOC are described. Furthermore, differential diagnoses, current treatment options and the recurrence rates of this of entity are discussed. PMID:24633391

  15. Proteomics of the human endometrial glandular epithelium and stroma from the proliferative and secretory phases of the menstrual cycle.

    PubMed

    Hood, Brian L; Liu, Baoquan; Alkhas, Addie; Shoji, Yutaka; Challa, Rusheeswar; Wang, Guisong; Ferguson, Susan; Oliver, Julie; Mitchell, Dave; Bateman, Nicholas W; Zahn, Christopher M; Hamilton, Chad A; Payson, Mark; Lessey, Bruce; Fazleabas, Asgerally T; Maxwell, G Larry; Conrads, Thomas P; Risinger, John I

    2015-04-01

    Despite its importance in reproductive biology and women's health, a detailed molecular-level understanding of the human endometrium is lacking. Indeed, no comprehensive studies have been undertaken to elucidate the important protein expression differences between the endometrial glandular epithelium and surrounding stroma during the proliferative and midsecretory phases of the menstrual cycle. We utilized laser microdissection to harvest epithelial cells and stromal compartments from proliferative and secretory premenopausal endometrial tissue and performed a global, quantitative mass spectrometry-based proteomics analysis. This analysis identified 1224 total proteins from epithelial cells, among which 318 were differentially abundant between the proliferative and secretory phases (q < 0.05), and 1005 proteins from the stromal compartments, 19 of which were differentially abundant between the phases (q < 0.05). Several proteins were chosen for validation by immunohistochemistry in an independent set of uterine tissues, including carboxypeptidase M, tenascin C, neprilysin, and ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3). ENPP3, which was elevated in epithelial glandular cells in the secretory phase, was confirmed to be elevated in midsecretory-phase baboon uterine lavage samples and also observed to have an N-linked glycosylated form that was not observed in the proliferative phase. This study provides a detailed view into the global proteomic alterations of the epithelial cells and stromal compartments of the cycling premenopausal endometrium. These proteomic alterations during endometrial remodeling provide a basis for numerous follow-up investigations on the function of these differentially regulated proteins and their role in reproductive biology and endometrial pathologies. PMID:25695723

  16. Glandular Proteome Identifies Antiprotease Cystatin C as a Critical Modulator of Airway Hydration and Clearance.

    PubMed

    Evans, T Idil Apak; Joo, Nam Soo; Keiser, Nicholas W; Yan, Ziying; Tyler, Scott R; Xie, Weiliang; Zhang, Yulong; Hsiao, Jordy J; Cho, Hyung-Ju; Wright, Michael E; Wine, Jeffrey J; Engelhardt, John F

    2016-04-01

    Defects in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel lead to viscous secretions from submucosal glands that cannot be properly hydrated and cleared by beating cilia in cystic fibrosis (CF) airways. The mechanisms by which CFTR, and the predominant epithelial sodium channel (ENaC), control the hydration and clearance of glandular secretions remain unclear. We used a proteomics approach to characterize the proteins contained in CF and non-CF submucosal gland fluid droplets and found that differentially regulated proteases (cathepsin S and H) and their antiprotease (cystatin C) influenced the equilibration of fluid on the airway surface and tracheal mucociliary clearance (MCC). Contrary to prevailing models of airway hydration and clearance, cystatin C, or raising the airway surface liquid (ASL) pH, inhibited cathepsin-dependent ENaC-mediated fluid absorption and raised the height of ASL, and yet decreased MCC velocity. Importantly, coupling of both CFTR and ENaC activities were required for effective MCC and for effective ASL height equilibration after volume challenge. Cystatin C-inhibitable cathepsins controlled initial phases of ENaC-mediated fluid absorption, whereas CFTR activity was required to prevent ASL dehydration. Interestingly, CF airway epithelia absorbed fluid more slowly owing to reduced cysteine protease activity in the ASL but became abnormally dehydrated with time. Our findings demonstrate that, after volume challenge, pH-dependent protease-mediated coupling of CFTR and ENaC activities are required for rapid fluid equilibration at the airway surface and for effective MCC. These findings provide new insights into how glandular fluid secretions may be equilibrated at the airway surface and how this process may be impaired in CF. PMID:26334941

  17. A novel texture descriptor for detection of glandular structures in colon histology images

    NASA Astrophysics Data System (ADS)

    Sirinukunwattana, Korsuk; Snead, David R.; Rajpoot, Nasir M.

    2015-03-01

    The first step prior to most analyses on most histopathology images is the detection of area of interest. In this work, we present a superpixel-based approach for glandular structure detection in colon histology images. An image is first segmented into superpixels with the constraint on the presence of glandular boundaries. Texture and color information is then extracted from each superpixel to calculate the probability of that superpixel belonging to glandular regions, resulting in a glandular probability map. In addition, we present a novel texture descriptor derived from a region covariance matrix of scattering coefficients. Our approach shows encouraging results for the detection of glandular structures in colon tissue samples.

  18. Fate of the major outer membrane protein P.IA in early and late events of gonococcal infection of epithelial cells.

    PubMed

    Weel, J F; van Putten, J P

    1991-01-01

    We investigated the fate of the major outer membrane protein of Neisseria gonorrhoeae, P.IA, during gonococcal infection of Chang conjunctiva epithelial cells by using immunoelectron microscopy. Probing of P.IA epitopes with mono- and polyclonal antibodies revealed variable, fixation-dependent P.IA epitope exposure in the gonococci used as an inoculum in the infection experiments. Detection of invariable exposed P.IA epitopes in cryosections of infected epithelial cells with a polyclonal antiserum revealed unaltered P.IA exposure on the bacterial membranes during early attachment of the bacteria to the eukaryotic cells. Upon entry of the bacteria into the host cells, however, labelling was extended to membraneous structures that intercalated between the bacteria and the host cell surface, and, occasionally, to the host cell plasma membrane. The latter observation is consistent with the suggested active role of P.I. in the uptake process (as shown in 1985 by E.C. Gotschlich). Once inside the epithelial cells, both morphologically intact and disintegrating bacteria could be distinguished. The disintegration of the bacteria was accompanied by a loss of P.IA immunoreactivity. PMID:1725221

  19. Detecting uterine glandular lesions: Role of cervical cytology

    PubMed Central

    Bansal, Baneet; Gupta, Parikshaa; Gupta, Nalini; Rajwanshi, Arvind; Suri, Vanita

    2016-01-01

    Background: The sensitivity of cervical cytology for detection of glandular lesions is reported to be low. We conducted this study to assess the diagnostic accuracy of cervical Papanicolaou (Pap) smears for uterine glandular lesions and to compare the diagnostic utility of conventional and liquid-based cytology (LBC) smears for glandular lesions. Materials and Methods: Archived histopathology records of all cases reported as endocervical and endometrial adenocarcinoma in the study period were identified and the available corresponding Pap smears (in preceding 1 year) were retrieved. In addition, the Pap smears reported as glandular cell abnormalities (GCA) during the same study period were retrieved. The overall prevalence of GCA, sensitivity, and specificity of Pap smears for the detection of GCA was calculated. The diagnostic accuracy of conventional and LBC smears for the diagnosis of GCA was also compared. Results: The prevalence of GCA in our study was 0.32%. The overall specificity of Pap smears for the diagnosis of GCA was 60.8%, this was not significantly different between conventional and LBC smears (P = 0.4). The overall sensitivity of Pap smears for the detection of GCA was 41.8%; LBC smears had significantly better sensitivity as compared to conventional smears for the detection of endometrial as compared to endocervical adenocarcinoma (P < 0.05). Conclusions: The prevalence of GCA in Pap smears is low. The specificity of Pap smears, for diagnosis of GCA, was found to be moderate. However, the overall sensitivity of Pap smears for the detection of GCA was low, though better for LBC as compared to conventional smears. PMID:27014363

  20. Genetic basis for glandular trichome formation in cotton.

    PubMed

    Ma, Dan; Hu, Yan; Yang, Changqing; Liu, Bingliang; Fang, Lei; Wan, Qun; Liang, Wenhua; Mei, Gaofu; Wang, Lingjian; Wang, Haiping; Ding, Linyun; Dong, Chenguang; Pan, Mengqiao; Chen, Jiedan; Wang, Sen; Chen, Shuqi; Cai, Caiping; Zhu, Xiefei; Guan, Xueying; Zhou, Baoliang; Zhu, Shuijin; Wang, Jiawei; Guo, Wangzhen; Chen, Xiaoya; Zhang, Tianzhen

    2016-01-01

    Trichomes originate from epidermal cells and can be classified as either glandular or non-glandular. Gossypium species are characterized by the presence of small and darkly pigmented lysigenous glands that contain large amounts of gossypol. Here, using a dominant glandless mutant, we characterize GoPGF, which encodes a basic helix-loop-helix domain-containing transcription factor, that we propose is a positive regulator of gland formation. Silencing GoPGF leads to a completely glandless phenotype. A single nucleotide insertion in GoPGF, introducing a premature stop codon is found in the duplicate recessive glandless mutant (gl2gl3). The characterization of GoPGF helps to unravel the regulatory network of glandular structure biogenesis, and has implications for understanding the production of secondary metabolites in glands. It also provides a potential molecular basis to generate glandless seed and glanded cotton to not only supply fibre and oil but also provide a source of protein for human consumption. PMID:26795254

  1. Genetic basis for glandular trichome formation in cotton

    PubMed Central

    Ma, Dan; Hu, Yan; Yang, Changqing; Liu, Bingliang; Fang, Lei; Wan, Qun; Liang, Wenhua; Mei, Gaofu; Wang, Lingjian; Wang, Haiping; Ding, Linyun; Dong, Chenguang; Pan, Mengqiao; Chen, Jiedan; Wang, Sen; Chen, Shuqi; Cai, Caiping; Zhu, Xiefei; Guan, Xueying; Zhou, Baoliang; Zhu, Shuijin; Wang, Jiawei; Guo, Wangzhen; Chen, Xiaoya; Zhang, Tianzhen

    2016-01-01

    Trichomes originate from epidermal cells and can be classified as either glandular or non-glandular. Gossypium species are characterized by the presence of small and darkly pigmented lysigenous glands that contain large amounts of gossypol. Here, using a dominant glandless mutant, we characterize GoPGF, which encodes a basic helix-loop-helix domain-containing transcription factor, that we propose is a positive regulator of gland formation. Silencing GoPGF leads to a completely glandless phenotype. A single nucleotide insertion in GoPGF, introducing a premature stop codon is found in the duplicate recessive glandless mutant (gl2gl3). The characterization of GoPGF helps to unravel the regulatory network of glandular structure biogenesis, and has implications for understanding the production of secondary metabolites in glands. It also provides a potential molecular basis to generate glandless seed and glanded cotton to not only supply fibre and oil but also provide a source of protein for human consumption. PMID:26795254

  2. Genetic and epigenetic changes in mammary epithelial cells identify a subpopulation of cells involved in early carcinogenesis.

    PubMed

    Berman, H; Zhang, J; Crawford, Y G; Gauthier, M L; Fordyce, C A; McDermott, K M; Sigaroudinia, M; Kozakiewicz, K; Tlsty, T D

    2005-01-01

    Morphologically normal foci of epithelial cells exhibiting p16 inactivation have been found in several tissues and may be precursors to cancer. Our previous work demonstrates that cells lacking p16(INK4A) activity exhibit phenotypes associated with malignancy (Romanov et al. 2001). The acquisition of genomic instability occurs through the activation of telomeric and centrosomal dysfunction. Additionally, the activation of stress pathways such as COX-2 provides these cells with the mutagenic potential to survive adverse environments as well as the ability to migrate, evade apoptosis and immune surveillance, and summon sustaining vasculature. Examination of archived tissue from women with DCIS (ductal carcinoma in situ) reveals epithelial cells that overexpress markers of premalignant stress activation pathways and mirror the distinctive expression patterns of these markers observed in vitro. These epithelial cells are found within the premalignant lesion as well as in the field of morphologically normal tissue that surrounds the lesion. Here, we show that p16(INK4A)-silenced vHMEC cells exhibit a gene expression profile which is distinct, reproducible, and extends beyond the changes mediated by p16(INK4A) inactivation. The present work suggests that cells lacking p16(INK4A) activity exhibit critical activities which allow cells to evade differentiation processes that would be expected to terminate proliferation. All of these properties are critical to malignancy. These events may be useful biomarkers to detect the earliest events in breast cancer. PMID:16869768

  3. Whole-Genome Analysis of Temporal Gene Expression during Early Transdifferentiation of Human Lung Alveolar Epithelial Type 2 Cells In Vitro

    PubMed Central

    Johansson, Helena Morales; Newman, Donna R.; Sannes, Philip L.

    2014-01-01

    It is generally accepted that the surfactant-producing pulmonary alveolar epithelial type II (AT2) cell acts as the progenitor of the type I (AT1) cell, but the regulatory mechanisms involved in this relationship remain the subject of active investigation. While previous studies have established a number of specific markers that are expressed during transdifferentiation from AT2 to AT1 cells, we hypothesized that additional, previously unrecognized, signaling pathways and relevant cellular functions are transcriptionally regulated at early stages of AT2 transition. In this study, a discovery-based gene expression profile analysis was undertaken of freshly isolated human AT2 (hAT2) cells grown on extracellular matrix (ECM) substrata known to either support (type I collagen) or retard (Matrigel) the early transdifferentiation process into hAT1-like cells over the first three days. Cell type-specific expression patterns analyzed by Illumina Human HT-12 BeadChip yielded over 300 genes that were up- or down-regulated. Candidate genes significantly induced or down-regulated during hAT2 transition to hAT1-like cells compared to non-transitioning hAT2 cells were identified. Major functional groups were also recognized, including those of signaling and cytoskeletal proteins as well as genes of unknown function. Expression of established signatures of hAT2 and hAT1 cells, such as surfactant proteins, caveolin-1, and channels and transporters, was confirmed. Selected novel genes further validated by qRT-PCR, protein expression analysis, and/or cellular localization included SPOCK2, PLEKHO1, SPRED1, RAB11FIP1, PTRF/CAVIN-1 and RAP1GAP. These results further demonstrate the utility of genome-wide analysis to identify relevant, novel cell type-specific signatures of early ECM-regulated alveolar epithelial transdifferentiation processes in vitro. PMID:24690998

  4. Identification of cholinergic chemosensory cells in mouse tracheal and laryngeal glandular ducts.

    PubMed

    Krasteva-Christ, G; Soultanova, A; Schütz, B; Papadakis, T; Weiss, C; Deckmann, K; Chubanov, V; Gudermann, T; Voigt, A; Meyerhof, W; Boehm, U; Weihe, E; Kummer, W

    2015-11-01

    Specialized epithelial cells in the respiratory tract such as solitary chemosensory cells and brush cells sense the luminal content and initiate protective reflexes in response to the detection of potentially harmful substances. The majority of these cells are cholinergic and utilize the canonical taste signal transduction cascade to detect "bitter" substances such as bacterial quorum sensing molecules. Utilizing two different mouse strains reporting expression of choline acetyltransferase (ChAT), the synthesizing enzyme of acetylcholine (ACh), we detected cholinergic cells in the submucosal glands of the murine larynx and trachea. These cells were localized in the ciliated glandular ducts and were neither found in the collecting ducts nor in alveolar or tubular segments of the glands. ChAT expression in tracheal gland ducts was confirmed by in situ hybridization. The cholinergic duct cells expressed the brush cell marker proteins, villin and cytokeratin-18, and were immunoreactive for components of the taste signal transduction cascade (Gα-gustducin, transient receptor potential melastatin-like subtype 5 channel = TRPM5, phospholipase C(β2)), but not for carbonic anhydrase IV. Furthermore, these cells expressed the bitter taste receptor Tas2r131, as demonstrated utilizing an appropriate reporter mouse strain. Our study identified a previously unrecognized presumptive chemosensory cell type in the duct of the airway submucosal glands that likely utilizes ACh for paracrine signaling. We propose that these cells participate in infection-sensing mechanisms and initiate responses assisting bacterial clearance from the lower airways. PMID:26033492

  5. New method for generating breast models featuring glandular tissue spatial distribution

    NASA Astrophysics Data System (ADS)

    Paixão, L.; Oliveira, B. B.; Oliveira, M. A.; Teixeira, M. H. A.; Fonseca, T. C. F.; Nogueira, M. S.

    2016-02-01

    Mammography is the main radiographic technique used for breast imaging. A major concern with mammographic imaging is the risk of radiation-induced breast cancer due to the high sensitivity of breast tissue. The mean glandular dose (DG) is the dosimetric quantity widely accepted to characterize the risk of radiation induced cancer. Previous studies have concluded that DG depends not only on the breast glandular content but also on the spatial distribution of glandular tissue within the breast. In this work, a new method for generating computational breast models featuring skin composition and glandular tissue distribution from patients undergoing digital mammography is proposed. Such models allow a more accurate way of calculating individualized breast glandular doses taking into consideration the glandular tissue fraction. Sixteen breast models of four patients with different glandularity breasts were simulated and the results were compared with those obtained from recommended DG conversion factors. The results show that the internationally recommended conversion factors may be overestimating the mean glandular dose to less dense breasts and underestimating the mean glandular dose for denser breasts. The methodology described in this work constitutes a powerful tool for breast dosimetry, especially for risk studies.

  6. ICAM-1 regulates the survival of influenza virus in lung epithelial cells during the early stages of infection.

    PubMed

    Othumpangat, Sreekumar; Noti, John D; McMillen, Cynthia M; Beezhold, Donald H

    2016-01-01

    Intercellular cell adhesion molecule-1 (ICAM-1) is an inducible cell surface glycoprotein that is expressed on many cell types. Influenza virus infection enhanced ICAM-1 expression and messenger RNA levels. Human bronchial epithelial cells (HBEpC) and nasal epithelial cells, on exposure to different strains of influenza virus (H1N1, H3N2, and H9N1) showed significant increase in ICAM-1 gene expression (p<0.001) along with the ICAM-1 protein levels (surface and secreted). Depleting ICAM-1 in HBEpC with ICAM-1 siRNA and subsequently infecting with H1N1 showed increased viral copy numbers. Influenza virus infection in HBEpC resulted in up-regulation of NF-ĸB protein and the lack of ICAM-1 decreased NF-ĸB activity in NF-ĸB luciferase reporter assay. Addition of exogenous IL-1β to HBEpC induced the ICAM-1 expression and decreased matrix gene copy number. Taken together, HBEpC induced ICAM-1 plays a key role in modulating the influenza virus survival possibly through the NF-ĸB pathway. PMID:26499045

  7. Agent-based model of human alveoli predicts chemotactic signaling by epithelial cells during early Aspergillus fumigatus infection.

    PubMed

    Pollmächer, Johannes; Figge, Marc Thilo

    2014-01-01

    Aspergillus fumigatus is one of the most important human fungal pathogens, causing life-threatening diseases. Since humans inhale hundreds to thousands of fungal conidia every day, the lower respiratory tract is the primary site of infection. Current interaction networks of the innate immune response attribute fungal recognition and detection to alveolar macrophages, which are thought to be the first cells to get in contact with the fungus. At present, these networks are derived from in vitro or in situ assays, as the peculiar physiology of the human lung makes in vivo experiments, including imaging on the cell-level, hard to realize. We implemented a spatio-temporal agent-based model of a human alveolus in order to perform in silico experiments of a virtual infection scenario, for an alveolus infected with A. fumigatus under physiological conditions. The virtual analog captures the three-dimensional alveolar morphology consisting of the two major alveolar epithelial cell types and the pores of Kohn as well as the dynamic process of respiration. To the best of our knowledge this is the first agent-based model of a dynamic human alveolus in the presence of respiration. A key readout of our simulations is the first-passage-time of alveolar macrophages, which is the period of time that elapses until the first physical macrophage-conidium contact is established. We tested for random and chemotactic migration modes of alveolar macrophages and varied their corresponding parameter sets. The resulting first-passage-time distributions imply that randomly migrating macrophages fail to find the conidium before the start of germination, whereas guidance by chemotactic signals derived from the alveolar epithelial cell associated with the fungus enables a secure and successful discovery of the pathogen in time. PMID:25360787

  8. Epigenetic alteration of Wnt pathway antagonists in progressive glandular neoplasia of the lung

    PubMed Central

    Licchesi, Julien D.F.; Westra, William H.; Hooker, Craig M.; Machida, Emi O.; Baylin, Stephen B.; Herman, James G.

    2008-01-01

    Background: Atypical adenomatous hyperplasia (AAH) is now recognized as a precursor lesion from which lung adenocarcinomas arise and thus represents an ideal target for studying the early genetic and epigenetic alterations associated with lung tumorigenesis such as alterations of the Wnt pathway. Methods: We assessed the level of Wnt signaling activity in lung cancer cell lines by determining the level of active β-catenin and determined the level of expression of Wnt antagonists APC, DKK1, DKK3, LKB1, SFRP1, 2, 4, 5, WIF1 and RUNX3 using reverse transcription–polymerase chain reaction. Using multiplex nested methylation-specific polymerase chain reaction, we analyzed promoter region methylation of these genes in resected lung tissue in the histopathologic sequence of glandular neoplasia (normal lung parenchyma, low-grade and high-grade AAH, adenocarcinoma). Results: The majority of non-small cell lung cancer cell lines (11 of 16, 69%) have evidence of active Wnt signaling and silencing of Wnt antagonists correlated with promoter hypermethylation. Promoter region methylation of Wnt antagonists was common in primary lung adenocarcinoma and there was a significant increase in the frequency of methylation for Wnt antagonist genes and the number of genes methylated with each stage of tumorigenesis (test for rend P ≤ 0.01). Additionally, odds ratios for promoter hypermethylation of individual or multiple Wnt antagonist genes and adenocarcinomas were statistically significantly elevated and ranged between 3.64 and 48.17. Conclusion: These results show that gene silencing of Wnt antagonists by promoter hypermethylation occurs during the earliest stages of glandular neoplasia of the lung and accumulates with progression toward malignancy. PMID:18308762

  9. Comparative Functional Genomic Analysis of Solanum Glandular Trichome Types1[W][OA

    PubMed Central

    McDowell, Eric T.; Kapteyn, Jeremy; Schmidt, Adam; Li, Chao; Kang, Jin-Ho; Descour, Anne; Shi, Feng; Larson, Matthew; Schilmiller, Anthony; An, Lingling; Jones, A. Daniel; Pichersky, Eran; Soderlund, Carol A.; Gang, David R.

    2011-01-01

    Glandular trichomes play important roles in protecting plants from biotic attack by producing defensive compounds. We investigated the metabolic profiles and transcriptomes to characterize the differences between different glandular trichome types in several domesticated and wild Solanum species: Solanum lycopersicum (glandular trichome types 1, 6, and 7), Solanum habrochaites (types 1, 4, and 6), Solanum pennellii (types 4 and 6), Solanum arcanum (type 6), and Solanum pimpinellifolium (type 6). Substantial chemical differences in and between Solanum species and glandular trichome types are likely determined by the regulation of metabolism at several levels. Comparison of S. habrochaites type 1 and 4 glandular trichomes revealed few differences in chemical content or transcript abundance, leading to the conclusion that these two glandular trichome types are the same and differ perhaps only in stalk length. The observation that all of the other species examined here contain either type 1 or 4 trichomes (not both) supports the conclusion that these two trichome types are the same. Most differences in metabolites between type 1 and 4 glands on the one hand and type 6 glands on the other hand are quantitative but not qualitative. Several glandular trichome types express genes associated with photosynthesis and carbon fixation, indicating that some carbon destined for specialized metabolism is likely fixed within the trichome secretory cells. Finally, Solanum type 7 glandular trichomes do not appear to be involved in the biosynthesis and storage of specialized metabolites and thus likely serve another unknown function, perhaps as the site of the synthesis of protease inhibitors. PMID:21098679

  10. Variation in the number of capitate glandular trichomes in wild and cultivated sunflower germplasm and potential for use in host plant resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Capitate glandular trichomes of wild sunflower (Helianthus spp.) are considered an effective defense against the sunflower moth, Homoeosoma electellum (Hulst), but cultivated sunflowers are reportedly deficient in glandular trichomes. To investigate whether glandular trichomes have a role in protect...

  11. Estimation of mean glandular dose for mammography of augmented breasts

    NASA Astrophysics Data System (ADS)

    Beckett, J. R.; Kotre, C. J.

    2000-11-01

    The standard quantity used to relate breast surface exposure to radiation risk is the mean dose received by the radiation sensitive tissue contained within the female breast, the mean glandular dose (MGD). At present, little is known about the MGD received by women with breast implants as there is no technique available to facilitate its calculation. The present work has involved modification of the conventional method for MGD estimation to make it applicable to women with augmented breasts. The technique was used to calculate MGDs for a cohort of 80 women with breast implants, which were compared with similar data calculated for a total of 1258 non-augmented women. Little difference was found in median MGD at low compressed breast thickness. At high breast thickness, however, the MGDs received by women with augmented breasts were found to be considerably lower than those relating to their non-augmented counterparts.

  12. Recurrent Glandular Odontogenic Cyst of Maxilla- A Case Report

    PubMed Central

    Jafarian, Amir Hosein; Rahpeyma, Amin; Khajehahmadi, Saeedeh

    2015-01-01

    The glandular odontogenic cyst (GOC) is a rare lesion with odontogenic origin. It shows a propensity for recurrence revealed in 30% of all case. This investigation reports a case of recurrent GOC in a 35-year-old female in the anterior region of the maxilla, which is uncommon and discusses about IHC finding, surgical methods, and differential diagnosis. Under general anesthesia, peripheral bone ostectomy via large round bur for removal of remaining epithelium of the cyst wall was done. Finally liquid nitrogen was used to remaining bone. This article recommends that soft tissue adjacent to the cortical bone perforation should be excised, as well as peripheral bone ostectomy by large round bur for removal of remaining epithelium of the cyst and liquid nitrogen application to the bony cavity. Because of high recurrence rate of the lesion close follow up of the patients is needed. PMID:26351478

  13. Use of laser capture microdissection for the assessment of equine lamellar basal epithelial cell signalling in the early stages of laminitis

    PubMed Central

    Leise, B. S.; Watts, M.; Roy, S.; Yilmaz, S.; Alder, H.; Belknap, J. K.

    2016-01-01

    Summary Reason for performing study Dysadhesion of the laminar basal epithelial cells (LBEC) from the underlying dermis is the central event leading to structural failure in equine laminitis. Although many studies of sepsis-related laminitis have reported multiple events occurring throughout the lamellar tissue, there is minimal information regarding signalling events occurring specifically in the LBEC. Objectives To determine the signalling events in the LBECs during the early stages of carbohydrate induced laminitis. Study Design Experimental study. Methods Eight horses were given an overload of carbohydrate (corn starch mixture, CHO) via nasogastric tube. Prior to administration of CHO, lamellar biopsies were taken from the left fore foot (CON). Biopsies were taken from the left hind foot at the onset of fever (DEV) and from the right fore foot at the onset of lameness (OG1). Laminar basal epithelial cells (LBECs) were isolated from cryosections using a LCM microscope. Next generation sequencing (RNA-Seq) was used to identify transcripts expressed in the LBECs for each time point and bioinformatic analysis was performed with thresholds for between group comparisons set at a greater than 2-fold change and p-value ≤0.05. Results Forty genes (22 increased/18 decreased) were significantly different from DEV time vs. CON and 107 genes (57 increased/50 decreased) were significantly different from OG1 time vs. CON. Significant increases in inflammatory genes were present in addition to significantly altered expression of genes related to extracellular matrix composition, stability and turnover. Conclusions Inflammatory response and extracellular matrix regulation signalling was strongly represented at the DEV and OG1 times. These results indicate that the LBEC is not only a casualty but also an active participant in lamellar events leading to structural failure of the digital lamellae in equine laminitis. PMID:24750316

  14. Early soy exposure via maternal diet regulates rat mammary epithelial differentiation by paracrine signaling from stromal adipocytes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diet-mediated changes in transcriptional programs that promote the early differentiation of the mammary gland may lead to reduced breast cancer risk. The disparity in adult breast cancer incidence between Asian women and Western counterparts is attributed partly to high soy food intake. Here, we con...

  15. Early pregnancy IGF-I and placental GH and risk of epithelial ovarian cancer: A nested case-control study

    PubMed Central

    Schock, Helena; Fortner, Renée T; Surcel, Heljä-Marja; Grankvist, Kjell; Pukkala, Eero; Lehtinen, Matti; Lundin, Eva

    2014-01-01

    Insulin-like growth factor-I (IGF-I) signaling may promote ovarian tumor development by exerting mitotic, anti-apoptotic, and pro-angiogenic effects. During pregnancy, maternal production of IGF-I is regulated by placental growth hormone (GH). Parity is an established protective factor for ovarian cancer, however, no prior study has evaluated placental GH and IGF-I in pregnancy and epithelial ovarian cancer (EOC). Prior prospective studies on the association between IGF-I and EOC in non-pregnant populations were inconclusive and did not address associations in subtypes of EOC. Among members of the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort we identified 1,045 EOC cases, diagnosed after recruitment (1975-2008) and before March 2011, and 2,658 individually matched controls. Placental GH and IGF-I were measured in serum from the last pregnancy before EOC diagnosis or selection as control. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals [CI] for tertiles and a doubling of hormone concentrations. Higher IGFI was associated with a non-significant decrease in risk for invasive (ORT3 vs. T1: 0.79 [0.62-1.02]; ptrend=0.07) and endometrioid tumors (ORT3 vs. T1: 0.55 [0.28-1.07]; ptrend=0.07). The protective association between higher IGF-I levels and risk of invasive EOC was stronger in analyses limited to women aged <55 years at diagnosis (ORT3 vs. T1: 0.74 [0.57-0.96]; ptrend=0.03). Our study provides the first data on placental GH and IGF-I in pregnancy and EOC risk overall and by subtype. Our data suggest higher IGF-I levels in pregnancy may be associated with lower risk of invasive and endometrioid EOC. PMID:25516257

  16. Early changes in gene expression induced by blue light irradiation of A2E-laden retinal pigment epithelial cells

    PubMed Central

    van der Burght, Barbro W.; Hansen, Morten; Olsen, Jørgen; Zhou, Jilin; Wu, Yalin; Nissen, Mogens H.; Sparrow, Janet R.

    2016-01-01

    Purpose Accumulation of bisretinoids as lipofuscin in retinal pigment epithelial (RPE) cells is implicated in the pathogenesis of some blinding diseases including age-related macular degeneration (AMD). To identify genes whose expression may change under conditions of bisretinoid accumulation, we investigated the differential gene expression in RPE cells that had accumulated the lipofuscin fluorophore A2E and were exposed to blue light (430 nm). Methods A2E-laden RPE cells were exposed to blue light (A2E/430 nm) at various time intervals. Cell death was quantified using Dead Red staining, and RNA levels for the entire genome was determined using DNA microarrays (Affymetrix GeneChip Human Genome 2.0 Plus). Array results for selected genes were confirmed by real-time reverse-transcriptase polymerase chain reaction. Results Principal component analysis revealed that the A2E-laden RPE cells irradiated with blue light were clearly distinguishable from the control samples. We found differential regulation of genes belonging to the following functional groups: transcription factors, stress response, apoptosis and immune response. Among the last mentioned were downregulation of four genes that coded for proteins that have an inhibitory effect on the complement cascade: (complement factor H, complement factor H-related 1, complement factor I and vitronectin) and of two belonging to the classical pathway (complement component 1, s subcomponent and complement component 1, r subcomponent). Conclusion This study demonstrates that blue light irradiation of A2E-laden RPE cells can alter the transcription of genes belonging to different functional pathways including stress response, apoptosis and the immune response. We suggest that these molecules may be associated to the pathogenesis of AMD and can potentially serve as future therapeutic targets. PMID:23742627

  17. Early pregnancy IGF-I and placental GH and risk of epithelial ovarian cancer: A nested case-control study.

    PubMed

    Schock, Helena; Fortner, Renée T; Surcel, Heljä-Marja; Grankvist, Kjell; Pukkala, Eero; Lehtinen, Matti; Lundin, Eva

    2015-07-15

    Insulin-like growth factor-I (IGF-I) signaling may promote ovarian tumor development by exerting mitotic, antiapoptotic and proangiogenic effects. During pregnancy, maternal production of IGF-I is regulated by placental growth hormone (GH). Parity is an established protective factor for ovarian cancer, however, no prior study has evaluated placental GH and IGF-I in pregnancy and epithelial ovarian cancer (EOC). Prior prospective studies on the association between IGF-I and EOC in nonpregnant populations were inconclusive and did not address associations in subtypes of EOC. Among members of the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort, we identified 1,045 EOC cases, diagnosed after recruitment (1975-2008) and before March 2011 and 2,658 individually matched controls. Placental GH and IGF-I were measured in serum from the last pregnancy before EOC diagnosis or selection as control. We used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles and a doubling of hormone concentrations. Higher IGF-I was associated with a nonsignificant decrease in risk for invasive [ORT3 vs. T1 : 0.79 (0.62-1.02); ptrend  = 0.07] and endometrioid tumors [ORT3 vs. T1 : 0.55 (0.28-1.07); ptrend  = 0.07]. The protective association between higher IGF-I levels and risk of invasive EOC was stronger in analyses limited to women aged <55 years at diagnosis [ORT3 vs. T1 : 0.74 (0.57-0.96); ptrend  = 0.03]. Our study provides the first data on placental GH and IGF-I in pregnancy and EOC risk overall and by subtype. Our data suggest higher IGF-I levels in pregnancy may be associated with lower risk of invasive and endometrioid EOC. PMID:25516257

  18. Tissue expression of glandular kallikrein and its response to 17 beta-estradiol in the acclimatized carp.

    PubMed

    Haussmann, Denise; Vidal, Rene; Figueroa, Jaime

    2006-06-01

    Cyprinus carpio skeletal muscle kallikrein was isolated to apparent homogeneity, and a polyclonal antiserum against the purified protein was generated. Glandular kallikrein expression and tissue distribution were assessed using both Western blots and immunohistochemistry. A 39-kDa protein was detected in skeletal muscle, the gill, kidney, and pituitary gland, where an additional 72-kDa immunoreactive band was observed. Immunohistochemistry revealed immunoreactive kallikrein in the intermuscle tissue, epithelial gill cells, apical portion of distal and proximal tubular cells in the kidney, mucus and epithelial cells of the skin, intestinal tube, and prolactin-producing cells of the pituitary gland. In addition, the effect of 17beta-estradiol on kallikrein expression was analyzed in three different tissues of winter- and summer-acclimatized male carps. A 2.5-fold (p<0.05) increase in kallikrein immunoreactivity due to estrogen treatment was observed in winter-acclimatized carp muscle, but not in summer-acclimatized fish. In contrast, the gill responded differently, since a 2-fold (p<0.05) increase was found only in summer-acclimatized carps. Kallikrein immunoreactivity in the kidney increased both in summer- (2.5 fold) and in winter-acclimatized carps (1.5 fold). The signals obtained demonstrate the existence of tissue-specific variable responses to estrogen treatment in vivo, between winter and summer-acclimatized carp. PMID:16849838

  19. Immunolocalization of E-cadherin and β-catenin in the cyclic and early pregnant canine endometrium.

    PubMed

    Payan-Carreira, R; Pires, M A; Santos, C; Holst, B Ström; Colaço, J; Rodriguez-Martinez, H

    2016-09-01

    Putative changes in E-cadherin and β-catenin during implantation in dogs are of interest to study, as they are relevant proteins for epithelial integrity. E-cadherin and β-catenin were immunolocalized in the canine endometrium during the estrous cycle and early pregnancy, using monoclonal antibodies. Both proteins were detected in all types of endometrial epithelia (surface epithelium [SE], superficial glandular, and deep glandular epithelia) at all stages of the estrous cycle and in early placental structures. E-cadherin depicted a gradient of intensity apparently being lowest in the SE to progressively increase toward the deepness of the endometrial glands, regardless of the stage of estrous cycle. The overall immunostaining was, however, weaker at diestrus. In pregnant samples, the trophoblast was conspicuously immunolabeled compared with the endometrial surface lining epithelium. In the latter, the cytoplasmic pattern predominated over the membrane-bound, as was also seen in the decidual cells of the placental labyrinth. In the early placenta, only trophoblast cells and lacunae retained membrane signals. β-Catenin membrane labeling appeared relatively constant throughout the cycle, although a tendency toward a decrease in intensity was detected at the secretory stages. In addition, a dislocation of the immunoreaction from membrane to the cytoplasm was observed in both the SE and the glandular epithelia at particular stages of the cycle. In early pregnancy, a loss of the membranous pattern was observed in the SE and labyrinth, but neither on trophoblast nor in lacunae. The results show the existence of a softening of the adherens junctional complex in progestagen-dominated stages favoring embryo-maternal interactions and endometrial invasion during canine implantation. PMID:27155731

  20. Breast dose in mammography is about 30% lower when realistic heterogeneous glandular distributions are considered

    SciTech Connect

    Hernandez, Andrew M.; Seibert, J. Anthony; Boone, John M.

    2015-11-15

    Purpose: Current dosimetry methods in mammography assume that the breast is comprised of a homogeneous mixture of glandular and adipose tissues. Three-dimensional (3D) dedicated breast CT (bCT) data sets were used previously to assess the complex anatomical structure within the breast, characterizing the statistical distribution of glandular tissue in the breast. The purpose of this work was to investigate the effect of bCT-derived heterogeneous glandular distributions on dosimetry in mammography. Methods: bCT-derived breast diameters, volumes, and 3D fibroglandular distributions were used to design realistic compressed breast models comprised of heterogeneous distributions of glandular tissue. The bCT-derived glandular distributions were fit to biGaussian functions and used as probability density maps to assign the density distributions within compressed breast models. The MCNPX 2.6.0 Monte Carlo code was used to estimate monoenergetic normalized mean glandular dose “DgN(E)” values in mammography geometry. The DgN(E) values were then weighted by typical mammography x-ray spectra to determine polyenergetic DgN (pDgN) coefficients for heterogeneous (pDgN{sub hetero}) and homogeneous (pDgN{sub homo}) cases. The dependence of estimated pDgN values on phantom size, volumetric glandular fraction (VGF), x-ray technique factors, and location of the heterogeneous glandular distributions was investigated. Results: The pDgN{sub hetero} coefficients were on average 35.3% (SD, 4.1) and 24.2% (SD, 3.0) lower than the pDgN{sub homo} coefficients for the Mo–Mo and W–Rh x-ray spectra, respectively, across all phantom sizes and VGFs when the glandular distributions were centered within the breast phantom in the coronal plane. At constant breast size, increasing VGF from 7.3% to 19.1% lead to a reduction in pDgN{sub hetero} relative to pDgN{sub homo} of 23.6%–27.4% for a W–Rh spectrum. Displacement of the glandular distribution, at a distance equal to 10% of the

  1. P11: 18FDG-PET/CT for early prediction of response to first line platinum chemotherapy in advanced thymic epithelial tumors

    PubMed Central

    Palmieri, Giovannella; Ottaviano, Margaret; Del Vecchio, Silvana; Segreto, Sabrina; Tucci, Irene; Damiano, Vincenzo

    2015-01-01

    Background To investigate the value of the metabolic tumor response assessed with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), compared with clinicobiological markers, to predict the response disease to first line platinum based chemotherapy in advanced thymic epithelial tumors (TETs). Methods Twenty patients with diagnosis of TET and stage of disease III and IV sec, Masaoka-Koga, were retrospectively included in this monocentric study. Different pre-treatment clinical, biological and pathological parameters, including histotype sec, WHO 2004 and stage of disease sec, Masaoka-Koga were assessed. Tumor glucose metabolism at baseline and its change after the first line platinum based chemotherapy (from 4 to 6 cycles) were assessed using FDG-PET, moreover the response disease was assessed using total body CT scan for the evaluation of RECIST criteria 1.1. Results Twelve patients had an objective response to the first line platinum based chemotherapy according RECIST criteria 1.1 and all of them started with a SUVmax at baseline major than 5, indeed the other eight patients, non-responders to chemotherapy, had a SUVmax at baseline minor than 5. Conclusions It is important to define the chemosensitivity of advanced TETs early. Combining bio-pathological parameters with the metabolism at baseline assessed with FDG-PET can help the physician to early predict the probability of obtaining a disease response to first line platinum based chemotherapy. The SUVmax cut off of 5 at 18FDG-PET/CT performed at baseline treatment might be a new parameter for choosing the most powerful first line of chemotherapy. Given these results, further prospective studies are needed to establish a new first line therapy in advanced TETs with a low SUVmax at baseline, non-responders to conventional chemotherapy.

  2. Dosimetry in Mammography: Average Glandular Dose Based on Homogeneous Phantom

    NASA Astrophysics Data System (ADS)

    Benevides, Luis A.; Hintenlang, David E.

    2011-05-01

    The objective of this study was to demonstrate that a clinical dosimetry protocol that utilizes a dosimetric breast phantom series based on population anthropometric measurements can reliably predict the average glandular dose (AGD) imparted to the patient during a routine screening mammogram. AGD was calculated using entrance skin exposure and dose conversion factors based on fibroglandular content, compressed breast thickness, mammography unit parameters and modifying parameters for homogeneous phantom (phantom factor), compressed breast lateral dimensions (volume factor) and anatomical features (anatomical factor). The patient fibroglandular content was evaluated using a calibrated modified breast tissue equivalent homogeneous phantom series (BRTES-MOD) designed from anthropomorphic measurements of a screening mammography population and whose elemental composition was referenced to International Commission on Radiation Units and Measurements Report 44 and 46 tissues. The patient fibroglandular content, compressed breast thickness along with unit parameters and spectrum half-value layer were used to derive the currently used dose conversion factor (DgN). The study showed that the use of a homogeneous phantom, patient compressed breast lateral dimensions and patient anatomical features can affect AGD by as much as 12%, 3% and 1%, respectively. The protocol was found to be superior to existing methodologies. The clinical dosimetry protocol developed in this study can reliably predict the AGD imparted to an individual patient during a routine screening mammogram.

  3. Dosimetry in Mammography: Average Glandular Dose Based on Homogeneous Phantom

    SciTech Connect

    Benevides, Luis A.; Hintenlang, David E.

    2011-05-05

    The objective of this study was to demonstrate that a clinical dosimetry protocol that utilizes a dosimetric breast phantom series based on population anthropometric measurements can reliably predict the average glandular dose (AGD) imparted to the patient during a routine screening mammogram. AGD was calculated using entrance skin exposure and dose conversion factors based on fibroglandular content, compressed breast thickness, mammography unit parameters and modifying parameters for homogeneous phantom (phantom factor), compressed breast lateral dimensions (volume factor) and anatomical features (anatomical factor). The patient fibroglandular content was evaluated using a calibrated modified breast tissue equivalent homogeneous phantom series (BRTES-MOD) designed from anthropomorphic measurements of a screening mammography population and whose elemental composition was referenced to International Commission on Radiation Units and Measurements Report 44 and 46 tissues. The patient fibroglandular content, compressed breast thickness along with unit parameters and spectrum half-value layer were used to derive the currently used dose conversion factor (DgN). The study showed that the use of a homogeneous phantom, patient compressed breast lateral dimensions and patient anatomical features can affect AGD by as much as 12%, 3% and 1%, respectively. The protocol was found to be superior to existing methodologies. The clinical dosimetry protocol developed in this study can reliably predict the AGD imparted to an individual patient during a routine screening mammogram.

  4. Evidence for estrogen-dependent uterine serpin (SERPINA14) expression during estrus in the bovine endometrial glandular epithelium and lumen.

    PubMed

    Ulbrich, Susanne E; Frohlich, Thomas; Schulke, Katy; Englberger, Eva; Waldschmitt, Nadine; Arnold, Georg J; Reichenbach, Horst-Dieter; Reichenbach, Myriam; Wolf, Eckhard; Meyer, Heinrich H D; Bauersachs, Stefan

    2009-10-01

    Uterine secretions have a dominant impact on the environment in which embryo development takes place. The uterine serpins (SERPINA14, previously known as UTMP) are found most abundantly during pregnancy in the uterus of ruminants. Although progesterone is currently assumed to be the major regulator of SERPINA14 expression, our recent study of transcriptome changes in bovine endometrium during the estrous cycle unexpectedly detected a marked upregulation of SERPINA14 mRNA levels at estrus. The present study describes the full-length mRNA sequence, genomic organization, and putative promoter elements of the SERPINA14 gene. The SERPINA14 mRNA abundance was quantified by real-time RT-PCR in intercaruncular endometrium at several time points during the estrous cycle and early pregnancy. Highest levels were found at estrus, followed by a dramatic decrease and a moderate expression during the luteal phase. Transcript levels were higher in pregnant endometrium compared with controls at Day 18. At estrus, immunoreactive protein was localized in deep glandular epithelium, and Western blotting concomitantly showed the 52-kDa form in uterine flushings. SERPINA14 mRNA was significantly upregulated in glandular endometrial cells in vitro after stimulation with estradiol-17beta and progesterone, but not after interferon-tau treatment. Our results clearly demonstrate that SERPINA14 appears distinctly in bovine endometrium during the estrus phase. A supporting role toward providing a well-prepared endometrial environment for passing gametes, especially sperm, is assumed. PMID:19494250

  5. IN VIVO AND IN VITRO CHARACTERISTICS OF EARLY CARCINOGEN-INDUCED PREMALIGNANT PHENOTYPES IN CULTURED RAT TRACHEAL EPITHELIAL CELLS (JOURNAL VERSION)

    EPA Science Inventory

    The initial stages of neoplastic transformation in respiratory tract epithelial cells were defined and studied by characterizing a series of morphologically transformed cell colonies from carcinogen-exposed rat tracheal epithelial (TRE) cell cultures both in vivo and in vitro. RT...

  6. [Study on characteristics of non-glandular hairs of cultivated Lonicera japonica].

    PubMed

    Zhang, Shan-shan; Yuan, Yuan; Huang, Lu-qi; Chen, Ping

    2015-02-01

    We collected 22 cultivated population of Lonicera japonica from 17 areas. The characteristics of non-glandular hairs were observed and measured by the scanning electron microscopy. The principal components analysis and correlation analysis were conduct based on length and density of L. japonica. The results showed a significant negative correlation between length and density of non-glandular hairs, and the characteristics of non-glandular was not corrrelated significantly with latitude. The correlation results indicated that the density was a key to separate "Damaohua" and "Jizhuahua". The contribution of climate and soil was important to the cultivated population. This reminded that the characteristics of non-glandular hairs were affected by environmental and genetic interaction. PMID:26084157

  7. In-vitro co-culture of early stage caprine embryos with oviduct and uterine epithelial cells.

    PubMed

    Prichard, J F; Thibodeaux, J K; Pool, S H; Blakewood, E G; Menezo, Y; Godke, R A

    1992-04-01

    Early stage caprine embryos were incubated with goat oviduct and uterine cells to evaluate whether these cells could be used as a somatic cell culture system to enhance development through the developmental block at the 8- to 16-cell stage during in-vitro culture. Following gonadotrophin treatment and natural mating, 2- to 4-cell embryos were surgically recovered from donor females for in-vitro culture studies. In Experiment 1, embryos were equally and randomly allotted to culture treatments of either culture medium plus caprine oviduct cells or culture medium alone. In both treatment groups, embryos were incubated in Medium-199 with 10% fetal bovine serum, 0.25% lactalbumin and 1% antibiotic-antimycotic at 37 degrees C in a humidified atmosphere of 5% CO2 in air. In Experiment 2, similar embryos were cultured in the same medium with either caprine oviduct cells, caprine uterine cells or sequentially incubated with oviduct cells and then uterine cells during a corresponding incubation interval. The culture conditions in Experiment 2 were the same as in Experiment 1. Following 72 h in culture, (Experiment 1), significantly more embryos developed through the in-vitro developmental block into blastocysts and hatched blastocysts when cultured with oviduct cells compared with no embryos developing through the in-vitro block when incubated with medium alone. In Experiment 2, caprine embryos co-cultured with oviduct cells alone resulted in more embryos developing into blastocysts and hatched blastocysts compared with those co-cultured with uterine cells alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1522202

  8. Autofluorescence as a Signal to Sort Developing Glandular Trichomes by Flow Cytometry.

    PubMed

    Bergau, Nick; Navarette Santos, Alexander; Henning, Anja; Balcke, Gerd U; Tissier, Alain

    2016-01-01

    The industrial relevance of a number of metabolites produced in plant glandular trichomes (GTs) has spurred research on these specialized organs for a number of years. Most of the research, however, has focused on the elucidation of secondary metabolite pathways and comparatively little has been undertaken on the development and differentiation of GTs. One way to gain insight into these developmental processes is to generate stage-specific transcriptome and metabolome data. The difficulty for this resides in the isolation of early stages of development of the GTs. Here we describe a method for the separation and isolation of intact young and mature type VI trichomes from the wild tomato species Solanum habrochaites. The final and key step of the method uses cell sorting based on distinct autofluorescence signals of the young and mature trichomes. We demonstrate that sorting by flow cytometry allows recovering pure fractions of young and mature trichomes. Furthermore, we show that the sorted trichomes can be used for transcript and metabolite analyses. Because many plant tissues or cells have distinct autofluorescence components, the principles of this method can be generally applicable for the isolation of specific cell types without prior labeling. PMID:27446176

  9. Autofluorescence as a Signal to Sort Developing Glandular Trichomes by Flow Cytometry

    PubMed Central

    Bergau, Nick; Navarette Santos, Alexander; Henning, Anja; Balcke, Gerd U.; Tissier, Alain

    2016-01-01

    The industrial relevance of a number of metabolites produced in plant glandular trichomes (GTs) has spurred research on these specialized organs for a number of years. Most of the research, however, has focused on the elucidation of secondary metabolite pathways and comparatively little has been undertaken on the development and differentiation of GTs. One way to gain insight into these developmental processes is to generate stage-specific transcriptome and metabolome data. The difficulty for this resides in the isolation of early stages of development of the GTs. Here we describe a method for the separation and isolation of intact young and mature type VI trichomes from the wild tomato species Solanum habrochaites. The final and key step of the method uses cell sorting based on distinct autofluorescence signals of the young and mature trichomes. We demonstrate that sorting by flow cytometry allows recovering pure fractions of young and mature trichomes. Furthermore, we show that the sorted trichomes can be used for transcript and metabolite analyses. Because many plant tissues or cells have distinct autofluorescence components, the principles of this method can be generally applicable for the isolation of specific cell types without prior labeling. PMID:27446176

  10. Glandular trichomes as an inflorescence defence mechanism against insect herbivores in Iberian columbines.

    PubMed

    Jaime, Rafael; Rey, Pedro J; Alcántara, Julio M; Bastida, Jesús M

    2013-08-01

    Glandular trichomes play a defensive role against herbivores in the leaves of many plant species. However, their functional role in inflorescences has not been studied, even though theory suggests that tissues with a higher fitness value, such as inflorescences, should be better defended. Using manipulative experiments, we analysed the defensive role of glandular trichomes against herbivorous insects in the inflorescence of Iberian columbines (genus Aquilegia), and its inter-population and inter-taxa variation in relation to herbivore abundance and potential selective pressure. The experiments were conducted in eight populations belonging to four subspecies of two columbines (Aquilegia vulgaris and Aquilegia pyrenaica). For each population, we estimated the density of glandular trichomes in the inflorescences, the abundance of insects stuck in the inflorescences, the abundance of small herbivorous insects, the incidence of damage on flowers and fruits, and the fruit set. The density of glandular trichomes on the inflorescence of A. vulgaris and A. pyrenaica was higher in regions of higher herbivore abundance. We also found that when the plants lose the protection of glandular trichomes, small insects have better access to flowers and fruits, causing more damage and reducing plant fitness. This study concludes that glandular trichomes are part of an adaptive response against phytophagous insect herbivory. The observed variation in herbivore pressure between taxa, likely caused by habitat differentiation, might have played a role in trait differentiation through divergent selection. This result adds evidence to the differentiation of the Iberian columbines through habitat specialization. PMID:23247688

  11. Retinal pigment epithelial expression of complement regulator CD46 is altered early in the course of geographic atrophy.

    PubMed

    Vogt, Susan D; Curcio, Christine A; Wang, Lan; Li, Chuan-Ming; McGwin, Gerald; Medeiros, Nancy E; Philp, Nancy J; Kimble, James A; Read, Russell W

    2011-10-01

    In geographic atrophy (GA), the non-neovascular end stage of age-related macular degeneration (AMD), the macular retinal pigment epithelium (RPE) progressively degenerates. Membrane cofactor protein (MCP, CD46) is the only membrane-bound regulator of complement expressed on the human RPE basolateral surface. Based on evidence of the role of complement in AMD, we hypothesized that altered CD46 expression on the RPE would be associated with GA development and/or progression. Here we report the timeline of CD46 protein expression changes across the GA transition zone, relative to control eyes, and relative to events in other chorioretinal layers. Eleven donor eyes (mean age 87.0 ± 4.1 yr) with GA and 5 control eyes (mean age 84.0 ± 8.9 yr) without GA were evaluated. Macular cryosections were stained with PASH for basal deposits, von Kossa for calcium, and for CD46 immunoreactivity. Internal controls for protein expression were provided by an independent basolateral protein, monocarboxylate transporter 3 (MCT3) and an apical protein, ezrin. Within zones defined by 8 different semi-quantitative grades of RPE morphology, we determined the location and intensity of immunoreactivity, outer segment length, and Bruch's membrane calcification. Differences between GA and control eyes and between milder and more severe RPE stages in GA eyes were assessed statistically. Increasing grades of RPE degeneration were associated with progressive loss of polarity and loss of intensity of staining of CD46, beginning with the stages that are considered normal aging (grades 0-1). Those GA stages with affected CD46 immunoreactivity exhibited basal laminar deposit, still-normal photoreceptors, and concomitant changes in control protein expression. Activated or anteriorly migrated RPE (grades 2-3) exhibited greatly diminished CD46. Changes in RPE CD46 expression thus occur early in GA, before there is evidence of morphological RPE change. At later stages of degeneration, CD46

  12. Computation of the glandular radiation dose in digital tomosynthesis of the breast

    PubMed Central

    Sechopoulos, Ioannis; Suryanarayanan, Sankararaman; Vedantham, Srinivasan; D’Orsi, Carl; Karellas, Andrew

    2008-01-01

    Tomosynthesis of the breast is currently a topic of intense interest as a logical next step in the evolution of digital mammography. This study reports on the computation of glandular radiation dose in digital tomosynthesis of the breast. Previously, glandular dose estimations in tomosynthesis have been performed using data from studies of radiation dose in conventional planar mammography. This study evaluates, using Monte Carlo methods, the normalized glandular dose (DgN) to the breast during a tomosynthesis study, and characterizes its dependence on breast size, tissue composition, and x-ray spectrum. The conditions during digital tomosynthesis imaging of the breast were simulated using a computer program based on the Geant4 toolkit. With the use of simulated breasts of varying size, thickness and tissue composition, the DgN to the breast tissue was computed for varying x-ray spectra and tomosynthesis projection angle. Tomosynthesis projections centered about both the cranio-caudal (CC) and medio-lateral oblique (MLO) views were simulated. For each projection angle, the ratio of the glandular dose for that projection to the glandular dose for the zero degree projection was computed. This ratio was denoted the relative glandular dose (RGD) coefficient, and its variation under different imaging parameters was analyzed. Within mammographic energies, the RGD was found to have a weak dependence on glandular fraction and x-ray spectrum for both views. A substantial dependence on breast size and thickness was found for the MLO view, and to a lesser extent for the CC view. Although RGD values deviate substantially from unity as a function of projection angle, the RGD averaged over all projections in a complete tomosynthesis study varies from 0.91 to 1.01. The RGD results were fit to mathematical functions and the resulting equations are provided. PMID:17278508

  13. Computation of the glandular radiation dose in digital tomosynthesis of the breast

    SciTech Connect

    Sechopoulos, Ioannis; Suryanarayanan, Sankararaman; Vedantham, Srinivasan; D'Orsi, Carl; Karellas, Andrew

    2007-01-15

    Tomosynthesis of the breast is currently a topic of intense interest as a logical next step in the evolution of digital mammography. This study reports on the computation of glandular radiation dose in digital tomosynthesis of the breast. Previously, glandular dose estimations in tomosynthesis have been performed using data from studies of radiation dose in conventional planar mammography. This study evaluates, using Monte Carlo methods, the normalized glandular dose (D{sub g}N) to the breast during a tomosynthesis study, and characterizes its dependence on breast size, tissue composition, and x-ray spectrum. The conditions during digital tomosynthesis imaging of the breast were simulated using a computer program based on the Geant4 toolkit. With the use of simulated breasts of varying size, thickness and tissue composition, the D{sub g}N to the breast tissue was computed for varying x-ray spectra and tomosynthesis projection angle. Tomosynthesis projections centered about both the cranio-caudal (CC) and medio-lateral oblique (MLO) views were simulated. For each projection angle, the ratio of the glandular dose for that projection to the glandular dose for the zero degree projection was computed. This ratio was denoted the relative glandular dose (RGD) coefficient, and its variation under different imaging parameters was analyzed. Within mammographic energies, the RGD was found to have a weak dependence on glandular fraction and x-ray spectrum for both views. A substantial dependence on breast size and thickness was found for the MLO view, and to a lesser extent for the CC view. Although RGD values deviate substantially from unity as a function of projection angle, the RGD averaged over all projections in a complete tomosynthesis study varies from 0.91 to 1.01. The RGD results were fit to mathematical functions and the resulting equations are provided.

  14. Benign epithelial inclusions in axillary lymph nodes: report of 18 cases and review of the literature.

    PubMed

    Fellegara, Giovanni; Carcangiu, Maria Luisa; Rosai, Juan

    2011-08-01

    The occurrence of various types of heterotopic epithelial structures in lymph nodes is a well-documented phenomenon. Here, we report on the presence of such inclusions in axillary lymph nodes. A total of 18 cases were identified. All patients were women, their ages ranging from 32 to 79 years (median, 57 y). Thirteen patients had concomitant or antecedent breast abnormalities, and 12 of them had undergone nodal sampling for staging purposes. The other 5 patients had noted enlarging axillary masses, with no clinical evidence of previous or concomitant breast or genital tract pathology. We classified the nodal inclusions on morphologic grounds into 3 main categories: those composed exclusively of glandular structures (glandular-type inclusions; 10 cases, 56%); those made up only of squamous cysts (squamous-type inclusions; 2 cases, 11%); and those containing both glandular and squamous epithelia (mixed glandular-squamous-type inclusions; 6 cases, 33%). We speculate about the possible mechanism for the migration of the epithelial cells into the lymph nodes, discuss the modifications that they may later undergo as a result of local and systemic factors, and consider the differential diagnosis with other conditions, particularly with metastatic well-differentiated breast carcinoma. PMID:21753696

  15. Up-regulation of early growth response gene 1 (EGR-1) via ERK1/2 signals attenuates sulindac sulfide-mediated cytotoxicity in the human intestinal epithelial cells

    SciTech Connect

    Moon, Yuseok Yang, Hyun; Kim, Yung Bu

    2007-09-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are used to relieve pain and inflammation and have also received considerable attention because of their preventive effects against human cancer. However, the drug application is sometimes limited by the severe gastrointestinal ulcers and mucosal complications. In the present study, NSAID sulindac sulfide was investigated for the cytotoxic injury in the intestinal epithelial cells in association with an immediate inducible factor, early growth response gene 1 (EGR-1). Previously we reported that sulindac sulfide can suppress tumor cell invasion by inducing EGR-1. Extending the previous study, EGR-1 induction by sulindac sulfide was observed both in the non-transformed and transformed human intestinal epithelial cell lines. In terms of signaling pathway, ERK1/2 MAP kinases and its substrate Elk-1 transcription factor were involved in the sulindac sulfide-induced EGR-1 gene expression. Moreover, sulindac sulfide stimulated the nuclear translocation of the transcription factor EGR-1, which was also mediated by ERK1/2 signaling pathway. The roles of EGR-1 signals in the apoptotic cell death were assessed in the intestinal epithelial cells. Suppression of EGR-1 expression retarded cellular growth and colony forming activity in the intestinal epithelial cells. Moreover, induced EGR-1 ameliorated sulindac sulfide-mediated apoptotic cell death and enhanced the cellular survival. Taken all together, sulindac sulfide activated ERK1/2 MAP kinases which then mediated EGR-1 induction and nuclear translocation, all of which played important roles in the cellular survival from NSAID-mediated cytotoxicity in the human intestinal epithelial cells, implicating the protective roles of EGR-1 in the NSAID-mediated mucosal injuries.

  16. Claudin immunolocalization in neonatal mouse epithelial tissues.

    PubMed

    Troy, Tammy-Claire; Arabzadeh, Azadeh; Yerlikaya, Seda; Turksen, Kursad

    2007-11-01

    Emerging evidence supports the notion that claudins (Cldns) are dynamically regulated under normal conditions to respond to the selective permeability requirements of various tissues, and that their expression is developmentally controlled. We describe the localization of those Cldns that we have previously demonstrated to be functionally important in epidermal differentiation and the formation of the epidermal permeability barrier, e.g., Cldn1, Cldn6, Cldn11, and Cldn18, and the presence of Cldn3 and Cldn5 in various neonatal mouse epithelia including the epidermis, nail, oral mucosa, tongue, and stomach. Cldn1 is localized in the differentiated and/or undifferentiated compartments of the epidermis and nail and in the dorsal surface of the tongue and glandular compartment of the stomach but is absent from the oral mucosa and the keratinized compartment of the stomach. Cldn3 is present in the basal cells of the nail matrix and both compartments of the murine stomach but not in the epidermis, oral mucosa, or tongue. Cldn5 is found in the glandular compartment of the stomach but not in the epidermis, nail unit, oral mucosa, forestomach, and tongue. Cldn6, Cldn11, and Cldn18 occur in the differentiating suprabasal compartment of the epidermis, nail, and oral mucosa and in the dorsal and ventral surfaces of the tongue and the keratinized squamous epithelium of the stomach. The simple columnar epithelium of the glandular stomach stains for Cldn18 and reveals a non-membranous pattern for Cldn6 and Cldn11 expression. Our results demonstrate differential Cldn protein profiles in various epithelial tissues and their differentiation stages. Although the molecular mechanisms regulating Cldn expression are unknown, elucidation of their differential localization patterns in tissues with diverse permeability requirements should provide a better understanding of the role of tight junctions in tissue function. PMID:17828607

  17. Influence of Environment on Glandular Trichomes and Composition of Essential Oil of Perovskia abrotanoides Karel.

    PubMed Central

    Oreizi, Elaheh; Rahiminejad, Mohammad Reza; Asghari, Gholamreza

    2014-01-01

    Background: Perovskia abrotanoides Karel. is a medicinal plant used in Iranian folk medicine as a pain killer. Forty-one components have been identified in P. abrotanoides samples collected from Baluchistan Province, and 29 components have been recognized in samples collected from Khorasan Province. The leaves of P. abrotanoides have glandular trichomes (capitates and peltate) on both sides of the lamina. Objectives: This study aimed to evaluate the variation of oil constituents of the plant and illustrate the glandular trichomes types and then show the influence of environment on oil constituents and glandular trichomes. Materials and Methods: The essential oil of the plant was obtained using hydrodistillation and the analysis of oils carried out using GC-MS. The anatomical analysis of leaves was done by fixing, coloring, and photoing the sections. Results: Glandular trichomes composed of capitates and peltate trichomes. The essential oil composition differs. Viridiflora and neryl acetate were not identified in yellow glandular trichomes. Conclusions: It seems that there is no relation between anatomical characteristics of the plant leaves and its essential oil composition. PMID:25625046

  18. Comparison of oxalate formation from ascorbic and glyoxyl acids in detached glandular heads of tobacco trichomes

    SciTech Connect

    Vogeli-Lange, R.; Wagner, G.J.

    1987-08-01

    Ca-oxalate crystal containing cells from detached glandular heads of trichomes from Nicotiana tabacum, TI 1068, are capable of converting (1-/sup 14/C) ascorbic acid (AA) and (1-/sup 14/C) glyoxylic acid (GA) to oxalate. AA was found to be a better precursor for oxalate formation than GA. In detached glandular heads, 3.6x more label was converted to oxalate from AA than from GA, in the epidermis the factor was 3x while that with petiole tissue was 7x. Oxalate formation from AA, in detached glandular heads, was only partially inhibited in the dark and in the presence of metabolic inhibitors, suggesting that a nonenzymatic component might be involved. Oxalate formation from GA increased in the presence of metabolic inhibitors. During treatment of detached glandular heads with 2 mM Ca-acetate for 2 days, oxalate formation from AA was stimulated 3 fold, while the presence of 2mM Ca-acetate had no effect on the oxalate formation from GA. These results suggest that Ca/sup 2 +/ stimulates the formation of Ca-oxalate crystals in glandular head cells, and that AA can serve as a precursor for oxalate production.

  19. Plant Glandular Trichomes as Targets for Breeding or Engineering of Resistance to Herbivores

    PubMed Central

    Glas, Joris J.; Schimmel, Bernardus C. J.; Alba, Juan M.; Escobar-Bravo, Rocío; Schuurink, Robert C.; Kant, Merijn R.

    2012-01-01

    Glandular trichomes are specialized hairs found on the surface of about 30% of all vascular plants and are responsible for a significant portion of a plant’s secondary chemistry. Glandular trichomes are an important source of essential oils, i.e., natural fragrances or products that can be used by the pharmaceutical industry, although many of these substances have evolved to provide the plant with protection against herbivores and pathogens. The storage compartment of glandular trichomes usually is located on the tip of the hair and is part of the glandular cell, or cells, which are metabolically active. Trichomes and their exudates can be harvested relatively easily, and this has permitted a detailed study of their metabolites, as well as the genes and proteins responsible for them. This knowledge now assists classical breeding programs, as well as targeted genetic engineering, aimed to optimize trichome density and physiology to facilitate customization of essential oil production or to tune biocide activity to enhance crop protection. We will provide an overview of the metabolic diversity found within plant glandular trichomes, with the emphasis on those of the Solanaceae, and of the tools available to manipulate their activities for enhancing the plant’s resistance to pests. PMID:23235331

  20. Digital breast tomosynthesis and digital mammography: A comparison of figures of merit for various average glandular doses

    NASA Astrophysics Data System (ADS)

    Kim, Ye-seul; Park, Hye-Suk; Park, SuJin; Kim, Hee-Joung; Choi, Jae-Gu; Choi, Young-Wook; Park, Jun-Ho; Lee, Jae-Jun

    2013-05-01

    Previous studies on the application of tomosynthesis to breast imaging have demonstrated the potential of digital breast tomosynthesis (DBT). DBT can improve the specificity of digital mammography (DM) through improved marginal visibility of lesions and early breast cancer detection for women with dense breasts. To investigate possible improvements in the accuracy of lesion detection with DBT systems as compared to DM, we conducted a quantitative evaluation by using simulated lesions embedded in a breast phantom. A prototype DBT and dedicated DM system were used in this study. For the DBT system, the average glandular dose (AGD) was calculated using a formalism that was a simple extension of mammography dosimetry. The DBT and the DM images were acquired with average glandular doses (AGDs) ranging from 1 to 4 mGy. To analyze the results objectively, we calculated metrics for in-plane lesion visibility in the form of the contrast-to-noise ratio for the in-focus plane from the DBT reconstruction image and from the craniocaudal (CC) image from the DM system. The imaging performance of DBT was quantitatively compared with that of DM in terms of the figure of merit. Although the DM showed better results in terms of the contrast-to-noise ratio (CNR) of the mass due to the reduced overlapping of tissue and lesion, an increase in breast thickness of over 3 cm increased the CNR of the mass with the DBT system. For microcalcification detection, the DBT system showed significantly higher CNR than the DM system and gave better predictions of the microcalcification size. We compared the performances of the DM and the DBT systems for various AGDs and breast thicknesses. In conclusion, the results indicate that the DBT systems can play an important role in the detection of masses or microcalcifications without severe compression.

  1. Epithelial Cell Adhesion Molecule

    PubMed Central

    Trzpis, Monika; McLaughlin, Pamela M.J.; de Leij, Lou M.F.H.; Harmsen, Martin C.

    2007-01-01

    The epithelial cell adhesion molecule (EpCAM, CD326) is a glycoprotein of ∼40 kd that was originally identified as a marker for carcinoma, attributable to its high expression on rapidly proliferating tumors of epithelial origin. Normal epithelia express EpCAM at a variable but generally lower level than carcinoma cells. In early studies, EpCAM was proposed to be a cell-cell adhesion molecule. However, recent insights revealed a more versatile role for EpCAM that is not limited only to cell adhesion but includes diverse processes such as signaling, cell migration, proliferation, and differentiation. Cell surface expression of EpCAM may actually prevent cell-cell adhesion. Here, we provide a comprehensive review of the current knowledge on EpCAM biology in relation to other cell adhesion molecules. We discuss the implications of the newly identified functions of EpCAM in view of its prognostic relevance in carcinoma, inflammatory pathophysiology, and tissue development and regeneration as well as its role in normal epithelial homeostasis. PMID:17600130

  2. Epithelial hyperplasia, alveoli —

    Cancer.gov

    Solitary or multiple foci of increased cellularity distal to terminal bronchioles. The background of broncho-alveolar architecture remains detectable, and epithelial cells are usually single layered. Round to oval hypertrophic type II pneumocytes with abundant eosinophilic cytoplasm line alveolar walls. In bronchiolar subvariant, also called bronchiolization of alveoli, alveolar walls are lined by cuboidal to columnar cells with features of bronchiolar differentiation, such as formation of cilia, Clara cell resemblance, and presence of mucous granules. Foci of consolidation may indicate early stages of adenoma formation. Macrophages may be present in the alveolar lumens.

