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Sample records for muc1 limits helicobacter

  1. Higher levels of salivary MUC5B and MUC7 in individuals with gastric diseases who harbor Helicobacter pylori

    NARCIS (Netherlands)

    Silva, D.G.; Stevens, R.H.; Macedo, J.M.B.; Hirata, R.; Pinto, A.C.; Alves, L.M.; Veerman, E.C.I.; Tinoco, E.M.B.

    2009-01-01

    Objective: The aim of the present study was to assess the salivary levels of MUC5B and MUC7 in individuals with dyspeptic disease and Helicobacter pylori (H. pylori) in the stomach, compared to individuals without dyspeptic disease. Methods: 30 individuals with dyspeptic disease, who underwent

  2. Molecular interactions between MUC1 epithelial mucin, β-catenin, and CagA proteins

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    Wei eGuang

    2012-05-01

    Full Text Available Interleukin (IL-8-driven neutrophil infiltration of the gastric mucosa is pathognomonic of persistent Helicobacter pylori infection. Our prior study showed that ectopic over-expression of MUC1 in human AGS gastric epithelial cells reduced H. pylori-stimulated IL-8 production compared with cells expressing MUC1 endogenously. Conversely, Muc1 knockout (Muc1-/- mice displayed an increased level of transcripts encoding the keratinocyte chemoattractant (KC, the murine equivalent of human IL-8, in gastric mucosa compared with Muc1(+/+ mice during experimental H. pylori infection. The current study tested the hypothesis that a decreased IL-8 level observed following MUC1 over-expression is mediated through the ability of MUC1 to associate with β-catenin, thereby inhibiting H. pylori-induced β-catenin nuclear translocation. Increased neutrophil infiltration of the gastric mucosa of H. pylori-infected Muc1(-/- mice was observed compared with Muc1(+/+ wild type littermates, thus defining the functional consequences of increased KC expression in the Muc1-null animals. Protein co-immunoprecipitation (coIP studies using lysates of untreated or H. pylori-treated AGS cells demonstrated that (a MUC1 formed a coIP complex with β-catenin and CagA, (b MUC1 over-expression reduced CagA/β-catenin coIP, and (c in the absence of MUC1 over-expression, H. pylori infection increased the nuclear level of β-catenin, (d whereas MUC1 over-expression decreased bacteria-driven β-catenin nuclear localization. These results suggest that manipulation of MUC1 expression in gastric epithelia may be an effective therapeutic strategy to inhibit H. pylori-dependent IL-8 production, neutrophil infiltration, and stomach inflammation.

  3. Analysis of a cholera toxin B subunit (CTB) and human mucin 1 (MUC1) conjugate protein in a MUC1-tolerant mouse model.

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    Pinkhasov, Julia; Alvarez, M Lucrecia; Pathangey, Latha B; Tinder, Teresa L; Mason, Hugh S; Walmsley, Amanda M; Gendler, Sandra J; Mukherjee, Pinku

    2010-12-01

    Since epithelial mucin 1 (MUC1) is associated with several adenocarcinomas at the mucosal sites, it is pertinent to test the efficacy of a mucosally targeted vaccine formulation. The B subunit of the Vibrio cholerae cholera toxin (CTB) has great potential to act as a mucosal carrier for subunit vaccines. In the present study we evaluated whether a MUC1 tandem repeat (TR) peptide chemically linked to CTB would break self-antigen tolerance in the transgenic MUC1-tolerant mouse model (MUC1.Tg) through oral or parenteral immunizations. We report that oral immunization with the CTB-MUC1 conjugate along with mucosal adjuvant, unmethylated CpG oligodeoxynucleotide (ODN) and interleukin-12 (IL-12) did not break self-antigen tolerance in MUC1.Tg mice, but induced a strong humoral response in wild-type C57BL/6 mice. However, self-antigen tolerance in the MUC1.Tg mouse model was broken after parenteral immunizations with different doses of the CTB-MUC1 conjugate protein and with the adjuvant CpG ODN co-delivered with CTB-MUC1. Importantly, mice immunized systemically with CpG ODN alone and with CTB-MUC1 exhibited decreased tumor burden when challenged with a mammary gland tumor cell line that expresses human MUC1.

  4. Analysis of a Cholera Toxin B Subunit (CTB) and Human Mucin 1 (MUC1) Conjugate Protein in a MUC1 Tolerant Mouse Model

    Science.gov (United States)

    Pinkhasov, Julia; Alvarez, M. Lucrecia; Pathangey, Latha B.; Tinder, Teresa L.; Mason, Hugh S.; Walmsley, Amanda M.; Gendler, Sandra J.; Mukherjee, Pinku

    2011-01-01

    Since epithelial mucin 1 (MUC1) is associated with several adenocarcinomas at mucosal sites, it is pertinent to test the efficacy of a mucosally targeted vaccine formulation. The B subunit of the Vibrio cholerae cholera toxin (CTB) has great potential to act as a mucosal carrier for subunit vaccines. In the present study we evaluated whether a MUC1 tandem repeat (TR) peptide chemically linked to CTB would break self-antigen tolerance in the transgenic MUC1 tolerant mouse model (MUC1.Tg) through oral or parenteral immunizations. We report that oral immunization with the CTB-MUC1 conjugate along with mucosal adjuvant, unmethylated CpG oligodeoxynucleotide (ODN) and interleukin-12 (IL-12), did not break self-antigen tolerance in MUC1.Tg mice, but induced a strong humoral response in wild-type C57BL/6 mice. However, self-antigen tolerance in the MUC1.Tg mouse model was broken after parenteral immunizations with different doses of the CTB-MUC1 conjugate protein and with the adjuvant CpG ODN co-delivered with CTB-MUC1. Importantly, mice immunized systemically with CpG ODN alone and with CTB-MUC1 exhibited decreased tumor burden when challenged with a mammary gland tumor cell line that expresses human MUC1. PMID:20824430

  5. MUC1 expression and anti-MUC1 serum immune response in head and neck squamous cell carcinoma (HNSCC): a multivariate analysis

    International Nuclear Information System (INIS)

    Rabassa, Martín E; Croce, María V; Pereyra, Adrián; Segal-Eiras, Amada

    2006-01-01

    HNSCC progression to adjacent tissue and nodes may be mediated by altered glycoproteins and glycolipids such as MUC1 mucin. This report constitutes a detailed statistical study about MUC1 expression and anti-MUC1 immune responses in relation to different clinical and pathological parameters which may be useful to develop new anti HNSCC therapeutic strategies. Fifty three pre treatment HNSCC patients were included: 26 (49.1%) bearing oral cavity tumors, 17 (32.1%) localized in the larynx and 10 (18.8%) in the pharynx. Three patients (5.7%) were at stage I, 5 (9.4%) stage II, 15 (28.3%) stage III and 30 (56.6%) at stage IV. MUC1 tumor expression was studied by immunohistochemistry employing two anti-MUC1 antibodies: CT33, anti cytoplasmic tail MUC1 polyclonal antibody (Ab) and C595 anti-peptidic core MUC1 monoclonal antibody. Serum levels of MUC1 and free anti-MUC1 antibodies were detected by ELISA and circulating immune complexes (CIC) by precipitation in polyethylene glycol (PEG) 3.5%; MUC1 isolation from circulating immune complexes was performed by protein A-sepharose CL-4B affinity chromatography followed by SDS-PAGE and Western blot. Statistical analysis consisted in Multivariate Principal Component Analysis (PCA); ANOVA test (Tukey's test) was employed to find differences among groups; nonparametrical correlations (Kendall's Tau) were applied when necessary. Statistical significance was set to p < 0.05 in all cases. MUC1 cytoplasmic tail was detected in 40/50 (80%) and MUC1 protein core in 9/50 (18%) samples while serum MUC1 levels were elevated in 8/53 (15%) patients. A significant statistical correlation was found between MUC1 serum levels and anti-MUC1 IgG free antibodies, while a negative correlation between MUC1 serum levels and anti-MUC1 IgM free antibodies was found. Circulating immune complexes were elevated in 16/53 (30%) samples and were also statistically associated with advanced tumor stage. MUC1 was identified as an antigenic component

  6. MUC1-specific immune therapy generates a strong anti-tumor response in a MUC1-tolerant colon cancer model.

    Science.gov (United States)

    Mukherjee, P; Pathangey, L B; Bradley, J B; Tinder, T L; Basu, G D; Akporiaye, E T; Gendler, S J

    2007-02-19

    A MUC1-based vaccine was used in a preclinical model of colon cancer. The trial was conducted in a MUC1-tolerant immune competent host injected with MC38 colon cancer cells expressing MUC1. The vaccine included: MHC class I-restricted MUC1 peptides, MHC class II-restricted pan-helper-peptide, unmethylated CpG oligodeoxynucleotide, and granulocyte macrophage-colony stimulating factor. Immunization was successful in breaking MUC1 self-tolerance, and in eliciting a robust anti-tumor response. The vaccine stimulated IFN-gamma-producing CD4(+) helper and CD8(+) cytotoxic T cells against MUC1 and other undefined MC38 tumor antigens. In the prophylactic setting, immunization caused complete rejection of tumor cells, while in the therapeutic regimen, tumor burden was significantly reduced.

  7. Novel MUC1 aptamer selectively delivers cytotoxic agent to cancer cells in vitro.

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    Yan Hu

    Full Text Available Chemotherapy is a primary treatment for cancer, but its efficacy is often limited by the adverse effects of cytotoxic agents. Targeted drug delivery may reduce the non-specific toxicity of chemotherapy by selectively directing anticancer drugs to tumor cells. MUC1 protein is an attractive target for tumor-specific drug delivery owning to its overexpression in most adenocarcinomas. In this study, a novel MUC1 aptamer is exploited as the targeting ligand for carrying doxorubicin (Dox to cancer cells. We developed an 86-base DNA aptamer (MA3 that bound to a peptide epitope of MUC1 with a K(d of 38.3 nM and minimal cross reactivity to albumin. Using A549 lung cancer and MCF-7 breast cancer cells as MUC1-expressing models, MA3 was found to preferentially bind to MUC1-positive but not MUC1-negative cells. An aptamer-doxorubicin complex (Apt-Dox was formulated by intercalating doxorubicin into the DNA structure of MA3. Apt-Dox was found capable of carrying doxorubicin into MUC1-positive tumor cells, while significantly reducing the drug intake by MUC1-negative cells. Moreover, Apt-Dox retained the efficacy of doxorubicin against MUC1-positive tumor cells, but lowered the toxicity to MUC1-negative cells (P<0.01. The results suggest that the MUC1 aptamer may have potential utility as a targeting ligand for selective delivery of cytotoxic agent to MUC1-expressing tumors.

  8. Muc1 deficiency exacerbates pulmonary fibrosis in a mouse model of silicosis.

    Science.gov (United States)

    Kato, Kosuke; Zemskova, Marina A; Hanss, Alec D; Kim, Marianne M; Summer, Ross; Kim, Kwang Chul

    2017-11-25

    . Altogether, our results indicate that Muc1 has anti-fibrotic properties in the mouse lung and suggest that elevated levels of MUC1 in patients with interstitial lung disease may serve a protective role, which aims to limit the severity of tissue remodeling in the lung. Copyright © 2017. Published by Elsevier Inc.

  9. Targeting MUC1-C suppresses polycomb repressive complex 1 in multiple myeloma.

    Science.gov (United States)

    Tagde, Ashujit; Markert, Tahireh; Rajabi, Hasan; Hiraki, Masayuki; Alam, Maroof; Bouillez, Audrey; Avigan, David; Anderson, Kenneth; Kufe, Donald

    2017-09-19

    The polycomb repressive complex 1 (PRC1) includes the BMI1, RING1 and RING2 proteins. BMI1 is required for survival of multiple myeloma (MM) cells. The MUC1-C oncoprotein is aberrantly expressed by MM cells, activates MYC and is also necessary for MM cell survival. The present studies show that targeting MUC1-C with (i) stable and inducible silencing and CRISPR/Cas9 editing and (ii) the pharmacologic inhibitor GO-203, which blocks MUC1-C function, downregulates BMI1, RING1 and RING2 expression. The results demonstrate that MUC1-C drives BMI1 transcription by a MYC-dependent mechanism. MUC1-C thus promotes MYC occupancy on the BMI1 promoter and thereby activates BMI1 expression. We also show that the MUC1-C→MYC pathway induces RING2 expression. Moreover, in contrast to BMI1 and RING2, we found that MUC1-C drives RING1 by an NF-κB p65-dependent mechanism. Targeting MUC1-C and thereby the suppression of these key PRC1 proteins was associated with downregulation of the PRC1 E3 ligase activity as evidenced by decreases in ubiquitylation of histone H2A. Targeting MUC1-C also resulted in activation of the PRC1-repressed tumor suppressor genes, PTEN, CDNK2A and BIM . These findings identify a heretofore unrecognized role for MUC1-C in the epigenetic regulation of MM cells.

  10. Natural and Induced Humoral Responses to MUC1

    International Nuclear Information System (INIS)

    Mensdorff-Pouilly, Silvia von; Moreno, Maria; Verheijen, René H. M.

    2011-01-01

    MUC1 is a membrane-tethered mucin expressed on the ductal cell surface of glandular epithelial cells. Loss of polarization, overexpression and aberrant glycosylation of MUC1 in mucosal inflammation and in adenocarcinomas induces humoral immune responses to the mucin. MUC1 IgG responses have been associated with a benefit in survival in patients with breast, lung, pancreatic, ovarian and gastric carcinomas. Antibodies bound to the mucin may curb tumor progression by restoring cell-cell interactions altered by tumor-associated MUC1, thus preventing metastatic dissemination, as well as counteracting the immune suppression exerted by the molecule. Furthermore, anti-MUC1 antibodies are capable of effecting tumor cell killing by antibody-dependent cell-mediated cytotoxicity. Although cytotoxic T cells are indispensable to achieve anti-tumor responses in advanced disease, abs to tumor-associated antigens are ideally suited to address minimal residual disease and may be sufficient to exert adequate immune surveillance in an adjuvant setting, destroying tumor cells as they arise or maintaining occult disease in an equilibrium state. Initial evaluation of MUC1 peptide/glycopeptide mono and polyvalent vaccines has shown them to be immunogenic and safe; anti-tumor responses are scarce. Progress in carbohydrate synthesis has yielded a number of sophisticated substrates that include MUC1 glycopeptide epitopes that are at present in preclinical testing. Adjuvant vaccination with MUC1 glycopeptide polyvalent vaccines that induce strong humoral responses may prevent recurrence of disease in patients with early stage carcinomas. Furthermore, prophylactic immunotherapy targeting MUC1 may be a strategy to strengthen immune surveillance and prevent disease in subjects at hereditary high risk of breast, ovarian and colon cancer

  11. Natural and Induced Humoral Responses to MUC1

    Energy Technology Data Exchange (ETDEWEB)

    Mensdorff-Pouilly, Silvia von, E-mail: s.vonmensdorff@vumc.nl; Moreno, Maria [Department of Obstetrics and Gynecology, VU University Medical Center, De Boelelaan 1117, Amsterdam 1081 HV (Netherlands); Verheijen, René H. M. [Department of Woman & Baby, Division of Surgical & Oncological Gynaecology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht 3508 GA (Netherlands)

    2011-07-29

    MUC1 is a membrane-tethered mucin expressed on the ductal cell surface of glandular epithelial cells. Loss of polarization, overexpression and aberrant glycosylation of MUC1 in mucosal inflammation and in adenocarcinomas induces humoral immune responses to the mucin. MUC1 IgG responses have been associated with a benefit in survival in patients with breast, lung, pancreatic, ovarian and gastric carcinomas. Antibodies bound to the mucin may curb tumor progression by restoring cell-cell interactions altered by tumor-associated MUC1, thus preventing metastatic dissemination, as well as counteracting the immune suppression exerted by the molecule. Furthermore, anti-MUC1 antibodies are capable of effecting tumor cell killing by antibody-dependent cell-mediated cytotoxicity. Although cytotoxic T cells are indispensable to achieve anti-tumor responses in advanced disease, abs to tumor-associated antigens are ideally suited to address minimal residual disease and may be sufficient to exert adequate immune surveillance in an adjuvant setting, destroying tumor cells as they arise or maintaining occult disease in an equilibrium state. Initial evaluation of MUC1 peptide/glycopeptide mono and polyvalent vaccines has shown them to be immunogenic and safe; anti-tumor responses are scarce. Progress in carbohydrate synthesis has yielded a number of sophisticated substrates that include MUC1 glycopeptide epitopes that are at present in preclinical testing. Adjuvant vaccination with MUC1 glycopeptide polyvalent vaccines that induce strong humoral responses may prevent recurrence of disease in patients with early stage carcinomas. Furthermore, prophylactic immunotherapy targeting MUC1 may be a strategy to strengthen immune surveillance and prevent disease in subjects at hereditary high risk of breast, ovarian and colon cancer.

  12. Androgen-Dependent Regulation of Human MUC1 Mucin Expression

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    Stephen Mitchell

    2002-01-01

    Full Text Available MUC1 mucin is transcriptionally regulated by estrogen, progesterone, and glucocorticoids. Our objective was to determine whether androgen receptor. (20AR activation regulates expression of MUC1. The following breast and prostatic cell lines were phenotyped and grouped according to AR and MUC1protein expression: 1 AR+MUCi + [DAR17+19. (20AR transfectants of DU-145, ZR-75-1, MDA-MB-453, and T47D]; 2 AR-MUCi+ [DZeoi. (20AR- vector control, DU-145, BT20, MDA-MB231, and MCF7]; 3 AIR +MUCi -. (20LNCaP and LNCaP-r. Cell proliferation was determined using the MTT assay in the presence of synthetic androgen R1881, 0.1 pM to 1 µM. Cell surface MUC1expression was determined by flow cytometry in the presence or absence of oestradiol, medroxy progesterone acetate or R1881, with and without 4 hydroxy-flutamide. (204-OH, a nonsteroidal AR antagonist. The functional significance of MUC1expression was investigated with a cell-cell aggregation assay. Only AR+ MUC1 + cell lines showed a significant increase in MUC1expression with AR activation. (20P. (20range =.01 to .0001, reversed in the presence of 4-OHF. Cell proliferation was unaffected. Increased expression of MUC1was associated with a significant. (20P. (20range =.002 to .001 reduction in cell-cell adhesion. To our knowledge, this is the first description of androgen-dependent regulation of MUC1mucin. This is also functionally associated with decreased cell-cell adhesion, a recognised feature of progressive malignancy. These findings have important implications for physiological and pathological processes.

  13. MUC1 intra-cellular trafficking is clathrin, dynamin, and rab5 dependent

    International Nuclear Information System (INIS)

    Liu Xiaolong; Yuan Zhenglong; Chung, Maureen

    2008-01-01

    MUC1, a transmembrane glycoprotein, is abnormally over-expressed in most human adenocarcinomas. MUC1 association with cytoplasmic cell signal regulators and nuclear accumulation are important for its tumor related activities. Little is known about how MUC1 translocates from the cell membrane to the cytoplasm. In this study, live cell imaging was used to study MUC1 intracellular trafficking. The interaction between EGFR and MUC1 was mapped by FRET analysis and EGF stimulated MUC1 endocytosis was observed directly through live cell imaging. MUC1-CT endocytosis was clathrin and dynamin dependent. Rab5 over-expression resulted in decreased cell membrane localization of MUC1, with accumulation of MUC1 endocytic vesicles in the peri-nuclear region. Conversely, over-expression of a Rab5 dominant negative mutant (S34N) resulted in redistribution of MUC1 from the peri-nuclear region to the cytoplasm. Collectively, these results indicated that MUC1 intra-cellular trafficking occurs through a regulated process that was stimulated by direct EGFR and MUC1 interaction, mediated by clathrin coated pits that were dynamin dependent and regulated by Rab5

  14. Chemoenzymatically synthesized multimeric Tn/STn MUC1 glycopeptides elicit cancer-specific anti-MUC1 antibody responses and override tolerance

    DEFF Research Database (Denmark)

    Sørensen, Anne Louise; Reis, Celso A; Tarp, Mads A

    2005-01-01

    The MUC1 mucin represents a prime target antigen for cancer immunotherapy because it is abundantly expressed and aberrantly glycosylated in carcinomas. Attempts to generate strong humoral immunity to MUC1 by immunization with peptides have generally failed partly because of tolerance. In this stu...