  3. Early secreted antigenic target of 6 kDa (ESAT-6) protein of Mycobacterium tuberculosis induces interleukin-8 (IL-8) expression in lung epithelial cells via protein kinase signaling and reactive oxygen species.

    PubMed

    Boggaram, Vijay; Gottipati, Koteswara R; Wang, Xisheng; Samten, Buka

    2013-08-30

    Early secreted antigenic target of 6 kDa (ESAT-6) of Mycobacterium tuberculosis is critical for the virulence and pathogenicity of M. tuberculosis. IL-8, a major chemotactic cytokine for neutrophils and T lymphocytes, plays important roles in the development of lung injury. To further understand the role of ESAT-6 in lung pathology associated with tuberculosis development, we studied the effects of ESAT-6 on the regulation of IL-8 expression in lung epithelial cells. ESAT-6 induced IL-8 expression by increasing IL-8 gene transcription and mRNA stability. ESAT-6 induction of IL-8 promoter activity was dependent on nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) binding and sensitive to pharmacological inhibition of PKC and ERK and p38 MAPK pathways. ESAT-6 activated ERK and p38 MAPK phosphorylation and rapidly induced reactive oxygen species (ROS) production. Dimethylthiourea but not mannitol inhibited IL-8 induction by ESAT-6, further supporting the involvement of ROS in the induction of IL-8 expression. Exposure of mice to ESAT-6 induced localized inflammatory cell aggregate formation with characteristics of early granuloma concomitant with increased keratinocyte chemoattractant CXCL1 staining in bronchiolar and alveolar type II epithelial cells and alveolar macrophages. Our studies have identified a signal transduction pathway involving ROS, PKC, ERK, and p38 MAPKs and NF-κB and AP-1 in the ESAT-6 induction of IL-8 expression in lung epithelial cells. This has important implications for the understanding of lung innate immune responses to tuberculosis and the pathogenesis of lung injury in tuberculosis. PMID:23867456

  4. Engineering of Tomato Glandular Trichomes for the Production of Specialized Metabolites.

    PubMed

    Kortbeek, R W J; Xu, J; Ramirez, A; Spyropoulou, E; Diergaarde, P; Otten-Bruggeman, I; de Both, M; Nagel, R; Schmidt, A; Schuurink, R C; Bleeker, P M

    2016-01-01

    Glandular trichomes are specialized tissues on the epidermis of many plant species. On tomato they synthesize, store, and emit a variety of metabolites such as terpenoids, which play a role in the interaction with insects. Glandular trichomes are excellent tissues for studying the biosynthesis of specialized plant metabolites and are especially suitable targets for metabolic engineering. Here we describe the strategy for engineering tomato glandular trichomes, first with a transient expression system to provide proof of trichome specificity of selected promoters. Using microparticle bombardment, the trichome specificity of a terpene-synthase promoter could be validated in a relatively fast way. Second, we describe a method for stable expression of genes of interest in trichomes. Trichome-specific expression of another terpene-synthase promoter driving the yellow-fluorescence protein-gene is presented. Finally, we describe a case of the overexpression of farnesyl diphosphate synthase (FPS), specifically in tomato glandular trichomes, providing an important precursor in the biosynthetic pathway of sesquiterpenoids. FPS was targeted to the plastid aiming to engineer sesquiterpenoid production, but interestingly leading to a loss of monoterpenoid production in the transgenic tomato trichomes. With this example we show that trichomes are amenable to engineering though, even with knowledge of a biochemical pathway, the result of such engineering can be unexpected. PMID:27480691

  5. Biochemical and histochemical localization of monoterpene biosynthesis in the glandular trichomes of spearmint (Mentha spicata)

    SciTech Connect

    Gershenzon, J.; Maffei, M.; Croteau, R. )

    1989-04-01

    The primary monoterpene accumulated in the glandular trichomes of spearmint (Mentha spicata) is the ketone (-)-carvone which is formed by cyclization of the C{sub 10} isoprenoid intermediate geranyl pyrophosphate to the olefin (-)-limonene, hydroxylation to (-)-trans-carveol and subsequent dehydrogenation. Selective extraction of the contents of the glandular trichomes indicated that essentially all of the cyclase and hydroxylase activities resided in these structures, whereas only about 30% of the carveol dehydrogenase was located here with the remainder located in the rest of the leaf. This distribution of carveol dehydrogenase activity was confirmed by histochemical methods. Electrophoretic analysis of the partially purified carveol dehydrogenase from extracts of both the glands and the leaves following gland removal indicated the presence of a unique carveol dehydrogenase species in the glandular trichomes, suggesting that the other dehydrogenase found throughout the leaf probably utilizes carveol only as an adventitious substrate. These results demonstrate that carvone biosynthesis takes place exclusively in the glandular trichomes in which this natural product accumulates.

  6. Biochemical and Histochemical Localization of Monoterpene Biosynthesis in the Glandular Trichomes of Spearmint (Mentha spicata) 12

    PubMed Central

    Gershenzon, Jonathan; Maffei, Massimo; Croteau, Rodney

    1989-01-01

    The primary monoterpene accumulated in the glandular trichomes of spearmint (Mentha spicata) is the ketone (−)-carvone which is formed by cyclization of the C10 isoprenoid intermediate geranyl pyrophosphate to the olefin (−)-limonene, hydroxylation to (−)-trans-carveol and subsequent dehydrogenation. Selective extraction of the contents of the glandular trichomes indicated that essentially all of the cyclase and hydroxylase activities resided in these structures, whereas only about 30% of the carveol dehydrogenase was located here with the remainder located in the rest of the leaf. This distribution of carveol dehydrogenase activity was confirmed by histochemical methods. Electrophoretic analysis of the partially purified carveol dehydrogenase from extracts of both the glands and the leaves following gland removal indicated the presence of a unique carveol dehydrogenase species in the glandular trichomes, suggesting that the other dehydrogenase found throughout the leaf probably utilizes carveol only as an adventitious substrate. These results demonstrate that carvone biosynthesis takes place exclusively in the glandular trichomes in which this natural product accumulates. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:16666709

  7. Bidirectional secretions from glandular trichomes of pyrethrum enable immunization of seedlings.

    PubMed

    Ramirez, Aldana M; Stoopen, Geert; Menzel, Tila R; Gols, Rieta; Bouwmeester, Harro J; Dicke, Marcel; Jongsma, Maarten A

    2012-10-01

    Glandular trichomes are currently known only to store mono- and sesquiterpene compounds in the subcuticular cavity just above the apical cells of trichomes or emit them into the headspace. We demonstrate that basipetal secretions can also occur, by addressing the organization of the biosynthesis and storage of pyrethrins in pyrethrum (Tanacetum cinerariifolium) flowers. Pyrethrum produces a diverse array of pyrethrins and sesquiterpene lactones for plant defense. The highest concentrations accumulate in the flower achenes, which are densely covered by glandular trichomes. The trichomes of mature achenes contain sesquiterpene lactones and other secondary metabolites, but no pyrethrins. However, during achene maturation, the key pyrethrin biosynthetic pathway enzyme chrysanthemyl diphosphate synthase is expressed only in glandular trichomes. We show evidence that chrysanthemic acid is translocated from trichomes to pericarp, where it is esterified into pyrethrins that accumulate in intercellular spaces. During seed maturation, pyrethrins are then absorbed by the embryo, and during seed germination, the embryo-stored pyrethrins are recruited by seedling tissues, which, for lack of trichomes, cannot produce pyrethrins themselves. The findings demonstrate that plant glandular trichomes can selectively secrete in a basipetal direction monoterpenoids, which can reach distant tissues, participate in chemical conversions, and immunize seedlings against insects and fungi. PMID:23104830

  8. Phytotoxicity of Constituents of Glandular Trichomes and the Leaf Surface of Camphorweed, Heterotheca subaxillaris

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Camphorweed, Heterotheca subaxillaris (Lam.) Britt. & Rusby has a camphor-like odor, and its leaf surfaces contain glandular trichomes of the type shown to contain high levels of isoprenoids in other species. Phytotoxic calamenene-type sesquiterpenes (1-4, 8-10), borneol (11) and methylated flavone...

  9. Method for the evaluation of a average glandular dose in mammography

    SciTech Connect

    Okunade, Akintunde Akangbe

    2006-04-15

    This paper concerns a method for accurate evaluation of average glandular dose (AGD) in mammography. At different energies, the interactions of photons with tissue are not uniform. Thus, optimal accuracy in the estimation of AGD is achievable when the evaluation is carried out using the normalized glandular dose values, g(x,E), that are determined for each (monoenergetic) x-ray photon energy, E, compressed breast thickness (CBT), x, breast glandular composition, and data on photon energy distribution of the exact x-ray beam used in breast imaging. A generalized model for the values of g(x,E) that is for any arbitrary CBT ranging from 2 to 9 cm (with values that are not whole numbers inclusive, say, 4.2 cm) was developed. Along with other dosimetry formulations, this was integrated into a computer software program, GDOSE.FOR, that was developed for the evaluation of AGD received from any x-ray tube/equipment (irrespective of target-filter combination) of up to 50 kVp. Results are presented which show that the implementation of GDOSE.FOR yields values of normalized glandular dose that are in good agreement with values obtained from methodologies reported earlier in the literature. With the availability of a portable device for real-time acquisition of spectra, the model and computer software reported in this work provide for the routine evaluation of AGD received by a specific woman of known age and CBT.

  10. Bidirectional Secretions from Glandular Trichomes of Pyrethrum Enable Immunization of Seedlings[W

    PubMed Central

    Ramirez, Aldana M.; Stoopen, Geert; Menzel, Tila R.; Gols, Rieta; Bouwmeester, Harro J.; Dicke, Marcel; Jongsma, Maarten A.

    2012-01-01

    Glandular trichomes are currently known only to store mono- and sesquiterpene compounds in the subcuticular cavity just above the apical cells of trichomes or emit them into the headspace. We demonstrate that basipetal secretions can also occur, by addressing the organization of the biosynthesis and storage of pyrethrins in pyrethrum (Tanacetum cinerariifolium) flowers. Pyrethrum produces a diverse array of pyrethrins and sesquiterpene lactones for plant defense. The highest concentrations accumulate in the flower achenes, which are densely covered by glandular trichomes. The trichomes of mature achenes contain sesquiterpene lactones and other secondary metabolites, but no pyrethrins. However, during achene maturation, the key pyrethrin biosynthetic pathway enzyme chrysanthemyl diphosphate synthase is expressed only in glandular trichomes. We show evidence that chrysanthemic acid is translocated from trichomes to pericarp, where it is esterified into pyrethrins that accumulate in intercellular spaces. During seed maturation, pyrethrins are then absorbed by the embryo, and during seed germination, the embryo-stored pyrethrins are recruited by seedling tissues, which, for lack of trichomes, cannot produce pyrethrins themselves. The findings demonstrate that plant glandular trichomes can selectively secrete in a basipetal direction monoterpenoids, which can reach distant tissues, participate in chemical conversions, and immunize seedlings against insects and fungi. PMID:23104830

  11. [About a case of a recurrent glandular cardiac myxoma in a child].

    PubMed

    Meurgey, Alexandra; Henaine, Roland; Bouvagnet, Patrice; Chalabreysse, Lara

    2016-06-01

    Primary cardiac tumors are extremely rare and mainly benign. The majority of these are myxomas (40%). Myxoma are generally sporadic tumors which occur most commonly in adult females between 30 and 40 years, and are seldom found in the paediatric population (5%). Seven percent are associated with igenetic diseases. We report the case of an eight-year-old boy presenting a recurrent glandular cardiac myxoma. In 2011, he presented a deterioration of the general state. An echocardiography highlighted a left atrial mass on the interatrial septum, with a pedicular insertion. On the microscope, it consisted of a proliferation of stellate cells isolated or clustered in rudimentary vessels in a myxoid stroma presenting haemorrhage changes. These cells expressed CD34 and calretinine. Glandular elements without atypia were clustered within the myxomatous proliferation. They expressed cytokeratin (CK) 7. Surgical resection was macroscopically complete. In 2014, the boy had a sudden neurological deficit during a football match. An echocardiography revealed a recurrence at the same location. The lesion was excised and addressed in several fragments. Classical myxoma was associated with glands without atypia. This last component expressed CKAE1/AE3 and CK7. Ki67 index of proliferation was low. The surgical reintervention was macroscopically complete. The final diagnosis was glandular cardiac myxoma. A genetic survey was conducted, showing the presence of Carney complex. This is the first description in the litterature of a recurrent glandular cardiac myxoma occuring in a child. PMID:27234518

  12. Peltate glandular trichomes of Colquhounia seguinii harbor new defensive clerodane diterpenoids.

    PubMed

    Li, Chun-Huan; Liu, Yan; Hua, Juan; Luo, Shi-Hong; Li, Sheng-Hong

    2014-09-01

    Glandular trichomes produce a wide variety of secondary metabolites that are considered as major defensive chemicals against herbivore attack. The morphology and secondary metabolites of the peltate glandular trichomes of a lianoid Labiatae, Colquhounia seguinii Vaniot, were investigated. Three new clerodane diterpenoids, seguiniilactones A-C (1-3), were identified through precise trichome collection with laser microdissection, metabolic analysis with ultra performance liquid chromatography-tandem mass spectrometer, target compound isolation with classical phytochemical techniques, structure elucidation with spectroscopic methods. All compounds showed significant antifeedant activity against a generalist plant-feeding insect Spodoptera exigua. Seguiniilactone A (1) was approximately 17-fold more potent than the commercial neem oil. α-Substituted α,β-unsaturated γ-lactone functionality was found to be crucial for strong antifeedant activity of this class of compounds. Quantitative results indicated that the levels of these compounds in the peltate glandular trichomes and leaves were sufficiently high to deter the feeding by generalist insects. Moderate antifungal activity was observed for seguiniilactone C (3) against six predominant fungal species isolated from the diseased leaves of C. seguinii, while seguiniilactones A and B were generally inactive. These findings suggested that seguiniilactones A-C might be specialized secondary metabolites in peltate glandular trichomes for the plant defense against insect herbivores and pathogens. PMID:25048077

  13. Hypercalcemic encephalopathy in a patient on anti-TB treatment for glandular tuberculosis.

    PubMed

    Abraham, G; Sadasivam, P B; Gaspar, J H; Isphani, N; Lawrence, R

    1992-08-01

    An 84 years old male patient presented with hypercalcemic encephalopathy and mild azotemia while on anti-tuberculous treatment for glandular tuberculosis. He recovered fully during treatment with hydration, intravenous frusemide and oral prednisolone while continuing on the antituberculous therapy. PMID:1308493

  14. Automatic glandular and tubule region segmentation in histological grading of breast cancer

    NASA Astrophysics Data System (ADS)

    Nguyen, Kien; Barnes, Michael; Srinivas, Chukka; Chefd'hotel, Christophe

    2015-03-01

    In the popular Nottingham histologic score system for breast cancer grading, the pathologist analyzes the H and E tissue slides and assigns a score, in the range of 1-3, for tubule formation, nuclear pleomorphism and mitotic activity in the tumor regions. The scores from these three factors are added to give a final score, ranging from 3-9 to grade the cancer. Tubule score (TS), which reflects tubular formation, is a value in 1-3 given by manually estimating the percentage of glandular regions in the tumor that form tubules. In this paper, given an H and E tissue image representing a tumor region, we propose an automated algorithm to detect glandular regions and detect the presence of tubules in these regions. The algorithm first detects all nuclei and lumen candidates in the input image, followed by identifying tumor nuclei from the detected nuclei and identifying true lumina from the lumen candidates using a random forest classifier. Finally, it forms the glandular regions by grouping the closely located tumor nuclei and lumina using a graph-cut-based method. The glandular regions containing true lumina are considered as the ones that form tubules (tubule regions). To evaluate the proposed method, we calculate the tubule percentage (TP), i.e., the ratio of the tubule area to the total glandular area for 353 H and E images of the three TSs, and plot the distribution of these TP values. This plot shows the clear separation among these three scores, suggesting that the proposed algorithm is useful in distinguishing images of these TSs.

  15. Uterine morphology during diapause and early pregnancy in the tammar wallaby (Macropus eugenii).

    PubMed

    Laird, Melanie K; Hearn, Cyrma M; Shaw, Geoff; Renfree, Marilyn B

    2016-09-01

    In mammals, embryonic diapause, or suspension of embryonic development, occurs when embryos at the blastocyst stage are arrested in growth and metabolism. In the tammar wallaby (Macropus eugenii), there are two separate uteri, only one of which becomes gravid with the single conceptus at a post-partum oestrus, so changes during pregnancy can be compared between the gravid and non-gravid uterus within the same individual. Maintenance of the viable blastocyst and inhibition of further conceptus growth during diapause in the tammar is completely dependent on the uterine environment. Although the specific endocrine and seasonal signals are well established, much less is known about the cellular changes required to create this environment. Here we present the first detailed study of uterine morphology during diapause and early pregnancy of the tammar wallaby. We combined transmission electron microscopy and light microscopy to describe the histological and ultrastructural changes to luminal and glandular epithelial cells. At entry into diapause after the post-partum oestrus and formation of the new conceptus, there was an increase in abundance of organelles associated with respiration in the endometrial cells of the newly gravid uterus, particularly in the endoplasmic reticulum and mitochondria, as well as an increase in secretory activity. Organelle changes and active secretion then ceased in these cells as they became quiescent and remained so for the duration of diapause. In contrast, cells of the non-gravid, post-partum, contralateral uterus underwent sloughing and remodelling during this time and some organelle changes in glandular epithelial cells continued throughout diapause, suggesting these cells are not completely quiescent during diapause, although no active secretion occurred. These findings demonstrate that diapause, like pregnancy, is under unilateral endocrine control in the tammar, and that preparation for and maintenance of diapause requires

  16. An improved method for isolation of epithelial and stromal cells from the human endometrium

    PubMed Central

    MASUDA, Ayako; KATOH, Noriko; NAKABAYASHI, Kazuhiko; KATO, Kiyoko; SONODA, Kenzo; KITADE, Mari; TAKEDA, Satoru; HATA, Kenichiro; TOMIKAWA, Junko

    2016-01-01

    We aimed to improve the efficiency of isolating endometrial epithelial and stromal cells (EMECs and EMSCs) from the human endometrium. We revealed by immunohistochemical staining that the large tissue fragments remaining after collagenase treatment, which are usually discarded after the first filtration in the conventional protocol, consisted of glandular epithelial and stromal cells. Therefore, we established protease treatment and cell suspension conditions to dissociate single cells from the tissue fragments and isolated epithelial (EPCAM-positive) and stromal (CD13-positive) cells by fluorescence-activated cell sorting. Four independent experiments showed that, on average, 1.2 × 106 of EMECs and 2.8 × 106 EMSCs were isolated from one hysterectomy specimen. We confirmed that the isolated cells presented transcriptomic features highly similar to those of epithelial and stromal cells obtained by the conventional method. Our improved protocol facilitates future studies to better understand the molecular mechanisms underlying the dynamic changes of the endometrium during the menstrual cycle. PMID:26853786

  17. Mineral nutrient uptake from prey and glandular phosphatase activity as a dual test of carnivory in semi-desert plants with glandular leaves suspected of carnivory

    PubMed Central

    Płachno, Bartosz Jan; Adamec, Lubomír; Huet, Hervé

    2009-01-01

    Background and Aims Ibicella lutea and Proboscidea parviflora are two American semi-desert species of glandular sticky plants that are suspected of carnivory as they can catch small insects. The same characteristics might also hold for two semi-desert plants with glandular sticky leaves from Israel, namely Cleome droserifolia and Hyoscyamus desertorum. The presence of proteases on foliar hairs, either secreted by the plant or commensals, detected using a simple test, has long been considered proof of carnivory. However, this test does not prove whether nutrients are really absorbed from insects by the plant. To determine the extent to which these four species are potentially carnivorous, hair secretion of phosphatases and uptake of N, P, K and Mg from fruit flies as model prey were studied in these species and in Roridula gorgonias and Drosophyllum lusitanicum for comparison. All species examined possess morphological and anatomical adaptations (hairs or emergences secreting sticky substances) to catch and kill small insects. Methods The presence of phosphatases on foliar hairs was tested using the enzyme-labelled fluorescence method. Dead fruit flies were applied to glandular sticky leaves of experimental plants and, after 10–15 d, mineral nutrient content in their spent carcasses was compared with initial values in intact flies after mineralization. Key Results Phosphatase activity was totally absent on Hyoscyamus foliar hairs, a certain level of activity was usually found in Ibicella, Proboscidea and Cleome, and a strong response was found in Drosophyllum. Roridula exhibited only epidermal activity. However, only Roridula and Drosophyllum took up nutrients (N, P, K and Mg) from applied fruit flies. Conclusions Digestion of prey and absorption of their nutrients are the major features of carnivory in plants. Accordingly, Roridula and Drosophyllum appeared to be fully carnivorous; by contrast, all other species examined are non-carnivorous as they did not meet

  18. Zeb1 Regulates E-cadherin and Epcam (Epithelial Cell Adhesion Molecule) Expression to Control Cell Behavior in Early Zebrafish Development*

    PubMed Central

    Vannier, Corinne; Mock, Kerstin; Brabletz, Thomas; Driever, Wolfgang

    2013-01-01

    The ZEB1 transcription factor is best known as an inducer of epithelial-mesenchymal transitions (EMT) in cancer metastasis, acting through transcriptional repression of CDH1 (encoding E-cadherin) and the EMT-suppressing microRNA-200s (miR-200s). Here we analyze roles of the ZEB1 zebrafish orthologs, Zeb1a and Zeb1b, and of miR-200s in control of cell adhesion and morphogenesis during gastrulation and segmentation stages. Loss and gain of function analyses revealed that Zeb1 represses cdh1 expression to fine-tune adhesiveness of migrating deep blastodermal cells. Furthermore, Zeb1 acts as a repressor of epcam in the deep cells of the blastoderm and may contribute to control of epithelial integrity of enveloping layer cells, the outermost cells of the blastoderm. We found a similar ZEB1-dependent repression of EPCAM expression in human pancreatic and breast cancer cell lines, mediated through direct binding of ZEB1 to the EPCAM promoter. Thus, Zeb1 proteins employ several evolutionary conserved mechanisms to regulate cell-cell adhesion during development and cancer. PMID:23667256

  19. Glandular mast cells with distinct phenotype are highly elevated in chronic rhinosinusitis with nasal polyps

    PubMed Central

    Takabayashi, Tetsuji; Kato, Atsushi; Peters, Anju T.; Suh, Lydia A.; Carter, Roderick; Norton, James; Grammer, Leslie C.; Tan, Bruce K.; Chandra, Rakesh K.; Conley, David B.; Kern, Robert C.; Fujieda, Shigeharu; Schleimer, Robert P.

    2012-01-01

    Background Although chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by Th2 inflammation, the role of mast cells is poorly understood. Objective The objective of this study was to investigate the presence, localization and phenotype of mast cells in patients with chronic rhinosinusitis (CRS). Methods We collected nasal tissue and nasal lavage fluid from patients with CRS and control subjects. We analyzed mRNA for the mast cell proteases tryptase, chymase and carboxypeptidase A3 (CPA3), using real-time PCR, and measured mast cell protease proteins using ELISA, immunohistochemistry, and immunofluorescence. Results Tryptase mRNA was significantly increased in nasal polyps (NPs) from patients with CRSwNP (P < .001) compared with uncinate tissue (UT) from patients with CRS or control subjects. Tryptase protein was also elevated in NPs and in nasal lavage fluids from patients with CRSwNP. Immnohistochemistry showed increased numbers of mast cells in epithelium and glands but not within the lamina propria in NPs. The mast cells detected in epithelium in NPs were characterized by expression of tryptase and CPA3 but not chymase. Mast cells expressing all three proteases were abundant within glandular epithelium of NPs but were not found in normal glandular structures. Conclusion: Herein we demonstrate a unique localization of mast cells within glandular epithelium of NPs, and show that NPs mast cells have distinct phenotypes that vary by tissue location. Glandular mast cells and the diverse subsets of mast cells detected may contribute to the pathogenesis of CRSwNP. PMID:22534535

  20. Mayolenes: labile defensive lipids from the glandular hairs of a caterpillar (Pieris rapae).

    PubMed

    Smedley, Scott R; Schroeder, Frank C; Weibel, Douglas B; Meinwald, Jerrold; Lafleur, Katie A; Renwick, J Alan; Rutowski, Ronald; Eisner, Thomas

    2002-05-14

    Larvae of the European cabbage butterfly, Pieris rapae (Pieridae), are beset with glandular hairs, bearing droplets of a clear oily secretion at their tip. The fluid consists primarily of a series of chemically labile, unsaturated lipids, the mayolenes, which are derived from 11-hydroxylinolenic acid. In bioassays with the ant Crematogaster lineolata, the secretion was shown to be potently deterrent, indicating that the fluid plays a defensive role in nature. PMID:11997469

  1. Leaf Peltate Glandular Trichomes of Vernonia galamensis ssp. galamensis var. ethiopica Gilbert: Development, Ultrastructure and Chemical Composition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plants from the genus Vernonia produce a variety of flavonoids and bitter sesquiterpene lactones important for agriculture and human health. Leaf glandular trichomes of Vernonia galamensis ssp. galamensis var. ethiopica Gilbert (VGAE) were investigated for ultrastructural development and content com...

  2. Examination of equine glandular stomach lesions for bacteria, including Helicobacter spp by fluorescence in situ hybridisation

    PubMed Central

    2010-01-01

    Background The equine glandular stomach is commonly affected by erosion and ulceration. The aim of this study was to assess whether bacteria, including Helicobacter, could be involved in the aetiology of gastric glandular lesions seen in horses. Results Stomach lesions, as well as normal appearing mucosa were obtained from horses slaughtered for human consumption. All samples were tested for urease activity using the Pyloritek® assay, while mucosal bacterial content was evaluated using Fluorescence In Situ Hybridisation. In selected sub samples, bacteria characterisation was pursued further by cloning and sequencing. Mucosal lesions were found in 36/63 stomachs and included hyperplastic rugae, polypoid structures and focal erosions. None of the samples were tested positive for urease activity or for FISH using the Helicobacter genus specific probe. In samples of lesions, as well as normal samples, clones with 99% similarities to Lactobacillus salivarius and Sarcina ventriculi were found. Escherichia like bacterium clones and Enterococcus clones were demonstrated in one focal erosion. Based on a phylogenetic tree these clones had 100% similarity to Escherichia fergusonii and Enterococcus faecium. The Enterococcus were found colonising the mucosal surface, while E. fergusonii organisms were also demonstrated intraepithelial. Conclusion Gastric Helicobacter spp. could not be verified as being involved in lesions of the glandular stomach of the horse. Since E. fergusonii has been described as an emerging pathogen in both humans and animals, the finding of this bacterium in gastric erosion warrants further clarification to whether gastric infection with this type bacterium is important for horses. PMID:20298612

  3. Effect of the glandular composition on digital breast tomosynthesis image quality and dose optimisation.

    PubMed

    Marques, T; Ribeiro, A; Di Maria, S; Belchior, A; Cardoso, J; Matela, N; Oliveira, N; Janeiro, L; Almeida, P; Vaz, P

    2015-07-01

    In the image quality assessment for digital breast tomosynthesis (DBT), a breast phantom with an average percentage of 50 % glandular tissue is seldom used, which may not be representative of the breast tissue composition of the women undergoing such examination. This work aims at studying the effect of the glandular composition of the breast on the image quality taking into consideration different sizes of lesions. Monte Carlo simulations were performed using the state-of-the-art computer program PENELOPE to validate the image acquisition system of the DBT equipment as well as to calculate the mean glandular dose for each projection image and for different breast compositions. The integrated PENELOPE imaging tool (PenEasy) was used to calculate, in mammography, for each clinical detection task the X-ray energy that maximises the figure of merit. All the 2D cranial-caudal projections for DBT were simulated and then underwent the reconstruction process applying the Simultaneous Algebraic Reconstruction Technique. Finally, through signal-to-noise ratio analysis, the image quality in DBT was assessed. PMID:25836692

  4. Symmetry breaking mechanism for epithelial cell polarization

    NASA Astrophysics Data System (ADS)

    Veglio, A.; Gamba, A.; Nicodemi, M.; Bussolino, F.; Serini, G.

    2009-09-01

    In multicellular organisms, epithelial cells form layers separating compartments responsible for different physiological functions. At the early stage of epithelial layer formation, each cell of an aggregate defines an inner and an outer side by breaking the symmetry of its initial state, in a process known as epithelial polarization. By integrating recent biochemical and biophysical data with stochastic simulations of the relevant reaction-diffusion system, we provide evidence that epithelial cell polarization is a chemical phase-separation process induced by a local bistability in the signaling network at the level of the cell membrane. The early symmetry breaking event triggering phase separation is induced by adhesion-dependent mechanical forces localized in the point of convergence of cell surfaces when a threshold number of confluent cells is reached. The generality of the emerging phase-separation scenario is likely common to many processes of cell polarity formation.

  5. Histomorphometric analysis of early epithelialization and dermal changes in mid-partial-thickness burn wounds in humans treated with porcine small intestinal submucosa and silver-containing hydrofiber.

    PubMed

    Salgado, Rosa M; Bravo, Leonardo; García, Mario; Melchor, Juan M; Krötzsch, Edgar

    2014-01-01

    The objective of this study was to determine the healing rates of mid-partial-thickness burns treated with a porcine intestinal submucosa (SIS) vs. silver-containing cellulose hydrofiber (AgH) dressings. This was done by comparing healing response of burn wounds treated with SIS vs that of burns treated with AgH dressings. Five patients with mid-partial-thickness burns ≤10% of body surface were treated simultaneously, but in different areas, with SIS and AgH dressings; full-thickness biopsies were taken at days 0 and 7. Tissues treated with SIS presented higher epithelial maturation index (6.2 ± 0.84 vs. 3.2 ± 3.28; [mean ± standard deviation], P = .029), better orientation and differentiation of epithelial cells, as well as an appropriate basal lamina structure, collagen deposition, and higher transforming growth factor-β3 expression (7.4 ± 8.1 vs. 2.1 ± 2.6; P = .055) than tissues treated with AgH dressings. Importantly, after the treatment SIS was not integrated in healed tissues. After 3 months of treatment, SIS produced a lower score according to Vancouver Scar Scale (3.6 ± 2.6 vs. 7.2 ± 2.5, P = .025).The submucosa dressing does not simply act as scaffolding for the wound, it provides stimulation in the healing area, probably via growth factors initially present in SIS or matrikines derived from its digestion in the wound site. In conclusion, the present study demonstrated that biological matrices favor the wound-healing process. PMID:24823330

  6. Identifying Three Ecological Chemotypes of Xanthium strumarium Glandular Trichomes Using a Combined NMR and LC-MS Method

    PubMed Central

    Gou, Junbo; Lu, Dayan; Gong, Fujun; Tang, Huiru; Zhang, Yansheng

    2013-01-01

    Xanthanolides, as the sesquiterpene lactones, are reportedly the major components for the pharmacological properties of X. strumarium L. species. Phytochemical studies indicated that the glandular structures on the surface of plant tissues would form the primary sites for the accumulation of this class of the compounds. As the interface between plants and their natural enemies, glandular trichomes may vary with respect to which of their chemicals are sequestered against different herbivores in different ecologies. However, to date, no data are available on the chemical characterisation of X. strumarium glandular cells. In this study, the trichome secretions of the X. strumarium species originating from nineteen unique areas across eleven provinces in China, were analysed by HPLC, LC-ESI-MS and NMR. For the first time three distinct chemotypes of X. strumarium glandular trichomes were discovered along with the qualitative and quantitative evaluations of their presence of xanthanolides; these were designated glandular cell Types I, II, and III, respectively. The main xanthanolides in Type I cells were 8-epi-xanthatin and xanthumin while no xanthatin was detected. Xanthatin, 8-epi-xanthatin, and xanthumin dominated in Type II cells with comparable levels of each being present. For Type III cells, significantly higher concentrations of 8-epi-xanthatin or xanthinosin (relative to xanthatin) were detected with xanthinosin only being observed in this type. Further research will focus on understanding the ecological and molecular mechanism causing these chemotype differences in X. strumarium glandular structures. PMID:24098541

  7. Identifying three ecological chemotypes of Xanthium strumarium glandular trichomes using a combined NMR and LC-MS method.

    PubMed

    Chen, Fangfang; Hao, Fuhua; Li, Changfu; Gou, Junbo; Lu, Dayan; Gong, Fujun; Tang, Huiru; Zhang, Yansheng

    2013-01-01

    Xanthanolides, as the sesquiterpene lactones, are reportedly the major components for the pharmacological properties of X. strumarium L. species. Phytochemical studies indicated that the glandular structures on the surface of plant tissues would form the primary sites for the accumulation of this class of the compounds. As the interface between plants and their natural enemies, glandular trichomes may vary with respect to which of their chemicals are sequestered against different herbivores in different ecologies. However, to date, no data are available on the chemical characterisation of X. strumarium glandular cells. In this study, the trichome secretions of the X. strumarium species originating from nineteen unique areas across eleven provinces in China, were analysed by HPLC, LC-ESI-MS and NMR. For the first time three distinct chemotypes of X. strumarium glandular trichomes were discovered along with the qualitative and quantitative evaluations of their presence of xanthanolides; these were designated glandular cell Types I, II, and III, respectively. The main xanthanolides in Type I cells were 8-epi-xanthatin and xanthumin while no xanthatin was detected. Xanthatin, 8-epi-xanthatin, and xanthumin dominated in Type II cells with comparable levels of each being present. For Type III cells, significantly higher concentrations of 8-epi-xanthatin or xanthinosin (relative to xanthatin) were detected with xanthinosin only being observed in this type. Further research will focus on understanding the ecological and molecular mechanism causing these chemotype differences in X. strumarium glandular structures. PMID:24098541

  8. A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus.

    PubMed

    Simitsidellis, Ioannis; Gibson, Douglas A; Cousins, Fiona L; Esnal-Zufiaurre, Arantza; Saunders, Philippa T K

    2016-05-01

    The endometrium consists of stromal and epithelial compartments (luminal and glandular) with distinct functions in the regulation of uterine homeostasis. Ovarian sex steroids, namely 17β-estradiol and progesterone, play essential roles in modulating uterine cell proliferation, stromal-epithelial cross-talk and differentiation in preparation for pregnancy. The effect of androgens on uterine function remains poorly understood. The current study investigated the effect of the non-aromatizable androgen dihydrotestosterone (DHT) on mouse endometrial function. Ovx female mice were given a single sc injection (short treatment) or 7 daily injections (long treatment) of vehicle alone (5% ethanol, 0.4% methylcellulose) or vehicle with the addition of 0.2 mg DHT (n=8/group) and a single injection of bromodeoxyuridine 2 hours prior to tissue recovery. Treatment with DHT increased uterine weight, the area of the endometrial compartment and immunoexpression of the androgen receptor in the luminal and glandular epithelium. Treatment-dependent proliferation of epithelial cells was identified by immunostaining for MKi67 and bromodeoxyuridine. Real-time PCR identified significant DHT-dependent changes in the concentrations of mRNAs encoded by genes implicated in the regulation of the cell cycle (Wee1, Ccnd1, Rb1) and stromal-epithelial interactions (Wnt4, Wnt5a, Wnt7a, Cdh1, Vcl, Igf1, Prl8, Prlr) as well as a striking effect on the number of endometrial glands. This study has revealed a novel role for androgens in regulating uterine function with an effect on the glandular compartment of the endometrium. This previously unrecognized role for androgens has implications for our understanding of the role of androgens in regulation of endometrial function and fertility in women. PMID:26963473

  9. A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus

    PubMed Central

    Simitsidellis, Ioannis; Gibson, Douglas A.; Cousins, Fiona L.; Esnal-Zufiaurre, Arantza

    2016-01-01

    The endometrium consists of stromal and epithelial compartments (luminal and glandular) with distinct functions in the regulation of uterine homeostasis. Ovarian sex steroids, namely 17β-estradiol and progesterone, play essential roles in modulating uterine cell proliferation, stromal-epithelial cross-talk and differentiation in preparation for pregnancy. The effect of androgens on uterine function remains poorly understood. The current study investigated the effect of the non-aromatizable androgen dihydrotestosterone (DHT) on mouse endometrial function. Ovx female mice were given a single sc injection (short treatment) or 7 daily injections (long treatment) of vehicle alone (5% ethanol, 0.4% methylcellulose) or vehicle with the addition of 0.2 mg DHT (n=8/group) and a single injection of bromodeoxyuridine 2 hours prior to tissue recovery. Treatment with DHT increased uterine weight, the area of the endometrial compartment and immunoexpression of the androgen receptor in the luminal and glandular epithelium. Treatment-dependent proliferation of epithelial cells was identified by immunostaining for MKi67 and bromodeoxyuridine. Real-time PCR identified significant DHT-dependent changes in the concentrations of mRNAs encoded by genes implicated in the regulation of the cell cycle (Wee1, Ccnd1, Rb1) and stromal-epithelial interactions (Wnt4, Wnt5a, Wnt7a, Cdh1, Vcl, Igf1, Prl8, Prlr) as well as a striking effect on the number of endometrial glands. This study has revealed a novel role for androgens in regulating uterine function with an effect on the glandular compartment of the endometrium. This previously unrecognized role for androgens has implications for our understanding of the role of androgens in regulation of endometrial function and fertility in women. PMID:26963473

  10. Evidence that an early pregnancy causes a persistent decrease in the number of functional mammary epithelial stem cells—implications for pregnancy-induced protection against breast cancer

    PubMed Central

    Siwko, Stefan K.; Dong, Jie; Lewis, Michael T.; Liu, Hao; Hilsenbeck, Susan G.; Li, Yi

    2009-01-01

    A completed pregnancy at a young age reduces a woman’s lifetime risk of breast cancer by up to 50%. A similar protective effect of an early pregnancy has been observed in rodent models using chemical carcinogens. However, the mechanisms responsible for this protective effect remain unclear. Stem cells have been proposed to be the cells of origin for breast cancer. We hypothesized that an early pregnancy reduces adult levels of either mammary stem cells or mammary multipotent progenitor cells. Unsorted mammary cells from adult mice that had undergone an early parity had the same mammosphere formation efficiency as cells from age-matched virgin mice. However, when we transplanted adult mammary cells in limiting dilutions into cleared fat pads of syngeneic mice, we found a significant reduction in the outgrowth potential of the cells from early parous mice as compared with age-matched virgin mice. The extent of fat pad filling in successful outgrowths did not change, suggesting that while mammary stem cells in parous mice retained their functional competence, the number of mammary stem cells was reduced. Our results provide the first direct evidence that an early pregnancy has an effect on mammary stem cells. PMID:18787212

  11. Clinical significance and expression of the PRSS3 and Wiskott-Aldrich syndrome protein family verprolin-homologous protein 1 for the early detection of epithelial ovarian cancer.

    PubMed

    Azizmohammadi, Sima; Safari, Aghdas; Seifoleslami, Mehri; Rabati, Rahman Ghaffarzadegan; Mohammadi, Mohsen; Yahaghi, Hamid; Azizmohammadi, Susan

    2016-05-01

    In this study, we evaluate the clinical significance of the PRSS3 and Wiskott-Aldrich syndrome protein family verprolin-homologous protein 1 (WAVE1) in patients with epithelial ovarian cancer (EOC) by immunohistochemistry.In current study, all adjacent non-cancerous tissues showed absent or low expression of PRSS3. The expression of PRSS3 was significantly increased in the EOCs than adjacent non-cancerous tissues. Moreover, the expression of WAVE1 was significantly observed in all EOC tissues when compared with normal tissues. Furthermore, WAVE1 expression was absent in 35 (89.74 %) adjacent non-cancerous tissues.Our findings showed that high expression of PRSS3 was markedly linked to FIGO stage (P = 0.02), advanced grade (P = 0.017), and lymph node metastases (P = 0.001), but no relationship was determined with other clinicopathological parameters. Furthermore, high expression of WAVE1 was significantly correlated with FIGO stage (P = 0.001), grade of tumor (P = 0.011), and residual tumor size (P = 0.041), but no significant associations were found between WAVE1 expression and age, lymph node metastasis, and histological subtypes (all P > 0.05). In conclusion, our study showed that increased expression of PRSS3 and WAVE1 may be involved in development of EOC. PMID:26662304

  12. Harnessing 3D models of mammary epithelial morphogenesis: An off the beaten path approach to identify candidate biomarkers of early stage breast cancer.

    PubMed

    Rossetti, Stefano; Bshara, Wiam; Reiners, Johanna A; Corlazzoli, Francesca; Miller, Austin; Sacchi, Nicoletta

    2016-10-01

    Regardless of the etiological factor, an aberrant morphology is the common hallmark of ductal carcinoma in situ (DCIS), which is a highly heterogeneous disease. To test if critical core morphogenetic mechanisms are compromised by different mutations, we performed proteomics analysis of five mammary epithelial HME1 mutant lines that develop a DCIS-like morphology in three dimensional (3D) culture. Here we show first, that all HME1 mutant lines share a common protein signature highlighting an inverse deregulation of two annexins, ANXA2 and ANXA8. Either ANXA2 downregulation or ANXA8 upregulation in the HME1 cell context are per se sufficient to confer a 3D DCIS-like morphology. Seemingly, different mutations impinged on a common mechanism that differentially regulates the two annexins. Second, we show that ANXA8 expression is significantly higher in DCIS tissue samples versus normal breast tissue and atypical ductal hyperplasia (ADH). Apparently, ANXA8 expression is significantly more upregulated in ER-negative versus ER-positive cases, and significantly correlates with tumor stage, grade and positive lymph node. Based on our study, 3D mammary morphogenesis models can be an alternate/complementary strategy for unraveling new DCIS mechanisms and biomarkers. PMID:27422542

  13. Cell Division Drives Epithelial Cell Rearrangements during Gastrulation in Chick.

    PubMed

    Firmino, Joao; Rocancourt, Didier; Saadaoui, Mehdi; Moreau, Chloe; Gros, Jerome

    2016-02-01

    During early embryonic development, cells are organized as cohesive epithelial sheets that are continuously growing and remodeled without losing their integrity, giving rise to a wide array of tissue shapes. Here, using live imaging in chick embryo, we investigate how epithelial cells rearrange during gastrulation. We find that cell division is a major rearrangement driver that powers dramatic epithelial cell intercalation events. We show that these cell division-mediated intercalations, which represent the majority of epithelial rearrangements within the early embryo, are absolutely necessary for the spatial patterning of gastrulation movements. Furthermore, we demonstrate that these intercalation events result from overall low cortical actomyosin accumulation within the epithelial cells of the embryo, which enables dividing cells to remodel junctions in their vicinity. These findings uncover a role for cell division as coordinator of epithelial growth and remodeling that might underlie various developmental, homeostatic, or pathological processes in amniotes. PMID:26859350

  14. Airway epithelial cell responses to ozone injury

    SciTech Connect

    Leikauf, G.D.; Simpson, L.G.; Zhao, Qiyu

    1995-03-01

    The airway epithelial cell is an important target in ozone injury. Once activated, the airway epithelium responds in three phases. The initial, or immediate phase, involves activation of constitutive cells, often through direct covalent interactions including the formation of secondary ozonolysis products-hydroxyhydroperoxides, aldehydes, and hydrogen peroxide. Recently, we found hydroxyhydroperoxides to be potent agonists; of bioactive eicosanoid formation by human airway epithelial cells in culture. Other probable immediate events include activation and inactivation of enzymes present on the epithelial surface (e.g., neutral endopeptidase). During the next 2 to 24 hr, or early phase, epithelial cells respond by synthesis and release of chemotactic factors, including chemokines-macrophage inflammatory protein-2, RANTES, and interleukin-8. Infiltrating leukocytes during this period also release elastase, an important agonist of epithelial cell mucus secretion and additional chemokine formation. The third (late) phase of ozone injury is characterized by eosinophil or monocyte infiltration. Cytokine expression leads to alteration of structural protein synthesis, with increases in fibronectin evident by in situ hybridization. Synthesis of epithelial antiproteases, e.g., secretary leukocyte protease inhibitor, may also increase locally 24 to 48 hr after elastase concentrations become excessive. Thus, the epithelium is not merely a passive barrier to ozone injury but has a dynamic role in directing the migration, activating, and then counteracting inflammatory cells. Through these complex interactions, epithelial cells can be viewed as the initiators (alpha) and the receptors (omega) of ozone-induced airway disease. 51 refs., 2 figs., 3 tabs.

  15. Capitate glandular trichomes in Aldama discolor (Heliantheae - Asteraceae): morphology, metabolite profile and sesquiterpene biosynthesis.

    PubMed

    Bombo, A B; Appezzato-da-Glória, B; Aschenbrenner, A-K; Spring, O

    2016-05-01

    The capitate glandular trichome is the most common type described in Asteraceae species. It is known for its ability to produce various plant metabolites of ecological and economic importance, among which sesquiterpene lactones are predominant. In this paper, we applied microscopy, phytochemical and molecular genetics techniques to characterise the capitate glandular trichome in Aldama discolor, a native Brazilian species of Asteraceae, with pharmacological potential. It was found that formation of trichomes on leaf primordia of germinating seeds starts between 24 h and 48 h after radicle growth indicates germination. The start of metabolic activity of trichomes was indicated by separation of the cuticle from the cell wall of secretory cells at the trichome tip after 72 h. This coincided with the accumulation of budlein A, the major sesquiterpene lactone of A. discolor capitate glandular trichomes, in extracts of leaf primordia after 96 h. In the same timeframe of 72-96 h post-germination, gene expression studies showed up-regulation of the putative germacrene A synthase (pGAS2) and putative germacrene A oxidase (pGAO) of A. discolor in the transcriptome of these samples, indicating the start of sesquiterpene lactone biosynthesis. Sequencing of the two genes revealed high similarity to HaGAS and HaGAO from sunflower, which shows that key steps of this pathway are highly conserved. The processes of trichome differentiation, metabolic activity and genetic regulation in A. discolor and in sunflower appear to be typical for other species of the subtribe Helianthinae. PMID:26642998

  16. Differential Expression of Wnt Signaling Molecules Between Pre- and Postmenopausal Endometrial Epithelial Cells Suggests a Population of Putative Epithelial Stem/Progenitor Cells Reside in the Basalis Layer

    PubMed Central

    Nguyen, Hong P. T.; Sprung, Carl N.

    2012-01-01

    The human endometrium undergoes extensive monthly regeneration in response to fluctuating levels of circulating estrogen and progesterone in premenopausal (Pre-M) women. In contrast, postmenopausal (Post-M) endometrium is thin and quiescent with low mitotic activity, similar to the Pre-M endometrial basalis layer. Clonogenic epithelial stem/progenitor (ESP) cells, likely responsible for regenerating endometrial epithelium, have been identified in Pre-M and Post-M endometrium, but their location is unknown. We undertook transcriptional profiling of highly purified epithelial cells from full-thickness Pre-M and Post-M endometrium to identify differentially regulated genes that may indicate a putative ESP cell population resides in the basalis of Pre-M and basalis-like Post-M endometrium. Of 1077 differentially expressed genes identified, the Wnt signaling pathway, important in endometrial development and stem cell regulation, was one of the main gene families detected, including 22 Wnt-associated genes. Twelve genes were validated using quantitative RT-PCR, and all were concordant with microarray data. Immunostaining showed glandular epithelial location of Wnt-regulated genes, Axin-related protein 2 and β-catenin. Axin2 localized to the nucleus of basalis Pre-M and Post-M and cytoplasm of functionalis Pre-M endometrium, suggesting that it regulates β-catenin. Comparison of our Post-M gene profile with published gene microarray datasets revealed similarities to Pre-M basalis epithelial profiles. This differential expression of multiple Wnt-associated genes in human Pre-M and Post-M endometrial epithelial cells and the similar gene profile of Post-M and Pre-M basalis epithelium suggests that a population of putative endometrial ESP may reside in the basalis of Pre-M endometrium, which may be responsible for regenerating glandular epithelium each month. PMID:22474188

  17. [Cytophysiology of the glandular lobe of the corpora cardiaca: ergastoplasmic granules and their significance].

    PubMed

    Lafon-Cazal, M; Michel, R

    1977-01-01

    The number of ergastoplasmic granules in the glandular lobe of the corpora cardiaca is counted in Locusta migratoria migratorioides R. and F. and Schistocerca gregaria Forsk., male adults of different ages, grouped or isolated, having flown or not, and reared in various conditions of hygrometry and temperature. A good correlation was found between the number of ergastoplasmic granules and the utilization of the adipokinetic hormone. Ergastoplasmic granules may représent an original mechanism of hormonal storage used in view of heavy metabolic requirements. PMID:615543

  18. Apoptotic wing degeneration and formation of an altruism-regulating glandular appendage (gemma) in the ponerine ant Diacamma sp. from Japan (Hymenoptera, Formicidae, Ponerinae).

    PubMed

    Gotoh, A; Sameshima, S; Tsuji, K; Matsumoto, T; Miura, T

    2005-02-01

    We here show an example of morphological novelties, which have evolved from insect wings into the specific structures controlling social behaviour in an ant species. Most ant colonies consist of winged queen(s) and wingless workers. In the queenless ponerine ant Diacamma sp. from Japan, however, all female workers have a pair of small thoracic appendages, called "gemmae", which are homologous to the forewings and acts as an organ regulating altruism expression. Most workers, whose gemmae are clipped off by other colony members, become nonreproductive helpers, while only a single individual with complete gemmae becomes functionally reproductive. We examined histologically the development of gemmae, and compared it with that of functional wings in males. Female larvae had well-developed wing discs for both fore- and hindwings. At pupation, however, the wing discs started to evaginate and later degenerate. The hindwing discs completely degenerated, while the degeneration of forewing discs was incomplete, leading to the formation of gemmae. The degeneration process involved apoptotic cell death as confirmed by TUNEL assay. In addition, glandular cells differentiated from the epithelial cells of the forewing buds after completion of pupation. The mechanism of developmental transition from wing to gemma can be regarded as an evolutionary gain of new function, which can be seen in insect appendages and vertebrate limbs. PMID:15647944

  19. Glandular kallikreins in the teleost Cyprinus carpio: tissue distribution, possible involvement in prolactin processing, and effect of 17 beta-estradiol in vivo.

    PubMed

    Figueroa, J; Fernández, K; Haussmann, D; Richards, G; Barra, V; Kausel, G

    2002-09-01

    We examined glandular kallikrein (GK), a putative prolactin processing protease, in the teleost Cyprinus carpio. When employing an anti-Centropristis striata GK antibody proteins of 39 kDa in muscle, 52 kDa in gill, 52 kDa in kidney, and two proteins of 46 and 72 kDa in pituitary gland were detected. Immunoreactive kallikreins were recognized in intermuscle cell tissue, epithelial gill cells, apical region of tubular cells, and prolactin producing lactotrophs in pituitary gland, suggesting a osmoregulatory role for this enzyme. We found three prolactin (PRL) variants using anti-tilapia PRL antibodies, in pituitary gland 23 and 16 kDa, and in plasma 23 and 22 kDa forms. Clearly co-localization of GK and PRL in lactotrophs could be demonstrated. In winter-acclimatized male carp, where the pituitary PRL level is low, 17beta-estradiol treatment increased PRL but not GK immunoreactivity. In contrast to GK and PRL co-regulation by estrogen in mammalian pituitary gland, no similar effect on immunoreactive PRL and GK was observed in the ichtyc pituitary. No changes in GK immunostaining occurred in gill or muscle tissue in response to estrogen treatment. These results, taken with the observation of significantly increased GK immunoreactivity in the apical region of kidney tubular cells in estrogen treated male carp, indicate that the regulation of GK expression in pituitary and kidney could be different in fish with respect to mammals. PMID:12392686

  20. Molecular cloning and functional characterization of borneol dehydrogenase from the glandular trichomes of Lavandula x intermedia.

    PubMed

    Sarker, Lukman S; Galata, Mariana; Demissie, Zerihun A; Mahmoud, Soheil S

    2012-12-15

    Several varieties of Lavandula x intermedia (lavandins) are cultivated for their essential oils (EOs) for use in cosmetic, hygiene and personal care products. These EOs are mainly constituted of monoterpenes including camphor, which contributes an off odor reducing the olfactory appeal of the oil. We have recently constructed a cDNA library from the glandular trichomes (the sites of EO synthesis) of L. x intermedia plants. Here, we describe the cloning of a borneol dehydrogenase cDNA (LiBDH) from this library. The 780 bp open reading frame of the cDNA encoded a 259 amino acid short chain alcohol dehydrogenase with a predicted molecular mass of ca. 27.5 kDa. The recombinant LiBDH was expressed in Escherichia coli, purified by Ni-NTA agarose affinity chromatography, and functionally characterized in vitro. The bacterially produced enzyme specifically converted borneol to camphor as the only product with K(m) and k(cat) values of 53 μM and 4.0 × 10(-4) s(-1), respectively. The LiBDH transcripts were specifically expressed in glandular trichomes of mature flowers indicating that like other Lavandula monoterpene synthases the expression of this gene is regulated in a tissue-specific manner. The cloning of LiBDH has far reaching implications in improving the quality of Lavandula EOs through metabolic engineering. PMID:23058847

  1. Cloning of a sesquiterpene synthase from Lavandula x intermedia glandular trichomes.

    PubMed

    Sarker, Lukman S; Demissie, Zerihun A; Mahmoud, Soheil S

    2013-11-01

    The essential oil (EO) of Lavandula is dominated by monoterpenes, but can also contain small amounts of sesquiterpenes, depending on species and environmental conditions. For example, the sesquiterpene 9-epi-caryophyllene can make up to 8 % of the EO in a few species, including those commercially propagated for EO production. Here, we report the cloning and functional characterization of 9-epi-caryophyllene synthase (LiCPS) from the glandular trichomes of Lavandula x intermedia, cv. Grosso. The 1,617 bp open reading frame of LiCPS, which did not encode a transit peptide, was expressed in Escherichia coli and the recombinant protein purified by Ni-NTA agarose affinity chromatography. The ca. 60 kDa recombinant protein specifically converted farnesyl diphosphate to 9-epi-caryophyllene. LiCPS also produced a few monoterpenes when assayed with the monoterpene precursor geranyl diphosphate (GPP), but--unlike most monoterpene synthases--was not able to derive detectable amounts of any products from the cis isomer of GPP, neryl diphosphate. The LiCPS transcripts accumulated in developing L. x intermedia flowers and were highly enriched in glandular trichomes, but were not detected in leaves suggesting that the transcriptional expression of this gene is spatially and developmentally regulated. PMID:23918183

  2. Toad Glandular Secretions and Skin Extractions as Anti-Inflammatory and Anticancer Agents

    PubMed Central

    Tan, C. K.; Hashimi, Saeed M.; Zulfiker, Abu Hasanat Md.; Wei, Ming Q.

    2014-01-01

    Toad glandular secretions and skin extractions contain many natural agents which may provide a unique resource for novel drug development. The dried secretion from the auricular and skin glands of Chinese toad (Bufo bufo gargarizans) is named Chansu, which has been used in Traditional Chinese Medicine (TCM) for treating infection and inflammation for hundreds of years. The sterilized hot water extraction of dried toad skin is named Huachansu (Cinobufacini) which was developed for treating hepatitis B virus (HBV) and several types of cancers. However, the mechanisms of action of Chansu, Huachansu, and their constituents within are not well reported. Existing studies have suggested that their anti-inflammation and anticancer potential were via targeting Nuclear Factor (NF)-κB and its signalling pathways which are crucial hallmarks of inflammation and cancer in various experimental models. Here, we review some current studies of Chansu, Huachansu, and their compounds in terms of their use as both anti-inflammatory and anticancer agents. We also explored the potential use of toad glandular secretions and skin extractions as alternate resources for treating human cancers in combinational therapies. PMID:24734105

  3. A polynomial hyperelastic model for the mixture of fat and glandular tissue in female breast.

    PubMed

    Calvo-Gallego, Jose L; Martínez-Reina, Javier; Domínguez, Jaime

    2015-09-01

    In the breast of adult women, glandular and fat tissues are intermingled and cannot be clearly distinguished. This work studies if this mixture can be treated as a homogenized tissue. A mechanical model is proposed for the mixture of tissues as a function of the fat content. Different distributions of individual tissues and geometries have been tried to verify the validity of the mixture model. A multiscale modelling approach was applied in a finite element model of a representative volume element (RVE) of tissue, formed by randomly assigning fat or glandular elements to the mesh. Both types of tissues have been assumed as isotropic, quasi-incompressible hyperelastic materials, modelled with a polynomial strain energy function, like the homogenized model. The RVE was subjected to several load cases from which the constants of the polynomial function of the homogenized tissue were fitted in the least squares sense. The results confirm that the fat volume ratio is a key factor in determining the properties of the homogenized tissue, but the spatial distribution of fat is not so important. Finally, a simplified model of a breast was developed to check the validity of the homogenized model in a geometry similar to the actual one. PMID:25950862

  4. Further Studies on Barretts Mucosa in Baboons: Metaplastic Glandular Cells Produce Sialomucin

    PubMed Central

    RUBIO, CARLOS A.; OWSTON, MICHAEL; ORREGO, ABIEL; DICK, EDWARD J.

    2012-01-01

    Background In humans and in baboons, protracted gastro-esophageal reflux (GER) transforms the squamous-lined esophagus into columnar-lined (that is Barrett's mucosa, BM). Alcian blue stain (AB) is used to evidence sialomucin-producing goblet cells in human BM. Aim To assess the frequency and distribution of sialomucin-producing cells in BM in baboons. Materials and Methods Sections from 137 consecutive baboon esophagi were alternatively stained with hematoxylin-eosin (H&E) and with AB (pH 2.5), without counterstain. Results Out of 137 baboons, 131 (95.6%) had BM. Columnar and intramucosal glandular cells produced sialomucin in all 131 of these animals. Many BM cells were ballooned and filled with sialomucins, despite goblet cells not being found in H&E sections. Conclusion In humans, protracted GER is a disease requiring medication that may lead to BM; AB stains mainly goblet cells and occasional columnar cells in BM. In baboons, in contrast, BM is a natural postnatal process of adaptation to GER, triggered by regurgitation and rumination. AB stains all columnar and intra-mucosal glandular cells. Sialomucin-overstuffed cells were more frequent and larger in baboons than in humans. The extra load of sialomucin in BM might be an integrated part of the postnatal life-long process of adaptation to regurgitation and rumination in baboons. PMID:21036729

  5. Changes in Structure and Histochemistry of Glandular Trichomes of Thymus quinquecostatus Celak

    PubMed Central

    Jia, Ping; Gao, Ting; Xin, Hua

    2012-01-01

    The types, morphology, distribution, structure, and development process of the glandular trichomes on the leaves of Thymus quinquecostatus Celak had been investigated in this study. Two different types of glandular trichomes were determined in detail, namely, capitate trichomes and peltate ones. Besides, there were distinct differences on morphology, distribution, structure, and development process between the two kinds of trichomes. As the peltate trichome stepping into senium stage, it caved in the epidermis integrally, which was different from the capitate one. The secretion of the capitate trichome contained essential oil, polyphenols, and flavonoids, while, in addition to these three components, the secretion of the peltate one also contained acid polysaccharides. A distinctive difference was also seen in the secretory pathway of the secretion between the two types of trichomes. The secretion of capitate one was extruded through the cuticle of the head cell, but the secretion of the peltate one kept accumulating in the subcuticular space of the head cells until it was released by cuticle rupture. PMID:22545009

  6. Development and Structure of Internal Glands and External Glandular Trichomes in Pogostemon cablin

    PubMed Central

    Guo, Jiansheng; Yuan, Yongming; Liu, Zhixue; Zhu, Jian

    2013-01-01

    Pogostemon cablin possesses two morphologically and ontogenetically different types of glandular trichomes, one type of bristle hair on the surfaces of leaves and stems and one type of internal gland inside the leaves and stems. The internal gland originates from elementary meristem and is associated with the biosynthesis of oils present inside the leaves and stems. However, there is little information on mechanism for the oil biosynthesis and secretion inside the leaves and stems. In this study, we identified three kinds of glandular trichome types and two kinds of internal gland in the Pogostemon cablin. The oil secretions from internal glands of stems and leaves contained lipids, flavones and terpenes. Our results indicated that endoplasmic reticulum and plastids and vacuoles are likely involved in the biosynthesis of oils in the internal glands and the synthesized oils are transported from endoplasmic reticulum to the cell wall via connecting endoplasmic reticulum membranes to the plasma membrane. And the comparative analysis of the development, distribution, histochemistry and ultrastructures of the internal and external glands in Pogostemon cablin leads us to propose that the internal gland may be a novel secretory structure which is different from external glands. PMID:24205002

  7. Promoters of AaGL2 and AaMIXTA-Like1 genes of Artemisia annua direct reporter gene expression in glandular and non-glandular trichomes

    PubMed Central

    Jindal, Sunita; Longchar, Bendangchuchang; Singh, Alka; Gupta, Vikrant

    2015-01-01

    Herein, we report cloning and analysis of promoters of GLABRA2 (AaGL2) homolog and a MIXTA-Like (AaMIXTA-Like1) gene from Artemisia annua. The upstream regulatory regions of AaGL2 and AaMIXTA-Like1 showed the presence of several crucial cis-acting elements. Arabidopsis and A. annua seedlings were transiently transfected with the promoter-GUS constructs using a robust agro-infiltration method. Both AaGL2 and AaMIXTA-Like1 promoters showed GUS expression preferentially in Arabidopsis single-celled trichomes and glandular as well as T-shaped trichomes of A. annua. Transgenic Arabidopsis harboring constructs in which AaGL2 or AaMIXTA-Like1 promoters would control GFP expression, showed fluorescence emanating specifically from trichome cells. Our study provides a fast and efficient method to study trichome-specific expression, and 2 promoters that have potential for targeted metabolic engineering in plants. PMID:26340695

  8. TU-F-18C-05: Evaluation of a Method to Calculate Patient-Oriented MGD Coefficients Using Estimates of Glandular Tissue Distribution

    SciTech Connect

    Porras-Chaverri, M; Galavis, P; Bakic, P; Vetter, J

    2014-06-15

    Purpose: Evaluate mammographic mean glandular dose (MGD) coefficients for particular known tissue distributions using a novel formalism that incorporates the effect of the heterogeneous glandular tissue distribution, by comparing them with MGD coefficients derived from the corresponding anthropomorphic computer breast phantom. Methods: MGD coefficients were obtained using MCNP5 simulations with the currently used homogeneous assumption and the heterogeneously-layered breast (HLB) geometry and compared against those from the computer phantom (ground truth). The tissue distribution for the HLB geometry was estimated using glandularity map image pairs corrected for the presence of non-glandular fibrous tissue. Heterogeneity of tissue distribution was quantified using the glandular tissue distribution index, Idist. The phantom had 5 cm compressed breast thickness (MLO and CC views) and 29% whole breast glandular percentage. Results: Differences as high as 116% were found between the MGD coefficients with the homogeneous breast core assumption and those from the corresponding ground truth. Higher differences were found for cases with more heterogeneous distribution of glandular tissue. The Idist for all cases was in the [−0.8{sup −}+0.3] range. The use of the methods presented in this work results in better agreement with ground truth with an improvement as high as 105 pp. The decrease in difference across all phantom cases was in the [9{sup −}105] pp range, dependent on the distribution of glandular tissue and was larger for the cases with the highest Idist values. Conclusion: Our results suggest that the use of corrected glandularity image pairs, as well as the HLB geometry, improves the estimates of MGD conversion coefficients by accounting for the distribution of glandular tissue within the breast. The accuracy of this approach with respect to ground truth is highly dependent on the particular glandular tissue distribution studied. Predrag Bakic discloses

  9. Adult ciliary epithelial stem cells generate functional neurons and differentiate into both early and late born retinal neurons under non-cell autonomous influences

    PubMed Central

    2013-01-01

    Background The neural stem cells discovered in the adult ciliary epithelium (CE) in higher vertebrates have emerged as an accessible source of retinal progenitors; these cells can self-renew and possess retinal potential. However, recent studies have cast doubt as to whether these cells could generate functional neurons and differentiate along the retinal lineage. Here, we have systematically examined the pan neural and retinal potential of CE stem cells. Results Molecular and cellular analysis was carried out to examine the plasticity of CE stem cells, obtained from mice expressing green fluorescent protein (GFP) under the influence of the promoter of the rod photoreceptor-specific gene, Nrl, using the neurospheres assay. Differentiation was induced by specific culture conditions and evaluated by both transcripts and protein levels of lineage-specific regulators and markers. Temporal pattern of their levels were examined to determine the expression of genes and proteins underlying the regulatory hierarchy of cells specific differentiation in vitro. Functional attributes of differentiation were examined by the presence of current profiles and pharmacological mobilization of intracellular calcium using whole cell recordings and Fura-based calcium imaging, respectively. We demonstrate that stem cells in adult CE not only have the capacity to generate functional neurons, acquiring the expression of sodium and potassium channels, but also respond to specific cues in culture and preferentially differentiate along the lineages of retinal ganglion cells (RGCs) and rod photoreceptors, the early and late born retinal neurons, respectively. The retinal differentiation of CE stem cells was characterized by the temporal acquisition of the expression of the regulators of RGCs and rod photoreceptors, followed by the display of cell type-specific mature markers and mobilization of intracellular calcium. Conclusions Our study demonstrates the bonafide retinal potential of adult CE

  10. Incidence of anti-intermediate filament antibody in serum samples of students with suspected glandular fever.

    PubMed Central

    Kataaha, P K; Holborow, E J; Edwards, J M

    1985-01-01

    Serum samples from 40 students with suspected infectious mononucleosis were tested for the presence of antibodies to intermediate filaments (AIFA) of the cytoskeleton. Twenty had antibodies to the Epstein-Barr virus capsid antigen before their illness, and during it their sera remained negative by the Paul-Bunnell test. The other 20 patients did not have antibodies to the Epstein-Barr virus capsid antigen before their illness and seroconverted during the illness. These patients (true infectious mononucleosis group) developed positive Paul-Bunnell tests. Sera from normal subjects (blood donors) were also tested for AIFA. AIFA was present in titres greater than 1/10 in 80% of the infectious mononucleosis group (mean titre 1/40-1/80), 10% of the Paul-Bunnell negative glandular fever group, and 8.5% of the normal blood donors. PMID:2982922

  11. PTEN Phosphatase-Independent Maintenance of Glandular Morphology in a Predictive Colorectal Cancer Model System1

    PubMed Central

    Jagan, Ishaan C; Deevi, Ravi K; Fatehullah, Aliya; Topley, Rebecca; Eves, Joshua; Stevenson, Michael; Loughrey, Maurice; Arthur, Kenneth; Campbell, Frederick Charles

    2013-01-01

    Organotypic models may provide mechanistic insight into colorectal cancer (CRC) morphology. Three-dimensional (3D) colorectal gland formation is regulated by phosphatase and tensin homologue deleted on chromosome 10 (PTEN) coupling of cell division cycle 42 (cdc42) to atypical protein kinase C (aPKC). This study investigated PTEN phosphatase-dependent and phosphatase-independent morphogenic functions in 3D models and assessed translational relevance in human studies. Isogenic PTEN-expressing or PTEN-deficient 3D colorectal cultures were used. In translational studies, apical aPKC activity readout was assessed against apical membrane (AM) orientation and gland morphology in 3D models and human CRC. We found that catalytically active or inactive PTEN constructs containing an intact C2 domain enhanced cdc42 activity, whereas mutants of the C2 domain calcium binding region 3 membrane-binding loop (M-CBR3) were ineffective. The isolated PTEN C2 domain (C2) accumulated in membrane fractions, but C2 M-CBR3 remained in cytosol. Transfection of C2 but not C2 M-CBR3 rescued defective AM orientation and 3D morphogenesis of PTEN-deficient Caco-2 cultures. The signal intensity of apical phospho-aPKC correlated with that of Na+/H+ exchanger regulatory factor-1 (NHERF-1) in the 3D model. Apical NHERF-1 intensity thus provided readout of apical aPKC activity and associated with glandular morphology in the model system and human colon. Low apical NHERF-1 intensity in CRC associated with disruption of glandular architecture, high cancer grade, and metastatic dissemination. We conclude that the membrane-binding function of the catalytically inert PTEN C2 domain influences cdc42/aPKC-dependent AM dynamics and gland formation in a highly relevant 3D CRC morphogenesis model system. PMID:24348097

  12. Comparison of mammography sensitivity after reduction mammoplasty targeting the glandular and fat tissue

    PubMed Central

    Çakır, Murat; Küçükkartallar, Tevfik; Tekin, Ahmet; Selimoğlu, Nebil; Poyraz, Necdet; Belviranlı, Mehmet Metin; Kartal, Adil

    2015-01-01

    Objective: Mammography may have some limitations in the diagnosis and screening of breast cancer for women who have previously undergone breast reduction surgery. This study aimed to investigate how the structural defects in the breast tissue formed by postoperative changes are reflected on mammography. Material and Methods: The records of patients who had previously undergone breast reduction surgery and who were requested to undergo mammography for breast cancer screening by the general surgery clinic were retrospectively studied. The patients’ ages, surgical procedures, postoperative follow-up periods, amount of removed material, and histopathological and mammographic results were studied. The patients were classified into 3 groups: those older than 40 years who underwent reduction mammoplasty targeting predominantly the glandular tissue (group 1), those younger than 40 years who underwent reduction mammoplasty targeting predominantly the fat tissue (group 2), and those older than 40 years who were diagnosed with breast hypertrophy and were not operated (group 3). Results: The mean follow-up period of the patients was 6 (2–10) years. The mean value of resected tissue was 1120 g (680–2070) in group 1 and 1220 g (720–1980) in group 2. The mean age at the time of surgery was 45 (40–70) years for group 1 and 35 (24–40) years for group 2. All patients in group 1 were classified in Breast Imaging-Reporting and Data System (BI-RADS) category 1–2; 28 patients in group 2 were classified in BI-RADS 1–2, 4 were classified in BI-RADS 3, and 8 were classified in BI-RADS 0. In group 3, 35 patients were classified in BI-RADS 1–2, 4 were classified in BI-RADS 3, and 1 was classified in BI-RADS 0. Conclusion: We believe that breast reduction surgery targeting predominantly the glandular tissue in patients older than 40 years increases mammographic sensitivity. PMID:26170752

  13. Effect of filter on average glandular dose and image quality in digital mammography

    NASA Astrophysics Data System (ADS)

    Songsaeng, C.; Krisanachinda, A.; Theerakul, K.