  15. Investigating MUC1/ICAM-1 Binding Induced Signaling in Breast Cancer Metastasis

    Science.gov (United States)

    2011-05-01

    at the molecular weight expected for a CD8/MUC1 dimer (Fig 4.9C). MUC1-CD contains SH2 and SH3 binding domains which act to recruit Src kinase To...recruitment of Src kinase , we assayed dimerization in MUC1-CFP-Fv cells with SH2 and/or SH3 domains mutated (Fig 4.11). As described below, MUC1-CFP-Fv...contains SH2 and SH3 binding domains for Src kinase . MUCI-CFP-Fv cells with mutations of the SH2 (Y46F; b.SH2) and/ or the putative Src SH3 binding

  16. Electrochemical Sandwich Immunoassay for the Ultrasensitive Detection of Human MUC1 Cancer Biomarker

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    Zahra Taleat

    2013-01-01

    Full Text Available A new electrochemical sandwich immunoassay for the ultrasensitive detection of human MUC1 cancer biomarker using protein G-functionalized magnetic beads (MBs and graphite-based screen-printed electrodes (SPEs was developed. Magnetic beads were employed as the platforms for the immobilization and immunoreaction process. A pair of primary and secondary antibodies was used to capture the MUC1 protein. After labeling with a third antibody conjugated with horseradish peroxidase (HRP, the resulting conjugate was trapped at the surface of the graphite-based SPEs and MUC1 determination was carried out by differential pulse voltammetry (DPV at 0.4 V upon H2O2 addition using acetaminophen (APAP as the redox mediator. A linear relationship was obtained for the detection of human MUC1 over a range of 0–25 ppb with the lowest detection limit of 1.34 ppb when HRP was applied as a label. Preliminary experiments were performed using disposable electrochemical sensors in order to optimize some parameters (i.e., incubation times, concentrations, and blocking agent.

  17. Detection of glyco-mucin profiles improves specificity of MUC16 and MUC1 biomarkers in ovarian serous tumours

    DEFF Research Database (Denmark)

    Ricardo, Sara; da Silva, Lara Patricia Marcos; Pereira, Daniela

    2015-01-01

    The CA125 assay detects circulating MUC16 and is one of the most widely used cancer biomarkers for the follow-up of ovarian cancer. We previously demonstrated that detection of aberrant cancer-associated glycoforms of MUC16 as well as MUC1 in circulation could improve the yield of these serum ass...

  18. Flow cytometry-based assay to evaluate human serum MUC1-Tn antibodies

    DEFF Research Database (Denmark)

    Van Elssen, Catharina H M J; Clausen, Henrik; Germeraad, Wilfred T V

    2011-01-01

    Mucin-1 (MUC1) is a heavily O-glycosylated, transmembrane protein that is expressed on the apical surface of most secretory epithelia. In malignantly transformed epithelia, MUC1 has lost its apical distribution, is underglycosylated and is secreted into the circulation. Due to the underglycosylat......Mucin-1 (MUC1) is a heavily O-glycosylated, transmembrane protein that is expressed on the apical surface of most secretory epithelia. In malignantly transformed epithelia, MUC1 has lost its apical distribution, is underglycosylated and is secreted into the circulation. Due...... to detect antibodies binding to the underglycosylated MUC1 protein. This cellular system is complementary to the previously published methods to detect MUC1 serum antibodies, since the antibodies to the native protein are evaluated and therefore it can be effectively used for MUC1 antibody monitoring...... in vaccination studies as well as for functional assays....

  19. Expressão de CDX2 e mucinas (MUC1, MUC2, MUC5AC e MUC6 em esôfago de Barrett antes e após fundoplicatura de Nissen Expression of CDX2 and mucins (MUC1, MUC2, MUC5AC and MUC6 in Barrett's esophagus before and after Nissen fundoplication

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    Luciana Rodrigues de Meirelles

    2012-10-01

    Full Text Available INTRODUÇÃO: O esôfago de Barrett (EB corresponde à substituição do epitélio escamoso por um do tipo intestinal, em resposta ao refluxo crônico nos pacientes com doença do refluxo gastroesofágico (DRGE. É um importante precursor do adenocarcinoma esofágico. A fundoplicatura de Nissen (FN é uma cirurgia antirrefluxo que visa a reduzir a agressão à mucosa esofágica. Alterações no padrão de expressão imuno-histoquímica de mucinas e de CDX2 no EB antes e depois da FN podem ser úteis na identificação de um padrão de expressão desses marcadores e, eventualmente, na identificação de casos com risco de evolução para malignidade. OBJETIVOS: Avaliar e comparar a imunoexpressão de CDX2 e mucinas no EB de pacientes com DRGE submetidos à FN antes e após a cirurgia. MATERIAIS E MÉTODOS: Estudo retrospectivo de 25 pacientes com diagnóstico de DRGE e EB submetidos à FN, acompanhados por, pelo menos, três anos. Foram feitos análise histológica e estudo imuno-histoquímico das biópsias endoscópicas antes e após a cirurgia, comparando-se a inflamação e a imunoexpressão de MUC1, MUC2, MUC5AC, MUC6 e CDX2. Estimou-se a porcentagem de células com expressão para os marcadores estudados na mucosa de Barrett: 0%-25%, 25%-75% e 75%-100% das células positivas. Foram utilizados os testes de McNemar e Stuart-William e adotou-se o nível de 5% de significância estatística. RESULTADOS E CONCLUSÃO: Não houve diferenças significativas quanto a presença ou intensidade de inflamação, nem da imunoexpressão de mucinas e CDX2 no EB antes e após a FN. O tratamento cirúrgico não influenciou a mudança da expressão dessas glicoproteínas no EB.INTRODUCTION: Barrett´s esophagus (BE is characterized by the exchange of esophageal squamous epithelium for intestinal type in response to chronic reflux in patients with gastroesophageal reflux disease (GERD.It is an important precursor of esophageal adenocarcinoma. Nissen

  20. MUC1 selectively targets human pancreatic cancer in orthotopic nude mouse models.

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    Jeong Youp Park

    Full Text Available The goal of this study was to determine whether MUC1 antibody conjugated with a fluorophore could be used to visualize pancreatic cancer. Anti-MUC1 (CT2 antibody was conjugated with 550 nm or 650 nm fluorophores. Nude mouse were used to make subcutaneous and orthotopic models of pancreatic cancer. Western blot and flow cytometric analysis confirmed the expression of MUC1 in human pancreatic cancer cell lines including BxPC-3 and Panc-1. Immunocytochemistry with fluorophore conjugated anti-MUC1 antibody demonstrated fluorescent areas on the membrane of Panc-1 cancer cells. After injecting the conjugated anti-MUC1 antibodies via the tail vein, subcutaneously transplanted Panc-1 and BxPC-3 tumors emitted strong fluorescent signals. In the subcutaneous tumor models, the fluorescent signal from the conjugated anti-MUC1 antibody was noted around the margin of the tumor and space between the cells. The conjugated anti-MUC1 antibody bound the tumor in orthotopically-transplanted Panc-1 and BxPC-3 models enabling the tumors to be imaged. This study showed that fluorophore conjugated anti-MUC1 antibodies could visualize pancreatic tumors in vitro and in vivo and may help to improve the diagnosis and treatment of pancreatic cancer.

  1. Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis.

    Science.gov (United States)

    Bozkaya, Giray; Korhan, Peyda; Cokaklı, Murat; Erdal, Esra; Sağol, Ozgül; Karademir, Sedat; Korch, Christopher; Atabey, Neşe

    2012-09-11

    Hepatocyte growth factor (HGF) induced c-Met activation is known as the main stimulus for hepatocyte proliferation and is essential for liver development and regeneration. Activation of HGF/c-Met signaling has been correlated with aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC). MUC1 is a transmembrane mucin, whose over-expression is reported in most cancers. Many of the oncogenic effects of MUC1 are believed to occur through the interaction of MUC1 with signaling molecules. To clarify the role of MUC1 in HGF/c-Met signaling, we determined whether MUC1 and c-Met interact cooperatively and what their role(s) is in hepatocarcinogenesis. MUC1 and c-Met over-expression levels were determined in highly motile and invasive, mesenchymal-like HCC cell lines, and in serial sections of cirrhotic and HCC tissues, and these levels were compared to those in normal liver tissues. Co-expression of both c-Met and MUC1 was found to be associated with the differentiation status of HCC. We further demonstrated an interaction between c-Met and MUC1 in HCC cells. HGF-induced c-Met phosphorylation decreased this interaction, and down-regulated MUC1 expression. Inhibition of c-Met activation restored HGF-mediated MUC1 down-regulation, and decreased the migratory and invasive abilities of HCC cells via inhibition of β-catenin activation and c-Myc expression. In contrast, siRNA silencing of MUC1 increased HGF-induced c-Met activation and HGF-induced cell motility and invasion. These findings indicate that the crosstalk between MUC1 and c-Met in HCC could provide an advantage for invasion to HCC cells through the β-catenin/c-Myc pathway. Thus, MUC1 and c-Met could serve as potential therapeutic targets in HCC.

  2. Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis

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    Bozkaya Giray

    2012-09-01

    Full Text Available Abstract Background Hepatocyte growth factor (HGF induced c-Met activation is known as the main stimulus for hepatocyte proliferation and is essential for liver development and regeneration. Activation of HGF/c-Met signaling has been correlated with aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC. MUC1 is a transmembrane mucin, whose over-expression is reported in most cancers. Many of the oncogenic effects of MUC1 are believed to occur through the interaction of MUC1 with signaling molecules. To clarify the role of MUC1 in HGF/c-Met signaling, we determined whether MUC1 and c-Met interact cooperatively and what their role(s is in hepatocarcinogenesis. Results MUC1 and c-Met over-expression levels were determined in highly motile and invasive, mesenchymal-like HCC cell lines, and in serial sections of cirrhotic and HCC tissues, and these levels were compared to those in normal liver tissues. Co-expression of both c-Met and MUC1 was found to be associated with the differentiation status of HCC. We further demonstrated an interaction between c-Met and MUC1 in HCC cells. HGF-induced c-Met phosphorylation decreased this interaction, and down-regulated MUC1 expression. Inhibition of c-Met activation restored HGF-mediated MUC1 down-regulation, and decreased the migratory and invasive abilities of HCC cells via inhibition of β-catenin activation and c-Myc expression. In contrast, siRNA silencing of MUC1 increased HGF-induced c-Met activation and HGF-induced cell motility and invasion. Conclusions These findings indicate that the crosstalk between MUC1 and c-Met in HCC could provide an advantage for invasion to HCC cells through the β-catenin/c-Myc pathway. Thus, MUC1 and c-Met could serve as potential therapeutic targets in HCC.

  3. The MUC1 extracellular domain subunit is found in nuclear speckles and associates with spliceosomes.

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    Priyadarsini Kumar

    Full Text Available MUC1 is a large transmembrane glycoprotein and oncogene expressed by epithelial cells and overexpressed and underglycosylated in cancer cells. The MUC1 cytoplasmic subunit (MUC1-C can translocate to the nucleus and regulate gene expression. It is frequently assumed that the MUC1 extracellular subunit (MUC1-N does not enter the nucleus. Based on an unexpected observation that MUC1 extracellular domain antibody produced an apparently nucleus-associated staining pattern in trophoblasts, we have tested the hypothesis that MUC1-N is expressed inside the nucleus. Three different antibodies were used to identify MUC1-N in normal epithelial cells and tissues as well as in several cancer cell lines. The results of immunofluorescence and confocal microscopy analyses as well as subcellular fractionation, Western blotting, and siRNA/shRNA studies, confirm that MUC1-N is found within nuclei of all cell types examined. More detailed examination of its intranuclear distribution using a proximity ligation assay, subcellular fractionation, and immunoprecipitation suggests that MUC1-N is located in nuclear speckles (interchromatin granule clusters and closely associates with the spliceosome protein U2AF65. Nuclear localization of MUC1-N was abolished when cells were treated with RNase A and nuclear localization was altered when cells were incubated with the transcription inhibitor 5,6-dichloro-1-b-d-ribofuranosylbenzimidazole (DRB. While MUC1-N predominantly associated with speckles, MUC1-C was present in the nuclear matrix, nucleoli, and the nuclear periphery. In some nuclei, confocal microscopic analysis suggest that MUC1-C staining is located close to, but only partially overlaps, MUC1-N in speckles. However, only MUC1-N was found in isolated speckles by Western blotting. Also, MUC1-C and MUC1-N distributed differently during mitosis. These results suggest that MUC1-N translocates to the nucleus where it is expressed in nuclear speckles and that MUC1-N and MUC

  4. Impact of MUC1 mucin downregulation in the phenotypic characteristics of MKN45 gastric carcinoma cell line.

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    Natália R Costa

    Full Text Available BACKGROUND: Gastric carcinoma is the second leading cause of cancer-associated death worldwide. The high mortality associated with this disease is in part due to limited knowledge about gastric carcinogenesis and a lack of available therapeutic and prevention strategies. MUC1 is a high molecular weight transmembrane mucin protein expressed at the apical surface of most glandular epithelial cells and a major component of the mucus layer above gastric mucosa. Overexpression of MUC1 is found in approximately 95% of human adenocarcinomas, where it is associated with oncogenic activity. The role of MUC1 in gastric cancer progression remains to be clarified. METHODOLOGY: We downregulated MUC1 expression in a gastric carcinoma cell line by RNA interference and studied the effects on cellular proliferation (MTT assay, apoptosis (TUNEL assay, migration (migration assay, invasion (invasion assay and aggregation (aggregation assay. Global gene expression was evaluated by microarray analysis to identify alterations that are regulated by MUC1 expression. In vivo assays were also performed in mice, in order to study the tumorigenicity of cells with and without MUC1 downregulation in MKN45 gastric carcinoma cell line. RESULTS: Downregulation of MUC1 expression increased proliferation and apoptosis as compared to controls, whereas cell-cell aggregation was decreased. No significant differences were found in terms of migration and invasion between the downregulated clones and the controls. Expression of TCN1, KLK6, ADAM29, LGAL4, TSPAN8 and SHPS-1 was found to be significantly different between MUC1 downregulated clones and the control cells. In vivo assays have shown that mice injected with MUC1 downregulated cells develop smaller tumours when compared to mice injected with the control cells. CONCLUSIONS: These results indicate that MUC1 downregulation alters the phenotype and tumorigenicity of MKN45 gastric carcinoma cells and also the expression of several

  5. MUC1-specific cytotoxic T lymphocytes eradicate tumors when adoptively transferred in vivo.

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    Mukherjee, P; Ginardi, A R; Tinder, T L; Sterner, C J; Gendler, S J

    2001-03-01

    We have reported previously that MUC1 transgenic mice with spontaneous tumors of the pancreas (designated MET) naturally develop MHC class I-restricted, MUC1-specific CTLs as tumors progress (P. Mukherjee et al., J. Immunol., 165: 3451-3460, 2000). From these MET mice, we have isolated, expanded, and cloned naturally occurring MUC1-specific CTLs in vitro. In this report, we show that the CTL line is predominantly CD8+ T cells and expresses T-cell receptor Vbeta chains 5.1/5.2, 11, 13, and 2 and Valpha chains 2, 8.3, 3.2, and 11.1/11.2. These CTLs recognize several epitopes on the MUC1 tandem repeat with highest affinity to APGSTAPPA. The CTL clone, on the other hand, is 100% CD8+ cells and expresses a single Vbeta chain of 5.1/5.2 and Valpha2. It recognizes only the H-2Db class I-restricted epitope of MUC1, APGSTAPPA. When adoptively transferred, the CTLs were effective in eradicating MUC1-expressing injected tumor cells including mammary gland cells (C57mg) and B16 melanomas. These results suggest that MUC1-specific CTLs are capable of possibly preventing, or at least substantially delaying, MUC1-expressing tumor formation. To our knowledge, this is the first evidence that demonstrates that the naturally occurring MUC1-specific CTLs isolated from one tumor model has antitumor effects on other MUC1-expressing tumors in vivo. Therefore, our data confirm that MUC1 is an important tumor rejection antigen and can serve as a target for immunotherapy.

  6. Muc1 based breast cancer vaccines: role of post translational modifications

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    Begum, M.; Khurshid, R.; Nagra, S.A.

    2008-01-01

    Vaccine development is one of the most promising fields in cancer research. After autologous transplantation, due to low tumour burden, patients are more likely to respond immunologically to a cancer vaccine. MUC1 with its adhesive and anti adhesive functions, immunostimulatory and immunosuppressive activities, is therefore a good candidate for breast cancer vaccine. A structure-based insight into the immunogenicity of natural MUC1 glyco forms, of its sub-domains, motifs and post translational modification like glycosylation and myriostoylation may aid the design of tumour vaccines. Primary sequences of human MUC1 were retrieved from the SWISSPROT data bank. Protein pattern search: The primary sequence of Human MUC1 was searched at PROSITE (a dictionary of protein sites and patterns) database. Our study observes that post-translational modifications play an important role in presenting MUC1 as a candidate for breast cancer vaccine. It is found that the phosphorylation and glycosylation of important functional motifs of MUC1 may take part in the production of cytokines that may provide immunization. (author)

  7. Complex of MUC1, CIN85 and Cbl in Colon Cancer Progression and Metastasis

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    Cascio, Sandra; Finn, Olivera J.

    2015-01-01

    We previously reported that CIN85, an 85 KDa protein known to be involved in tumor cell migration and metastasis through its interaction with Cbl, associates with MUC1 in tumor cells. MUC1/CIN85 complex also regulates migration and invasion of tumor cells in vitro. Here, we examined specifically human colon carcinoma tissue microarrays (TMA) by immunohistochemistry for the expression of MUC1 and CIN85 and their potential role in cancer progression and metastasis. We detected a significant increase in expression of both MUC1 and CIN85 associated with advanced tumor stage and lymph node metastasis. We further investigated if Cbl could also be present in the MUC1/CIN85 complex. Co-immunoprecipitation assay showed that Cbl co-localized both with CIN85 and with MUC1 in a human colon cancer cell line. To begin to investigate the in vivo relevance of MUC1 overexpression and association with CIN85 and Cbl in cancer development and progression, we used human MUC1 transgenic mice that express MUC1 on the colonic epithelial cells, treated with azoxymethane to initiate and dextran sulfate sodium (AOM/DSS) to promote colorectal carcinogenesis. MUC1.Tg mice showed higher tumor incidence and decreased survival when compared with wild-type mice. Consistent with the in vitro data, the association of MUC1, CIN85 and Cbl was detected in colon tissues of AOM/DSS-treated MUC1 transgenic mice. MUC1/CIN85/Cbl complex appears to contribute to promotion and progression of colon cancer and thus increased expression of MUC1, CIN85 and Cbl in early stage colon cancer might be predictive of poor prognosis

  8. Complex of MUC1, CIN85 and Cbl in Colon Cancer Progression and Metastasis

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    Cascio, Sandra, E-mail: sac131@pitt.edu [Department of Immunology, University of Pittsburgh School of Medicine, E1040 Biomedical Science Tower, Pittsburgh, PA 15261 (United States); Fondazione Ri.Med, via Bandiera, Palermo 90133 (Italy); Finn, Olivera J., E-mail: sac131@pitt.edu [Department of Immunology, University of Pittsburgh School of Medicine, E1040 Biomedical Science Tower, Pittsburgh, PA 15261 (United States)

    2015-02-10

    We previously reported that CIN85, an 85 KDa protein known to be involved in tumor cell migration and metastasis through its interaction with Cbl, associates with MUC1 in tumor cells. MUC1/CIN85 complex also regulates migration and invasion of tumor cells in vitro. Here, we examined specifically human colon carcinoma tissue microarrays (TMA) by immunohistochemistry for the expression of MUC1 and CIN85 and their potential role in cancer progression and metastasis. We detected a significant increase in expression of both MUC1 and CIN85 associated with advanced tumor stage and lymph node metastasis. We further investigated if Cbl could also be present in the MUC1/CIN85 complex. Co-immunoprecipitation assay showed that Cbl co-localized both with CIN85 and with MUC1 in a human colon cancer cell line. To begin to investigate the in vivo relevance of MUC1 overexpression and association with CIN85 and Cbl in cancer development and progression, we used human MUC1 transgenic mice that express MUC1 on the colonic epithelial cells, treated with azoxymethane to initiate and dextran sulfate sodium (AOM/DSS) to promote colorectal carcinogenesis. MUC1.Tg mice showed higher tumor incidence and decreased survival when compared with wild-type mice. Consistent with the in vitro data, the association of MUC1, CIN85 and Cbl was detected in colon tissues of AOM/DSS-treated MUC1 transgenic mice. MUC1/CIN85/Cbl complex appears to contribute to promotion and progression of colon cancer and thus increased expression of MUC1, CIN85 and Cbl in early stage colon cancer might be predictive of poor prognosis.

  9. High beta-palmitate fat controls the intestinal inflammatory response and limits intestinal damage in mucin Muc2 deficient mice.

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    Peng Lu

    Full Text Available BACKGROUND: Palmitic-acid esterified to the sn-1,3 positions of the glycerol backbone (alpha, alpha'-palmitate, the predominant palmitate conformation in regular infant formula fat, is poorly absorbed and might cause abdominal discomfort. In contrast, palmitic-acid esterified to the sn-2 position (beta-palmitate, the main palmitate conformation in human milk fat, is well absorbed. The aim of the present study was to examine the influence of high alpha, alpha'-palmitate fat (HAPF diet and high beta-palmitate fat (HBPF diet on colitis development in Muc2 deficient (Muc2(-/- mice, a well-described animal model for spontaneous enterocolitis due to the lack of a protective mucus layer. METHODS: Muc2(-/- mice received AIN-93G reference diet, HAPF diet or HBPF diet for 5 weeks after weaning. Clinical symptoms, intestinal morphology and inflammation in the distal colon were analyzed. RESULTS: Both HBPF diet and AIN-93G diet limited the extent of intestinal erosions and morphological damage in Muc2(-/- mice compared with HAPF diet. In addition, the immunosuppressive regulatory T (Treg cell response as demonstrated by the up-regulation of Foxp3, Tgfb1 and Ebi3 gene expression levels was enhanced by HBPF diet compared with AIN-93G and HAPF diets. HBPF diet also increased the gene expression of Pparg and enzymatic antioxidants (Sod1, Sod3 and Gpx1, genes all reported to be involved in promoting an immunosuppressive Treg cell response and to protect against colitis. CONCLUSIONS: This study shows for the first time that HBPF diet limits the intestinal mucosal damage and controls the inflammatory response in Muc2(-/- mice by inducing an immunosuppressive Treg cell response.