    2016-03-01

    To determine the average glandular dose and entrance surface air kerma in both phantoms and patients to assess image quality for different target-filters (W/Rh and W/Ag) in digital mammography system. The compressed breast thickness, compression force, average glandular dose, entrance surface air kerma, peak kilovoltage and tube current time were recorded and compared between W/Rh and W/Ag target filter. The CNR and the figure of merit were used to determine the effect of target filter on image quality. The mean AGD of the W/Rh target filter was 1.75 mGy, the mean ESAK was 6.67 mGy, the mean CBT was 54.1 mm, the mean CF was 14 1bs. The mean AGD of W/Ag target filter was 2.7 mGy, the mean ESAK was 12.6 mGy, the mean CBT was 75.5 mm, the mean CF was 15 1bs. In phantom study, the AGD was 1.2 mGy at 4 cm, 3.3 mGy at 6 cm and 3.83 mGy at 7 cm thickness. The FOM was 24.6, CNR was 9.02 at thickness 6 cm. The FOM was 18.4, CNR was 8.6 at thickness 7 cm. The AGD from Digital Mammogram system with W/Rh of thinner CBT was lower than the AGD from W/Ag target filter.

  14. Estimates of Average Glandular Dose with Auto-modes of X-ray Exposures in Digital Breast Tomosynthesis

    PubMed Central

    Kamal, Izdihar; Chelliah, Kanaga K.; Mustafa, Nawal

    2015-01-01

    Objectives: The aim of this research was to examine the average glandular dose (AGD) of radiation among different breast compositions of glandular and adipose tissue with auto-modes of exposure factor selection in digital breast tomosynthesis. Methods: This experimental study was carried out in the National Cancer Society, Kuala Lumpur, Malaysia, between February 2012 and February 2013 using a tomosynthesis digital mammography X-ray machine. The entrance surface air kerma and the half-value layer were determined using a 100H thermoluminescent dosimeter on 50% glandular and 50% adipose tissue (50/50) and 20% glandular and 80% adipose tissue (20/80) commercially available breast phantoms (Computerized Imaging Reference Systems, Inc., Norfolk, Virginia, USA) with auto-time, auto-filter and auto-kilovolt modes. Results: The lowest AGD for the 20/80 phantom with auto-time was 2.28 milliGray (mGy) for two dimension (2D) and 2.48 mGy for three dimensional (3D) images. The lowest AGD for the 50/50 phantom with auto-time was 0.97 mGy for 2D and 1.0 mGy for 3D. Conclusion: The AGD values for both phantoms were lower against a high kilovolt peak and the use of auto-filter mode was more practical for quick acquisition while limiting the probability of operator error. PMID:26052465

  15. Opposing Roles of Foliar and Glandular Trichome Volatile Components in Cultivated Nightshade Interaction with a Specialist Herbivore.

    PubMed

    Murungi, Lucy Kananu; Kirwa, Hillary; Salifu, Daisy; Torto, Baldwyn

    2016-01-01

    Plant chemistry is an important contributor to the interaction with herbivores. Here, we report on a previously unknown role for foliar and glandular trichome volatiles in their interaction with the specialist herbivore of solanaceous plants, the tomato red spider mite Tetranychus evansi. We used various bioassays and chemical analyses including coupled gas chromatography-mass spectrometry (GC/MS) and liquid chromatography coupled to quadrupole time of flight mass spectrometry (LC-QToF-MS) to investigate this interaction between cultivated African nightshades and T. evansi. We show that, whereas morphologically different cultivated African nightshade species released similar foliar volatile organic compounds (VOCs) that attracted T. evansi, VOCs released from exudates of ruptured glandular trichomes of one nightshade species influenced local defense on the leaf surface. VOCs from ruptured glandular trichomes comprising mainly saturated and unsaturated fatty acids deterred T. evansi oviposition. Of the fatty acids, the unsaturated fatty acids accounted for >40% of the oviposition deterrent activity. Our findings point to a defense strategy in a plant, based on opposing roles for volatiles released by foliar and glandular trichomes in response to attack by a specialist herbivore. PMID:27556560

  16. Opposing Roles of Foliar and Glandular Trichome Volatile Components in Cultivated Nightshade Interaction with a Specialist Herbivore

    PubMed Central

    Murungi, Lucy Kananu; Kirwa, Hillary; Salifu, Daisy; Torto, Baldwyn

    2016-01-01

    Plant chemistry is an important contributor to the interaction with herbivores. Here, we report on a previously unknown role for foliar and glandular trichome volatiles in their interaction with the specialist herbivore of solanaceous plants, the tomato red spider mite Tetranychus evansi. We used various bioassays and chemical analyses including coupled gas chromatography-mass spectrometry (GC/MS) and liquid chromatography coupled to quadrupole time of flight mass spectrometry (LC-QToF-MS) to investigate this interaction between cultivated African nightshades and T. evansi. We show that, whereas morphologically different cultivated African nightshade species released similar foliar volatile organic compounds (VOCs) that attracted T. evansi, VOCs released from exudates of ruptured glandular trichomes of one nightshade species influenced local defense on the leaf surface. VOCs from ruptured glandular trichomes comprising mainly saturated and unsaturated fatty acids deterred T. evansi oviposition. Of the fatty acids, the unsaturated fatty acids accounted for >40% of the oviposition deterrent activity. Our findings point to a defense strategy in a plant, based on opposing roles for volatiles released by foliar and glandular trichomes in response to attack by a specialist herbivore. PMID:27556560

  17. Glandular trichome density and essential oil composition in leaves and inflorescences of Lippia origanoides Kunth (Verbenaceae) in the Brazilian Cerrado.

    PubMed

    Tozin, Luiz R S; Marques, Marcia O M; Rodrigues, Tatiane M

    2015-01-01

    The essential oils from leaves and inflorescences of Lippia origanoides Kunth present aromatic and medicinal potential and have been used to treat several diseases, including melanoma. In Brazil, L. origanoides is commonly found in campo cerrado and cerrado stricto sensu, physiognomies featured mainly by the differential light conditions to which short and medium-sized plants are subjected. Our aim was to investigate the glandular trichome density and the yield and chemical composition of the essential oils in leaves and inflorescences of L. origanoides from campo cerrado and cerrado stricto sensu. For glandular density analysis, leaves and inflorescences were processed according to conventional techniques for scanning electron microscopy. The essential oils of leaves and inflorescences were obtained by hydrodistillation and identified with gas chromatography. Bracts and sepals showed the highest glandular density, followed by petals and leaves. The glandular density in the abaxial leaf surface was higher in individuals from the campo cerrado. In both populations the essential oil yield was higher in inflorescences than in leaves. The chemical composition of the essential oils varied among individuals from different areas and inside a same population. Our results demonstrated the chemical plasticity of L. origanoides suggesting the importance of monitoring its popular use. PMID:26131639

  18. Optimizing the anode-filter combination in the sense of image quality and average glandular dose in digital mammography

    NASA Astrophysics Data System (ADS)

    Varjonen, Mari; Strömmer, Pekka

    2008-03-01

    This paper presents the optimized image quality and average glandular dose in digital mammography, and provides recommendations concerning anode-filter combinations in digital mammography, which is based on amorphous selenium (a-Se) detector technology. The full field digital mammography (FFDM) system based on a-Se technology, which is also a platform of tomosynthesis prototype, was used in this study. X-ray tube anode-filter combinations, which we studied, were tungsten (W) - rhodium (Rh) and tungsten (W) - silver (Ag). Anatomically adaptable fully automatic exposure control (AAEC) was used. The average glandular doses (AGD) were calculated using a specific program developed by Planmed, which automates the method described by Dance et al. Image quality was evaluated in two different ways: a subjective image quality evaluation, and contrast and noise analysis. By using W-Rh and W-Ag anode-filter combinations can be achieved a significantly lower average glandular dose compared with molybdenum (Mo) - molybdenum (Mo) or Mo-Rh. The average glandular dose reduction was achieved from 25 % to 60 %. In the future, the evaluation will concentrate to study more filter combinations and the effect of higher kV (>35 kV) values, which seems be useful while optimizing the dose in digital mammography.

  19. Abnormal ion content, hydration and granule expansion of the secretory granules from cystic fibrosis airway glandular cells

    SciTech Connect

    Baconnais, S.; Delavoie, F. |; Zahm, J.M.; Milliot, M.; Castillon, N.; Terryn, C.; Banchet, V.; Michel, J.; Danos, O.; Merten, M.; Chinet, T.; Zierold, K.; Bonnet, N.; Puchelle, E. , E-Mail: edith.puchelle@univ-reims.fr; Balossier, G.

    2005-10-01

    The absence or decreased expression of cystic fibrosis transmembrane conductance regulator (CFTR) induces increased Na{sup +} absorption and hyperabsorption of the airway surface liquid (ASL) resulting in a dehydrated and hyperviscous ASL. Although the implication of abnormal airway submucosal gland function has been suggested, the ion and water content in the Cystic Fibrosis (CF) glandular secretory granules, before exocytosis, is unknown. We analyzed, in non-CF and CF human airway glandular cell lines (MM-39 and KM4, respectively), the ion content in the secretory granules by electron probe X-ray microanalysis and the water content by quantitative dark field imaging on freeze-dried cryosections. We demonstrated that the ion content (Na{sup +}, Mg{sup 2+}, P, S and Cl{sup -}) is significantly higher and the water content significantly lower in secretory granules from the CF cell line compared to the non-CF cell line. Using videomicroscopy, we observed that the secretory granule expansion was deficient in CF glandular cells. Transfection of CF cells with CFTR cDNA or inhibition of non-CF cells with CFTR{sub inh}-172, respectively restored or decreased the water content and granule expansion, in parallel with changes in ion content. We hypothesize that the decreased water and increased ion content in glandular secretory granules may contribute to the dehydration and increased viscosity of the ASL in CF.

  20. Early Diagnosis and Staging.

    PubMed

    Lilja, H; Lilja, D R H

    1999-01-01

    This report reviews developments in the early diagnosis and staging of prostate cancer and updated on the incidence of postate cancer to discuss the pros and cons of population based screening. Refinements and reliability of various diagnosic procedures are described such as PSA testing, transrectal ultrasound, ratio beteen PSA-level and ultrasound measured prostate volume, rate of change of PSA-level, combination factor equations computed by neural network programs to predict likelihood of prostate cancer, artificial neural network analysis of subvisual transrectal ultrasound information, measurements of different PSA-forms of PSA (in particular percent free PSA), and glandular kallikrein 2. PMID:12496851

  1. Synovial sarcoma specific translocation associated with both epithelial and spindle cell components.

    PubMed

    Birdsall, S; Osin, P; Lu, Y J; Fisher, C; Shipley, J

    1999-08-12

    The biphasic subtype of synovial sarcoma consists of both epithelial and spindle cell components. To address the relationship between the different cellular components found in synovial sarcoma, we deduced the presence of the synovial sarcoma-specific der(X)t(X;18)(p11.2;q11.2), and involvement of the SSX1 gene in both the epithelial/glandular and spindle cell components of 3 biphasic synovial sarcomas with wide ranging proportions of each of the 2 elements. This has been achieved using a 2-color fluorescence in situ hybridization (FISH) methodology that we had developed recently for analysis paraffin-embedded material. The presence of the rearrangement could be deduced in histologically defined regions and the results showed clearly that the rearrangement was present in both cellular components. This finding provides direct genetic evidence for biphasic synovial sarcomas being clonal and truly biphasic. PMID:10404078

  2. Epithelial surfaces of the trachea and principal bronchi in the rat.

    PubMed Central

    Alexander, I; Ritchie, B C; Maloney, J E; Hunter, C R

    1975-01-01

    The epithelial surfaces in the trachea and principal bronchi of healthy rats were examined by scanning electron microscopy. A system of four cell types, ciliated, microvillous, brush, and goblet cells, in this order of frequency, were found and intermediate type cells were not seen. An extensive area of the surface examined was covered by densely ciliated epithelium. The presence of other cell types beneath the cilia was confirmed by transmission electron microscopy. Areas up to 1 mm in diameter and randomly distributed were observed where microvillous cells predominated and only occasional ciliated cells were found. Most ciliated cells in these areas were adjacent to glandular openings or goblet cells. The larger microvilli of the brush cells were arranged in a coronal configuration elucidated by the scanning electron microscope. Preparatory techniques recently introduced for the examination of soft tissue in the scanning electron microscope facilitated the confirmation of cell types present and the microarchitecture of the epithelial surface. Images PMID:1179314

  3. Mean glandular dose estimation using MCNPX for a digital breast tomosynthesis system with tungsten/aluminum and tungsten/aluminum+silver x-ray anode-filter combinations

    SciTech Connect

    Ma, Andy K. W.; Darambara, Dimitra G.; Stewart, Alexander; Gunn, Spencer; Bullard, Edward

    2008-12-15

    Breast cancer screening with x-ray mammography, using one or two projection images of the breast, is an indispensible tool in the early detection of breast cancer in women. Digital breast tomosynthesis (DBT) is a 3D imaging technique that promises higher sensitivity and specificity in breast cancer screening at a similar radiation dose to conventional two-view screening mammography. In DBT a 3D volume is reconstructed with anisotropic voxels from a limited number of x-ray projection images acquired over a limited angle. Although the benefit of early cancer detection through screening mammography outweighs the potential risks associated with radiation, the radiation dosage to women in terms of mean glandular dose (MGD) is carefully monitored. This work studies the MGD arising from a prototype DBT system under various parameters. Two anode/filter combinations (W/Al and W/Al+Ag) were investigated; the tube potential ranges from 20 to 50 kVp; and the breast size varied between 4 and 10 cm chest wall-to-nipple distance and between 3 and 7 cm compressed breast thickness. The dosimetric effect of breast positioning with respect to the imaging detector was also reviewed. It was found that the position of the breast can affect the MGD by as much as 5% to 13% depending on the breast size.

  4. Klebsiella pneumoniae Is Able to Trigger Epithelial-Mesenchymal Transition Process in Cultured Airway Epithelial Cells

    PubMed Central

    Leone, Laura; Mazzetta, Francesca; Martinelli, Daniela; Valente, Sabatino; Alimandi, Maurizio; Raffa, Salvatore; Santino, Iolanda

    2016-01-01

    The ability of some bacterial pathogens to activate Epithelial-Mesenchymal Transition normally is a consequence of the persistence of a local chronic inflammatory response or depends on a direct interaction of the pathogens with the host epithelial cells. In this study we monitored the abilities of the K. pneumoniae to activate the expression of genes related to EMT-like processes and the occurrence of phenotypic changes in airway epithelial cells during the early steps of cell infection. We describe changes in the production of intracellular reactive oxygen species and increased HIF-1α mRNA expression in cells exposed to K. pneumoniae infection. We also describe the upregulation of a set of transcription factors implicated in the EMT processes, such as Twist, Snail and ZEB, indicating that the morphological changes of epithelial cells already appreciable after few hours from the K. pneumoniae infection are tightly regulated by the activation of transcriptional pathways, driving epithelial cells to EMT. These effects appear to be effectively counteracted by resveratrol, an antioxidant that is able to exert a sustained scavenging of the intracellular ROS. This is the first report indicating that strains of K. pneumoniae may promote EMT-like programs through direct interaction with epithelial cells without the involvement of inflammatory cells. PMID:26812644

  5. Transcriptional profiling unravels potential metabolic activities of the olive leaf non-glandular trichome.

    PubMed

    Koudounas, Konstantinos; Manioudaki, Maria E; Kourti, Anna; Banilas, Georgios; Hatzopoulos, Polydefkis

    2015-01-01

    The olive leaf trichomes are multicellular peltate hairs densely distributed mainly at the lower leaf epidermis. Although, non-glandular, they have gained much attention since they significantly contribute to abiotic and biotic stress tolerance of olive leaves. The exact mechanisms by which olive trichomes achieve these goals are not fully understood. They could act as mechanical barrier but they also accumulate high amounts of flavonoids among other secondary metabolites. However, little is currently known about the exact compounds they produce and the respective metabolic pathways. Here we present the first EST analysis from olive leaf trichomes by using 454-pyrosequencing. A total of 5368 unigenes were identified out of 7258 high quality reads with an average length of 262 bp. Blast search revealed that 27.5% of them had high homologies to known proteins. By using Blast2GO, 1079 unigenes (20.1%) were assigned at least one Gene Ontology (GO) term. Most of the genes were involved in cellular and metabolic processes and in binding functions followed by catalytic activity. A total of 521 transcripts were mapped to 67 KEGG pathways. Olive trichomes represent a tissue of highly unique transcriptome as per the genes involved in developmental processes and the secondary metabolism. The results indicate that mature olive trichomes are trancriptionally active, mainly through the potential production of enzymes that contribute to phenolic compounds with important roles in biotic and abiotic stress responses. PMID:26322070

  6. Transcriptional profiling unravels potential metabolic activities of the olive leaf non-glandular trichome

    PubMed Central

    Koudounas, Konstantinos; Manioudaki, Maria E.; Kourti, Anna; Banilas, Georgios; Hatzopoulos, Polydefkis

    2015-01-01

    The olive leaf trichomes are multicellular peltate hairs densely distributed mainly at the lower leaf epidermis. Although, non-glandular, they have gained much attention since they significantly contribute to abiotic and biotic stress tolerance of olive leaves. The exact mechanisms by which olive trichomes achieve these goals are not fully understood. They could act as mechanical barrier but they also accumulate high amounts of flavonoids among other secondary metabolites. However, little is currently known about the exact compounds they produce and the respective metabolic pathways. Here we present the first EST analysis from olive leaf trichomes by using 454-pyrosequencing. A total of 5368 unigenes were identified out of 7258 high quality reads with an average length of 262 bp. Blast search revealed that 27.5% of them had high homologies to known proteins. By using Blast2GO, 1079 unigenes (20.1%) were assigned at least one Gene Ontology (GO) term. Most of the genes were involved in cellular and metabolic processes and in binding functions followed by catalytic activity. A total of 521 transcripts were mapped to 67 KEGG pathways. Olive trichomes represent a tissue of highly unique transcriptome as per the genes involved in developmental processes and the secondary metabolism. The results indicate that mature olive trichomes are trancriptionally active, mainly through the potential production of enzymes that contribute to phenolic compounds with important roles in biotic and abiotic stress responses. PMID:26322070

  7. Single-cell analysis of glandular T cell receptors in Sjögren’s syndrome

    PubMed Central

    Joachims, Michelle L.; Leehan, Kerry M.; Lawrence, Christina; Pelikan, Richard C.; Moore, Jacen S.; Pan, Zijian; Rasmussen, Astrid; Radfar, Lida; Lewis, David M.; Grundahl, Kiely M.; Kelly, Jennifer A.; Wiley, Graham B.; Shugay, Mikhail; Chudakov, Dmitriy M.; Lessard, Christopher J.; Stone, Donald U.; Scofield, R. Hal; Montgomery, Courtney G.; Sivils, Kathy L.; Thompson, Linda F.; Farris, A. Darise

    2016-01-01

    CD4+ T cells predominate in salivary gland (SG) inflammatory lesions in Sjögren’s syndrome (SS). However, their antigen specificity, degree of clonal expansion, and relationship to clinical disease features remain unknown. We used multiplex reverse-transcriptase PCR to amplify paired T cell receptor α (TCRα) and β transcripts of single CD4+CD45RA− T cells from SG and peripheral blood (PB) of 10 individuals with primary SS, 9 of whom shared the HLA DR3/DQ2 risk haplotype. TCRα and β sequences were obtained from a median of 91 SG and 107 PB cells per subject. The degree of clonal expansion and frequency of cells expressing two productively rearranged α genes were increased in SG versus PB. Expanded clones from SG exhibited complementary-determining region 3 (CDR3) sequence similarity both within and among subjects, suggesting antigenic selection and shared antigen recognition. CDR3 similarities were shared among expanded clones from individuals discordant for canonical Ro and La autoantibodies, suggesting recognition of alternative SG antigen(s). The extent of SG clonal expansion correlated with reduced saliva production and increased SG fibrosis, linking expanded SG T cells with glandular dysfunction. Knowledge of paired TCRα and β sequences enables further work toward identification of target antigens and development of novel therapies. PMID:27358913

  8. Localization of sesquiterpene lactone biosynthesis in cells of capitate glandular trichomes of Helianthus annuus (Asteraceae).

    PubMed

    Amrehn, Evelyn; Aschenbrenner, Anna-Katharina; Heller, Annerose; Spring, Otmar

    2016-03-01

    Capitate glandular trichomes (CGT) of sunflower, Helianthus annuus, synthesize bioactive sesquiterpene lactones (STLs) within a short period of only a few days during trichome development. In the current project, the subcellular localization of H. annuus germacrene A monooxygenase (HaGAO), a key enzyme of the STL biosynthesis in sunflower CGT, was investigated. A polyclonal antibody raised against this enzyme was used for immunolabelling. HaGAO was found in secretory and stalk cells of CGT. This correlated with the appearance of smooth endoplasmic reticulum in both cell types. Stalk cells and secretory cells differed in form, size and types of plastids, but both had structures necessary for secretion. No HaGAO-specific immunoreaction was found in sunflower leaf tissue outside of CGT or in developing CGT before the secretory phase had started. Our results indicated that not only secretory cells but also nearly all cells of the CGT were involved in the biosynthesis of STL and that this process was not linked to the presence or absence of a specific type of plastid. PMID:25956500

  9. Mixed squamous cell and glandular papilloma of the lung: a case study and literature review.

    PubMed

    Inamura, Kentaro; Kumasaka, Toshio; Furuta, Reiko; Shimada, Kei; Hiyama, Noriko; Furuhata, Yoshiaki; Tanaka, Isao; Takemura, Tamiko

    2011-04-01

    Mixed squamous cell and glandular papilloma (mixed papilloma) of the lung is an extremely rare neoplasm, with only 10 cases reported so far in the English literature. We present a case study of endobronchial mixed papilloma with immunohistochemical and etiological investigations. A 49-year-old male with a smoking history complained of hemoptysis, presented with a lung mass closely adjacent to large vessels in the computed tomography findings, and underwent lobectomy. The 3.0-cm sized polypoid tumor was histologically diagnosed as endobronchial mixed papilloma. Immunohistochemically, intracellular mucin was positive for MUC5AC, which is expressed in tracheobronchial goblet cells. CAM5.2 and CK19 were diffusely positive, indicating that the tumor originated from the columnar epithelium by squamous metaplasia. CEA and CA19-9 were focally positive. A human papillomavirus (HPV) investigation with in situ hybridization using a wide spectrum probe and a newly-developed PCR system did not detect any HPV infection. Including this case with a detailed HPV investigation, all of the reported cases of mixed papilloma were HPV-negative, and a literature review including newly-reported cases indicated a high frequency of smoking in such cases. Endobronchial mixed papillomas might have a smoking-related etiology. PMID:21418399

  10. Terpene Biosynthesis in Glandular Trichomes of Hop12[W][OA

    PubMed Central

    Wang, Guodong; Tian, Li; Aziz, Naveed; Broun, Pierre; Dai, Xinbin; He, Ji; King, Andrew; Zhao, Patrick X.; Dixon, Richard A.

    2008-01-01

    Hop (Humulus lupulus L. Cannabaceae) is an economically important crop for the brewing industry, where it is used to impart flavor and aroma to beer, and has also drawn attention in recent years due to its potential pharmaceutical applications. Essential oils (mono- and sesquiterpenes), bitter acids (prenylated polyketides), and prenylflavonoids are the primary phytochemical components that account for these traits, and all accumulate at high concentrations in glandular trichomes of hop cones. To understand the molecular basis for terpene accumulation in hop trichomes, a trichome cDNA library was constructed and 9,816 cleansed expressed sequence tag (EST) sequences were obtained from random sequencing of 16,152 cDNA clones. The ESTs were assembled into 3,619 unigenes (1,101 contigs and 2,518 singletons). Putative functions were assigned to the unigenes based on their homology to annotated sequences in the GenBank database. Two mono- and two sesquiterpene synthases identified from the EST collection were expressed in Escherichia coli. Hop MONOTERPENE SYNTHASE2 formed the linear monterpene myrcene from geranyl pyrophosphate, whereas hop SESQUITERPENE SYNTHASE1 (HlSTS1) formed both caryophyllene and humulene from farnesyl pyrophosphate. Together, these enzymes account for the production of the major terpene constituents of the hop trichomes. HlSTS2 formed the minor sesquiterpene constituent germacrene A, which was converted to β-elemene on chromatography at elevated temperature. We discuss potential functions for other genes expressed at high levels in developing hop trichomes. PMID:18775972

  11. Glandular Odontogenic Cyst: Report of Two Cases and Review of Literature

    PubMed Central

    Sherlin, Herald J.; Ramalingam, Karthikeyan; Natesan, Anuja; Premkumar, Priya; Ramani, Pratibha; Chandrasekar, Thiruvengadam

    2009-01-01

    Glandular odontogenic cyst (GOC) is an uncommon jaw bone cyst of odontogenic origin described in 1987 by Gardner et al. It is a cyst having an unpredictable and potentially aggressive behaviour. It also has the propensity to grow to a large size and tendency to recur with only 111 cases having been reported thus far. The first case occurred in a 42-year-old female and presented as a localized swelling extending from 19 to 29 regions. There was a history of traumatic injury at the site. There was evidence of bicortical expansion and radiographs revealed a multilocular radiolucency. The second case occurred in a 21-year-old male, as a large swelling in the mandible and radiograph revealed radiolucency in the region. On histopathological examination, these lesions were diagnosed as GOC. It was concluded that, two cases submitted by us correlate with the existing literature that GOC’s affect more commonly in the middle age group, having predilection for mandible and that trauma could be a precipitating factor for its occurrence. The increased recurrence rates can be due to its intrinsic biological behavior, multilocularity of the cyst, and incomplete removal of the lining following conservative treatment. PMID:19644539

  12. miR-200c regulates FGFR-dependent epithelial proliferation via Vldlr during submandibular gland branching morphogenesis

    PubMed Central

    Rebustini, Ivan T.; Hayashi, Toru; Reynolds, Andrew D.; Dillard, Melvin L.; Carpenter, Ellen M.; Hoffman, Matthew P.

    2012-01-01

    The regulation of epithelial proliferation during organ morphogenesis is crucial for normal development, as dysregulation is associated with tumor formation. Non-coding microRNAs (miRNAs), such as miR-200c, are post-transcriptional regulators of genes involved in cancer. However, the role of miR-200c during normal development is unknown. We screened miRNAs expressed in the mouse developing submandibular gland (SMG) and found that miR-200c accumulates in the epithelial end buds. Using both loss- and gain-of-function, we demonstrated that miR-200c reduces epithelial proliferation during SMG morphogenesis. To identify the mechanism, we predicted miR-200c target genes and confirmed their expression during SMG development. We discovered that miR-200c targets the very low density lipoprotein receptor (Vldlr) and its ligand reelin, which unexpectedly regulate FGFR-dependent epithelial proliferation. Thus, we demonstrate that miR-200c influences FGFR-mediated epithelial proliferation during branching morphogenesis via a Vldlr-dependent mechanism. miR-200c and Vldlr may be novel targets for controlling epithelial morphogenesis during glandular repair or regeneration. PMID:22115756

  13. Impact of the Stem Extract of Thevetia neriifolia on the Feeding Potential and Histological Architecture of the Midgut Epithelial Tissue of Early Fourth Instars of Helicoverpa armigera Hübner

    PubMed Central

    Mishra, Monika; Gupta, Kamal Kumar; Kumar, Sarita

    2015-01-01

    Helicoverpa armigera Hübner is one of the most important agricultural crop pests in the world causing heavy crop yield losses. The continued and indiscriminate use of synthetic insecticides in agriculture for their control has received wide public apprehension because of multifarious problems, including insecticide resistance, resurgence of pest species, environmental pollution, and toxic hazards to humans and nontarget organisms. These problems have necessitated the need to explore and develop alternative strategies using eco-friendly and biodegradable plant products. In view of this, the efficacy of Thevetia neriifolia methanol stem extract was evaluated against the early fourth instars of H. armigera as an antifeedant and stomach poison agent. Feeding of larvae with the diet containing 0.005%–5.0% extract resulted in 2.06%–37.35% antifeedant index; the diet with 5.0% extract caused 54.3% reduced consumption. The negative impact of extract on larval feeding resulted in 37.5%–77.7% starvation, causing adverse effects on the larval weight. Choice between control and experimental diet resulted in feeding preference of larvae for the control diet, leading to 7.3%–42.9% reduced consumption of extract-containing diet. The only exception was the diet with 0.005% extract, which could not cause any deterrence. The midgut histological architecture of H. armigera larvae fed with 0.005%–0.05% extract-containing diet with negligible antifeedant potential showed significant damage, shrinkage, and distortion and vacuolization of gut tissues and peritrophic membrane, causing the disintegration of epithelial, goblet, and regenerative cells; the damage increased with the increase in concentration. These changes in the gut caused negative impact on the digestion and absorption of food and thus nutritional deficiency in the larvae, which could probably affect their growth and development. This study reveal the appreciable stomach poison potential of T. neriifolia stem

  14. Autoantibodies to tumor-associated antigens in epithelial ovarian carcinoma.

    PubMed

    Piura, Benjamin; Piura, Ettie

    2009-01-01

    This review will focus on recent knowledge related to circulating autoantibodies (AAbs) to tumor-associated antigens (TAAs) in epithelial ovarian carcinoma. So far, the following TAAs have been identified to elicit circulating AAbs in epithelial ovarian carcinoma: p53, homeobox proteins (HOXA7, HOXB7), heat shock proteins (HSP-27, HSP-90), cathepsin D, cancer-testis antigens (NY-ESO-1/LAGE-1), MUC1, GIPC-1, IL-8, Ep-CAM, and S100A7. Since AAbs to TAAs have been identified in the circulation of patients with early-stage cancer, it has been speculated that the assessment of a panel of AAbs specific for epithelial ovarian carcinoma TAAs might hold great potential as a novel tool for early diagnosis of epithelial ovarian carcinoma. PMID:20145720

  15. Characteristic and Functional Analysis of a Newly Established Porcine Small Intestinal Epithelial Cell Line

    PubMed Central

    Wang, Jing; Hu, Guangdong; Lin, Zhi; He, Lei; Xu, Lei; Zhang, Yanming

    2014-01-01

    The mucosal surface of intestine is continuously exposed to both potential pathogens and beneficial commensal microorganisms. Recent findings suggest that intestinal epithelial cells, which once considered as a simple physical barrier, are a crucial cell lineage necessary for maintaining intestinal immune homeostasis. Therefore, establishing a stable and reliable intestinal epithelial cell line for future research on the mucosal immune system is necessary. In the present study, we established a porcine intestinal epithelial cell line (ZYM-SIEC02) by introducing the human telomerase reverse transcriptase (hTERT) gene into small intestinal epithelial cells derived from a neonatal, unsuckled piglet. Morphological analysis revealed a homogeneous cobblestone-like morphology of the epithelial cell sheets. Ultrastructural indicated the presence of microvilli, tight junctions, and a glandular configuration typical of the small intestine. Furthermore, ZYM-SIEC02 cells expressed epithelial cell-specific markers including cytokeratin 18, pan-cytokeratin, sucrase-isomaltase, E-cadherin and ZO-1. Immortalized ZYM-SIEC02 cells remained diploid and were not transformed. In addition, we also examined the host cell response to Salmonella and LPS and verified the enhanced expression of mRNAs encoding IL-8 and TNF-α by infection with Salmonella enterica serovars Typhimurium (S. Typhimurium). Results showed that IL-8 protein expression were upregulated following Salmonella invasion. TLR4, TLR6 and IL-6 mRNA expression were upregulated following stimulation with LPS, ZYM-SIEC02 cells were hyporeponsive to LPS with respect to IL-8 mRNA expression and secretion. TNFα mRNA levels were significantly decreased after LPS stimulation and TNF-α secretion were not detected challenged with S. Typhimurium neither nor LPS. Taken together, these findings demonstrate that ZYM-SIEC02 cells retained the morphological and functional characteristics typical of primary swine intestinal epithelial

  16. Ultrastructure of posterior sternal glands of Macrotermes annandalei (Silvestri): new members of the sexual glandular set found in termites (Insecta).

    PubMed

    Quennedey, André; Peppuy, Alexis; Courrent, Annie; Robert, Alain; Everaerts, Claude; Bordereau, Christian

    2004-12-01

    In female alates of Macrotermes annandalei, two types of abdominal glands are involved in the secretion of sex pheromone. Tergal glands are found at the anterior margin of tergites 6-10 and posterior sternal glands (PSGs) are located at the anterior margin of sternites 6-7. The cytological features of both types of glands are quite similar. The fine structural organization of PSGs is studied more precisely and described for the first time. The glandular cuticle is pitted with narrow apertures corresponding to the openings of numerous subcuticular pouches. Several Class 3 glandular units open in each pouch. One canal cell and one secretory cell make an individual glandular unit. The canal cell is enlarged apically and is connected with the other canal cells to form a common pouch. Based on the structural features found in these glands, we propose a common secretory process for PSGs and tergal glands. During the physiological maturation of alates inside the nest, secretory vesicles amass in the cytoplasm of secretory cells, while large intercellular spaces collapse the cuticular pouches. At the time of dispersal flight, pouches are filled with the content of secretory vesicles while intercellular spaces are sharply reduced. After calling behavior, no secretion remains in the glands and pouches collapse again, while secretory cells are drastically reduced in size. The structure and the secretory processes of PSGs and tergal glands are compared to those of abdominal sexual glands known in termites. PMID:15487007

  17. Glandular trichomes and essential oil composition of endemic Sideritis italica (Mill.) Greuter et Burdet from central Italy.

    PubMed

    Giuliani, Claudia; Bini, Laura Maleci; Papa, Fabrizio; Cristalli, Gloria; Sagratini, Gianni; Vittori, Sauro; Lucarini, Domenico; Maggi, Filippo

    2011-12-01

    Sideritis italica (Mill.) Greuter et Burdet belongs to the Lamiaceae family and is endemic to Italy. The glandular trichomes (morphology, distribution, histochemistry, and ultrastructure) of the plant were studied for the first time, along with the chemical composition of the essential oils. Abundant non-glandular hairs and peltate (type A) and capitate (types B, C(1), and C(x)) glandular trichomes were observed both on the vegetative and reproductive organs. The histochemical procedures and the ultrastructural investigation enabled specific location of the main site of essential oil production mainly in type-A peltate hairs. Particular emphasis is given to the release mechanism of the secreted material in all of the types of glands, and the potential taxonomic value of the indumentum in the Lamiaceae family is briefly discussed. Essential oils were hydrodistilled from flowering aerial parts of S. italica, and 136 compounds (112 in flowerheads, 79 in vegetative parts) were identified. The quantitative prevalence of diterpenoids (43.4% in flowerheads and 22.3% in vegetative parts) was the most significant characteristic of the essential oil of S. italica that could be classified as a diterpene-rich essential oil according to the classification of Kirimer. PMID:22162157

  18. Epithelial expression of keratinocytes growth factor in oral precancer lesions

    PubMed Central

    Jimson, Sudha; Murali, S.; Zunt, Susan L.; Goldblatt, Lawrence I.; Srinivasan, Mythily

    2016-01-01

    Background: Keratinocyte growth factor (KGF) is a potent epithelial mitogen that acts by binding the KGF receptors (KGFRs) expressed on epithelial cells and regulates proliferation and differentiation. The objective of this study was to investigate the expression of KGF in the epithelium in oral precancer. Materials and Methods: Archival tissues of oral submucous fibrosis (SMF) and leukoplakia were assessed for epithelial KGF expression by immunohistochemistry and real-time quantitative polymerase chain reaction. Results: KGF was predominantly expressed in the basal and parabasal cells in the epithelium of SMF tissues. KGF transcript in the epithelial cells increased with increasing severity of epithelial dysplasia in oral leukoplakia. Conclusion: Although widely reported as a product secreted by the mesenchymal cells, our data suggest that the KGF is also expressed in oral epithelial cells much like the expression in ovarian epithelial cells. Based on the localization of KGF in cells at the epithelial mesenchymal junction and that of the reported presence of KGFR in oral keratinocytes, a potential mechanism involving paracrine and autocrine interactions of KGF and KGFR in early stages of oral precancer is postulated. PMID:27274338

  19. Fungal glycan interactions with epithelial cells in allergic airway disease

    PubMed Central

    Roy, René M.; Klein, Bruce S.

    2014-01-01

    Human exposure to fungi results in a wide range of health outcomes, from invasive disease or allergy to immune tolerance. Inhaled fungi contact airway epithelial cells as an early event, and this host:fungal interaction can shape the eventual immunological outcome. Emerging evidence points to exposure to fungal cell wall carbohydrates in the development of allergic airway disease. Herein, we describe determinants of fungal allergenicity, and review the responses of airway epithelial cells to fungal carbohydrates. A greater understanding of the recognition of and response to fungal carbohydrates by airway epithelial cells may lead to the development of targeted therapies that ameliorate allergic airway disease. PMID:23602359

  20. Ontogeny of Intestinal Epithelial Innate Immune Responses

    PubMed Central

    Hornef, Mathias W.; Fulde, Marcus

    2014-01-01

    Emerging evidence indicates that processes during postnatal development might significantly influence the establishment of mucosal host-microbial homeostasis. Developmental and adaptive immunological processes but also environmental and microbial exposure early after birth might thus affect disease susceptibility and health during adult life. The present review aims at summarizing the current understanding of the intestinal epithelial innate immune system and its developmental and adaptive changes after birth. PMID:25346729

  1. Light, Conventional and Environmental Scanning Electron Microscopy of the Trichomes of Cucurbita pepo subsp. pepo var. styriaca and Histochemistry of Glandular Secretory Products

    PubMed Central

    KOLB, DAGMAR; MÜLLER, MARIA

    2004-01-01

    • Background and Aims In the present study, the differences between glandular and non-glandular trichomes, the secretory process and the method of secretion were studied. Previous studies on leaves of Styrian oil pumpkin (Cucurbia pepo var. styriaca) plants have shown that four morphologically and ontogenetically independent glandular and non-glandular trichome types and one bristle hair type can be distinguished. The four types of trichomes can be categorized into three glandular trichome types: type I, a short-stalked trichome with four head cells including a ‘middle-cell’, two stalk cells and one basal cell; type II, a long-stalked trichome with two head cells, a ‘neck-cell’ region and a long stalk area; type IV, a ‘stipitate-capitate’ trichome with a mesophyll cell basement, a short stalk and a multicellular head; type III, a non-glandular ‘columnar-digit’ trichome, which consists of two head cells continuous with three-celled stalk, and the basal cell. • Methods The histochemical studies (the main classes of metabolite in secreted material of glandular trichomes) were conducted in fresh and fixed hand sections, using the following tests: Sudan black B, Nile blue A, osmium tetroxide, neutral red, Naturstoffreagent A, FSA (fuchsin–safranin–astra blue), NADI (naphthol + dimethylparaphenylenediamine) and ruthenium red. Each suggested differences in the intercalations during the ontogenetical development of each trichome during the development stage. • Key Results The histochemical reactions revealed the main components of the materials secreted by all types of trichomes, which include lipids, flavones and terpenes and the different cell wall compositions. Glandular secretions were observed during environmental scanning electron microscopy (ESEM) and the trichomes compared with those seen by conventional scanning electron microscopy (CSEM). • Conclusions Scanning electron microscopy and histochemical analysis demonstrated that each of

  2. Angiogenin expression during early human placental development; association with blood vessel formation.

    PubMed

    Pavlov, Nadine; Frendo, Jean-Louis; Guibourdenche, Jean; Degrelle, Séverine A; Evain-Brion, Danièle; Badet, Josette

    2014-01-01

    The placenta is a transient organ essential for fetal development. During human placental development, chorionic villi grow in coordination with a large capillary network resulting from both vasculogenesis and angiogenesis. Angiogenin is one of the most potent inducers of neovascularisation in experimental models in vivo. We and others have previously mapped angiogenin expression in the human term placenta. Here, we explored angiogenin involvement in early human placental development. We studied, angiogenin expression by in situ hybridisation and/or by RT-PCR in tissues and primary cultured trophoblastic cells and angiogenin cellular distribution by coimmunolabelling with cell markers: CD31 (PECAM-1), vascular endothelial cadherin (VE-cadherin), vascular endothelial growth factor receptor-2 (VEGF-R2), Tie-2, von Willebrand factor, CD34, erythropoeitin receptor (Epo-R), alpha-smooth muscle actin, CD45, cytokeratin 7, and Ki-67. Extravillous and villous cytotrophoblasts, isolated and differentiated in vitro, expressed and secreted angiogenin. Angiogenin was detected in villous trophoblastic layers, and structured and nascent fetal vessels. In decidua, it was expressed by glandular epithelial cells, vascular cells and macrophages. The observed pattern of angiogenin expression is compatible with a role in blood vessel formation and in cross-talk between trophoblasts and endothelial cells. In view of angiogenin properties, we suggest that angiogenin may participate in placental vasculogenesis and organogenesis. PMID:25093183

  3. Bovine myocardial epithelial inclusions.

    PubMed

    Baker, D C; Schmidt, S P; Langheinrich, K A; Cannon, L; Smart, R A

    1993-01-01

    Light microscopic, histochemical, immunohistochemical, and ultrastructural methods were used to examine myocardial epithelial masses in the hearts of ten cattle. The tissues consisted of paraffin-embedded or formalin-fixed samples from eight hearts that were being inspected in slaughter houses and from two hearts from calves that died of septicemia. The ages of the cattle ranged from 4 days to 12 years; the breeds were unspecified for all but one Hereford female and the two Holstein calves; and there were three males, four females, and three steers. The masses in these cases were compared with similar appearing lesions found in other animal species. The lesions in the bovine hearts were single to multiple, well circumscribed, found in the left ventricle wall, and composed of squamous to cuboidal epithelial cells that formed tubular, ductular, and acinar structures with lumens that were void or filled with amorphous protein globules. Electron microscopic examination revealed epithelial cells that had sparse apical microvilli, tight apical intercellular junctions, perinuclear bundles of filaments, and rare cilia. Almost half of the bovine epithelial masses (4/9) had occasional diastase-resistant periodic acid-Schiff-positive granules in their cytoplasm, and few had hyaluronidase-resistant alcian blue-positive granules (2/9) or colloidal iron-positive granules (1/9). All myocardial masses had abundant collagen surrounding the tubular and acinar structures, and 2/9 had elastin fibers as well. None of the myocardial masses had Churukian-Schenk or Fontana Masson's silver staining granules in epithelial cells. Immunohistochemically, all bovine myocardial tumors stained positively for cytokeratin (8/8), and occasional masses stained positively for vimentin (3/8) or carcinoembryonic antigen (3/8). None of the masses stained positively for desmin. The myocardial epithelial tumors most likely represent endodermal rests of tissue misplaced during organogenesis. PMID:7680178

  4. Epithelial tight junctions in intestinal inflammation.

    PubMed

    Schulzke, Joerg D; Ploeger, Svenja; Amasheh, Maren; Fromm, Anja; Zeissig, Sebastian; Troeger, Hanno; Richter, Jan; Bojarski, Christian; Schumann, Michael; Fromm, Michael

    2009-05-01

    The epithelium in inflamed intestinal segments of patients with Crohn's disease is characterized by a reduction of tight junction strands, strand breaks, and alterations of tight junction protein content and composition. In ulcerative colitis, epithelial leaks appear early due to micro-erosions resulting from upregulated epithelial apoptosis and in addition to a prominent increase of claudin-2. Th1-cytokine effects by interferon-gamma in combination with TNFalpha are important for epithelial damage in Crohn's disease, while interleukin-13 (IL-13) is the key effector cytokine in ulcerative colitis stimulating apoptosis and upregulation of claudin-2 expression. Focal lesions caused by apoptotic epithelial cells contribute to barrier disturbance in IBD by their own conductivity and by confluence toward apoptotic foci or erosions. Another type of intestinal barrier defect can arise from alpha-hemolysin harboring E. coli strains among the physiological flora, which can gain pathologic relevance in combination with proinflammatory cytokines under inflammatory conditions. On the other hand, intestinal barrier impairment can also result from transcellular antigen translocation via an initial endocytotic uptake into early endosomes, and this is intensified by proinflammatory cytokines as interferon-gamma and may thus play a relevant role in the onset of IBD. Taken together, barrier defects contribute to diarrhea by a leak flux mechanism (e.g., in IBD) and can cause mucosal inflammation by luminal antigen uptake. Immune regulation of epithelial functions by cytokines may cause barrier dysfunction not only by tight junction impairments but also by apoptotic leaks, transcytotic mechanisms, and mucosal gross lesions. PMID:19538319

  5. Negative ion 'chip-based' nanospray tandem mass spectrometry for the analysis of flavonoids in glandular trichomes of Lychnophora ericoides Mart. (Asteraceae).

    PubMed

    Gobbo-Neto, Leonardo; Gates, Paul J; Lopes, Norberto P

    2008-12-01

    This paper reports a method for the analysis of secondary metabolites stored in glandular trichomes, employing negative ion 'chip-based' nanospray tandem mass spectrometry. The analyses of glandular trichomes from Lychnophora ericoides, a plant endemic to the Brazilian 'cerrado' and used in traditional medicine as an anti-inflammatory and analgesic agent, led to the identification of five flavonoids (chrysin, pinocembrin, pinostrobin, pinobanksin and 3-O-acetylpinobanksin) by direct infusion of the extracts of glandular trichomes into the nanospray ionisation source. All the flavonoids have no oxidation at ring B, which resulted in a modification of the fragmentation pathways compared with that of the oxidised 3,4-dihydroflavonoids already described in the literature. The absence of the anti-inflammatory and antioxidant di-C-glucosylflavone vicenin-2, or any other flavonoid glycosides, in the glandular trichomes was also demonstrated. The use of the 'chip-based' nanospray QqTOF apparatus is a new fast and useful tool for the identification of secondary metabolites stored in the glandular trichomes, which can be useful for chemotaxonomic studies based on metabolites from glandular trichomes. PMID:18980260

  6. Risk of invasive cervical cancer after atypical glandular cells in cervical screening: nationwide cohort study

    PubMed Central

    Andrae, Bengt; Sundström, Karin; Ström, Peter; Ploner, Alexander; Elfström, K Miriam; Arnheim-Dahlström, Lisen; Dillner, Joakim; Sparén, Pär

    2016-01-01

    Objectives To investigate the risks of invasive cervical cancer after detection of atypical glandular cells (AGC) during cervical screening. Design Nationwide population based cohort study. Setting Cancer and population registries in Sweden. Participants 3 054 328 women living in Sweden at any time between 1 January 1980 and 1 July 2011 who had any record of cervical cytological testing at ages 23-59. Of these, 2 899 968 women had normal cytology results at the first screening record. The first recorded abnormal result was atypical glandular cells (AGC) in 14 625, high grade squamous intraepithelial lesion (HSIL) in 65 633, and low grade squamous intraepithelial lesions (LSIL) in 244 168. Main outcome measures Cumulative incidence of invasive cervical cancer over 15.5 years; proportion of invasive cervical cancer within six months of abnormality (prevalence); crude incidence rates for invasive cervical cancer over 0.5-15.5 years of follow-up; incidence rate ratios compared with women with normal cytology, estimated with Poisson regression adjusted for age and stratified by histopathology of cancer; distribution of clinical assessment within six months after the abnormality. Results The prevalence of cervical cancer was 1.4% for women with AGC, which was lower than for women with HSIL (2.5%) but higher than for women with LSIL (0.2%); adenocarcinoma accounted for 73.2% of the prevalent cases associated with AGC. The incidence rate of invasive cervical cancer after AGC was significantly higher than for women with normal results on cytology for up to 15.5 years and higher than HSIL and LSIL for up to 6.5 years. The incidence rate of adenocarcinoma was 61 times higher than for women with normal results on cytology in the first screening round after AGC, and remained nine times higher for up to 15.5 years. Incidence and prevalence of invasive cervical cancer was highest when AGC was found at ages 30-39. Only 54% of women with AGC underwent histology assessment

  7. Asymmetric Expression of Connexins between luminal epithelial- and myoepithelial- cells is Essential for Contractile Function of the Mammary Gland

    PubMed Central

    Mroue, Rana; Inman, Jamie; Mott, Joni; Budunova, Irina; Bissell, Mina J.

    2016-01-01

    Intercellular communication is essential for glandular functions and tissue homeostasis. Gap junctions couple cells homotypically and heterotypically and coordinate reciprocal responses between the different cell types. Connexins (Cxs) are the main mammalian gap junction proteins, and the distribution of some Cx subtypes in the heterotypic gap junctions is not symmetrical; in the murine mammary gland, Cx26, Cx30 and Cx32 are expressed only in the luminal epithelial cells and Cx43 is expressed only in myoepithelial cells. Expression of all four Cxs peaks during late pregnancy and throughout lactation suggesting essential roles for these proteins in the functional secretory activity of the gland. Transgenic (Tg) mice over-expressing Cx26 driven by keratin 5 promoter had an unexpected mammary phenotype: the mothers were unable to feed their pups to weaning age leading to litter starvation and demise in early to mid-lactation. The mammary gland of K5-Cx26 female mice developed normally and produced normal levels of milk protein, suggesting a defect in delivery rather than milk production. Because the mammary gland of K5-Cx26 mothers contained excessive milk, we hypothesized that the defect may be in an inability to eject the milk. Using ex vivo three-dimensional mammary organoid cultures, we showed that tissues isolated from wild-type FVB females contracted upon treatment with oxytocin, whereas, organoids from Tg mice failed to do so. Unexpectedly, we found that ectopic expression of Cx26 in myoepithelial cells altered the expression of endogenous Cx43 resulting in impaired gap junction communication, demonstrated by defective dye coupling in mammary epithelial cells of Tg mice. Inhibition of gap junction communication or knock-down of Cx43 in organoids from wild-type mice impaired contraction in response to oxytocin, recapitulating the observations from the mammary glands of Tg mice. We conclude that Cx26 acts as a trans-dominant negative for Cx43 function in

  8. Circulating progenitor epithelial cells traffic via CXCR4/CXCL12 in response to airway injury.

    PubMed

    Gomperts, Brigitte N; Belperio, John A; Rao, P Nagesh; Randell, Scott H; Fishbein, Michael C; Burdick, Marie D; Strieter, Robert M

    2006-02-01

    Recipient airway epithelial cells are found in human sex-mismatched lung transplants, implying that circulating progenitor epithelial cells contribute to the repair of the airway epithelium. Markers of circulating progenitor epithelial cells and mechanisms for their trafficking remain to be elucidated. We demonstrate that a population of progenitor epithelial cells exists in the bone marrow and the circulation of mice that is positive for the early epithelial marker cytokeratin 5 (CK5) and the chemokine receptor CXCR4. We used a mouse model of sex-mismatched tracheal transplantation and found that CK5+ circulating progenitor epithelial cells contribute to re-epithelialization of the airway and re-establishment of the pseudostratified epithelium. The presence of CXCL12 in tracheal transplants provided a mechanism for CXCR4+ circulating progenitor epithelial cell recruitment to the airway. Depletion of CXCL12 resulted in the epithelium defaulting to squamous metaplasia, which was derived solely from the resident tissue progenitor epithelial cells. Our findings demonstrate that CK5+CXCR4+ cells are markers of circulating progenitor epithelial cells in the bone marrow and circulation and that CXCR4/CXCL12-mediated recruitment of circulating progenitor epithelial cells is necessary for the re-establishment of a normal pseudostratified epithelium after airway injury. These findings support a novel paradigm for the development of squamous metaplasia of the airway epithelium and for developing therapeutic strategies for circulating progenitor epithelial cells in airway diseases. PMID:16424223

  9. SU-E-I-04: A Mammography Phantom to Measure Mean Glandular Dose and Image Quality

    SciTech Connect

    Lopez-Pineda, E; Ruiz-Trejo, C; E, Brandan M

    2014-06-01

    Purpose: To evaluate mean glandular dose (MGD) and image quality in a selection of mammography systems using a novel phantom based on thermoluminescent dosemeters and the ACR wax insert. Methods: The phantom consists of two acrylic, 19 cm diameter, 4.5 cm thick, semicircular modules, used in sequence. The image quality module contains the ACR insert and is used to obtain a quality control image under automatic exposure conditions. The dosimetric module carries 15 TLD-100 chips, some under Al foils, to determine air kerma and half-value-layer. TL readings take place at our laboratory under controlled conditions. Calibration was performed using an ionization chamber and a Senographe 2000D unit for a variety of beam qualities, from 24 to 40 kV, Mo and Rh anodes and filters. Phantom MGD values agree, on the average, within 3% with ionization chamber data, and their precision is better than 10% (k=1). Results: MGD and image quality have been evaluated in a selection of mammography units currently used in Mexican health services. The sample includes analogic (screen/film), flexible digital (CR), and full-field digital image receptors. The highest MDG are associated to the CR technology. The most common image quality failure is due to artifacts (dust, intensifying screen scratches, and processor marks for film/screen, laser reader defects for CR). Conclusion: The developed phantom permits the MGD measurement without the need of a calibrated ionization chamber at the mammography site and can be used by a technician without the presence of a medical physicist. The results indicate the urgent need to establish quality control programs for mammography.

  10. Average glandular dose in digital mammography and digital breast tomosynthesis: comparison of phantom and patient data

    NASA Astrophysics Data System (ADS)

    Bouwman, R. W.; van Engen, R. E.; Young, K. C.; den Heeten, G. J.; Broeders, M. J. M.; Schopphoven, S.; Jeukens, C. R. L. P. N.; Veldkamp, W. J. H.; Dance, D. R.

    2015-10-01

    For the evaluation of the average glandular dose (AGD) in digital mammography (DM) and digital breast tomosynthesis (DBT) phantoms simulating standard model breasts are used. These phantoms consist of slabs of polymethyl methacrylate (PMMA) or a combination of PMMA and polyethylene (PE). In the last decades the automatic exposure control (AEC) increased in complexity and became more sensitive to (local) differences in breast composition. The question is how well the AGD estimated using these simple dosimetry phantoms agrees with the average patient AGD. In this study the AGDs for both dosimetry phantoms and for patients have been evaluated for 5 different x-ray systems in DM and DBT modes. It was found that the ratios between patient and phantom AGD did not differ considerably using both dosimetry phantoms. These ratios averaged over all breast thicknesses were 1.14 and 1.15 for the PMMA and PMMA-PE dosimetry phantoms respectively in DM mode and 1.00 and 1.02 in the DBT mode. These ratios were deemed to be sufficiently close to unity to be suitable for dosimetry evaluation in quality control procedures. However care should be taken when comparing systems for DM and DBT since depending on the AEC operation, ratios for particular breast thicknesses may differ substantially (0.83-1.96). Although the predictions of both phantoms are similar we advise the use of PMMA  +  PE slabs for both DM and DBT to harmonize dosimetry protocols and avoid any potential issues with the use of spacers with the PMMA phantoms.

  11. Normalized mean glandular dose computation from mammography using GATE: a validation study

    NASA Astrophysics Data System (ADS)

    Myronakis, Marios E.; Zvelebil, Marketa; Darambara, Dimitra G.

    2013-04-01

    Mean glandular dose (MGD) is the figure of merit to assess breast dose after a mammographic acquisition. The use of normalized MGD obtained from Monte Carlo computations with measured incident air kerma determines the MGD delivered to patients. The Geant4 Application for Tomographic Emission (GATE) toolkit is a modern Monte Carlo application specifically designed for medical imaging systems modelling. Although there is an increasing number of publications using GATE worldwide for a wide range of medical imaging and therapeutic applications, there is currently no means to obtain normalized MGD. In this work, the GATE toolkit is extended, through the development of two new modules, to provide normalized MGD information for compressed breast phantoms based on simple geometries. The normalized MGD values were validated against published work and provided results at half value layers lower than 0.3 and greater than 0.6 mmAl. In addition, the skin thickness and composition were considered. Normalized MGD was computed after substitution of the adipose layer surrounding the standard breast phantom with skin tissue and the relative difference is reported. Spectrum generation was facilitated by further development of previously published work by other authors. Validation of the new GATE extension showed good agreement with published data and can be used to assess breast dose from mammographic as well as more complex x-ray imaging techniques. Changing skin thickness and composition revealed substantial changes in normalized MGD specifically for compressed breast thickness different than 5 cm and a possible revision of the structure of the standard breast model may be necessary.

  12. Average glandular dose in digital mammography and digital breast tomosynthesis: comparison of phantom and patient data.

    PubMed

    Bouwman, R W; van Engen, R E; Young, K C; den Heeten, G J; Broeders, M J M; Schopphoven, S; Jeukens, C R L P N; Veldkamp, W J H; Dance, D R

    2015-10-21

    For the evaluation of the average glandular dose (AGD) in digital mammography (DM) and digital breast tomosynthesis (DBT) phantoms simulating standard model breasts are used. These phantoms consist of slabs of polymethyl methacrylate (PMMA) or a combination of PMMA and polyethylene (PE). In the last decades the automatic exposure control (AEC) increased in complexity and became more sensitive to (local) differences in breast composition. The question is how well the AGD estimated using these simple dosimetry phantoms agrees with the average patient AGD. In this study the AGDs for both dosimetry phantoms and for patients have been evaluated for 5 different x-ray systems in DM and DBT modes. It was found that the ratios between patient and phantom AGD did not differ considerably using both dosimetry phantoms. These ratios averaged over all breast thicknesses were 1.14 and 1.15 for the PMMA and PMMA-PE dosimetry phantoms respectively in DM mode and 1.00 and 1.02 in the DBT mode. These ratios were deemed to be sufficiently close to unity to be suitable for dosimetry evaluation in quality control procedures. However care should be taken when comparing systems for DM and DBT since depending on the AEC operation, ratios for particular breast thicknesses may differ substantially (0.83-1.96). Although the predictions of both phantoms are similar we advise the use of PMMA  +  PE slabs for both DM and DBT to harmonize dosimetry protocols and avoid any potential issues with the use of spacers with the PMMA phantoms. PMID:26407015

  13. Predominant Glandular Cholinergic Dysautonomia in Patients with Primary Sjögren’s Syndrome

    PubMed Central

    Imrich, Richard; Alevizos, Ilias; Bebris, Lolita; Goldstein, David S.; Holmes, Courtney S.; Illei, Gabor G.; Nikolov, Nikolay P.

    2015-01-01

    Objectives The autonomic nervous system (ANS) modulates exocrine gland function. Available data show poor correlation between the degree of exocrine gland function and destruction in primary Sjögren’s syndrome (pSS) suggesting other mechanisms, such as autonomic dysfunction may be important in these patients. We performed a comprehensive analysis of sympathoneural and sympathetic cholinergic function in well-characterized patients with pSS. Methods 21 pSS patients (mean±SE age 44±3 years) and in 13 healthy controls (51±2 years) were assessed during orthostasis and intravenous injection of edrophonium (10 mg). The postganglionic sympathetic cholinergic system was evaluated by assessing sweat production by the quantitative sudomotor axon reflex test (QSART). Gastric empting testing assessed the gastro-intestinal ANS in pSS patients. Results Velocity index and acceleration index were significantly higher (p<0.05) in pSS compared to controls before and during the orthostatic and edrophonium tests. Other hemodynamic and neurochemical parameters did not differ between pSS patients and controls during the orthostasis and edrophonium test, however, edrophonium-induced saliva increment was lower in pSS (p=0.002). Abnormally low sweat production was found in four (N=4) pSS patients but in none of the controls in the QSART. Gastric empting was delayed in 53 % of pSS patients. Conclusion We observed subtle differences in several ANS domains, including gastrointestinal and sympathocholinergic system suggesting a complex ANS dysfunction in pSS. The impact was the largest on the exocrine glands with subtle differences in the cardiac parasympathetic function independent of glandular inflammation and atrophy, suggesting an alternative pathogenesis mechanism of the disease in pSS. PMID:25622919

  14. Normalized mean glandular dose computation from mammography using GATE: a validation study.

    PubMed

    Myronakis, Marios E; Zvelebil, Marketa; Darambara, Dimitra G

    2013-04-01

    Mean glandular dose (MGD) is the figure of merit to assess breast dose after a mammographic acquisition. The use of normalized MGD obtained from Monte Carlo computations with measured incident air kerma determines the MGD delivered to patients. The Geant4 Application for Tomographic Emission (GATE) toolkit is a modern Monte Carlo application specifically designed for medical imaging systems modelling. Although there is an increasing number of publications using GATE worldwide for a wide range of medical imaging and therapeutic applications, there is currently no means to obtain normalized MGD. In this work, the GATE toolkit is extended, through the development of two new modules, to provide normalized MGD information for compressed breast phantoms based on simple geometries. The normalized MGD values were validated against published work and provided results at half value layers lower than 0.3 and greater than 0.6 mmAl. In addition, the skin thickness and composition were considered. Normalized MGD was computed after substitution of the adipose layer surrounding the standard breast phantom with skin tissue and the relative difference is reported. Spectrum generation was facilitated by further development of previously published work by other authors. Validation of the new GATE extension showed good agreement with published data and can be used to assess breast dose from mammographic as well as more complex x-ray imaging techniques. Changing skin thickness and composition revealed substantial changes in normalized MGD specifically for compressed breast thickness different than 5 cm and a possible revision of the structure of the standard breast model may be necessary. PMID:23475310

  15. Glandular odontogenic cyst – Literature review and report of a paediatric case

    PubMed Central

    Faisal, Mohammad; Ahmad, Syed Ansar; Ansari, Uzma

    2015-01-01

    Glandular odontogenic cyst (GOC) is an extremely rare lesion occurring in the jawbones. The present paper is a review of 181 cases of GOCs reported in English literature, since it was first reported by Padayache and Van Wyk in 1987. Mandible was involved in 130 cases and maxilla in 51 cases. Anterior mandible was the most common area of involvement. Radiographic appearance was that of a unilocular radiolucency in 98 of 176 reported cases. Rest presented as multilocular radiolucency. Cortical expansion was observed in 136 of the 180 reported cases while cortex breach or perforation was seen in 81 cases. The treatment of choice was that of minor procedures that included enucleation with or without curettage, peripheral ostectomy, cryotherapy, etc. in 157 of the total 177 reported cases. Marginal jaw resection, segmental mandibulectomy etc. was reported in 20 cases. Although minor surgical procedures were the treatment of choice in most studies, two major studies of Kaplan et al. and Fowler et al. involving 111 and 46 cases, recorded a recurrence rate of 35.9 and 19.6%, respectively. The age range was between 11 and 82 years. The respective mean age of patients in the above mentioned studies was 45.7 for Kaplan's and 51 years for Fowler's whereas in our study, the mean age was 45.9 years. Very rarely does GOC presents itself in a paediatric patient. The paper also reports a case of an 11-year-old child whose histopathogy came out to be a case of a GOC. PMID:26587384

  16. Thrombomodulin Promotes Corneal Epithelial Wound Healing

    PubMed Central

    Huang, Yi-Hsun; I, Ching-Chang; Kuo, Cheng-Hsiang; Hsu, Yun-Yan; Lee, Fang-Tzu; Shi, Guey-Yueh; Tseng, Sung-Huei; Wu, Hua-Lin

    2015-01-01

    Purpose To determine the role of thrombomodulin (TM) in corneal epithelial wound healing, and to investigate whether recombinant TM epidermal growth factor-like domain plus serine/threonine-rich domain (rTMD23) has therapeutic potential in corneal epithelial wound healing. Methods TM localization and expression in the murine cornea were examined by immunofluorescence staining. TM expression after injury was also studied. The effect of rTMD23 on corneal wound healing was evaluated by in vitro and in vivo assays. Results TM was expressed in the cornea in normal adult mice. TM expression increased in the early phase of wound healing and decreased after wound recovery. In the in vitro study, platelet-derived growth factor-BB (PDGF-BB) induced TM expression in murine corneal epithelial cells by mediating E26 transformation-specific sequence-1 (Ets-1) via the mammalian target of rapamycin (mTOR) signaling pathway. The administration of rTMD23 increased the rate of corneal epithelial wound healing. Conclusions TM expression in corneal epithelium was modulated during the corneal wound healing process, and may be regulated by PDGF-BB. In addition, rTMD23 has therapeutic potential in corneal injury. PMID:25816372

  17. Epithelial hyperplasia, airways —

    Cancer.gov

    Number of respiratory epithelial cells is increased diffusely or focally. Frequently luminal protrusions are observed, sometimes forming papillae. Mucous (goblet) cell metaplastic hyperplasia is a variant, in which the respiratory epithelium of conducting airways is replaced by mucous cells either as a single or a pseudostratified layer.

  18. Epithelial-mesenchymal transition in gastric cancer

    PubMed Central

    Huang, Lei; Wu, Ruo-Lin; Xu, A-Man

    2015-01-01

    Gastric cancer (GC) is one of the most common malignancies worldwide with poor prognosis for lack of early detection and effective treatment modalities. The significant influence of tumor microenvironment on malignant cells has been extensively investigated in this targeted-therapy era. Epithelial-mesenchymal transition (EMT) is a highly conserved and fundamental process that is critical for embryogenesis and some other pathophysiological processes, especially tumor genesis and progression. Aberrant gastric EMT activation could endow gastric epithelial cells with increased mesenchymal characteristics and less epithelial features, and promote cancer cell stemness, initiation, invasion, metastasis, and chemo-resistance with cellular adhesion molecules especially E-cadherin concomitantly repressed, which allows tumor cells to disseminate and spread throughout the body. Some pathogens, stress, and hypoxia could induce and aggravate GC via EMT, which is significantly correlated with prognosis. GC EMT is modulated by diverse micro-environmental, membrane, and intracellular cues, and could be triggered by various overexpressed transcription factors, which are downstream of several vital cross-talking signaling pathways including TGF-β, Wnt/β-catenin, Notch, etc. microRNAs also contribute significantly to GC EMT modulation. There are currently some agents which could suppress GC EMT, shedding light on novel anti-malignancy strategies. Investigating potential mechanisms modulating GC cell EMT and discovering novel EMT regulators will further elucidate GC biology, and may provide new biomarkers for early GC detection and potentially efficient targets for preventative and curative anti-GC intervention approaches to prevent local and distant invasions. PMID:26807164

  19. EMT and stem cell-like properties associated with miR-205 and miR-200 epigenetic silencing are early manifestations during carcinogen-induced transformation of human lung epithelial cells

    PubMed Central

    Tellez, Carmen S.; Juri, Daniel E.; Do, Kieu; Bernauer, Amanda M.; Thomas, Cindy L.; Damiani, Leah A.; Tessema, Mathewos; Leng, Shuguang; Belinsky, Steven A.

    2011-01-01

    Epithelial mesenchymal transition (EMT) is strongly associated with cancer progression, but its potential role during premalignant development has not been studied. Here we show that a four-week exposure of immortalized human bronchial epithelial cells (HBECs) to tobacco carcinogens can induce a persistent, irreversible, and multifaceted dedifferentiation program marked by EMT and the emergence of stem cell-like properties. EMT induction was epigenetically driven, initially by chromatin remodeling through H3K27me3 enrichment and later by ensuing DNA methylation to sustain silencing of tumor suppressive microRNAs miR-200b, miR-200c, and miR-205, which were implicated in the dedifferentiation program in HBECs and also in primary lung tumors. Carcinogen-treated HBECs acquired stem-like features characterized by their ability to form spheroids with branching tubules and enrichment of the CD44high/CD24low, CD133, and ALDH1 stem cell-like markers. miRNA overexpression studies indicated that regulation of the EMT, stem-like, and transformed phenotypes in HBECs were distinct events. Our findings extend present concepts of how EMT participates in cancer pathophysiology by showing that EMT induction can participate in cancer initiation to promote the clonal expansion of premalignant lung epithelial cells. PMID:21363915

  20. Image quality, threshold contrast and mean glandular dose in CR mammography

    NASA Astrophysics Data System (ADS)

    Jakubiak, R. R.; Gamba, H. R.; Neves, E. B.; Peixoto, J. E.