  10. High beta-palmitate fat controls the intestinal inflammatory response and limits intestinal damage in mucin Muc2 deficient mice.

    Science.gov (United States)

    Lu, Peng; Bar-Yoseph, Fabiana; Levi, Liora; Lifshitz, Yael; Witte-Bouma, Janneke; de Bruijn, Adrianus C J M; Korteland-van Male, Anita M; van Goudoever, Johannes B; Renes, Ingrid B

    2013-01-01

    Palmitic-acid esterified to the sn-1,3 positions of the glycerol backbone (alpha, alpha'-palmitate), the predominant palmitate conformation in regular infant formula fat, is poorly absorbed and might cause abdominal discomfort. In contrast, palmitic-acid esterified to the sn-2 position (beta-palmitate), the main palmitate conformation in human milk fat, is well absorbed. The aim of the present study was to examine the influence of high alpha, alpha'-palmitate fat (HAPF) diet and high beta-palmitate fat (HBPF) diet on colitis development in Muc2 deficient (Muc2(-/-)) mice, a well-described animal model for spontaneous enterocolitis due to the lack of a protective mucus layer. Muc2(-/-) mice received AIN-93G reference diet, HAPF diet or HBPF diet for 5 weeks after weaning. Clinical symptoms, intestinal morphology and inflammation in the distal colon were analyzed. Both HBPF diet and AIN-93G diet limited the extent of intestinal erosions and morphological damage in Muc2(-/-) mice compared with HAPF diet. In addition, the immunosuppressive regulatory T (Treg) cell response as demonstrated by the up-regulation of Foxp3, Tgfb1 and Ebi3 gene expression levels was enhanced by HBPF diet compared with AIN-93G and HAPF diets. HBPF diet also increased the gene expression of Pparg and enzymatic antioxidants (Sod1, Sod3 and Gpx1), genes all reported to be involved in promoting an immunosuppressive Treg cell response and to protect against colitis. This study shows for the first time that HBPF diet limits the intestinal mucosal damage and controls the inflammatory response in Muc2(-/-) mice by inducing an immunosuppressive Treg cell response.

  11. MUC1 enhances invasiveness of pancreatic cancer cells by inducing epithelial to mesenchymal transition.

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    Roy, L D; Sahraei, M; Subramani, D B; Besmer, D; Nath, S; Tinder, T L; Bajaj, E; Shanmugam, K; Lee, Y Y; Hwang, S I L; Gendler, S J; Mukherjee, P

    2011-03-24

    Increased motility and invasiveness of pancreatic cancer cells are associated with epithelial to mesenchymal transition (EMT). Snai1 and Slug are zinc-finger transcription factors that trigger this process by repressing E-cadherin and enhancing vimentin and N-cadherin protein expression. However, the mechanisms that regulate this activation in pancreatic tumors remain elusive. MUC1, a transmembrane mucin glycoprotein, is associated with the most invasive forms of pancreatic ductal adenocarcinomas (PDA). In this study, we show that over expression of MUC1 in pancreatic cancer cells triggers the molecular process of EMT, which translates to increased invasiveness and metastasis. EMT was significantly reduced when MUC1 was genetically deleted in a mouse model of PDA or when all seven tyrosines in the cytoplasmic tail of MUC1 were mutated to phenylalanine (mutated MUC1 CT). Using proteomics, RT-PCR and western blotting, we revealed a significant increase in vimentin, Slug and Snail expression with repression of E-Cadherin in MUC1-expressing cells compared with cells expressing the mutated MUC1 CT. In the cells that carried the mutated MUC1 CT, MUC1 failed to co-immunoprecipitate with β-catenin and translocate to the nucleus, thereby blocking transcription of the genes associated with EMT and metastasis. Thus, functional tyrosines are critical in stimulating the interactions between MUC1 and β-catenin and their nuclear translocation to initiate the process of EMT. This study signifies the oncogenic role of MUC1 CT and is the first to identify a direct role of the MUC1 in initiating EMT during pancreatic cancer. The data may have implications in future design of MUC1-targeted therapies for pancreatic cancer.

  12. Mucin 1 (MUC1 is a novel partner for MAL2 in breast carcinoma cells

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    McGuckin Michael A

    2009-01-01

    Full Text Available Abstract Background The MAL2 gene, encoding a four-transmembrane protein of the MAL family, is amplified and overexpressed in breast and other cancers, yet the significance of this is unknown. MAL-like proteins have trafficking functions, but their molecular roles are largely obscure, partly due to a lack of known binding partners. Methods Yeast two-hybrid screening of a breast carcinoma cDNA expression library was performed using a full-length MAL2 bait, and subsequent deletion mapping experiments were performed. MAL2 interactions were confirmed by co-immunoprecipitation analyses and confocal microscopy was employed to compare protein sub-cellular distributions. Sucrose density gradient centrifugation of membranes extracted in cold Triton X-100 was employed to compare protein distributions between Triton X-100-soluble and -insoluble fractions. Results The tumor-associated protein mucin 1 (MUC1 was identified as a potential MAL2 partner, with MAL2/MUC1 interactions being confirmed in myc-tagged MAL2-expressing MCF-10A cells using co-immunoprecipitation assays. Deletion mapping experiments demonstrated a requirement for the first MAL2 transmembrane domain for MUC1 binding, whereas the MAL2 N-terminal domain was required to bind D52-like proteins. Confocal microscopy identified cytoplasmic co-localisation of MUC1 and MAL2 in breast cell lines, and centrifugation of cell lysates to equilibrium in sucrose density gradients demonstrated that MAL2 and MUC1 proteins were co-distributed between Triton X-100-soluble and -insoluble fractions. However co-immunoprecipitation analyses detected MAL2/MUC1 interactions in Triton X-100-soluble fractions only. Myc-MAL2 expression in MCF-10A cells was associated with both increased MUC1 detection within Triton X-100-soluble and -insoluble fractions, and increased MUC1 detection at the cell surface. Conclusion These results identify MUC1 as a novel MAL2 partner, and suggest a role for MAL2 in regulating MUC1

  13. Targeting MUC1-C suppresses BCL2A1 in triple-negative breast cancer.

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    Hiraki, Masayuki; Maeda, Takahiro; Mehrotra, Neha; Jin, Caining; Alam, Maroof; Bouillez, Audrey; Hata, Tsuyoshi; Tagde, Ashujit; Keating, Amy; Kharbanda, Surender; Singh, Harpal; Kufe, Donald

    2018-01-01

    B-cell lymphoma 2-related protein A1 (BCL2A1) is a member of the BCL-2 family of anti-apoptotic proteins that confers resistance to treatment with anti-cancer drugs; however, there are presently no agents that target BCL2A1. The MUC1-C oncoprotein is aberrantly expressed in triple-negative breast cancer (TNBC) cells, induces the epithelial-mesenchymal transition (EMT) and promotes anti-cancer drug resistance. The present study demonstrates that targeting MUC1-C genetically and pharmacologically in TNBC cells results in the downregulation of BCL2A1 expression. The results show that MUC1-C activates the BCL2A1 gene by an NF-κB p65-mediated mechanism, linking this pathway with the induction of EMT. The MCL-1 anti-apoptotic protein is also of importance for the survival of TNBC cells and is an attractive target for drug development. We found that inhibiting MCL-1 with the highly specific MS1 peptide results in the activation of the MUC1-C→NF-κB→BCL2A1 pathway. In addition, selection of TNBC cells for resistance to ABT-737, which inhibits BCL-2, BCL-xL and BCL-W but not MCL-1 or BCL2A1, is associated with the upregulation of MUC1-C and BCL2A1 expression. Targeting MUC1-C in ABT-737-resistant TNBC cells suppresses BCL2A1 and induces death, which is of potential therapeutic importance. These findings indicate that MUC1-C is a target for the treatment of TNBCs unresponsive to agents that inhibit anti-apoptotic members of the BCL-2 family.

  14. The membrane-associated MUC1 improves adhesion of salivary MUC5B on buccal cells. Application to development of an in vitro cellular model of oral epithelium.

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    Ployon, Sarah; Belloir, Christine; Bonnotte, Aline; Lherminier, Jeannine; Canon, Francis; Morzel, Martine

    2016-01-01

    The mucosal pellicle is a thin layer of salivary proteins, mostly MUC5B mucins, anchored to epithelial oral cells. This pellicle is involved in protection of oral mucosae against abrasion, pathogenic microorganisms or chemical xenobiotics. The present study aimed at studying the involvement of MUC1 in mucosal pellicle formation and more specifically in salivary MUC5B binding using a cell-based model of oral epithelium. MUC1 mRNAs were not detected in TR146 cells, and therefore a stable cell line named TR146/MUC1 expressing this protein was developed by transfection. TR146 and TR146/MUC1 were incubated with human saliva in order to evaluate retention of MUC5B by epithelial cells. The cell surface of both TR146 and TR146/MUC1 was typical of a squamous non-keratinized epithelium, with the presence of numerous microplicae. After incubation for 2h with saliva diluted in culture medium (1:1) and two washes with PBS, saliva deposits on cells appeared as a loose filamentous thin network. MUC5B fluorescent immunostaining evidenced a heterogeneous lining of confluent cell cultures by this salivary mucin but with higher fluorescence on TR146/MUC1 cells. Semi-quantification of MUC5B bound to cells confirmed a better retention by TR146/MUC1, evaluated by Dot Blot (+34.1%, p<0.05) or by immunocytochemistry (+44%, p<0.001). The membrane-bound mucin MUC1 is a factor enhancing the formation of the mucosal pellicle by increasing the binding of salivary MUC5B to oral epithelial cells. An in vitro model suitable to study specifically the function and properties of the mucosal pellicle is proposed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. IL-1β upregulates Muc5ac expression via NF-κB-induced HIF-1α in asthma.

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    Wu, Shouzhen; Li, Hailong; Yu, Lijuan; Wang, Ning; Li, Xu; Chen, Wei

    2017-12-01

    The manifest and important feature in respiratory diseases, including asthma and COPD (chronic obstructive pulmonary disease), is the increased numbers and hypersecretion of goblet cells and overexpression of mucins, especially Muc5ac. Many proinflammatory cytokines play important roles in goblet cell metaplasia and overproduction of Muc5ac. However, the effect of IL-1β on Muc5ac expression in asthma remains unknown. Here, we detected the correlation between IL-1β and Muc5ac in asthma patients and further explored the mechanism of IL-1β-induced Muc5ac overexpression. Our results showed that Muc5ac and IL-1β were up-regulated in 41 patients with asthma and that Muc5ac overexpression was related with IL-1β in asthma (R 2 =0.668, p≪0.001). Furthermore, the correlation between IL-1β and Muc5ac is higher in severe group than that in moderate group. In vitro experiments with normal human bronchial epithelial cells (NHBECs) showed that IL-1β up-regulated Muc5ac expression in NHBEC in a time- and dosage-dependent manner. Hypoxia-induced HIF-1α was responsible for Muc5ac expression mediated by IL-1β. Knocking down HIF-1α by siRNA decreased Muc5ac expression under hypoxia even in IL-1β-treated NHBEC cells. Luciferase reporter assay showed that HIF-1α enhanced Muc5ac promoter activity in HEK293T cells. HIF-1α could specifically bind to the promoter of Muc5ac by EMSA. The correlation among IL-1β, HIF-1α and Muc5ac was observed in patients with asthma. Mechanically, NF-κB activation was essential to IL-1β-induced HIF-1α upregulation via the canonical pathway of NF-κB. The level of nuclear p65, a subunit of NF-κB, was obviously increased in NHBEC cells under IL-1β treatment. IL-1β did not change either HIF-1α or Muc5ac expression when inhibiting NF-κB signaling with Bay11-7082, an inhibitor of NF-κB. Collectively, we concluded that IL-1β up-regulated Muc5ac expression via NF-κB-induced HIF-1α in asthma and provided a potential therapeutic target for

  16. MUC1-specific CTLs are non-functional within a pancreatic tumor microenvironment.

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    Mukherjee, P; Ginardi, A R; Madsen, C S; Tinder, T L; Jacobs, F; Parker, J; Agrawal, B; Longenecker, B M; Gendler, S J

    2001-01-01

    Pancreatic cancer is a highly aggressive, treatment refractory disease and is the fourth leading cause of death in the United States. In humans, 90% of pancreatic adenocarcinomas over-express altered forms of a tumor-associated antigen, MUC1 (an epithelial mucin glycoprotein), which is a target for immunotherapy. Using a clinically relevant mouse model of pancreas cancer that demonstrates peripheral and central tolerance to human MUC1 and develops spontaneous tumors of the pancreas, we have previously reported the presence of functionally active, low affinity, MUC1-specific precursor cytotoxic T cells (pCTLs). Hypothesis for this study is that MUC1-based immunization may enhance the low level MUC1-specific immunity that may lead to an effective anti-tumor response. Data demonstrate that MUC1 peptide-based immunization elicits mature MUC1-specific CTLs in the peripheral lymphoid organs. The mature CTLs secrete IFN-gamma and are cytolytic against MUC1-expressing tumor cells in vitro. However, active CTLs that infiltrate the pancreas tumor microenvironment become cytolytically anergic and are tolerized to MUC1 antigen, allowing the tumor to grow. We demonstrate that the CTL tolerance could be reversed at least in vitro with the use of anti-CD40 co-stimulation. The pancreas tumor cells secrete immunosuppressive cytokines, including IL-10 and TGF-beta that are partly responsible for the down-regulation of CTL activity. In addition, they down-regulate their MHC class I molecules to avoid immune recognition. CD4+ CD25+ T regulatory cells, which secrete IL-10, were also found in the tumor environment. Together these data indicate the use of several immune evasion mechanisms by tumor cells to evade CTL killing. Thus altering the tumor microenvironment to make it more conducive to CTL killing may be key in developing a successful anti-cancer immunotherapy.

  17. Autosomal Dominant Tubulointerstitial Kidney Disease: Clinical Presentation of Patients With ADTKD-UMOD and ADTKD-MUC1.

    Science.gov (United States)

    Ayasreh, Nadia; Bullich, Gemma; Miquel, Rosa; Furlano, Mónica; Ruiz, Patricia; Lorente, Laura; Valero, Oliver; García-González, Miguel Angel; Arhda, Nisrine; Garin, Intza; Martínez, Víctor; Pérez-Gómez, Vanessa; Fulladosa, Xavier; Arroyo, David; Martínez-Vea, Alberto; Espinosa, Mario; Ballarín, Jose; Ars, Elisabet; Torra, Roser

    2018-05-18

    Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare underdiagnosed cause of end-stage renal disease (ESRD). ADTKD is caused by mutations in at least 4 different genes: MUC1, UMOD, HNF1B, and REN. Retrospective cohort study. 56 families (131 affected individuals) with ADTKD referred from different Spanish hospitals. Clinical, laboratory, radiologic, and pathologic data were collected, and genetic testing for UMOD, MUC1, REN, and HNF1B was performed. Hyperuricemia, ultrasound findings, renal histology, genetic mutations. Age at ESRD, rate of decline in estimated glomerular filtration rate. ADTKD was diagnosed in 25 families (45%), 9 carried UMOD pathogenic variants (41 affected members), and 16 carried the MUC1 pathogenic mutation c.(428)dupC (90 affected members). No pathogenic variants were identified in REN or HNF1B. Among the 77 individuals who developed ESRD, median age at onset of ESRD was 51 years for those with ADTKD-MUC1 versus 56 years (P=0.1) for those with ADTKD-UMOD. Individuals with the MUC1 duplication presented higher risk for developing ESRD (HR, 2.24; P=0.03). The slope of decline in estimated glomerular filtration rate showed no significant difference between groups (-3.0mL/min/1.73m 2 per year in the ADTKD-UMOD group versus -3.9mL/min/1.73m 2 per year in the ADTKD-MUC1 group; P=0.2). The prevalence of hyperuricemia was significantly higher in individuals with ADTKD-UMOD (87% vs 54%; P=0.006). Although gout occurred more frequently in this group, the difference was not statistically significant (24% vs 7%; P=0.07). Relatively small Spanish cohort. MUC1 analysis limited to cytosine duplication. The main genetic cause of ADTKD in our Spanish cohort is the MUC1 pathogenic mutation c.(428)dupC. Renal survival may be worse in individuals with the MUC1 mutation than in those with UMOD mutations. Clinical presentation does not permit distinguishing between these variants. However, hyperuricemia and gout are more frequent in individuals

  18. MUC1-C activates EZH2 expression and function in human cancer cells.

    Science.gov (United States)

    Rajabi, Hasan; Hiraki, Masayuki; Tagde, Ashujit; Alam, Maroof; Bouillez, Audrey; Christensen, Camilla L; Samur, Mehmet; Wong, Kwok-Kin; Kufe, Donald

    2017-08-07

    The EZH2 histone methyltransferase is a member of the polycomb repressive complex 2 (PRC2) that is highly expressed in diverse human cancers and is associated with a poor prognosis. MUC1-C is an oncoprotein that is similarly overexpressed in carcinomas and has been linked to epigenetic regulation. A role for MUC1-C in regulating EZH2 and histone methylation is not known. Here, we demonstrate that targeting MUC1-C in diverse human carcinoma cells downregulates EZH2 and other PRC2 components. MUC1-C activates (i) the EZH2 promoter through induction of the pRB→E2F pathway, and (ii) an NF-κB p65 driven enhancer in exon 1. We also show that MUC1-C binds directly to the EZH2 CXC region adjacent to the catalytic SET domain and associates with EZH2 on the CDH1 and BRCA1 promoters. In concert with these results, targeting MUC1-C downregulates EZH2 function as evidenced by (i) global and promoter-specific decreases in H3K27 trimethylation (H3K27me3), and (ii) activation of tumor suppressor genes, including BRCA1. These findings highlight a previously unreported role for MUC1-C in activating EZH2 expression and function in cancer cells.

  19. Decreased expression of MUC1 induces apoptosis and inhibits migration in pancreatic cancer PANC-1 cells via regulation of Slug pathway.

    Science.gov (United States)

    Zhao, Ping; Meng, Meng; Xu, Bin; Dong, Aiping; Ni, Guangzhen; Lu, Lianfang

    2017-12-06

    MUC1, a membrane tethered mucin glycoprotein, is overexpressed in > 60% of human pancreatic cancers (PCs), and is associated with poor prognosis and enhanced metastasis. Here, we report the effect of silencing MUC1 expression on the growth, migration and invasive ability of pancreatic cancer cells, and explored its mechanisms. We observed that siRNA mediated suppression of the MUC1 expression significantly reduced invasive and migrative capability and induced apoptosis of the pancreatic cancer PANC-1 cells. We found that Slug was inhibited in the MUC1 siRNA transfected PANC-1 cells (MUC1 siRNA/PANC-1 cells). Expression of PUMA and E-cadherin was increased in the MUC1 siRNA/PANC-1 cells. PANC-1 cells overexpressing full long Slug gene (when transfected with Slug cDNA plasmid) significantly inhibited PUMA and E-cadherin expression in the MUC1 siRNA/PANC-1 cells. Silencing PUMA expression inhibited apoptosis in the MUC1 siRNA transfected PANC-1 cells (MUC1 siRNA/PANC-1 cells). Silencing E-cadherin expression restored the invasion and migration ability in the MUC1 siRNA/PANC-1 cells. We therefore concluded that silencing MUC1 expression inhibited migration and invasion, and induced apoptosis of PANC-1 cells via downregulation of Slug and upregulation of Slug dependent PUMA and E-cadherin expression. MUC1 could serve as a potential therapeutic target in pancreatic cancer.