    2013-09-01

    In many countries, computed radiography (CR) systems represent the majority of equipment used in digital mammography. This study presents a method for optimizing image quality and dose in CR mammography of patients with breast thicknesses between 45 and 75 mm. Initially, clinical images of 67 patients (group 1) were analyzed by three experienced radiologists, reporting about anatomical structures, noise and contrast in low and high pixel value areas, and image sharpness and contrast. Exposure parameters (kV, mAs and target/filter combination) used in the examinations of these patients were reproduced to determine the contrast-to-noise ratio (CNR) and mean glandular dose (MGD). The parameters were also used to radiograph a CDMAM (version 3.4) phantom (Artinis Medical Systems, The Netherlands) for image threshold contrast evaluation. After that, different breast thicknesses were simulated with polymethylmethacrylate layers and various sets of exposure parameters were used in order to determine optimal radiographic parameters. For each simulated breast thickness, optimal beam quality was defined as giving a target CNR to reach the threshold contrast of CDMAM images for acceptable MGD. These results were used for adjustments in the automatic exposure control (AEC) by the maintenance team. Using optimized exposure parameters, clinical images of 63 patients (group 2) were evaluated as described above. Threshold contrast, CNR and MGD for such exposure parameters were also determined. Results showed that the proposed optimization method was effective for all breast thicknesses studied in phantoms. The best result was found for breasts of 75 mm. While in group 1 there was no detection of the 0.1 mm critical diameter detail with threshold contrast below 23%, after the optimization, detection occurred in 47.6% of the images. There was also an average MGD reduction of 7.5%. The clinical image quality criteria were attended in 91.7% for all breast thicknesses evaluated in both

  1. Image quality, threshold contrast and mean glandular dose in CR mammography.

    PubMed

    Jakubiak, R R; Gamba, H R; Neves, E B; Peixoto, J E

    2013-09-21

    In many countries, computed radiography (CR) systems represent the majority of equipment used in digital mammography. This study presents a method for optimizing image quality and dose in CR mammography of patients with breast thicknesses between 45 and 75 mm. Initially, clinical images of 67 patients (group 1) were analyzed by three experienced radiologists, reporting about anatomical structures, noise and contrast in low and high pixel value areas, and image sharpness and contrast. Exposure parameters (kV, mAs and target/filter combination) used in the examinations of these patients were reproduced to determine the contrast-to-noise ratio (CNR) and mean glandular dose (MGD). The parameters were also used to radiograph a CDMAM (version 3.4) phantom (Artinis Medical Systems, The Netherlands) for image threshold contrast evaluation. After that, different breast thicknesses were simulated with polymethylmethacrylate layers and various sets of exposure parameters were used in order to determine optimal radiographic parameters. For each simulated breast thickness, optimal beam quality was defined as giving a target CNR to reach the threshold contrast of CDMAM images for acceptable MGD. These results were used for adjustments in the automatic exposure control (AEC) by the maintenance team. Using optimized exposure parameters, clinical images of 63 patients (group 2) were evaluated as described above. Threshold contrast, CNR and MGD for such exposure parameters were also determined. Results showed that the proposed optimization method was effective for all breast thicknesses studied in phantoms. The best result was found for breasts of 75 mm. While in group 1 there was no detection of the 0.1 mm critical diameter detail with threshold contrast below 23%, after the optimization, detection occurred in 47.6% of the images. There was also an average MGD reduction of 7.5%. The clinical image quality criteria were attended in 91.7% for all breast thicknesses evaluated in

  2. Glandular neoplasms of the urachus: a report of 55 cases emphasizing mucinous cystic tumors with proposed classification.

    PubMed

    Amin, Mahul B; Smith, Steven C; Eble, John N; Rao, Priya; Choi, William W L; Tamboli, Pheroze; Young, Robert H

    2014-08-01

    Published experience remains limited for glandular neoplasms of the urachus, especially mucinous cystic tumors. We reviewed 55 glandular urachal neoplasms to evaluate their clinical features and histopathologic spectrum and to devise a classification system for the mucinous cystic forms. Within the 55 cases studied, we observed 2 groups with differing clinical, gross, and histopathologic features. The first group, invasive, noncystic adenocarcinomas (n=24), had clinicopathologic features in accord with the known spectrum of urachal adenocarcinoma (mean age 50 y, female:male ratio 1.7, with recurrence or death from disease in 9/16 cases over a 45 mo mean follow-up). The second group, mucinous cystic tumors (n=31), morphologically resembled mucinous cystic tumors of the ovary and appeared classifiable by the same approach (mean age 47 y, female:male ratio 1.4) and included mucinous cystadenoma (n=4), mucinous cystic tumor of low malignant potential (n=22, including 2 cases with intraepithelial carcinoma), and mucinous cystadenocarcinoma with microscopic (n=4) or frank invasion (n=1). Follow-up information was available for 13 patients with mucinous cystic tumors (mean 41 mo); we observed no local recurrence or distant metastasis. This experience suggests that there is a distinct group of glandular, cystic tumors of the urachus that is classifiable in a manner similar to ovarian neoplasms and that has a favorable prognosis after complete excision. As with cystic neoplasms of other organs, rigorous sampling is recommended to identify potentially small foci of carcinoma that could be missed by inadequate sampling. Accordingly, classification based on methods other than complete surgical excision may be hazardous. PMID:25025366

  3. Molecular responses of rat tracheal epithelial cells to transmembrane pressure.

    PubMed

    Ressler, B; Lee, R T; Randell, S H; Drazen, J M; Kamm, R D

    2000-06-01

    Smooth muscle constriction in asthma causes the airway to buckle into a rosette pattern, folding the epithelium into deep crevasses. The epithelial cells in these folds are pushed up against each other and thereby experience compressive stresses. To study the epithelial cell response to compressive stress, we subjected primary cultures of rat tracheal epithelial cells to constant elevated pressures on their apical surface (i.e., a transmembrane pressure) and examined changes in the expression of genes that are important for extracellular matrix production and maintenance of smooth muscle activation. Northern blot analysis of RNA extracted from cells subjected to transmembrane pressure showed induction of early growth response-1 (Egr-1), endothelin-1, and transforming growth factor-beta1 in a pressure-dependent and time-dependent manner. Increases in Egr-1 protein were detected by immunohistochemistry. Our results demonstrate that airway epithelial cells respond rapidly to compressive stresses. Potential transduction mechanisms of transmembrane pressure were also investigated. PMID:10835333

  4. The Key Role of Peltate Glandular Trichomes in Symbiota Comprising Clavicipitaceous Fungi of the Genus Periglandula and Their Host Plants

    PubMed Central

    Steiner, Ulrike; Hellwig, Sabine; Ahimsa-Müller, Mahalia A.; Grundmann, Nicola; Li, Shu-Ming; Drewke, Christel; Leistner, Eckhard

    2015-01-01

    Clavicipitaceous fungi producing ergot alkaloids were recently discovered to be epibiotically associated with peltate glandular trichomes of Ipomoea asarifolia and Turbina corymbosa, dicotyledonous plants of the family Convolvulaceae. Mediators of the close association between fungi and trichomes may be sesquiterpenes, main components in the volatile oil of different convolvulaceous plants. Molecular biological studies and microscopic investigations led to the observation that the trichomes do not only secrete sesquiterpenes and palmitic acid but also seem to absorb ergot alkaloids from the epibiotic fungal species of the genus Periglandula. Thus, the trichomes are likely to have a dual and key function in a metabolic dialogue between fungus and host plant. PMID:25894995

  5. The key role of peltate glandular trichomes in symbiota comprising clavicipitaceous fungi of the genus periglandula and their host plants.

    PubMed

    Steiner, Ulrike; Kucht, Sabine Hellwig neé; Ahimsa-Müller, Mahalia A; Grundmann, Nicola; Li, Shu-Ming; Drewke, Christel; Leistner, Eckhard

    2015-04-01

    Clavicipitaceous fungi producing ergot alkaloids were recently discovered to be epibiotically associated with peltate glandular trichomes of Ipomoea asarifolia and Turbina corymbosa, dicotyledonous plants of the family Convolvulaceae. Mediators of the close association between fungi and trichomes may be sesquiterpenes, main components in the volatile oil of different convolvulaceous plants. Molecular biological studies and microscopic investigations led to the observation that the trichomes do not only secrete sesquiterpenes and palmitic acid but also seem to absorb ergot alkaloids from the epibiotic fungal species of the genus Periglandula. Thus, the trichomes are likely to have a dual and key function in a metabolic dialogue between fungus and host plant. PMID:25894995

  6. Angiomyolipoma With Epithelial Cysts.

    PubMed

    LeRoy, Michael A; Rao, Priya

    2016-06-01

    Angiomyolipoma with epithelial cysts is a rare mesenchymal tumor of the kidney that enters in the differential diagnosis of adult cystic renal neoplasms. These tumors demonstrate a slight female predominance and can present either incidentally or with symptoms, commonly flank pain and hematuria. Unlike conventional angiomyolipoma, this variant is characterized grossly by both solid and cystic areas, and histologically by the presence of single or multiple cysts lined by epithelial cells, a subepithelial "cambium-like" layer of small stromal cells with a prominent capillary vasculature, and a thick exterior wall composed of poorly formed fascicles of smooth muscle and thick-walled dysplastic blood vessels. Tumors show a distinct immunohistochemical profile and are often reactive for melanocytic markers (HMB-45 and Melan-A), as well as estrogen receptor and progesterone receptor. These tumors have an indolent clinical course, with no reports of progression or metastasis in reported cases thus far. PMID:27232352

  7. Epithelial cells as alternative human biomatrices for comet assay

    PubMed Central

    Rojas, Emilio; Lorenzo, Yolanda; Haug, Kristiane; Nicolaissen, Bjørn; Valverde, Mahara

    2014-01-01

    The comet assay is a valuable experimental tool aimed at mapping DNA damage in human cells in vivo for environmental and occupational monitoring, as well as for therapeutic purposes, such as storage prior to transplant, during tissue engineering, and in experimental ex vivo assays. Furthermore, due to its great versatility, the comet assay allows to explore the use of alternative cell types to assess DNA damage, such as epithelial cells. Epithelial cells, as specialized components of many organs, have the potential to serve as biomatrices that can be used to evaluate genotoxicity and may also serve as early effect biomarkers. Furthermore, 80% of solid cancers are of epithelial origin, which points to the importance of studying DNA damage in these tissues. Indeed, studies including comet assay in epithelial cells have either clear clinical applications (lens and corneal epithelial cells) or examine genotoxicity within human biomonitoring and in vitro studies. We here review improvements in determining DNA damage using the comet assay by employing lens, corneal, tear duct, buccal, and nasal epithelial cells. For some of these tissues invasive sampling procedures are needed. Desquamated epithelial cells must be obtained and dissociated prior to examination using the comet assay, and such procedures may induce varying amounts of DNA damage. Buccal epithelial cells require lysis enriched with proteinase K to obtain free nucleosomes. Over a 30 year period, the comet assay in epithelial cells has been little employed, however its use indicates that it could be an extraordinary tool not only for risk assessment, but also for diagnosis, prognosis of treatments and diseases. PMID:25506353

  8. Aquaporin 3 is regulated by estrogen in the chicken oviduct and is involved in progression of epithelial cell-derived ovarian carcinomas.

    PubMed

    Yang, C; Lim, W; Bae, H; Song, G

    2016-04-01

    Aquaporins (AQPs) are membrane proteins that passively deliver water across the plasma membrane to play an important role in maintaining cell shape. Members of the AQP family are distributed in most of the tissues in the human body and perform a variety of functions based on the water homeostasis suitable for each organ. However, there is little known about the expression and regulation of AQP family members in chickens. Therefore, we determined the expression of AQPs in various tissues of chickens. Among 13 isotypes, AQP3 was highly expressed in the chicken oviduct. Expression of AQP3 messenger RNA (mRNA) increased in the magnum (P < 0.001) and isthmus (P < 0.001) of chick oviducts treated with diethylstilbestrol. Consistent with these results, the localization of AQP3 was detected in the glandular and luminal epithelia of the magnum and isthmus of oviducts of diethylstilbestrol-treated chicks. In addition, the pattern of expression of AQP3 changed in an estrogen-dependent manner during the molting period. During the regenerative period of the oviduct after molting, expression of AQP3 mRNA increased coordinately with increasing concentrations of estradiol (P < 0.001), whereas expression of AQP3 mRNA decreased as concentrations of estradiol in plasma decreased in response to induced molting (P < 0.001). Also, expression of the AQP3 increased (P < 0.001) in cancerous ovaries of laying hens. In conclusion, AQP3 does not simply function to transport water into and out of cells but also appears to be closely involved in development of the chicken oviduct, which is regulated by estrogens. Furthermore, our results suggest AQP3 as a new diagnostic for early detection and treatment of epithelial cell-derived ovarian carcinomas. PMID:26808975

  9. The physiological expression of scavenger receptor SR-B1 in canine endometrial and placental epithelial cells and its potential involvement in pathogenesis of pyometra.

    PubMed

    Gabriel, C; Becher-Deichsel, A; Hlavaty, J; Mair, G; Walter, I

    2016-06-01

    Pyometra, the purulent inflammation of the uterus, is a common uterine disease of bitches that has potentially life-threatening consequences. The opportunistic bacterial infection of the uterus often progresses into the serious systemic inflammatory response syndrome. In a previous study, we characterized epithelial foam cells in the canine endometrial surface occurring in metestrus, and we regularly observed pronounced epithelial foam-cell formations in pyometra-affected uteri. Therefore, it was assumed that the mechanism behind lipid droplet accumulation in surface epithelial cells might even increase bacterial binding capacity and promote pyometra development. Lipid droplet accumulation in epithelial cells is accomplished via specialized lipid receptors called scavenger receptors (SR). Scavenger receptor class B type 1 (SR-B1) is an important receptor for lipid accumulation in diverse cell types, but it is also a strong binding partner for bacteria, and thereby enhances bacterial adhesion and clinical signs of systemic inflammatory response syndrome. In the present study, after the isolation of metestrous surface epithelial cells from canine uteri by laser capture microdissection, SR-B1 was identified at the messenger RNA (mRNA) level by quantitative real time polymerase chain reaction and also at the protein level by means of immunohistochemistry. In pyometra-affected uteri, SR-B1 mRNA expression was higher than that in the healthy control samples, and SR-B1 protein was expressed in the surface and crypt epithelial cells. Furthermore, to understand the physiological role of SR-B1 expression in the metestrus surface epithelial cells, we investigated its expression in the epithelial cells of the glandular chambers of canine placenta in different stages of gestation because these cells are also characterized by lipid droplet accumulation. SR-B1 was present in the placental epithelial cells of the glandular chambers from 25 to 30 and 45 to 50 days of gestation

  10. Serum placental-type alkaline phosphatase activity in women with squamous and glandular malignancies of the reproductive tract.

    PubMed Central

    Ind, T E; Iles, R K; Carter, P G; Lowe, D G; Shepherd, J H; Hudson, C N; Chard, T

    1994-01-01

    AIM--To investigate serum placental-type alkaline phosphatase (PLAP-type) activities in women with squamous and glandular malignancies of the reproductive tract using an immunoradiometric assay. METHODS--PLAP-type immunoreactivity was measured in 180 women with non-ovarian malignancies of the reproductive tract and the values were compared with those from 334 controls. The cases comprised 18 vulval, nine vaginal, 103 cervical, 46 endometrial, and five fallopian tube cancers. RESULTS--Serum PLAP-type activities were no different from controls in patients with squamous cell tumours. Women with adenocarcinoma of the cervix, endometrium, and fallopian tube had increased values: women with endometrial cancer had a median value nearly four times greater than that of controls. There was no direct correlation between PLAP-type activities and stage of disease in patients with endometrial cancer, but values reverted to normal after treatment. CONCLUSIONS--Serum PLAP-type measurements are of no value in the management of patients with squamous cell tumours of the female reproductive tract. Raised activities can, however, be found in glandular tumours, in particular endometrial cancer where serum PLAP-type measurements may be of value in predicting remission. PMID:7829680

  11. Integration of co-localized glandular morphometry and protein biomarker expression in immunofluorescent images for prostate cancer prognosis

    NASA Astrophysics Data System (ADS)

    Scott, Richard; Khan, Faisal M.; Zeineh, Jack; Donovan, Michael; Fernandez, Gerardo

    2015-03-01

    Immunofluorescent (IF) image analysis of tissue pathology has proven to be extremely valuable and robust in developing prognostic assessments of disease, particularly in prostate cancer. There have been significant advances in the literature in quantitative biomarker expression as well as characterization of glandular architectures in discrete gland rings. However, while biomarker and glandular morphometric features have been combined as separate predictors in multivariate models, there is a lack of integrative features for biomarkers co-localized within specific morphological sub-types; for example the evaluation of androgen receptor (AR) expression within Gleason 3 glands only. In this work we propose a novel framework employing multiple techniques to generate integrated metrics of morphology and biomarker expression. We demonstrate the utility of the approaches in predicting clinical disease progression in images from 326 prostate biopsies and 373 prostatectomies. Our proposed integrative approaches yield significant improvements over existing IF image feature metrics. This work presents some of the first algorithms for generating innovative characteristics in tissue diagnostics that integrate co-localized morphometry and protein biomarker expression.

  12. Experimental endocrine therapies promote epithelial cytodifferentiation and ciliogenesis in the gerbil female prostate.

    PubMed

    Santos, Fernanda Cristina Alcântara; Falleiros-Júnior, Luiz Roberto; Corradi, Lara Silvia; Vilamaior, Patricia Simone Leite; Taboga, Sebastião Roberto

    2007-06-01

    The incidence of ciliated cells in the prostate gland of the female gerbil (Meriones unguiculatus) is uncommon and apparently becomes more frequent during androgen (testosterone cypionate) and anti-estrogen (letrozole) endocrine therapies. To evaluate the effects of such drug therapies on the induction of ciliogenesis in the glandular epithelium of female prostate glands, adult female gerbils aged 90 days were treated for 14 days with testosterone and letrozole after which their prostate glands were removed for histological, ultrastructural, and serological analyses. The cytodifferentiation of the ciliated phenotype in the alveolar epithelium became more frequent after both the testosterone and the letrozole treatments. The ciliogenesis phenomenon of the epithelial cells in the prostate gland of female gerbils thus appears to be induced by variations in the increase of androgen levels. PMID:17347814

  13. Nasal Cavity Masses Resembling Chondro-osseous Respiratory Epithelial Adenomatoid Hamartomas in 3 Dogs.

    PubMed

    LaDouceur, E E B; Michel, A O; Lindl Bylicki, B J; Cifuentes, F F; Affolter, V K; Murphy, B G

    2016-05-01

    Chondro-osseous respiratory epithelial adenomatoid hamartomas (COREAHs) are rare tumors in the nasal cavity of people, which have not been described in other species. COREAHs in people are minimally invasive and rarely recur following excision. Histologically, these tumors are composed of disorganized, mature, nasal turbinate tissue that is organized into polypoid growths. These growths are lined by respiratory epithelium, contain glandular elements, and are organized around central cores of chondro-osseous matrix. This report describes 3 cases of dogs with nasal tumors that have histomorphology similar to that of COREAH in people. The tumors were all identified within the nasal cavity and were associated with regional bony lysis of the turbinates and surrounding skull bones, a feature that has not been reported in COREAH in people. There was no evidence of metastasis or extension beyond the nasal cavity in any of the 3 cases. PMID:26253881

  14. Effects of EGFR Inhibitor on Helicobacter pylori Induced Gastric Epithelial Pathology in Vivo

    PubMed Central

    Crabtree, Jean E.; Jeremy, Anthony H.T.; Duval, Cedric; Dixon, Michael F.; Danjo, Kazuma; Carr, Ian M.; Pritchard, D. Mark; Robinson, Philip A.

    2013-01-01

    Helicobacter pylori transactivates the Epidermal Growth Factor Receptor (EGFR) and predisposes to gastric cancer development in humans and animal models. To examine the importance of EGFR signalling to gastric pathology, this study investigated whether treatment of Mongolian gerbils with a selective EGFR tyrosine kinase inhibitor, EKB-569, altered gastric pathology in chronic H. pylori infection. Gerbils were infected with H. pylori and six weeks later received either EKB-569-supplemented, or control diet, for 32 weeks prior to sacrifice. EKB-569-treated H. pylori-infected gerbils had no difference in H. pylori colonisation or inflammation scores compared to infected animals on control diet, but showed significantly less corpus atrophy, mucous metaplasia and submucosal glandular herniations along with markedly reduced antral and corpus epithelial proliferation to apoptosis ratios. EKB-569-treated infected gerbils had significantly decreased abundance of Cox-2, Adam17 and Egfr gastric transcripts relative to infected animals on control diet. EGFR inhibition by EKB-569 therefore reduced the severity of pre-neoplastic gastric pathology in chronically H. pylori-infected gerbils. EKB-569 increased gastric epithelial apoptosis in H. pylori-infected gerbils which counteracted some of the consequences of increased gastric epithelial cell proliferation. Similar chemopreventative strategies may be useful in humans who are at high risk of developing H. pylori- induced gastric adenocarcinoma. PMID:25437333

  15. Goat uterine epithelial cells are susceptible to infection with Caprine Arthritis Encephalitis Virus (CAEV) in vivo

    PubMed Central

    2012-01-01

    The aim of this study was to determine, using immunofluorescence and in situ hybridization, whether CAEV is capable of infecting goat uterine epithelial cells in vivo. Five CAEV seropositive goats confirmed as infected using double nested polymerase chain reaction (dnPCR) on leucocytes and on vaginal secretions were used as CAEV positive goats. Five CAEV-free goats were used as controls. Samples from the uterine horn were prepared for dnPCR, in situ hybridization, and immunofluorescence. The results from dnPCR confirmed the presence of CAEV proviral DNA in the uterine horn samples of infected goats whereas no CAEV proviral DNA was detected in samples taken from the uninfected control goats. The in situ hybridization probe was complementary to part of the CAEV gag gene and confirmed the presence of CAEV nucleic acids in uterine samples. The positively staining cells were seen concentrated in the mucosa of the lamina propria of uterine sections. Finally, laser confocal analysis of double p28/cytokeratin immunolabelled transverse sections of CAEV infected goat uterus, demonstrated that the virus was localized in glandular and epithelial cells. This study clearly demonstrates that goat uterine epithelial cells are susceptible to CAEV infection in vivo. This finding could help to further our understanding of the epidemiology of CAEV, and in particular the possibility of vertical transmission. PMID:22276529

  16. Salivary gland acinar cells regenerate functional glandular structures in modified hydrogels

    NASA Astrophysics Data System (ADS)

    Pradhan, Swati

    Xerostomia, a condition resulting from irradiation of the head and neck, affects over 40,000 cancer patients each year in the United States. Direct radiation damage of the acinar cells that secrete fluid and protein results in salivary gland hypofunction. Present medical management for xerostomia for patients treated for upper respiratory cancer is largely ineffective. Patients who have survived their terminal diagnosis are often left with a diminished quality of life and are unable to enjoy the simple pleasures of eating and drinking. This project aims to ultimately reduce human suffering by developing a functional implantable artificial salivary gland. The goal was to create an extracellular matrix (ECM) modified hyaluronic acid (HA) based hydrogel culture system that allows for the growth and differentiation of salivary acinar cells into functional acini-like structures capable of secreting large amounts of protein and fluid unidirectionally and to ultimately engineer a functional artificial salivary gland that can be implanted into an animal model. A tissue collection protocol was established and salivary gland tissue was obtained from patients undergoing head and neck surgery. The tissue specimen was assessed by histology and immunohistochemistry to establish the phenotype of normal salivary gland cells including the native basement membranes. Hematoxylin and eosin staining confirmed normal glandular tissue structures including intercalated ducts, striated ducts and acini. alpha-Amylase and periodic acid schiff stain, used for structures with a high proportion of carbohydrate macromolecules, preferentially stained acinar cells in the tissue. Intercalated and striated duct structures were identified using cytokeratins 19 and 7 staining. Myoepithelial cells positive for cytokeratin 14 were found wrapped around the serous and mucous acini. Tight junction components including ZO-1 and E-cadherin were present between both ductal and acinar cells. Ductal and acinar

  17. MAPPING OF SUCCINATE DEHYDROGENASE LOSSES IN 2258 EPITHELIAL NEOPLASMS

    PubMed Central

    Miettinen, Markku; Sarlomo-Rikala, Maarit; Cue, Peter Mc.; Czapiewski, Piotr; Langfor, Renata; Waloszczyk, Piotr; Wazny, Krzysztof; Biernat, Wojciech; Lasota, Jerzy; Wang, Zengfeng

    2013-01-01

    Losses in the succinate dehydrogenase (SDH) complex characterize 20–30% of extra-adrenal paragangliomas and 7–8% of gastric GISTs, and rare renal cell carcinomas. This loss is reflected as lack of the normally ubiquitous immunohistochemical expression of the SDH subunit B (SDHB). In paragangliomas, SDHB loss correlates with homozygous loss of any of the SDH subunits, typically by loss-of-function mutations. The occurrence of SDHB losses in other epithelial malignancies is unknown. In this study, we immunohistochemically examined 2258 epithelial, mostly malignant neoplasms including common carcinomas of all sites. Among renal cell carcinomas, SDHB loss was observed in 4 of 711 cases (0.6%) including a patient with an SDHB-deficient GIST. Histologically the SDHB-negative renal carcinomas varied. There was one clear cell carcinoma with a high nuclear grade, one papillary carcinoma type 2, one unclassified carcinoma with a glandular pattern, and one oncocytoid low-grade carcinoma as previously described for SDHB-negative renal carcinoma. None of these patients was known to have paragangliomas or had loss of SDHA expression in the tumor. Three of these patients had metastases at presentation (2 in the adrenal, one in the retroperitoneal lymph nodes). There were no cases with SDHB-loss among 64 renal oncocytomas. SDHB-losses were not seen in other carcinomas, except in one prostatic adenocarcinoma (1/57), one lymphoepithelial carcinoma of the stomach, and one (1/40) seminoma. Based on this study, SDHB-losses occur in 0.6% of renal cell carcinomas and extremely rarely in other carcinomas. Some of these renal carcinomas may be clinically aggressive. The clinical significance and molecular genetics of these SDHB-negative tumors requires further study. PMID:23531856

  18. Uterine Epithelial Estrogen Receptor-α Controls Decidualization via a Paracrine Mechanism.

    PubMed

    Pawar, S; Laws, M J; Bagchi, I C; Bagchi, M K

    2015-09-01

    Steroid hormone-regulated differentiation of uterine stromal cells, known as decidualization, is essential for embryo implantation. The role of the estrogen receptor-α (ESR1) during this differentiation process is unclear. Development of conditional Esr1-null mice showed that deletion of this gene in both epithelial and stromal compartments of the uterus leads to a complete blockade of decidualization, indicating a critical role of ESR1 during this process. To further elucidate the cell type-specific function of ESR1 in the uterus, we created WE(d/d) mice in which Esr1 is ablated in uterine luminal and glandular epithelia but is retained in the stroma. Uteri of WE(d/d) mice failed to undergo decidualization, indicating that epithelial ESR1 contributes to stromal differentiation via a paracrine mechanism. We noted markedly reduced production of the leukemia inhibitory factor (LIF) in WE(d/d) uteri. Supplementation with LIF restored decidualization in WE(d/d) mice. Our study indicated that LIF acts synergistically with progesterone to induce the expression of Indian hedgehog (IHH) in uterine epithelium and its receptor patched homolog 1 in the stroma. IHH then induces the expression of chicken ovalbumin upstream promoter-transcription factor II, a transcription factor that promotes stromal differentiation. To address the mechanism by which LIF induces IHH expression, we used mice lacking uterine epithelial signal transducer and activator of transcription 3, a well-known mediator of LIF signaling. Our study revealed that LIF-mediated induction of IHH occurs without the activation of epithelial signal transducer and activator of transcription 3 but uses an alternate pathway involving the activation of the ERK1/2 kinase. Collectively our results provide unique insights into the paracrine mechanisms by which ESR1 directs epithelial-stromal dialogue during pregnancy establishment. PMID:26241389

  19. Epithelial stem cells.

    PubMed

    Draheim, Kyle M; Lyle, Stephen

    2011-01-01

    It is likely that adult epithelial stem cells will be useful in the treatment of diseases, such as ectodermal dysplasias, monilethrix, Netherton syndrome, Menkes disease, hereditary epidermolysis bullosa, and alopecias. Additionally, other skin problems such as burn wounds, chronic wounds, and ulcers will benefit from stem cell-related therapies. However, there are many questions that need to be answered before this goal can be realized. The most important of these questions is what regulates the adhesion of stem cells to the niche versus migration to the site of injury. We have started to identify the mechanisms involved in this decision-making process. PMID:21618097

  20. Forces driving epithelial wound healing

    NASA Astrophysics Data System (ADS)

    Brugués, Agustí; Anon, Ester; Conte, Vito; Veldhuis, Jim H.; Gupta, Mukund; Colombelli, Julien; Muñoz, José J.; Brodland, G. Wayne; Ladoux, Benoit; Trepat, Xavier

    2014-09-01

    A fundamental feature of multicellular organisms is their ability to self-repair wounds through the movement of epithelial cells into the damaged area. This collective cellular movement is commonly attributed to a combination of cell crawling and `purse-string’ contraction of a supracellular actomyosin ring. Here we show by direct experimental measurement that these two mechanisms are insufficient to explain force patterns observed during wound closure. At early stages of the process, leading actin protrusions generate traction forces that point away from the wound, showing that wound closure is initially driven by cell crawling. At later stages, we observed unanticipated patterns of traction forces pointing towards the wound. Such patterns have strong force components that are both radial and tangential to the wound. We show that these force components arise from tensions transmitted by a heterogeneous actomyosin ring to the underlying substrate through focal adhesions. The structural and mechanical organization reported here provides cells with a mechanism to close the wound by cooperatively compressing the underlying substrate.

  1. Forces driving epithelial wound healing

    PubMed Central

    Veldhuis, Jim H.; Gupta, Mukund; Colombelli, Julien; Muñoz, José J.; Brodland, G. Wayne; Ladoux, Benoit; Trepat, Xavier

    2015-01-01

    A fundamental feature of multicellular organisms is their ability to self-repair wounds through the movement of epithelial cells into the damaged area. This collective cellular movement is commonly attributed to a combination of cell crawling and “purse-string” contraction of a supracellular actomyosin ring. Here we show by direct experimental measurement that these two mechanisms are insufficient to explain force patterns observed during wound closure. At early stages of the process, leading actin protrusions generate traction forces that point away from the wound, showing that wound closure is initially driven by cell crawling. At later stages, we observed unanticipated patterns of traction forces pointing towards the wound. Such patterns have strong force components that are both radial and tangential to the wound. We show that these force components arise from tensions transmitted by a heterogeneous actomyosin ring to the underlying substrate through focal adhesions. The structural and mechanical organization reported here provides cells with a mechanism to close the wound by cooperatively compressing the underlying substrate. PMID:27340423

  2. Induction of apoptosis in oral epithelial cells by Candida albicans.

    PubMed

    Villar, C Cunha; Chukwuedum Aniemeke, J; Zhao, X-R; Huynh-Ba, G

    2012-12-01

    During infection, interactions between Candida albicans and oral epithelial cells result in oral epithelial cell death. This is clinically manifested by the development of oral mucosal ulcerations generally associated with discomfort. In vitro studies have shown that C. albicans induces early apoptotic alterations in oral epithelial cells; however, these studies have also shown that treatment of infected cells with caspase inhibitors does not prevent their death. The reasons for these contradictory results are unknown and it is still not clear if C. albicans stimulates oral epithelial signaling pathways that promote apoptotic cell death. Activation of specific death pathways in response to microbial organisms plays an essential role in modulating the pathogenesis of a variety of infectious diseases. The aim of this study was to (i) characterize C. albicans-induced apoptotic morphological alterations in oral epithelial cells, and (ii) investigate the activation of apoptotic signaling pathways and expression of apoptotic genes during infection. Candida albicans induced early apoptotic changes in over 50% of oral epithelial cells. However, only 15% of those showed mid-late apoptotic alterations. At the molecular level, C. albicans caused a loss of the mitochondrial transmembrane potential and translocation of mitochondrial cytochrome c. Caspase-3/9 activities increased only during the first hours of infection. Moreover, poly[ADP ribose] polymerase 1 was cleaved into apoptotic and necrotic-like fragments. Finally, five anti-apoptotic genes were significantly upregulated and two pro-apoptotic genes were downregulated during infection. Altogether, these findings indicate that epithelial apoptotic pathways are activated in response to C. albicans, but fail to progress and promote apoptotic cell death. PMID:23134609

  3. Primary cultures of female swine genital epithelial cells in vitro: a new approach for the study of hormonal modulation of Chlamydia infection.

    PubMed

    Guseva, Natalia V; Knight, Stephen T; Whittimore, Judy D; Wyrick, Priscilla B

    2003-08-01

    Previous studies have demonstrated that female reproductive hormones influence chlamydial infection both in vivo and in vitro. Due to the reduced availability of human genital tissues for research purposes, an alternative hormone-responsive model system was sought to study chlamydial pathogenesis. Mature female swine eliminated from breeding programs were selected as the animals of choice because of the similarity of a sexually transmitted disease syndrome and sequelae in swine to a disease syndrome and sequelae found in humans, because of the near identity of a natural infectious chlamydial isolate from swine to Chlamydia trachomatis serovar D from humans, and because a pig's epithelial cell physiology and the mean length of its estrous cycle are similar to those in humans. Epithelial cells from the cervix, uterus, and horns of the uterus were isolated, cultivated in vitro in Dulbecco's minimum essential medium-Hanks' F-12 (DMEM-F-12) medium with and without exogenous hormone supplementation, and analyzed for Chlamydia suis S-45 infectivity. The distribution of chlamydial inclusions in swine epithelial cells was uneven and was influenced by the genital tract site and hormone status. This study confirmed that, like primary human endometrial epithelial cells, estrogen-dominant swine epithelial cells are more susceptible to chlamydial infection than are progesterone-dominant cells. Further, the more differentiated luminal epithelial cells were more susceptible to infection than were glandular epithelial cells. Interestingly, chlamydial growth in mature luminal epithelia was morphologically more active than in glandular epithelia, where persistent chlamydial forms predominated. Attempts to reprogram epithelial cell physiology and thereby susceptibility to chlamydial infection by reverse-stage, exogenous hormonal supplementation were unsuccessful. Freshly isolated primary pig epithelial cells frozen at -80 degrees C in DMEM-F-12 medium with 10% dimethyl sulfoxide for

  4. Mean glandular dose coefficients (D(g)N) for x-ray spectra used in contemporary breast imaging systems.

    PubMed

    Nosratieh, Anita; Hernandez, Andrew; Shen, Sam Z; Yaffe, Martin J; Seibert, J Anthony; Boone, John M

    2015-09-21

    To develop tables of normalized glandular dose coefficients D(g)N for a range of anode-filter combinations and tube voltages used in contemporary breast imaging systems. Previously published mono-energetic D(g)N values were used with various spectra to mathematically compute D(g)N coefficients. The tungsten anode spectra from TASMICS were used; molybdenum and rhodium anode-spectra were generated using MCNPX Monte Carlo code. The spectra were filtered with various thicknesses of Al, Rh, Mo or Cu. An initial half value layer (HVL) calculation was made using the anode and filter material. A range of the HVL values was produced with the addition of small thicknesses of polymethyl methacrylate (PMMA) as a surrogate for the breast compression paddle, to produce a range of HVL values at each tube voltage. Using a spectral weighting method, D(g)N coefficients for the generated spectra were calculated for breast glandular densities of 0%, 12.5%, 25%, 37.5%, 50% and 100% for a range of compressed breast thicknesses from 3 to 8 cm. Eleven tables of normalized glandular dose (D(g)N) coefficients were produced for the following anode/filter combinations: W + 50 μm Ag, W + 500 μm Al, W + 700 μm Al, W + 200 μm Cu, W + 300 μm Cu, W + 50 μm Rh, Mo + 400 μm Cu, Mo + 30 μm Mo, Mo + 25 μm Rh, Rh + 400 μm Cu and Rh + 25 μm Rh. Where possible, these results were compared to previously published D(g)N values and were found to be on average less than 2% different than previously reported values.Over 200 pages of D(g)N coefficients were computed for modeled x-ray system spectra that are used in a number of new breast imaging applications. The reported values were found to be in excellent agreement when compared to published values. PMID:26348995

  5. Oestrogen-induced angiogenesis promotes adenomyosis by activating the Slug-VEGF axis in endometrial epithelial cells.

    PubMed

    Huang, Tze-Sing; Chen, Yi-Jen; Chou, Teh-Ying; Chen, Chih-Yao; Li, Hsin-Yang; Huang, Ben-Shian; Tsai, Hsiao-Wen; Lan, Hsin-Yi; Chang, Cheng-Hsuan; Twu, Nae-Fang; Yen, Ming-Shyen; Wang, Peng-Hui; Chao, Kuan-Chong; Lee, Chun-Chung; Yang, Muh-Hwa

    2014-07-01

    Adenomyosis is an oestrogen-dependent disease characterized by the invasion of endometrial epithelial cells into the myometrium of uterus, and angiogenesis is thought to be required for the implantation of endometrial glandular tissues during the adenomyotic pathogenesis. In this study, we demonstrate that compared with eutopic endometria, adenomyotic lesions exhibited increased vascularity as detected by sonography. Microscopically, the lesions also exhibited an oestrogen-associated elevation of microvascular density and VEGF expression in endometrial epithelial cells. We previously reported that oestrogen-induced Slug expression was critical for endometrial epithelial-mesenchymal transition and development of adenomyosis. Our present studies demonstrated that estradiol (E2) elicited a Slug-VEGF axis in endometrial epithelial cells, and also induced pro-angiogenic activity in vascular endothelial cells. The antagonizing agents against E2 or VEGF suppressed endothelial cells migration and tubal formation. Animal experiments furthermore confirmed that blockage of E2 or VEGF was efficient to attenuate the implantation of adenomyotic lesions. These results highlight the importance of oestrogen-induced angiogenesis in adenomyosis development and provide a potential strategy for treating adenomyosis through intercepting the E2-Slug-VEGF pathway. PMID:24758741

  6. Effects of ezrin knockdown on the structure of gastric glandular epithelia.

    PubMed

    Yoshida, Saori; Yamamoto, Hiroto; Tetsui, Takahito; Kobayakawa, Yuka; Hatano, Ryo; Mukaisho, Ken-ichi; Hattori, Takanori; Sugihara, Hiroyuki; Asano, Shinji

    2016-01-01

    Ezrin, an adaptor protein that cross-links plasma membrane-associated proteins with the actin cytoskeleton, is concentrated on apical surfaces of epithelial cells, especially in microvilli of the small intestine and stomach. In the stomach, ezrin is predominantly expressed on the apical canalicular membrane of parietal cells. Transgenic ezrin knockdown mice in which the expression level of ezrin was reduced to <7% compared with the wild-type suffered from achlorhydria because of impairment of membrane fusion between tubulovesicles and apical membranes. We observed, for the first time, hypergastrinemia and foveolar hyperplasia in the gastric fundic region of the knockdown mice. Dilation of fundic glands was observed, the percentage of parietal and chief cells was reduced, and that of mucous-secreting cells was increased. The parietal cells of knockdown mice contained dilated tubulovesicles and abnormal mitochondria, and subsets of these cells contained abnormal vacuoles and multilamellar structures. Therefore, lack of ezrin not only causes achlorhydria and hypergastrinemia but also changes the structure of gastric glands, with severe perturbation of the secretory membranes of parietal cells. PMID:26329936

  7. Hydraulic fracture during epithelial stretching

    NASA Astrophysics Data System (ADS)

    Casares, Laura; Vincent, Romaric; Zalvidea, Dobryna; Campillo, Noelia; Navajas, Daniel; Arroyo, Marino; Trepat, Xavier

    2015-03-01

    The origin of fracture in epithelial cell sheets subject to stretch is commonly attributed to excess tension in the cells’ cytoskeleton, in the plasma membrane, or in cell-cell contacts. Here, we demonstrate that for a variety of synthetic and physiological hydrogel substrates the formation of epithelial cracks is caused by tissue stretching independently of epithelial tension. We show that the origin of the cracks is hydraulic; they result from a transient pressure build-up in the substrate during stretch and compression manoeuvres. After pressure equilibration, cracks heal readily through actomyosin-dependent mechanisms. The observed phenomenology is captured by the theory of poroelasticity, which predicts the size and healing dynamics of epithelial cracks as a function of the stiffness, geometry and composition of the hydrogel substrate. Our findings demonstrate that epithelial integrity is determined in a tension-independent manner by the coupling between tissue stretching and matrix hydraulics.

  8. Hydraulic fracture during epithelial stretching.

    PubMed

    Casares, Laura; Vincent, Romaric; Zalvidea, Dobryna; Campillo, Noelia; Navajas, Daniel; Arroyo, Marino; Trepat, Xavier

    2015-03-01

    The origin of fracture in epithelial cell sheets subject to stretch is commonly attributed to excess tension in the cells' cytoskeleton, in the plasma membrane, or in cell-cell contacts. Here, we demonstrate that for a variety of synthetic and physiological hydrogel substrates the formation of epithelial cracks is caused by tissue stretching independently of epithelial tension. We show that the origin of the cracks is hydraulic; they result from a transient pressure build-up in the substrate during stretch and compression manoeuvres. After pressure equilibration, cracks heal readily through actomyosin-dependent mechanisms. The observed phenomenology is captured by the theory of poroelasticity, which predicts the size and healing dynamics of epithelial cracks as a function of the stiffness, geometry and composition of the hydrogel substrate. Our findings demonstrate that epithelial integrity is determined in a tension-independent manner by the coupling between tissue stretching and matrix hydraulics. PMID:25664452

  9. Hydraulic fracture during epithelial stretching

    PubMed Central

    Casares, Laura; Vincent, Romaric; Zalvidea, Dobryna; Campillo, Noelia; Navajas, Daniel; Arroyo, Marino; Trepat, Xavier

    2015-01-01

    The origin of fracture in epithelial cell sheets subject to stretch is commonly attributed to excess tension in the cells’ cytoskeleton, in the plasma membrane, or in cell-cell contacts. Here we demonstrate that for a variety of synthetic and physiological hydrogel substrates the formation of epithelial cracks is caused by tissue stretching independently of epithelial tension. We show that the origin of the cracks is hydraulic; they result from a transient pressure build-up in the substrate during stretch and compression maneuvers. After pressure equilibration cracks heal readily through actomyosin-dependent mechanisms. The observed phenomenology is captured by the theory of poroelasticity, which predicts the size and healing dynamics of epithelial cracks as a function of the stiffness, geometry and composition of the hydrogel substrate. Our findings demonstrate that epithelial integrity is determined in a tension-independent manner by the coupling between tissue stretching and matrix hydraulics. PMID:25664452

  10. Salivary gland acinar cells regenerate functional glandular structures in modified hydrogels

    NASA Astrophysics Data System (ADS)

    Pradhan, Swati

    Xerostomia, a condition resulting from irradiation of the head and neck, affects over 40,000 cancer patients each year in the United States. Direct radiation damage of the acinar cells that secrete fluid and protein results in salivary gland hypofunction. Present medical management for xerostomia for patients treated for upper respiratory cancer is largely ineffective. Patients who have survived their terminal diagnosis are often left with a diminished quality of life and are unable to enjoy the simple pleasures of eating and drinking. This project aims to ultimately reduce human suffering by developing a functional implantable artificial salivary gland. The goal was to create an extracellular matrix (ECM) modified hyaluronic acid (HA) based hydrogel culture system that allows for the growth and differentiation of salivary acinar cells into functional acini-like structures capable of secreting large amounts of protein and fluid unidirectionally and to ultimately engineer a functional artificial salivary gland that can be implanted into an animal model. A tissue collection protocol was established and salivary gland tissue was obtained from patients undergoing head and neck surgery. The tissue specimen was assessed by histology and immunohistochemistry to establish the phenotype of normal salivary gland cells including the native basement membranes. Hematoxylin and eosin staining confirmed normal glandular tissue structures including intercalated ducts, striated ducts and acini. alpha-Amylase and periodic acid schiff stain, used for structures with a high proportion of carbohydrate macromolecules, preferentially stained acinar cells in the tissue. Intercalated and striated duct structures were identified using cytokeratins 19 and 7 staining. Myoepithelial cells positive for cytokeratin 14 were found wrapped around the serous and mucous acini. Tight junction components including ZO-1 and E-cadherin were present between both ductal and acinar cells. Ductal and acinar

  11. Effects of Plant Density on the Number of Glandular Trichomes and on Yield and Quality of Essential Oils from Oregano.

    PubMed

    Tuttolomondo, Teresa; La Bella, Salvatore; Leto, Claudio; Bonsangue, Giuseppe; Leone, Raffaele; Gennaro, Maria Cristina; Virga, Giuseppe; Inguanta, Rosalinda; Licata, Mario

    2016-06-01

    Plants yields are influenced by agronomic techniques. Plant density is a complex issue and extremely important when maximizing both crop quality, and biomass and essential oil yields. Plants belonging to the Origanum vulgare subspecies hirtum (Link) Ietswaart were grown adopting four types of plant density and were characterized in biometric and chemical terms. The samples were analyzed using the ANOVA (Principal Component Analysis) statistical method regarding biometric aspects, EO yield and peltate hair density. Essential oil (EO) was extracted by hydrodistillation and analyzed using GC-FID and GC-MS. GC-FID and GC-MS analysis led to the identification of 45 compounds from the EO. Plant density affected production both in terms of biomass and EO. However, it was not found to have affected peltate glandular trichome density or EO quality. PMID:27534133

  12. Cell proliferation, DNA repair, and p53 function are not required for programmed death of prostatic glandular cells induced by androgen ablation.

    PubMed Central

    Berges, R R; Furuya, Y; Remington, L; English, H F; Jacks, T; Isaacs, J T

    1993-01-01

    Androgen ablation induces programmed death of androgen-dependent prostatic glandular cells, resulting in fragmentation of their genomic DNA and the cells themselves into apoptotic bodies. Twenty percent of prostatic glandular cells undergo programmed death per day between day 2 and 5 after castration. During this same period, < 1% of prostatic glandular cells enter the S phase of the cell cycle, documenting that > 95% of these die in G0. During the programmed death of these G0 glandular cells, a futile DNA repair process is induced secondary to the DNA fragmentation. This futile DNA repair is not required, however, since inhibition of this process by > 90% with an appropriately timed hydroxy-urea dosing regimen had no effect upon the extent of the programmed death of these cells after castration. Likewise, p53 gene expression is not required since the same degree of cell death occurred in prostates and seminal vesicles after castration of wild-type and p53-deficient mice. PMID:8415631

  13. Histochemical evidence of β-chitin in parapodial glandular organs and tubes of Spiophanes (Annelida, Sedentaria: Spionidae), and first studies on selected Annelida.

    PubMed

    Guggolz, Theresa; Henne, Stephan; Politi, Yael; Schütz, Roman; Mašić, Admir; Müller, Carsten H G; Meißner, Karin

    2015-12-01

    A generic character of the genus Spiophanes (Annelida, Sedentaria: Spionidae) is the presence of parapodial glandular organs. Parapodial glandular organs in Spiophanes species include secretory cells with cup-shaped microvilli, similar to those present in deep-sea inhabiting vestimentiferans and frenulate Siboglinidae. These cells are supposed to secrete β-chitin for tube-building. In this study, transverse histological and/or ultrathin sections of parapodial glandular organs and tubes of Spiophanes spp. as well as of Glandulospio orestes (Spionidae) and Owenia fusiformis (Oweniidae) were examined. Fluorescent markers together with confocal laser scanning microscopy, and Raman spectroscopy were used to detect chitin in the parapodial glandular organs of Spiophanes and/or in the glands of Owenia and Glandulospio. Tubes of these taxa were tested for chitin to elucidate the use of it for tube-building. The examinations revealed a distinct labelling of the gland contents. Raman spectroscopy documented the presence of β-chitin in both gland types of Spiophanes. The tubes of Spiophanes were found to have a grid-like structure that seems to be built with this β-chitin. Tests of tubes of Dipolydora quadrilobata (Spionidae) for chitin were negative. However, the results of our study provide strong evidence that Spiophanes species, O. fusiformis and probably also G. orestes produce chitin and supposedly use it for tube-building. This implies that the production of chitin and its use as a constituent part of tube-building is more widespread among polychaetes as yet known. The histochemical data presented in this study support previous assumptions inferring homology of parapodial glandular organs of Spionidae and Siboglinidae based on ultrastructure. Furthermore, transmission electron microscopy-based evidence of secretory cells with nail-headed microvilli in O. fusiformis suggests homology of parapodial grandular organs across annelids including Sipuncula. PMID:26291785

  14. Increased secretion of glandular-kallikrein in the bronchial washings induced by intravenous injection of leukotriene C4 in guinea-pigs.

    PubMed Central

    Jin, H. Y.; Katori, M.; Majima, M.; Sunahara, N.

    1992-01-01

    1. Intravenous administration of leukotriene C4 (LTC4) and LTD4 (1-10 nmol kg-1) caused a dose-dependent increase in secretion of glandular-kallikrein in the bronchial washings of guinea-pigs, as measured by cleavage of a synthetic substrate and the formation of kinin. LTC4 was more potent than LTD4 and pilocarpine was much less potent than peptide leukotrienes on a molecular basis. 2. The increases in levels of glandular-kallikrein in the bronchial washings that were induced by LTC4 (3 nmol kg-1, i.v.) were almost completely inhibited by pretreatment with an antagonist of leukotrienes (ONO-1078), with an antagonist of thromboxane (S-1452), with an inhibitor of thromboxane synthetase (OKY-046), with indomethacin, with atropine or with scopolamine. These results indicate that the LTC4-induced increase in levels of glandular-kallikrein may have been mediated by the formation of thromboxane and the release of acetylcholine. 3. The increases in levels of glandular-kallikrein in the bronchial washings induced by STA2 (20 pmol kg-1, i.v.), a stable analogue of thromboxane A2, were completely blocked by pretreatment with atropine, whereas increases induced by pilocarpine (41 mumol kg-1, i.v.) were not blocked by pretreatment with indomethacin, although such increases were inhibited by atropine. This result indicates that secretion of kallikrein stimulated by LTC4 may have been mediated by the successive formation of thromboxane A2 and release of acetylcholine. 4. Intravenous administration of bradykinin (3-30 nmol kg-1) caused a dose-dependent increase in levels of glandular-kallikrein in the bronchial washings. This increase was completely inhibited by pretreatment with atropine, with indomethacin or with an antagonist of thromboxane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1628150

  15. Actin-interacting protein 1 controls assembly and permeability of intestinal epithelial apical junctions

    PubMed Central

    Baranwal, Somesh

    2015-01-01

    Adherens junctions (AJs) and tight junctions (TJs) are crucial regulators of the integrity and restitution of the intestinal epithelial barrier. The structure and function of epithelial junctions depend on their association with the cortical actin cytoskeleton that, in polarized epithelial cells, is represented by a prominent perijunctional actomyosin belt. The assembly and stability of the perijunctional cytoskeleton is controlled by constant turnover (disassembly and reassembly) of actin filaments. Actin-interacting protein (Aip) 1 is an emerging regulator of the actin cytoskeleton, playing a critical role in filament disassembly. In this study, we examined the roles of Aip1 in regulating the structure and remodeling of AJs and TJs in human intestinal epithelium. Aip1 was enriched at apical junctions in polarized human intestinal epithelial cells and normal mouse colonic mucosa. Knockdown of Aip1 by RNA interference increased the paracellular permeability of epithelial cell monolayers, decreased recruitment of AJ/TJ proteins to steady-state intercellular contacts, and attenuated junctional reassembly in a calcium-switch model. The observed defects of AJ/TJ structure and functions were accompanied by abnormal organization and dynamics of the perijunctional F-actin cytoskeleton. Moreover, loss of Aip1 impaired the apico-basal polarity of intestinal epithelial cell monolayers and inhibited formation of polarized epithelial cysts in 3-D Matrigel. Our findings demonstrate a previously unanticipated role of Aip1 in regulating the structure and remodeling of intestinal epithelial junctions and early steps of epithelial morphogenesis. PMID:25792565

  16. Morphological appearances of human lens epithelial cells in culture.

    PubMed

    Power, W; Neylan, D; Collum, L

    1993-01-01

    A system for culturing human lens epithelial cells in the laboratory was developed. The morphological appearances of the cells was studied using phase contrast, scanning and transmission electron microscopy. Cell marker studies using monoclonal antibodies to cytokeratin, vimentin and epithelial membrane antigen were also performed. There was a marked increase in cell size as a function of time in culture. After 3 to 4 weeks cells showed early signs of ageing. By 6 to 8 weeks the majority of the cells had become very irregular in shape and demonstrated irregularities of the plasma membrane and intra-cytoplasmic vacuole formation. The cells stained strongly for vimentin and epithelial membrane antigen. Staining with cytokeratin was somewhat weaker. This culture technique provides us with a suitable model for studying the growth behavior of these cells. PMID:7512459

  17. Intestinal epithelial dysplasia (tufting enteropathy).

    PubMed

    Goulet, Olivier; Salomon, Julie; Ruemmele, Frank; de Serres, Natacha Patey-Mariaud; Brousse, Nicole

    2007-01-01

    Intestinal epithelial dysplasia (IED), also known as tufting enteropathy, is a congenital enteropathy presenting with early-onset severe intractable diarrhea causing sometimes irreversible intestinal failure. To date, no epidemiological data are available, however, the prevalence can be estimated at around 1/50,000-100,000 live births in Western Europe. The prevalence seems higher in areas with high degree of consanguinity and in patients of Arabic origin. Infants develop within the first days after birth a watery diarrhea persistent in spite of bowel rest and parenteral nutrition. Some infants are reported to have associated choanal rectal or esophageal atresia. IED is thought to be related to abnormal enterocytes development and/or differentiation. Nonspecific punctuated keratitis was reported in more than 60% of patients. Histology shows various degree of villous atrophy, with low or without mononuclear cell infiltration of the lamina propria but specific histological abnormalities involving the epithelium with disorganization of surface enterocytes with focal crowding, resembling tufts. Several associated specific features were reported, including abnormal deposition of laminin and heparan sulfate proteoglycan (HSPG) in the basement membrane, increased expression of desmoglein and ultrastructural changes in the desmosomes, and abnormal distribution of alpha2beta1 integrin adhesion molecules. One model of transgenic mice in which the gene encoding the transcription factor Elf3 is disrupted have morphologic features resembling IED. Parental consanguinity and/or affected siblings suggest an autosomal recessive transmission but the causative gene(s) have not been yet identified making prenatal diagnosis unavailable. Some infants have a milder phenotype than others but in most patients, the severity of the intestinal malabsorption even with enteral feeding make them totally dependent on daily long-term parenteral nutrition with a subsequent risk of complications

  18. Bacillus anthracis Lethal Toxin Reduces Human Alveolar Epithelial Barrier Function

    PubMed Central

    Langer, Marybeth; Duggan, Elizabeth Stewart; Booth, John Leland; Patel, Vineet Indrajit; Zander, Ryan A.; Silasi-Mansat, Robert; Ramani, Vijay; Veres, Tibor Zoltan; Prenzler, Frauke; Sewald, Katherina; Williams, Daniel M.; Coggeshall, Kenneth Mark; Awasthi, Shanjana; Lupu, Florea; Burian, Dennis; Ballard, Jimmy Dale; Braun, Armin

    2012-01-01

    The lung is the site of entry for Bacillus anthracis in inhalation anthrax, the deadliest form of the disease. Bacillus anthracis produces virulence toxins required for disease. Alveolar macrophages were considered the primary target of the Bacillus anthracis virulence factor lethal toxin because lethal toxin inhibits mouse macrophages through cleavage of MEK signaling pathway components, but we have reported that human alveolar macrophages are not a target of lethal toxin. Our current results suggest that, unlike human alveolar macrophages, the cells lining the respiratory units of the lung, alveolar epithelial cells, are a target of lethal toxin in humans. Alveolar epithelial cells expressed lethal toxin receptor protein, bound the protective antigen component of lethal toxin, and were subject to lethal-toxin-induced cleavage of multiple MEKs. These findings suggest that human alveolar epithelial cells are a target of Bacillus anthracis lethal toxin. Further, no reduction in alveolar epithelial cell viability was observed, but lethal toxin caused actin rearrangement and impaired desmosome formation, consistent with impaired barrier function as well as reduced surfactant production. Therefore, by compromising epithelial barrier function, lethal toxin may play a role in the pathogenesis of inhalation anthrax by facilitating the dissemination of Bacillus anthracis from the lung in early disease and promoting edema in late stages of the illness. PMID:23027535

  19. Lateral adhesion drives reintegration of misplaced cells into epithelial monolayers.

    PubMed

    Bergstralh, Dan T; Lovegrove, Holly E; St Johnston, Daniel

    2015-11-01

    Cells in simple epithelia orient their mitotic spindles in the plane of the epithelium so that both daughter cells are born within the epithelial sheet. This is assumed to be important to maintain epithelial integrity and prevent hyperplasia, because misaligned divisions give rise to cells outside the epithelium. Here we test this assumption in three types of Drosophila epithelium; the cuboidal follicle epithelium, the columnar early embryonic ectoderm, and the pseudostratified neuroepithelium. Ectopic expression of Inscuteable in these tissues reorients mitotic spindles, resulting in one daughter cell being born outside the epithelial layer. Live imaging reveals that these misplaced cells reintegrate into the tissue. Reducing the levels of the lateral homophilic adhesion molecules Neuroglian or Fasciclin 2 disrupts reintegration, giving rise to extra-epithelial cells, whereas disruption of adherens junctions has no effect. Thus, the reinsertion of misplaced cells seems to be driven by lateral adhesion, which pulls cells born outside the epithelial layer back into it. Our findings reveal a robust mechanism that protects epithelia against the consequences of misoriented divisions. PMID:26414404

  20. Epithelial impedance analysis in experimentally induced colon cancer.

    PubMed Central

    Davies, R J; Joseph, R; Kaplan, D; Juncosa, R D; Pempinello, C; Asbun, H; Sedwitz, M M

    1987-01-01

    Epithelial impedance analysis was used to measure the alterations in resistance of the large bowel in a murine model of large bowel cancer. The technique was able to resolve the epithelial resistance from the total resistance of the bowel wall. A progressive decrease in resistance of the bowel epithelium occurs during carcinogenesis induced with dimethyhydrazine. About a 21% decrease in epithelial resistance from 22.0 +/- 1.3 omega.cm-2 to 17.5 +/- 1.1 omega cm-2 (p less than 0.025) was observed after 20 wk of carcinogen administration. The sensitivity of the technique in detecting altered epithelial resistance in premalignant bowel mucosa was improved by examining the impedance profile in a sodium-free Ringer's solution where the epithelium of control colons had a resistance of 24.4 +/- 1.8 omega.cm-2 compared with 19.0 +/- 1.1 omega.cm-2 (p less than 0.02) in colons from animals treated for only 4 wk with the carcinogen. Epithelial impedance analysis would seem to be a sensitive technique capable of identifying changes in the electrical properties or the large bowel early in disease states. PMID:3427187

  1. Porphyromonas gingivalis invades oral epithelial cells in vitro.

    PubMed

    Sandros, J; Papapanou, P; Dahlén, G

    1993-05-01

    The aim of the present study was to analyze the adhesive and invasive potential of a number of P. gingivalis strains, in an in vitro system utilizing cultures of human oral epithelial cells (KB cell line, ATCC CCL 17). P. gingivalis strains W50 and FDC 381 (laboratory strains) and OMGS 1738, 1743 and 1439 (clinical isolates) as well as E. coli strain HB 101 (non-adhering, non-invasive control) were used. Adherence was assessed by means of scintillation counting and light microscopy, after incubation of radiolabelled bacteria with epithelial cells. In the invasion assay, monolayers were infected with the P. gingivalis and E. coli strains and further incubated with an antibiotic mixture (metronidazole 0.1 mg/ml and gentamicin 0.5 mg/ml). Invasion was evaluated by (i) assessing presence of bacteria surviving the antibiotic treatment, and (ii) electron microscopy. All P. gingivalis strains adhered to and entered into the oral epithelial cells. After 3 hours of incubation, bacteria were frequently identified intracellularly by means of electron microscopy. The cellular membranes, encapsulating the microorganisms in early stages of the invasive process, appeared later to disintegrate. The presence of coated pits on the epithelial cell surfaces suggested that internalization of P. gingivalis was associated with receptor-mediated endocytosis (RME). Formation of outer membrane vesicles (blebs) by intracellular bacteria indicated that internalized P. gingivalis was able to retain its viability. E. coli strain HB 101 neither adhered to nor invaded epithelial cells. PMID:8388449

  2. Structure and properties of the glandular surface in the digestive zone of the pitcher in the carnivorous plant Nepenthes ventrata and its role in insect trapping and retention.

    PubMed

    Gorb, Elena; Kastner, Victoria; Peressadko, Andrei; Arzt, Eduard; Gaume, Laurence; Rowe, Nick; Gorb, Stanislav

    2004-08-01

    Carnivorous plants of the genus Nepenthes grow in nutrient-poor habitats and have evolved specialised trapping organs, known as pitchers. These are composed of different surface zones serving the functions of attraction, capture and digestion of insects, which represent a main source of nitrogen. To investigate the role of the glandular digestive zone in the trapping mechanism of the pitcher, structural, mechanical and physico-chemical studies were applied to N. ventrata and combined with insect behavioural experiments. It was found that the glandular surface is microscopically rough since it is regularly structured with multicellular glands situated in epidermal depressions. The presence of downward-directed 'hoods' over the upper part of glands and sloped depressions in the proximal direction of the pitcher causes a marked anisotropy of the surface. The glandular zone surface is composed of relatively stiff material (Young's modulus, 637.19+/-213.44 kPa). It is not homogeneous, in terms of adhesive properties, and contains numerous areas without adhesion as well as adhesive areas differing greatly in tenacity values (range, 1.39-28.24 kPa). The surface is readily wettable with water (contact angle, 31.9-36.0 degrees C) and has a high surface free energy (56.84-61.93 mN m(-1)) with a relatively high polar component (33.09-52.70 mN m(-1)). To examine the effect of the glandular secretion on attachment systems of insects having hairy and smooth adhesive pads, forces generated on different surfaces by Calliphora vicina flies and Pyrrhocoris apterus bugs, respectively, were measured. Flies attached equally well to both fresh and air-dried glandular surfaces whereas bugs generated a significantly lower force on the fresh glandular surface compared with the air-dried one. It is assumed that the contribution of the glandular surface to insect retention, due to its effect on insect attachment, differs depending on insect weight and the type of insect attachment system

  3. Theory of epithelial elasticity

    NASA Astrophysics Data System (ADS)

    Krajnc, Matej; Ziherl, Primož

    2015-11-01

    We propose an elastic theory of epithelial monolayers based on a two-dimensional discrete model of dropletlike cells characterized by differential surface tensions of their apical, basal, and lateral sides. We show that the effective tissue bending modulus depends on the apicobasal differential tension and changes sign at the transition from the flat to the fold morphology. We discuss three mechanisms that stabilize the finite-wavelength fold structures: Physical constraint on cell geometry, hard-core interaction between non-neighboring cells, and bending elasticity of the basement membrane. We show that the thickness of the monolayer changes along the waveform and thus needs to be considered as a variable rather than a parameter. Next we show that the coupling between the curvature and the thickness is governed by the apicobasal polarity and that the amplitude of thickness modulation along the waveform is proportional to the apicobasal differential tension. This suggests that intracellular stresses can be measured indirectly by observing easily measurable morphometric parameters. We also study the mechanics of three-dimensional structures with cylindrical symmetry.

  4. Methods toward in vivo measurement of zebrafish epithelial and deep cell proliferation.

    PubMed

    Campana, Matteo; Maury, Benoit; Dutreix, Marie; Peyriéras, Nadine; Sarti, Alessandro

    2010-05-01

    We present a strategy for automatic classification and density estimation of epithelial enveloping layer (EVL) and deep layer (DEL) cells, throughout zebrafish early embryonic stages. Automatic cells classification provides the bases to measure the variability of relevant parameters, such as cells density, in different classes of cells and is finalized to the estimation of effectiveness and selectivity of anticancer drug in vivo. We aim at approaching these measurements through epithelial/deep cells classification, epithelial area and thickness measurement, and density estimation from scattered points. Our procedure is based on Minimal Surfaces, Otsu clustering, Delaunay Triangulation, and Within-R cloud of points density estimation approaches. In this paper, we investigated whether the distance between nuclei and epithelial surface is sufficient to discriminate epithelial cells from deep cells. Comparisons of different density estimators, experimental results, and extensively accuracy measurements are included. PMID:19781805

  5. The Shroom family proteins play broad roles in the morphogenesis of thickened epithelial sheets

    PubMed Central

    Lee, Chanjae; Le, Minh-Phuong; Wallingford, John B.

    2009-01-01

    Thickened epithelial sheets are found in most organ systems, but the mechanisms governing their morphogenesis remain poorly defined. We show here that Shroom family proteins are broadly involved in generating thickened epithelial sheets. Through in situ hybridization, we report temporal and spatial expression patterns of the four Shroom family members during early Xenopus development from oocytes to tadpole stages. Shroom1 and 2 mRNAs are maternally expressed, while Shroom3 and Shroom4 are zygotic transcripts. During later development, all four Shroom family proteins are broadly expressed in developing epithelial organs, and the epithelial cells that express Shrooms are elongated. Moreover, we show that ectopic expression of Shroom2, like Shroom3, is able to increase cell height and that loss of Shroom2 function results in a failure of cell elongation in the neural epithelium. These data suggest that Shroom family proteins play an important role in the morphogenesis of several different embryonic epithelial tissues. PMID:19384856

  6. Epithelial Sodium Channels in Pulmonary Epithelial Progenitor and Stem Cells

    PubMed Central

    Liu, Yang; Jiang, Bi-Jie; Zhao, Run-Zhen; Ji, Hong-Long

    2016-01-01

    Regeneration of the epithelium of mammalian lungs is essential for restoring normal function following injury, and various cells and mechanisms contribute to this regeneration and repair. Club cells, bronchioalveolar stem cells (BASCs), and alveolar type II epithelial cells (ATII) are dominant stem/progenitor cells for maintaining epithelial turnover and repair. Epithelial Na+ channels (ENaC), a critical pathway for transapical salt and fluid transport, are expressed in lung epithelial progenitors, including club and ATII cells. Since ENaC activity and expression are development- and differentiation-dependent, apically located ENaC activity has therefore been used as a functional biomarker of lung injury repair. ENaC activity may be involved in the migration and differentiation of local and circulating stem/progenitor cells with diverse functions, eventually benefiting stem cells spreading to re-epithelialize injured lungs. This review summarizes the potential roles of ENaC expressed in native progenitor and stem cells in the development and regeneration of the respiratory epithelium. PMID:27570489

  7. Oestrogen-induced angiogenesis promotes adenomyosis by activating the Slug-VEGF axis in endometrial epithelial cells

    PubMed Central

    Huang, Tze-Sing; Chen, Yi-Jen; Chou, Teh-Ying; Chen, Chih-Yao; Li, Hsin-Yang; Huang, Ben-Shian; Tsai, Hsiao-Wen; Lan, Hsin-Yi; Chang, Cheng-Hsuan; Twu, Nae-Fang; Yen, Ming-Shyen; Wang, Peng-Hui; Chao, Kuan-Chong; Lee, Chun-Chung; Yang, Muh-Hwa

    2014-01-01

    Adenomyosis is an oestrogen-dependent disease characterized by the invasion of endometrial epithelial cells into the myometrium of uterus, and angiogenesis is thought to be required for the implantation of endometrial glandular tissues during the adenomyotic pathogenesis. In this study, we demonstrate that compared with eutopic endometria, adenomyotic lesions exhibited increased vascularity as detected by sonography. Microscopically, the lesions also exhibited an oestrogen-associated elevation of microvascular density and VEGF expression in endometrial epithelial cells. We previously reported that oestrogen-induced Slug expression was critical for endometrial epithelial–mesenchymal transition and development of adenomyosis. Our present studies demonstrated that estradiol (E2) elicited a Slug-VEGF axis in endometrial epithelial cells, and also induced pro-angiogenic activity in vascular endothelial cells. The antagonizing agents against E2 or VEGF suppressed endothelial cells migration and tubal formation. Animal experiments furthermore confirmed that blockage of E2 or VEGF was efficient to attenuate the implantation of adenomyotic lesions. These results highlight the importance of oestrogen-induced angiogenesis in adenomyosis development and provide a potential strategy for treating adenomyosis through intercepting the E2-Slug-VEGF pathway. PMID:24758741

  8. Diagnosis of gastric epithelial neoplasia: Dilemma for Korean pathologists.

    PubMed

    Kim, Joon Mee; Cho, Mee-Yon; Sohn, Jin Hee; Kang, Dae Young; Park, Cheol Keun; Kim, Woo Ho; Jin, So-Young; Kim, Kyoung Mee; Chang, Hee Kyung; Yu, Eunsil; Jung, Eun Sun; Chang, Mee Soo; Joo, Jong Eun; Joo, Mee; Kim, Youn Wha; Park, Do Youn; Kang, Yun Kyung; Park, Sun Hoo; Han, Hye Seung; Kim, Young Bae; Park, Ho Sung; Chae, Yang Seok; Kwon, Kye Won; Chang, Hee Jin

    2011-06-01

    The histopathological diagnosis of gastric mucosal biopsy and endoscopic mucosal resection/endoscopic submucosal dissection specimens is important, but the diagnostic criteria, terminology, and grading system are not the same in the East and West. A structurally invasive focus is necessary to diagnose carcinoma for most Western pathologists, but Japanese pathologists make a diagnosis of cancer based on severe dysplastic cytologic atypia irrespective of the presence of invasion. Although the Vienna classification was introduced to reduce diagnostic discrepancies, it has been difficult to adopt due to different concepts for gastric epithelial neoplastic lesions. Korean pathologists experience much difficulty making a diagnosis because we are influenced by Japanese pathologists as well as Western medicine. Japan is geographically close to Korea, and academic exchanges are active. Additionally, Korean doctors are familiar with Western style medical terminology. As a result, the terminology, definitions, and diagnostic criteria for gastric intraepithelial neoplasia are very heterogeneous in Korea. To solve this problem, the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists has made an effort and has suggested guidelines for differential diagnosis: (1) a diagnosis of carcinoma is based on invasion; (2) the most important characteristic of low grade dysplasia is the architectural pattern such as regular distribution of crypts without severe branching, budding, or marked glandular crowding; (3) if nuclear pseudostratification occupies more than the basal half of the cryptal cells in three or more adjacent crypts, the lesion is considered high grade dysplasia; (4) if severe cytologic atypia is present, careful inspection for invasive foci is necessary, because the risk for invasion is very high; and (5) other structural or nuclear atypia should be evaluated to make a final decision such as cribriform pattern, papillae, ridges, vesicular nuclei

  9. The SYT-SSX fusion protein and histological epithelial differentiation in synovial sarcoma: relationship with extracellular matrix remodeling.