  20. Differential Muc2 and Muc5ac secretion by stimulated guinea pig tracheal epithelial cells in vitro

    Directory of Open Access Journals (Sweden)

    Adler Kenneth B

    2006-02-01

    Full Text Available Abstract Background Mucus overproduction is a characteristic of inflammatory pulmonary diseases including asthma, chronic bronchitis, and cystic fibrosis. Expression of two mucin genes, MUC2 and MUC5AC, and their protein products (mucins, is modulated in certain disease states. Understanding the signaling mechanisms that regulate the production and secretion of these major mucus components may contribute significantly to development of effective therapies to modify their expression in inflamed airways. Methods To study the differential expression of Muc2 and Muc5ac, a novel monoclonal antibody recognizing guinea pig Muc2 and a commercially-available antibody against human MUC5AC were optimized for recognition of specific guinea pig mucins by enzyme-linked immunosorbent assay (ELISA, Western blot, and immunohistochemistry (IHC. These antibodies were then used to analyze expression of Muc2 and another mucin subtype (likely Muc5ac in guinea pig tracheal epithelial (GPTE cells stimulated with a mixture of pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α, interleukin 1β (IL-1β, and interferon- γ (IFN-γ]. Results The anti-Muc2 (C4 and anti-MUC5AC (45M1 monoclonal antibodies specifically recognized proteins located in Muc2-dominant small intestinal and Muc5ac-dominant stomach mucosae, respectively, in both Western and ELISA experimental protocols. IHC protocols confirmed that C4 recognizes murine small intestine mucosal proteins while 45M1 does not react. C4 and 45M1 also stained specific epithelial cells in guinea pig lung sections. In the resting state, Muc2 was recognized as a highly expressed intracellular mucin in GPTE cells in vitro. Following cytokine exposure, secretion of Muc2, but not the mucin recognized by the 45M1 antibody (likely Muc5ac, was increased from the GPTE cells, with a concomitant increase in intracellular expression of both mucins. Conclusion Given the tissue specificity in IHC and the differential hybridization

  1. No evidence of association of MUC-1 genetic polymorphism with embryo implantation failure

    Directory of Open Access Journals (Sweden)

    D.B. Dentillo

    2007-06-01

    Full Text Available Pregnancy loss can be caused by several factors involved in human reproduction. Although up to 50% of cases remain unexplained, it has been postulated that the major cause of failed pregnancy is an error of embryo implantation. Transmembrane mucin-1 (MUC-1 is a glycoprotein expressed on the endometrial cell surface which acts as a barrier to implantation. The gene that codes for this molecule is composed of a polymorphic tandem repeat of 60 nucleotides. Our objective was to determine if MUC-1 genetic polymorphism is associated with implantation failure in patients with a history of recurrent abortion. The study was conducted on 10 women aged 25 to 35 years with no history of successful pregnancy and with a diagnosis of infertility. The control group consisted of 32 patients aged 25 to 35 years who had delivered at least two full-term live children and who had no history of abortions or fetal losses. MUC-1 amplicons were obtained by PCR and observed on agarose and polyacrylamide gel after electrophoresis. Statistical analysis showed no significant difference in the number of MUC-1 variable number of tandem repeats between these groups (P > 0.05. Our results suggest that there is no effect of the polymorphic MUC-1 sequence on the implantation failure. However, the data do not exclude MUC-1 relevance during embryo implantation. The process is related to several associated factors such as the mechanisms of gene expression in the uterus, specific MUC-1 post-translational modifications and appropriate interactions with other molecules during embryo implantation.

  2. Potential for novel MUC1 glycopeptide-specific antibody in passive cancer immunotherapy

    DEFF Research Database (Denmark)

    Madsen, Caroline B; Wandall, Hans H; Pedersen, Anders Elm

    2013-01-01

    MUC1 is an important target for antibodies in passive cancer immunotherapy. Antibodies against mucin glycans or mucin peptide backbone alone may give rise to cross reactivity with normal tissues. Therefore, attempts to identify antibodies against cancer-specific MUC1 glycopeptide epitopes havebeen...

  3. Prognostic Significance of Mucin Antigen MUC1 in Various Human Epithelial Cancers

    Science.gov (United States)

    Xu, Feng; Liu, Fuquan; Zhao, Hongwei; An, Guangyu; Feng, Guosheng

    2015-01-01

    Abstract Accumulating evidence indicates that mucin antigen MUC1 plays a fundamental role in the initiation and progression of several types of epithelial carcinomas. However, whether the expression of MUC1 on tumor cells is associated with patients’ survival remains controversial. Medline/PubMed, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) databases, and Grey literature were searched up to 15 August 2015 for eligible studies of the association between the MUC1 expression and overall survival (OS) in various epithelial cancers. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated from the included studies. Moreover, the odds ratio (OR) was also extracted to evaluate the association between the clinicopathological parameters of participants and MUC1 expression. A total of 3425 patients covering 23 studies were included in the analysis. The pooled results showed that positive MUC1 staining was a negative predictor of OS (HRFEM = 1.98,95% CIFEM: 1.76–2.22, PFEM = 0.479; HRREM = 2.16,95% CIREM: 1.58–2.94, PREM = 0.355) in various epithelial carcinomas. Subgroup analysis revealed that the increased MUC1 expression was significantly associated with poor OS in patients with gastric cancer (HRFEM = 2.12, 95%CIFEM: 1.75–2.57, PFEM = 0.359; HRREM = 1.89, 95% CIREM: 1.05–3.41, PREM = 0.238), colorectal cancer (HRFEM = 1.73, 95%CIFEM: 1.41–2.13, PFEM = 0.048; HRREM = 2.00,95% CIREM: 1.46–2.73, PREM = 0.019), cholangiocarcinoma (HRFEM = 2.52, 95% CIFEM: 1.42–4.49, PFEM = 0.252; HRREM = 2.34, 95% CIREM: 1.30–4.22, PREM = 0.244), and nonsmall cell lung cancer (NSCLC) (HRFEM = 2.14, 95% CIFEM: 1.46–3.14, PFEM = 0.591; HRREM = 2.81, 95% CIREM: 1.40–5.64, PREM = 0.280). In addition, MUC1 overexpression was more likely to be found in colorectal cancer patients with an advanced tumor node metastasis stage (ORREM = 1.55, 95

  4. Induction of protective and therapeutic anti-pancreatic cancer immunity using a reconstructed MUC1 DNA vaccine

    International Nuclear Information System (INIS)

    Rong, Yefei; Jin, Dayong; Wu, Wenchuan; Lou, Wenhui; Wang, Danshong; Kuang, Tiantao; Ni, Xiaoling; Qin, Xinyu

    2009-01-01

    Pancreatic cancer is a common, highly lethal disease with a rising incidence. MUC1 is a tumor-associated antigen that is over-expressed in pancreatic adenocarcinoma. Active immunotherapy that targets MUC1 could have great treatment value. Here we investigated the preventive and therapeutic effect of a MUC1 DNA vaccine on the pancreatic cancer. MUC1-various tandem repeat units(VNTR) DNA vaccine was produced by cloning one repeat of VNTR and inserting the cloned gene into the pcDNA3.1. In the preventive group, female C57BL/6 mice were immunized with the vaccine, pcDNA3.1 or PBS; and challenged with panc02-MUC1 or panc02 cell. In the therapeutic group the mice were challenged with panc02-MUC1 or panc02 cell, and then immunized with the vaccine, pcDNA3.1 or PBS. The tumor size and the survival time of the animals were compared between these groups. The DNA vaccine pcDNA3.1-VNTR could raise cytotoxic T lymphocyte (CTL) activity specific for MUC1. In the preventive experiment, the mice survival time was significantly longer in the vaccine group than in the control groups (P < 0.05). In the therapeutic experiment, the DNA vaccine prolonged the survival time of the panc02-MUC1-bearing mice (P < 0.05). In both the preventive and therapeutic experiments, the tumor size was significantly less in the vaccine group than in the control groups (P < 0.05). This pcDNA3.1-VNTR vaccine, however, could not prevent the mice attacked by panc02 cells and had no therapeutic effect on the mice attacked by panc02 cells. The MUC1 DNA vaccine pcDNA3.1-VNTR could induce a significant MUC1-specific CTL response; and had both prophylactic and therapeutic effect on panc02-MUC1 tumors. This vaccine might be used as a new adjuvant strategy against pancreatic cancer

  5. MUC1 enhances tumor progression and contributes toward immunosuppression in a mouse model of spontaneous pancreatic adenocarcinoma.

    Science.gov (United States)

    Tinder, Teresa L; Subramani, Durai B; Basu, Gargi D; Bradley, Judy M; Schettini, Jorge; Million, Arefayene; Skaar, Todd; Mukherjee, Pinku

    2008-09-01

    MUC1, a membrane tethered mucin glycoprotein, is overexpressed and aberrantly glycosylated in >80% of human ductal pancreatic adenocarcinoma. However, the role of MUC1 in pancreatic cancer has been elusive, partly due to the lack of an appropriate model. We report the characterization of a novel mouse model that expresses human MUC1 as a self molecule (PDA.MUC1 mice). Pancreatic tumors arise in an appropriate MUC1-tolerant background within an immune-competent host. Significant enhancement in the development of pancreatic intraepithelial preneoplastic lesions and progression to adenocarcinoma is observed in PDA.MUC1 mice, possibly due to increased proliferation. Tumors from PDA.MUC1 mice express higher levels of cyclooxygenase-2 and IDO compared with PDA mice lacking MUC1, especially during early stages of tumor development. The increased proinflammatory milieu correlates with an increased percentage of regulatory T cells and myeloid suppressor cells in the pancreatic tumor and tumor draining lymph nodes. Data shows that during pancreatic cancer progression, MUC1-mediated mechanisms enhance the onset and progression of the disease, which in turn regulate the immune responses. Thus, the mouse model is ideally suited for testing novel chemopreventive and therapeutic strategies against pancreatic cancer.

  6. MUC1 enhances tumor progression and contributes towards immunosuppression in a mouse model of spontaneous pancreatic adenocarcinoma

    Science.gov (United States)

    Tinder, Teresa L.; Subramani, Durai B.; Basu, Gargi D.; Bradley, Judy M.; Schettini, Jorge; Million, Arefayene; Skaar, Todd

    2008-01-01

    MUC1, a membrane tethered mucin glycoprotein, is overexpressed and aberrantly glycosylated in >80% of human ductal pancreatic adenocarcinoma. However, the role of MUC1 in pancreatic cancer has been elusive, partly due to the lack of an appropriate model. We report the characterization of a novel mouse model that expresses human MUC1 as a self molecule (PDA.MUC1 mice). Pancreatic tumors arise in an appropriate MUC1-tolerant background within an immune competent host. Significant enhancement in the development of pancreatic intraepithelial pre-neoplastic lesions (PanINs) and progression to adenocarcinoma is observed in PDA.MUC1 mice, possibly due to increased proliferation. Tumors from PDA.MUC1 mice express higher levels of cyclooxygenase-2 and indoleamine 2,3, dioxygenase compared to PDA mice lacking MUC1, especially during early stages of tumor development. The increased pro-inflammatory milieu correlates with an increased percentage of regulatory T cells and myeloid suppressor cells in the pancreatic tumor and tumor draining lymph nodes. Data shows that during pancreatic cancer progression, MUC1-mediated mechanisms enhance the onset and progression of the disease which in turn regulate the immune responses. Thus, the mouse model is ideally-suited for testing novel chemopreventive and therapeutic strategies against pancreatic cancer. PMID:18713982

  7. MUC1-C Represses the Crumbs Complex Polarity Factor CRB3 and Downregulates the Hippo Pathway

    Science.gov (United States)

    Alam, Maroof; Bouillez, Audrey; Tagde, Ashujit; Ahmad, Rehan; Rajabi, Hasan; Maeda, Takahiro; Hiraki, Masayuki; Suzuki, Yozo; Kufe, Donald

    2016-01-01

    Apical-basal polarity and epithelial integrity are maintained in part by the Crumbs (CRB) complex. The C-terminal subunit of MUC1 (MUC1-C) is a transmembrane protein that is expressed at the apical border of normal epithelial cells and aberrantly at high levels over the entire surface of their transformed counterparts. However, it is not known if MUC1-C contributes to this loss of polarity that is characteristic of carcinoma cells. Here it is demonstrated that MUC1-C downregulates expression of the Crumbs complex CRB3 protein in triple-negative breast cancer (TNBC) cells. MUC1-C associates with ZEB1 on the CRB3 promoter and represses CRB3 transcription. Notably, CRB3 activates the core kinase cassette of the Hippo pathway, which includes LATS1 and LATS2. In this context, targeting MUC1-C was associated with increased phosphorylation of LATS1, consistent with activation of the Hippo pathway, which is critical for regulating cell contact, tissue repair, proliferation and apoptosis. Also shown is that MUC1-C-mediated suppression of CRB3 and the Hippo pathway is associated with dephosphorylation and activation of the oncogenic YAP protein. In turn, MUC1-C interacts with YAP, promotes formation of YAP/β-catenin complexes and induces the WNT target gene MYC. These data support a previously unrecognized model in which targeting MUC1-C in TNBC cells (i) induces CRB3 expression, (ii) activates the CRB3-driven Hippo pathway, (iii) inactivates YAP, and thereby (iv) suppresses YAP/β-catenin-mediated induction of MYC expression. Implications These findings demonstrate a previously unrecognized role for the MUC1-C oncoprotein in the regulation of polarity and the Hippo pathway in breast cancer. PMID:27658423

  8. MUC1-C Oncoprotein Integrates a Program of EMT, Epigenetic Reprogramming and Immune Evasion in Human Carcinomas.

    Science.gov (United States)

    Rajabi, Hasan; Kufe, Donald

    2017-08-01

    The MUC1 gene evolved in mammalian species to provide protection of epithelia. The transmembrane MUC1 C-terminal subunit (MUC1-C) signals stress to the interior of the epithelial cell and, when overexpressed as in most carcinomas, functions as an oncoprotein. MUC1-C induces the epithelial-mesenchymal transition (EMT) by activating the inflammatory NF-κB p65 pathway and, in turn, the EMT-transcriptional repressor ZEB1. Emerging evidence has indicated that MUC1-C drives a program integrating the induction of EMT with activation of stem cell traits, epigenetic reprogramming and immune evasion. This mini-review focuses on the potential importance of this MUC1-C program in cancer progression. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. MUC1-C activates polycomb repressive complexes and downregulates tumor suppressor genes in human cancer cells.

    Science.gov (United States)

    Rajabi, Hasan; Hiraki, Masayuki; Kufe, Donald

    2018-04-01

    The PRC2 and PRC1 complexes are aberrantly expressed in human cancers and have been linked to decreases in patient survival. MUC1-C is an oncoprotein that is also overexpressed in diverse human cancers and is associated with a poor prognosis. Recent studies have supported a previously unreported function for MUC1-C in activating PRC2 and PRC1 in cancer cells. In the regulation of PRC2, MUC1-C (i) drives transcription of the EZH2 gene, (ii) binds directly to EZH2, and (iii) enhances occupancy of EZH2 on target gene promoters with an increase in H3K27 trimethylation. Regarding PRC1, which is recruited to PRC2 sites in the hierarchical model, MUC1-C induces BMI1 transcription, forms a complex with BMI1, and promotes H2A ubiquitylation. MUC1-C thereby contributes to the integration of PRC2 and PRC1-mediated repression of tumor suppressor genes, such as CDH1, CDKN2A, PTEN and BRCA1. Like PRC2 and PRC1, MUC1-C is associated with the epithelial-mesenchymal transition (EMT) program, cancer stem cell (CSC) state, and acquisition of anticancer drug resistance. In concert with these observations, targeting MUC1-C downregulates EZH2 and BMI1, inhibits EMT and the CSC state, and reverses drug resistance. These findings emphasize the significance of MUC1-C as a therapeutic target for inhibiting aberrant PRC function and reprogramming the epigenome in human cancers.

  10. Interleukin-13-induced MUC5AC is regulated by 15-lipoxygenase 1 pathway in human bronchial epithelial cells.

    Science.gov (United States)

    Zhao, Jinming; Maskrey, Ben; Balzar, Silvana; Chibana, Kazuyuki; Mustovich, Anthony; Hu, Haizhen; Trudeau, John B; O'Donnell, Valerie; Wenzel, Sally E

    2009-05-01

    15-Lipoxygenase-1 (15LO1) and MUC5AC are highly expressed in asthmatic epithelial cells. IL-13 is known to induce 15LO1 and MUC5AC in human airway epithelial cells in vitro. Whether 15LO1 and/or its product 15-HETE modulate MUC5AC expression is unknown. To determine the expression of 15LO1 in freshly harvested epithelial cells from subjects with asthma and normal control subjects and to determine whether IL-13-induced 15LO1 expression and activation regulate MUC5AC expression in human bronchial epithelial cells in vitro. Human airway epithelial cells from subjects with asthma and normal subjects were evaluated ex vivo for 15LO1 and MUC5AC expression. The impact of 15LO1 on MUC5AC expression in vitro was analyzed by inhibiting 15LO1 through pharmacologic (PD146176) and siRNA approaches in human bronchial epithelial cells cultured under air-liquid interface. We analyzed 15 hydroxyeicosatetraenoic acid (15-HETE) by liquid chromatography/UV/mass spectrometry. MUC5AC and 15LO1 were analyzed by real-time RT-PCR, immunofluoresence, and Western blot. Epithelial 15LO1 expression increased with asthma severity (P < 0.0001). 15LO1 significantly correlated with MUC5AC ex vivo and in vitro. IL-13 increased 15LO1 expression and stimulated formation of two molecular species of 15-HETE esterified to phosphotidylethanolamine (15-HETE-PE). Inhibition of 15LO1 suppressed 15-HETE-PE and decreased MUC5AC expression in the presence of IL-13 stimulation. The addition of exogenous 15-HETE partially restored MUC5AC expression. Epithelial 15LO1 expression increases with increasing asthma severity. IL-13 induction of 15-HETE-PE enhances MUC5AC expression in human airway epithelial cells. High levels of 15LO1 activity could contribute to the increases of MUC5AC observed in asthma.

  11. MUC1-C integrates PD-L1 induction with repression of immune effectors in non-small-cell lung cancer.

    Science.gov (United States)

    Bouillez, A; Rajabi, H; Jin, C; Samur, M; Tagde, A; Alam, M; Hiraki, M; Maeda, T; Hu, X; Adeegbe, D; Kharbanda, S; Wong, K-K; Kufe, D

    2017-07-13

    Immunotherapeutic approaches, particularly programmed death 1/programmed death ligand 1 (PD-1/PD-L1) blockade, have improved the treatment of non-small-cell lung cancer (NSCLC), supporting the premise that evasion of immune destruction is of importance for NSCLC progression. However, the signals responsible for upregulation of PD-L1 in NSCLC cells and whether they are integrated with the regulation of other immune-related genes are not known. Mucin 1 (MUC1) is aberrantly overexpressed in NSCLC, activates the nuclear factor-κB (NF-κB) p65→︀ZEB1 pathway and confers a poor prognosis. The present studies demonstrate that MUC1-C activates PD-L1 expression in NSCLC cells. We show that MUC1-C increases NF-κB p65 occupancy on the CD274/PD-L1 promoter and thereby drives CD274 transcription. Moreover, we demonstrate that MUC1-C-induced activation of NF-κB→︀ZEB1 signaling represses the TLR9 (toll-like receptor 9), IFNG, MCP-1 (monocyte chemoattractant protein-1) and GM-CSF genes, and that this signature is associated with decreases in overall survival. In concert with these results, targeting MUC1-C in NSCLC tumors suppresses PD-L1 and induces these effectors of innate and adaptive immunity. These findings support a previously unrecognized central role for MUC1-C in integrating PD-L1 activation with suppression of immune effectors and poor clinical outcome.

  12. Cancer-associated autoantibodies to MUC1 and MUC4--a blinded case–control study of colorectal cancer in UK collaborative trial of ovarian cancer screening

    DEFF Research Database (Denmark)

    Pedersen, Johannes W; Gentry-Maharaj, Aleksandra; Nøstdal, Alexander

    2014-01-01

    of colorectal cancer diagnosis and healthy controls. Subsequently, the selected biomarkers were evaluated in a blinded nested case–control study using stored serum samples from among the 50,640 women randomized to the multimodal arm of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), where......, at 95% specificity. IgA to MUC4 glycoforms were unable to discriminate between cases and controls in the UKCTOCS sera. Additional analysis was undertaken by combining the data of MUC1-STn and MUC1-Core3 with previously generated data on autoantibodies to p53 peptides, which increased the sensitivity...

  13. Polymorphisms of interleukin-1β and MUC7 genes in burning mouth syndrome.

    Science.gov (United States)

    Kim, Moon-Jong; Kim, Jihoon; Chang, Ji-Youn; Kim, Yoon-Young; Kho, Hong-Seop

    2017-04-01

    The objectives of the present study are to compare polymorphisms of the IL-1β and MUC7 genes between patients with burning mouth syndrome (BMS) and controls and to investigate relationships between these polymorphisms and clinical characteristics in BMS patients. Forty female BMS patients and 40 gender- and age-matched controls were included. Genomic DNA was extracted from saliva samples. Single-nucleotide polymorphisms of IL-1β -511 and +3954 and variation in number of tandem repeat (VNTR) polymorphism of MUC7 were analyzed. Relationships between genotypic polymorphism data and clinical characteristics in BMS patients were also analyzed. There were no significant differences in the genotypes of IL-1β -511 and +3954 and of MUC7 between the groups. There were no significant differences in symptom duration and intensity of BMS patients according to their IL-1β and MUC7 genotypes. The T allele of IL-1β -511 showed associations with psychometry results in BMS patients: paranoid ideation (P = 0.014), Global Severity Index (P = 0.025), and Positive Symptom Total (P = 0.008). The genotypic polymorphisms of IL-1β -511 and +3954, and of MUC7 VNTR, had no direct associations with the development of BMS. However, the T allele of IL-1β -511 may increase the risk of BMS by increasing psychological asthenia. The genotypic polymorphisms of IL-1β -511 may increase the risk for the development of BMS by increasing psychological asthenia.

  14. MicroRNA-128 suppresses paclitaxel-resistant lung cancer by inhibiting MUC1-C and BMI-1 in cancer stem cells.

    Science.gov (United States)

    Koh, Hyebin; Park, Hyeri; Chandimali, Nisansala; Huynh, Do Luong; Zhang, Jiao Jiao; Ghosh, Mrinmoy; Gera, Meeta; Kim, Nameun; Bak, Yesol; Yoon, Do-Young; Park, Yang Ho; Kwon, Taeho; Jeong, Dong Kee

    2017-12-15

    The existence of cancer stem cells (CSCs) is the main reason for failure of cancer treatment caused by drug resistance. Therefore, eradicating cancers by targeting CSCs remains a significant challenge. In the present study, because of the important role of BMI-1 proto-oncogene, polycomb ring finger (BMI-1) and C-terminal Mucin1 (MUC1-C) in tumor growth and maintenance of CSCs, we aimed to confirm that microRNA miR-128, as an inhibitor of BMI-1 and MUC1-C, could effectively suppress paclitaxel (PTX)-resistant lung cancer stem cells. We showed that CSCs have significantly higher expression levels of BMI-1, MUC1-C, stemness proteins, signaling factors, and higher malignancy compared with normal tumor cells. After transfection with miR-128, the BMI-1 and MUC1-C levels in CSCs were suppressed. When miR-128 was stably expressed in PTX-resistant lung cancer stem cells, the cells showed decreased proliferation, metastasis, self-renewal, migration, invasive ability, clonogenicity, and tumorigenicity in vitro and in vivo and increased apoptosis compared with miR-NC (negative control) CSCs. Furthermore, miR-128 effectively decreased the levels of β-catenin and intracellular signaling pathway-related factors in CSCs. MiR-128 also decreased the luciferase activity of MUC1 reporter constructs and reduced the levels of transmembrane MUC1-C and BMI-1. These results suggested miR-128 as an attractive therapeutic strategy for PTX-resistant lung cancer via inhibition of BMI-1 and MUC1-C.

  15. Co-expression of HER3 and MUC1 is associated with a favourable prognosis in patients with bladder cancer

    DEFF Research Database (Denmark)

    Nielsen, Trine O; Borre, Michael; Nexo, Ebba

    2015-01-01

    OBJECTIVES: To investigate the functional impact of the interaction of MUC1 with the epidermal growth factor receptors HER3 and HER4 in patients with bladder cancer. PATIENTS AND METHODS: Using reverse transcription quantitative polymerase chain reaction, we examined MUC1 expression in 82 bladder...... the prognostic value of MUC1 (P = 0.488). MUC1 expression had no correlation with survival, tumour stage or grade, or to the prognostic value of HER4. CONCLUSIONS: A high MUC1 expression was associated with a favourable prognosis in patients with bladder cancer when the expression of HER3 was also high....... This suggests an involvement of HER3 in MUC1 function in bladder cancer....

  16. MUC1 (CD227) interacts with lck tyrosine kinase in Jurkat lymphoma cells and normal T cells.

    Science.gov (United States)

    Mukherjee, P; Tinder, T L; Basu, G D; Gendler, S J

    2005-01-01

    MUC1 (CD227) is a large transmembrane epithelial mucin glycoprotein, which is aberrantly overexpressed in most adenocarcinomas and is a target for immune therapy for epithelial tumors. Recently, MUC1 has been detected in a variety of hematopoietic cell malignancies including T and B cell lymphomas and myelomas; however, its function in these cells is not clearly defined. Using the Jurkat T cell lymphoma cell line and normal human T cells, we demonstrate that MUC1 is not only expressed in these cells but is also phosphorylated upon T cell receptor (TCR) ligation and associates with the Src-related T cell tyrosine kinase, p56lck. Upon TCR-mediated activation of Jurkat cells, MUC1 is found in the low-density membrane fractions, where linker of T cell activation is contained. Abrogation of MUC1 expression in Jurkat cells by MUC1-specific small interfering RNA resulted in defects in TCR-mediated downstream signaling events associated with T cell activation. These include reduction in Ca2+ influx and extracellular signal-regulated kinase 1/2 phosphorylation, leading to a decrease in CD69 expression, proliferation, and interleukin-2 production. These results suggest a regulatory role of MUC1 in modulating proximal signal transduction events through its interaction with proteins of the activation complex.

  17. Characterization of a novel weak interaction between MUC1 and Src-SH3 using nuclear magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Gunasekara, Nirosha [Department of Laboratory Medicine and Pathology, University of Alberta, 5B4.21 WCM Health Science Centre, 8440-112th Street, Edmonton, Alberta, Canada T6G 2R7 (Canada); Sykes, Brian, E-mail: brian.sykes@ualberta.ca [Department of Biochemistry, 4-19B Medical Sciences Bldg., University of Alberta Edmonton, Alberta, Canada T6G 2H7 (Canada); Hugh, Judith, E-mail: judithh@ualberta.ca [Department of Laboratory Medicine and Pathology, University of Alberta, 5B4.21 WCM Health Science Centre, 8440-112th Street, Edmonton, Alberta, Canada T6G 2R7 (Canada)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer MUC1 binds the Src-SH3 domain potentially triggering Src dependent cell migration. Black-Right-Pointing-Pointer NMR Spectroscopy was used to monitor MUC1-CD and Src SH3 domain titrations. Black-Right-Pointing-Pointer MUC1-CD peptides bind with a low affinity (K{sub d} of 2-3 mM) to a non-canonical site. Black-Right-Pointing-Pointer Weak interactions may mediate dynamic processes like migration. Black-Right-Pointing-Pointer The MUC1-CD and Src-SH3 interaction may be a prime target to inhibit cell migration. -- Abstract: Breast cancer causes death through cancer cell migration and subsequent metastasis to distant organs. In vitro, the MUC1 mucin can mediate breast cancer cell migration by binding to intercellular adhesion molecule-1 (ICAM-1). This migration is dependent on MUC1 cytoplasmic domain (MUC1-CD) activation of the non-receptor tyrosine kinase, Src, possibly through competitive displacement of an inhibitory Src intramolecular SH3 binding. Therefore, we characterized the binding site and affinity of the MUC1-CD for Src-SH3 using multidimensional nuclear magnetic resonance (NMR) spectroscopy to monitor the titration of the {sup 15}N labeled Src-SH3 domain with synthetic native and mutant peptides of MUC1-CD. The results revealed that the dissociation constant (K{sub d}) for the interaction of the native MUC1-CD peptides and Src-SH3 domain was weak with a K{sub d} of 2-3 mM. Notably, the SH3 residues most perturbed upon peptide binding were located outside the usual hydrophobic binding cleft in a previously described alternate binding site on the Src-SH3, suggesting that MUC1-CD binds to a non-canonical site. The binding characteristics outlined here suggest that the interaction between Src-SH3 and MUC1-CD represents a novel weak electrostatic interaction of the type which is increasingly recognized as important in transient and dynamic protein complexes required for cell migration and signal transduction. As such, this

  18. The Cytoplasmic Domain of MUC1 Induces Hyperplasia in the Mammary Gland and Correlates with Nuclear Accumulation of β-Catenin

    Science.gov (United States)

    Li, Yuan; Yi, Haiying; Yao, Yixin; Liao, Xiaodong; Xie, Yiqun; Yang, Jie; Yan, Zheng; Wang, Long; Lu, Shunyuan; Kuang, Ying; Gu, Mingmin; Fei, Jian; Wang, Zhugang; Huang, Lei

    2011-01-01

    MUC1 is an oncoprotein that is overexpressed in up to 90% of breast carcinomas. A previous in vitro study by our group demonstrated that the cytoplasmic domain of MUC1 (MUC1-CD), the minimal functional unit of MUC1, contributes to the malignant phenotype in cells by binding directly to β-catenin and protecting β-catenin from GSK3β-induced degradation. To understand the in vivo role of MUC1-CD in breast development, we generated a MUC1-CD transgenic mouse model under the control of the MMTV promoter in a C57BL/6J background, which is more resistant to breast tumor. We show that the expression of MUC1-CD in luminal epithelial cells of the mammary gland induced a hyperplasia phenotype characterized by the development of hyper-branching and extensive lobuloalveoli in transgenic mice. In addition to this hyperplasia, there was a marked increase in cellular proliferation in the mouse mammary gland. We further show that MUC1-CD induces nuclear localization of β-catenin, which is associated with a significant increase of β-catenin activity, as shown by the elevated expression of cyclin D1 and c-Myc in MMTV-MUC1-CD mice. Consistent with this finding, we observed that overexpression of MUC1-C is associated with β-catenin nuclear localization in tumor tissues and increased expression of Cyclin D1 and c-Myc in breast carcinoma specimens. Collectively, our data indicate a critical role for MUC1-CD in the development of mammary gland preneoplasia and tumorigenesis, suggesting MUC1-CD as a potential target for the diagnosis and chemoprevention of human breast cancer. PMID:21533058

  19. The cytoplasmic domain of MUC1 induces hyperplasia in the mammary gland and correlates with nuclear accumulation of β-catenin.

    Directory of Open Access Journals (Sweden)

    Yuan Li

    Full Text Available MUC1 is an oncoprotein that is overexpressed in up to 90% of breast carcinomas. A previous in vitro study by our group demonstrated that the cytoplasmic domain of MUC1 (MUC1-CD, the minimal functional unit of MUC1, contributes to the malignant phenotype in cells by binding directly to β-catenin and protecting β-catenin from GSK3β-induced degradation. To understand the in vivo role of MUC1-CD in breast development, we generated a MUC1-CD transgenic mouse model under the control of the MMTV promoter in a C57BL/6J background, which is more resistant to breast tumor. We show that the expression of MUC1-CD in luminal epithelial cells of the mammary gland induced a hyperplasia phenotype characterized by the development of hyper-branching and extensive lobuloalveoli in transgenic mice. In addition to this hyperplasia, there was a marked increase in cellular proliferation in the mouse mammary gland. We further show that MUC1-CD induces nuclear localization of β-catenin, which is associated with a significant increase of β-catenin activity, as shown by the elevated expression of cyclin D1 and c-Myc in MMTV-MUC1-CD mice. Consistent with this finding, we observed that overexpression of MUC1-C is associated with β-catenin nuclear localization in tumor tissues and increased expression of Cyclin D1 and c-Myc in breast carcinoma specimens. Collectively, our data indicate a critical role for MUC1-CD in the development of mammary gland preneoplasia and tumorigenesis, suggesting MUC1-CD as a potential target for the diagnosis and chemoprevention of human breast cancer.

  20. Interleukin-13–induced MUC5AC Is Regulated by 15-Lipoxygenase 1 Pathway in Human Bronchial Epithelial Cells

    Science.gov (United States)

    Zhao, Jinming; Maskrey, Ben; Balzar, Silvana; Chibana, Kazuyuki; Mustovich, Anthony; Hu, Haizhen; Trudeau, John B.; O'Donnell, Valerie; Wenzel, Sally E.

    2009-01-01

    Rationale: 15-Lipoxygenase-1 (15LO1) and MUC5AC are highly expressed in asthmatic epithelial cells. IL-13 is known to induce 15LO1 and MUC5AC in human airway epithelial cells in vitro. Whether 15LO1 and/or its product 15-HETE modulate MUC5AC expression is unknown. Objectives: To determine the expression of 15LO1 in freshly harvested epithelial cells from subjects with asthma and normal control subjects and to determine whether IL-13–induced 15LO1 expression and activation regulate MUC5AC expression in human bronchial epithelial cells in vitro. Methods: Human airway epithelial cells from subjects with asthma and normal subjects were evaluated ex vivo for 15LO1 and MUC5AC expression. The impact of 15LO1 on MUC5AC expression in vitro was analyzed by inhibiting 15LO1 through pharmacologic (PD146176) and siRNA approaches in human bronchial epithelial cells cultured under air–liquid interface. We analyzed 15 hydroxyeicosatetraenoic acid (15-HETE) by liquid chromatography/UV/mass spectrometry. MUC5AC and 15LO1 were analyzed by real-time RT-PCR, immunofluoresence, and Western blot. Measurements and Main Results: Epithelial 15LO1 expression increased with asthma severity (P < 0.0001). 15LO1 significantly correlated with MUC5AC ex vivo and in vitro. IL-13 increased 15LO1 expression and stimulated formation of two molecular species of 15-HETE esterified to phosphotidylethanolamine (15-HETE-PE). Inhibition of 15LO1 suppressed 15-HETE-PE and decreased MUC5AC expression in the presence of IL-13 stimulation. The addition of exogenous 15-HETE partially restored MUC5AC expression. Conclusions: Epithelial 15LO1 expression increases with increasing asthma severity. IL-13 induction of 15-HETE-PE enhances MUC5AC expression in human airway epithelial cells. High levels of 15LO1 activity could contribute to the increases of MUC5AC observed in asthma. PMID:19218191

  1. Therapeutic efficacy of MUC1-specific cytotoxic T lymphocytes and CD137 co-stimulation in a spontaneous breast cancer model.

    Science.gov (United States)

    Mukherjee, Pinku; Tinder, Teresa L; Basu, Gargi D; Pathangey, Latha B; Chen, Lieping; Gendler, Sandra J

    2004-01-01

    To study immunology in breast tumors, we have utilized a mammary gland adenocarcinoma model in which mice develop spontaneous tumors of the mammary gland which are initiated at puberty and express a human tumor antigen, MUC1. MUC1 (CD227) is over-expressed in 90% of human breast cancers and its glycosylation status and pattern of expression in cancer cells is altered. Humoral and cellular responses to MUC1 have been reported in breast cancer patients and therefore, MUC1 is being evaluated as a target for immune intervention. This mouse model of spontaneous breast cancer allows the evaluation of anti-MUC1 immune responses at all stages of the disease. In this report, we review the model as it pertains to a) the development of the tumor, b) MUC1 expression, and the native immune responses against MUC1 as tumors progress, and c) the immune suppressive microenvironment within the developing tumor. Finally, we report our latest findings describing the therapeutic efficacy of adoptively transferred MUC1-specific cytotoxic T lymphocytes (MUC1-CTL) in these mice and discuss ways to increase their effectiveness by agonistic monoclonal antibody against CD137 T cell costimulatory molecule.

  2. A soluble form of Siglec-9 provides an antitumor benefit against mammary tumor cells expressing MUC1 in transgenic mice

    International Nuclear Information System (INIS)

    Tomioka, Yukiko; Morimatsu, Masami; Nishijima, Ken-ichi; Usui, Tatsufumi; Yamamoto, Sayo; Suyama, Haruka; Ozaki, Kinuyo; Ito, Toshihiro

    2014-01-01

    Highlights: • Tumor-associated antigen MUC1 binds to Siglec-9. • Soluble Siglec-9 reduced proliferation of MUC1-positive tumor in transgenic mice. • Soluble Siglec-9 and MUC1 on tumor cells were colocalized in transgenic mice. • MUC1 expression on tumor cells were reduced in soluble Siglec-9 transgenic mice. - Abstract: Tumor-associated MUC1 binds to Siglec-9, which is expected to mediate tumor cell growth and negative immunomodulation. We hypothesized that a soluble form of Siglec-9 (sSiglec-9) competitively inhibits a binding of MUC1 to its receptor molecules like human Siglec-9, leading to provide antitumor benefit against MUC1-expressing tumor, and generated transgenic mouse lines expressing sSiglec-9 (sSiglec-9 Tg). When mammary tumor cells expressing MUC1 were intraperitoneally transplanted into sSiglec-9 Tg, tumor proliferation was slower with the lower histological malignancy as compared with non-transgenic mice. The sSiglec-9 was detected in the ascites caused by the tumor in the sSiglec-9 Tg, and sSiglec-9 and MUC1 were often colocalized on surfaces of the tumor cells. PCNA immunohistochemistry also revealed the reduced proliferation of the tumor cells in sSiglec-9 Tg. In sSiglec-9 Tg with remarkable suppression of tumor proliferation, MUC1 expressions were tend to be reduced. In the ascites of sSiglec-9 Tg bearing the tumor, T cells were uniformly infiltrated, whereas aggregations of degenerative T cells were often observed in the non-transgenic mice. These results suggest that sSiglec-9 has an antitumor benefit against MUC1-expressing tumor in the transgenic mice, which may avoid the negative immunomodulation and/or suppress tumor-associated MUC1 downstream signal transduction, and subsequent tumor proliferation

  3. A soluble form of Siglec-9 provides an antitumor benefit against mammary tumor cells expressing MUC1 in transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Tomioka, Yukiko, E-mail: ytomi@muses.tottori-u.ac.jp [Division of Disease Model Innovation, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815 (Japan); Avian Zoonosis Research Center, Faculty of Agriculture, Tottori University, Tottori 680-8553 (Japan); Morimatsu, Masami, E-mail: mmorimat@vetmed.hokudai.ac.jp [Division of Disease Model Innovation, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815 (Japan); Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818 (Japan); Nishijima, Ken-ichi, E-mail: nishijma@nubio.nagoya-u.ac.jp [Department of Biotechnology, Graduate School of Engineering, Nagoya University, Nagoya 464-8603 (Japan); Usui, Tatsufumi, E-mail: usutatsu@muses.tottori-u.ac.jp [Avian Zoonosis Research Center, Faculty of Agriculture, Tottori University, Tottori 680-8553 (Japan); Yamamoto, Sayo, E-mail: ysayo@anim.med.kyushu-u.ac.jp [Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan); Suyama, Haruka, E-mail: sharuka@anim.med.kyushu-u.ac.jp [Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan); Ozaki, Kinuyo, E-mail: k-ozaki@anim.med.kyushu-u.ac.jp [Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan); Ito, Toshihiro, E-mail: toshiito@muses.tottori-u.ac.jp [Avian Zoonosis Research Center, Faculty of Agriculture, Tottori University, Tottori 680-8553 (Japan); and others

    2014-07-18

    Highlights: • Tumor-associated antigen MUC1 binds to Siglec-9. • Soluble Siglec-9 reduced proliferation of MUC1-positive tumor in transgenic mice. • Soluble Siglec-9 and MUC1 on tumor cells were colocalized in transgenic mice. • MUC1 expression on tumor cells were reduced in soluble Siglec-9 transgenic mice. - Abstract: Tumor-associated MUC1 binds to Siglec-9, which is expected to mediate tumor cell growth and negative immunomodulation. We hypothesized that a soluble form of Siglec-9 (sSiglec-9) competitively inhibits a binding of MUC1 to its receptor molecules like human Siglec-9, leading to provide antitumor benefit against MUC1-expressing tumor, and generated transgenic mouse lines expressing sSiglec-9 (sSiglec-9 Tg). When mammary tumor cells expressing MUC1 were intraperitoneally transplanted into sSiglec-9 Tg, tumor proliferation was slower with the lower histological malignancy as compared with non-transgenic mice. The sSiglec-9 was detected in the ascites caused by the tumor in the sSiglec-9 Tg, and sSiglec-9 and MUC1 were often colocalized on surfaces of the tumor cells. PCNA immunohistochemistry also revealed the reduced proliferation of the tumor cells in sSiglec-9 Tg. In sSiglec-9 Tg with remarkable suppression of tumor proliferation, MUC1 expressions were tend to be reduced. In the ascites of sSiglec-9 Tg bearing the tumor, T cells were uniformly infiltrated, whereas aggregations of degenerative T cells were often observed in the non-transgenic mice. These results suggest that sSiglec-9 has an antitumor benefit against MUC1-expressing tumor in the transgenic mice, which may avoid the negative immunomodulation and/or suppress tumor-associated MUC1 downstream signal transduction, and subsequent tumor proliferation.

  4. Genes from plasmid pKM101 in Haemophilus influenzae: separation of functions of mucA and mucB

    International Nuclear Information System (INIS)

    Balganesh, M.; Setlow, J.K.