    PubMed

    Saito, Tsuyoshi

    2013-01-01

    Synovial sarcoma (SS) tumor cells, which have the chromosomal translocation t(X;18)(p11.2;q11.2), have an inherently greater propensity for epithelial differentiation than other mesenchymal tumors, especially spindle cell sarcomas. This is caused by de-repression of the transcription of E-cadherin by SYT-SSX1 and SYT-SSX2, which dissociate Snail or Slug, respectively, from the E-cadherin promoter. However, a subset of SS with SYT-SSX1 loses E-cadherin expression despite adequate de-repression because of mutations in E-cadherin, resulting in monophasic histology. The ratio of the expression levels of SYT-SSX1 and Snail is also associated with E-cadherin expression: the lower the SYT-SSX1/Snail ratio, the lower the level of E-cadherin expression, and vice versa, thus affecting tumor histology. In addition, Wnt signal activation caused by mutation of β-catenin, APC, or Axin 1 and 2 is associated with monophasic histology. Remodeling of the extracellular matrix is also important. Only cells that survive all of these steps can finally exhibit biphasic histology. On the other hand, the SYT-SSX2 fusion has a weaker de-repression effect on the E-cadherin promoter than does SYT-SSX1, so it is difficult for SYT-SSX2-expressing tumors to achieve sufficient capacity for epithelial differentiation to form glandular structures. This review provides an interesting model for this epithelial differentiation that shows a possible mechanism for the aberrant mesenchymal to epithelial transition of SS and suggests that it might better be considered an epithelial to mesenchymal transition. PMID:24228088

  10. Generation of Induced Pluripotent Stem Cells from Bovine Epithelial Cells and Partial Redirection Toward a Mammary Phenotype In Vitro.

    PubMed

    Cravero, Diego; Martignani, Eugenio; Miretti, Silvia; Accornero, Paulo; Pauciullo, Alfredo; Sharma, Ruchi; Donadeu, Francesco Xavier; Baratta, Mario

    2015-06-01

    In contrast to adult stem cells, induced pluripotent stem cells (iPSCs) can be grown robustly in vitro and differentiated into virtually any tissue, thus providing an attractive alternative for biomedical applications. Although iPSC technology is already being used in human biomedicine, its potential in animal production has not been investigated. Herein, we investigated the potential application of iPSCs in dairy production by generating bovine iPSCs and establishing their ability to generate mammary epithelial tissue. iPSCs were derived by retrovirus-mediated expression of murine Oct4, Sox2, Klf4, and c-Myc in mammary epithelium and dermal fibroblasts. The resulting reprogrammed cells stained positive for alkaline phosphatase and showed renewed expression of pluripotency genes, including Lin28, Rex1, Oct4, Sox2, and Nanog. In addition, injection of epithelial- or fibroblast-derived reprogrammed cells into nonobese diabetic (NOD/NOD) mice resulted in the formation of teratomas containing differentiated derivatives of the three germ layers, including cartilage, membranous ossification, stratified squamous epithelial tissue, hair follicles, neural pinwheels, and different types of glandular tissue. Finally, mammary epithelium-derived iPSCs could be induced to differentiate back to a mammary phenotype characterized by epithelial cells expressing cytokeratin 14 (CK14), CK18, and smooth muscle actin (SMA) as a result of treatment with 10 nM progesterone. This study reports for the first time the generation of iPSCs from bovine epithelial cells and demonstrates the potential of using iPSCs technology for generating bovine mammary tissue in vitro. PMID:26053520

  11. Quantitative determination of enhydrin in leaf rinse extracts and in glandular trichomes of Smallanthus sonchifolius (Asteraceae) by reversed-phase high-performance liquid chromatography.

    PubMed

    Schorr, Karin; Da Costa, Fernando B

    2005-01-01

    A simple, reliable and rapid reversed-phase HPLC-PAD procedure for the characterisation and quantitative determination of the anti-diabetic sesquiterpene lactone enhydrin (1) from Smallanthus sonchifolius (yacón) has been evaluated and validated. The approach focused on the analysis of various leaf rinse extracts, as well as the glandular trichomes of intact leaves, in which 1 was the major compound detected. The best sample preparation of a rinse extract yielded 0.67 mg/mL of 1, whilst a rapid rinse of a small piece of one dried leaf gave 0.09 mg/mL of 1; the highest concentration obtained from a glandular extract was 0.07 mg/mL. The dried leaves of S. sonchifolius were found to contain a total of 0.97% of 1. PMID:15997848

  12. Identification and characterization of two bisabolene synthases from linear glandular trichomes of sunflower (Helianthus annuus L., Asteraceae).

    PubMed

    Aschenbrenner, Anna-Katharina; Kwon, Moonhyuk; Conrad, Jürgen; Ro, Dae-Kyun; Spring, Otmar

    2016-04-01

    Sunflower is known to produce a variety of bisabolene-type sesquiterpenes and accumulates these substances in trichomes of leaves, stems and flowering parts. A bioinformatics approach was used to identify the enzyme responsible for the initial step in the biosynthesis of these compounds from its precursor farnesyl pyrophosphate. Based on sequence similarity with a known bisabolene synthases from Arabidopsis thaliana AtTPS12, candidate genes of Helianthus were searched in EST-database and used to design specific primers. PCR experiments identified two candidates in the RNA pool of linear glandular trichomes of sunflower. Their sequences contained the typical motifs of sesquiterpene synthases and their expression in yeast functionally characterized them as bisabolene synthases. Spectroscopic analysis identified the stereochemistry of the product of both enzymes as (Z)-γ-bisabolene. The origin of the two sunflower bisabolene synthase genes from the transcripts of linear trichomes indicates that they may be involved in the synthesis of sesquiterpenes produced in these trichomes. Comparison of the amino acid sequences of the sunflower bisabolene synthases showed high similarity with sesquiterpene synthases from other Asteracean species and indicated putative evolutionary origin from a β-farnesene synthase. PMID:26880289

  13. Genes Regulating Epithelial Polarity Are Critical Suppressors of Esophageal Oncogenesis

    PubMed Central

    Li, Xiu-Min; Wang, Hui; Zhu, Li-Li; Zhao, Run-Zhen; Ji, Hong-Long

    2015-01-01

    Esophageal cancer is an aggressive disease featured by early lymphatic and hematogenous dissemination, and is the sixth leading cause of cancer-related deaths worldwide. The proper formation of apicobasal polarity is essential for normal epithelium physiology and tissue homeostasis, while loss of polarity is a hallmark of cancer development including esophageal oncogenesis. In this review, we summarized the stages of esophageal cancer development associated with the loss or deregulation of epithelial cell apicobasal polarity. Loss of epithelial apicobasal polarity exerts an indispensable role in the initiation of esophageal oncogenesis, tumor progression, and the advancement of tumors from benign to malignant. In particular, we reviewed the involvement of several critical genes, including Lkb1, claudin-4, claudin-7, Par3, Lgl1, E-cadherin, and the Scnn1 gene family. Understanding the role of apicobasal regulators may lead to new paradigms for treatment of esophageal tumors, including improvement of prognostication, early diagnosis, and individually tailored therapeutic interventions in esophageal oncology. PMID:26185530

  14. Integrins and epithelial cell polarity

    PubMed Central

    Lee, Jessica L.; Streuli, Charles H.

    2014-01-01

    ABSTRACT Cell polarity is characterised by differences in structure, composition and function between at least two poles of a cell. In epithelial cells, these spatial differences allow for the formation of defined apical and basal membranes. It has been increasingly recognised that cell–matrix interactions and integrins play an essential role in creating epithelial cell polarity, although key gaps in our knowledge remain. This Commentary will discuss the mounting evidence for the role of integrins in polarising epithelial cells. We build a model in which both inside-out signals to polarise basement membrane assembly at the basal surface, and outside-in signals to control microtubule apical–basal orientation and vesicular trafficking are required for establishing and maintaining the orientation of epithelial cell polarity. Finally, we discuss the relevance of the basal integrin polarity axis to cancer. This article is part of a Minifocus on Establishing polarity. For further reading, please see related articles: ‘ERM proteins at a glance’ by Andrea McClatchey (J. Cell Sci. 127, 3199–3204). ‘Establishment of epithelial polarity – GEF who's minding the GAP?’ by Siu Ngok et al. (J. Cell Sci. 127, 3205–3215). PMID:24994933

  15. Sequestration of human cytomegalovirus by human renal and mammary epithelial cells

    SciTech Connect

    Twite, Nicolas; Andrei, Graciela; Kummert, Caroline; Donner, Catherine; Perez-Morga, David; De Vos, Rita; Snoeck, Robert; Marchant, Arnaud

    2014-07-15

    Urine and breast milk represent the main routes of human cytomegalovirus (HCMV) transmission but the contribution of renal and mammary epithelial cells to viral excretion remains unclear. We observed that kidney and mammary epithelial cells were permissive to HCMV infection and expressed immediate early, early and late antigens within 72 h of infection. During the first 24 h after infection, high titers of infectious virus were measured associated to the cells and in culture supernatants, independently of de novo synthesis of virus progeny. This phenomenon was not observed in HCMV-infected fibroblasts and suggested the sequestration and the release of HCMV by epithelial cells. This hypothesis was supported by confocal and electron microscopy analyses. The sequestration and progressive release of HCMV by kidney and mammary epithelial cells may play an important role in the excretion of the virus in urine and breast milk and may thereby contribute to HCMV transmission. - Highlights: • Primary renal and mammary epithelial cells are permissive to HCMV infection. • HCMV is sequestered by epithelial cells and this phenomenon does not require viral replication. • HCMV sequestration by epithelial cells is reduced by antibodies and IFN-γ.

  16. STAT3 in Epithelial Cells Regulates Inflammation and Tumor Progression to Malignant State in Colon1

    PubMed Central

    Nguyen, Andrew V; Wu, Yuan-Yuan; Liu, Qiang; Wang, Donghai; Nguyen, Stephanie; Loh, Ricky; Pang, Joey; Friedman, Kenneth; Orlofsky, Amos; Augenlicht, Leonard; Pollard, Jeffrey W; Lin, Elaine Y

    2013-01-01

    Chronic inflammation is an important risk factor for the development of colorectal cancer; however, the mechanism of tumorigenesis especially tumor progression to malignancy in the inflamed colon is still unclear. Our study shows that epithelial signal transducer and activator of transcription 3 (STAT3), persistently activated in inflamed colon, is not required for inflammation-induced epithelial overproliferation and the development of early-stage tumors; however, it is essential for tumor progression to advanced malignancy. We found that one of the mechanisms that epithelial STAT3 regulates in tumor progression might be to modify leukocytic infiltration in the large intestine. Activation of epithelial STAT3 promotes the infiltration of the CD8+ lymphocyte population but inhibits the recruitment of regulatory T (Treg) lymphocytes. The loss of Stat3 in epithelial cells promoted the expression of cytokines/chemokines including CCL19, CCL28, and RANTES, which are known to be able to recruit Treg lymphocytes. Linked to these changes was the pathway mediated by sphingosine 1-phosphate receptor 1 and sphingosine 1-phosphate kinases, which is activated in colonic epithelial cells in inflamed colon with functional STAT3 but not in epithelial cells deleted of STAT3. Our data suggest that epithelial STAT3 plays a critical role in inflammation-induced tumor progression through regulation of leukocytic recruitment especially the infiltration of Treg cells in the large intestine. PMID:24027425

  17. Single-Cell Metabolite Profiling of Stalk and Glandular Cells of Intact Trichomes with Internal Electrode Capillary Pressure Probe Electrospray Ionization Mass Spectrometry.

    PubMed

    Nakashima, Taiken; Wada, Hiroshi; Morita, Satoshi; Erra-Balsells, Rosa; Hiraoka, Kenzo; Nonami, Hiroshi

    2016-03-15

    In this report, we developed the pressure probe electrospray ionization-mass spectrometry with internal electrode capillary (IEC-PPESI-MS) which enables high spatial-resolution cell sampling, precise postsampling manipulation, and high detection sensitivity. Using this technique, a comparative in situ single-cell metabolite profiling of stalk and glandular cells, the two adjacent cell types comprising a trichome unit in tomato plants (Solanum lycopersicum L.), were performed to clarify the extent of metabolic differentiation between two cell types as well as among different types of trichomes. Owing to high sensitivity of the system, less than a picoliter cell sap from a single stalk cell sufficiently yielded a number of peaks of amino acids, organic acids, carbohydrates, and flavonoids. The minimal cell sap removal from a stalk cell without severe disturbance of trichome structure enabled sequential analysis of adjacent glandular cell on the same trichome, which showed the presence of striking differences in metabolite compositions between two adjacent cell types. Comparison among different types of trichome also revealed significant variations in metabolite profiles, particularly in flavonoids and acyl sugars compositions. Some metabolites were found only in specific cell types or particular trichome types. Although extensive metabolomics analysis of glandular cells of tomato trichomes has been previously documented, this is the first report describing cell-to-cell variations in metabolite compositions of stalk and glandular cells as well as in different trichome types. Further application of this technique may provide new insights into distinct metabolism in plant cells displaying variations in shape, size, function and physicochemical properties. PMID:26845634

  18. Determination of Tube Output (kVp) and Exposure Mode for Breast Phantom of Various Thicknesses/Glandularity for Digital Mammography

    PubMed Central

    IZDIHAR, Kamal; KANAGA, Kumari Chelliah; KRISHNAPILLAI, Vijayalakshimi; SULAIMAN, Tamanang

    2015-01-01

    Background: Optimisation of average glandular dose (AGD) for two-dimensional (2D) mammography is important, as imaging using ionizing radiation has the probability to induce cancer resulting from stochastic effects. This study aims to observe the effects of kVp, anode/filter material, and exposure mode on the dose and image quality of 2D mammography. Methods: This experimental study was conducted using full-field digital mammography. The entrance surface air kerma was determined using thermoluminescent dosimeter (TLD) 100H and ionization chamber (IC) on three types of Computerized Imaging Reference System (CIRS) phantom with 50/50, 30/70, and 20/80 breast glandularity, respectively, in the auto-time mode and auto-filter mode. The Euref protocol was used to calculate the AGD while the image quality was evaluated using contrast-to-noise ratio (CNR), figure of merit (FOM), and image quality figure (IQF). Results: It is shown that AGD values in the auto-time mode did not decrease significantly with the increasing tube voltage of the silver filter (r = −0.187, P > 0.05) and rhodium filter (r = −0.131, P > 0.05) for all the phantoms. The general linear model showed that AGD for all phantoms had a significant effect between different exposure factors [F (6,12.3) = 4.48 and mode of exposure F (1,86) = 4.17, P < 0.05, respectively] but there is no significant difference between the different anode/filter combination [F (1,4) = 0.571]. Conclusion: In summary, the 28, 29, and 31 kVp are the optimum kVp for 50%, 30%, and 20% breast glandularity, respectively. Besides the auto-filter mode is suitable for 50%, 30%, and 20% breast glandularity because it is automatic, faster, and may avoid error done by the operator. PMID:25892949

  19. Differential microRNA Analysis of Glandular Trichomes and Young Leaves in Xanthium strumarium L. Reveals Their Putative Roles in Regulating Terpenoid Biosynthesis.

    PubMed

    Fan, Rongyan; Li, Yuanjun; Li, Changfu; Zhang, Yansheng

    2015-01-01

    The medicinal plant Xanthium strumarium L. (X. strumarium) is covered with glandular trichomes, which are the sites for synthesizing pharmacologically active terpenoids such as xanthatin. MicroRNAs (miRNAs) are a class of 21-24 nucleotide (nt) non-coding RNAs, most of which are identified as regulators of plant growth development. Identification of miRNAs involved in the biosynthesis of plant secondary metabolites remains limited. In this study, high-throughput Illumina sequencing, combined with target gene prediction, was performed to discover novel and conserved miRNAs with potential roles in regulating terpenoid biosynthesis in X. strumarium glandular trichomes. Two small RNA libraries from leaves and glandular trichomes of X. strumarium were established. In total, 1,185 conserved miRNAs and 37 novel miRNAs were identified, with 494 conserved miRNAs and 18 novel miRNAs being differentially expressed between the two tissue sources. Based on the X. strumarium transcriptome data that we recently constructed, 3,307 annotated mRNA transcripts were identified as putative targets of the differentially expressed miRNAs. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis suggested that some of the differentially expressed miRNAs, including miR6435, miR5021 and miR1134, might be involved in terpenoid biosynthesis in the X. strumarium glandular trichomes. This study provides the first comprehensive analysis of miRNAs in X. strumarium, which forms the basis for further understanding of miRNA-based regulation on terpenoid biosynthesis. PMID:26406988

  20. Differential microRNA Analysis of Glandular Trichomes and Young Leaves in Xanthium strumarium L. Reveals Their Putative Roles in Regulating Terpenoid Biosynthesis

    PubMed Central

    Fan, Rongyan; Li, Yuanjun; Li, Changfu; Zhang, Yansheng

    2015-01-01

    The medicinal plant Xanthium strumarium L. (X. strumarium) is covered with glandular trichomes, which are the sites for synthesizing pharmacologically active terpenoids such as xanthatin. MicroRNAs (miRNAs) are a class of 21–24 nucleotide (nt) non-coding RNAs, most of which are identified as regulators of plant growth development. Identification of miRNAs involved in the biosynthesis of plant secondary metabolites remains limited. In this study, high-throughput Illumina sequencing, combined with target gene prediction, was performed to discover novel and conserved miRNAs with potential roles in regulating terpenoid biosynthesis in X. strumarium glandular trichomes. Two small RNA libraries from leaves and glandular trichomes of X. strumarium were established. In total, 1,185 conserved miRNAs and 37 novel miRNAs were identified, with 494 conserved miRNAs and 18 novel miRNAs being differentially expressed between the two tissue sources. Based on the X. strumarium transcriptome data that we recently constructed, 3,307 annotated mRNA transcripts were identified as putative targets of the differentially expressed miRNAs. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis suggested that some of the differentially expressed miRNAs, including miR6435, miR5021 and miR1134, might be involved in terpenoid biosynthesis in the X. strumarium glandular trichomes. This study provides the first comprehensive analysis of miRNAs in X. strumarium, which forms the basis for further understanding of miRNA-based regulation on terpenoid biosynthesis. PMID:26406988

  1. Evidence of progenitor cells of glandular and myoepithelial cell lineages in the human adult female breast epithelium: a new progenitor (adult stem) cell concept.

    PubMed

    Boecker, Werner; Buerger, Horst

    2003-10-01

    Although experimental data clearly confirm the existence of self-renewing mammary stem cells, the characteristics of such progenitor cells have never been satisfactorily defined. Using a double immunofluorescence technique for simultaneous detection of the basal cytokeratin 5, the glandular cytokeratins 8/18 and the myoepithelial differentiation marker smooth muscle actin (SMA), we were able to demonstrate the presence of CK5+ cells in human adult breast epithelium. These cells have the potential to differentiate to either glandular (CK8/18+) or myoepithelial cells (SMA+) through intermediary cells (CK5+ and CK8/18+ or SMA+). We therefore proceeded on the assumption that the CK5+ cells are phenotypically and behaviourally progenitor (committed adult stem) cells of human breast epithelium. Furthermore, we furnish evidence that most of these progenitor cells are located in the luminal epithelium of the ductal lobular tree. Based on data obtained in extensive analyses of proliferative breast disease lesions, we have come to regard usual ductal hyperplasia as a progenitor cell-derived lesion, whereas most breast cancers seem to evolve from differentiated glandular cells. Double immunofluorescence experiments provide a new tool to characterize phenotypically progenitor (adult stem) cells and their progenies. This model has been shown to be of great value for a better understanding not only of normal tissue regeneration but also of proliferative breast disease. Furthermore, this model provides a new tool for unravelling further the regulatory mechanisms that govern normal and pathological cell growth. PMID:14521517

  2. Methylerythritol and mevalonate pathway contributions to biosynthesis of mono-, sesqui-, and diterpenes in glandular trichomes and leaves of Stevia rebaudiana Bertoni.

    PubMed

    Wölwer-Rieck, Ursula; May, Bianca; Lankes, Christa; Wüst, Matthias

    2014-03-19

    The biosynthesis of the diterpenoid steviol glycosides rebaudioside A and stevioside in nonrooted cuttings of Stevia rebaudiana was investigated by feeding experiments using the labeled key precursors [5,5-(2)H2]-mevalonic acid lactone (d2-MVL) and [5,5-(2)H2]-1-deoxy-d-xylulose (d2-DOX). Labeled glycosides were extracted from the leaves and stems and were directly analyzed by LC-(-ESI)-MS/MS and by GC-MS after hydrolysis and derivatization of the resulting isosteviol to the corresponding TMS-ester. Additionally, the incorporation of the proffered d2-MVL and d2-DOX into volatile monoterpenes, sesquiterpenes, and diterpenes in glandular trichomes on leaves and stems was investigated by headspace-solid phase microextraction-GC-MS (HS-SPME-GC-MS). Incorporation of the labeled precursors indicated that diterpenes in leaves and monoterpenes and diterpenes in glandular trichomes are predominately biosynthesized via the methylerythritol phosphate (MEP) pathway, whereas both the MEP and mevalonate (MVA) pathways contribute to the biosynthesis of sesquiterpenes at equal rates in glandular trichomes. These findings give evidence for a transport of MEP pathway derived farnesyl diphosphate precursors from plastids to the cytosol. Contrarily, the transport of MVA pathway derived geranyl diphosphate and geranylgeranyl diphosphate precursors from the cytosol to the plastid is limited. PMID:24579920

  3. NME genes in epithelial morphogenesis

    PubMed Central

    2012-01-01

    The NME family of genes encodes highly conserved multifunctional proteins that have been shown to participate in nucleic acid metabolism, energy homeostasis, cell signaling, and cancer progression. Some family members, particularly isoforms 1 and 2, have attracted extensive interests because of their potential anti-metastasis activity. Unfortunately, there have been few consensus mechanistic explanations for this critical function because of the numerous molecular functions ascribed to these proteins, including nucleoside diphosphate kinase, protein kinase, nuclease, transcription factor, growth factor, among others. In addition, different studies showed contradictory prognostic correlations between NME expression levels and tumor progression in clinical samples. Thus, analyses using pliable in vivo systems have become critical for unraveling at least some aspects of the complex functions of this family of genes. Recent works using the Drosophila genetic system have suggested a role for NME in regulating epithelial cell motility and morphogenesis, which has also been demonstrated in mammalian epithelial cell culture. This function is mediated by promoting internalization of growth factor receptors in motile epithelial cells, and the adherens junction components such as E-cadherin and β-catenin in epithelia that form the tissue linings. Interestingly, NME genes in epithelial cells appear to function in a defined range of expression levels. Either down-regulation or over-expression can perturb epithelial integrity, resulting in different aspects of epithelial abnormality. Such biphasic functions provide a plausible explanation for the documented anti-metastatic activity and the suspected oncogenic function. This review summarizes these recent findings and discusses their implications. PMID:21336542

  4. Ion Channels in Epithelial Cells

    NASA Astrophysics Data System (ADS)

    Palmer, Lawrence G.

    Ion channels in epithelial cells serve to move ions, and in some cases fluid, between compartments of the body. This function of the transfer of material is fundamentally different from that of the transfer of information, which is the main job of most channels in excitable cells. Nevertheless the basic construction of the channels is similar in many respects in the two tissue types. This chapter reviews the nature of channels in epithelia and discusses how their functions have evolved to accomplish the basic tasks for which they are responsible. I will focus on three channel types: epithelial Na+ channels, inward-rectifier K+ channels, and CFTR Cl- channels.

  5. Remodeling of the Epithelial-Connective Tissue Interface in Oral Epithelial Dysplasia as Visualized by Noninvasive 3D Imaging.

    PubMed

    Pal, Rahul; Shilagard, Tuya; Yang, Jinping; Villarreal, Paula; Brown, Tyra; Qiu, Suimin; McCammon, Susan; Resto, Vicente; Vargas, Gracie

    2016-08-15

    Early neoplastic features in oral epithelial dysplasia are first evident at the basal epithelium positioned at the epithelial-connective tissue interface (ECTI), separating the basal epithelium from the underlying lamina propria. The ECTI undergoes significant deformation in early neoplasia due to focal epithelial expansion and proteolytic remodeling of the lamina propria, but few studies have examined these changes. In the present study, we quantitated alterations in ECTI topography in dysplasia using in vivo volumetric multiphoton autofluorescence microscopy and second harmonic generation microscopy. The label-free method allows direct noninvasive visualization of the ECTI surface without perturbing the epithelium. An image-based parameter, "ECTI contour," is described that indicates deformation of the ECTI surface. ECTI contour was higher in dysplasia than control or inflamed specimens, indicating transition from flat to a deformed surface. Cellular parameters of nuclear area, nuclear density, coefficient of variation in nuclear area in the basal epithelium and collagen density in areas adjacent to ECTI were measured. ECTI contour differentiated dysplasia from control/benign mucosa with higher sensitivity and specificity than basal nuclear density or basal nuclear area, comparable with coefficient of variation in nuclear area and collagen density. The presented method offers a unique opportunity to study ECTI in intact mucosa with simultaneous assessment of cellular and extracellular matrix features, expanding opportunities for studies of early neoplastic events near this critical interface and potentially leading to development of new approaches for detecting neoplasia in vivo Cancer Res; 76(16); 4637-47. ©2016 AACR. PMID:27302162

  6. Temporal Monitoring of Differentiated Human Airway Epithelial Cells Using Microfluidics

    PubMed Central

    Blume, Cornelia; Reale, Riccardo; Held, Marie; Millar, Timothy M.; Collins, Jane E.; Davies, Donna E.; Morgan, Hywel; Swindle, Emily J.

    2015-01-01

    The airway epithelium is exposed to a variety of harmful agents during breathing and appropriate cellular responses are essential to maintain tissue homeostasis. Recent evidence has highlighted the contribution of epithelial barrier dysfunction in the development of many chronic respiratory diseases. Despite intense research efforts, the responses of the airway barrier to environmental agents are not fully understood, mainly due to lack of suitable in vitro models that recapitulate the complex in vivo situation accurately. Using an interdisciplinary approach, we describe a novel dynamic 3D in vitro model of the airway epithelium, incorporating fully differentiated primary human airway epithelial cells at the air-liquid interface and a basolateral microfluidic supply of nutrients simulating the interstitial flow observed in vivo. Through combination of the microfluidic culture system with an automated fraction collector the kinetics of cellular responses by the airway epithelium to environmental agents can be analysed at the early phases for the first time and with much higher sensitivity compared to common static in vitro models. Following exposure of primary differentiated epithelial cells to pollen we show that CXCL8/IL–8 release is detectable within the first 2h and peaks at 4–6h under microfluidic conditions, a response which was not observed in conventional static culture conditions. Such a microfluidic culture model is likely to have utility for high resolution temporal profiling of toxicological and pharmacological responses of the airway epithelial barrier, as well as for studies of disease mechanisms. PMID:26436734

  7. Metabolic cooperativity between epithelial cells and adipocytes of mice

    SciTech Connect

    Bartley, J.C.; Emerman, J.T.; Bissell, M.J.

    1981-01-01

    We have demonstrated that glycogen and lipid synthesis in adipocytes is modulated by the lactational state and that this modulation in mammary adipocytes requires the presence of the adjacent epithelial cells. Glycogen and lipid synthesis from (/sup 14/C)glucose was measured in mammary fat pads cleared of epithelium, in abdominal fat pads, and in adipocytes from both sources and from intact mammary gland of mature virgin, pregnant, and lactating mice. Accumulation of glycogen, the activity of glycogen synthase, and the lipogenic rate in abdominal and mammary adipocytes remained high during pregnancy but decreased to insignificant levels by early lactation. The depressant effects of lactation were observed solely in those mammary adipocytes isolated from intact glands. The presence of mammary epithelial cells was also required to effect the stimulated lipogenesis in mammary adipocytes during pregnancy. We conclude that the metabolic activity of adipocytes is modulated both during pregnancy and lactation to channel nutrients to the mammary epithelial cell. The fact that the changes occur in mammary adipocytes only when epithelial cells are present indicates that local as well as systemic factors are operating in these modulations.

  8. Lateral adhesion drives reintegration of misplaced cells into epithelial monolayers

    PubMed Central

    St Johnston, Daniel

    2016-01-01

    Cells in simple epithelia orient their mitotic spindles in the plane of the epithelium so that both daughter cells are born within the epithelial sheet. This is assumed to be important to maintain epithelial integrity and prevent hyperplasia, because misaligned divisions give rise to cells outside the epithelium1,2. Here we test this assumption in three types of Drosophila epithelia; the cuboidal follicle epithelium, the columnar early embryonic ectoderm, and the pseudostratified neuroepithelium. Ectopic expression of Inscuteable in these tissues reorients mitotic spindles, resulting in one daughter cell being born outside of the epithelial layer. Live imaging reveals that these misplaced cells reintegrate into the tissue. Reducing the levels of the lateral homophilic adhesion molecules Neuroglian or Fasciclin 2 disrupts reintegration, giving rise to extra-epithelial cells, whereas disruption of adherens junctions has no effect. Thus, the reinsertion of misplaced cells appears to be driven by lateral adhesion, which pulls cells born outside the epithelia layer back into it. Our findings reveal a robust mechanism that protects epithelia against the consequences of misoriented divisions. PMID:26414404

  9. Temporal Monitoring of Differentiated Human Airway Epithelial Cells Using Microfluidics.

    PubMed

    Blume, Cornelia; Reale, Riccardo; Held, Marie; Millar, Timothy M; Collins, Jane E; Davies, Donna E; Morgan, Hywel; Swindle, Emily J

    2015-01-01

    The airway epithelium is exposed to a variety of harmful agents during breathing and appropriate cellular responses are essential to maintain tissue homeostasis. Recent evidence has highlighted the contribution of epithelial barrier dysfunction in the development of many chronic respiratory diseases. Despite intense research efforts, the responses of the airway barrier to environmental agents are not fully understood, mainly due to lack of suitable in vitro models that recapitulate the complex in vivo situation accurately. Using an interdisciplinary approach, we describe a novel dynamic 3D in vitro model of the airway epithelium, incorporating fully differentiated primary human airway epithelial cells at the air-liquid interface and a basolateral microfluidic supply of nutrients simulating the interstitial flow observed in vivo. Through combination of the microfluidic culture system with an automated fraction collector the kinetics of cellular responses by the airway epithelium to environmental agents can be analysed at the early phases for the first time and with much higher sensitivity compared to common static in vitro models. Following exposure of primary differentiated epithelial cells to pollen we show that CXCL8/IL-8 release is detectable within the first 2h and peaks at 4-6h under microfluidic conditions, a response which was not observed in conventional static culture conditions. Such a microfluidic culture model is likely to have utility for high resolution temporal profiling of toxicological and pharmacological responses of the airway epithelial barrier, as well as for studies of disease mechanisms. PMID:26436734

  10. Virtual clinical trials using inserted pathology in clinical images: investigation of assumptions for local glandularity and noise

    NASA Astrophysics Data System (ADS)

    Rashidnasab, Alaleh; Elangovan, Premkumar; Mackenzie, Alistair; Dance, David R.; Young, Kenneth C.; Bosmans, Hilde; Wells, Kevin

    2015-03-01

    Virtual clinical trials have been proposed as a viable alternative to clinical trials for testing and comparing the performance of breast imaging systems. One of the main simulation methodologies used in virtual trials employs clinical images of patients in which simulated models of cancer are inserted using a physics-based template multiplication technique. The purpose of this work is to investigate two assumptions commonly considered in this simulation approach: Firstly, given the absence of useful depth information in a clinical situation, an average measure of the local breast glandularity is commonly used as an estimate of the breast composition at the insertion site; secondly, it is also assumed that any change in the relative noise in the image at the insertion site, after insertion of a mass, is negligible. In order to test the validity of these assumptions, spheres representing idealised masses and anthropomorphic computational breast phantoms with perfect prior knowledge of local tissue composition and distribution were used. Results from several region of interest (ROI) insertions demonstrated a lack of variation obtained in contrast with insertion depth using the template multiplication insertion method as compared to the true depth-wise variation contrast values obtained from voxel replacement in a heterogeneous phantom. It was also found that the amount of noise is underestimated by insertion of spherical masses using template multiplication method by 8% - 29% compared to voxel replacement for the test conditions. This resulted in up to 12% variation in contrast-to-noise-ratio (CNR) values between template multiplication and voxel replacement methods.

  11. Human papillomavirus prevalence and type-distribution in cervical glandular neoplasias: Results from a European multinational epidemiological study.

    PubMed

    Holl, Katsiaryna; Nowakowski, Andrzej M; Powell, Ned; McCluggage, W Glenn; Pirog, Edyta C; Collas De Souza, Sabrina; Tjalma, Wiebren A; Rosenlund, Mats; Fiander, Alison; Castro Sánchez, Maria; Damaskou, Vasileia; Joura, Elmar A; Kirschner, Benny; Koiss, Robert; O'Leary, John; Quint, Wim; Reich, Olaf; Torné, Aureli; Wells, Michael; Rob, Lukas; Kolomiets, Larisa; Molijn, Anco; Savicheva, Alevtina; Shipitsyna, Elena; Rosillon, Dominique; Jenkins, David

    2015-12-15

    Cervical glandular neoplasias (CGN) present a challenge for cervical cancer prevention due to their complex histopathology and difficulties in detecting preinvasive stages with current screening practices. Reports of human papillomavirus (HPV) prevalence and type-distribution in CGN vary, providing uncertain evidence to support prophylactic vaccination and HPV screening. This study [108288/108290] assessed HPV prevalence and type-distribution in women diagnosed with cervical adenocarcinoma in situ (AIS, N = 49), adenosquamous carcinoma (ASC, N = 104), and various adenocarcinoma subtypes (ADC, N = 461) from 17 European countries, using centralised pathology review and sensitive HPV testing. The highest HPV-positivity rates were observed in AIS (93.9%), ASC (85.6%), and usual-type ADC (90.4%), with much lower rates in rarer ADC subtypes (clear-cell: 27.6%; serous: 30.4%; endometrioid: 12.9%; gastric-type: 0%). The most common HPV types were restricted to HPV16/18/45, accounting for 98.3% of all HPV-positive ADC. There were variations in HPV prevalence and ADC type-distribution by country. Age at diagnosis differed by ADC subtype, with usual-type diagnosed in younger women (median: 43 years) compared to rarer subtypes (medians between 57 and 66 years). Moreover, HPV-positive ADC cases were younger than HPV-negative ADC. The six years difference in median age for women with AIS compared to those with usual-type ADC suggests that cytological screening for AIS may be suboptimal. Since the great majority of CGN are HPV16/18/45-positive, the incorporation of prophylactic vaccination and HPV testing in cervical cancer screening are important prevention strategies. Our results suggest that special attention should be given to certain rarer ADC subtypes as most appear to be unrelated to HPV. PMID:26096203

  12. Classification of spatial textures in benign and cancerous glandular tissues by stereology and stochastic geometry using artificial neural networks.

    PubMed

    Mattfeldt, T; Gottfried, H; Schmidt, V; Kestler, H A

    2000-05-01

    Stereology and stochastic geometry can be used as auxiliary tools for diagnostic purposes in tumour pathology. Whether first-order parameters or stochastic-geometric functions are more important for the classification of the texture of biological tissues is not known. In the present study, volume and surface area per unit reference volume, the pair correlation function and the centred quadratic contact density function of epithelium were estimated in three case series of benign and malignant lesions of glandular tissues. The information provided by the latter functions was summarized by the total absolute areas between the estimated curves and their horizontal reference lines. These areas are considered as indicators of deviation of the tissue texture from a completely uncorrelated volume process and from the Boolean model with convex grains, respectively. We used both areas and the first-order parameters for the classification of cases using artificial neural networks (ANNs). Learning vector quantization and multilayer feedforward networks with backpropagation were applied as neural paradigms. Applications included distinction between mastopathy and mammary cancer (40 cases), between benign prostatic hyperplasia and prostatic cancer (70 cases) and between chronic pancreatitis and pancreatic cancer (60 cases). The same data sets were also classified with linear discriminant analysis. The stereological estimates in combination with ANNs or discriminant analysis provided high accuracy in the classification of individual cases. The question of which category of estimator is the most informative cannot be answered globally, but must be explored empirically for each specific data set. Using learning vector quantization, better results could often be obtained than by multilayer feedforward networks with backpropagation. PMID:10810010

  13. Epithelial histogenesis during tooth development.

    PubMed

    Lesot, H; Brook, A H

    2009-12-01

    This paper reviews the current understanding of the progressive changes mediating dental epithelial histogenesis as a basis for future collaborative studies. Tooth development involves morphogenesis, epithelial histogenesis and cell differentiation. The consecutive morphological stages of lamina, bud, cap and bell are also characterized by changes in epithelial histogenesis. Differential cell proliferation rates, apoptosis, and alterations in adhesion and shape lead to the positioning of groups of cells with different functions. During tooth histo-morphogenesis changes occur in basement membrane composition, expression of signalling molecules and the localization of cell surface components. Cell positional identity may be related to cell history. Another important parameter is cell plasticity. Independently of signalling molecules, which play a major role in inducing or modulating specific steps, cell-cell and cell-matrix interactions regulate the plasticity/rigidity of particular domains of the enamel organ. This involves specifying in space the differential growth and influences the progressive tooth morphogenesis by shaping the epithelial-mesenchymal junction. Deposition of a mineralized matrix determines the final shape of the crown. All data reviewed in this paper were investigated in the mouse. PMID:18656852

  14. A Nasal Epithelial Receptor for Staphylococcus aureus WTA Governs Adhesion to Epithelial Cells and Modulates Nasal Colonization

    PubMed Central

    Faulstich, Manuela; Grau, Timo; Severin, Yannik; Unger, Clemens; Hoffmann, Wolfgang H.; Rudel, Thomas; Autenrieth, Ingo B.; Weidenmaier, Christopher

    2014-01-01

    Nasal colonization is a major risk factor for S. aureus infections. The mechanisms responsible for colonization are still not well understood and involve several factors on the host and the bacterial side. One key factor is the cell wall teichoic acid (WTA) of S. aureus, which governs direct interactions with nasal epithelial surfaces. We report here the first receptor for the cell wall glycopolymer WTA on nasal epithelial cells. In several assay systems this type F-scavenger receptor, termed SREC-I, bound WTA in a charge dependent manner and mediated adhesion to nasal epithelial cells in vitro. The impact of WTA and SREC-I interaction on epithelial adhesion was especially pronounced under shear stress, which resembles the conditions found in the nasal cavity. Most importantly, we demonstrate here a key role of the WTA-receptor interaction in a cotton rat model of nasal colonization. When we inhibited WTA mediated adhesion with a SREC-I antibody, nasal colonization in the animal model was strongly reduced at the early onset of colonization. More importantly, colonization stayed low over an extended period of 6 days. Therefore we propose targeting of this glycopolymer-receptor interaction as a novel strategy to prevent or control S. aureus nasal colonization. PMID:24788600

  15. MicroRNAs and Epithelial Immunity

    PubMed Central

    Liu, Jun; Drescher, Kristen M.; Chen, Xian-Ming

    2009-01-01

    MicroRNAs are required for development and maintenance of the epithelial barrier. It is hypothesized that microRNAs are involved in regulating epithelial anti-microbial defenses by targeting key epithelial effector molecules and/or influencing intracellular signaling pathways. Additionally, aberrant microRNA expression has been implicated in the pathogenesis of various diseases at the skin and mucosa. Increased understanding of the role of microRNAs in epithelial immunoregulation and identification of microRNAs of pathogenetic significance will enhance our understanding of epithelial immunobiology and immunopathology. PMID:19811319

  16. Epithelial TRPV1 signaling accelerates gingival epithelial cell proliferation.

    PubMed

    Takahashi, N; Matsuda, Y; Yamada, H; Tabeta, K; Nakajima, T; Murakami, S; Yamazaki, K

    2014-11-01

    Transient receptor potential cation channel subfamily V member 1 (TRPV1), a member of the calcium-permeable thermosensitive transient receptor potential superfamily, is a sensor of thermal and chemical stimuli. TRPV1 is activated by noxious heat (> 43°C), acidic conditions (pH < 6.6), capsaicin, and endovanilloids. This pain receptor was discovered on nociceptive fibers in the peripheral nervous system. TRPV1 was recently found to be expressed by non-neuronal cells, such as epithelial cells. The oral gingival epithelium is exposed to multiple noxious stimuli, including heat and acids derived from endogenous and exogenous substances; however, whether gingival epithelial cells (GECs) express TRPV1 is unknown. We show that both TRPV1 mRNA and protein are expressed by GECs. Capsaicin, a TRPV1 agonist, elevated intracellular Ca(2+) levels in the gingival epithelial cell line, epi 4. Moreover, TRPV1 activation in epi 4 cells accelerated proliferation. These responses to capsaicin were inhibited by a specific TRPV1 antagonist, SB-366791. We also observed GEC proliferation in capsaicin-treated mice in vivo. No effects were observed on GEC apoptosis by epithelial TRPV1 signaling. To examine the molecular mechanisms underlying this proliferative effect, we performed complementary (c)DNA microarray analysis of capsaicin-stimulated epi 4 cells. Compared with control conditions, 227 genes were up-regulated and 232 genes were down-regulated following capsaicin stimulation. Several proliferation-related genes were validated by independent experiments. Among them, fibroblast growth factor-17 and neuregulin 2 were significantly up-regulated in capsaicin-treated epi 4 cells. Our results suggest that functional TRPV1 is expressed by GECs and contributes to the regulation of cell proliferation. PMID:25266715

  17. Facile Bench-Top Fabrication of Enclosed Circular Microchannels Provides 3D Confined Structure for Growth of Prostate Epithelial Cells

    PubMed Central

    Dolega, Monika E.; Wagh, Jayesh; Gerbaud, Sophie; Kermarrec, Frederique; Alcaraz, Jean-Pierre; Martin, Donald K.; Gidrol, Xavier; Picollet-D’hahan, Nathalie

    2014-01-01

    We present a simple bench-top method to fabricate enclosed circular channels for biological experiments. Fabricating the channels takes less than 2 hours by using glass capillaries of various diameters (from 100 µm up to 400 µm) as a mould in PDMS. The inner surface of microchannels prepared in this way was coated with a thin membrane of either Matrigel or a layer-by-layer polyelectrolyte to control cellular adhesion. The microchannels were then used as scaffolds for 3D-confined epithelial cell culture. To show that our device can be used with several epithelial cell types from exocrine glandular tissues, we performed our biological studies on adherent epithelial prostate cells (non-malignant RWPE-1 and invasive PC3) and also on breast (non-malignant MCF10A) cells We observed that in static conditions cells adhere and proliferate to form a confluent layer in channels of 150 µm in diameter and larger, whereas cellular viability decreases with decreasing diameter of the channel. Matrigel and PSS (poly (sodium 4-styrenesulphonate)) promote cell adhesion, whereas the cell proliferation rate was reduced on the PAH (poly (allylamine hydrochloride))-terminated surface. Moreover infusing channels with a continuous flow did not induce any cellular detachment. Our system is designed to simply grow cells in a microchannel structure and could be easily fabricated in any biological laboratory. It offers opportunities to grow epithelial cells that support the formation of a light. This system could be eventually used, for example, to collect cellular secretions, or study cell responses to graduated hypoxia conditions, to chemicals (drugs, siRNA, …) and/or physiological shear stress. PMID:24945245

  18. SGK1 regulation of epithelial sodium transport.

    PubMed

    Pearce, David

    2003-01-01

    Epithelial ion transport is regulated in vertebrates by a variety of hormonal and non-hormonal factors, including mineralocorticoids, insulin, and osmotic shock. SGK1 has been established as an important convergence point for multiple regulators of Na+transport. Unlike most serine-threonine kinases, SGK1 is under dual control: protein levels are controlled through effects on its gene transcription, while its activity is dependent on phosphatidylinositol-3-kinase (PI3K) activity. Aldosterone is the most notable regulator of SGK1 protein level in ion transporting epithelia, while insulin and other activators of the of PI3K are key regulators of its activity. Activated SGK1 regulates a variety of ion transporters, the best characterized of which is the epithelial sodium channel (ENaC). The apical targeting of ENaC is controlled by the ubiquitin ligase, Nedd4-2, and SGK1 acts, at least in part, through phosphorylation-dependent inhibition of Nedd4-2. This effect of SGK1 requires physical associations of Nedd4-2 with both SGK1 and ENaC. Moreover, direct physical association between SGK1 and ENaC may also be implicated in the formation of a tertiary complex. Osmotic shock is likely the most important non-hormonal regulator of SGK1 expression, and surprisingly, SGK1 expression can be induced by hypotonic or hypertonic stress in a cell-type dependent fashion. The SGK family represents an ancient arm of the serine-threonine kinase family, present in all eukaryotes that have been examined, including yeast. SGK1 appears to have been implicated in membrane trafficking and possibly in the control of ion transport and cell volume in early single cell eukaryotes. In metazoan epithelia, it seems likely that SGK1 was adapted to the regulation of ion transport in response to hormonal and osmotic signals. PMID:12649598

  19. Henipavirus Pathogenesis in Human Respiratory Epithelial Cells

    PubMed Central

    Escaffre, Olivier; Borisevich, Viktoriya; Carmical, J. Russ; Prusak, Deborah; Prescott, Joseph; Feldmann, Heinz

    2013-01-01

    Hendra virus (HeV) and Nipah virus (NiV) are deadly zoonotic viruses for which no vaccines or therapeutics are licensed for human use. Henipavirus infection causes severe respiratory illness and encephalitis. Although the exact route of transmission in human is unknown, epidemiological studies and in vivo studies suggest that the respiratory tract is important for virus replication. However, the target cells in the respiratory tract are unknown, as are the mechanisms by which henipaviruses can cause disease. In this study, we characterized henipavirus pathogenesis using primary cells derived from the human respiratory tract. The growth kinetics of NiV-Malaysia, NiV-Bangladesh, and HeV were determined in bronchial/tracheal epithelial cells (NHBE) and small airway epithelial cells (SAEC). In addition, host responses to infection were assessed by gene expression analysis and immunoassays. Viruses replicated efficiently in both cell types and induced large syncytia. The host response to henipavirus infection in NHBE and SAEC highlighted a difference in the inflammatory response between HeV and NiV strains as well as intrinsic differences in the ability to mount an inflammatory response between NHBE and SAEC. These responses were highest during HeV infection in SAEC, as characterized by the levels of key cytokines (interleukin 6 [IL-6], IL-8, IL-1α, monocyte chemoattractant protein 1 [MCP-1], and colony-stimulating factors) responsible for immune cell recruitment. Finally, we identified virus strain-dependent variability in type I interferon antagonism in NHBE and SAEC: NiV-Malaysia counteracted this pathway more efficiently than NiV-Bangladesh and HeV. These results provide crucial new information in the understanding of henipavirus pathogenesis in the human respiratory tract at an early stage of infection. PMID:23302882

  20. Henipavirus pathogenesis in human respiratory epithelial cells.

    PubMed

    Escaffre, Olivier; Borisevich, Viktoriya; Carmical, J Russ; Prusak, Deborah; Prescott, Joseph; Feldmann, Heinz; Rockx, Barry

    2013-03-01

    Hendra virus (HeV) and Nipah virus (NiV) are deadly zoonotic viruses for which no vaccines or therapeutics are licensed for human use. Henipavirus infection causes severe respiratory illness and encephalitis. Although the exact route of transmission in human is unknown, epidemiological studies and in vivo studies suggest that the respiratory tract is important for virus replication. However, the target cells in the respiratory tract are unknown, as are the mechanisms by which henipaviruses can cause disease. In this study, we characterized henipavirus pathogenesis using primary cells derived from the human respiratory tract. The growth kinetics of NiV-Malaysia, NiV-Bangladesh, and HeV were determined in bronchial/tracheal epithelial cells (NHBE) and small airway epithelial cells (SAEC). In addition, host responses to infection were assessed by gene expression analysis and immunoassays. Viruses replicated efficiently in both cell types and induced large syncytia. The host response to henipavirus infection in NHBE and SAEC highlighted a difference in the inflammatory response between HeV and NiV strains as well as intrinsic differences in the ability to mount an inflammatory response between NHBE and SAEC. These responses were highest during HeV infection in SAEC, as characterized by the levels of key cytokines (interleukin 6 [IL-6], IL-8, IL-1α, monocyte chemoattractant protein 1 [MCP-1], and colony-stimulating factors) responsible for immune cell recruitment. Finally, we identified virus strain-dependent variability in type I interferon antagonism in NHBE and SAEC: NiV-Malaysia counteracted this pathway more efficiently than NiV-Bangladesh and HeV. These results provide crucial new information in the understanding of henipavirus pathogenesis in the human respiratory tract at an early stage of infection. PMID:23302882

  1. Structural and functional analysis of endosomal compartments in epithelial cells.

    PubMed

    Bay, Andres E Perez; Schreiner, Ryan; Rodriguez-Boulan, Enrique

    2015-01-01

    Epithelial cells display segregated early endosomal compartments, termed apical sorting endosomes and basolateral sorting endosomes, that converge into a common late endosomal-lysosomal degradative compartment and common recycling endosomes (CREs). Unlike recycling endosomes of nonpolarized cells, CREs have the ability to sort apical and basolateral plasma membrane proteins into distinct apical and basolateral recycling routes, utilizing mechanisms similar to those employed by the trans Golgi network in the biosynthetic pathway. The apical recycling route includes an additional compartment, the apical recycling endosomes, consisting of multiple vesicles bundled around the basal body. Recent evidence indicates that, in addition to their role in internalizing ligands and recycling their receptors back to the cell surface, endosomal compartments act as intermediate stations in the biosynthetic routes to the plasma membrane. Here we review methods employed by our laboratory to study the endosomal compartments of epithelial cells and their multiple trafficking roles. PMID:26360040

  2. An innate antiviral pathway acting before interferons at epithelial surfaces.

    PubMed

    Iversen, Marie B; Reinert, Line S; Thomsen, Martin K; Bagdonaite, Ieva; Nandakumar, Ramya; Cheshenko, Natalia; Prabakaran, Thaneas; Vakhrushev, Sergey Y; Krzyzowska, Malgosha; Kratholm, Sine K; Ruiz-Perez, Fernando; Petersen, Steen V; Goriely, Stanislas; Bibby, Bo Martin; Eriksson, Kristina; Ruland, Jürgen; Thomsen, Allan R; Herold, Betsy C; Wandall, Hans H; Frische, Sebastian; Holm, Christian K; Paludan, Søren R

    2016-02-01

    Mucosal surfaces are exposed to environmental substances and represent a major portal of entry for microorganisms. The innate immune system is responsible for early defense against infections and it is believed that the interferons (IFNs) constitute the first line of defense against viruses. Here we identify an innate antiviral pathway that works at epithelial surfaces before the IFNs. The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. This study therefore identifies a previously unknown layer of antiviral defense that exerts its action on epithelial surfaces before the classical IFN response is operative. PMID:26595890

  3. Visualization of epithelial morphology using autofluorescence microscopy under ultraviolet excitation

    NASA Astrophysics Data System (ADS)

    Lin, Bevin; Urayama, Shiro; Saroufeem, Ramez M. G.; Matthews, Dennis L.; Demos, Stavros G.

    2010-02-01

    Epithelial microstructures related to early stage carcinoma are currently invisible to traditional white light endoscopy. We recently demonstrated that autofluorescence microscopy under ultraviolet excitation can visualize superficial microstructures without the use of contrast agents, sectioning methods, or tissue preparation. Spectroscopic analysis allowed a better understanding of autofluorescence signal characteristics at the microscopic level and the mechanism for achieving high quality imaging of the superficial epithelial layer with conventional wide-field microscopy. The designing parameters for the adaptation of this technology into an endoscope probe for real-time in vivo microscopy are tested using a bench-top prototype system. This approach may provide a powerful tool for the detection and staging of carcinomas.

  4. Quantitative Morphology of Epithelial Folds.

    PubMed

    Štorgel, Nick; Krajnc, Matej; Mrak, Polona; Štrus, Jasna; Ziherl, Primož

    2016-01-01

    The shape of spatially modulated epithelial morphologies such as villi and crypts is usually associated with the epithelium-stroma area mismatch leading to buckling. We propose an alternative mechanical model based on intraepithelial stresses generated by differential tensions of apical, lateral, and basal sides of cells as well as on the elasticity of the basement membrane. We use it to theoretically study longitudinal folds in simple epithelia and we identify four types of corrugated morphologies: compact, invaginated, evaginated, and wavy. The obtained tissue contours and thickness profiles are compared to epithelial folds observed in invertebrates and vertebrates, and for most samples, the agreement is within the estimated experimental error. Our model establishes the groove-crest modulation of tissue thickness as a morphometric parameter that can, together with the curvature profile, be used to estimate the relative differential apicobasal tension in the epithelium. PMID:26745429

  5. Characterization of the formation of branched short-chain fatty acid:CoAs for bitter acid biosynthesis in hop glandular trichomes.

    PubMed

    Xu, Haiyang; Zhang, Fengxia; Liu, Baoxiu; Huhman, David V; Sumner, Lloyd W; Dixon, Richard A; Wang, Guodong

    2013-07-01

    Bitter acids, known for their use as beer flavoring and for their diverse biological activities, are predominantly formed in hop (Humulus lupulus) glandular trichomes. Branched short-chain acyl-CoAs (e.g. isobutyryl-CoA, isovaleryl-CoA and 2-methylbutyryl-CoA), derived from the degradation of branched-chain amino acids (BCAAs), are essential building blocks for the biosynthesis of bitter acids in hops. However, little is known regarding what components are needed to produce and maintain the pool of branched short-chain acyl-CoAs in hop trichomes. Here, we present several lines of evidence that both CoA ligases and thioesterases are likely involved in bitter acid biosynthesis. Recombinant HlCCL2 (carboxyl CoA ligase) protein had high specific activity for isovaleric acid as a substrate (K cat /K m = 4100 s(-1) M(-1)), whereas recombinant HlCCL4 specifically utilized isobutyric acid (Kcat/K m = 1800 s(-1) M(-1)) and 2-methylbutyric acid (Kcat/K m = 6900 s(-1) M(-1)) as substrates. Both HlCCLs, like hop valerophenone synthase (HlVPS), were expressed strongly in glandular trichomes and localized to the cytoplasm. Co-expression of HlCCL2 and HlCCL4 with HlVPS in yeast led to significant production of acylphloroglucinols (the direct precursors for bitter acid biosynthesis), which further confirmed the biochemical function of these two HlCCLs in vivo. Functional identification of a thioesterase that catalyzed the reverse reaction of CCLs in mitochondria, together with the comprehensive analysis of genes involved BCAA catabolism, supported the idea that cytosolic CoA ligases are required for linking BCAA degradation and bitter acid biosynthesis in glandular trichomes. The evolution and other possible physiological roles of branched short-chain fatty acid:CoA ligases in planta are also discussed. PMID:23300257

  6. [Epithelial hepatoblastomas in the adult].

    PubMed

    Mondragón Sánchez, R; Bernal Maldonado, R; Sada Navarro, L A; Hernández, A I; Hurtado Andrade, H; Cortés Espinoza, T; Sánchez Cisneros, R

    1994-01-01

    Hepatoblastoma is the most frequent primary malignant liver neoplasm in childhood; in adults it is extremely rare and only 27 cases have been published. The prognosis of this neoplasm is poor because it is usually discovered late. Surgery, chemotherapy and liver transplantation have been tried with poor results. We present two adult patients who were diagnosed with an epithelial hepatoblastoma. The pathogenesis, histologic features and current management is reviewed. PMID:7716366

  7. Structure of the glandular layer and koilin membrane in the gizzard of the adult domestic fowl (Gallus gallus domesticus).

    PubMed Central

    Akester, A R

    1986-01-01

    The koilin membrane is formed by the secretions of gland, crypt and surface epithelial cells. Glands form a continuous layer and are arranged in groups of 10-20. They are straight tubes about 500 microns long and 15 microns in diameter and produce rodlets of hard koilin. Hard koilin rodlets (5 microns diameter) form clusters of five or six as they pass through the crypts and enter the koilin membrane. Each rodlet hardens within its gland and maintains its individuality throughout its entire length. Rodlet clusters have previously been called 'rods'. Most of the softer koilin, which fills the spaces between the rodlet clusters, is produced by the surface epithelial cells. These cells form gentle arches between the cavities of adjacent crypts. Horizontal branches between rodlet clusters ('rods') do not exist. There is approximately twice as much surface koilin as rodlet koilin within the membrane. Abrasion of the koilin membrane is not uniform but occurs in a patchy fashion. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 PMID:3693065

  8. Epithelial cells and Von Gierke's disease.

    PubMed

    Negishi, H; Benke, P J

    1977-08-01

    Epithelial cells and not fibroblasts from human liver and amniotic fluid contain inducible glucose-6-phosphatase (G-6-Pase) activity. The diagnosis of Von Gierke's disease has been made in a patient with hepatomegaly utilizing cultured epithelial cells grown from a liver biopsy. G-6-Pase activity in epithelial cells from this patient could not be induced by dibutyryl cyclic AMP and theophylline. This is the first use of epithelial cells for diagnosis of a metabolic disease. G-6-Pase activity in cloned epithelial cells from amniotic fluid increases 2- to 3-fold after 24-hr exposure to dibutyryl cyclic AMP and theophylline. The prenatal diagnosis of Von Gierke's disease may be possible in a laboratory experienced with these techniques if epithelial cell growth is obtained from amniotic fluid. PMID:196249

  9. Study of dynamic process of acetic acid induced-whitening in epithelial tissues at cellular level

    NASA Astrophysics Data System (ADS)

    Wu, Tao T.; Qu, Jianan Y.; Cheung, Tak Hong; Yim, So Fan; Wong, Yick Fu

    2005-06-01

    Acetic acid, inducing transient whitening (acetowhitening) when applied to epithelial tissues, is a commonly used contrast agent for detecting early cervical cancer. The goals of this research are to investigate the temporal characteristics of acetowhitening process in cervical epithelial tissue at cellular level and develop a clear understanding of the diagnostic information carried in the acetowhitening signal. A system measuring time-resolved reflectance was built to study the rising and decay processes of acetowhitening signal from the monolayered cell cultures of normal and cancerous cervical squamous cells. It is found that the dynamic processes of acetowhitening in normal and cancerous cells are significantly different. The results of this study provide insight valuable to further understand the acetowhitening process in epithelial cells and to encourage the development of an objective procedure to detect the early cervical cancers based on quantitative monitoring of the dynamic process of acetowhitening

  10. Comparison of N-linked Glycoproteins in Human Whole Saliva, Parotid, Submandibular, and Sublingual Glandular Secretions Identified using Hydrazide Chemistry and Mass Spectrometry.

    PubMed

    Ramachandran, Prasanna; Boontheung, Pinmanee; Pang, Eric; Yan, Weihong; Wong, David T; Loo, Joseph A

    2008-12-01

    INTRODUCTION: Saliva is a body fluid that holds promise for use as a diagnostic fluid for detecting diseases. Salivary proteins are known to be heavily glycosylated and are known to play functional roles in the oral cavity. We identified N-linked glycoproteins in human whole saliva, as well as the N-glycoproteins in parotid, submandibular, and sublingual glandular fluids. MATERIALS AND METHODS: We employed hydrazide chemistry to affinity enrich for N-linked glycoproteins and glycopeptides. PNGase F releases the N-peptides/proteins from the agarose-hydrazide resin, and liquid chromatography-tandem mass spectrometry was used to identify the salivary N-glycoproteins. RESULTS: A total of 156 formerly N-glycosylated peptides representing 77 unique N-glycoproteins were identified in salivary fluids. The total number of N-glycoproteins identified in the individual fluids was: 62, 34, 44, and 53 in whole saliva, parotid fluid, submandibular fluid, and sublingual fluid, respectively. The majority of the N-glycoproteins were annotated as extracellular proteins (40%), and several of the N-glycoproteins were annotated as membrane proteins (14%). A number of glycoproteins were differentially found in submandibular and sublingual glandular secretions. CONCLUSIONS: Mapping the N-glycoproteome of parotid, submandibular, and sublingual saliva is important for a thorough understanding of biological processes occurring in the oral cavity and to realize the role of saliva in the overall health of human individuals. Moreover, identifying glycoproteins in saliva may also be valuable for future disease biomarker studies. PMID:21960768

  11. A Geranylfarnesyl Diphosphate Synthase Provides the Precursor for Sesterterpenoid (C25) Formation in the Glandular Trichomes of the Mint Species Leucosceptrum canum.