    1985-01-01

    Haemophilus influenzae, normally not mutable by UV, became UV mutable with a recombinant plasmid insertion. A 7.8-kilobase-pair (kbp) fragment of the plasmid pKM101 containing the mucA and mucB genes was ligated to the shuttle vector pDM2, and a Rec- strain of H. influenzae was transformed with the ligated mixture. All of the transformants, unlike the parent Rec- strain, were resistant to UV, could carry out postreplication repair and Weigle reactivation, showed greatly increased spontaneous mutation, and contained a plasmid carrying an insert of only 1.2 rather than 7.8 kbp. This plasmid in a umuC mutant strain of Escherichia coli complemented a pKM101 derivative lacking mucA function but with an intact mucB gene, although there was no complementation with a mucA+ mucB- plasmid, suggesting that the newly constructed plasmid coded for the mucA protein; this is in accord with the restriction analysis and hybridization between the plasmid and a probe containing all of the mucA gene but only a small fraction of mucB. When one of the H. influenzae Rec- transformants lost the plasmid, the resistance to UV was retained but the high spontaneous mutation and UV mutability were not. The fact that there was hybridization between the chromosome of the cured strain and a probe containing both muc genes but none when almost no mucB was present suggested that at least part of the mucB gene had been integrated into the Rec- chromosome. Five different postreplication repair-proficient strains became UV mutable and had high spontaneous mutation rates caused by the putative mucA plasmid, indicating that these strains already possessed a chromosomal equivalent of the mucB gene

  5. Distinguishing Truncated and Normal MUC1 Glycoform Targeting from Tn-MUC1-Specific CAR T Cells

    DEFF Research Database (Denmark)

    Posey, Avery D; Clausen, Henrik; June, Carl H

    2016-01-01

    Genetically modified T cells expressing chimeric antigen receptors (CARs) demonstrate potent clinical antitumor effects in a variety of blood cancers. However, clinical activity in solid tumors has been disappointing and toxicity has been a serious concern (Lamers et al., 2013; Morgan et al., 2010......). We recently found that a CAR composed of a scFv antibody fragment specific for the Tn-glycoform of MUC1 had potent activity in preclinical models of blood cancer and adenocarcinoma (Posey et al., 2016)....

  6. Prognostic Significance of Mucin Antigen MUC1 in Various Human Epithelial Cancers: A Meta-Analysis.

    Science.gov (United States)

    Xu, Feng; Liu, Fuquan; Zhao, Hongwei; An, Guangyu; Feng, Guosheng

    2015-12-01

    Accumulating evidence indicates that mucin antigen MUC1 plays a fundamental role in the initiation and progression of several types of epithelial carcinomas. However, whether the expression of MUC1 on tumor cells is associated with patients' survival remains controversial. Medline/PubMed, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) databases, and Grey literature were searched up to 15 August 2015 for eligible studies of the association between the MUC1 expression and overall survival (OS) in various epithelial cancers. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated from the included studies. Moreover, the odds ratio (OR) was also extracted to evaluate the association between the clinicopathological parameters of participants and MUC1 expression. A total of 3425 patients covering 23 studies were included in the analysis. The pooled results showed that positive MUC1 staining was a negative predictor of OS (HRFEM = 1.98,95% CIFEM: 1.76-2.22, PFEM = 0.479; HRREM = 2.16,95% CIREM: 1.58-2.94, PREM = 0.355) in various epithelial carcinomas. Subgroup analysis revealed that the increased MUC1 expression was significantly associated with poor OS in patients with gastric cancer (HRFEM = 2.12, 95%CIFEM: 1.75-2.57, PFEM = 0.359; HRREM = 1.89, 95% CIREM: 1.05-3.41, PREM = 0.238), colorectal cancer (HRFEM = 1.73, 95%CIFEM: 1.41-2.13, PFEM = 0.048; HRREM = 2.00,95% CIREM: 1.46-2.73, PREM = 0.019), cholangiocarcinoma (HRFEM = 2.52, 95% CIFEM: 1.42-4.49, PFEM = 0.252; HRREM = 2.34, 95% CIREM: 1.30-4.22, PREM = 0.244), and nonsmall cell lung cancer (NSCLC) (HRFEM = 2.14, 95% CIFEM: 1.46-3.14, PFEM = 0.591; HRREM = 2.81, 95% CIREM: 1.40-5.64, PREM = 0.280). In addition, MUC1 overexpression was more likely to be found in colorectal cancer patients with an advanced tumor node metastasis stage (ORREM = 1.55, 95% CIREM: 1.06-2.27; PREM = 0

  7. Relationships between oral MUC1 expression and salivary hormones in burning mouth syndrome.

    Science.gov (United States)

    Kang, Jeong-Hyun; Kim, Yoon-Young; Chang, Ji-Youn; Kho, Hong-Seop

    2017-06-01

    To investigate possible relationships among oral mucosal epithelial MUC1 expression, salivary female gonadal hormones and stress markers, and clinical characteristics in patients with burning mouth syndrome (BMS). Thirty post-menopausal female patients with BMS (60.0±5.0 years) were included. Clinical and psychological evaluations were performed and the expression level of oral mucosal epithelial MUC1 was analyzed. The levels of cortisol, dehydroepiandrosterone (DHEA), 17β-estradiol, progesterone, chromogranin A, and blood contamination were determined from unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) samples. Salivary progesterone level had significant positive correlations with oral mucosal epithelial MUC1 expression level and with salivary cortisol and DHEA levels. The salivary level of 17β-estradiol showed significant positive correlations with period of symptom duration, severity of effects of oral complaints on daily life, and results from psychological evaluations. Cortisol level in UWS and cortisol/DHEA ratio in UWS and SWS had negative correlations with severity of oral burning sensation significantly. The severity of taste disturbance had positive correlations with results from psychometry significantly. Dysregulated psychoendocrinological interactions might affect oral mucosal MUC1 expression and severity of oral burning sensation in post-menopausal BMS patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. MUC1 Expression by Immunohistochemistry Is Associated with Adverse Pathologic Features in Prostate Cancer: A Multi-Institutional Study.

    Directory of Open Access Journals (Sweden)

    Okyaz Eminaga

    Full Text Available The uncertainties inherent in clinical measures of prostate cancer (CaP aggressiveness endorse the investigation of clinically validated tissue biomarkers. MUC1 expression has been previously reported to independently predict aggressive localized prostate cancer. We used a large cohort to validate whether MUC1 protein levels measured by immunohistochemistry (IHC predict aggressive cancer, recurrence and survival outcomes after radical prostatectomy independent of clinical and pathological parameters.MUC1 IHC was performed on a multi-institutional tissue microarray (TMA resource including 1,326 men with a median follow-up of 5 years. Associations with clinical and pathological parameters were tested by the Chi-square test and the Wilcoxon rank sum test. Relationships with outcome were assessed with univariable and multivariable Cox proportional hazard models and the Log-rank test.The presence of MUC1 expression was significantly associated with extracapsular extension and higher Gleason score, but not with seminal vesicle invasion, age, positive surgical margins or pre-operative serum PSA levels. In univariable analyses, positive MUC1 staining was significantly associated with a worse recurrence free survival (RFS (HR: 1.24, CI 1.03-1.49, P = 0.02, although not with disease specific survival (DSS, P>0.5. On multivariable analyses, the presence of positive surgical margins, extracapsular extension, seminal vesicle invasion, as well as higher pre-operative PSA and increasing Gleason score were independently associated with RFS, while MUC1 expression was not. Positive MUC1 expression was not independently associated with disease specific survival (DSS, but was weakly associated with overall survival (OS.In our large, rigorously designed validation cohort, MUC1 protein expression was associated with adverse pathological features, although it was not an independent predictor of outcome after radical prostatectomy.

  9. MUC-1-ESA+ progenitor cells in normal benign and malignant human breast epithelial cells

    OpenAIRE

    Lu, Xinquan; Li, Huixiang; Xu, Kejia; Nesland, Jahn M.; Suo, Zhenhe

    2009-01-01

    The existence of mammary epithelial stem/progenitor cells has been demonstrated in MUC-1-/ ESA+ subpopulations of breast epithelial cells. However, knowledge about the expression and localization in benign and malignant breast lesions is unknown. Using a double-staining immunohistochemistry method, we investigated MUC-1-/ESA+ cells in 10 normal breast tissues, 49 cases with fibrocystic disease, 40 fibroadenomas, 36 invasive ductal carcinomas and the breast cancer ce...

  10. In vivo and in vitro studies of MUC1 regulation in sheep endometrium.

    Science.gov (United States)

    Raheem, Kabir A; Marei, Waleed F A; Campbell, Bruce K; Fouladi-Nashta, Ali A

    2016-06-01

    In this study, we investigated the expression of mucin 1 (MUC1) mRNA and protein in sheep endometrium at different time points during follicular and luteal phases of estrous cycle, and also determined the effect of steroid hormone treatments and interferon tau (IFNτ) on MUC1 mRNA expression in endometrial cell culture in vitro. In experiment one, 15 Welsh mountain ewes were synchronized to a common estrus and killed at precise stages of estrous cycle corresponding to (1) pre-LH peak, (2) LH peak, (3) post-LH peak, (4) early luteal, and (5) mid-luteal. Reproductive tracts were harvested and mRNA was extracted from the endometrial tissues. Parts of the uterine horns were fixed for immunohistochemistry. In experiment two, mixed populations of ovine endometrial cells (from slaughterhouse material collected at the postovulatory stage of the estrous cycle) were cultured to 70% confluence before treatment with (1) progesterone (P4, 10 ng/mL, for 48 hours), (2) estradiol (E2, 100 pg/mL, for 48 hours), or with (3) E2 priming for 12 hours (100 pg/mL) followed by P4 (10 ng/mL) for 36 hours. These were compared with: (4) IFNτ (10 ng/mL, for 48 hours), and (5) basic medium (Dulbecco Modified Eagle Medium /F12) as control. The results showed that MUC1 mRNA and protein expression in sheep endometrium were highest during the midluteal stage and very low during the post-LH period compared with the other stages (P < 0.05). MUC1 immunostaining in the luminal epithelium was apically restricted and was not significantly different across all stages of estrous cycle except at the post-LH peak where it was significantly low. In cell culture, MUC1 mRNA expression was significantly upregulated by both steroids either singly or in combination (P < 0.05), and downregulated in the presence of IFNτ. In conclusion, endometrial MUC1 expression is cyclically regulated by both E2 and P4in vivo and in vitro, and directly downregulated by IFNτ treatment in vitro. Copyright © 2016

  11. Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis

    DEFF Research Database (Denmark)

    Blixt, Ola; Bueti, Deanna; Burford, Brian

    2011-01-01

    associated glycoforms of MUC1 in a proportion of early breast cancer patients (54/198). Five positive sera were selected for detailed definition of the reactive epitopes using on chip glycosylation technology and a panel of glycopeptides based on a single MUC1 tandem repeat carrying specific glycans...

  12. Molecular mimics of the tumour antigen MUC1.

    Directory of Open Access Journals (Sweden)

    Tharappel C James

    Full Text Available A key requirement for the development of cancer immunotherapy is the identification of tumour-associated antigens that are differentially or exclusively expressed on the tumour and recognized by the host immune system. However, immune responses to such antigens are often muted or lacking due to the antigens being recognized as "self", and further complicated by the tumour environment and regulation of immune cells within. In an effort to circumvent the lack of immune responses to tumour antigens, we have devised a strategy to develop potential synthetic immunogens. The strategy, termed mirror image phage display, is based on the concept of molecular mimicry as demonstrated by the idiotype/anti-idiotype paradigm in the immune system. Here as 'proof of principle' we have selected molecular mimics of the well-characterised tumour associated antigen, the human mucin1 protein (MUC1 from two different peptide phage display libraries. The putative mimics were compared in structure and function to that of the native antigen. Our results demonstrate that several of the mimic peptides display T-cell stimulation activity in vitro when presented by matured dendritic cells. The mimic peptides and the native MUC1 antigenic epitopes can cross-stimulate T-cells. The data also indicate that sequence homology and/or chemical properties to the original epitope are not the sole determining factors for the observed immunostimulatory activity of the mimic peptides.

  13. Hath1 inhibits proliferation of colon cancer cells probably through up-regulating expression of Muc2 and p27 and down-regulating expression of cyclin D1.

    Science.gov (United States)

    Zhu, Dai-Hua; Niu, Bai-Lin; Du, Hui-Min; Ren, Ke; Sun, Jian-Ming; Gong, Jian-Ping

    2012-01-01

    Previous studies showed that Math1 homologous to human Hath1 can cause mouse goblet cells to differentiate. In this context it is important that the majority of colon cancers have few goblet cells. In the present study, the potential role of Hath1 in colon carcinogenesis was investigated. Sections of paraffin-embedded tissues were used to investigate the goblet cell population of normal colon mucosa, mucosa adjacent colon cancer and colon cancer samples from 48 patients. Hath1 and Muc2 expression in these samples were tested by immunohistochemistry, quantitative real-time reverse transcription -PCR and Western blotting. After the recombinant plasmid, pcDNA3.1(+)-Hath1 had been transfected into HT29 colon cancer cells, three clones were selected randomly to test the levels of Hath1 mRNA, Muc2 mRNA, Hath1, Muc2, cyclin D1 and p27 by quantitative real-time reverse transcription-PCR and Western blotting. Moreover, the proliferative ability of HT29 cells introduced with Hath1 was assessed by means of colony formation assay and xenografting. Expression of Hath1, Muc2, cyclin D1 and p27 in the xenograft tumors was also detected by Western blotting. No goblet cells were to be found in colon cancer and levels of Hath1 mRNA and Hath1, Muc2 mRNA and Muc2 were significantly down-regulated. Hath1 could decrease cyclin D1, increase p27 and Muc2 in HT29 cells and inhibit their proliferation. Hath1 may be an anti-oncogene in colon carcinogenesis.

  14. Expression of MUC17 is regulated by HIF1α-mediated hypoxic responses and requires a methylation-free hypoxia responsible element in pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Sho Kitamoto

    Full Text Available MUC17 is a type 1 membrane-bound glycoprotein that is mainly expressed in the digestive tract. Recent studies have demonstrated that the aberrant overexpression of MUC17 is correlated with the malignant potential of pancreatic ductal adenocarcinomas (PDACs; however, the exact regulatory mechanism of MUC17 expression has yet to be identified. Here, we provide the first report of the MUC17 regulatory mechanism under hypoxia, an essential feature of the tumor microenvironment and a driving force of cancer progression. Our data revealed that MUC17 was significantly induced by hypoxic stimulation through a hypoxia-inducible factor 1α (HIF1α-dependent pathway in some pancreatic cancer cells (e.g., AsPC1, whereas other pancreatic cancer cells (e.g., BxPC3 exhibited little response to hypoxia. Interestingly, these low-responsive cells have highly methylated CpG motifs within the hypoxia responsive element (HRE, 5'-RCGTG-3', a binding site for HIF1α. Thus, we investigated the demethylation effects of CpG at HRE on the hypoxic induction of MUC17. Treatment of low-responsive cells with 5-aza-2'-deoxycytidine followed by additional hypoxic incubation resulted in the restoration of hypoxic MUC17 induction. Furthermore, DNA methylation of HRE in pancreatic tissues from patients with PDACs showed higher hypomethylation status as compared to those from non-cancerous tissues, and hypomethylation was also correlated with MUC17 mRNA expression. Taken together, these findings suggested that the HIF1α-mediated hypoxic signal pathway contributes to MUC17 expression, and DNA methylation of HRE could be a determinant of the hypoxic inducibility of MUC17 in pancreatic cancer cells.

  15. Relação entre a expressão da MUC1 e os estadiamentos TNM e Astler-Coller no câncer colorretal Relation between the expression of MUC1 and TNM and Astler-Coller staging systems in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Paula Gabriela Melo Morais

    2008-06-01

    Full Text Available A expressão de marcadores tumorais que se correlacionam com a agressividade dos cânceres vem sendo investigada com vigor. Tendo o câncer colorretal significativa incidência, biomarcadores que possam avaliá-lo quanto a esse aspecto, não são exceção nesta investigação. OBJETIVO: estabelecer a relação entre agressividade do câncer colorretal de acordo com os estadiamentos TNM e Astler-Coller e a expressão da Mucina1 (MUC1 em uma determinada amostra de tumores. METODOLOGIA: foram examinados 36 cânceres colorretais ressecados pelos coloproctologistas do Hospital Universitário da UFAL quanto à presença de uma reação imuno-histoquímica positiva para MUC1 em padrão citoplasmático. Em seguida, correlacionou-se esta com os estádios dos tumores. RESULTADOS: A imunoexpressão da MUC1 ocorreu em 50% dos casos. Destes, 61% estavam entre os estádios T3 e T4; 39% entre N1 e N2; todos os casos do estudo eram M0; e 40% encontravam-se entre os estádios C1 e C3 de Astler-Coller. Avaliada a positividade por cada estádio em separado, percebeu-se que estes aumentaram proporcionalmente, principalmente em relação aos estadios "N" e Astler-Coller. CONCLUSÃO: a ausência da reatividade imuno-histoquímica à MUC1 não excluiu a possibilidade de evolução para um estadio avançado. Porém, sua presença denota a evolução do câncer colorretal para estádios mais agressivos.The expression of tumor markers that correlates with the aggressiveness of cancers has been strongly investigated. Having colorectal cancer a significant incidence, biomarkers that can evaluate it concerning this aspect are not an exception in this inquiry. AIM: To establish a relation between aggressiveness of colorectal cancer according to TNM and Astler-Coller staging systems and the expression of Mucin1 (MUC1 in a determined sample of tumors. METHODS: 36 colorectal cancers resected by proctologists of the University Hospital of UFAL were examined regarding the

  16. The Breast Cancer-Associated Glycoforms of MUC1, MUC1-Tn and sialyl-Tn, Are Expressed in COSMC Wild-Type Cells and Bind the C-Type Lectin MGL.

    Directory of Open Access Journals (Sweden)

    Richard Beatson

    Full Text Available Aberrant glycosylation occurs in the majority of human cancers and changes in mucin-type O-glycosylation are key events that play a role in the induction of invasion and metastases. These changes generate novel cancer-specific glyco-antigens that can interact with cells of the immune system through carbohydrate binding lectins. Two glyco-epitopes that are found expressed by many carcinomas are Tn (GalNAc-Ser/Thr and STn (NeuAcα2,6GalNAc-Ser/Thr. These glycans can be carried on many mucin-type glycoproteins including MUC1. We show that the majority of breast cancers carry Tn within the same cell and in close proximity to extended glycan T (Galβ1,3GalNAc the addition of Gal to the GalNAc being catalysed by the T synthase. The presence of active T synthase suggests that loss of the private chaperone for T synthase, COSMC, does not explain the expression of Tn and STn in breast cancer cells. We show that MUC1 carrying both Tn or STn can bind to the C-type lectin MGL and using atomic force microscopy show that they bind to MGL with a similar dead adhesion force. Tumour associated STn is associated with poor prognosis and resistance to chemotherapy in breast carcinomas, inhibition of DC maturation, DC apoptosis and inhibition of NK activity. As engagement of MGL in the absence of TLR triggering may lead to anergy, the binding of MUC1-STn to MGL may be in part responsible for some of the characteristics of STn expressing tumours.

  17. Muc5b is required for airway defence

    Science.gov (United States)

    Roy, Michelle G.; Livraghi-Butrico, Alessandra; Fletcher, Ashley A.; McElwee, Melissa M.; Evans, Scott E.; Boerner, Ryan M.; Alexander, Samantha N.; Bellinghausen, Lindsey K.; Song, Alfred S.; Petrova, Youlia M.; Tuvim, Michael J.; Adachi, Roberto; Romo, Irlanda; Bordt, Andrea S.; Bowden, M. Gabriela; Sisson, Joseph H.; Woodruff, Prescott G.; Thornton, David J.; Rousseau, Karine; de La Garza, Maria M.; Moghaddam, Seyed J.; Karmouty-Quintana, Harry; Blackburn, Michael R.; Drouin, Scott M.; Davis, C. William; Terrell, Kristy A.; Grubb, Barbara R.; O'Neal, Wanda K.; Flores, Sonia C.; Cota-Gomez, Adela; Lozupone, Catherine A.; Donnelly, Jody M.; Watson, Alan M.; Hennessy, Corinne E.; Keith, Rebecca C.; Yang, Ivana V.; Barthel, Lea; Henson, Peter M.; Janssen, William J.; Schwartz, David A.; Boucher, Richard C.; Dickey, Burton F.; Evans, Christopher M.

    2014-01-01

    Respiratory surfaces are exposed to billions of particulates and pathogens daily. A protective mucus barrier traps and eliminates them through mucociliary clearance (MCC). However, excessive mucus contributes to transient respiratory infections and to the pathogenesis of numerous respiratory diseases. MUC5AC and MUC5B are evolutionarily conserved genes that encode structurally related mucin glycoproteins, the principal macromolecules in airway mucus. Genetic variants are linked to diverse lung diseases, but specific roles for MUC5AC and MUC5B in MCC, and the lasting effects of their inhibition, are unknown. Here we show that mouse Muc5b (but not Muc5ac) is required for MCC, for controlling infections in the airways and middle ear, and for maintaining immune homeostasis in mouse lungs, whereas Muc5ac is dispensable. Muc5b deficiency caused materials to accumulate in upper and lower airways. This defect led to chronic infection by multiple bacterial species, including Staphylococcus aureus, and to inflammation that failed to resolve normally. Apoptotic macrophages accumulated, phagocytosis was impaired, and interleukin-23 (IL-23) production was reduced in Muc5b-/- mice. By contrast, in mice that transgenically overexpress Muc5b, macrophage functions improved. Existing dogma defines mucous phenotypes in asthma and chronic obstructive pulmonary disease (COPD) as driven by increased MUC5AC, with MUC5B levels either unaffected or increased in expectorated sputum. However, in many patients, MUC5B production at airway surfaces decreases by as much as 90%. By distinguishing a specific role for Muc5b in MCC, and by determining its impact on bacterial infections and inflammation in mice, our results provide a refined framework for designing targeted therapies to control mucin secretion and restore MCC.