    PubMed

    Liu, Yan; Luo, Shi-Hong; Schmidt, Axel; Wang, Guo-Dong; Sun, Gui-Ling; Grant, Marcus; Kuang, Ce; Yang, Min-Jie; Jing, Shu-Xi; Li, Chun-Huan; Schneider, Bernd; Gershenzon, Jonathan; Li, Sheng-Hong

    2016-03-01

    Plant sesterterpenoids, an important class of terpenoids, are widely distributed in various plants, including food crops. However, little is known about their biosynthesis. Here, we cloned and functionally characterized a plant geranylfarnesyl diphosphate synthase (Lc-GFDPS), the enzyme producing the C25 prenyl diphosphate precursor to all sesterterpenoids, from the glandular trichomes of the woody plant Leucosceptrum canum. GFDPS catalyzed the formation of GFDP after expression in Escherichia coli. Overexpressing GFDPS in Arabidopsis thaliana also gave an extract catalyzing GFDP formation. GFDPS was strongly expressed in glandular trichomes, and its transcript profile was completely in accordance with the sesterterpenoid accumulation pattern. GFDPS is localized to the plastids, and inhibitor studies indicated its use of isoprenyl diphosphate substrates supplied by the 2-C-methyl-D-erythritol 4-phosphate pathway. Application of a jasmonate defense hormone induced GFDPS transcript and sesterterpenoid accumulation, while reducing feeding and growth of the generalist insect Spodoptera exigua, suggesting that these C25 terpenoids play a defensive role. Phylogenetic analysis suggested that GFDPS probably evolved from plant geranylgeranyl diphosphate synthase under the influence of positive selection. The isolation of GFDPS provides a model for investigating sesterterpenoid formation in other species and a tool for manipulating the formation of this group in plants and other organisms. PMID:26941091

  12. p40 as a Basal Cell Marker in the Diagnosis of Prostate Glandular Proliferations: A Comparative Immunohistochemical Study with 34betaE12

    PubMed Central

    Brustmann, Hermann

    2015-01-01

    Immunohistochemistry is important for the accurate diagnosis of basal cells in atypical glandular proliferations of the prostate. p40, an isoform of p63, may be an adjunct to a marker panel in this setting. Biopsies of 68 patients were analyzed by immunohistochemistry using antibodies to 34betaE12 and p40. Basal cell staining was classified as negative, partial (<60%), or diffuse (≥60%); irregular staining was defined as discordant staining patterns. In acinar proliferations (N = 41), partial staining for both markers was seen in 42%, and diffuse staining in 46% of reactive cases. An irregular reactivity was noted in one case only (2%). Finally, these lesions were signed out as benign. Acinar proliferations negative for both markers and limited amount of glands (≤4) were termed atypical small acinar proliferations (ASAP). Out of six PIN lesions two cases showed partial, three cases showed diffuse reactivity for both markers, and one case was stained irregular. All cases diagnosed as prostate carcinomas (N = 20) had no evidence of basal cell staining for neither of the markers. p40 expression is closely correlated to 34betaE12 with respect to demonstration of basal cells of prostate glands and may provide further information on the dignity of glandular proliferations of the prostate. PMID:25852959

  13. Cytoskeletal changes induced by allosteric modulators of calcium-sensing receptor in esophageal epithelial cells

    PubMed Central

    Abdulnour-Nakhoul, Solange; Brown, Karen L; Rabon, Edd C; Al-Tawil, Youhanna; Islam, Mohammed T; Schmieg, John J; Nakhoul, Nazih L

    2015-01-01

    The calcium-sensing receptor (CaSR), a G-protein-coupled receptor, plays a role in glandular and fluid secretion in the gastrointestinal tract, and regulates differentiation and proliferation of epithelial cells. We examined the expression of CaSR in normal and pathological conditions of human esophagus and investigated the effect of a CaSR agonist, cinacalcet (CCT), and antagonist, calhex (CHX), on cell growth and cell–cell junctional proteins in primary cultures of porcine stratified squamous esophageal epithelium. We used immunohistochemistry and Western analysis to monitor expression of CaSR and cell–cell adhesion molecules, and MTT assay to monitor cell proliferation in cultured esophageal cells. CCT treatment significantly reduced proliferation, changed the cell shape from polygonal to spindle-like, and caused redistribution of E-cadherin and β-catenin from the cell membrane to the cytoplasm. Furthermore, it reduced expression of β-catenin by 35% (P < 0.02) and increased expression of a proteolysis cleavage fragment of E-cadherin, Ecad/CFT2, by 2.3 folds (P < 0.01). On the other hand, CHX treatment enhanced cell proliferation by 27% (P < 0.01), increased the expression of p120-catenin by 24% (P < 0.04), and of Rho, a GTPase involved in cytoskeleton remodeling, by 18% (P < 0.03). In conclusion, CaSR is expressed in normal esophagus as well as in Barrett’s, esophageal adenocarcinoma, squamous cell carcinoma, and eosinophilic esophagitis. Long-term activation of CaSR with CCT disrupted the cadherin–catenin complex, induced cytoskeletal remodeling, actin fiber formation, and redistribution of CaSR to the nuclear area. These changes indicate a significant and complex role of CaSR in epithelial remodeling and barrier function of esophageal cells. PMID:26603452

  14. Intraepithelial ischemia is a principal factor promoting cancerization of the covering epithelial tissues.

    PubMed

    Karseladze, A I

    2016-09-01

    Prominent angiogenesis, which is a hallmark of invasive cancer is preceded at the precancerous stage by marked ischemia. Our hypothesis proposes a structural mechanism responsible for altering blood flow in the covering epithelium and leading to marked reduction of vascularization in the foci of dysplasia. This mechanism varies from one type of epithelium to another. In squamous epithelium only basal cells are in direct contact with stromal vessels. To supply nutrients to the rest of the cells located at different levels, the subjacent stroma forms excrescences which penetrate upward together with blood capillaries. As soon as precancerous dysplastic alterations start and progress the number of intraepithelial blood vessels simultaneously decreases, thus leading to ischemia which precedes or promotes malignization of the covering squamous epithelium. To compensate for the deficit in blood supply, the dysplastic cells penetrate deeper into the underlying stroma, commencing invasion. Thus, the cells destroy the subjacent stroma not because they are initially "malignant", but due to ischemia which provokes the search for nutrients. Comparing squamous epithelium with glandular respiratory epithelium shows that the latter contains no blood capillaries at all. However, unlike squamous epithelial coverings, in respiratory epithelial covering, each cell is attached directly to the basal membrane and has ample access to the blood supply. Covering respiratory epithelium itself seldom gives rise directly to malignant growth. Cancerization of this type of epithelium occurs in the foci of squamous metaplasia. The latter are not supplied by a sufficient amount of blood vessels and in the majority of cases remain fragile and vulnerable structures, easily prone to malignization. Further study of these phenomenon should include the clarification of the influence of carcinogenic agents on the mechanism of adequate vascularization at the precancerous stage. PMID:27515223

  15. Epithelial ovarian cancer: An overview

    PubMed Central

    Desai, Arpita; Xu, Jingyao; Aysola, Kartik; Qin, Yunlong; Okoli, Chika; Hariprasad, Ravipati; Chinemerem, Ugorji; Gates, Candace; Reddy, Avinash; Danner, Omar; Franklin, Geary; Ngozi, Anachebe; Cantuaria, Guilherme; Singh, Karan; Grizzle, William; Landen, Charles; Partridge, Edward E; Rice, Valerie Montgomery; Reddy, E Shyam P; Rao, Veena N

    2014-01-01

    Ovarian cancer is the second most common gynecological cancer and the leading cause of death in the United States. In this article we review the diagnosis and current management of epithelial ovarian cancer which accounts for over 95 percent of the ovarian malignancies. We will present various theories about the potential origin of ovarian malignancies. We will discuss the genetic anomalies and syndromes that may cause ovarian cancers with emphasis on Breast cancer type 1/2 mutations. The pathology and pathogenesis of ovarian carcinoma will also be presented. Lastly, we provide a comprehensive overview of treatment strategies and staging of ovarian cancer, conclusions and future directions. PMID:25525571

  16. Tetanus neurotoxin-mediated cleavage of cellubrevin impairs epithelial cell migration and integrin-dependent cell adhesion

    PubMed Central

    Proux-Gillardeaux, Véronique; Gavard, Julie; Irinopoulou, Theano; Mège, René-Marc; Galli, Thierry

    2005-01-01

    A role for endocytosis and exocytosis in cell migration has been proposed but not yet demonstrated. Here, we show that cellubrevin (Cb), an early endosomal v-SNARE, mediates trafficking in the lamellipod of migrating epithelial cells and partially colocalizes with markers of focal contacts. Expression of tetanus neurotoxin, which selectively cleaves Cb, significantly reduced the speed of migrating epithelial cells. Furthermore, expression of tetanus neurotoxin enhanced the adhesion of epithelial cells to collagen, laminin, fibronectin, and E-cadherin; altered spreading on collagen; and impaired the recycling of β1 integrins. These results suggest that Cb-dependent membrane trafficking participates in cell motility through the regulation of cell adhesion. PMID:15851685

  17. Interleukin-23-Independent IL-17 Production Regulates Intestinal Epithelial Permeability.

    PubMed

    Lee, Jacob S; Tato, Cristina M; Joyce-Shaikh, Barbara; Gulen, Muhammet F; Gulan, Fatih; Cayatte, Corinne; Chen, Yi; Blumenschein, Wendy M; Judo, Michael; Ayanoglu, Gulesi; McClanahan, Terrill K; Li, Xiaoxia; Cua, Daniel J

    2015-10-20

    Whether interleukin-17A (IL-17A) has pathogenic and/or protective roles in the gut mucosa is controversial and few studies have analyzed specific cell populations for protective functions within the inflamed colonic tissue. Here we have provided evidence for IL-17A-dependent regulation of the tight junction protein occludin during epithelial injury that limits excessive permeability and maintains barrier integrity. Analysis of epithelial cells showed that in the absence of signaling via the IL-17 receptor adaptor protein Act-1, the protective effect of IL-17A was abrogated and inflammation was enhanced. We have demonstrated that after acute intestinal injury, IL-23R(+) γδ T cells in the colonic lamina propria were the primary producers of early, gut-protective IL-17A, and this production of IL-17A was IL-23 independent, leaving protective IL-17 intact in the absence of IL-23. These results suggest that IL-17-producing γδ T cells are important for the maintenance and protection of epithelial barriers in the intestinal mucosa. PMID:26431948

  18. Genetic control of epithelial tube fusion during Drosophila tracheal development.

    PubMed

    Samakovlis, C; Manning, G; Steneberg, P; Hacohen, N; Cantera, R; Krasnow, M A

    1996-11-01

    During development of tubular networks such as the mammalian vascular system, the kidney and the Drosophila tracheal system, epithelial tubes must fuse to each other to form a continuous network. Little is known of the cellular mechanisms or molecular control of epithelial tube fusion. We describe the cellular dynamics of a tracheal fusion event in Drosophila and identify a gene regulatory hierarchy that controls this extraordinary process. A tracheal cell located at the developing fusion point expresses a sequence of specific markers as it grows out and contacts a similar cell from another tube; the two cells adhere and form an intercellular junction, and they become doughnut-shaped cells with the lumen passing through them. The early fusion marker Fusion-1 is identified as the escargot gene. It lies near the top of the regulatory hierarchy, activating the expression of later fusion markers and repressing genes that promote branching. Ectopic expression of escargot activates the fusion process and suppresses branching throughout the tracheal system, leading to ectopic tracheal connections that resemble certain arteriovenous malformations in humans. This establishes a simple genetic system to study fusion of epithelial tubes. PMID:8951068

  19. Epithelial plasticity in urothelial carcinoma: Current advancements and future challenges

    PubMed Central

    Garg, Minal

    2016-01-01

    Urothelial carcinoma (UC) of the bladder is characterized by high recurrence rate where a subset of these cells undergoes transition to deadly muscle invasive disease and later metastasizes. Urothelial cancer stem cells (UroCSCs), a tumor subpopulation derived from transformation of urothelial stem cells, are responsible for heterogeneous tumor formation and resistance to systemic treatment in UC of the bladder. Although the precise reason for pathophysiologic spread of tumor is not clear, transcriptome analysis of microdissected cancer cells expressing multiple progenitor/stem cell markers validates the upregulation of genes that derive epithelial-to-mesenchymal transition. Experimental studies on human bladder cancer xenografts describe the mechanistic functions and regulation of epithelial plasticity for its cancer-restraining effects. It has been further examined to be associated with the recruitment of a pool of UroCSCs into cell division in response to damages induced by adjuvant therapies. This paper also discusses the various probable therapeutic approaches to attenuate the progressive manifestation of chemoresistance by co-administration of inhibitors of epithelial plasticity and chemotherapeutic drugs by abrogating the early tumor repopulation as well as killing differentiated cancer cells. PMID:27621760

  20. A distinct molecular profile associated with mucinous epithelial ovarian cancer

    PubMed Central

    Heinzelmann-Schwarz, V A; Gardiner-Garden, M; Henshall, S M; Scurry, J P; Scolyer, R A; Smith, A N; Bali, A; Bergh, P Vanden; Baron-Hay, S; Scott, C; Fink, D; Hacker, N F; Sutherland, R L; O'Brien, P M

    2006-01-01

    Mucinous epithelial ovarian cancers (MOC) are clinically and morphologically distinct from the other histological subtypes of ovarian cancer. To determine the genetic basis of MOC and to identify potential tumour markers, gene expression profiling of 49 primary ovarian cancers of different histological subtypes was performed using a customised oligonucleotide microarray containing >59 000 probesets. The results show that MOC express a genetic profile that both differs and overlaps with other subtypes of epithelial ovarian cancer. Concordant with its histological phenotype, MOC express genes characteristic of mucinous carcinomas of varying epithelial origin, including intestinal carcinomas. Differences in gene expression between MOC and other histological subtypes of ovarian cancer were confirmed by RT–PCR and/or immunohistochemistry. In particular, galectin 4 (LGALS4) was highly and specifically expressed in MOC, but expressed at lower levels in benign mucinous cysts and borderline (atypical proliferative) tumours, supporting a malignant progression model of MOC. Hence LGALS4 may have application as an early and differential diagnostic marker of MOC. PMID:16508639

  1. Epithelial plasticity in urothelial carcinoma: Current advancements and future challenges.

    PubMed

    Garg, Minal

    2016-08-26

    Urothelial carcinoma (UC) of the bladder is characterized by high recurrence rate where a subset of these cells undergoes transition to deadly muscle invasive disease and later metastasizes. Urothelial cancer stem cells (UroCSCs), a tumor subpopulation derived from transformation of urothelial stem cells, are responsible for heterogeneous tumor formation and resistance to systemic treatment in UC of the bladder. Although the precise reason for pathophysiologic spread of tumor is not clear, transcriptome analysis of microdissected cancer cells expressing multiple progenitor/stem cell markers validates the upregulation of genes that derive epithelial-to-mesenchymal transition. Experimental studies on human bladder cancer xenografts describe the mechanistic functions and regulation of epithelial plasticity for its cancer-restraining effects. It has been further examined to be associated with the recruitment of a pool of UroCSCs into cell division in response to damages induced by adjuvant therapies. This paper also discusses the various probable therapeutic approaches to attenuate the progressive manifestation of chemoresistance by co-administration of inhibitors of epithelial plasticity and chemotherapeutic drugs by abrogating the early tumor repopulation as well as killing differentiated cancer cells. PMID:27621760

  2. Gut microbiota protects against gastrointestinal tumorigenesis caused by epithelial injury.

    PubMed

    Zhan, Yu; Chen, Po-Ju; Sadler, William D; Wang, Fuyuan; Poe, Sara; Núñez, Gabriel; Eaton, Kathryn A; Chen, Grace Y

    2013-12-15

    Inflammation is a critical player in the development of both colitis-associated and sporadic colon cancers. Several studies suggest that the microbiota contribute to inflammation and tumorigenesis; however, studies to understand the role of the microbiota in colon tumor development in germ-free (GF) mice are limited. We therefore studied the effects of the microbiota on the development of inflammation and tumors in GF and conventionally raised specific pathogen-free (SPF) mice treated with azoxymethane (AOM) and dextran sulfate sodium (DSS). We discovered that GF mice developed significantly more and larger tumors compared with that in SPF mice after AOM and DSS treatment despite the lack of early acute inflammation in response to chemically induced injury by DSS. Although the extent of intestinal epithelial damage and apoptosis was not significantly different in GF and SPF mice, there was a delay in intestinal epithelial repair to DSS-induced injury in GF mice resulting in a late onset of proinflammatory and protumorigenic responses and increased epithelial proliferation and microadenoma formation. Recolonization of GF mice with commensal bacteria or administration of lipopolysaccharide reduced tumorigenesis. Thus, although commensal bacteria are capable of driving chronic inflammation and tumorigenesis, the gut microbiota also have important roles in limiting chemically induced injury and proliferative responses that lead to tumor development. PMID:24165160

  3. Differentiated kidney epithelial cells repair injured proximal tubule.

    PubMed

    Kusaba, Tetsuro; Lalli, Matthew; Kramann, Rafael; Kobayashi, Akio; Humphreys, Benjamin D

    2014-01-28

    Whether kidney proximal tubule harbors a scattered population of epithelial stem cells is a major unsolved question. Lineage-tracing studies, histologic characterization, and ex vivo functional analysis results conflict. To address this controversy, we analyzed the lineage and clonal behavior of fully differentiated proximal tubule epithelial cells after injury. A CreER(T2) cassette was knocked into the sodium-dependent inorganic phosphate transporter SLC34a1 locus, which is expressed only in differentiated proximal tubule. Tamoxifen-dependent recombination was absolutely specific to proximal tubule. Clonal analysis after injury and repair showed that the bulk of labeled cells proliferate after injury with increased clone size after severe compared with mild injury. Injury to labeled proximal tubule epithelia induced expression of CD24, CD133, vimentin, and kidney-injury molecule-1, markers of putative epithelial stem cells in the human kidney. Similar results were observed in cultured proximal tubules, in which labeled clones proliferated and expressed dedifferentiation and injury markers. When mice with completely labeled kidneys were subject to injury and repair there was no dilution of fate marker despite substantial proliferation, indicating that unlabeled progenitors do not contribute to kidney repair. During nephrogenesis and early kidney growth, single proximal tubule clones expanded, suggesting that differentiated cells also contribute to tubule elongation. These findings provide no evidence for an intratubular stem-cell population, but rather indicate that terminally differentiated epithelia reexpress apparent stem-cell markers during injury-induced dedifferentiation and repair. PMID:24127583

  4. Epithelial β1 integrin is required for lung branching morphogenesis and alveolarization.

    PubMed

    Plosa, Erin J; Young, Lisa R; Gulleman, Peter M; Polosukhin, Vasiliy V; Zaynagetdinov, Rinat; Benjamin, John T; Im, Amanda M; van der Meer, Riet; Gleaves, Linda A; Bulus, Nada; Han, Wei; Prince, Lawrence S; Blackwell, Timothy S; Zent, Roy

    2014-12-01

    Integrin-dependent interactions between cells and extracellular matrix regulate lung development; however, specific roles for β1-containing integrins in individual cell types, including epithelial cells, remain incompletely understood. In this study, the functional importance of β1 integrin in lung epithelium during mouse lung development was investigated by deleting the integrin from E10.5 onwards using surfactant protein C promoter-driven Cre. These mutant mice appeared normal at birth but failed to gain weight appropriately and died by 4 months of age with severe hypoxemia. Defects in airway branching morphogenesis in association with impaired epithelial cell adhesion and migration, as well as alveolarization defects and persistent macrophage-mediated inflammation were identified. Using an inducible system to delete β1 integrin after completion of airway branching, we showed that alveolarization defects, characterized by disrupted secondary septation, abnormal alveolar epithelial cell differentiation, excessive collagen I and elastin deposition, and hypercellularity of the mesenchyme occurred independently of airway branching defects. By depleting macrophages using liposomal clodronate, we found that alveolarization defects were secondary to persistent alveolar inflammation. β1 integrin-deficient alveolar epithelial cells produced excessive monocyte chemoattractant protein 1 and reactive oxygen species, suggesting a direct role for β1 integrin in regulating alveolar homeostasis. Taken together, these studies define distinct functions of epithelial β1 integrin during both early and late lung development that affect airway branching morphogenesis, epithelial cell differentiation, alveolar septation and regulation of alveolar homeostasis. PMID:25395457

  5. Periderm prevents pathological epithelial adhesions during embryogenesis

    PubMed Central

    Richardson, Rebecca J.; Hammond, Nigel L.; Coulombe, Pierre A.; Saloranta, Carola; Nousiainen, Heidi O.; Salonen, Riitta; Berry, Andrew; Hanley, Neil; Headon, Denis; Karikoski, Riitta; Dixon, Michael J.

    2014-01-01

    Appropriate development of stratified, squamous, keratinizing epithelia, such as the epidermis and oral epithelia, generates an outer protective permeability barrier that prevents water loss, entry of toxins, and microbial invasion. During embryogenesis, the immature ectoderm initially consists of a single layer of undifferentiated, cuboidal epithelial cells that stratifies to produce an outer layer of flattened periderm cells of unknown function. Here, we determined that periderm cells form in a distinct pattern early in embryogenesis, exhibit highly polarized expression of adhesion complexes, and are shed from the outer surface of the embryo late in development. Mice carrying loss-of-function mutations in the genes encoding IFN regulatory factor 6 (IRF6), IκB kinase-α (IKKα), and stratifin (SFN) exhibit abnormal epidermal development, and we determined that mutant animals exhibit dysfunctional periderm formation, resulting in abnormal intracellular adhesions. Furthermore, tissue from a fetus with cocoon syndrome, a lethal disorder that results from a nonsense mutation in IKKA, revealed an absence of periderm. Together, these data indicate that periderm plays a transient but fundamental role during embryogenesis by acting as a protective barrier that prevents pathological adhesion between immature, adhesion-competent epithelia. Furthermore, this study suggests that failure of periderm formation underlies a series of devastating birth defects, including popliteal pterygium syndrome, cocoon syndrome, and Bartsocas-Papas syndrome. PMID:25133425

  6. Gene expression analysis of early stage endometrial cancers reveals unique transcripts associated with grade and histology but not depth of invasion.

    PubMed

    Risinger, John I; Allard, Jay; Chandran, Uma; Day, Roger; Chandramouli, Gadisetti V R; Miller, Caela; Zahn, Christopher; Oliver, Julie; Litzi, Tracy; Marcus, Charlotte; Dubil, Elizabeth; Byrd, Kevin; Cassablanca, Yovanni; Becich, Michael; Berchuck, Andrew; Darcy, Kathleen M; Hamilton, Chad A; Conrads, Thomas P; Maxwell, G Larry

    2013-01-01

    Endometrial cancer is the most common gynecologic malignancy in the United States but it remains poorly understood at the molecular level. This investigation was conducted to specifically assess whether gene expression changes underlie the clinical and pathologic factors traditionally used for determining treatment regimens in women with stage I endometrial cancer. These include the effect of tumor grade, depth of myometrial invasion and histotype. We utilized oligonucleotide microarrays to assess the transcript expression profile in epithelial glandular cells laser microdissected from 79 endometrioid and 12 serous stage I endometrial cancers with a heterogeneous distribution of grade and depth of myometrial invasion, along with 12 normal post-menopausal endometrial samples. Unsupervised multidimensional scaling analyses revealed that serous and endometrioid stage I cancers have similar transcript expression patterns when compared to normal controls where 900 transcripts were identified to be differentially expressed by at least fourfold (univariate t-test, p < 0.001) between the cancers and normal endometrium. This analysis also identified transcript expression differences between serous and endometrioid cancers and tumor grade, but no apparent differences were identified as a function of depth of myometrial invasion. Four genes were validated by quantitative PCR on an independent set of cancer and normal endometrium samples. These findings indicate that unique gene expression profiles are associated with histologic type and grade, but not myometrial invasion among early stage endometrial cancers. These data provide a comprehensive perspective on the molecular alterations associated with stage I endometrial cancer, particularly those subtypes that have the worst prognosis. PMID:23785665

  7. The shroom family proteins play broad roles in the morphogenesis of thickened epithelial sheets.

    PubMed

    Lee, Chanjae; Le, Minh-Phuong; Wallingford, John B

    2009-06-01

    Thickened epithelial sheets are found in a wide variety of organ systems and the mechanisms governing their morphogenesis remain poorly defined. We show here, through expression patterns and functional studies, that Shroom family proteins are broadly involved in generating thickened epithelial sheets. Through in situ hybridization, we report the temporal and spatial expression patterns of the four Shroom family members during early Xenopus development, from oocytes to tadpole stage embryos. Further, we show that Shroom1 and 2 mRNAs are maternally expressed, while Shroom3 and Shroom4 are zygotic transcripts. In addition, maternal Shroom1 and 2 mRNAs localize in the animal hemisphere of the Xenopus egg and early blastula. During later development, all four Shroom family proteins are broadly expressed in developing epithelial organs, and the epithelial cells that express Shrooms are elongated. Moreover, we show that ectopic expression of Shroom2, like Shroom3, is able to increase cell height and that loss of Shroom2 function results in a failure of cell elongation in the neural epithelium. Together, these data suggest that Shroom family proteins play an important role in the morphogenesis of several different epithelial tissues during development. Developmental Dynamics 238:1480-1491, 2009. (c) 2009 Wiley-Liss, Inc. PMID:19384856

  8. Young, proliferative thymic epithelial cells engraft and function in aging thymuses

    PubMed Central

    Kim, Mi-Jeong; Miller, Christine M.; Shadrach, Jennifer L.; Wagers, Amy J.; Serwold, Thomas

    2015-01-01

    The thymus reaches its maximum size early in life and then begins to shrink, producing fewer T cells with increasing age. This thymic decline is thought to contribute to age-related T cell lymphopenias and hinder T cell recovery following bone marrow transplantation. While several cellular and molecular processes have been implicated in age-related thymic involution, their relative contributions are not known. Using heterochronic parabiosis, we observe that young circulating factors are not sufficient to drive regeneration of the aged thymus. In contrast, we find that resupplying young, engraftable thymic epithelial cells to a middle-aged or defective thymus leads to thymic growth and increased T cell production. Intrathymic transplantation and in vitro colony forming assays reveal that the engraftment and proliferative capacities of thymic epithelial cells diminish early in life, whereas the receptivity of the thymus to thymic epithelial cell engraftment remains relatively constant with age. These results support a model in which thymic growth and subsequent involution are driven by cell intrinsic changes in the proliferative capacity of thymic epithelial cells, and further show that young thymic epithelial cells can engraft and directly drive the growth of involuted thymuses. PMID:25870244

  9. Shape Transformations of Epithelial Shells.

    PubMed

    Misra, Mahim; Audoly, Basile; Kevrekidis, Ioannis G; Shvartsman, Stanislav Y

    2016-04-12

    Regulated deformations of epithelial sheets are frequently foreshadowed by patterning of their mechanical properties. The connection between patterns of cell properties and the emerging tissue deformations is studied in multiple experimental systems, but the general principles remain poorly understood. For instance, it is in general unclear what determines the direction in which the patterned sheet is going to bend and whether the resulting shape transformation will be discontinuous or smooth. Here these questions are explored computationally, using vertex models of epithelial shells assembled from prismlike cells. In response to rings and patches of apical cell contractility, model epithelia smoothly deform into invaginated or evaginated shapes similar to those observed in embryos and tissue organoids. Most of the observed effects can be captured by a simpler model with polygonal cells, modified to include the effects of the apicobasal polarity and natural curvature of epithelia. Our models can be readily extended to include the effects of multiple constraints and used to describe a wide range of morphogenetic processes. PMID:27074691

  10. Epithelialization in Wound Healing: A Comprehensive Review

    PubMed Central

    Pastar, Irena; Stojadinovic, Olivera; Yin, Natalie C.; Ramirez, Horacio; Nusbaum, Aron G.; Sawaya, Andrew; Patel, Shailee B.; Khalid, Laiqua; Isseroff, Rivkah R.; Tomic-Canic, Marjana

    2014-01-01

    Significance: Keratinocytes, a major cellular component of the epidermis, are responsible for restoring the epidermis after injury through a process termed epithelialization. This review will focus on the pivotal role of keratinocytes in epithelialization, including cellular processes and mechanisms of their regulation during re-epithelialization, and their cross talk with other cell types participating in wound healing. Recent Advances: Discoveries in epidermal stem cells, keratinocyte immune function, and the role of the epidermis as an independent neuroendocrine organ will be reviewed. Novel mechanisms of gene expression regulation important for re-epithelialization, including microRNAs and histone modifications, will also be discussed. Critical Issues: Epithelialization is an essential component of wound healing used as a defining parameter of a successful wound closure. A wound cannot be considered healed in the absence of re-epithelialization. The epithelialization process is impaired in all types of chronic wounds. Future Directions: A comprehensive understanding of the epithelialization process will ultimately lead to the development of novel therapeutic approaches to promote wound closure. PMID:25032064

  11. Epithelial organization, cell polarity and tumorigenesis.

    PubMed

    McCaffrey, Luke Martin; Macara, Ian G

    2011-12-01

    Epithelial cells comprise the foundation for the majority of organs in the mammalian body, and are the source of approximately 90% of all human cancers. Characteristically, epithelial cells form intercellular adhesions, exhibit apical/basal polarity, and orient their mitotic spindles in the plane of the epithelial sheet. Defects in these attributes result in the tissue disorganization associated with cancer. Epithelia undergo self-renewal from stem cells, which might in some cases be the cell of origin for cancers. The PAR polarity proteins are master regulators of epithelial organization, and are closely linked to signaling pathways such as Hippo, which orchestrate proliferation and apoptosis to control organ size. 3D ex vivo culture systems can now faithfully recapitulate epithelial organ morphogenesis, providing a powerful approach to study both normal development and the initiating events in carcinogenesis. PMID:21782440

  12. [Recent studies on corneal epithelial barrier function].

    PubMed

    Liu, F F; Li, W; Liu, Z G; Chen, W S

    2016-08-01

    Corneal epithelium, the outermost layer of eyeball, is the main route for foreign materials to enter the eye. Under physiological conditions, the corneal epithelial superficial cells form a functionally selective permeability barrier. Integral corneal epithelial barrier function not only ensures the enrolling of nutrients which is required for regular metabolism, but also prevents foreign bodies, or disease-causing microorganism invasion. Recently, a large number of clinical and experimental studies have shown that abnormal corneal epithelial barrier function is the pathological basis for many ocular diseases. In addition, some study found that corneal epithelial barrier constitutes a variety of proteins involved in cell proliferation, differentiation, apoptosis, and a series of physiological and pathological processes. This paper reviewed recent studies specifically on the corneal epithelial barrier, highlights of its structure, function and influence factors. (Chin J Ophthalmol, 2016, 52: 631-635). PMID:27562284

  13. Biosynthesis of platelet-activating factor in glandular gastric mucosa. Evidence for the involvement of the 'de novo' pathway and modulation by fatty acids.

    PubMed

    Fernandez-Gallardo, S; Gijon, M A; Garcia, M C; Cano, E; Sanchez Crespo, M

    1988-09-15

    The biosynthesis of platelet-activating factor (PAF), a phospholipid autocoid with potent ulcerogenic properties that is produced in secretory exocrine glands by physiological secretagogues, was assessed in microsomal preparations of glandular gastric mucosa. For this purpose, 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine (lyso-PAF):acetyl-CoA acetyltransferase (EC 2.3.1.67); the enzymes of the 'de novo' pathway: 1-O-alkyl-2-lyso-sn-glycero-3-phosphate (alkyl-lyso-GP):acetyl-CoA acetyltransferase and 1-O-alkyl-2-acetyl-sn-glycerol (alkylacetyl-G):CDP-choline cholinephosphotransferase (EC 2.7.8.16); and some enzymes involved in the catabolism of PAF and lyso-PAF were assayed. Only the enzymes of the 'de novo' pathway and small amounts of PAF acetylhydrolase, phospholipase A2 and a lysophospholipase D acting on either lipids could be detected in the gastric preparations, whereas lyso-PAF:acetyl-CoA acetyltransferase activity was undetectable. The specific activity of alkyl-lyso-GP:acetyl-CoA acetyltransferase in the gastric mucosa was about one-tenth of that found in spleen microsomes and its apparent Km for acetyl-CoA was 454 microM compared with 277 microM in spleen microsomes. Glandular mucosa homogenates contained preformed PAF at a concentration of 2.7 +/- 0.7 ng equivalents of PAF (hexadecyl)/mg of protein. When gastric microsomes were incubated with micromolar concentrations of fatty acids (arachidonic, palmitic and oleic) prior to the assay of dithiothreitol (DTT)-insensitive cholinephosphotransferase, a dose-dependent reduction in the formation of PAF was observed, arachidonic acid being the most potent inhibitor, followed by linoleic acid (only tested on spleen microsomes) and oleic acid. By contrast, 1,2-diolein and phosphatidylcholine (dipalmitoyl) showed no or little effect. These results indicate that glandular gastric mucosa can produce PAF through the 'de novo' pathway, and that fatty acids, especially unsaturated, can reduce that synthesis by

  14. Clinical Use of Cancer Biomarkers in Epithelial Ovarian Cancer

    PubMed Central

    Sölétormos, György; Duffy, Michael J.; Othman Abu Hassan, Suher; Verheijen, René H.M.; Tholander, Bengt; Bast, Robert C.; Gaarenstroom, Katja N.; Sturgeon, Catharine M.; Bonfrer, Johannes M.; Petersen, Per Hyltoft; Troonen, Hugo; CarloTorre, Gian; Kanty Kulpa, Jan; Tuxen, Malgorzata K.; Molina, Raphael

    2016-01-01

    Objective To present an update of the European Group on Tumor Markers guidelines for serum markers in epithelial ovarian cancer. Methods Systematic literature survey from 2008 to 2013. The articles were evaluated by level of evidence and strength of recommendation. Results Because of its low sensitivity (50–62% for early stage epithelial ovarian cancer) and limited specificity (94–98.5%), cancer antigen (CA) 125 (CA125) is not recommended as a screening test in asymptomatic women. The Risk of Malignancy Index, which includes CA125, transvaginal ultrasound, and menopausal status, is recommended for the differential diagnosis of a pelvic mass. Because human epididymis protein 4 has been reported to have superior specificity to CA125, especially in premenopausal women, it may be considered either alone or as part of the risk of ovarian malignancy algorithm, in the differential diagnosis of pelvic masses, especially in such women. CA125 should be used to monitor response to first-line chemotherapy using the previously published criteria of the Gynecological Cancer Intergroup, that is, at least a 50% reduction of a pretreatment sample of 70 kU/L or greater. The value of CA125 in posttherapy surveillance is less clear. Although a prospective randomized trial concluded that early administration of chemotherapy based on increasing CA125 levels had no effect on survival, European Group on Tumor Markers state that monitoring with CA125 in this situation should occur, especially if the patient is a candidate for secondary cytoreductive surgery. Conclusions At present, CA125 remains the most important biomarker for epithelial ovarian cancer, excluding tumors of mucinous origin. PMID:26588231

  15. A four-day oral treatment regimen for simultaneous micronucleus analyses in the glandular stomach, colon, and bone marrow of rats.

    PubMed

    Okada, Emiko; Fujiishi, Yohei; Narumi, Kazunori; Yasutake, Nobuyoshi; Ohyama, Wakako

    2013-12-12

    Our aim was to develop a multi-tissue micronucleus (MN) test method for the simultaneous analysis of rat glandular stomach, colon, and bone marrow. We have evaluated the multi-tissue MN test method with a regimen in which rats were administered chemicals orally once per day for four days and the cells of each tissue were collected 24 h after the final dose. The following compounds were studied: N-nitroso-N-methylurea (MNU), 4-nitroquinoline-1-oxide (4NQO), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), N-methyl-N-nitrosourethane (NMUT), 1,2-dimethylhydrazine 2HCl (DMH), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine HCl (PhIP), KBrO(3), amaranth (AM), and quercetin (QN). The gastrointestinal tract carcinogens increased the frequencies of micronucleated (MNed) cells in target tissue in a dose-dependent manner: MNU in gastric- and colonic-cells; 4NQO, MNNG, and NMUT in gastric cells; DMH and PhIP in colonic cells. In immature erythrocytes, MNU, 4NQO, DMH, and PhIP increased the frequency of MNed cells but MNNG and NMUT did not. The food additive KBrO(3), which is known to be a renal carcinogen, increased the frequencies of MNed cells in the glandular stomach and bone marrow. The food additive AM and the plant flavonoid QN, which are non-carcinogenic in most studies, did not cause increased MNed cells in any of the three tissues. Our results indicate that this multi-tissue MN test method is useful for the comprehensive evaluation of the genotoxicity of orally administered compounds. PMID:24140632

  16. Identification of Epithelial Ovarian Tumor-Specific Aptamers

    PubMed Central

    Benedetto, Gregory; Hamp, Timothy J.; Wesselman, Peter J.

    2015-01-01

    Ovarian cancer is often diagnosed in late stages with few treatment options and poor long-term prognosis. New clinical tools for early detection of ovarian malignancies will significantly help reduce mortality and improve current long-term survival rates. The objective of this work was to identify ovarian tumor-specific single-stranded DNA aptamers that bind to malignant ovarian tumor cells and internalize with high affinity and specificity. Aptamers can identify unique tumor biomarkers, can aid in early detection and diagnosis of neoplastic disorders, and can be functionalized by conjugation to small molecules. To identify aptamers from random single-stranded DNA pools (60 bases long), we used whole Cell-SELEX (systematic evolution of ligands by exponential enrichment) to enrich and isolate tumor-specific aptamers that bind to tumor-specific receptors in their native state on the cell surface. Next-Generation sequencing identified seven novel aptamers and detailed analyses of three are described. Aptamers bound to, and were internalized by, target Caov-3 cell populations, but not nontarget nonmalignant ovarian epithelial HOSE 6-3 cells or multiple other epithelial tumor cell lines. Furthermore, aptamers showed unique binding affinities with apparent dissociation constants (Kd) measuring in the submicromolar range supporting their physiological relevance and potential use in clinical applications. PMID:25894736

  17. Esophageal epithelial cells acquire functional characteristics of activated myofibroblasts after undergoing an epithelial to mesenchymal transition

    PubMed Central

    Muir, Amanda B.; Dods, Kara; Noah, Yuli; Toltzis, Sarit; Chandramouleeswaran, Prasanna Modayur; Lee, Anna; Benitez, Alain; Bedenbaugh, Adam; Falk, Gary W.; Wells, Rebecca G.; Nakagawa, Hiroshi; Wang, Mei-Lun

    2015-01-01

    Background and Aims Eosinophilic esophagitis (EoE) is an allergic inflammatory disease that leads to esophageal fibrosis and stricture. We have recently shown that in EoE, esophageal epithelial cells undergo an epithelial to mesenchymal transition (EMT), characterized by gain of mesenchymal markers and loss of epithelial gene expression. Whether epithelial cells exposed to profibrotic cytokines can also acquire the functional characteristics of activated myofibroblasts, including migration, contraction, and extracellular matrix deposition, is relevant to our understanding and treatment of EoE-associated fibrogenesis. In the current study, we characterize cell migration, contraction, and collagen production by esophageal epithelial cells that have undergone cytokine-induced EMT in vitro. Methods and Results Stimulation of human non-transformed immortalized esophageal epithelial cells (EPC2-hTERT) with profibrotic cytokines TNFα, TGFβ, and IL1β for three weeks led to acquisition of mesenchymal αSMA and vimentin, and loss of epithelial E-cadherin expression. Upon removal of the profibrotic stimulus, epithelial characteristics were partially rescued. TGFβ stimulation had a robust effect upon epithelial collagen production. Surprisingly, TNFα stimulation had the most potent effect upon cell migration and contraction, exceeding the effects of the prototypical profibrotic cytokine TGFβ. IL1β stimulation alone had minimal effect upon esophageal epithelial migration, contraction, and collagen production. Conclusions Esophageal epithelial cells that have undergone EMT acquire functional characteristics of activated myofibroblasts in vitro. Profibrotic cytokines exert differential effects upon esophageal epithelial cells, underscoring complexities of fibrogenesis in EoE, and implicating esophageal epithelial cells as effector cells in EoE-associated fibrogenesis. PMID:25183431

  18. Epithelial Inclusion Cyst in Conjunctival Melanoma.

    PubMed

    Esposito, Evangelina; Zoroquiain, Pablo; Mastromonaco, Christina; Morales, Melina C; Belfort Neto, Rubens; Burnier, Miguel

    2016-09-01

    Conjunctival melanoma is the second most common conjunctival malignancy. Its differential diagnosis with other conjunctival melanocytic neoplasms is inherently difficult. The presence of epithelial cysts is a useful feature in conjunctival tumors and favors a benign lesion. Herein 2 cases of conjunctival melanoma with cysts are presented. To the best of our knowledge, this is the first series of conjunctival melanoma with epithelial inclusion cysts. This series emphasizes the importance of considering several malignant features when reviewing conjunctival melanocytic lesions, as malignancy can exist even in the presence of epithelial inclusion cysts. PMID:27160434

  19. Interactions of Aspergillus fumigatus Conidia with Airway Epithelial Cells: A Critical Review

    PubMed Central

    Croft, Carys A.; Culibrk, Luka; Moore, Margo M.; Tebbutt, Scott J.

    2016-01-01

    Aspergillus fumigatus is an environmental filamentous fungus that also acts as an opportunistic pathogen able to cause a variety of symptoms, from an allergic response to a life-threatening disseminated fungal infection. The infectious agents are inhaled conidia whose first point of contact is most likely to be an airway epithelial cell (AEC). The interaction between epithelial cells and conidia is multifaceted and complex, and has implications for later steps in pathogenesis. Increasing evidence has demonstrated a key role for the airway epithelium in the response to respiratory pathogens, particularly at early stages of infection; therefore, elucidating the early stages of interaction of conidia with AECs is essential to understand the establishment of infection in cohorts of at-risk patients. Here, we present a comprehensive review of the early interactions between A. fumigatus and AECs, including bronchial and alveolar epithelial cells. We describe mechanisms of adhesion, internalization of conidia by AECs, the immune response of AECs, as well as the role of fungal virulence factors, and patterns of fungal gene expression characteristic of early infection. A clear understanding of the mechanisms involved in the early establishment of infection by A. fumigatus could point to novel targets for therapy and prophylaxis. PMID:27092126

  20. Relevance of the stroma and epithelial-mesenchymal transition (EMT) for the rheumatic diseases

    PubMed Central

    Zvaifler, Nathan J

    2006-01-01

    Epithelial-mesenchymal transition (EMT) is a term applied to the process whereby cells undergo a switch from an epithelial phenotype with tight junctions, lateral, apical, and basal membranes, and lack of mobility into mesenchymal cells that have loose interactions with other cells, are non-polarized, motile and produce an extracellular matrix. The importance of this process was initially recognized from a very early step in embryology, but more recently as a potential mechanism for the progression and spread of epithelial cancers. As the sequence of morphological changes has become understood in molecular terms, diseases characterized by alterations in stromal elements and fibrosis are being considered as examples of EMT. This review will focus on the pathogenetic features of immune-mediated renal disease, systemic sclerosis and rheumatoid arthritis that could be explained by EMT. PMID:16689999

  1. Sox2+ Stem Cells Contribute to All Epithelial Lineages of the Tooth via Sfrp5+ Progenitors

    PubMed Central

    Juuri, Emma; Saito, Kan; Ahtiainen, Laura; Seidel, Kerstin; Tummers, Mark; Hochedlinger, Konrad; Klein, Ophir D.; Thesleff, Irma; Michon, Frederic

    2012-01-01

    SUMMARY The continuously growing mouse incisor serves as a valuable model to study stem cell regulation during organ renewal. Epithelial stem cells are localized in the proximal end of the incisor in the labial cervical loop. Here, we show that the transcription factor Sox2 is a specific marker for these stem cells. Sox2+ cells became restricted to the labial cervical loop during tooth morphogenesis, and they contributed to the renewal of enamel-producing ameloblasts as well as all other epithelial cell lineages of the tooth. The early progeny of Sox2-positive stem cells transiently expressed the Wnt inhibitor Sfrp5. Sox2 expression was regulated by the tooth initiation marker FGF8 and specific miRNAs, suggesting a fine-tuning to maintain homeostasis of the dental epithelium. The identification of Sox2 as a marker for the dental epithelial stem cells will facilitate further studies on their lineage segregation and differentiation during tooth renewal. PMID:22819339

  2. Minor ipsilateral simple limbal epithelial transplantation (mini-SLET) for pterygium treatment

    PubMed Central

    Hernández-Bogantes, Erick; Amescua, Guillermo; Navas, Alejandro; Garfias, Yonathan; Ramirez-Miranda, Arturo; Lichtinger, Alejandro; Graue-Hernández, Enrique O

    2015-01-01

    We describe a novel surgical technique for pterygium removal taking advantage of the properties of amniotic membrane and limbal epithelial stem cells. A total of 10 eyes underwent pterygium excision with amniotic membrane coverage of the bare sclera and placement of pieces of limbal epithelium in a linear fashion in the affected limbal area covered by a second amniotic membrane using fibrin glue. After up to 8 months of follow-up, there were no signs of early recurrence or sight-threatening complications. The minor ipsilateral simple limbal epithelial transplantation technique for the treatment of pterygium requires less tissue than the conventional conjunctival autograft, leaving healthy conjunctiva if needed for another procedure in the future and offers the advantages of epithelial stem cells, which in the long term may reduce the rate of recurrence significantly. PMID:26130669

  3. An epithelial tissue in Dictyostelium challenges the traditional origin of metazoan multicellularity.

    PubMed

    Dickinson, Daniel J; Nelson, W James; Weis, William I

    2012-10-01

    We hypothesize that aspects of animal multicellularity originated before the divergence of metazoans from fungi and social amoebae. Polarized epithelial tissues are a defining feature of metazoans and contribute to the diversity of animal body plans. The recent finding of a polarized epithelium in the non-metazoan social amoeba Dictyostelium discoideum demonstrates that epithelial tissue is not a unique feature of metazoans, and challenges the traditional paradigm that multicellularity evolved independently in social amoebae and metazoans. An alternative view, presented here, is that the common ancestor of social amoebae, fungi, and animals spent a portion of its life cycle in a multicellular state and possessed molecular machinery necessary for forming an epithelial tissue. Some descendants of this ancestor retained multicellularity, while others reverted to unicellularity. This hypothesis makes testable predictions regarding tissue organization in close relatives of metazoans and provides a novel conceptual framework for studies of early animal evolution. PMID:22930590

  4. IL-4 attenuates pulmonary epithelial cell-mediated suppression of T cell priming.

    PubMed

    Albrecht, Melanie; Arnhold, Markus; Lingner, Sandra; Mahapatra, Subhashree; Bruder, Dunja; Hansen, Gesine; Dittrich, Anna-Maria

    2012-01-01

    We have previously shown that Th2-polarized airway inflammation facilitates sensitization towards new, protein antigens. In this context, we could demonstrate that IL-4 needs to act on cells of the hematopoetic and the structural compartment in order to facilitate sensitization towards new antigens. We thus aimed to elucidate possible mechanisms of action of IL-4 on structural cells choosing to analyze pulmonary epithelial cells as an important part of the lung's structural system. We used a co-culture system of DC- or APC-dependent in vitro priming of T cells, co-cultivated on a layer of cells of a murine pulmonary epithelial cell line (LA-4) pretreated with or without IL-4. Effects on T cell priming were analyzed via CFSE-dilution and flow cytometric assessment of activation status. Pulmonary epithelial cells suppressed T cell proliferation in vitro but this effect was attenuated by pre-treatment of the epithelial cells with IL-4. Transwell experiments suggest that epithelial-mediated suppression of T cell activation is mostly cell-contact dependent and leads to attenuation in an early naive T cell phenotype. Secretion of soluble factors like TARC, TSLP, GM-CSF and CCL20 by epithelial cells did not change after IL-4 treatment. However, analysis of co-stimulatory expression on pulmonary epithelial cells revealed that pre-treatment of epithelial cells with IL-4 changed expression GITR-L, suggesting a possible mechanism for the effects observed. Our studies provide new insight into the role of IL-4 during the early phases of pulmonary sensitization: The inhibitory activity of pulmonary epithelial cells in homeostasis is reversed in the presence of IL-4, which is secreted in the context of Th2-dominated allergic airway inflammation. This mechanism might serve to explain facilitated sensitization in the clinical context of polysensitization where due to a pre-existing sensitization increased levels of IL-4 in the airways might facilitate T cell priming towards new

  5. Stromal Clues in Endometrial Carcinoma: Loss of Expression of β-Catenin, Epithelial-Mesenchymal Transition Regulators, and Estrogen-Progesterone Receptor

    PubMed Central

    Sayar, Ilyas; Ceyran, Ayse B.; Ibiloglu, Ibrahim; Akalin, Ibrahim; Firat, Ugur; Kosemetin, Duygu; Engin Zerk, Pinar; Aydin, Abdullah

    2016-01-01

    Epithelial-stroma interactions in the endometrium are known to be responsible for physiological functions and emergence of several pathologic lesions. Periglandular stromal cells act on endometrial cells in a paracrine manner through sex hormones. In this study, we immunohistochemically evaluated the expression of epithelial-mesenchymal transition regulators (SNAIL/SLUG, TWIST, ZEB1), adhesion molecules (β-catenin and E-cadhenin), estrogen (ER)-progesterone (PR) receptor and their correlation with each other in 30 benign, 148 hyperplastic (EH), and 101 endometrioid-type endometrial carcinoma (EC) endometria. In the epithelial component, loss of expression in E-cadherin, ER and PR, and overexpression of TWIST and ZEB1 were significantly higher in EC than in EH (P<0.01). In the periglandular stromal component, β-catenin and SNAIL/SLUG expression were significantly higher in normal endometrium and simple without atypical EH compared with complex atypical EH and EC (P<0.01). In addition, periglandular stromal TWIST expression was significantly higher in EH group compared with EC (P<0.05). There was significantly negative correlation between β-catenin and ER, TWIST and ER, and TWIST and PR in hyperplastic and carcinomatous glandular epithelium, whereas there was a significantly positive correlation between β-catenin and SNAIL-SLUG, β-catenin and TWIST, β-catenin and ER, β-catenin and PR, SNAIL-SLUG and ER, SNAIL-SLUG and PR, TWIST and ER, TWIST and PR, in periglandular/cancer-associated stromal cells (P<0.01). In conclusion, the pattern of positive and negative correlations in the expression of epithelial-mesenchymal transition regulators (SNAIL-SLUG and TWIST), sex hormone receptors (ER and PR), and β-catenin between ECs and hyperplasia, as well as between epithelium and stroma herein, is suggestive of a significant role for these proteins and their underlying molecular processes in the development of endometrial carcinomas. PMID:26367784

  6. Epithelial-mesenchymal transition, the tumor microenvironment, and metastatic behavior of epithelial malignancies

    PubMed Central

    Talbot, Lindsay J; Bhattacharya, Syamal D; Kuo, Paul C

    2012-01-01

    Objective The mechanisms of cancer metastasis have been intensely studied recently and may provide vital therapeutic targets for metastasis prevention. We sought to review the contribution of epithelial-mesenchymal transition and the tumor microenvironment to cancer metastasis. Summary Background Data Epithelial-mesenchymal transition is the process by which epithelial cells lose cell-cell junctions and baso-apical polarity and acquire plasticity, mobility, invasive capacity, stemlike characteristics, and resistance to apoptosis. This cell biology program is active in embryology, wound healing, and pathologically in cancer metastasis, and along with the mechanical and cellular components of the tumor microenvironment, provides critical impetus for epithelial malignancies to acquire metastatic capability. Methods A literature review was performed using PubMed for “epithelial-mesenchymal transition”, “tumor microenvironment”, “TGF-β and cancer”, “Wnt and epithelial-mesenchymal transition”, “Notch and epithelial-mesenchymal transition”, “Hedgehog and epithelial-mesenchymal transition” and “hypoxia and metastasis”. Relevant primary studies and review articles were assessed. Results Major signaling pathways involved in epithelial-mesenchymal transition include TGF-β, Wnt, Notch, Hedgehog, and others. These pathways converge on several transcription factors, including zinc finger proteins Snail and Slug, Twist, ZEB 1/2, and Smads. These factors interact with one another and others to provide crosstalk between the relevant signaling pathways. MicroRNA suppression and epigenetic changes also influence the changes involved in epithelial-mesenchymal transition. Cellular and mechanical components of the tumor microenvironment are also critical in determining metastatic potential. Conclusions While the mechanisms promoting metastasis are extremely wide ranging and still under intense investigation, the epithelial-mesenchymal transition program and

  7. Differentiation-Dependent KLF4 Expression Promotes Lytic Epstein-Barr Virus Infection in Epithelial Cells

    PubMed Central

    Nawandar, Dhananjay M.; Wang, Anqi; Makielski, Kathleen; Lee, Denis; Ma, Shidong; Barlow, Elizabeth; Reusch, Jessica; Jiang, Ru; Wille, Coral K.; Greenspan, Deborah; Greenspan, John S.; Mertz, Janet E.; Hutt-Fletcher, Lindsey; Johannsen, Eric C.; Lambert, Paul F.; Kenney, Shannon C.

    2015-01-01

    Epstein-Barr virus (EBV) is a human herpesvirus associated with B-cell and epithelial cell malignancies. EBV lytically infects normal differentiated oral epithelial cells, where it causes a tongue lesion known as oral hairy leukoplakia (OHL) in immunosuppressed patients. However, the cellular mechanism(s) that enable EBV to establish exclusively lytic infection in normal differentiated oral epithelial cells are not currently understood. Here we show that a cellular transcription factor known to promote epithelial cell differentiation, KLF4, induces differentiation-dependent lytic EBV infection by binding to and activating the two EBV immediate-early gene (BZLF1 and BRLF1) promoters. We demonstrate that latently EBV-infected, telomerase-immortalized normal oral keratinocyte (NOKs) cells undergo lytic viral reactivation confined to the more differentiated cell layers in organotypic raft culture. Furthermore, we show that endogenous KLF4 expression is required for efficient lytic viral reactivation in response to phorbol ester and sodium butyrate treatment in several different EBV-infected epithelial cell lines, and that the combination of KLF4 and another differentiation-dependent cellular transcription factor, BLIMP1, is highly synergistic for inducing lytic EBV infection. We confirm that both KLF4 and BLIMP1 are expressed in differentiated, but not undifferentiated, epithelial cells in normal tongue tissue, and show that KLF4 and BLIMP1 are both expressed in a patient-derived OHL lesion. In contrast, KLF4 protein is not detectably expressed in B cells, where EBV normally enters latent infection, although KLF4 over-expression is sufficient to induce lytic EBV reactivation in Burkitt lymphoma cells. Thus, KLF4, together with BLIMP1, plays a critical role in mediating lytic EBV reactivation in epithelial cells. PMID:26431332

  8. The Ets transcription factor EHF as a regulator of cornea epithelial cell identity.

    PubMed

    Stephens, Denise N; Klein, Rachel Herndon; Salmans, Michael L; Gordon, William; Ho, Hsiang; Andersen, Bogi

    2013-11-29

    The cornea is the clear, outermost portion of the eye composed of three layers: an epithelium that provides a protective barrier while allowing transmission of light into the eye, a collagen-rich stroma, and an endothelium monolayer. How cornea development and aging is controlled is poorly understood. Here we characterize the mouse cornea transcriptome from early embryogenesis through aging and compare it with transcriptomes of other epithelial tissues, identifying cornea-enriched genes, pathways, and transcriptional regulators. Additionally, we profiled cornea epithelium and stroma, defining genes enriched in these layers. Over 10,000 genes are differentially regulated in the mouse cornea across the time course, showing dynamic expression during development and modest expression changes in fewer genes during aging. A striking transition time point for gene expression between postnatal days 14 and 28 corresponds with completion of cornea development at the transcriptional level. Clustering classifies co-expressed, and potentially co-regulated, genes into biologically informative categories, including groups that exhibit epithelial or stromal enriched expression. Based on these findings, and through loss of function studies and ChIP-seq, we show that the Ets transcription factor EHF promotes cornea epithelial fate through complementary gene activating and repressing activities. Furthermore, we identify potential interactions between EHF, KLF4, and KLF5 in promoting cornea epithelial differentiation. These data provide insights into the mechanisms underlying epithelial development and aging, identifying EHF as a regulator of cornea epithelial identity and pointing to interactions between Ets and KLF factors in promoting epithelial fate. Furthermore, this comprehensive gene expression data set for the cornea is a powerful tool for discovery of novel cornea regulators and pathways. PMID:24142692

  9. Macrophages regulate expression of α1,2-fucosyltransferase genes in human endometrial epithelial cells.

    PubMed

    Nakamura, Hitomi; Jasper, Melinda J; Hull, M Louise; Aplin, John D; Robertson, Sarah A

    2012-04-01

    The epithelial cell surface of the endometrium undergoes substantial biochemical changes to allow embryo attachment and implantation in early pregnancy. We hypothesized that tissue macrophages influence these events to promote uterine receptivity. To investigate the role of macrophages in regulating epithelial cell expression of genes linked to glycan-mediated embryo adhesion, Ishikawa, RL95-2 and HEC1A endometrial epithelial cells were cultured alone or with unactivated or lipopolysaccharide-activated monocytic U937 cells, separated using transwell inserts. Expression of mRNAs encoding two α1,2-fucosyltransferases (FUT1, FUT2) was increased in all three epithelial cell lines following co-culture with U937 cells, and was associated with increased fucosylation of cell surface glycoproteins detected using lectins from Ulex europaeus (UEA-1) and Dolichos biflorus (DBA). FUT1 induction by U937 cells also occurred in primary endometrial epithelial cells collected in luteal but not proliferative phase. Activation of the interleukin-6 (IL6)/leukemia inhibitory factor (LIF) cytokine signaling pathway with phosphorylation of STAT3 and elevated SOCS3 mRNA expression was evident in epithelial cells stimulated by U937 co-culture. Several recombinant macrophage-secreted cytokines exerted stimulatory or inhibitory effects on FUT1 and FUT2 mRNA expression, and the macrophage-derived cytokine LIF partially replicated the effects of U937 cells on both FUT1 and FUT2 expression and UEA-1 and DBA lectin reactivity in Ishikawa cells. These results suggest that macrophage-derived factors including LIF might facilitate development of an implantation-receptive endometrium by regulating surface glycan structures in epithelial cells. Abnormal phenotypes or altered abundance of uterine macrophages could contribute to the pathophysiology of primary unexplained infertility in women. PMID:22053055

  10. The Ets Transcription Factor EHF as a Regulator of Cornea Epithelial Cell Identity*

    PubMed Central

    Stephens, Denise N.; Klein, Rachel Herndon; Salmans, Michael L.; Gordon, William; Ho, Hsiang; Andersen, Bogi

    2013-01-01

    The cornea is the clear, outermost portion of the eye composed of three layers: an epithelium that provides a protective barrier while allowing transmission of light into the eye, a collagen-rich stroma, and an endothelium monolayer. How cornea development and aging is controlled is poorly understood. Here we characterize the mouse cornea transcriptome from early embryogenesis through aging and compare it with transcriptomes of other epithelial tissues, identifying cornea-enriched genes, pathways, and transcriptional regulators. Additionally, we profiled cornea epithelium and stroma, defining genes enriched in these layers. Over 10,000 genes are differentially regulated in the mouse cornea across the time course, showing dynamic expression during development and modest expression changes in fewer genes during aging. A striking transition time point for gene expression between postnatal days 14 and 28 corresponds with completion of cornea development at the transcriptional level. Clustering classifies co-expressed, and potentially co-regulated, genes into biologically informative categories, including groups that exhibit epithelial or stromal enriched expression. Based on these findings, and through loss of function studies and ChIP-seq, we show that the Ets transcription factor EHF promotes cornea epithelial fate through complementary gene activating and repressing activities. Furthermore, we identify potential interactions between EHF, KLF4, and KLF5 in promoting cornea epithelial differentiation. These data provide insights into the mechanisms underlying epithelial development and aging, identifying EHF as a regulator of cornea epithelial identity and pointing to interactions between Ets and KLF factors in promoting epithelial fate. Furthermore, this comprehensive gene expression data set for the cornea is a powerful tool for discovery of novel cornea regulators and pathways. PMID:24142692

  11. Survivin expression is associated with lens epithelial cell proliferation and fiber cell differentiation

    PubMed Central

    Mansergh, Fiona C.; Boulton, Michael E.; Gunhaga, Lena

    2012-01-01

    Purpose Survivin (Birc5) is the smallest member of the inhibitor of apoptosis (IAP) protein family, which regulates the cell cycle/apoptosis balance. The purpose of this study was to examine Survivin expression in the embryonic chick lens, in chick lens epithelial cell cultures, and in the postnatal mouse lens. Methods Survivin expression was examined using a combination of quantitative real-time polymerase chain reaction, western blotting, and immunocytochemistry. To correlate Survivin expression with the timing of proliferation, we determined the profile of cell proliferation in the developing lens using the cell cycle marker proliferating cell nuclear antigen (PCNA) in quantitative western blotting and immunocytochemistry studies. We also examined the expression of PCNA and the extent of denucleation using terminal deoxynucleotidyl transferase (TdT)-mediated biotin-dUTP nick-end labeling (TUNEL) of lentoids (lens fiber-like cells) during chick lens epithelial cell differentiation in vitro. Results At embryonic day (ED) 4, Survivin immunostaining was present in two pools in lens epithelial cells and fiber cells: cytoplasmic and nuclear. The nuclear staining became more pronounced as the lens epithelial cells differentiated into lens fiber cells. At ED12, Survivin staining was observed in lens fiber cell nuclei containing marginalized chromatin, indicative of early denucleation events. Using western blotting, Survivin expression peaked at ED6, diminishing thereafter. This profile of expression correlated with the events in chick lens epithelial cell cultures: i) increased Survivin expression was associated with an increase in PCNA staining up to day 6 of culture and ii) downregulation of Survivin expression at day 8 of culture was coincident with a dramatic decrease in PCNA staining and an increase in TdT-mediated biotin-dUTP nick-end labeling in lentoids. In early postnatal mouse lenses, Survivin and PCNA were highly expressed and decreased thereafter during

  12. General Information about Ovarian Epithelial Cancer

    MedlinePlus

    ... Primary Peritoneal Cancer Treatment (PDQ®)–Patient Version General Information About Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  13. Respiratory epithelial cysts of the orbit.

    PubMed

    Goh, Rachel L Z; Hardy, Thomas G; Williams, Richard A; McNab, Alan A

    2016-10-01

    To describe post-traumatic and congenital respiratory epithelial cysts in the orbit, which are rare lesions with only 5 and 13 published cases, respectively. We reviewed all cases of respiratory epithelial cysts diagnosed at three institutions (two tertiary referral hospitals, one private clinic) between 1995 and 2015. We describe 10 cases of post-traumatic respiratory epithelial cyst (age range 23 - 82), presenting a mean of 17.4 years after their original trauma; and 3 congenital cases (age range 17-34). All but one case underwent surgical excision of the cyst and its lining, along with any surgical implant within the cyst. Two were recurrent after incomplete excision. Three presented with acute infection within the cyst. Respiratory epithelial orbital cysts are probably commoner than the paucity of published reports would suggest. Post-traumatic cysts often present many years after trauma, and may become secondarily infected. Complete surgical removal is recommended to prevent future recurrence. PMID:27468088

  14. Misexpression of ELF5 Disrupts Lung Branching and Inhibits Epithelial Differentiation

    PubMed Central

    Metzger, David E.; Stahlman, Mildred T.; Shannon, John M.

    2008-01-01

    ELF5, an Ets family transcription factor found exclusively in epithelial cells, is expressed in the distal lung epithelium during embryogenesis, then becomes restricted to proximal airways at the end of gestation and postnatally. To test the hypothesis that ELF5 represses distal epithelial differentiation, we generated a transgenic mouse model in which a doxycycline inducible HA-tagged mouse Elf5 transgene was placed under the control of the lung epithelium-specific human SFTPC promoter. We found that expressing high levels of ELF5 during early lung development disrupted branching morphogenesis and produced a dilated epithelium. The effects of ELF5 on morphogenesis were stage dependent, since inducing the transgene on E16.5 had no effect on branching. ELF5 reduced expression of the distal lung epithelial differentiation markers Erm, Napsa and Sftpc, and type II cell ultrastructural differentiation was immature. ELF5 overexpression did not induce the proximal airway epithelial markers Ccsp and Foxj1, but did induce expression of p63, a marker of basal cells in the trachea and esophagus. High ELF5 levels also induced the expression of genes found in other endodermal epithelia but not normally associated with the lung. These results suggest that precise levels of ELF5 regulate the specification and differentiation of epithelial cells in the lung. PMID:18544451

  15. p120 catenin is required for normal tubulogenesis but not epithelial integrity in developing mouse pancreas

    PubMed Central

    Hendley, Audrey M.; Provost, Elayne; Bailey, Jennifer M.; Wang, Yue J.; Cleveland, Megan H.; Blake, Danielle; Bittman, Ross W.; Roeser, Jeffrey C.; Maitra, Anirban; Reynolds, Albert B.; Leach, Steven D.

    2015-01-01

    The intracellular protein p120 catenin aids in maintenance of cell-cell adhesion by regulating E-cadherin stability in epithelial cells. In an effort to understand the biology of p120 catenin in pancreas development, we ablated p120 catenin in mouse pancreatic progenitor cells, which resulted in deletion of p120 catenin in all epithelial lineages of the developing mouse pancreas: islet, acinar, centroacinar, and ductal. Loss of p120 catenin resulted in formation of dilated epithelial tubules, expansion of ductal epithelia, loss of acinar cells, and the induction of pancreatic inflammation. Aberrant branching morphogenesis and tubulogenesis were also observed. Throughout development, the phenotype became more severe, ultimately resulting in an abnormal pancreas comprised primarily of duct-like epithelium expressing early progenitor markers. In pancreatic tissue lacking p120 catenin, overall epithelial architecture remained intact; however, actin cytoskeleton organization was disrupted, an observation associated with increased cytoplasmic PKCζ. Although we observed reduced expression of adherens junction proteins E-cadherin, β-catenin, and α-catenin, p120 catenin family members p0071, ARVCF, and δ-catenin remained present at cell membranes in homozygous p120f/f pancreases, potentially providing stability for maintenance of epithelial integrity during development. Adult mice homozygous for deletion of p120 catenin displayed dilated main pancreatic ducts, chronic pancreatitis, acinar to ductal metaplasia (ADM), and mucinous metaplasia that resembles PanIN1a. Taken together, our data demonstrate an essential role for p120 catenin in pancreas development. PMID:25523391

  16. Alveolar epithelial disintegrity in pulmonary fibrosis.

    PubMed

    Kulkarni, Tejaswini; de Andrade, Joao; Zhou, Yong; Luckhardt, Tracy; Thannickal, Victor J

    2016-08-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive decline in lung function, resulting in significant morbidity and mortality. Current concepts of the pathogenesis of IPF primarily center on dysregulated epithelial cell repair and altered epithelial-mesenchymal communication and extracellular matrix deposition following chronic exposure to cigarette smoke or environmental toxins. In recent years, increasing attention has been directed toward the role of the intercellular junctional complex in determining the specific properties of epithelia in pulmonary diseases. Additionally, recent genomewide association studies suggest that specific genetic variants predictive of epithelial cell dysfunction may confer susceptibility to the development of sporadic idiopathic pulmonary fibrosis. A number of genetic disorders linked to pulmonary fibrosis and familial interstitial pneumonias are associated with loss of epithelial integrity. However, the potential links between extrapulmonary clinical syndromes associated with defects in epithelial cells and the development of pulmonary fibrosis are not well understood. Here, we report a case of hereditary mucoepithelial dysplasia that presented with pulmonary fibrosis and emphysema on high-resolution computed tomography. This case illustrates a more generalizable concept of epithelial disintegrity in the development of fibrotic lung diseases, which is explored in greater detail in this review article. PMID:27233996

  17. Medullary thymic epithelial stem cells: role in thymic epithelial cell maintenance and thymic involution.

    PubMed

    Hamazaki, Yoko; Sekai, Miho; Minato, Nagahiro

    2016-05-01

    The thymus consists of two distinct anatomical regions, the cortex and the medulla; medullary thymic epithelial cells (mTECs) play a crucial role in establishing central T-cell tolerance for self-antigens. Although the understanding of mTEC development in thymic organogenesis as well as the regulation of their differentiation and maturation has improved, the mechanisms of postnatal maintenance remain poorly understood. This issue has a central importance in immune homeostasis and physiological thymic involution as well as autoimmune disorders in various clinicopathological settings. Recently, several reports have demonstrated the existence of TEC stem or progenitor cells in the postnatal thymus, which are either bipotent or unipotent. We identified stem cells specified for mTEC-lineage that are generated in the thymic ontogeny and may sustain mTEC regeneration and lifelong central T-cell self-tolerance. This finding suggested that the thymic medulla is maintained autonomously by its own stem cells. Although several issues, including the relationship with other putative TEC stem/progenitors, remain unclear, further examination of mTEC stem cells (mTECSCs) and their regulatory mechanisms may contribute to the understanding of postnatal immune homeostasis. Possible relationships between decline of mTECSC activity and early thymic involution as well as various autoimmune disorders are discussed. PMID:27088906

  18. p120 Catenin Suppresses Basal Epithelial Cell Extrusion in Invasive Pancreatic Neoplasia.

    PubMed

    Hendley, Audrey M; Wang, Yue J; Polireddy, Kishore; Alsina, Janivette; Ahmed, Ishrat; Lafaro, Kelly J; Zhang, Hao; Roy, Nilotpal; Savidge, Samuel G; Cao, Yanna; Hebrok, Matthias; Maitra, Anirban; Reynolds, Albert B; Goggins, Michael; Younes, Mamoun; Iacobuzio-Donahue, Christine A; Leach, Steven D; Bailey, Jennifer M

    2016-06-01

    Aberrant regulation of cellular extrusion can promote invasion and metastasis. Here, we identify molecular requirements for early cellular invasion using a premalignant mouse model of pancreatic cancer with conditional knockout of p120 catenin (Ctnnd1). Mice with biallelic loss of p120 catenin progressively develop high-grade pancreatic intraepithelial neoplasia (PanIN) lesions and neoplasia accompanied by prominent acute and chronic inflammatory processes, which is mediated, in part, through NF-κB signaling. Loss of p120 catenin in the context of oncogenic Kras also promotes remarkable apical and basal epithelial cell extrusion. Abundant single epithelial cells exit PanIN epithelium basally, retain epithelial morphology, survive, and display features of malignancy. Similar extrusion defects are observed following p120 catenin knockdown in vitro, and these effects are completely abrogated by the activation of S1P/S1pr2 signaling. In the context of oncogenic Kras, p120 catenin loss significantly reduces expression of genes mediating S1P/S1pr2 signaling in vivo and in vitro, and this effect is mediated at least, in part, through activation of NF-κB. These results provide insight into mechanisms controlling early events in the metastatic process and suggest that p120 catenin and S1P/S1pr2 signaling enhance cancer progression by regulating epithelial cell invasion. Cancer Res; 76(11); 3351-63. ©2016 AACR. PMID:27032419

  19. Characterization of Long-Term Cultured Murine Submandibular Gland Epithelial Cells

    PubMed Central

    Tsunoda, Kazuyuki; Nakagawa, Taneaki; Tsubota, Kazuo

    2016-01-01

    Purpose Human and rat salivary gland cell lines derived from tumors or genetic modification are currently available for research. Here, we attempted to culture and characterize long-term cultured cells spontaneously derived from wild type murine submandibular glands (SGs). Methods SGs were removed from 3-week-old C57B/6J female mice and dissociated by collagenase type 1 and hyaluronidase digestion. Isolated SG epithelial cells were cultured in low calcium, serum-free growth media in the presence of cholera toxin (CT) during early passages. Single-cell colonies were isolated by limiting dilution culture after 25 passages. Early- and late-stage cell cultures were characterized for keratin 14, keratin 18, α-smooth muscle actin, and p63 by immunostaining and quantitative real-time PCR analysis. Results SG epithelial cells cultured in optimized media maintained their proliferative ability and morphology for over 80 passages. Long-term cultured cells expressed keratin 14, keratin 18, and p63, indicative of an epithelial phenotype. Conclusions Epithelial cells originating from wild type murine SGs could be cultured for longer periods of time and remain phenotypically similar to ductal basal epithelium. PMID:26800086

  20. N-acetylcysteine improves redox status, mitochondrial dysfunction, mucin-depleted crypts and epithelial hyperplasia in dextran sulfate sodium-induced oxidative colitis in mice.

    PubMed

    Amrouche-Mekkioui, Ilhem; Djerdjouri, Bahia

    2012-09-15

    The effect of N-acetylcysteine (NAC), a pharmacological antioxidant was investigated in a murine model of chronic colitis. Male NMRI mice were given 5% dextran sulfate sodium (DSS) in drinking water for 5 days followed by 10 days of water, three times. Compared to control mice given water, DSS-treated mice displayed severe imbalanced redox status with decreased glutathione and catalase, but increased malondialdehyde, protein carbonyls, nitric oxide and myeloperoxidase levels, at days 35th (active colitis) and 45th (recovery period). It also resulted in mitochondrial dysfunction, mucosal ulcers, mucin-depleted crypts and epithelial cell apoptosis. Crypt abscesses and glandular hyperplasia occurred selectively in distal colon. NAC (150 mg/kg) given in drinking water for 45 days along with 3 DSS cycles improved the hallmarks of DSS-colitis. Interestingly, the moderate impact of NAC on lipids and proteins oxidation correlated with myeloperoxidase and nitric oxide levels.NAC as a mucoregulator and a thiol restoring agent is protective on oxidative crypt alterations, mucin depletion, epithelial cell hyperplasia and apoptosis. Taken together, our results highlight the role of NAC as a scavenger of phagocytes-derived reactive oxygen species in mice DDS-colitis, suggesting that a long term NAC diet might be beneficial in inflammatory bowel diseases and colorectal cancer. PMID:22732651

  1. Epithelial phenotype in total sclerocornea

    PubMed Central

    Yeh, Lung-Kun; Chen, Hung-Chi; Chang, Anna Marie; Ho, Yi-Ju; Chang, Shirley H.L.; Yang, Unique

    2014-01-01

    Purpose To understand whether the epithelial phenotype in total sclerocornea is corneal or conjunctival in origin. Methods Four cases of total sclerocornea (male:female = 1:3; mean age = 5.4±4.3; 1–11 years old) who received penetrating keratoplasty (PKP) at our hospital between 2008 and 2011 were included. Corneal buttons obtained during PKP were used for transmission electron microscopy (TEM) as well as immunoconfocal microscopy for cytokeratins 3, 12, and 13, goblet cell mucin MUC5AC, connexin 43, stem cell markers p63 and ABCG2, laminin-5, and fibronectin. Results After a mean follow-up period of 38.8±14.0 (12–54) months, the grafts remained clear in half of the patients. TEM examination revealed a markedly attenuated Bowman’s layer in the scleralized corneas, with irregular and variably thinned collagen lamellar layers, and disorganization and random distribution of collagen fibrils, which were much larger in diameter compared with a normal cornea. Immunoconfocal microscopy showed that keratin 3 was expressed in all four patients, while p63, ABCG2, and MUC5AC were all absent. Cornea-specific keratin 12 was universally expressed in Patients 1 to 3, while mucosa (including conjunctiva)-specific keratin 13 was negative in these patients. Interestingly, keratin 12 and 13 were expressed in Patient 4 in a mutually exclusive manner. Linear expression of laminin-5 in the basement membrane zone and similar expression of fibronectin were observed. Conclusions The epithelia in total sclerocornea are essentially corneal in phenotype, but in the event of massive corneal angiogenesis, invasion by the conjunctival epithelium is possible. PMID:24744607

  2. Protective effects of Lactobacillus plantarum on epithelial barrier disruption caused by enterotoxigenic Escherichia coli in intestinal porcine epithelial cells.