  18. Rise and Fall of an Anti-MUC1 Specific Antibody

    Science.gov (United States)

    Li, Jiandong; von Wasielewski, Reinhard; Bastert, Gunther; Schirrmann, Thomas; Esteves, Isabel Tourais; Behrens, Christian K.; Fournes, Bénédict; Fournier, Nathalie; de Romeuf, Christophe; Hust, Michael; Dübel, Stefan

    2011-01-01

    Background So far, human antibodies with good affinity and specificity for MUC1, a transmembrane protein overexpressed on breast cancers and ovarian carcinomas, and thus a promising target for therapy, were very difficult to generate. Results A human scFv antibody was isolated from an immune library derived from breast cancer patients immunised with MUC1. The anti-MUC1 scFv reacted with tumour cells in more than 80% of 228 tissue sections of mamma carcinoma samples, while showing very low reactivity with a large panel of non-tumour tissues. By mutagenesis and phage display, affinity of scFvs was increased up to 500fold to 5,7×10−10 M. Half-life in serum was improved from below 1 day to more than 4 weeks and was correlated with the dimerisation tendency of the individual scFvs. The scFv bound to T47D and MCF-7 mammalian cancer cell lines were recloned into the scFv-Fc and IgG format resulting in decrease of affinity of one binder. The IgG variants with the highest affinity were tested in mouse xenograft models using MCF-7 and OVCAR tumour cells. However, the experiments showed no significant decrease in tumour growth or increase in the survival rates. To study the reasons for the failure of the xenograft experiments, ADCC was analysed in vitro using MCF-7 and OVCAR3 target cells, revealing a low ADCC, possibly due to internalisation, as detected for MCF-7 cells. Conclusions Antibody phage display starting with immune libraries and followed by affinity maturation is a powerful strategy to generate high affinity human antibodies to difficult targets, in this case shown by the creation of a highly specific antibody with subnanomolar affinity to a very small epitope consisting of four amino acids. Despite these “best in class” binding parameters, the therapeutic success of this antibody was prevented by the target biology. PMID:21264246

  19. Rise and fall of an anti-MUC1 specific antibody.

    Directory of Open Access Journals (Sweden)

    Holger Thie

    2011-01-01

    Full Text Available So far, human antibodies with good affinity and specificity for MUC1, a transmembrane protein overexpressed on breast cancers and ovarian carcinomas, and thus a promising target for therapy, were very difficult to generate.A human scFv antibody was isolated from an immune library derived from breast cancer patients immunised with MUC1. The anti-MUC1 scFv reacted with tumour cells in more than 80% of 228 tissue sections of mamma carcinoma samples, while showing very low reactivity with a large panel of non-tumour tissues. By mutagenesis and phage display, affinity of scFvs was increased up to 500fold to 5,7×10(-10 M. Half-life in serum was improved from below 1 day to more than 4 weeks and was correlated with the dimerisation tendency of the individual scFvs. The scFv bound to T47D and MCF-7 mammalian cancer cell lines were recloned into the scFv-Fc and IgG format resulting in decrease of affinity of one binder. The IgG variants with the highest affinity were tested in mouse xenograft models using MCF-7 and OVCAR tumour cells. However, the experiments showed no significant decrease in tumour growth or increase in the survival rates. To study the reasons for the failure of the xenograft experiments, ADCC was analysed in vitro using MCF-7 and OVCAR3 target cells, revealing a low ADCC, possibly due to internalisation, as detected for MCF-7 cells.Antibody phage display starting with immune libraries and followed by affinity maturation is a powerful strategy to generate high affinity human antibodies to difficult targets, in this case shown by the creation of a highly specific antibody with subnanomolar affinity to a very small epitope consisting of four amino acids. Despite these "best in class" binding parameters, the therapeutic success of this antibody was prevented by the target biology.

  20. Interleukin-17A promotes MUC5AC expression and goblet cell hyperplasia in nasal polyps via the Act1-mediated pathway.

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    Wentong Xia

    Full Text Available BACKGROUND: Recent studies demonstrated that nasal polyps (NP patients in China and other Asian regions possessed distinct Th17-dominant inflammation and enhanced tissue remodeling. However, the mechanism underlying these observations is not fully understood. This study sought to evaluate the association of interleukin (IL-17A with MUC5AC expression and goblet cell hyperplasia in Chinese NP patients and to characterize the signaling pathway underlying IL-17A-induced MUC5AC expression in vitro. METHOD: We enrolled 25 NP patients and 22 normal controls and examined the expression of IL-17A, MUC5AC and act1 in polyp tissues by immunohistochemical (IHC staining, quantitative polymerase chain reaction (qPCR and western blot. Moreover, by using an in vitro culture system of polyp epithelial cells (PECs, IL-17A-induced gene expression was screened in cultured PECs by DNA microarray. The expression of IL-17RA, IL-17RC, act1 and MUC5AC and the activation of the MAPK pathway (ERK, p38 and JNK, were further examined in cultured PECs and NCI-H292 cells by qPCR and western blotting, respectively. RESULTS: We found that increased IL-17A production was significantly correlated with MUC5AC and act1 expression and goblet cell hyperplasia in polyp tissues (p<0.05. IL-17A significantly stimulated the expression of IL-17RA, IL-17RC, act1 and MUC5AC, and the activation of the MAPK pathway in cultured PECs and NCI-H292 cells (p<0.05. In addition, IL-17RA, IL-17RC and act1 siRNA significantly blocked IL-17A-induced MUC5AC production in vitro (p<0.05. CONCLUSION: Our results suggest that IL-17A plays a crucial role in stimulating the production of MUC5AC and goblet cell hyperplasia through the act1-mediated signaling pathway and may suggest a promising strategy for the management of Th17-dominant NP patients.

  1. Helicobacter pylori as a crucial factor in intestinal metaplasia development of gastric mucosa

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    Sergii Vernygorodskyi

    2016-06-01

    Full Text Available Helicobacter pylori (H. pylori is detected on the surface of gastric epithelium and in goblet cells, predominantly in patients with chronic atrophic gastritis and incomplete intestinal metaplasia (IM. H. pylori infection persistence leads to the formation of gastrointestinal phenotype of IM. H. pylori can be considered as an etiological factor of IM. It inhibits the expression of SOX2 in gastric epithelial cells, hence activating transcription factor CDX2 as a counterpart to MUC5AC gene inhibition and MUC2 gene induction. Thus, in metaplastic cells, programming differentiation after intestinal phenotype will develop. The role of H. pylori in the origin of intestinal metaplasia of gastric mucosa was defined in this study to elucidate the probable mechanism of cell reprogramming. The activation of CDX2, with simultaneous inactivation and decreased number of genes (e.g., SHH, SOX2, and RUNX3 responsible for gastric differentiation, was identified to cause the appearance of IM.

  2. Targeting of the MUC1-C Oncoprotein in Colitis-Associated Colorectal Cancer

    Science.gov (United States)

    2014-11-01

    separated by infiltrates of inflammatory cells and the presence of crypt abscess (lower left panel). With progression to dysplasia, the crypts are...Rajabi, H, et al., MUC1-C oncoprotein induces TCF7L2 activation and promotes cyclin D1 expression in human breast cancer cells. J Biol Chem, 2012

  3. ERK and PI3K regulate different aspects of the epithelial to mesenchymal transition of mammary tumor cells induced by truncated MUC1

    International Nuclear Information System (INIS)

    Horn, Galit; Gaziel, Avital; Wreschner, Daniel H.; Smorodinsky, Nechama I.; Ehrlich, Marcelo

    2009-01-01

    Epithelial to mesenchymal transition (EMT) integrates changes to cell morphology and signaling pathways resulting from modifications to the cell's transcriptional response. Different combinations of stimuli ignite this process in the contexts of development or tumor progression. The human MUC1 gene encodes multiple alternatively spliced forms of a polymorphic oncoprotein that is aberrantly expressed in epithelial malignancies. MUC1 is endowed with various signaling modules and has the potential to mediate proliferative and morphological changes characteristic of the progression of epithelial tumors. The tyrosine-rich cytoplasmic domain and the heavily glycosylated extracellular domain both play a role in MUC1-mediated signal transduction. However, the attribution of function to specific domains of MUC1 is difficult due to the concomitant presence of multiple forms of the protein, which stem from alternative splicing and proteolytic cleavage. Here we show that DA3 mouse mammary tumor cells stably transfected with a truncated genomic fragment of human MUC1 undergo EMT. In their EMT, these cells demonstrate altered [i] morphology, [ii] signaling pathways and [iii] expression of epithelial and mesenchymal markers. Similarly to well characterized human breast cancer cell lines, cells transfected with truncated MUC1 show an ERK-dependent increased spreading on fibronectin, and a PI3K-dependent enhancement of their proliferative rate.

  4. Development of [⁶⁴Cu]-DOTA-PR81 radioimmunoconjugate for MUC-1 positive PET imaging.

    Science.gov (United States)

    Alirezapour, Behrouz; Rasaee, Mohammad Javad; Jalilian, Amir Reza; Rajabifar, Saeed; Mohammadnejad, Javad; Paknejad, Malihe; Maadi, Ehsan; Moradkhani, Sedigheh

    2016-01-01

    Breast cancer radioimmunoscintigraphy targeting MUC1 expression is a growing field of work in nuclear medicine research. PR81 is a monoclonal antibody that binds with high affinity to MUC1, which is over expressed on breast tumors. In this study, we report production, quality control and preclinical qualifications of a copper-64 labeled PR81 for PET imaging of breast cancer. PR81 was conjugated with DOTA-NHS-ester and purified by molecular filtration followed by chelate:mAb ratio determination by spectrophotometric method. DOTA-PR81 was labeled with (64)Cu followed by radiochemical purity, in vitro stability, in vitro internalization and immunoreactivity determination. The tissue biodistribution of the (64)Cu-DOTA-PR81 and (64)Cu-DOTA-hIgG was evaluated in BALB/c mice with breast carcinoma tumors using tissue counting and imaging. The radiochemical purity of radioimmunoconjugate was >95±1.9% (ITLC) (specific activity; 4.6 μCi/μg). The average number of chelators per antibody was 3.4±0.3:1. The (64)Cu-DOTA-PR81 showed immunoreactivity towards MUC1 antigen and MCF7 cell line with significant in vitro stability (>89% in PBS and 78±0.5% in human serum) over 48 h. Maximum internalized activity of radiolabeled PR81 in 4-8 h was 81.5%. The biodistribution and scintigraphy studies showed the accumulation of the complex at the site of tumors with high sensitivity and specificity compared to control probes. The results showed that (64)Cu-DOTA-PR81 may be considered as a potential PET tracer for diagnosis and follow-up of MUC1 expression in oncology. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Muc2 Protects against Lethal Infectious Colitis by Disassociating Pathogenic and Commensal Bacteria from the Colonic Mucosa

    Science.gov (United States)

    Bergstrom, Kirk S. B.; Kissoon-Singh, Vanessa; Gibson, Deanna L.; Ma, Caixia; Montero, Marinieve; Sham, Ho Pan; Ryz, Natasha; Huang, Tina; Velcich, Anna; Finlay, B. Brett; Chadee, Kris; Vallance, Bruce A.

    2010-01-01

    Despite recent advances in our understanding of the pathogenesis of attaching and effacing (A/E) Escherichia coli infections, the mechanisms by which the host defends against these microbes are unclear. The goal of this study was to determine the role of goblet cell-derived Muc2, the major intestinal secretory mucin and primary component of the mucus layer, in host protection against A/E pathogens. To assess the role of Muc2 during A/E bacterial infections, we inoculated Muc2 deficient (Muc2−/−) mice with Citrobacter rodentium, a murine A/E pathogen related to diarrheagenic A/E E. coli. Unlike wildtype (WT) mice, infected Muc2−/− mice exhibited rapid weight loss and suffered up to 90% mortality. Stool plating demonstrated 10–100 fold greater C. rodentium burdens in Muc2−/− vs. WT mice, most of which were found to be loosely adherent to the colonic mucosa. Histology of Muc2−/− mice revealed ulceration in the colon amid focal bacterial microcolonies. Metabolic labeling of secreted mucins in the large intestine demonstrated that mucin secretion was markedly increased in WT mice during infection compared to uninfected controls, suggesting that the host uses increased mucin release to flush pathogens from the mucosal surface. Muc2 also impacted host-commensal interactions during infection, as FISH analysis revealed C. rodentium microcolonies contained numerous commensal microbes, which was not observed in WT mice. Orally administered FITC-Dextran and FISH staining showed significantly worsened intestinal barrier disruption in Muc2−/− vs. WT mice, with overt pathogen and commensal translocation into the Muc2−/− colonic mucosa. Interestingly, commensal depletion enhanced C. rodentium colonization of Muc2−/− mice, although colonic pathology was not significantly altered. In conclusion, Muc2 production is critical for host protection during A/E bacterial infections, by limiting overall pathogen and commensal numbers associated with the colonic

  6. MicroRNA-200c modulates the expression of MUC4 and MUC16 by directly targeting their coding sequences in human pancreatic cancer.

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    Prakash Radhakrishnan

    Full Text Available Transmembrane mucins, MUC4 and MUC16 are associated with tumor progression and metastatic potential in human pancreatic adenocarcinoma. We discovered that miR-200c interacts with specific sequences within the coding sequence of MUC4 and MUC16 mRNAs, and evaluated the regulatory nature of this association. Pancreatic cancer cell lines S2.028 and T3M-4 transfected with miR-200c showed a 4.18 and 8.50 fold down regulation of MUC4 mRNA, and 4.68 and 4.82 fold down regulation of MUC16 mRNA compared to mock-transfected cells, respectively. A significant reduction of glycoprotein expression was also observed. These results indicate that miR-200c overexpression regulates MUC4 and MUC16 mucins in pancreatic cancer cells by directly targeting the mRNA coding sequence of each, resulting in reduced levels of MUC4 and MUC16 mRNA and protein. These data suggest that, in addition to regulating proteins that modulate EMT, miR-200c influences expression of cell surface mucins in pancreatic cancer.

  7. Macrophages are related to goblet cell hyperplasia and induce MUC5B but not MUC5AC in human bronchus epithelial cells.

    Science.gov (United States)

    Silva, Manuel A; Bercik, Premysl

    2012-06-01

    Airway goblet cell hyperplasia (GCH)--detectable by mucin staining--and abnormal macrophage infiltrate are pathological features present in many chronic respiratory disorders. However, it is unknown if both factors are associated. Using in-vivo and in-vitro models, we investigated whether macrophages are related with GCH and changes in mucin immunophenotypes. Lung sections from Sprague-Dawley rats treated for 48 h with one intra-tracheal dose of PBS or LPS (n=4-6 per group) were immunophenotyped for rat-goblet cells, immune, and proliferation markers. Human monocyte-derived macrophages (MDM) were pre-treated with or without LPS, immunophenotyped, and their supernatant, as well as cytokines at levels equivalent to supernatant were used to challenge primary culture of normal human bronchus epithelial cells (HBEC) in air-liquid interface, followed by MUC5B and MUC5AC mucin immunostaining. An association between increased bronchiolar goblet cells and terminal-bronchiolar proliferative epithelial cells confirmed the presence of GCH in our LPS rat model, which was related with augmented bronchiolar CD68 macrophage infiltration. The in-vitro experiments have shown that MUC5AC phenotype was inhibited when HBEC were challenged with supernatant from MDM pre-treated with or without LPS. In contrast, TNF-α and interleukin-1β at levels equivalent to supernatant from LPS-treated MDM increased MUC5AC. MUC5B was induced by LPS, supernatant from LPS-treated MDM, a mix of cytokines including TNF-α and TNF-α alone at levels present in supernatant from LPS-treated MDM. We demonstrated that macrophages are related with bronchiolar GCH, and that they induced MUC5B and inhibited MUC5AC in HBEC, suggesting a role for them in the pathogenesis of airway MUC5B-related GCH.

  8. Clinical significance of MUC13 in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Khan, Sheema; Zafar, Nadeem; Khan, Shabia S; Setua, Saini; Behrman, Stephen W; Stiles, Zachary E; Yallapu, Murali M; Sahay, Peeyush; Ghimire, Hemendra; Ise, Tomoko; Nagata, Satoshi; Wang, Lei; Wan, Jim Y; Pradhan, Prabhakar; Jaggi, Meena; Chauhan, Subhash C

    2018-01-15

    Poor prognosis of pancreatic cancer (PanCa) is associated with lack of an effective early diagnostic biomarker. This study elucidates significance of MUC13, as a diagnostic/prognostic marker of PanCa. MUC13 was assessed in tissues using our in-house generated anti-MUC13 mouse monoclonal antibody and analyzed for clinical correlation by immunohistochemistry, immunoblotting, RT-PCR, computational and submicron scale mass-density fluctuation analyses, ROC and Kaplan Meir curve analyses. MUC13 expression was detected in 100% pancreatic intraepithelial neoplasia (PanIN) lesions (Mean composite score: MCS = 5.8; AUC >0.8, P 0.8; P artificial intelligence based algorithm analyses also elucidated association of MUC13 with greater morphological disorder (P < 0.001) and nuclear MUC13 as strong predictor for cancer aggressiveness and poor patient survival. This study provides significant information regarding MUC13 expression/subcellular localization in PanCa samples and supporting the use anti-MUC13 MAb for the development of PanCa diagnostic/prognostic test. Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  9. Aberrantly glycosylated MUC1 is expressed on the surface of breast cancer cells and a target for antibody-dependent cell-mediated cytotoxicity

    DEFF Research Database (Denmark)

    Lavrsen, Kirstine; Madsen, Caroline B; Rasch, Morten G

    2013-01-01

    to Tn-MUC1 was investigated using BiaCore. The availability of Tn-MUC1 on the surface of breast cancer cells was evaluated by immunohistochemistry, confocal microscopy, and flow cytometry, followed by in vitro assessment of antibody-dependent cellular cytotoxicity by mAb 5E5. Biacore analysis...

  10. Salivary agglutinin/glycoprotein-340/DMBT1

    DEFF Research Database (Denmark)

    Ligtenberg, Antoon J M; Veerman, Enno C I; Nieuw Amerongen, Arie V

    2007-01-01

    and Helicobacter pylori, influenza viruses and HIV, but also with mucosal defence proteins, such as IgA, surfactant proteins and MUC5B. Stimulation of alveolar macrophage migration, suppression of neutrophil oxidative burst and activation of the complement cascade point further to an important role...

  11. Design of α-S-Neoglycopeptides Derived from MUC1 with a Flexible and Solvent-Exposed Sugar Moiety

    DEFF Research Database (Denmark)

    Rojas-Ocáriz, Víctor; Compañón, Ismael; Aydillo Miguel, Carlos

    2016-01-01

    in solution have been evaluated by combining NMR experiments and molecular dynamics simulations. The linker plays a key role in the modulation of the conformation of these compounds at different levels, blocking a direct contact between the sugar moiety and the backbone, promoting a helix-like conformation...... for the glycosylated residue and favoring the proper presentation of the sugar unit for molecular recognition events. The feasibility of these novel compounds as mimics of MUC1 antigens has been validated by the X-ray diffraction structure of one of these unnatural derivatives complexed to an anti-MUC1 monoclonal...

  12. A plasmid carrying mucA and mucB genes from pKM101 in Haemophilus influenzae and Escherichia coli

    International Nuclear Information System (INIS)

    Spikes, D.; Setlow, J.K.

    1989-01-01

    The plasmid pMucAMucB, constructed from the Haemophilus influenzae vector pDM2, and a similar plasmid, constructed from pBR322, increased the survival after UV irradiation of Escherichia coli AB1157 with the umu-36 mutation and also caused UV-induced mutation in the E. coli strain. In H. influenzae, pMucAMucB caused a small but reproducible increase in survival after UV irradiation in wild-type cells and in a rec-1 mutant, but there was no increase in spontaneous mutation in the wild type or in the rec-1 mutant and no UV-induced mutation

  13. Helicobacter-negative gastritis: a distinct entity unrelated to Helicobacter pylori infection.

    Science.gov (United States)

    Genta, R M; Sonnenberg, A

    2015-01-01

    Helicobacter-negative gastritis is diagnosed when no organisms are detected in a gastric mucosa with typical features of Helicobacter gastritis (Hp-gastritis). If Helicobacter-negative gastritis consisted mostly of 'missed' Helicobacter infections, its prevalence should represent a constant percentage of these infections in a population, and their clinico-epidemiological features would overlap. To compare the epidemiologic patterns of Hp-positive and Hp-negative gastritis. From a pathology database, we extracted demographic, clinical and histopathological data from patients with gastric biopsies (1.2008-12.2013). We allocated patients to high (≥12%) and low (≤6%) H. pylori prevalence regions defined by ZIP code-based data. The prevalence of H. pylori-positive and -negative gastritis by sex, age and state were expressed as a per cent of the total study population stratified accordingly. Of 895 323 patients, 10.6% had Hp-gastritis and 1.5% Helicobacter-negative gastritis. Hp-gastritis, but not Helicobacter-negative gastritis, was more common in males than females (OR 1.17, 95% CI: 1.16-1.19). While Hp-gastritis was more prevalent in high than in low-prevalence areas (OR 3.65, 95% CI: 3.57-3.74), Helicobacter-negative gastritis was only minimally affected by the underlying H. pylori prevalence (1.7% vs. 1.5%). The age-specific prevalence of Hp-gastritis peaked in the 4th to 5th decades; Helicobacter-negative gastritis exhibited a low and relatively flat pattern. The geographic distribution of H. pylori-positive and -negative gastritis showed no significant correlation. Intestinal metaplasia was found in 13.0% of patients with Hp-gastritis and in 6.1% of those with Helicobacter-negative gastritis (OR 0.43, 95% CI: 0.40-0.47). These data suggest that Helicobacter-negative gastritis is, in the vast majority of cases, a nosologically and epidemiologically distinct entity that deserves further investigation. © 2014 John Wiley & Sons Ltd.