    PubMed

    Wu, Yunpeng; Zhu, Cui; Chen, Zhuang; Chen, Zhongjian; Zhang, Weina; Ma, Xianyong; Wang, Li; Yang, Xuefen; Jiang, Zongyong

    2016-04-01

    Tight junctions (TJs) play an important role in maintaining the mucosal barrier function and gastrointestinal health of animals. Lactobacillus plantarum (L. plantarum) was reported to protect the intestinal barrier function of early-weaned piglets against enterotoxigenic Escherichia coli (ETEC) K88 challenge; however, the underlying cellular mechanism of this protection was unclear. Here, an established intestinal porcine epithelia cell (IPEC-J2) model was used to investigate the protective effects and related mechanisms of L. plantarum on epithelial barrier damages induced by ETEC K88. Epithelial permeability, expression of inflammatory cytokines, and abundance of TJ proteins, were determined. Pre-treatment with L. plantarum for 6h prevented the reduction in transepithelial electrical resistance (TEER) (P<0.05), inhibited the increased transcript abundances of interleukin-8 (IL-8) and tumor necrosis factor (TNF-α) (P<0.05), decreased expression of claudin-1, occludin and zonula occludens (ZO-1) (P<0.05) and protein expression of occludin (P<0.05) of IPEC-J2 cells caused by ETEC K88. Moreover, the mRNA expression of negative regulators of toll-like receptors (TLRs) [single Ig Il-1-related receptor (SIGIRR), B-cell CLL/lymphoma 3 (Bcl3), and mitogen-activated protein kinase phosphatase-1 (MKP-1)] in IPEC-J2 cells pre-treated with L. plantarum were higher (P<0.05) compared with those in cells just exposed to K88. Furthermore, L. plantarum was shown to regulate proteins of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. These results indicated that L. plantarum may improve epithelial barrier function by maintenance of TEER, inhibiting the reduction of TJ proteins, and reducing the expression of proinflammatory cytokines induced by ETEC K88, possibly through modulation of TLRs, NF-κB and MAPK pathways. PMID:27032504

  3. Retinoic acid promotes primary fetal alveolar epithelial type II cell proliferation and differentiation to alveolar epithelial type I cells.

    PubMed

    Gao, Rui-wei; Kong, Xiang-yong; Zhu, Xiao-xi; Zhu, Guo-qing; Ma, Jin-shuai; Liu, Xiu-xiang

    2015-05-01

    Retinoic acid (RA) plays an important role in lung development and maturation. Many stimuli can induce alveolar epithelial cell damage which will result in the injury of lung parenchyma. The aim of this study was to observe the effect of RA on the proliferation and differentiation of primary fetal alveolar epithelial type II cells (fAECIIs). Primary fAECIIs were isolated from fetal rats at 19 d of gestation and purified by a differential centrifugation and adhesion method. The cells were randomly divided into control (dimethyl sulfoxide, DMSO) and RA groups. Cell proliferation, viability, apoptosis, cycle, and expression of target protein were examined at 24, 48, and 72 h. We found that the proliferation and viability of cells in the RA-exposed group significantly increased compared with the DMSO control group. The proportion (%) of cells in the G2 and S phases in the RA group was significantly higher than that in control group cells. The proportion (%) of both early apoptotic cells and late apoptotic cells decreased significantly in cells exposed to RA compared with cells exposed to DMSO. RA significantly enhanced the expression of aquaporin 5 (AQP5). The expression level of pulmonary surfactant C (SPC) was elevated after cells were exposed to RA for 24 and 72 h but was inhibited when cells were exposed to RA for 48 h. These results suggest that RA promotes fAECII proliferation by improving cell viability, promoting S phase entry and inhibiting apoptosis and RA promotes fAECIIs differentiation to alveolar epithelial type I cells (AECIs). PMID:25515249

  4. The role of surgery in advanced epithelial ovarian cancer

    PubMed Central

    Martín-Cameán, María; Delgado-Sánchez, Elsa; Piñera, Antonio; Diestro, Maria Dolores; De Santiago, Javier; Zapardiel, Ignacio

    2016-01-01

    Nowadays, the standard management of advanced epithelial ovarian cancer is correct surgical staging and optimal tumour cytoreduction followed by platinum and taxane-based chemotherapy. Standard surgical staging consists of peritoneal washings, total hysterectomy, and bilateral salpingo-oophorectomy, inspection of all abdominal organs and the peritoneal surface, biopsies of suspicious areas or randomised biopsies if they are not present, omentectomy and para-aortic lymphadenectomy. After this complete surgical staging, the International Federation of Gynaecology and Obstetrics (FIGO) staging system for ovarian cancer is applied to determine the management and prognosis of the patient. Complete tumour cytoreduction has shown an improvement in survival. There are some criteria to predict cytoreduction outcomes based on serum biomarkers levels, preoperative imaging techniques, and laparoscopic-based scores. Optimised patient selection for primary cytoreduction would determine patients who could benefit from an optimal cytoreduction and might benefit from interval surgery. The administration of intraperitoneal chemotherapy after debulking surgery has shown an increase in progression-free survival and overall survival, especially in patients with no residual disease after surgery. It is considered that 3–17% of all epithelial ovarian carcinoma (EOC) occur in young women that have not fulfilled their reproductive desires. In these patients, fertility-sparing surgery is a worthy option in early ovarian cancer. PMID:27594911

  5. Role of uterine stromal-epithelial crosstalk in embryo implantation.

    PubMed

    Hantak, Alison M; Bagchi, Indrani C; Bagchi, Milan K

    2014-01-01

    Embryo implantation is a crucial step for successful pregnancy. Prior to implantation, the luminal epithelium undergoes steroid hormone-induced structural and functional changes that render it competent for embryo attachment. Subsequent invasion of the embryo into the maternal tissue triggers differentiation of the underlying stromal cells to form the decidua, a transient tissue which supports the developing embryo. Many molecular cues of both stromal and epithelial origin have been identified that are critical mediators of this process. An important aspect of uterine biology is the elaborate crosstalk that occurs between these tissue compartments during early pregnancy through expression of paracrine factors regulated by the steroid hormones estrogen and progesterone. Aberrant expression of these factors often leads to implantation failure and infertility. Genetically-engineered mouse models have been instrumental in elucidating what these paracrine factors are, what drives their expression, and what their effects are on neighboring cells. This review provides an overview of several well-characterized signaling pathways that span both epithelial and stromal compartments and their function during implantation in the mouse. PMID:25023679

  6. Characteristics of Long-Term Survivors of Epithelial Ovarian Cancer

    PubMed Central

    Cress, Rosemary D.; Chen, Yingjia S.; Morris, Cyllene R.; Petersen, Megan; Leiserowitz, Gary S.

    2015-01-01

    Objective To identify characteristics associated with long-term survival forepithelial ovarian cancer patients using the California Cancer Registry. Methods A descriptive analysis of survival of all California residents diagnosed with epithelial ovarian cancer between 1994 and 2001 was conducted using patients identified through the cancer registry with follow up through 2011. Characteristics of the patients who survived more than 10 years (long-term survivors) were compared to three other cohorts: patients who survived less than 2 years, those who survived at least 2 but no more than 5 years, and those who survived at least 5 but no more than 10 years. Results A total of 3,582 out of 11,541 (31% CI=30.2%, 31.8%) of the patients survived more than 10 years. Younger age, early stage, low-grade, and non-serous histology were significant predictors of long-term survival, but long-term survivors also included women with high-risk cancer. Conclusion Long-term survival is not unusual in patients with epithelial ovarian cancer, even in those with high-risk disease. Many of the prognostic factors are well known, but it remains to be determined why some patients with advanced stage high-grade cancers survive longer than others with the same histology. These findings are important for patient counseling. PMID:26244529

  7. The role of surgery in advanced epithelial ovarian cancer.

    PubMed

    Martín-Cameán, María; Delgado-Sánchez, Elsa; Piñera, Antonio; Diestro, Maria Dolores; De Santiago, Javier; Zapardiel, Ignacio

    2016-01-01

    Nowadays, the standard management of advanced epithelial ovarian cancer is correct surgical staging and optimal tumour cytoreduction followed by platinum and taxane-based chemotherapy. Standard surgical staging consists of peritoneal washings, total hysterectomy, and bilateral salpingo-oophorectomy, inspection of all abdominal organs and the peritoneal surface, biopsies of suspicious areas or randomised biopsies if they are not present, omentectomy and para-aortic lymphadenectomy. After this complete surgical staging, the International Federation of Gynaecology and Obstetrics (FIGO) staging system for ovarian cancer is applied to determine the management and prognosis of the patient. Complete tumour cytoreduction has shown an improvement in survival. There are some criteria to predict cytoreduction outcomes based on serum biomarkers levels, preoperative imaging techniques, and laparoscopic-based scores. Optimised patient selection for primary cytoreduction would determine patients who could benefit from an optimal cytoreduction and might benefit from interval surgery. The administration of intraperitoneal chemotherapy after debulking surgery has shown an increase in progression-free survival and overall survival, especially in patients with no residual disease after surgery. It is considered that 3-17% of all epithelial ovarian carcinoma (EOC) occur in young women that have not fulfilled their reproductive desires. In these patients, fertility-sparing surgery is a worthy option in early ovarian cancer. PMID:27594911

  8. [Stage III and IV epithelial ovarian cancers. Therapeutic problems].

    PubMed

    Picaud, A; Walter, P; Minko Mi Etoua, D; Faye, A; N'Sounda, C; Nlome Nze, A R; Lunven, B

    1992-01-01

    Between 1986 and 1989 (4 years), 11 epithelial malignant tumours of the ovary were treated in the department of gynecology and obstetrics of the Libreville teaching hospital group. Epithelial tumours accounted for 78 per cent of malignant tumours in the adult. Burkitt's lymphoma predominated in young girls. Cancer of the ovary takes sixth place among female cancers in Gabon, with an incidence identical to that of cancer of the liver. Cases involved stage III and IV malignancies. Four patients died (36 per cent) and seven are still alive (63.6 per cent) with a mean survival of 25 months at the time of the study (the longest living patient having a survival of 5 years). The fullest possible initial surgical excision is essential in ensuring the greater efficacy of polychemotherapy (including Cisplatin), the only guarantee of total second look surgery. Monitoring of residual disease was based upon ultrasonography. Pelvic radiotherapy was used in the presence of a residual pelvic mass measuring less than 3 cm. Future efforts must be direct towards early detection, in particular since more than 45 per cent of our patients were aged under 30. PMID:1565942

  9. Cingulin, a specific protein component of tight junctions, is expressed in normal and neoplastic human epithelial tissues.

    PubMed Central

    Citi, S.; Amorosi, A.; Franconi, F.; Giotti, A.; Zampi, G.

    1991-01-01

    Cingulin is a 140-kd protein localized on the cytoplasmic face of avian tight junctions. The expression of cingulin in human normal and neoplastic colonic tissue has been investigated with an antiserum against chicken cingulin. Human cingulin shares its apparent molecular mass and localization with avian cingulin. In normal colonic epithelium, villous adenomas, and differentiated adenocarcinomas, cingulin staining is observed in the junctional region of the polarized cells lining the surface, the crypts, and the glandular lumina. In poorly differentiated adenocarcinomas, labeling also is observed at the interface between cancer tissue and stroma, or in clumps of malignant cells, forming a pattern that highlights the presence of small, compressed lumina. The cingulin content of four adenocarcinomas, estimated by immunoblotting and densitometry, was higher than that of the normal tissue (150% to 230%). Cingulin was detected in a metastasis from a colon adenocarcinoma but not in nonepithelial tissues and neoplasias, suggesting that cingulin may be a useful marker in the characterization of colonic and probably other epithelial neoplasias. Images Figure 1 Figure 2 Figure 3 PMID:2012170

  10. B-Raf inhibitors induce epithelial differentiation in BRAF-mutant colorectal cancer cells.

    PubMed

    Herr, Ricarda; Köhler, Martin; Andrlová, Hana; Weinberg, Florian; Möller, Yvonne; Halbach, Sebastian; Lutz, Lisa; Mastroianni, Justin; Klose, Martin; Bittermann, Nicola; Kowar, Silke; Zeiser, Robert; Olayioye, Monilola A; Lassmann, Silke; Busch, Hauke; Boerries, Melanie; Brummer, Tilman

    2015-01-01

    BRAF mutations are associated with aggressive, less-differentiated and therapy-resistant colorectal carcinoma. However, the underlying mechanisms for these correlations remain unknown. To understand how oncogenic B-Raf contributes to carcinogenesis, in particular to aspects other than cellular proliferation and survival, we generated three isogenic human colorectal carcinoma cell line models in which we can dynamically modulate the expression of the B-Raf(V600E) oncoprotein. Doxycyclin-inducible knockdown of endogenous B-Raf(V600E) decreases cellular motility and invasion in conventional and three-dimensional (3D) culture, whereas it promotes cell-cell contacts and induces various hallmarks of differentiated epithelia. Importantly, all these effects are recapitulated by B-Raf (PLX4720, vemurafenib, and dabrafenib) or MEK inhibitors (trametinib). Surprisingly, loss of B-Raf(V600E) in HT29 xenografts does not only stall tumor growth, but also induces glandular structures with marked expression of CDX2, a tumor-suppressor and master transcription factor of intestinal differentiation. By performing the first transcriptome profiles of PLX4720-treated 3D cultures of HT29 and Colo-205 cells, we identify several upregulated genes linked to epithelial differentiation and effector functions, such as claudin-1, a Cdx-2 target gene encoding a critical tight junction component. Thereby, we provide a mechanism for the clinically observed correlation between mutant BRAF and the loss of Cdx-2 and claudin-1. PLX4720 also suppressed several metastasis-associated transcripts that have not been implicated as targets, effectors or potential biomarkers of oncogenic B-Raf signaling so far. Together, we identify a novel facet of clinically applied B-Raf or MEK inhibitors by showing that they promote cellular adhesion and differentiation of colorectal carcinoma cells. PMID:25381152

  11. Phenotype of circulating tumor cell: face-off between epithelial and mesenchymal masks.

    PubMed

    Hong, Yupeng; Zhang, Qi

    2016-05-01

    Most patients with cancers died of distant metastasis. It is always difficult to find cancer metastasis in early time, let alone to prevent or cure it. Currently, oncologists place high hopes on circulating tumor cell (CTC), which, compared to current imaging methods, is found more sensitive for early metastasis. Recently, techniques for CTC enrichment and identification are developing quickly. However, there are great challenges in the clinical interpretation of CTC assessments. Increasing studies have shown the heterogeneity of CTCs, which may play different roles in cancer metastasis. Epithelial-mesenchymal transition is not only the main mechanism of the cancer cells invading the circulation system but also a distinguished characteristic of CTCs. Investigators are trying to differentiate specific subgroups of CTCs that are truly responsible for cancer metastasis. Here, we reviewed the current evidences on epithelial-mesenchymal transition of CTCs from perspectives of enrichment methods, biology, and its subgroups. PMID:26758432

  12. Epithelial Cell Shedding and Barrier Function

    PubMed Central

    Williams, J. M.; Duckworth, C. A.; Burkitt, M. D.; Watson, A. J. M.; Campbell, B. J.

    2015-01-01

    The intestinal epithelium is a critical component of the gut barrier. Composed of a single layer of intestinal epithelial cells (IECs) held together by tight junctions, this delicate structure prevents the transfer of harmful microorganisms, antigens, and toxins from the gut lumen into the circulation. The equilibrium between the rate of apoptosis and shedding of senescent epithelial cells at the villus tip, and the generation of new cells in the crypt, is key to maintaining tissue homeostasis. However, in both localized and systemic inflammation, this balance may be disturbed as a result of pathological IEC shedding. Shedding of IECs from the epithelial monolayer may cause transient gaps or microerosions in the epithelial barrier, resulting in increased intestinal permeability. Although pathological IEC shedding has been observed in mouse models of inflammation and human intestinal conditions such as inflammatory bowel disease, understanding of the underlying mechanisms remains limited. This process may also be an important contributor to systemic and intestinal inflammatory diseases and gut barrier dysfunction in domestic animal species. This review aims to summarize current knowledge about intestinal epithelial cell shedding, its significance in gut barrier dysfunction and host-microbial interactions, and where research in this field is directed. PMID:25428410

  13. Epithelial dynamics of pancreatic branching morphogenesis

    PubMed Central

    Villasenor, Alethia; Chong, Diana C.; Henkemeyer, Mark; Cleaver, Ondine

    2010-01-01

    The mammalian pancreas is a highly branched gland, essential for both digestion and glucose homeostasis. Pancreatic branching, however, is poorly understood, both at the ultrastructural and cellular levels. In this article, we characterize the morphogenesis of pancreatic branches, from gross anatomy to the dynamics of their epithelial organization. We identify trends in pancreatic branch morphology and introduce a novel mechanism for branch formation, which involves transient epithelial stratification and partial loss of cell polarity, changes in cell shape and cell rearrangements, de novo tubulogenesis and epithelial tubule remodeling. In contrast to the classical epithelial budding and tube extension observed in other organs, a pancreatic branch takes shape as a multi-lumen tubular plexus coordinately extends and remodels into a ramifying, single-lumen ductal system. Moreover, our studies identify a role for EphB signaling in epithelial remodeling during pancreatic branching. Overall, these results illustrate distinct, step-wise cellular mechanisms by which pancreatic epithelium shapes itself to create a functional branching organ. PMID:21098570

  14. Epithelial repair mechanisms in the lung.

    PubMed

    Crosby, Lynn M; Waters, Christopher M

    2010-06-01

    The recovery of an intact epithelium following lung injury is critical for restoration of lung homeostasis. The initial processes following injury include an acute inflammatory response, recruitment of immune cells, and epithelial cell spreading and migration upon an autologously secreted provisional matrix. Injury causes the release of factors that contribute to repair mechanisms including members of the epidermal growth factor and fibroblast growth factor families (TGF-alpha, KGF, HGF), chemokines (MCP-1), interleukins (IL-1beta, IL-2, IL-4, IL-13), and prostaglandins (PGE(2)), for example. These factors coordinate processes involving integrins, matrix materials (fibronectin, collagen, laminin), matrix metalloproteinases (MMP-1, MMP-7, MMP-9), focal adhesions, and cytoskeletal structures to promote cell spreading and migration. Several key signaling pathways are important in regulating these processes, including sonic hedgehog, Rho GTPases, MAP kinase pathways, STAT3, and Wnt. Changes in mechanical forces may also affect these pathways. Both localized and distal progenitor stem cells are recruited into the injured area, and proliferation and phenotypic differentiation of these cells leads to recovery of epithelial function. Persistent injury may contribute to the pathology of diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. For example, dysregulated repair processes involving TGF-beta and epithelial-mesenchymal transition may lead to fibrosis. This review focuses on the processes of epithelial restitution, the localization and role of epithelial progenitor stem cells, the initiating factors involved in repair, and the signaling pathways involved in these processes. PMID:20363851

  15. Scattering attenuation microscopy of oral epithelial dysplasia

    NASA Astrophysics Data System (ADS)

    Tomlins, Pete H.; Adegun, Oluyori; Hagi-Pavli, Eleni; Piper, Kim; Bader, Dan; Fortune, Farida

    2010-11-01

    We present a new method for quantitative visualization of premalignant oral epithelium called scattering attenuation microscopy (SAM). Using low-coherence interferometry, SAM projects measurements of epithelial optical attenuation onto an image of the tissue surface as a color map. The measured attenuation is dominated by optical scattering that provides a metric of the severity of oral epithelial dysplasia (OED). Scattering is sensitive to the changes in size and distribution of nuclear material that are characteristic of OED, a condition recognized by the occurrence of basal-cell-like features throughout the epithelial depth. SAM measures the axial intensity change of light backscattered from epithelial tissue. Scattering measurements are obtained from sequential axial scans of a 3-D tissue volume and displayed as a 2-D SAM image. A novel segmentation method is used to confine scattering measurement to epithelial tissue. This is applied to oral biopsy samples obtained from 19 patients. Our results show that imaging of tissue scattering can be used to discriminate between different dysplastic severities and furthermore presents a powerful tool for identifying the most representative tissue site for biopsy.

  16. MicroRNA-145 Regulates Human Corneal Epithelial Differentiation

    PubMed Central

    Ng, Tsz-Kin; Huang, Li; Lei, Peng; Choy, Kwong-Wai; Liu, Yingpeng; Zhang, Mingzhi; Lam, Dennis Shun-Chiu; Yam, Gary Hin-Fai; Pang, Chi-Pui

    2011-01-01

    Background Epigenetic factors, such as microRNAs, are important regulators in the self-renewal and differentiation of stem cells and progenies. Here we investigated the microRNAs expressed in human limbal-peripheral corneal (LPC) epithelia containing corneal epithelial progenitor cells (CEPCs) and early transit amplifying cells, and their role in corneal epithelium. Methodology/Principal Findings Human LPC epithelia was extracted for small RNAs or dissociated for CEPC culture. By Agilent Human microRNA Microarray V2 platform and GeneSpring GX11.0 analysis, we found differential expression of 18 microRNAs against central corneal (CC) epithelia, which were devoid of CEPCs. Among them, miR-184 was up-regulated in CC epithelia, similar to reported finding. Cluster miR-143/145 was expressed strongly in LPC but weakly in CC epithelia (P = 0.0004, Mann-Whitney U-test). This was validated by quantitative polymerase chain reaction (qPCR). Locked nucleic acid-based in situ hybridization on corneal rim cryosections showed miR-143/145 presence localized to the parabasal cells of limbal epithelium but negligible in basal and superficial epithelia. With holoclone forming ability, CEPCs transfected with lentiviral plasmid containing mature miR-145 sequence gave rise to defective epithelium in organotypic culture and had increased cytokeratin-3/12 and connexin-43 expressions and decreased ABCG2 and p63 compared with cells transfected with scrambled sequences. Global gene expression was analyzed using Agilent Whole Human Genome Oligo Microarray and GeneSpring GX11.0. With a 5-fold difference compared to cells with scrambled sequences, miR-145 up-regulated 324 genes (containing genes for immune response) and down-regulated 277 genes (containing genes for epithelial development and stem cell maintenance). As validated by qPCR and luciferase reporter assay, our results showed miR-145 suppressed integrin β8 (ITGB8) expression in both human corneal epithelial cells and primary

  17. Tumor induction in the glandular stomach of rats after oral administration of a single or a few doses of N-methyl-N'-nitro-N-nitrosoguanidine during the newborn period.

    PubMed

    Sumi, Y; Miyakawa, M

    1978-12-01

    When N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was orally intubated to conventional newborn rats by the catheter technique, the rats were found with tumors almost exclusively developed in the glandular stomach, mostly until 280 days after the first intubation. Tumor incidence was about 50% in both sexs of rats that survived the intubation of a single dose of MNNG in rats of less than 24 hr after birth and almost 100% in both sexes of rats that survived the intubation of three consecutive daily doses of MNNG on 5th day after birth. Out of 52 rats treated with MNNG, 40.4% developed carcinomas (20 adenocarcinomas and 1 squamous cell carcinoma), three of them having metastatic lesions. The predilective localization of tumors in the glandular, especially fundic, portion of the stomach, might be attributed to the use of newborns and to the catheter technique devised here. PMID:750273

  18. Development of an Expert System as a Diagnostic Support of Cervical Cancer in Atypical Glandular Cells, Based on Fuzzy Logics and Image Interpretation

    PubMed Central

    Domínguez Hernández, Karem R.; Aguilar Lasserre, Alberto A.; Posada Gómez, Rubén; Palet Guzmán, José A.; González Sánchez, Blanca E.

    2013-01-01

    Cervical cancer is the second largest cause of death among women worldwide. Nowadays, this disease is preventable and curable at low cost and low risk when an accurate diagnosis is done in due time, since it is the neoplasm with the highest prevention potential. This work describes the development of an expert system able to provide a diagnosis to cervical neoplasia (CN) precursor injuries through the integration of fuzzy logics and image interpretation techniques. The key contribution of this research focuses on atypical cases, specifically on atypical glandular cells (AGC). The expert system consists of 3 phases: (1) risk diagnosis which consists of the interpretation of a patient's clinical background and the risks for contracting CN according to specialists; (2) cytology images detection which consists of image interpretation (IM) and the Bethesda system for cytology interpretation, and (3) determination of cancer precursor injuries which consists of in retrieving the information from the prior phases and integrating the expert system by means of a fuzzy logics (FL) model. During the validation stage of the system, 21 already diagnosed cases were tested with a positive correlation in which 100% effectiveness was obtained. The main contribution of this work relies on the reduction of false positives and false negatives by providing a more accurate diagnosis for CN. PMID:23690881

  19. Characterization and mechanism of (4S)-limonene synthase, a monoterpene cyclase from the glandular trichomes of peppermint (Mentha x piperita).

    PubMed

    Rajaonarivony, J I; Gershenzon, J; Croteau, R

    1992-07-01

    (4S)-Limonene synthase, a monoterpene cyclase isolated from the secretory cells of the glandular trichomes of Mentha x piperita (peppermint), catalyzes the cyclization of geranyl pyrophosphate to (4S)-limonene, a key intermediate in the biosynthesis of p-menthane monoterpenes in Mentha species. The enzyme synthesizes principally (-)-(4S)-limonene (greater than 94% of the total products), plus several other monoterpene olefins. The general properties of (4S)-limonene synthase resemble those of other monoterpene cyclases. The enzyme shows a pH optimum near 6.7, an isoelectric point of 4.35, and requires a divalent metal ion for catalysis, either Mg2+ or Mn2+, with Mn2+ preferred. The Km value measured for geranyl pyrophosphate was 1.8 microM. The activity of (4S)-limonene synthase was inhibited by sodium phosphate, sodium pyrophosphate, and reagents directed against the amino acids cysteine, methionine, and histidine. In the presence of Mn2+, geranyl pyrophosphate protected against cysteine-directed inhibition, suggesting that at least one cysteine residue is located at or near the active site. Experiments with alternate substrates and substrate analogs confirmed many elements of the proposed reaction mechanism, including the binding of geranyl pyrophosphate in the form of a complex with the divalent metal ion, the preliminary isomerization of geranyl pyrophosphate to linalyl pyrophosphate (a bound intermediate capable of cyclization), and the participation of a series of carbocation:pyrophosphate anion pairs in the reaction sequence. PMID:1605644

  20. Exposure dose reduction for the high energy spectrum in the photon counting mammography: simulation study based on Japanese breast glandularity and thickness

    NASA Astrophysics Data System (ADS)

    Niwa, Naoko; Yamazaki, Misaki; Kodera, Yoshie; Yamamuro, Mika; Yamada, Kanako; Asai, Yoshiyuki; Yamada, Koji

    2015-03-01

    Recently, digital mammography with a photon counting silicon detector has been developed. With the aim of reducing the exposure dose, we have proposed a new mammography system that uses a cadmium telluride series photon counting detector. In addition, we also propose to use a high energy X-ray spectrum with a tungsten anode. The purpose of this study was assessed that the effectiveness of the high X-ray energy spectrum in terms of image quality using a Monte Carlo simulation. The proposed photon counting system with the high energy X-ray is compared to a conventional flat panel detector system with a Mo/Rh spectrum. The contrast-to-noise ratio (CNR) is calculated from simulation images with the use of breast phantoms. The breast model phantoms differed by glandularity and thickness, which were determined from Japanese clinical mammograms. We found that the CNR values were higher in the proposed system than in the conventional system. The number of photons incident on the detector was larger in the proposed system, so that the noise values was lower in comparison with the conventional system. Therefore, the high energy spectrum yielded the same CNR as using the conventional spectrum while allowing a considerable dose reduction to the breast.

  1. Analysis of Natural and Induced Variation in Tomato Glandular Trichome Flavonoids Identifies a Gene Not Present in the Reference Genome[W][OPEN

    PubMed Central

    Kim, Jeongwoon; Matsuba, Yuki; Ning, Jing; Schilmiller, Anthony L.; Hammar, Dagan; Jones, A. Daniel; Pichersky, Eran; Last, Robert L.

    2014-01-01

    Flavonoids are ubiquitous plant aromatic specialized metabolites found in a variety of cell types and organs. Methylated flavonoids are detected in secreting glandular trichomes of various Solanum species, including the cultivated tomato (Solanum lycopersicum). Inspection of the sequenced S. lycopersicum Heinz 1706 reference genome revealed a close homolog of Solanum habrochaites MOMT1 3′/5′ myricetin O-methyltransferase gene, but this gene (Solyc06g083450) is missing the first exon, raising the question of whether cultivated tomato has a distinct 3′ or 3′/5′ O-methyltransferase. A combination of mining genome and cDNA sequences from wild tomato species and S. lycopersicum cultivar M82 led to the identification of Sl-MOMT4 as a 3′ O-methyltransferase. In parallel, three independent ethyl methanesulfonate mutants in the S. lycopersicum cultivar M82 background were identified as having reduced amounts of di- and trimethylated myricetins and increased monomethylated myricetin. Consistent with the hypothesis that Sl-MOMT4 is a 3′ O-methyltransferase gene, all three myricetin methylation defective mutants were found to have defects in MOMT4 sequence, transcript accumulation, or 3′-O-methyltransferase enzyme activity. Surprisingly, no MOMT4 sequence is found in the Heinz 1706 reference genome sequence, and this cultivar accumulates 3-methyl myricetin and is deficient in 3′-methyl myricetins, demonstrating variation in this gene among cultivated tomato varieties. PMID:25128240

  2. A comparison of mean glandular dose diagnostic reference levels within the all-digital Irish National Breast Screening Programme and the Irish Symptomatic Breast Services.

    PubMed

    O'Leary, Desiree; Rainford, Louise

    2013-03-01

    Data on image quality, compression and radiation dose were collected from symptomatic breast units within the Republic of Ireland. Quantitative and qualitative data were analysed using SPSS. Recommendations of mean glandular dose (MGD) diagnostic reference levels were made at various levels for film-screen and full field digital mammography units to match levels published worldwide. MGDs received by symptomatic breast patients within Ireland are higher than those received in the all-digital Irish Breast Screening service; 55-65 mm breast: 1.75 mGy (screening) vs. 2.4 mGy (symptomatic) at the 95th percentile; various reasons are proposed for the differences. MGDs achieved in the screening service may be lower because of the exacting requirements for radiographer training, characteristics of the patients and equipment quality assurance levels. More precise imaging guidelines, standards and training of symptomatic radiographers performing mammography are suggested to remediate MGDs delivered to the breasts of Irish women attending the symptomatic breast services. PMID:22740646

  3. Development and characterization of a primary culture of chicken embryonic tracheal epithelial cells and their use in avian studies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A major route of infection of avian influenza is through cells of the airway epithelium. To study the molecular mechanism of infection and early host responses we created a primary chicken tracheal cell culture. Epithelial cells were isolated from the trachea of 18 day old chicken embryos and cult...

  4. Uptake of /sup 3/H prednisolone by fetal lung explants: role of intercellular contacts in epithelial maturation

    SciTech Connect

    Leung, C.K.; Adamson, I.Y.; Bowden, D.H.

    1980-06-01

    Epithelial maturation in the developing lung is accelerated by glucocorticoids and it has been suggested that a fibroblast-derived factor may be important in regulating this response. In the present study, uptake of /sup 3/H prednisolone by cultured explants of fetal rat lung is used to correlate cellular location of the steroid with changes in epithelial--mesenchymal cell relationships at different stages of development. At days 17 and 18 of gestation, there is substantial incorporation of steroid by epithelial and interstitial cells with no morphologic evidence of accelerated maturation. At days 19 and 20, uptake of prednisolone is maximal with preferential incorporation by Type 2 cells which now contain an increased number of lamellar bodies. In the bronchioles, steroid uptake is observed in Clara cells but not in ciliated cells. Lung development results in a progressively closer anatomic relationship between alveolar epithelial and interstitial cells and at the time of maximal steroid response, day 19-20, narrow ''gap junctions'' are observed between these cell types. The results suggest that, although steroid is bound to several cell types from an early stage of development, the effects on epithelial maturation occur relatively late in gestation when close epithelial-mesenchymal cell contacts are made.

  5. Cell Chirality Induces Collective Cell Migration in Epithelial Sheets

    NASA Astrophysics Data System (ADS)

    Sato, Katsuhiko; Hiraiwa, Tetsuya; Shibata, Tatsuo

    2015-10-01

    During early development, epithelial cells form a monolayer sheet and migrate in a uniform direction. Here, we address how this collective migration can occur without breaking the cell-to-cell attachments. Repeated contraction and expansion of the cell-to-cell interfaces enables the cells to rearrange their positions autonomously within the sheet. We show that when the interface tension is strengthened in a direction that is tilted from the body axis, cell rearrangements occur in such a way that unidirectional movement is induced. We use a vertex model to demonstrate that such anisotropic tension can generate the unidirectional motion of cell sheets. Our results suggest that cell chirality facilitates collective cell migration during tissue morphogenesis.

  6. Intraosseous calcifying epithelial odontogenic (Pindborg) tumor: A rare entity

    PubMed Central

    More, Chandramani B; Vijayvargiya, Ritika

    2015-01-01

    Calcifying epithelial odontogenic tumor (CEOT) is a locally aggressive, rare benign odontogenic neoplasm that accounts for <1% of all odontogenic tumors. It was first described by a Dutch pathologist Jens Jorgen Pindborg in 1955. It is most often located in the posterior mandible. The tumor usually appears between the second and sixth decade of life and has no gender predilection. It is slow-growing neoplasm with a recurrence rate of 10–15% and with rare malignant transformation. Early diagnosis is essential to avoid oro-maxillofacial deformation and destruction. CEOT is rarely reported in India. We, herewith present a rare case of CEOT with unusual features associated with an impacted right third molar in the posterior mandible of 35 years male, with an emphasis on clinical, radiographic, histopathology and immunohistochemical features. PMID:26604515

  7. Expression of claudins -2 and -4 and cingulin is coordinated with the start of stratification and differentiation in corneal epithelial cells: retinoic acid reversibly disrupts epithelial barrier

    PubMed Central

    Ortiz-Melo, María Teresa; Sánchez-Guzmán, Erika; González-Robles, Arturo; Valdés, Jesús; Gómez-Flores, Eber; Castro-Muñozledo, Federico

    2013-01-01

    Summary Although tight junctions (TJ) have been extensively studied in simple epithelial cells, it is still unknown whether their organization is coupled to cell differentiation in stratified epithelia. We studied the expression of TJ in RCE1(5T5) cells, an in vitro model which mimics the sequential steps of rabbit corneal epithelial differentiation. RCE1(5T5) cells expressed TJ components which were assembled once cells constituted differentiated epithelia, as suggested by the increase of transepithelial electrical resistance (TER) which followed a similar kinetic to the expression of the early differentiation marker Pax-6. TJ were functional as indicated by the establishment of an epithelial barrier nonpermeable to ruthenium red or a biotin tracer. In immunostaining experiments, TJ were located at the superficial cells from the suprabasal layers; Western blot and RT-PCR suggested that TJ were composed of claudins (cldn) -1, -2, -4, cingulin (cgn), occludin (ocln) and ZO-1. Semi-quantitative RT-PCR and TER measurements showed that TJ became organized when cells began to form a 3–5 layers stratified epithelium; TER increased once cells reached confluence, with a time course comparable to the raise in the expression of cgn, cldn-2 and -4. Nevertheless, cldn-1, -2, ZO-1 and ocln were present in the cells from the beginning of cultivation, suggesting that TER increases mainly depend on TJ assembly. While EGF increased epithelial barrier strength, retinoic acid disrupted it, increasing paracellular flux about 2-fold; this effect was concentration dependent and completely reversible. Our results suggest that TJ assembly is tightly linked to the expression of corneal epithelial terminal phenotype. PMID:23429425

  8. Epithelial Cell Regulation of Allergic Diseases.

    PubMed

    Gour, Naina; Lajoie, Stephane

    2016-09-01

    Allergic diseases, which have escalated in prevalence in recent years, arise as a result of maladaptive immune responses to ubiquitous environmental stimuli. Why only certain individuals mount inappropriate type 2 immune responses to these otherwise harmless allergens has remained an unanswered question. Mounting evidence suggests that the epithelium, by sensing its environment, is the central regulator of allergic diseases. Once considered to be a passive barrier to allergens, epithelial cells at mucosal surfaces are now considered to be the cornerstone of the allergic diathesis. Beyond their function as maintaining barrier at mucosal surfaces, mucosal epithelial cells through the secretion of mediators like IL-25, IL-33, and TSLP control the fate of downstream allergic immune responses. In this review, we will discuss the advances in recent years regarding the process of allergen recognition and secretion of soluble mediators by epithelial cells that shape the development of the allergic response. PMID:27534656

  9. Gap geometry dictates epithelial closure efficiency

    PubMed Central

    Ravasio, Andrea; Cheddadi, Ibrahim; Chen, Tianchi; Pereira, Telmo; Ong, Hui Ting; Bertocchi, Cristina; Brugues, Agusti; Jacinto, Antonio; Kabla, Alexandre J.; Toyama, Yusuke; Trepat, Xavier; Gov, Nir; Neves de Almeida, Luís; Ladoux, Benoit

    2015-01-01

    Closure of wounds and gaps in tissues is fundamental for the correct development and physiology of multicellular organisms and, when misregulated, may lead to inflammation and tumorigenesis. To re-establish tissue integrity, epithelial cells exhibit coordinated motion into the void by active crawling on the substrate and by constricting a supracellular actomyosin cable. Coexistence of these two mechanisms strongly depends on the environment. However, the nature of their coupling remains elusive because of the complexity of the overall process. Here we demonstrate that epithelial gap geometry in both in vitro and in vivo regulates these collective mechanisms. In addition, the mechanical coupling between actomyosin cable contraction and cell crawling acts as a large-scale regulator to control the dynamics of gap closure. Finally, our computational modelling clarifies the respective roles of the two mechanisms during this process, providing a robust and universal mechanism to explain how epithelial tissues restore their integrity. PMID:26158873

  10. Epithelial-Mesenchymal Transition and Breast Cancer.

    PubMed

    Wu, Yanyuan; Sarkissyan, Marianna; Vadgama, Jaydutt V

    2016-01-01

    Breast cancer is the most common cancer in women and distant site metastasis is the main cause of death in breast cancer patients. There is increasing evidence supporting the role of epithelial-mesenchymal transition (EMT) in tumor cell progression, invasion, and metastasis. During the process of EMT, epithelial cancer cells acquire molecular alternations that facilitate the loss of epithelial features and gain of mesenchymal phenotype. Such transformation promotes cancer cell migration and invasion. Moreover, emerging evidence suggests that EMT is associated with the increased enrichment of cancer stem-like cells (CSCs) and these CSCs display mesenchymal characteristics that are resistant to chemotherapy and target therapy. However, the clinical relevance of EMT in human cancer is still under debate. This review will provide an overview of current evidence of EMT from studies using clinical human breast cancer tissues and its associated challenges. PMID:26821054

  11. Epithelial-Mesenchymal Transition and Breast Cancer

    PubMed Central

    Wu, Yanyuan; Sarkissyan, Marianna; Vadgama, Jaydutt V.

    2016-01-01

    Breast cancer is the most common cancer in women and distant site metastasis is the main cause of death in breast cancer patients. There is increasing evidence supporting the role of epithelial-mesenchymal transition (EMT) in tumor cell progression, invasion, and metastasis. During the process of EMT, epithelial cancer cells acquire molecular alternations that facilitate the loss of epithelial features and gain of mesenchymal phenotype. Such transformation promotes cancer cell migration and invasion. Moreover, emerging evidence suggests that EMT is associated with the increased enrichment of cancer stem-like cells (CSCs) and these CSCs display mesenchymal characteristics that are resistant to chemotherapy and target therapy. However, the clinical relevance of EMT in human cancer is still under debate. This review will provide an overview of current evidence of EMT from studies using clinical human breast cancer tissues and its associated challenges. PMID:26821054

  12. Gap geometry dictates epithelial closure efficiency.

    PubMed

    Ravasio, Andrea; Cheddadi, Ibrahim; Chen, Tianchi; Pereira, Telmo; Ong, Hui Ting; Bertocchi, Cristina; Brugues, Agusti; Jacinto, Antonio; Kabla, Alexandre J; Toyama, Yusuke; Trepat, Xavier; Gov, Nir; Neves de Almeida, Luís; Ladoux, Benoit

    2015-01-01

    Closure of wounds and gaps in tissues is fundamental for the correct development and physiology of multicellular organisms and, when misregulated, may lead to inflammation and tumorigenesis. To re-establish tissue integrity, epithelial cells exhibit coordinated motion into the void by active crawling on the substrate and by constricting a supracellular actomyosin cable. Coexistence of these two mechanisms strongly depends on the environment. However, the nature of their coupling remains elusive because of the complexity of the overall process. Here we demonstrate that epithelial gap geometry in both in vitro and in vivo regulates these collective mechanisms. In addition, the mechanical coupling between actomyosin cable contraction and cell crawling acts as a large-scale regulator to control the dynamics of gap closure. Finally, our computational modelling clarifies the respective roles of the two mechanisms during this process, providing a robust and universal mechanism to explain how epithelial tissues restore their integrity. PMID:26158873

  13. Odontogenic epithelial stem cells: hidden sources.

    PubMed

    Padma Priya, Sivan; Higuchi, Akon; Abu Fanas, Salem; Pooi Ling, Mok; Kumari Neela, Vasantha; Sunil, P M; Saraswathi, T R; Murugan, Kadarkarai; Alarfaj, Abdullah A; Munusamy, Murugan A; Kumar, Suresh

    2015-12-01

    The ultimate goal of dental stem cell research is to construct a bioengineered tooth. Tooth formation occurs based on the well-organized reciprocal interaction of epithelial and mesenchymal cells. The dental mesenchymal stem cells are the best explored, but because the human odontogenic epithelium is lost after the completion of enamel formation, studies on these cells are scarce. The successful creation of a bioengineered tooth is achievable only when the odontogenic epithelium is reconstructed to produce a replica of natural enamel. This article discusses the untapped sources of odontogenic epithelial stem cells in humans, such as those present in the active dental lamina in postnatal life, in remnants of dental lamina (the gubernaculum cord), in the epithelial cell rests of Malassez, and in reduced enamel epithelium. The possible uses of these stem cells in regenerative medicine, not just for enamel formation, are discussed. PMID:26367485

  14. Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells

    PubMed Central

    Celià-Terrassa, Toni; Meca-Cortés, Óscar; Mateo, Francesca; Martínez de Paz, Alexia; Rubio, Nuria; Arnal-Estapé, Anna; Ell, Brian J.; Bermudo, Raquel; Díaz, Alba; Guerra-Rebollo, Marta; Lozano, Juan José; Estarás, Conchi; Ulloa, Catalina; ρlvarez-Simón, Daniel; Milà, Jordi; Vilella, Ramón; Paciucci, Rosanna; Martínez-Balbás, Marian; García de Herreros, Antonio; Gomis, Roger R.; Kang, Yibin; Blanco, Jerónimo; Fernández, Pedro L.; Thomson, Timothy M.

    2012-01-01

    Malignant progression in cancer requires populations of tumor-initiating cells (TICs) endowed with unlimited self renewal, survival under stress, and establishment of distant metastases. Additionally, the acquisition of invasive properties driven by epithelial-mesenchymal transition (EMT) is critical for the evolution of neoplastic cells into fully metastatic populations. Here, we characterize 2 human cellular models derived from prostate and bladder cancer cell lines to better understand the relationship between TIC and EMT programs in local invasiveness and distant metastasis. The model tumor subpopulations that expressed a strong epithelial gene program were enriched in highly metastatic TICs, while a second subpopulation with stable mesenchymal traits was impoverished in TICs. Constitutive overexpression of the transcription factor Snai1 in the epithelial/TIC-enriched populations engaged a mesenchymal gene program and suppressed their self renewal and metastatic phenotypes. Conversely, knockdown of EMT factors in the mesenchymal-like prostate cancer cell subpopulation caused a gain in epithelial features and properties of TICs. Both tumor cell subpopulations cooperated so that the nonmetastatic mesenchymal-like prostate cancer subpopulation enhanced the in vitro invasiveness of the metastatic epithelial subpopulation and, in vivo, promoted the escape of the latter from primary implantation sites and accelerated their metastatic colonization. Our models provide new insights into how dynamic interactions among epithelial, self-renewal, and mesenchymal gene programs determine the plasticity of epithelial TICs. PMID:22505459

  15. Nitric Oxide and Airway Epithelial Barrier Function: Regulation of Tight Junction Proteins and Epithelial Permeability

    PubMed Central

    Olson, Nels; Greul, Anne-Katrin; Hristova, Milena; Bove, Peter F.; Kasahara, David I.; van der Vliet, Albert

    2008-01-01

    Acute airway inflammation is associated with enhanced production of nitric oxide (NO•) and altered airway epithelial barrier function, suggesting a role of NO• or its metabolites in epithelial permeability. While high concentrations of S-nitrosothiols disrupted transepithelial resistance (TER) and increased permeability in 16HBE14o- cells, no significant barrier disruption was observed by NONOates, in spite of altered distribution and expression of some TJ proteins. Barrier disruption of mouse tracheal epithelial (MTE) cell monolayers in response to inflammatory cytokines was independent of NOS2, based on similar effects in MTE cells from NOS2-/- mice and a lack of effect of the NOS2-inhibitor 1400W. Cell pre-incubation with LPS protected MTE cells from TER loss and increased permeability by H2O2, which was independent of NOS2. However, NOS2 was found to contribute to epithelial wound repair and TER recovery after mechanical injury. Overall, our results demonstrate that epithelial NOS2 is not responsible for epithelial barrier dysfunction during inflammation, but may contribute to restoration of epithelial integrity. PMID:19100237

  16. Mesenchymal-epithelial interactions during digestive tract development and epithelial stem cell regeneration.

    PubMed

    Le Guen, Ludovic; Marchal, Stéphane; Faure, Sandrine; de Santa Barbara, Pascal

    2015-10-01

    The gastrointestinal tract develops from a simple and uniform tube into a complex organ with specific differentiation patterns along the anterior-posterior and dorso-ventral axes of asymmetry. It is derived from all three germ layers and their cross-talk is important for the regulated development of fetal and adult gastrointestinal structures and organs. Signals from the adjacent mesoderm are essential for the morphogenesis of the overlying epithelium. These mesenchymal-epithelial interactions govern the development and regionalization of the different gastrointestinal epithelia and involve most of the key morphogens and signaling pathways, such as the Hedgehog, BMPs, Notch, WNT, HOX, SOX and FOXF cascades. Moreover, the mechanisms underlying mesenchyme differentiation into smooth muscle cells influence the regionalization of the gastrointestinal epithelium through interactions with the enteric nervous system. In the neonatal and adult gastrointestinal tract, mesenchymal-epithelial interactions are essential for the maintenance of the epithelial regionalization and digestive epithelial homeostasis. Disruption of these interactions is also associated with bowel dysfunction potentially leading to epithelial tumor development. In this review, we will discuss various aspects of the mesenchymal-epithelial interactions observed during digestive epithelium development and differentiation and also during epithelial stem cell regeneration. PMID:26126787

  17. PAX8 Expression in Ovarian Surface Epithelial Cells

    PubMed Central

    Adler, Emily; Mhawech-Fauceglia, Paulette; Gayther, Simon A; Lawrenson, Kate

    2015-01-01

    High-grade serous ovarian carcinoma (HGSOC) is usually diagnosed at a late stage and is associated with poor prognosis. Understanding early stage disease biology is essential in developing clinical biomarkers to detect HGSOC earlier. While recent studies indicate that HGSOCs arise from fallopian tube secretory epithelial cells (FTSECs), a considerable body of evidence also suggests that HGSOC can also arise from ovarian surface epithelial cells (OSECs). PAX8 is overexpressed in HGSOCs and expressed in FTSECs, but there are conflicting reports about PAX8 expression in OSECs. The purpose of this study was to comprehensively characterize PAX8 expression in a large series of OSECs, and to investigate the role of PAX8 in early HGSOC development. PAX8 protein expression was analyzed in the OSECs of 27 normal ovaries and 7 primary OSEC cultures using immunohistochemistry and immunofluorescent cytochemistry. PAX8 mRNA expression was quantified in 66 primary OSEC cultures. Cellular transformation was evaluated in OSECs expressing a PAX8 construct. PAX8 was expressed by 44-71% of OSECs. Calretinin and E-cadherin were frequently co-expressed with PAX8. Expression of PAX8 in OSECs decreased cellular migration (P=0.028), but had no other effects on cellular transformation. In addition, PAX8 expression was significantly increased (P=0.003) in an in vitro stepwise model of neoplastic transformation. In conclusion, PAX8 is frequently expressed by OSECs and endogenous levels of PAX8 expression are non-transforming. These data indicate that in OSECs PAX8 expression may represent a normal state and that OSECs may represent an origin of HGSOCs. PMID:26079312

  18. Claudins: Gatekeepers of lung epithelial function.

    PubMed

    Schlingmann, Barbara; Molina, Samuel A; Koval, Michael

    2015-06-01

    The lung must maintain a proper barrier between airspaces and fluid filled tissues in order to maintain lung fluid balance. Central to maintaining lung fluid balance are epithelial cells which create a barrier to water and solutes. The barrier function of these cells is mainly provided by tight junction proteins known as claudins. Epithelial barrier function varies depending on the different needs within the segments of the respiratory tree. In the lower airways, fluid is required to maintain mucociliary clearance, whereas in the terminal alveolar airspaces a thin layer of surfactant enriched fluid lowers surface tension to prevent airspace collapse and is critical for gas exchange. As the epithelial cells within the segments of the respiratory tree differ, the composition of claudins found in these epithelial cells is also different. Among these differences is claudin-18 which is uniquely expressed by the alveolar epithelial cells. Other claudins, notably claudin-4 and claudin-7, are more ubiquitously expressed throughout the respiratory epithelium. Claudin-5 is expressed by both pulmonary epithelial and endothelial cells. Based on in vitro and in vivo model systems and histologic analysis of lungs from human patients, roles for specific claudins in maintaining barrier function and protecting the lung from the effects of acute injury and disease are being identified. One surprising finding is that claudin-18 and claudin-4 control lung cell phenotype and inflammation beyond simply maintaining a selective paracellular permeability barrier. This suggests claudins have more nuanced roles for the control of airway and alveolar physiology in the healthy and diseased lung. PMID:25951797

  19. The Pseudomonas aeruginosa Type III Translocon Is Required for Biofilm Formation at the Epithelial Barrier

    PubMed Central

    Tran, Cindy S.; Rangel, Stephanie M.; Almblad, Henrik; Kierbel, Arlinet; Givskov, Michael; Tolker-Nielsen, Tim; Hauser, Alan R.; Engel, Joanne N.

    2014-01-01

    Clinical infections by Pseudomonas aeruginosa, a deadly Gram-negative, opportunistic pathogen of immunocompromised hosts, often involve the formation of antibiotic-resistant biofilms. Although biofilm formation has been extensively studied in vitro on glass or plastic surfaces, much less is known about biofilm formation at the epithelial barrier. We have previously shown that when added to the apical surface of polarized epithelial cells, P. aeruginosa rapidly forms cell-associated aggregates within 60 minutes of infection. By confocal microscopy we now show that cell-associated aggregates exhibit key characteristics of biofilms, including the presence of extracellular matrix and increased resistance to antibiotics compared to planktonic bacteria. Using isogenic mutants in the type III secretion system, we found that the translocon, but not the effectors themselves, were required for cell-associated aggregation on the surface of polarized epithelial cells and at early time points in a murine model of acute pneumonia. In contrast, the translocon was not required for aggregation on abiotic surfaces, suggesting a novel function for the type III secretion system during cell-associated aggregation. Supernatants from epithelial cells infected with wild-type bacteria or from cells treated with the pore-forming toxin streptolysin O could rescue aggregate formation in a type III secretion mutant, indicating that cell-associated aggregation requires one or more host cell factors. Our results suggest a previously unappreciated function for the type III translocon in the formation of P. aeruginosa biofilms at the epithelial barrier and demonstrate that biofilms may form at early time points of infection. PMID:25375398

  20. Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells

    SciTech Connect

    Weng, Yu-I; Hsu, Pei-Yin; Liyanarachchi, Sandya; Liu, Joseph; Deatherage, Daniel E.; Huang Yiwen; Zuo Tao; Rodriguez, Benjamin; Lin, Ching-Hung; Cheng, Ann-Lii; Huang, Tim H.-M.

    2010-10-15

    Substantial evidence indicates that exposure to bisphenol A (BPA) during early development may increase breast cancer risk later in life. The changes may persist into puberty and adulthood, suggesting an epigenetic process being imposed in differentiated breast epithelial cells. The molecular mechanisms by which early memory of BPA exposure is imprinted in breast progenitor cells and then passed onto their epithelial progeny are not well understood. The aim of this study was to examine epigenetic changes in breast epithelial cells treated with low-dose BPA. We also investigated the effect of BPA on the ER{alpha} signaling pathway and global gene expression profiles. Compared to control cells, nuclear internalization of ER{alpha} was observed in epithelial cells preexposed to BPA. We identified 170 genes with similar expression changes in response to BPA. Functional analysis confirms that gene suppression was mediated in part through an ER{alpha}-dependent pathway. As a result of exposure to BPA or other estrogen-like chemicals, the expression of lysosomal-associated membrane protein 3 (LAMP3) became epigenetically silenced in breast epithelial cells. Furthermore, increased DNA methylation in the LAMP3 CpG island was this repressive mark preferentially occurred in ER{alpha}-positive breast tumors. These results suggest that the in vitro system developed in our laboratory is a valuable tool for exposure studies of BPA and other xenoestrogens in human cells. Individual and geographical differences may contribute to altered patterns of gene expression and DNA methylation in susceptible loci. Combination of our exposure model with epigenetic analysis and other biochemical assays can give insight into the heritable effect of low-dose BPA in human cells.

  1. The Pseudomonas aeruginosa type III translocon is required for biofilm formation at the epithelial barrier.

    PubMed

    Tran, Cindy S; Rangel, Stephanie M; Almblad, Henrik; Kierbel, Arlinet; Givskov, Michael; Tolker-Nielsen, Tim; Hauser, Alan R; Engel, Joanne N

    2014-11-01

    Clinical infections by Pseudomonas aeruginosa, a deadly Gram-negative, opportunistic pathogen of immunocompromised hosts, often involve the formation of antibiotic-resistant biofilms. Although biofilm formation has been extensively studied in vitro on glass or plastic surfaces, much less is known about biofilm formation at the epithelial barrier. We have previously shown that when added to the apical surface of polarized epithelial cells, P. aeruginosa rapidly forms cell-associated aggregates within 60 minutes of infection. By confocal microscopy we now show that cell-associated aggregates exhibit key characteristics of biofilms, including the presence of extracellular matrix and increased resistance to antibiotics compared to planktonic bacteria. Using isogenic mutants in the type III secretion system, we found that the translocon, but not the effectors themselves, were required for cell-associated aggregation on the surface of polarized epithelial cells and at early time points in a murine model of acute pneumonia. In contrast, the translocon was not required for aggregation on abiotic surfaces, suggesting a novel function for the type III secretion system during cell-associated aggregation. Supernatants from epithelial cells infected with wild-type bacteria or from cells treated with the pore-forming toxin streptolysin O could rescue aggregate formation in a type III secretion mutant, indicating that cell-associated aggregation requires one or more host cell factors. Our results suggest a previously unappreciated function for the type III translocon in the formation of P. aeruginosa biofilms at the epithelial barrier and demonstrate that biofilms may form at early time points of infection. PMID:25375398

  2. Dendritic cell-derived tumor necrosis factor α modifies airway epithelial cell responses.

    PubMed

    Lutfi, R; Ledford, J R; Zhou, P; Lewkowich, I P; Page, K

    2012-01-01

    Mucosal dendritic cells (DC) are intimately associated with the airway epithelium and thus are ideally situated to be first responders to pathogens. We hypothesize that DC drive innate immune responses through early release of tumor necrosis factor (TNF) α, which drives airway epithelial cell responses. In a mouse model, TNFα release was significantly increased following a single exposure to German cockroach (GC) frass, an event independent of neutrophil recruitment into the airways. While lung epithelial cells and alveolar macrophages failed to release TNFα following GC frass exposure, bone marrow-derived DC (BMDC) produced substantial amounts of TNFα suggesting their importance as early responding cells. This was confirmed by flow cytometry of pulmonary myeloid DC. Addition of GC frass-pulsed BMDC or conditioned media from GC frass-pulsed BMDC to primary mouse tracheal epithelial cells (MTEC) or MLE-15 cells induced chemokine (C-C) motif ligand (CCL) 20 and granulocyte macrophage (GM) colony-stimulating factor (CSF), both of which are important for DC recruitment, survival and differentiation. Importantly, DC do not produce CCL20 or GM-CSF following allergen exposure. Blocking TNFα receptor 1 (TNFR1) completely abolished chemokine production, suggesting that BMDC-derived TNFα induced airway epithelial cell activation and enhancement of the innate immune response. Lastly, blocking TNFR1 in vivo resulted in significantly decreased CCL20 and GM-CSF production in the lungs of mice. Together, our data strongly suggest that DC-derived TNFα plays a crucial role in the initiation of innate immune responses through the modification of airway epithelial cell responses. PMID:22517116

  3. Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells

    PubMed Central

    Weng, Yu-I; Hsu, Pei-Yin; Liyanarachchi, Sandya; Liu, Joseph; Deatherage, Daniel E.; Huang, Yi-Wen; Zuo, Tao; Rodriguez, Benjamin; Lin, Ching-Hung; Cheng, Ann-Lii; Huang, Tim H.-M.

    2010-01-01

    Substantial evidence indicates that exposure to bisphenol A (BPA) during early development may increase breast cancer risk later in life. The changes may persist into puberty and adulthood, suggesting an epigenetic process being imposed in differentiated breast epithelial cells. The molecular mechanisms by which early memory of BPA exposure is imprinted in breast progenitor cells and then passed onto their epithelial progeny are not well understood. The aim of this study was to examine epigenetic changes in breast epithelial cells treated with low-dose BPA. We also investigated the effect of BPA on the ERα signaling pathway and global gene expression profiles. Compared to control cells, nuclear internalization of ERα was observed in epithelial cells preexposed to BPA. We identified 170 genes with similar expression changes in response to BPA. Functional analysis confirms that gene suppression was mediated in part through an ERα-dependent pathway. As a result of exposure to BPA or other estrogen-like chemicals, the expression of lysosomal-associated membrane protein 3 (LAMP3) became epigenetically silenced in breast epithelial cells. Furthermore, increased DNA methylation in the LAMP3 CpG island was this repressive mark preferentially occurred in ERα-positive breast tumors. These results suggest that the in vitro system developed in our laboratory is a valuable tool for exposure studies of BPA and other xenoestrogens in human cells. Individual and geographical differences may contribute to altered patterns of gene expression and DNA methylation in susceptible loci. Combination of our exposure model with epigenetic analysis and other biochemical assays can give insight into the heritable effect of low-dose BPA in human cells. PMID:20678512

  4. Uterine Epithelial Cell Estrogen Receptor Alpha-Dependent and -Independent Genomic Profiles That Underlie Estrogen Responses in Mice1

    PubMed Central

    Winuthayanon, Wipawee; Hewitt, Sylvia C.; Korach, Kenneth S.

    2014-01-01

    ABSTRACT Estrogens exert their activity through estrogen receptor alpha (ERalpha) to stimulate hypertrophy and hyperplasia in the uterus. A uterine epithelial ERalpha conditional knockout mouse model (Wnt7aCre+;Esr1f/f or cKO) demonstrated that ERalpha in the epithelial cells was dispensable for an initial uterine proliferative response to 17beta-estradiol (E2) but required for subsequent uterine biological responses. This study aimed to characterize the differential gene expression patterns induced by E2 in the presence or absence of epithelial ERalpha. RNA microarray analysis revealed that approximately 20% of the genes differentially expressed at 2 h were epithelial ERalpha independent, as they were preserved in the cKO uteri. This indicates that early uterine transcripts mediated by stromal ERalpha are sufficient to promote initial proliferative responses. However, more than 90% of the differentially expressed transcripts at 24 h were not regulated in the cKO, indicating that the majority of later transcriptional regulation required epithelial ERalpha, especially those involved in mitosis. This shows that loss of regulation of these later transcripts results in blunted subsequent uterine growth after 3 days of E2 treatment. Additionally, progesterone's ability to inhibit E2-induced epithelial cell proliferation was impaired, consistent with a uterine receptivity defect that contributes to cKO infertility. These transcriptional profiles correlate with our previously observed biological responses, in which the initial proliferative response is independent of epithelial ERalpha and thus dependent on stromal ERalpha, yet epithelial ERalpha is essential for subsequent tissue responsiveness. PMID:25210133

  5. Respiratory epithelial cells orchestrate pulmonary innate immunity.

    PubMed

    Whitsett, Jeffrey A; Alenghat, Theresa

    2015-01-01

    The epithelial surfaces of the lungs are in direct contact with the environment and are subjected to dynamic physical forces as airway tubes and alveoli are stretched and compressed during ventilation. Mucociliary clearance in conducting airways, reduction of surface tension in the alveoli, and maintenance of near sterility have been accommodated by the evolution of a multi-tiered innate host-defense system. The biophysical nature of pulmonary host defenses are integrated with the ability of respiratory epithelial cells to respond to and 'instruct' the professional immune system to protect the lungs from infection and injury. PMID:25521682

  6. Physiology of Epithelial Chloride and Fluid Secretion

    PubMed Central

    Frizzell, Raymond A.; Hanrahan, John W.

    2012-01-01

    Epithelial salt and water secretion serves a variety of functions in different organ systems, such as the airways, intestines, pancreas, and salivary glands. In cystic fibrosis (CF), the volume and/or composition of secreted luminal fluids are compromised owing to mutations in the gene encoding CFTR, the apical membrane anion channel that is responsible for salt secretion in response to cAMP/PKA stimulation. This article examines CFTR and related cellular transport processes that underlie epithelial anion and fluid secretion, their regulation, and how these processes are altered in CF disease to account for organ-specific secretory phenotypes. PMID:22675668

  7. Propagating Stress Waves During Epithelial Expansion

    NASA Astrophysics Data System (ADS)

    Banerjee, Shiladitya; Utuje, Kazage J. C.; Marchetti, M. Cristina

    2015-06-01

    Coordinated motion of cell monolayers during epithelial wound healing and tissue morphogenesis involves mechanical stress generation. Here we propose a model for the dynamics of epithelial expansion that couples mechanical deformations in the tissue to contractile activity and polarization in the cells. A new ingredient of our model is a feedback between local strain, polarization, and contractility that naturally yields a mechanism for viscoelasticity and effective inertia in the cell monolayer. Using a combination of analytical and numerical techniques, we demonstrate that our model quantitatively reproduces many experimental findings [Nat. Phys. 8, 628 (2012)], including the buildup of intercellular stresses, and the existence of traveling mechanical waves guiding the oscillatory monolayer expansion.

  8. Cell surface morphology in epithelial malignancy and its precursor lesions.

    PubMed

    Kenemans, P; Davina, J H; de Haan, R W; van der Zanden, P; Vooys, G P; Stolk, J G; Stadhouders, A M

    1981-01-01

    The cell surface organization of cancer cells is of potentially great significance, as it may not only allow (early) diagnosis, but as it may also harbour markers for refined prognosis (degree of oncogenetic and metastatic potential), and targets for selective cancer (chemo- and immuno) therapy. With these aspects in mind, the present review deals with SEM work done on (pre-) malignant cells, both in vivo and in vitro, and in animal models. Attention, however, is focused on human cancer cells. Cancer cells in vitro may lose many of their original malignant characteristics, and show adaptations to culture conditions. Many other factors have been shown to influence cell surface morphology, such as cell cycle, cell contacts, and preparations technique. Cancer cells differ in their surface morphology from normal cells, and have an extra ordinary amount of surface activity. Human malignant epithelial cells show abundant long. pleomorphic microvilli, especially those present in effusions. In squamous epithelium (bladder, cervix) microridge system present on normal superficial cells are progressively replaced by microvilli which increase in number and degree of pleomorphism during experimental and clinical oncogenesis. The question of whether or not the appearance of long. Pleomorphic microvilli reflects an irreversible alteration of the epithelium, and thus provides an early marker of irreversible neoplastic transformation is considered and assessed on the basis of our work with (pre-) malignant cells of the human uterine cervix. Although SEM has contributed significantly to the description of oncogenesis, up to now it has no early diagnostic, prognostic or therapeutic significance. PMID:7199203

  9. Colony Stimulating Factor-1 exerts direct effects on the proliferation and invasiveness of endometrial epithelial cells

    PubMed Central

    Aligeti, Sabitha; Kirma, Nameer B.; Binkely, Peter A; Schenken, Robert S.; Tekmal, Rajeshwar Rao

    2011-01-01

    Although macrophage colony stimulating factor (CSF-1) has been suggested to play a role in part in maintaining the chronic inflammatory response in endometriosis, our previous data suggest that CSF-1 may also play a role in early endometriosis lesion formation. In the current studies, we have examined this possibility and have shown that CSF-1, in an autocrine fashion, has a direct effect on endometrial epithelial cell proliferation and attachment to peritoneal mesothelial cells, early steps in endometriosis lesion formation on the peritoneum. PMID:21481374

  10. Interaction with Epithelial Cells Modifies Airway Macrophage Response to Ozone

    EPA Science Inventory

    The initial innate immune response to ozone (03) in the lung is orchestrated by structural cells, such as epithelial cells, and resident immune cells, such as airway macrophages (Macs). We developed an epithelial cell-Mac coculture model to investigate how epithelial cell-derived...

  11. Exit of intracellular Porphyromonas gingivalis from gingival epithelial cells is mediated by endocytic recycling pathway.

    PubMed

    Takeuchi, Hiroki; Furuta, Nobumichi; Morisaki, Ichijiro; Amano, Atsuo

    2011-05-01

    Gingival epithelial cells function as an innate host defence system to prevent intrusion by periodontal bacteria. Nevertheless, Porphyromonas gingivalis, the most well-known periodontal pathogen, can enter gingival epithelial cells and pass through the epithelial barrier into deeper tissues. However, it is poorly understood how this pathogen exits from infected cells for further transcellular spreading. The present study was performed to elucidate the cellular machinery exploited by P. gingivalis to exit from immortalized human gingival epithelial cells. P. gingivalis was shown to be internalized with early endosomes positive for the FYVE domain of EEA1 and transferrin receptor, and about half of the intracellular bacteria were then sorted to lytic compartments, including autolysosomes and late endosomes/lysosomes, while a considerable number of the remaining organisms were sorted to Rab11- and RalA-positive recycling endosomes. Inhibition experiments revealed that bacterial exit was dependent on actin polymerization, lipid rafts and microtubule assembly. Dominant negative forms and RNAi knockdown of Rab11, RalA and exocyst complex subunits (Sec5, Sec6 and Exo84) significantly disturbed the exit of P. gingivalis. These results strongly suggest that the recycling pathway is exploited by intracellular P. gingivalis to exit from infected cells to neighbouring cells as a mechanism of cell-to-cell spreading. PMID:21155963

  12. Wnt-10b secreted from lymphocytes promotes differentiation of skin epithelial cells

    SciTech Connect

    Ouji, Yukiteru . E-mail: oujix@naramed-u.ac.jp; Yoshikawa, Masahide; Shiroi, Akira; Ishizaka, Shigeaki

    2006-04-21

    Wnt-10b was originally isolated from lymphoid tissue and is known to be involved in a wide range of biological actions, while recently it was found to be expressed early in the development of hair follicles. However, few studies have been conducted concerning the role of Wnt-10b with the differentiation of skin epithelial cells. To evaluate its role in epithelial differentiation, we purified Wnt-10b from the supernatant of a concanavalin A-stimulated lymphocyte culture using an affinity column and investigated its effects on the differentiation of adult mouse-derived primary skin epithelial cells (MPSEC). MPSEC cultured with Wnt-10b showed morphological changes from cuboidal to spindle-shaped with inhibited proliferation, and also obtained characteristics of the hair shaft and inner root sheath of the hair follicle, represented by red-colored Ayoub Shklar staining, and reactions to AE-13 and AE-15 as seen with immunocytology. Further, RT-PCR analysis demonstrated the expression of mRNA for keratin 1, keratin 2, loricrin, mHa5, and mHb5, in association with a decreased expression of the basal cell marker keratin 5, in Wnt-10b-treated MPSEC. In addition, involvement of the canonical Wnt signal pathway was demonstrated by a TCF reporter (pTOPFLASH) assay. These results suggest that Wnt-10b promotes the differentiation of MPSEC and may play an important role in hair follicle development by promoting differentiation of epithelial cells.

  13. Intranasal Immunization Strategy To Impede Pilin-Mediated Binding of Pseudomonas aeruginosa to Airway Epithelial Cells

    PubMed Central

    Hsieh, Jennifer C.; Tham, Doris M.; Feng, Weijun; Huang, Fan; Embaie, Selamawit; Liu, Keyi; Dean, Deborah; Hertle, Ralf; FitzGerald, David J.; Mrsny, Randall J.

    2005-01-01

    Prevention of pulmonary Pseudomonas aeruginosa infections represents a critical unmet medical need for cystic fibrosis (CF) patients. We have examined the tenet that a mucosal immunization approach can reduce interactions of a piliated form of this opportunistic pathogen with respiratory epithelial cells. Vaccinations were performed using ntPEpilinPAK, a protein chimera composed of a nontoxic form of P. aeruginosa exotoxin A (ntPE), where the C-terminal loop amino acid sequence of the PAK strain pilin protein was inserted in place of the ntPE Ib domain. Intranasal (i.n.) immunization of BALB/c mice with ntPEpilinPAK generated both serum and saliva immune responses. A series of in vitro studies showed that diluted samples of saliva obtained from immunized mice reduced pilin-dependent P. aeruginosa binding to polarized human tracheal epithelial cells, protected human pulmonary epithelial cells from cytotoxic actions associated with bacterial challenge, and reduced exotoxin A toxicity. Overall, i.n. administration of ntPEpilinPAK induced mucosal and systemic immune responses that may be beneficial for blocking early stage adhesion and/or infection events of epithelial cell-P. aeruginosa interactions at oropharyngeal surfaces. PMID:16239575

  14. Absence of inflammatory response from upper airway epithelial cells after X irradiation.

    PubMed

    Reiter, R; Deutschle, T; Wiegel, T; Riechelmann, H; Bartkowiak, D

    2009-03-01

    Radiotherapy of head and neck tumors causes adverse reactions in normal tissue, especially mucositis. The dose- and time-dependent response of upper airway cells to X radiation should be analyzed in terms of the pro-inflammatory potential. Immortalized BEAS-2B lung epithelial cells were treated with 2, 5 and 8 Gy. Out of 1232 genes, those that were transcribed differentially after 2, 6 and 24 h were assigned to biological themes according to the Gene Ontology Consortium. Enrichment of differentially regulated gene clusters was determined with GOTree ( http://bioinfo.vanderbilt.edu/gotm ). Eleven cytokines were measured in culture supernatants. The cell cycle response up to 24 h and induction of apoptosis up to 4 days after exposure were determined by flow cytometry. A significant dose- and time-dependent gene activation was observed for the categories response to DNA damage, oxidative stress, cell cycle arrest and cell death/apoptosis but not for immune/inflammatory response. This correlated with functional G(2) arrest and apoptosis. Pro-inflammatory cytokines accumulated in supernatants of control cells but not of X-irradiated cells. The complex gene expression pattern of X-irradiated airway epithelial cells is accompanied by cell cycle arrest and induction of apoptosis. In vivo, this may impair the epithelial barrier. mRNA and protein expression suggest at most an indirect contribution of epithelial cells to early radiogenic mucositis. PMID:19267554

  15. STAT3 accelerates uterine epithelial regeneration in a mouse model of decellularized uterine matrix transplantation

    PubMed Central

    Hiraoka, Takehiro; Hirota, Yasushi; Saito-Fujita, Tomoko; Matsuo, Mitsunori; Egashira, Mahiro; Matsumoto, Leona; Haraguchi, Hirofumi; Dey, Sudhansu K.; Furukawa, Katsuko S.; Fujii, Tomoyuki; Osuga, Yutaka

    2016-01-01

    Although a close connection between uterine regeneration and successful pregnancy in both humans and mice has been consistently observed, its molecular basis remains unclear. We here established a mouse model of decellularized uterine matrix (DUM) transplantation. Resected mouse uteri were processed with SDS to make DUMs without any intact cells. DUMs were transplanted into the mouse uteri with artificially induced defects, and all the uterine layers were recovered at the DUM transplantation sites within a month. In the regenerated uteri, normal hormone responsiveness in early pregnancy was observed, suggesting the regeneration of functional uteri. Uterine epithelial cells rapidly migrated and formed a normal uterine epithelial layer within a week, indicating a robust epithelial-regenerating capacity. Stromal and myometrial regeneration occurred following epithelial regeneration. In ovariectomized mice, uterine regeneration of the DUM transplantation was similarly observed, suggesting that ovarian hormones are not essential for this regeneration process. Importantly, the regenerating epithelium around the DUM demonstrated heightened STAT3 phosphorylation and cell proliferation, which was suppressed in uteri of Stat3 conditional knockout mice. These data suggest a key role of STAT3 in the initial step of the uterine regeneration process. The DUM transplantation model is a powerful tool for uterine regeneration research. PMID:27358915

  16. Immortalisation of human oesophageal epithelial cells by a recombinant SV40 adenovirus vector.

    PubMed Central

    Inokuchi, S.; Handa, H.; Imai, T.; Makuuchi, H.; Kidokoro, M.; Tohya, H.; Aizawa, S.; Shimamura, K.; Ueyama, Y.; Mitomi, T.

    1995-01-01

    We introduced the origin-defective SV40 early gene into cultured human oesophageal epithelial cells by infection of a recombinant SV40 adenovirus vector. The virus-infected cells formed colonies 3-4 weeks after infection in medium containing fetal calf serum. When the cells derived from 'serum-resistant' colonies were then maintained in the serum-free medium with a low calcium ion concentration, some of them passed the cell crisis and kept growing for over 12 months. These cells, regarded as immortalised cells, resembled the primarily cultured oesophageal epithelial cells in morphology and had some of their original characteristics. Treatment of the cells with a high calcium concentration induced phenotypic changes. These cells still responded to transforming growth factor beta. When the immortalised cells were injected into severe combined immunodeficient mice, they transiently formed epithelial cysts, although the typical differentiation pattern of the oesophageal epithelium was not observed. These cysts regressed within 2 months without development into tumours. The results indicated that human oesophageal epithelial cells were reproducibly immortalised by infection with a recombinant SV40 adenovirus vector at relatively high efficiency. The immortalised cells should be useful in studies on oesophageal carcinogenesis and in assessing the cooperative effects with other oncogene products or carcinogens. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:7536023

  17. Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling.

    PubMed

    Kamimoto, Kenji; Kaneko, Kota; Kok, Cindy Yuet-Yin; Okada, Hajime; Miyajima, Atsushi; Itoh, Tohru

    2016-01-01

    Dynamic remodeling of the intrahepatic biliary epithelial tissue plays key roles in liver regeneration, yet the cellular basis for this process remains unclear. We took an unbiased approach based on in vivo clonal labeling and tracking of biliary epithelial cells in the three-dimensional landscape, in combination with mathematical simulation, to understand their mode of proliferation in a mouse liver injury model where the nascent biliary structure formed in a tissue-intrinsic manner. An apparent heterogeneity among biliary epithelial cells was observed: whereas most of the responders that entered the cell cycle upon injury exhibited a limited and tapering growth potential, a select population continued to proliferate, making a major contribution in sustaining the biliary expansion. Our study has highlighted a unique mode of epithelial tissue dynamics, which depends not on a hierarchical system driven by fixated stem cells, but rather, on a stochastically maintained progenitor population with persistent proliferative activity. PMID:27431614

  18. Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

    SciTech Connect

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2004-07-14

    Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

  19. Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation

    PubMed Central

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2016-01-01

    Summary Cellular senescence suppresses cancer by arresting cells at risk of malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation and branching morphogenesis. Furthermore, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts – the ability to alter epithelial differentiation – that might also explain the loss of tissue function and organization that is a hallmark of aging. PMID:15657080

  20. Iris pigment epithelial cysts in a newborn

    PubMed Central

    Zargar, Shabnam; Prendiville, Kevin John; Martinez, Eladio

    2016-01-01

    Purpose: We report a case of iris pigment epithelial cysts in a newborn and discuss the importance of an accurate diagnosis for prevention of amblyopia. Methods: We describe a case of an abnormal red reflex seen on a newborn exam. Results: A full-term female born via normal spontaneous vaginal delivery without any complications was seen in the newborn nursery. She was noted to have an abnormal eye exam. Pupils were large with circular dark excrescences of the iris pigment epithelium. She was referred to a pediatric ophthalmologist where she was noted to fixate and follow faces. No afferent pupillary defect was seen. OD red reflex was normal whereas OS red reflex was blocked mostly by dark excrescences. A 2–3 mm dark brown lesion was seen in the OD iris and a 3–5 mm dark brown lesion was seen in the OS iris, consistent with a pupillary iris pigment epithelial cyst. Central visual axis was clear OU. Glaucoma was not present and patching was not performed. Observations and clinical photographs were recommended with follow-up in three months. Conclusion: Iris pigment epithelial cysts are uncommonly seen in children. The primary care provider first seeing a newborn must be aware of lesions obscuring a red reflex with appropriate follow-up. Follow-up in three months with IOP measurements is recommended. Iris pigment epithelial cysts in children may be a cause of amblyopia, thus prompt evaluation is important for prognostic purposes and the prevention of amblyopia. PMID:27625966

  1. The buffer capacity of airway epithelial secretions

    PubMed Central

    Kim, Dusik; Liao, Jie; Hanrahan, John W.

    2014-01-01

    The pH of airway epithelial secretions influences bacterial killing and mucus properties and is reduced by acidic pollutants, gastric reflux, and respiratory diseases such as cystic fibrosis (CF). The effect of acute acid loads depends on buffer capacity, however the buffering of airway secretions has not been well characterized. In this work we develop a method for titrating micro-scale (30 μl) volumes and use it to study fluid secreted by the human airway epithelial cell line Calu-3, a widely used model for submucosal gland serous cells. Microtitration curves revealed that HCO−3 is the major buffer. Peak buffer capacity (β) increased from 17 to 28 mM/pH during forskolin stimulation, and was reduced by >50% in fluid secreted by cystic fibrosis transmembrane conductance regulator (CFTR)-deficient Calu-3 monolayers, confirming an important role of CFTR in HCO−3 secretion. Back-titration with NaOH revealed non-volatile buffer capacity due to proteins synthesized and released by the epithelial cells. Lysozyme and mucin concentrations were too low to buffer Calu-3 fluid significantly, however model titrations of porcine gastric mucins at concentrations near the sol-gel transition suggest that mucins may contribute to the buffer capacity of ASL in vivo. We conclude that CFTR-dependent HCO−3 secretion and epithelially-derived proteins are the predominant buffers in Calu-3 secretions. PMID:24917822

  2. Odontogenic epithelial hamartomas in periodontal structures.

    PubMed

    Moskow, B S; Baden, E

    1989-02-01

    4 hamartomas apparently derived from remnants of the dental lamina and enamel organ are reported in a collection of human jaw specimens. These epithelial lesions represent a transitional stage between a developmental anomaly and a distinct odontogenic neoplasm. Earlier reports indicated that such lesions with clinical symptoms are rare; however, this study suggests a more common occurrence on a microscopic level. PMID:2921378

  3. Epithelial-mesenchymal transition in liver fibrosis

    PubMed Central

    ZHAO, YA-LEI; ZHU, RONG-TAO; SUN, YU-LING

    2016-01-01

    Liver fibrosis is the result of a sustained wound healing response to sustained chronic liver injury, which includes viral, alcoholic and autoimmune hepatitis. Hepatic regeneration is the dominant outcome of liver damage. The outcomes of successful repair are the replacement of dead epithelial cells with healthy epithelial cells, and reconstruction of the normal hepatic structure and function. Prevention of the development of epithelial-mesenchymal transition (EMT) may control and even reverse liver fibrosis. EMT is a critical process for an epithelial cell to undergo a conversion to a mesenchymal phenotype, and is believed to be an inflammation-induced response, which may have a central role in liver fibrosis. The origin of fibrogenic cells in liver fibrosis remains controversial. Numerous studies have investigated the origin of all fibrogenic cells within the liver and the mechanism of the signaling pathways that lead to the activation of EMT programs during numerous chronic liver diseases. The present study aimed to summarize the evidence to explain the possible role of EMT in liver fibrosis. PMID:26998262

  4. Multifocal epithelial hyperplasia. Report of nine cases.

    PubMed

    Ledesma-Montes, Constantino; Vega-Memije, Elisa; Garcés-Ortíz, Maricela; Cardiel-Nieves, Maritza; Juárez-Luna, Claudia

    2005-01-01

    Multifocal epithelial hyperplasia (MEH) is also known as focal epithelial hyperplasia, Heck's disease or multifocal papillomavirus-induced epithelial hyperplasia. It is characterised by the presence of multiple lesions in the oral mucosa of children and it has been associated with the presence of the human papillomavirus. The aim of this study was to determine the clinico-pathological features of the cases diagnosed as MEH in the Service of Dermatology of the Hospital Manuel Gea González (SDHMGG). The files of the SDHMGG were reviewed and all cases diagnosed as MEH were retrieved. Nine MEH cases were found. Most of the patients were 20 year-old or younger (67%) and females were more commonly affected (78%). All patients presented multiple lesions and always, close relatives with similar lesions were found. Lesions were located most commonly in the buccal mucosa, lower lip and commissures. MEH is a soft tissue intraoral condition that needs treatment solely of the traumatised lesions or those with cosmetic problems. Remaining lesions will disappear with the age of the patients. It is suggested that this entity should be named multifocal epithelial hyperplasia since this name describes better the clinico-pathological and microscopic features of the disease. PMID:16264387

  5. Adaptive epithelial cytoplasm segmentation and epithelial unit separation in immunoflurorescent images

    NASA Astrophysics Data System (ADS)

    Ramachandran, Janakiramanan; Scott, Richard; Ajemba, Peter; Karvir, Hrishikesh; Khan, Faisal; Zeineh, Jack; Donovan, Michael; Fernandez, Gerardo

    2012-02-01

    Tissue segmentation is one of the key preliminary steps in the morphometric analysis of tissue architecture. In multi-channel immunoflurorescent biomarker images, the primary segmentation steps consist of segmenting the nuclei (epithelial and stromal) and epithelial cytoplasm from 4',6-diamidino-2-phenylindole (DAPI) and cytokeratin 18 (CK18) biomarker images respectively. The epithelial cytoplasm segmentation can be very challenging due to variability in cytoplasm morphology and image staining. A robust and adaptive segmentation algorithm was developed for the purpose of both delineating the boundaries and separating thin gaps that separate the epithelial unit structures. This paper discusses novel methods that were developed for adaptive segmentation of epithelial cytoplasm and separation of epithelial units. The adaptive segmentation was performed by computing the non-epithelial background texture of every CK18 biomarker image. The epithelial unit separation was performed using two complementary techniques: a marker based, center-initialized watershed transform and a boundary initialized fast marching-watershed segmentation. The adaptive segmentation algorithm was tested on 926 CK18 biomarker biopsy images (326 patients) with limited background noise and 1030 prostatectomy images (374 patients) with noisy to very noisy background. The segmentation performance was measured using two different methods, namely; stability and background textural metrics. It was observed that the database of 1030 noisy prostatectomy images had a lower mean value (using stability and three background texture performance metrics) compared to the biopsy dataset of 926 images that had limited background noise. The average of all four performance metrics yielded 94.32% accuracy for prostatectomy images compared to 99.40% accuracy for biopsy images.

  6. Protons Sensitize Epithelial Cells to Mesenchymal Transition

    PubMed Central

    Wang, Minli; Hada, Megumi; Saha, Janapriya; Sridharan, Deepa M.; Pluth, Janice M.; Cucinotta, Francis A.

    2012-01-01

    Proton radiotherapy has gained more favor among oncologists as a treatment option for localized and deep-seated tumors. In addition, protons are a major constituent of the space radiation astronauts receive during space flights. The potential for these exposures to lead to, or enhance cancer risk has not been well studied. Our objective is to study the biological effects of low energy protons on epithelial cells and its propensity to enhance transforming growth factor beta 1 (TGFβ1)-mediated epithelial-mesenchymal transition (EMT), a process occurring during tumor progression and critical for invasion and metastasis. Non-transformed mink lung epithelial cells (Mv1Lu) and hTERT- immortalized human esophageal epithelial cells (EPC) were used in this study. EMT was identified by alterations in cell morphology, EMT-related gene expression changes determined using real-time PCR, and EMT changes in specific cellular markers detected by immunostaining and western blotting. Although TGFβ1 treatment alone is able to induce EMT in both Mv1Lu and EPC cells, low energy protons (5 MeV) at doses as low as 0.1 Gy can enhance TGFβ1 induced EMT. Protons alone can also induce a mild induction of EMT. SD208, a potent TGFβ Receptor 1 (TGFβR1) kinase inhibitor, can efficiently block TGFβ1/Smad signaling and attenuate EMT induction. We suggest a model for EMT after proton irradiation in normal and cancerous tissue based on our results that showed that low and high doses of protons can sensitize normal human epithelial cells to mesenchymal transition, more prominently in the presence of TGFβ1, but also in the absence of TGFβ1. PMID:22844446

  7. Epithelial odontogenic tumours in domestic animals.

    PubMed

    Walsh, K M; Denholm, L J; Cooper, B J

    1987-09-01

    Epithelial odontogenic tumours are uncommon, poorly understood and often difficult to diagnose, oral neoplasms. Dental organ pre-ameloblasts and basal lamina induce development of mesenchymal cells into odontoblasts, which produce dentin and induce pre-ameloblasts to mature into secretory ameloblasts. These reciprocal sequential inductive interactions between dental epithelium and mesenchyme form the basis for classifying epithelial odontogenic tumours. There are three tumours classified as non-inductive: ameloblastoma characterized by cords and islands of stellate reticulum with peripheral palisades of polarized columnar cells, adenomatoid ameloblastoma which has acini, rosettes and ducts of polarized columnar cells and stellate reticulum and calcifying epithelial odontogenic tumour which contains foci of Congo-red-positive material surrounded by pleomorphic polygonal epithelial cells. There are five tumours in which induction of mesenchymal tissue is evident: ameloblastic fibroma with characteristics of ameloblastoma plus proliferation of closely associated pulp-like mesenchyme; dentinoma consisting of masses of dentin, often with minimal cellular component; ameloblastic odontoma which contains palisaded epithelium and stellate reticulum as in ameloblastoma, as well as foci of dentin and/or enamel; complex odontoma which is a disorderly array of dentin, enamel, ameloblastic epithelium and odontoblasts; and compound odontoma containing denticles with well-organized tooth morphology. This paper reviews the embryogenesis of teeth and describes six types of epithelial odontogenic tumours in 13 animals. The literature concerning these tumours in nearly 250 animals is reviewed. The most commonly reported tumour is ameloblastoma and the species in which all types are most commonly reported is the dog. PMID:3316314

  8. Alveolar Epithelial Cells Undergo Epithelial-to-Mesenchymal Transition in Response to Endoplasmic Reticulum Stress*

    PubMed Central

    Tanjore, Harikrishna; Cheng, Dong-Sheng; Degryse, Amber L.; Zoz, Donald F.; Abdolrasulnia, Rasul; Lawson, William E.; Blackwell, Timothy S.

    2011-01-01

    Expression of mutant surfactant protein C (SFTPC) results in endoplasmic reticulum (ER) stress in type II alveolar epithelial cells (AECs). AECs have been implicated as a source of lung fibroblasts via epithelial-to-mesenchymal transition (EMT); therefore, we investigated whether ER stress contributes to EMT as a possible mechanism for fibrotic remodeling. ER stress was induced by tunicamyin administration or stable expression of mutant (L188Q) SFTPC in type II AEC lines. Both tunicamycin treatment and mutant SFTPC expression induced ER stress and the unfolded protein response. With tunicamycin or mutant SFTPC expression, phase contrast imaging revealed a change to a fibroblast-like appearance. During ER stress, expression of epithelial markers E-cadherin and Zonula occludens-1 decreased while expression of mesenchymal markers S100A4 and α-smooth muscle actin increased. Following induction of ER stress, we found activation of a number of pathways, including MAPK, Smad, β-catenin, and Src kinase. Using specific inhibitors, the combination of a Smad2/3 inhibitor (SB431542) and a Src kinase inhibitor (PP2) blocked EMT with maintenance of epithelial appearance and epithelial marker expression. Similar results were noted with siRNA targeting Smad2 and Src kinase. Together, these studies reveal that induction of ER stress leads to EMT in lung epithelial cells, suggesting possible cross-talk between Smad and Src kinase pathways. Dissecting pathways involved in ER stress-induced EMT may lead to new treatment strategies to limit fibrosis. PMID:21757695

  9. Non-Muscle Myosin II Regulation of Lung Epithelial Morphology

    PubMed Central

    Plosa, Erin J.; Gooding, Kimberly A.; Zent, Roy; Prince, Lawrence S.

    2012-01-01

    Background The regulation of epithelial cell shape and orientation during lung branching morphogenesis is not clearly understood. Non-muscle myosins regulate cell size, morphology, and planar cell polarity. Here we test the hypothesis that non-muscle myosin II (NM II) regulates lung epithelial morphology in a spatially restricted manner. Results Epithelial cell orientation at airway tips in fetal mouse lungs underwent a significant transformation at E17. Treatment of E15 lung explants with the NM II inhibitor blebbistatin increased airway branching, epithelial cell size, and the degree of anisotropy in epithelial cells lining the airway stalks. In cultured MLE-12 lung epithelial cells, blebbistatin increased cell velocity, but left the migratory response to FGF-10 unchanged. Conclusions In the developing lung, NM II acts to constrain cell morphology and orientation, but may be suppressed at sites of branching and cell migration. The regulation of epithelial orientation may therefore undergo dynamic variations from E15 to E17. PMID:22972683

  10. Fine structure of epithelial canal cells in petioles of Xanthium pensylvanicum

    SciTech Connect

    Maksymowych, R.; Ledbetter, M.C. Brookhaven National Lab., Upton, NY )

    1987-01-01

    Secretory canals were examined in petioles of Xanthium pensylvanicum (Cocklebur) grown under long day illumination to maintain vegetative growth. The fine structure of the canal and its epithelium was studied by electron microscopy of thin section cut transverse to the principal axis of petioles from leaves in an early stage of development. The canal proper is delimited by walls of epithelial cells which protrude into a scallop shaped cavity. In comparison to the surrounding parenchyma, the epithelial cells are smaller, cytoplasmically more dense, and less vacuolate. The epithelium contains pleomorphic starch-free plastids with planar thylakoids frequently stacked into grana; thus, the plastids are presumed photosynthetically active. Mitochondria are abundant and often dense. The cytoplasm is rich in free polysomes, and smooth endoplasmic reticulum predominates over the rough form. Spheroidal granules averaging about 530 nm in diameter are numerous in the epithelium and appear at lower concentration in neighboring cells. Many features of fine structure of the epithelial cells suggest that a high metabolic activity in present in this tissue during this early stage of development. A possible function of the canals is defense against insect predation and animal grazing.

  11. The microRNA bantam functions in epithelial cells to regulate scaling growth of dendrite arbors in Drosophila sensory neurons

    PubMed Central

    Parrish, Jay Z.; Xu, Peizhang; Kim, Charles C.; Jan, Lily Yeh; Jan, Yuh Nung

    2009-01-01

    Summary In addition to establishing dendritic coverage of the receptive field, neurons need to adjust their dendritic arbors to match changes of the receptive field. Here we show that dendrite arborization (da) sensory neurons establish dendritic coverage of the body wall early in Drosophila larval development and then grow in precise proportion to their substrate, the underlying body wall epithelium, as the larva more than triples in length. This phenomenon, referred to as scaling growth of dendrites, requires the function of the microRNA (miRNA) bantam (ban) in the epithelial cells rather than the da neurons themselves. We further show that ban in epithelial cells dampens Akt kinase activity in adjacent neurons to influence dendrite growth. This signaling between epithelial cells and neurons receiving sensory input from the body wall synchronizes their growth to ensure proper dendritic coverage of the receptive field. PMID:19778508

  12. Induced pluripotency of human prostatic epithelial cells.

    PubMed

    Zhao, Hongjuan; Sun, Ning; Young, Sarah R; Nolley, Rosalie; Santos, Jennifer; Wu, Joseph C; Peehl, Donna M

    2013-01-01

    Induced pluripotent stem (iPS) cells are a valuable resource for discovery of epigenetic changes critical to cell type-specific differentiation. Although iPS cells have been generated from other terminally differentiated cells, the reprogramming of normal adult human basal prostatic epithelial (E-PZ) cells to a pluripotent state has not been reported. Here, we attempted to reprogram E-PZ cells by forced expression of Oct4, Sox2, c-Myc, and Klf4 using lentiviral vectors and obtained embryonic stem cell (ESC)-like colonies at a frequency of 0.01%. These E-PZ-iPS-like cells with normal karyotype gained expression of pluripotent genes typical of iPS cells (Tra-1-81, SSEA-3, Nanog, Sox2, and Oct4) and lost gene expression characteristic of basal prostatic epithelial cells (CK5, CK14, and p63). E-PZ-iPS-like cells demonstrated pluripotency by differentiating into ectodermal, mesodermal, and endodermal cells in vitro, although lack of teratoma formation in vivo and incomplete demethylation of pluripotency genes suggested only partial reprogramming. Importantly, E-PZ-iPS-like cells re-expressed basal epithelial cell markers (CD44, p63, MAO-A) in response to prostate-specific medium in spheroid culture. Androgen induced expression of androgen receptor (AR), and co-culture with rat urogenital sinus further induced expression of prostate-specific antigen (PSA), a hallmark of secretory cells, suggesting that E-PZ-iPS-like cells have the capacity to differentiate into prostatic basal and secretory epithelial cells. Finally, when injected into mice, E-PZ-iPS-like cells expressed basal epithelial cell markers including CD44 and p63. When co-injected with rat urogenital mesenchyme, E-PZ-iPS-like cells expressed AR and expression of p63 and CD44 was repressed. DNA methylation profiling identified epigenetic changes in key pathways and genes involved in prostatic differentiation as E-PZ-iPS-like cells converted to differentiated AR- and PSA-expressing cells. Our results suggest that

  13. Combined FLIM and reflectance confocal microscopy for epithelial imaging

    NASA Astrophysics Data System (ADS)

    Jabbour, Joey M.; Cheng, Shuna; Shrestha, Sebina; Malik, Bilal; Jo, Javier A.; Applegate, Brian; Maitland, Kristen C.

    2012-03-01

    Current methods for detection of oral cancer lack the ability to delineate between normal and precancerous tissue with adequate sensitivity and specificity. The usual diagnostic mechanism involves visual inspection and palpation followed by tissue biopsy and histopathology, a process both invasive and time-intensive. A more sensitive and objective screening method can greatly facilitate the overall process of detection of early cancer. To this end, we present a multimodal imaging system with fluorescence lifetime imaging (FLIM) for wide field of view guidance and reflectance confocal microscopy for sub-cellular resolution imaging of epithelial tissue. Moving from a 12 x 12 mm2 field of view with 157 ìm lateral resolution using FLIM to 275 x 200 μm2 with lateral resolution of 2.2 μm using confocal microscopy, hamster cheek pouch model is imaged both in vivo and ex vivo. The results indicate that our dual modality imaging system can identify and distinguish between different tissue features, and, therefore, can potentially serve as a guide in early oral cancer detection..

  14. Lymphohaemopoietic antigens of cultured human glomerular epithelial cells.

    PubMed Central

    van der Woude, F. J.; Michael, A. F.; Muller, E.; van der Hem, G. K.; Vernier, R. L.; Kim, Y.

    1989-01-01

    Glomerular visceral epithelial cells (GVEC) from normal human glomeruli were grown in tissue culture. Cell surface markers were studied by immunofluorescence microscopy using antibodies against lymphohaemopoietic differentiation antigens which are known to be present early (BA-1, OKB2, BA-2) and late (J5, anti CR1) in renal ontogenesis. Like foetal human glomerular epithelium, the cultured cells reacted with BA-1 and OKB2 (identifying an antigen expressed on B cells and polymorphonuclear leucocytes), and BA-2 (leukaemia-associated antigen), but were consistently negative for CR1 (C3b receptor); J5 which identifies the common acute lymphoblastic leukaemia antigen (CALLA) stained variably. Reactivity with antimyosin or anti factor VIII were absent. The cells produced an extracellular matrix containing laminin, type IV collagen, and fibronectin. This study supports the notion that GVEC undergo dedifferentiation as shown by the acquisition of lymphohaemopoietic differentiation antigens present early in renal ontogeny. In addition, the production of extracellular matrix constituents in vitro may be useful for the investigation of human glomerular basement membranes. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:2647119

  15. Culture models of human mammary epithelial cell transformation

    SciTech Connect

    Stampfer, Martha R.; Yaswen, Paul

    2000-11-10

    Human pre-malignant breast diseases, particularly ductal carcinoma in situ (DCIS)3 already display several of the aberrant phenotypes found in primary breast cancers, including chromosomal abnormalities, telomerase activity, inactivation of the p53 gene and overexpression of some oncogenes. Efforts to model early breast carcinogenesis in human cell cultures have largely involved studies in vitro transformation of normal finite lifespan human mammary epithelial cells (HMEC) to immortality and malignancy. We present a model of HMEC immortal transformation consistent with the know in vivo data. This model includes a recently described, presumably epigenetic process, termed conversion, which occurs in cells that have overcome stringent replicative senescence and are thus able to maintain proliferation with critically short telomeres. The conversion process involves reactivation of telomerase activity, and acquisition of good uniform growth in the absence and presence of TFGB. We propose th at overcoming the proliferative constraints set by senescence, and undergoing conversion, represent key rate-limiting steps in human breast carcinogenesis, and occur during early stage breast cancer progression.

  16. The corneal fibrosis response to epithelial-stromal injury.

    PubMed

    Torricelli, Andre A M; Santhanam, Abirami; Wu, Jiahui; Singh, Vivek; Wilson, Steven E

    2016-01-01

    The corneal wound healing response, including the development of stromal opacity in some eyes, is a process that often leads to scarring that occurs after injury, surgery or infection to the cornea. Immediately after epithelial and stromal injury, a complex sequence of processes contributes to wound repair and regeneration of normal corneal structure and function. In some corneas, however, often depending on the type and extent of injury, the response may also lead to the development of mature vimentin+ α-smooth muscle actin+ desmin+ myofibroblasts. Myofibroblasts are specialized fibroblastic cells generated in the cornea from keratocyte-derived or bone marrow-derived precursor cells. The disorganized extracellular matrix components secreted by myofibroblasts, in addition to decreased expression of corneal crystallins in these cells, are central biological processes that result in corneal stromal fibrosis associated with opacity or "haze". Several factors are associated with myofibroblast generation and haze development after PRK surgery in rabbits, a reproducible model of scarring, including the amount of tissue ablated, which may relate to the extent of keratocyte apoptosis in the early response to injury, irregularity of stromal surface after surgery, and changes in corneal stromal proteoglycans, but normal regeneration of the epithelial basement membrane (EBM) appears to be a critical factor determining whether a cornea heals with relative transparency or vision-limiting stromal opacity. Structural and functional abnormalities of the regenerated EBM facilitate prolonged entry of epithelium-derived growth factors such as transforming growth factor β (TGF-β) and platelet-derived growth factor (PDGF) into the stroma that both drive development of mature myofibroblasts from precursor cells and lead to persistence of the cells in the anterior stroma. A major discovery that has contributed to our understanding of haze development is that keratocytes and corneal

  17. Novel human bronchial epithelial cell lines for cystic fibrosis research

    PubMed Central

    Fulcher, M. L.; Gabriel, S. E.; Olsen, J. C.; Tatreau, J. R.; Gentzsch, M.; Livanos, E.; Saavedra, M. T.; Salmon, P.; Randell, S. H.

    2009-01-01

    Immortalization of human bronchial epithelial (hBE) cells often entails loss of differentiation. Bmi-1 is a protooncogene that maintains stem cells, and its expression creates cell lines that recapitulate normal cell structure and function. We introduced Bmi-1 and the catalytic subunit of telomerase (hTERT) into three non-cystic fibrosis (CF) and three ΔF508 homozygous CF primary bronchial cell preparations. This treatment extended cell life span, although not as profoundly as viral oncogenes, and at passages 14 and 15, the new cell lines had a diploid karyotype. Ussing chamber analysis revealed variable transepithelial resistances, ranging from 200 to 1,200 Ω·cm2. In the non-CF cell lines, short-circuit currents were stimulated by forskolin and inhibited by CFTR(inh)-172 at levels mostly comparable to early passage primary cells. CF cell lines exhibited no forskolin-stimulated current and minimal CFTR(inh)-172 response. Amiloride-inhibitable and UTP-stimulated currents were present, but at lower and higher amplitudes than in primary cells, respectively. The cells exhibited a pseudostratified morphology, with prominent apical membrane polarization, few apoptotic bodies, numerous mucous secretory cells, and occasional ciliated cells. CF and non-CF cell lines produced similar levels of IL-8 at baseline and equally increased IL-8 secretion in response to IL-1β, TNF-α, and the Toll-like receptor 2 agonist Pam3Cys. Although they have lower growth potential and more fastidious growth requirements than viral oncogene transformed cells, Bmi-1/hTERT airway epithelial cell lines will be useful for several avenues of investigation and will help fill gaps currently hindering CF research and therapeutic development. PMID:18978040

  18. The effect of vitamin A on epithelial integrity.

    PubMed

    McCullough, F S; Northrop-Clewes, C A; Thurnham, D I

    1999-05-01

    Vitamin A is the generic term for a variety of fat-soluble substances including retinol, retinyl palmitate and the provitamin A carotenoids such as all-trans-beta-carotene. Vitamin A is commonly known as the anti-infective vitamin and has an essential role in vision and cellular differentiation, the latter providing a unique core mechanism helping to explain the influence of vitamin A on epithelial barriers. Alterations in the epithelial lining of vital organs occur early in deficiency, suggesting a potentially important role for the barrier function. Vitamin A deficiency (VAD) is most commonly recognized in the eye. The conjunctival-impression cytology test detects the presence of larger irregular keratinized cells and the absence of mucous-secreting goblet cells, indicative of VAD. The method is simple, quick and sensitive in populations where VAD is present. In the respiratory tract, observational studies all show an association with VAD, although vitamin A supplementation studies appear to have little effect on respiratory disease. Organ-specific targeting may improve success rates. The dual-sugar intestinal-permeability test allows the effect of vitamin A supplementation to be monitored on the gastrointestinal tract. Two vitamin A supplementation studies were carried out recently in Orissa State, India. Healthy infants of weaning age were administered orally eight weekly doses of 5.0 mg retinol equivalents and hospitalized infants received one large oral dose 60 mg retinol equivalents in the form of retinyl palmitate. Improvements in gut integrity and haematological status were observed in both studies. In summary, the response of the eye to vitamin A supplementation is well established; the present review highlights some of the more recent observations examining the effects of vitamin A. PMID:10466169

  19. Epithelial inactivation of Yy1 abrogates lung branching morphogenesis.

    PubMed

    Boucherat, Olivier; Landry-Truchon, Kim; Bérubé-Simard, Félix-Antoine; Houde, Nicolas; Beuret, Laurent; Lezmi, Guillaume; Foulkes, William D; Delacourt, Christophe; Charron, Jean; Jeannotte, Lucie

    2015-09-01

    Yin Yang 1 (YY1) is a multifunctional zinc-finger-containing transcription factor that plays crucial roles in numerous biological processes by selectively activating or repressing transcription, depending upon promoter contextual differences and specific protein interactions. In mice, Yy1 null mutants die early in gestation whereas Yy1 hypomorphs die at birth from lung defects. We studied how the epithelial-specific inactivation of Yy1 impacts on lung development. The Yy1 mutation in lung epithelium resulted in neonatal death due to respiratory failure. It impaired tracheal cartilage formation, altered cell differentiation, abrogated lung branching and caused airway dilation similar to that seen in human congenital cystic lung diseases. The cystic lung phenotype in Yy1 mutants can be partly explained by the reduced expression of Shh, a transcriptional target of YY1, in lung endoderm, and the subsequent derepression of mesenchymal Fgf10 expression. Accordingly, SHH supplementation partially rescued the lung phenotype in vitro. Analysis of human lung tissues revealed decreased YY1 expression in children with pleuropulmonary blastoma (PPB), a rare pediatric lung tumor arising during fetal development and associated with DICER1 mutations. No evidence for a potential genetic interplay between murine Dicer and Yy1 genes during lung morphogenesis was observed. However, the cystic lung phenotype resulting from the epithelial inactivation of Dicer function mimics the Yy1 lung malformations with similar changes in Shh and Fgf10 expression. Together, our data demonstrate the crucial requirement for YY1 in lung morphogenesis and identify Yy1 mutant mice as a potential model for studying the genetic basis of PPB. PMID:26329601

  20. Expression analysis of Matrix Metalloproteinase-9 in epithelialized and non-epithelialized apical periodontitis lesions

    PubMed Central

    Carneiro, Everdan; Menezes, Renato; Garlet, Gustavo Pompermaier; Garcia, Roberto Brandão; Bramante, Clóvis Monteiro; Figueira, Rita; Sogayar, Mari; Granjeiro, José Mauro

    2009-01-01

    OBJECTIVE To determine the expression of matrix metalloproteinase-9 (MMP-9) in apical periodontitis lesions. STUDY DESIGN Nineteen epithelialized and eighteen non-epithelialized apical periodontitis lesions were collected after periapical surgery. After histological processing, serial sectioning, H&E staining and microscopic analysis, 10 epithelialized and 10 non-epithelialized lesions were selected for immunohistochemical analysis for MMP-9 and CD 68. At least 1/3 of each specimen was frozen at −70°C for further mRNA isolation and reverse transcription into cDNA for Real-Time-PCR procedures. The relative expression of a target gene was determined in comparison with reference genes (GAPDH, HPRT, β-actin and BCRP). RESULTS Polymorphonuclear neutrophils, macrophages and lymphocytes were stained for MMP-9 in both types of lesions, and when present, epithelial cells were also stained. The number and the ratio of MMP-9+/total cells were greater in non-epithelialized than epithelialized lesions (p=0.0001) and showed a positive correlation to CD68+/total cells (p=0.045). No significant differences were observed for MMP-9 mRNA expression between ephithelized and non-ephithelized lesions. However, when compared to healthy periapical ligaments, both types of lesions presented increased MMP-9 expression (p<0.0001). CONCLUSION The present data suggest the participation of several inflammatory cells, mainlly CD68+ cells, in the MMP-9 expression in apical periodontitis lesions. MMP-9 could be actively enroled in the ECM degradation in apical periodontitis lesions. PMID:18926740

  1. Establishment of Hertwig's epithelial root sheath/epithelial rests of Malassez cell line from human periodontium.

    PubMed

    Nam, Hyun; Kim, Ji-Hye; Kim, Jae-Won; Seo, Byoung-Moo; Park, Joo-Cheol; Kim, Jung-Wook; Lee, Gene

    2014-07-01

    Human Hertwig's epithelial root sheath/epithelial rests of Malassez (HERS/ERM) cells are epithelial remnants of teeth residing in the periodontium. Although the functional roles of HERS/ERM cells have yet to be elucidated, they are a unique epithelial cell population in adult teeth and are reported to have stem cell characteristics. Therefore, HERS/ERM cells might play a role as an epithelial component for the repair or regeneration of dental hard tissues; however, they are very rare population in periodontium and the primary isolation of them is considered to be difficult. To overcome these problems, we immortalized primary HERS/ERM cells isolated from human periodontium using SV40 large T antigen (SV40 LT) and performed a characterization of the immortalized cell line. Primary HERS/ERM cells could not be maintained for more than 6 passages; however, immortalized HERS/ERM cells were maintained for more than 20 passages. There were no differences in the morphological and immunophenotypic characteristics of HERS/ERM cells and immortalized HERS/ERM cells. The expression of epithelial stem cell and embryonic stem cell markers was maintained in immortalized HERS/ERM cells. Moreover, immortalized HERS/ERM cells could acquire mesenchymal phenotypes through the epithelial-mesenchymal transition via TGF-β1. In conclusion, we established an immortalized human HERS/ERM cell line with SV40 LT and expect this cell line to contribute to the understanding of the functional roles of HERS/ERM cells and the tissue engineering of teeth. PMID:25081036

  2. Taxonomic Identification of Ruminal Epithelial Bacterial Diversity during Rumen Development in Goats.

    PubMed

    Jiao, Jinzhen; Huang, Jinyu; Zhou, Chuanshe; Tan, Zhiliang

    2015-05-15

    Understanding of the colonization process of epithelial bacteria attached to the rumen tissue during rumen development is very limited. Ruminal epithelial bacterial colonization is of great significance for the relationship between the microbiota and the host and can influence the early development and health of the host. MiSeq sequencing of 16S rRNA genes and quantitative real-time PCR (qPCR) were applied to characterize ruminal epithelial bacterial diversity during rumen development in this study. Seventeen goat kids were selected to reflect the no-rumination (0 and 7 days), transition (28 and 42 days), and rumination (70 days) phases of animal development. Alpha diversity indices (operational taxonomic unit [OTU] numbers, Chao estimate, and Shannon index) increased (P < 0.01) with age, and principal coordinate analysis (PCoA) revealed that the samples clustered together according to age group. Phylogenetic analysis revealed that Proteobacteria, Firmicutes, and Bacteroidetes were detected as the dominant phyla regardless of the age group, and the abundance of Proteobacteria declined quadratically with age (P < 0.001), while the abundances of Bacteroidetes (P = 0.088) and Firmicutes (P = 0.009) increased with age. At the genus level, Escherichia (80.79%) dominated at day zero, while Prevotella, Butyrivibrio, and Campylobacter surged (linearly; P < 0.01) in abundance at 42 and 70 days. qPCR showed that the total copy number of epithelial bacteria increased linearly (P = 0.013) with age. In addition, the abundances of the genera Butyrivibrio, Campylobacter, and Desulfobulbus were positively correlated with rumen weight, rumen papilla length, ruminal ammonia and total volatile fatty acid concentrations, and activities of carboxymethylcellulase (CMCase) and xylanase. Taking the data together, colonization by ruminal epithelial bacteria is age related (achieved at 2 months) and might participate in the anatomic and functional development of the rumen. PMID:25769827

  3. Taxonomic Identification of Ruminal Epithelial Bacterial Diversity during Rumen Development in Goats

    PubMed Central

    Jiao, Jinzhen; Huang, Jinyu; Zhou, Chuanshe

    2015-01-01

    Understanding of the colonization process of epithelial bacteria attached to the rumen tissue during rumen development is very limited. Ruminal epithelial bacterial colonization is of great significance for the relationship between the microbiota and the host and can influence the early development and health of the host. MiSeq sequencing of 16S rRNA genes and quantitative real-time PCR (qPCR) were applied to characterize ruminal epithelial bacterial diversity during rumen development in this study. Seventeen goat kids were selected to reflect the no-rumination (0 and 7 days), transition (28 and 42 days), and rumination (70 days) phases of animal development. Alpha diversity indices (operational taxonomic unit [OTU] numbers, Chao estimate, and Shannon index) increased (P < 0.01) with age, and principal coordinate analysis (PCoA) revealed that the samples clustered together according to age group. Phylogenetic analysis revealed that Proteobacteria, Firmicutes, and Bacteroidetes were detected as the dominant phyla regardless of the age group, and the abundance of Proteobacteria declined quadratically with age (P < 0.001), while the abundances of Bacteroidetes (P = 0.088) and Firmicutes (P = 0.009) increased with age. At the genus level, Escherichia (80.79%) dominated at day zero, while Prevotella, Butyrivibrio, and Campylobacter surged (linearly; P < 0.01) in abundance at 42 and 70 days. qPCR showed that the total copy number of epithelial bacteria increased linearly (P = 0.013) with age. In addition, the abundances of the genera Butyrivibrio, Campylobacter, and Desulfobulbus were positively correlated with rumen weight, rumen papilla length, ruminal ammonia and total volatile fatty acid concentrations, and activities of carboxymethylcellulase (CMCase) and xylanase. Taking the data together, colonization by ruminal epithelial bacteria is age related (achieved at 2 months) and might participate in the anatomic and functional development of the rumen. PMID:25769827

  4. The PI 3-kinase and mTOR signaling pathways are important modulators of epithelial tubule formation.

    PubMed

    Walid, Shereaf; Eisen, Randi; Ratcliffe, Don R; Dai, Kezhi; Hussain, M Mahmood; Ojakian, George K

    2008-08-01

    Using MDCK cells as a model system, evidence is presented demonstrating that the signaling pathways mammalian target of rapamycin (mTOR) and phosphoinositide 3-kinase (PI 3-kinase) play important roles in the regulation of epithelial tubule formation. Incubation of cells with collagen gel overlays induced early (4-8 h) reorganization of cells (epithelial remodeling) into three-dimensional multicellular tubular structures over 24 h. An MDCK cell line stably expressing the PH domain of Akt, a PI 3-kinase downstream effector, coupled to green fluorescent protein (GFP-Akt-PH) was used to determine the distribution of phosphatidyl inositol-3,4,5-P(3) (PIP(3)), a product of PI 3-kinase. GFP-Akt-PH was associated with lateral membranes in control cells. After incubation with collagen gel overlays, GFP-Akt-PH redistributed into the lamellipodia of migrating cells suggesting that PIP(3) plays a role in epithelial remodeling. Using the small molecule inhibitor LY-294002 that inhibits both mTOR and PI 3-kinase, we demonstrated that kinase activity was required for epithelial remodeling, disruption of cell junctions and subsequent modulation of tubule formation. Since the mTOR signaling pathway is downstream of PI 3-kinase, the effects of rapamycin, a specific mTOR inhibitor, on tubule formation were assessed. Rapamycin did not affect epithelial remodeling or GFP-Akt-PH redistribution but inhibited elongated tubule formation that occurred later (24 h) in morphogenesis. These results were further supported by using RNA interference to down-regulate mTOR and inhibit tubule formation. Our studies demonstrate that PI 3-kinase regulates early epithelial remodeling stages while mTOR modulates latter stages of tubule development. PMID:18366086

  5. Structural centrosome aberrations favor proliferation by abrogating microtubule-dependent tissue integrity of breast epithelial mammospheres.

    PubMed

    Schnerch, D; Nigg, E A

    2016-05-01

    Structural centrosome aberrations are frequently observed in early stage carcinomas, but their role in malignant transformation is poorly understood. Here, we examined the impact of overexpression of Ninein-like protein (Nlp) on the architecture of polarized epithelia in three-dimensional mammospheres. When Nlp was overexpressed to levels resembling those seen in human tumors, it formed striking centrosome-related bodies (CRBs), which sequestered Ninein and affected the kinetics of microtubule (MT) nucleation and release. In turn, the profound reorganization of the MT cytoskeleton resulted in mislocalization of several adhesion and junction proteins as well as the tumor suppressor Scribble, resulting in the disruption of epithelial polarity, cell-cell interactions and mammosphere architecture. Remarkably, cells harboring Nlp-CRBs displayed an enhanced proliferative response to epidermal growth factor. These results demonstrate that structural centrosome aberrations cause not only the disruption of epithelial polarity but also favor overproliferation, two phenotypes typically associated with human carcinomas. PMID:26364601

  6. TLR sorting by Rab11 endosomes maintains intestinal epithelial-microbial homeostasis

    PubMed Central

    Yu, Shiyan; Nie, Yingchao; Knowles, Byron; Sakamori, Ryotaro; Stypulkowski, Ewa; Patel, Chirag; Das, Soumyashree; Douard, Veronique; Ferraris, Ronaldo P; Bonder, Edward M; Goldenring, James R; Ip, Yicktung Tony; Gao, Nan

    2014-01-01

    Compartmentalization of Toll-like receptors (TLRs) in intestinal epithelial cells (IECs) regulates distinct immune responses to microbes; however, the specific cellular machinery that controls this mechanism has not been fully identified. Here we provide genetic evidences that the recycling endosomal compartment in enterocytes maintains a homeostatic TLR9 intracellular distribution, supporting mucosal tolerance to normal microbiota. Genetic ablation of a recycling endosome resident small GTPase, Rab11a, a gene adjacent to a Crohn's disease risk locus, in mouse IECs and in Drosophila midgut caused epithelial cell-intrinsic cytokine production, inflammatory bowel phenotype, and early mortality. Unlike wild-type controls, germ-free Rab11a-deficient mouse intestines failed to tolerate the intraluminal stimulation of microbial agonists. Thus, Rab11a endosome controls intestinal host-microbial homeostasis at least partially via sorting TLRs. PMID:25063677

  7. Mechanisms of Disease: Host-Pathogen Interactions between Burkholderia Species and Lung Epithelial Cells

    PubMed Central

    David, Jonathan; Bell, Rachel E.; Clark, Graeme C.

    2015-01-01

    Members of the Burkholderia species can cause a range of severe, often fatal, respiratory diseases. A variety of in vitro models of infection have been developed in an attempt to elucidate the mechanism by which Burkholderia spp. gain entry to and interact with the body. The majority of studies have tended to focus on the interaction of bacteria with phagocytic cells with a paucity of information available with regard to the lung epithelium. However, the lung epithelium is becoming more widely recognized as an important player in innate immunity and the early response to infections. Here we review the complex relationship between Burkholderia species and epithelial cells with an emphasis on the most pathogenic species, Burkholderia pseudomallei and Burkholderia mallei. The current gaps in knowledge in our understanding are highlighted along with the epithelial host-pathogen interactions that offer potential opportunities for therapeutic intervention. PMID:26636042

  8. Structural centrosome aberrations favor proliferation by abrogating microtubule-dependent tissue integrity of breast epithelial mammospheres

    PubMed Central

    Schnerch, D; Nigg, E A

    2016-01-01

    Structural centrosome aberrations are frequently observed in early stage carcinomas, but their role in malignant transformation is poorly understood. Here, we examined the impact of overexpression of Ninein-like protein (Nlp) on the architecture of polarized epithelia in three-dimensional mammospheres. When Nlp was overexpressed to levels resembling those seen in human tumors, it formed striking centrosome-related bodies (CRBs), which sequestered Ninein and affected the kinetics of microtubule (MT) nucleation and release. In turn, the profound reorganization of the MT cytoskeleton resulted in mislocalization of several adhesion and junction proteins as well as the tumor suppressor Scribble, resulting in the disruption of epithelial polarity, cell-cell interactions and mammosphere architecture. Remarkably, cells harboring Nlp-CRBs displayed an enhanced proliferative response to epidermal growth factor. These results demonstrate that structural centrosome aberrations cause not only the disruption of epithelial polarity but also favor overproliferation, two phenotypes typically associated with human carcinomas. PMID:26364601

  9. DNA typing of epithelial cells after strangulation.

    PubMed

    Wiegand, P; Kleiber, M

    1997-01-01

    DNA typing was carried out on epithelial cells which were transferred from the hands of the suspect onto the neck of the victim. In an experimental study 16 suspect-victim combinations were investigated for estimating the typing success. Alternatively to an attack against the neck, the upper arm was used for "strangulation". PCR typing was carried out using the short tandem repeat systems (STRs) HumCD4, HumVWF31A (VWA) and Hum-FIBRA (FGA) and the success rate was > 70% for all 3 systems. In most of the cases mixed patterns containing the phenotype of the suspect and the victim were obtained. In a case where strangulation was the cause of death, epithelial cells could be removed from the neck of the victim. The DNA pattern of the suspect could be successfully amplified using four STRs, demonstrating the applicability of this approach for practical casework. PMID:9274940

  10. Probiotic bacteria and intestinal epithelial barrier function.

    PubMed

    Ohland, Christina L; Macnaughton, Wallace K

    2010-06-01

    The intestinal tract is a diverse microenvironment where more than 500 species of bacteria thrive. A single layer of epithelium is all that separates these commensal microorganisms and pathogens from the underlying immune cells, and thus epithelial barrier function is a key component in the arsenal of defense mechanisms required to prevent infection and inflammation. The epithelial barrier consists of a dense mucous layer containing secretory IgA and antimicrobial peptides as well as dynamic junctional complexes that regulate permeability between cells. Probiotics are live microorganisms that confer benefit to the host and that have been suggested to ameliorate or prevent diseases including antibiotic-associated diarrhea, irritable bowel syndrome, and inflammatory bowel disease. Probiotics likely function through enhancement of barrier function, immunomodulation, and competitive adherence to the mucus and epithelium. This review summarizes the evidence about effects of the many available probiotics with an emphasis on intestinal barrier function and the mechanisms affected by probiotics. PMID:20299599

  11. Epithelial Proliferation on Curved Toroidal Surfaces

    NASA Astrophysics Data System (ADS)

    Chang, Ya-Wen; Cruz, Ricardo; Fragkopoulos, Alexandros; Marquez, Samantha; Garcia, Andres; Fernandez-Nieves, Alberto

    Cellular environment influences a multitude of cellular functions by providing chemical and physical signals that modulate cell behavior, dynamics, development, and eventually survival. In strongly interacting epithelial cells, cells coordinate their behavior to respond to mechanical constraints in 2D. Local differences in tissue tension has also been shown to impact cell reproduction within an epithelial-cell sheet. Much less is known about how cells respond to out-of-plane curvatures. Here, we describe the proliferation of MDCK on toroidal hydrogel substrates, which unlike spheres or planes, have regions of both positive and negative Gaussian curvature. Additionally, the range of curvatures can be controlled by varying the size and aspect ratio of the torus, allowing us to quantify the relation between substrate curvature and cell proliferation.

  12. Retinal pigment epithelial change and partial lipodystrophy.

    PubMed Central

    Davis, T. M.; Holdright, D. R.; Schulenberg, W. E.; Turner, R. C.; Joplin, G. F.

    1988-01-01

    Cuticular drusen and retinal pigment epithelial changes were found incidentally in a 27 year old Lebanese woman during assessment of partial lipodystrophy. Her vision was normal despite involvement of both maculae. The patient had hypocomplementaemia, but serum C3 nephritic factor was absent and renal function was normal. She had impaired glucose tolerance and a continuous infusion of glucose with model assessment (CIGMA) test revealed low normal tissue insulin sensitivity and high normal pancreatic beta cell function. Mild fasting hypertriglyceridaemia (2.0 mmol/l) may have been secondary to impaired insulin sensitivity. Endocrine function was otherwise normal apart from a completely absent growth hormone response to adequate hypoglycaemia. The simultaneous occurrence of partial lipodystrophy and retinal pigmentary epithelial and basement membrane changes appears to be a newly recognized syndrome. Images Figure 1 Figure 2 PMID:3255937

  13. Extensive Focal Epithelial Hyperplasia: A Case Report

    PubMed Central

    Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab

    2015-01-01

    Focal epithelial hyperplasia (FEH) or Heck’s disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and histopathological features. Dental practitioner should be aware of these types of lesions and histopathological examination together and a careful clinical observation should be carried out for a definitive diagnosis. PMID:26351501

  14. Live Imaging and Gene Expression Analysis in Zebrafish Identifies a Link between Neutrophils and Epithelial to Mesenchymal Transition

    PubMed Central

    Freisinger, Christina M.; Huttenlocher, Anna

    2014-01-01

    Chronic inflammation is associated with epithelial to mesenchymal transition (EMT) and cancer progression however the relationship between inflammation and EMT remains unclear. Here, we have exploited zebrafish to visualize and quantify the earliest events during epithelial cell transformation induced by oncogenic HRasV12. Live imaging revealed that expression of HRasV12 in the epidermis results in EMT and chronic neutrophil and macrophage infiltration. We have developed an in vivo system to probe and quantify gene expression changes specifically in transformed cells from chimeric zebrafish expressing oncogenic HRasV12 using translating ribosomal affinity purification (TRAP). We found that the expression of genes associated with EMT, including slug, vimentin and mmp9, are enriched in HRasV12 transformed epithelial cells and that this enrichment requires the presence of neutrophils. An early signal induced by HRasV12 in epithelial cells is the expression of il-8 (cxcl8) and we found that the chemokine receptor, Cxcr2, mediates neutrophil but not macrophage recruitment to the transformed cells. Surprisingly, we also found a cell autonomous role for Cxcr2 signaling in transformed cells for both neutrophil recruitment and EMT related gene expression associated with Ras transformation. Taken together, these findings implicate both autocrine and paracrine signaling through Cxcr2 in the regulation of inflammation and gene expression in transformed epithelial cells. PMID:25372289

  15. Fibro-epithelial hyperplasia mimicking mucocele.

    PubMed

    Jain, K; Singh, B D; Dubey, A; Avinash, A

    2014-01-01

    The effects of chronic local irritation have been seen commonly in the form of fibroma or mucocele in children. We report a ten year old girl with the chief complaint of swelling in the lower right region of labial mucosa which was diagnosed clinically as mucocele and histologically as fibro-epithelial hyperplasia. Surgical excision was done under local anesthesia with no post-operative complication. PMID:25552222

  16. Early years.

    PubMed

    2011-04-01

    Healthcare professionals in Scotland who are involved in early years work now have an additional resource in the shape of NHS Scotland's Maternal and Early Years website, aimed at practitioners at all levels. The site includes evidence updates, news and events, and can be accessed at www.maternal-and-early-years.org.uk. PMID:27368523

  17. [Early Intervention.

    ERIC Educational Resources Information Center

    Pawl, Jeree, Ed.

    1992-01-01

    This newsletter focuses on the theme of early intervention which infants and young children with special needs in nine brief articles: "Early Intervention: A Matter of Context" (Samuel J. Meisels); "Early Intervention Research: Asking and Answering Meaningful Questions" (Jack P. Shonkoff); "From Case Management to Service Coordination: Families,…

  18. Early Intervention.

    ERIC Educational Resources Information Center

    Abery, Brian, Ed.; McConnell, Scott, Ed.

    1989-01-01

    This "feature issue" focuses on early intervention with handicapped children, with an emphasis on: Project EDGE (Expanding Developmental Growth through Education), an early intervention research project initiated in 1968; strategies for developing family-friendly early intervention services; and progress reports from various states and programs.…

  19. Epithelial Notch signaling regulates lung alveolar morphogenesis and airway epithelial integrity.

    PubMed

    Tsao, Po-Nien; Matsuoka, Chisa; Wei, Shu-Chen; Sato, Atsuyasu; Sato, Susumu; Hasegawa, Koichi; Chen, Hung-Kuan; Ling, Thai-Yen; Mori, Munemasa; Cardoso, Wellington V; Morimoto, Mitsuru

    2016-07-19

    Abnormal enlargement of the alveolar spaces is a hallmark of conditions such as chronic obstructive pulmonary disease and bronchopulmonary dysplasia. Notch signaling is crucial for differentiation and regeneration and repair of the airway epithelium. However, how Notch influences the alveolar compartment and integrates this process with airway development remains little understood. Here we report a prominent role of Notch signaling in the epithelial-mesenchymal interactions that lead to alveolar formation in the developing lung. We found that alveolar type II cells are major sites of Notch2 activation and show by Notch2-specific epithelial deletion (Notch2(cNull)) a unique contribution of this receptor to alveologenesis. Epithelial Notch2 was required for type II cell induction of the PDGF-A ligand and subsequent paracrine activation of PDGF receptor-α signaling in alveolar myofibroblast progenitors. Moreover, Notch2 was crucial in maintaining the integrity of the epithelial and smooth muscle layers of the distal conducting airways. Our data suggest that epithelial Notch signaling regulates multiple aspects of postnatal development in the distal lung and may represent a potential target for intervention in pulmonary diseases. PMID:27364009

  20. Andrographolide suppresses epithelial mesenchymal transition by inhibition of MAPK signalling pathway in lens epithelial cells.

    PubMed

    Kayastha, Forum; Johar, Kaid; Gajjar, Devarshi; Arora, Anshul; Madhu, Hardik; Ganatra, Darshini; Vasavada, Abhay

    2015-06-01

    Epithelial mesenchymal transition (EMT) of lens epithelial cells (LECs) may contribute to the development of posterior capsular opacification (PCO), which leads to visual impairment. Andrographolide has been shown to have therapeutic potential against various cancers. However, its effect on human LECs is still unknown. The purpose of this study is to evaluate the effect of andrographolide on EMT induced by growth factors in the fetal human lens epithelial cell line (FHL 124). Initially the LECs were treated with growth factors (TGF-beta 2 and bFGF) to induce EMT. Subsequently these EMT-induced cells were treated with andrographolide at 100 and 500 nM concentrations for 24 h. Our results showed that FHL 124 cells treated with growth factors had a significant decrease in protein and m-RNA levels of epithelial markers pax6 and E-Cadherin. After administering andrographolide, these levels significantly increased. It was noticed that EMT markers alpha-SMA, fibronectin and collagen IV significantly decreased after treatment with andrographolide when compared to the other group. Treatment with andrographolide significantly inhibited phosphorylation of ERK and JNK. Cell cycle analysis showed that andrographolide did not arrest cells at G0/G1 or G2/M at tested concentrations. Our findings suggest that andrographolide helps sustain epithelial characteristics by modulating EMT markers and inhibiting the mitogen-activated protein kinase (MAPK) signalling pathway in LECs. Hence it can prove to be useful in curbing EMT-mediated PCO. PMID:25963259

  1. Epithelial-mesenchymal, mesenchymal-epithelial, and endothelial-mesenchymal transitions in malignant tumors: An update

    PubMed Central

    Gurzu, Simona; Turdean, Sabin; Kovecsi, Attila; Contac, Anca Otilia; Jung, Ioan

    2015-01-01

    Epithelial-to-mesenchymal transition (EMT) represents conversion of an epithelial cell in an elongated cell with mesenchymal phenotype, which can occur in physiologic and pathologic processes such as embryogenesis (type 1 EMT), wound healing and/or fibrosis (type 2 EMT) and malignant tumors (type 3 EMT). The proliferation rate, metastasizing and recurrence capacity, as also the individualized response at chemotherapics, in both epithelial and mesenchymal malignant tumors is known to be influenced by reversible switch between EMT and mesenchymal-to-epithelial transition (MET). Although much research work has already been done in these fields, the specific molecular pathways of EMT, relating to the tumor type and tumor localization, are yet to be elucidated. In this paper, based on the literature and personal experience of the authors, an update in the field of EMT vs MET in epithelial and mesenchymal tumors is presented. The authors tried to present the latest data about the particularities of these processes, and also of the so-called endothelial-to-mesenchymal transition, based on tumor location. The EMT-angiogenesis link is discussed as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management. The paper begins with presentation of the basic aspects of EMT, its classification and assessment possibilities, and concludes with prognostic and therapeutic perspectives. The particularities of EMT and MET in gastric and colorectal carcinomas, pancreatic cancer, hepatocellular and cholangiocarcinomas, and lung, breast and prostate cancers, respectively in sarcomas and gastrointestinal stromal tumors are presented in detail. PMID:25984514

  2. CUX1/Wnt signaling regulates Epithelial Mesenchymal Transition in EBV infected epithelial cells

    SciTech Connect

    Malizia, Andrea P.; Lacey, Noreen; Walls, Dermot; Egan, Jim J.; Doran, Peter P.

    2009-07-01

    Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGF{beta}1-mediated lytic phase. EBV lytic reactivation by TGF{beta}1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM{sub 1}81552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  3. Epithelial-mesenchymal, mesenchymal-epithelial, and endothelial-mesenchymal transitions in malignant tumors: An update.

    PubMed

    Gurzu, Simona; Turdean, Sabin; Kovecsi, Attila; Contac, Anca Otilia; Jung, Ioan

    2015-05-16

    Epithelial-to-mesenchymal transition (EMT) represents conversion of an epithelial cell in an elongated cell with mesenchymal phenotype, which can occur in physiologic and pathologic processes such as embryogenesis (type 1 EMT), wound healing and/or fibrosis (type 2 EMT) and malignant tumors (type 3 EMT). The proliferation rate, metastasizing and recurrence capacity, as also the individualized response at chemotherapics, in both epithelial and mesenchymal malignant tumors is known to be influenced by reversible switch between EMT and mesenchymal-to-epithelial transition (MET). Although much research work has already been done in these fields, the specific molecular pathways of EMT, relating to the tumor type and tumor localization, are yet to be elucidated. In this paper, based on the literature and personal experience of the authors, an update in the field of EMT vs MET in epithelial and mesenchymal tumors is presented. The authors tried to present the latest data about the particularities of these processes, and also of the so-called endothelial-to-mesenchymal transition, based on tumor location. The EMT-angiogenesis link is discussed as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management. The paper begins with presentation of the basic aspects of EMT, its classification and assessment possibilities, and concludes with prognostic and therapeutic perspectives. The particularities of EMT and MET in gastric and colorectal carcinomas, pancreatic cancer, hepatocellular and cholangiocarcinomas, and lung, breast and prostate cancers, respectively in sarcomas and gastrointestinal stromal tumors are presented in detail. PMID:25984514

  4. An epithelial armamentarium to sense the microbiota.

    PubMed

    Prescott, David; Lee, Jooeun; Philpott, Dana J

    2013-11-30

    Intestinal epithelial cells were once thought to be inert, non-responsive cells that simply acted as a physical barrier that prevents the contents of the intestinal lumen from accessing the underlying tissue. However, it is now clear that these cells express a full repertoire of Toll- and Nod-like receptors, and that their activation by components of the microbiota is vital for the development of a functional epithelium, maintenance of barrier integrity, and defense against pathogenic organisms. Additionally, mounting evidence suggests that epithelial sensing of bacteria plays a significant role in the management of the numbers and types of microbes present in the gut microbiota via the production of antimicrobial peptides and other microbe-modulatory products. This is a critical process, as it is now becoming apparent that alterations in the composition of the microbiota can predispose an individual to a wide variety of chronic diseases. In this review, we will discuss the bacterial pattern recognition receptors that are known to be expressed by the intestinal epithelium, and how each of them individually contributes to these vital protective functions. Moreover, we will review what is known about the communication between epithelial cells and various classes of underlying leukocytes, and discuss how they interact with the microbiota to form a three-part relationship that maintains homeostasis in the gut. PMID:24169517

  5. Normal and Abnormal Epithelial Differentiation in the Female Reproductive Tract

    PubMed Central

    Kurita, Takeshi

    2011-01-01

    In mammals, the female reproductive tract (FRT) develops from a pair of paramesonephric or Müllerian ducts (MDs), which arise from coelomic epithelial cells of mesodermal origin. During development, the MDs undergo a dynamic morphogenetic transformation from simple tubes consisting of homogeneous epithelium and surrounding mesenchyme into several distinct organs namely the oviduct, uterus, cervix and vagina. Following the formation of anatomically distinctive organs, the uniform MD epithelium (MDE) differentiates into diverse epithelial cell types with unique morphology and functions in each organ. Classic tissue recombination studies, in which the epithelium and mesenchyme isolated from the newborn mouse FRT were recombined, have established that the organ specific epithelial cell fate of MDE is dictated by the underlying mesenchyme. The tissue recombination studies have also demonstrated that there is a narrow developmental window for the epithelial cell fate determination in MD-derived organs. Accordingly, the developmental plasticity of epithelial cells is mostly lost in mature FRT. If the signaling that controls epithelial differentiation is disrupted at the critical developmental stage, the cell fate of MD-derived epithelial tissues will be permanently altered and can result in epithelial lesions in adult life. A disruption of signaling that maintains epithelial cell fate can also cause epithelial lesions in the FRT. In this review, the pathogenesis of cervical/vaginal adenoses and uterine squamous metaplasia is discussed as examples of such incidences. PMID:21612855

  6. Role of epithelial hyperplasia in regression following photorefractive keratectomy.

    PubMed Central

    Gauthier, C. A.; Holden, B. A.; Epstein, D.; Tengroth, B.; Fagerholm, P.; Hamberg-Nyström, H.

    1996-01-01

    AIM--To determine the relation between epithelial hyperplasia and regression of effect after photorefractive keratectomy (PRK). METHODS--Seventy unilaterally treated patients with PRK were examined. All eyes had been treated with the Summit excimer laser 27 (SD 7) months previously with zone diameters of 4.1 to 5.0 mm. The untreated fellow eyes served as controls. Epithelial thickness was measured centrally with a thin slit optical pachometer and manifest subjective refraction was performed. RESULTS--The epithelium was 21% thicker in the treated eye (p < 0.0001). The relation between refractive regression and epithelial hyperplasia was significant (r = 0.41; p < 0.001). CONCLUSIONS--Epithelial hyperplasia after PRK correlated with the myopic shift (including hyperopia reduction) after treatment with the Summit laser. A model is proposed suggesting that both subepithelial and epithelial layers contribute to regression in the Summit treated eyes with 18 microns of epithelial hyperplasia contributing each dioptre of regression. PMID:8759267

  7. Control of local immunity by airway epithelial cells.

    PubMed

    Weitnauer, M; Mijošek, V; Dalpke, A H

    2016-03-01

    The lung is ventilated by thousand liters of air per day. Inevitably, the respiratory system comes into contact with airborne microbial compounds, most of them harmless contaminants. Airway epithelial cells are known to have innate sensor functions, thus being able to detect microbial danger. To avoid chronic inflammation, the pulmonary system has developed specific means to control local immune responses. Even though airway epithelial cells can act as proinflammatory promoters, we propose that under homeostatic conditions airway epithelial cells are important modulators of immune responses in the lung. In this review, we discuss epithelial cell regulatory functions that control reactivity of professional immune cells within the microenvironment of the airways and how these mechanisms are altered in pulmonary diseases. Regulation by epithelial cells can be divided into two mechanisms: (1) mediators regulate epithelial cells' innate sensitivity in cis and (2) factors are produced that limit reactivity of immune cells in trans. PMID:26627458

  8. Innate lymphoid cells regulate intestinal epithelial cell glycosylation.

    PubMed

    Goto, Yoshiyuki; Obata, Takashi; Kunisawa, Jun; Sato, Shintaro; Ivanov, Ivaylo I; Lamichhane, Aayam; Takeyama, Natsumi; Kamioka, Mariko; Sakamoto, Mitsuo; Matsuki, Takahiro; Setoyama, Hiromi; Imaoka, Akemi; Uematsu, Satoshi; Akira, Shizuo; Domino, Steven E; Kulig, Paulina; Becher, Burkhard; Renauld, Jean-Christophe; Sasakawa, Chihiro; Umesaki, Yoshinori; Benno, Yoshimi; Kiyono, Hiroshi

    2014-09-12

    Fucosylation of intestinal epithelial cells, catalyzed by fucosyltransferase 2 (Fut2), is a major glycosylation mechanism of host-microbiota symbiosis. Commensal bacteria induce epithelial fucosylation, and epithelial fucose is used as a dietary carbohydrate by many of these bacteria. However, the molecular and cellular mechanisms that regulate the induction of epithelial fucosyl