  14. Nongenetically modified Lactococcus lactis-adjuvanted vaccination enhanced innate immunity against Helicobacter pylori.

    Science.gov (United States)

    Liu, Wei; Tan, Zhoulin; Liu, Hai; Zeng, Zhiqin; Luo, Shuanghui; Yang, Huimin; Zheng, Lufeng; Xi, Tao; Xing, Yingying

    2017-10-01

    Gram-positive enhancer matrix particles (GEM) produced by Lactococcus lactis can enhance vaccine-induced immune response. However, the mechanism under which this adjuvant mounts the efficacy of orally administered vaccines remains unexplored. We used a prophylactic mice model to investigate the mechanism of GEM-adjuvanted vaccination. Helicobacter pylori urease-specific antibody response was monitored and detected in murine serum by ELISA. Urease-specific splenic cytokine profile was examined. Gastric inflammatory responses were measured on day 43 or 71 by quantitative real-time PCR, flow cytometry and histology. We found that GEM enhanced the efficiency of oral H. pylori vaccine by promoting innate immunity. The vaccine CUE-GEM composed of GEM particles and recombinant antigen CTB-UE provided protection of immunized mice against H. pylori insult. The protective response was associated with induction of postimmunization gastritis and local Th1/Th17 cell-medicated immune response. We showed that innate inflammatory responses including neutrophil chemokines CXCL1-2, neutrophils, and antimicrobial proteins S100A8 and MUC1 were significantly elevated. Within all infected mice, S100A8 and MUC1 levels were negatively correlated with H. pylori burden. Strikingly, mice receiving GEM also show reduction of colonization, possibly through natural host response pathways to recruit CD4 + T cells and promote S100A8 expression. These findings suggest that GEM-based vaccine may impact Th1/Th17 immunity to orchestrate innate immune response against H. pylori infection. © 2017 John Wiley & Sons Ltd.

  15. Inhibition of acrolein-stimulated MUC5AC production by fucoidan in human bronchial epithelial cells.

    Science.gov (United States)

    Pokharel, Yuba Raj; Yoon, Se Young; Kim, Sang Kyum; Li, Jian-Dong; Kang, Keon Wook

    2008-10-01

    Fucoidan, a marine sulfated polysaccharide has both antithrombotic and anti-inflammatory effects. We determined the effect of fucoidan on MUC5AC expression in a human bronchial epithelial cell line, NCI-H292. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that fucoidan inhibited MUC5AC expression and protein secretion in cells stimulated with acrolein, a toxic aldehyde present in tobacco smoke. The activation of both nuclear factor-kappa B (NF-kappa B) and activator protein 1 (AP-1) are key steps in the transcriptional activation of MUC5AC. We found that the acrolein-mediated transactivation of MUC5AC was selectively dependent on AP-1 activation and was suppressed by fucoidan. Fucoidan-induced AP-1 inhibition and MUC5AC repression might be associated with fucoidan's protective effects against respiratory diseases.

  16. Preparation and preliminary studies of [64Cu]-antiMUC-1 for breast cancer targeting

    Directory of Open Access Journals (Sweden)

    Behrouz Alirezapour

    2016-06-01

    Full Text Available PR81 is a monoclonal antibody that binds with high affinity to MUC1 that over expressed on breast tumors. PR81 is considered a suitable targeting molecule that was radiolabeled using Cu-64 for positron imaging studies. The monoclonal antibody was conjugated with DOTA moiety and after purification was evaluated for radiochemical purity, immunoreactivity, cell toxicity and structure integrity as well as biodistribution study in normal rats. The radiolabeled antibody prepared with acceptable radiochemical purity (> 93.2 ± 0.6 %, ITLC; specific activity; 4.6 µCi/µg, protein structure integration, significant cytotoxicity and significant immunoreactivity retention was assessed by radioimmunoassay (RIA. Animal biodistribution of the 64Cu-DOTA-PR81 was consistent with other radiolabeled antibodies. The results showed that 64Cu-DOTA-PR81 may be considered for tumor imaging for ultimate diagnosis and follow-up of MUC1 expression in oncology.

  17. HN125: A Novel Immunoadhesin Targeting MUC16 with Potential for Cancer Therapy

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    Xinran Xiang, Mingqian Feng, Mildred Felder, Joseph P. Connor, Yan-gao Man, Manish S. Patankar, Mitchell Ho

    2011-01-01

    Full Text Available Background: The mucin MUC16 expresses the repeating peptide epitope CA125 that has been known for decades to be a well-validated cancer marker that is overexpressed on the cell surface of ovarian cancers and other malignant tumors. In spite of recent efforts to make mouse monoclonal antibodies to MUC16 to treat ovarian cancer, a human monoclonal antibody against this mucin has not been described. MUC16 interacts with mesothelin, a protein that mediates heterotypic cancer cell adhesion, indicating that MUC16 and mesothelin play an important role in the peritoneal implantation and metastasis of ovarian tumors. Therefore, a suitable candidate for therapeutic targeting of MUC16 would functionally block the interaction of MUC16 and mesothelin.Methodology/Principal Findings: Here we report the generation of a novel immunoadhesin, HN125, against MUC16 that consists of a functional MUC16 binding domain of mesothelin (IAB and the Fc portion of a human antibody IgG1. The yield for purified HN125 proteins is over 100 µg/mL of HEK-293 culture supernatant. We show that HN125 has high and specific affinity for MUC16-expressing cancer cells by flow cytometry and immunohistochemistry. HN125 has the ability to disrupt the heterotypic cancer cell adhesion mediated by the MUC16-mesothelin interaction. Moreover, it elicits strong antibody-dependent cell mediated cytotoxicity against MUC16-positive cancer cells in vitro.Conclusion/Significance: This report describes a novel human immunotherapeutic agent highly specific for MUC16 with potential for treating ovarian cancer and other MUC16-expressing tumors. Because of its lower immunogenicity in patients, a fully human protein is the most desirable format for clinical applications. We believe that the methods developed here may apply to the generation of other tumor-targeting immunoadhesins when it is difficult to obtain a human monoclonal antibody to a given antigen for clinical applications. The resultant

  18. Pathobiological implications of MUC16 expression in pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Dhanya Haridas

    Full Text Available MUC16 (CA125 belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC, the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 mRNA levels were also measured by RT-PCR in the normal human pancreatic, pancreatitis, and PC tissues. To investigate its expression pattern during PC metastasis, tissue samples from the primary pancreatic tumor and metastases (from the same patient in the lymph nodes, liver, lung and omentum from Stage IV PC patients were analyzed. To determine its association in the initiation of PC, tissues from PC patients containing pre-neoplastic lesions of varying grades were stained for MUC16. Finally, MUC16 expression was analyzed in 18 human PC cell lines. MUC16 is not expressed in the normal pancreatic ducts and is strongly upregulated in PC and detected in pancreatitis tissue. It is first detected in the high-grade pre-neoplastic lesions preceding invasive adenocarcinoma, suggesting that its upregulation is a late event during the initiation of this disease. MUC16 expression appears to be stronger in metastatic lesions when compared to the primary tumor, suggesting a role in PC metastasis. We have also identified PC cell lines that express MUC16, which can be used in future studies to elucidate its functional role in PC. Altogether, our results reveal that MUC16 expression is significantly increased in PC and could play a potential role in the progression of this disease.

  19. Brucella melitensis MucR, an orthologue of Sinorhizobium meliloti MucR, is involved in resistance to oxidative, detergent, and saline stresses and cell envelope modifications.

    Science.gov (United States)

    Mirabella, A; Terwagne, M; Zygmunt, M S; Cloeckaert, A; De Bolle, X; Letesson, J J

    2013-02-01

    Brucella spp. and Sinorhizobium meliloti are alphaproteobacteria that share not only an intracellular lifestyle in their respective hosts, but also a crucial requirement for cell envelope components and their timely regulation for a successful infectious cycle. Here, we report the characterization of Brucella melitensis mucR, which encodes a zinc finger transcriptional regulator that has previously been shown to be involved in cellular and mouse infections at early time points. MucR modulates the surface properties of the bacteria and their resistance to environmental stresses (i.e., oxidative stress, cationic peptide, and detergents). We show that B. melitensis mucR is a functional orthologue of S. meliloti mucR, because it was able to restore the production of succinoglycan in an S. meliloti mucR mutant, as detected by calcofluor staining. Similar to S. meliloti MucR, B. melitensis MucR also represses its own transcription and flagellar gene expression via the flagellar master regulator ftcR. More surprisingly, we demonstrate that MucR regulates a lipid A core modification in B. melitensis. These changes could account for the attenuated virulence of a mucR mutant. These data reinforce the idea that there is a common conserved circuitry between plant symbionts and animal pathogens that regulates the relationship they have with their hosts.

  20. Immunohistochemical expression profiles of mucin antigens in salivary gland mucoepidermoid carcinoma: MUC4- and MUC6-negative expression predicts a shortened survival in the early postoperative phase.

    Science.gov (United States)

    Honjo, Kie; Hiraki, Tsubasa; Higashi, Michiyo; Noguchi, Hirotsugu; Nomoto, Mitsuharu; Yoshimura, Takuya; Batra, Surinder K; Yonezawa, Suguru; Semba, Ichiro; Nakamura, Norifumi; Tanimoto, Akihide; Yamada, Sohsuke

    2018-02-01

    In mucoepidermoid carcinoma (MEC), the most common salivary gland carcinoma, there is a lack of novel prognostic markers, but post-operative early recurrence strongly affects the clinical course and a poor outcome. It is critical to predict which MEC patients are prone to develop recurrence/metastases. Mucins play pivotal roles in influencing cancer biology, thus affecting cell differentiation, adhesion, carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to elucidate the significance of expression profiles for mucins, particularly MUC4 and MUC6, and their correlations with various clinicopathological features and recurrence in salivary gland MECs. We performed immunohistochemical analyses on patients with surgically resected primary MEC using antibodies against mucin core proteins MUC4/8G7 and MUC6/CLH5 in 73 paraffin-embedded samples. Recurrence was noted in 15 of 73 (20.5%) patients. MUC4 or MUC6 expression was considered to be negative when <30% or 0% of the MEC cells showed positive staining, respectively. MUC4- and/or MUC6-negative expression respectively and variably showed a significant relationship to pathological tumor high-grade, the presence of lymphovascular invasion, lymph node metastasis and/or tumor-related death. In addition, MUC4 showed significantly negative co-expression with MUC6. Kaplan-Meier analyses revealed that not only single MUC4/6-negative expression but also the combination of both predicted significantly shorter disease-free and disease-specific survivals in MECs, especially within the first two years postoperatively. Therefore, each mucin plays a pivotal role in the pathogenesis of MEC progression. The detection of MUC4 and/or MUC6 might be a powerful parameter in the clinical management of MECs in the early postsurgical phase.

  1. Identification of salivary mucin MUC7 binding proteins from Streptococcus gordonii

    Directory of Open Access Journals (Sweden)

    Thornton David J

    2009-08-01

    Full Text Available Abstract Background The salivary mucin MUC7 (previously known as MG2 can adhere to various strains of streptococci that are primary colonizers and predominant microorganisms of the oral cavity. Although there is a growing interest in interaction between oral pathogens and salivary mucins, studies reporting the specific binding sites on the bacteria are rather limited. Identification and characterization of the specific interacting proteins on the bacterial cell surface, termed adhesins, are crucial to further understand host-pathogen interactions. Results We demonstrate here, using purified MUC7 to overlay blots of SDS-extracts of Streptococcus gordonii cell surface proteins, 4 MUC7-binding bands, with apparent molecular masses of 62, 78, 84 and 133 kDa from the Streptococcus gordonii strain, PK488. Putative adhesins were identified by in-gel digestion and subsequent nanoLC-tandem mass spectrometry analysis of resultant peptides. The 62 kDa and 84 kDa bands were identified as elongation factor (EF Tu and EF-G respectively. The 78 kDa band was a hppA gene product; the 74 kDa oligopeptide-binding lipoprotein. The 133 kDa band contained two proteins; alpha enolase and DNA-directed RNA polymerase, beta' subunit. Some of these proteins, for example alpha enolase are expected to be intracellular, however, flow cytometric analysis confirmed its location on the bacterial surface. Conclusion Our data demonstrated that S. gordonii expressed a number of putative MUC7 recognizing proteins and these contribute to MUC7 mucin binding of this streptococcal strain.

  2. MUC2 Expression Is Correlated with Tumor Differentiation and Inhibits Tumor Invasion in Gastric Carcinomas: A Systematic Review and Meta-analysis

    Directory of Open Access Journals (Sweden)

    Jung-Soo Pyo

    2015-05-01

    Full Text Available Background: While MUC2 is expressed in intestinal metaplasia and malignant lesions, the clinicopathological significance of MUC2 expression is not fully elucidated in gastric carcinoma (GC. Methods: The present study investigated the correlation between MUC2 expression and clinicopathological parameters in 167 human GCs. In addition, to confirm the clinicopathological significance of MUC2 expression, we performed a systematic review and meta-analysis in 1,832 GCs. Results: MUC2 expression was found in 58 of 167 GCs (34.7%. MUC2-expressing GC showed lower primary tumor (T, regional lymph node (N, and tumor node metastasis (TNM stages compared with GCs without MUC2 expression (p=.001, p=.001, and p=.011, respectively. However, MUC2 expression was not correlated with Lauren’s classification and tumor differentiation. In meta-analysis, MUC2 expression was significantly correlated with differentiation and lower tumor stage (odds ratio [OR], 1.303; 95% confidence interval [CI], 1.020 to 1.664; p = .034 and OR, 1.352; 95% CI, 1.055 to 1.734; p = .017, respectively but not with Lauren’s classification, pN stage, or pTNM stage. Conclusions: MUC2 expression was correlated with a lower tumor depth and lower lymph node metastasis in our study; the meta-analysis showed a correlation of MUC2 expression with tumor differentiation and lower tumor depth.

  3. Nucleotide variability and linkage disequilibrium patterns in the porcine MUC4 gene

    Directory of Open Access Journals (Sweden)

    Yang Ming

    2012-07-01

    similar nucleotide diversity but evolve divergently in the MUC4 region. Western breeds exhibited unusual low LD extent at the MUC4 locus, reflecting the complexity of nucleotide variability of pig genome. The finding suggests that high density (e.g. 1SNP/10 kb markers are required to capture the underlying causal variants at such regions.

  4. MUC16 provides immune protection by inhibiting synapse formation between NK and ovarian tumor cells

    Directory of Open Access Journals (Sweden)

    Migneault Martine

    2010-01-01

    Full Text Available Abstract Background Cancer cells utilize a variety of mechanisms to evade immune detection and attack. Effective immune detection largely relies on the formation of an immune synapse which requires close contact between immune cells and their targets. Here, we show that MUC16, a heavily glycosylated 3-5 million Da mucin expressed on the surface of ovarian tumor cells, inhibits the formation of immune synapses between NK cells and ovarian tumor targets. Our results indicate that MUC16-mediated inhibition of immune synapse formation is an effective mechanism employed by ovarian tumors to evade immune recognition. Results Expression of low levels of MUC16 strongly correlated with an increased number of conjugates and activating immune synapses between ovarian tumor cells and primary naïve NK cells. MUC16-knockdown ovarian tumor cells were more susceptible to lysis by primary NK cells than MUC16 expressing controls. This increased lysis was not due to differences in the expression levels of the ligands for the activating receptors DNAM-1 and NKG2D. The NK cell leukemia cell line (NKL, which does not express KIRs but are positive for DNAM-1 and NKG2D, also conjugated and lysed MUC16-knockdown cells more efficiently than MUC16 expressing controls. Tumor cells that survived the NKL challenge expressed higher levels of MUC16 indicating selective lysis of MUC16low targets. The higher csMUC16 levels on the NKL resistant tumor cells correlated with more protection from lysis as compared to target cells that were never exposed to the effectors. Conclusion MUC16, a carrier of the tumor marker CA125, has previously been shown to facilitate ovarian tumor metastasis and inhibits NK cell mediated lysis of tumor targets. Our data now demonstrates that MUC16 expressing ovarian cancer cells are protected from recognition by NK cells. The immune protection provided by MUC16 may lead to selective survival of ovarian cancer cells that are more efficient in

  5. Curcumin Inhibits NTHi-Induced MUC5AC Mucin Overproduction in Otitis Media via Upregulation of MAPK Phosphatase MKP-1

    Directory of Open Access Journals (Sweden)

    Anuhya Sharma Konduru

    2017-01-01

    Full Text Available Otitis media (OM, characterized by the presence of mucus overproduction and excess inflammation in the middle ear, is the most common childhood infection. Nontypeable Haemophilus influenzae (NTHi pathogen is responsible for approximately one-third of episodes of bacteria-caused OM. Current treatments for bacterial OM rely on the systemic use of antibiotics, which often leads to the emergence of multidrug resistant bacterial strains. Therefore there is an urgent need for developing alternative therapies strategies for controlling mucus overproduction in OM. MUC5AC mucin has been shown to play a critical role in the pathogenesis of OM. Here we show that curcumin derived from Curcuma longa plant is a potent inhibitor of NTHi-induced MUC5AC mucin expression in middle ear epithelial cells. Curcumin inhibited MUC5AC expression by suppressing activation of p38 MAPK by upregulating MAPK phosphatase MKP-1. Thus, our study identified curcumin as a potential therapeutic for inhibiting mucin overproduction in OM by upregulating MKP-1, a known negative regulator of inflammation.

  6. Acquired resistance to HSP90 inhibitor 17-AAG and increased metastatic potential are associated with MUC1 expression in colon carcinoma cells.

    Science.gov (United States)

    Liu, Xin; Ban, Li-Li; Luo, Gang; Li, Zhi-Yao; Li, Yun-Feng; Zhou, Yong-Chun; Wang, Xi-Cai; Jin, Cong-Guo; Ye, Jia-Gui; Ma, Ding-Ding; Xie, Qing; Huang, You-Guang

    2016-06-01

    Heat shock protein 90 (HSP90) is a molecular chaperone required for the stability and function of many proteins. The chaperoning of oncoproteins by HSP90 enhances the survival, growth, and invasive potential of cancer cells. HSP90 inhibitors are promising new anticancer agents, in which the benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin (17-AAG) is currently in clinical evaluation. However, the implications of acquired resistance to this class of drug remain largely unexplored. In the present study, we have generated isogenic human colon cancer cell lines that are resistant to 17-AAG by continued culturing in the compound. Cross-resistance was found with another HSP90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin. The resistant cells showed obvious morphology changes with a metastatic phenotype and significant increases in migration and adhesion to collagens. Western blotting analysis of epithelial-mesenchymal transition molecular markers found that expression of E-cadherin downregulated, whereas expression of N-cadherin and β-catenin upregulated in the resistant cells. Mucin 1 (MUC1) has been reported to mediate metastasis as well as chemical resistance in many cancers. Here, we found that MUC1 expression was significantly elevated in the acquired drug resistance cells. 17-AAG treatment could decrease MUC1 more in parental cells than in acquired 17-AAG-resistant cells. Further study found that knockdown of MUC1 expression by small interfering RNA could obviously re-sensitize the resistant cells to 17-AAG treatment, and decrease the cell migration and adhesion. These were coupled with a downregulation in N-cadherin and β-catenin. The results indicate that HSP90 inhibitor therapies in colon carcinomas could generate resistance and increase metastatic potential that might mediated by upregulation of MUC1 expression. Findings from this study further our understanding of the potential clinical effects of HSP90-directed therapies in

  7. Noninvasive Detection of Inflammation-Associated Colon Cancer in a Mouse Model

    Directory of Open Access Journals (Sweden)

    Aaron C. Ericsson

    2010-12-01

    Full Text Available Helicobacter bilis-infected Smad3-/- mice represent an attractive model of inflammation-associated colon cancer. Most infected mice develop mucinous adenocarcinoma (MUC by 6 weeks post inoculation (PI; however, approximately one third do not progress to MUC. The ability to predict the development of MUC in mice used in therapeutic studies would confer a considerable saving of time and money. In addition, the inadvertent use of mice without MUC may confound therapeutic studies by making treatments seem falsely efficacious. We assessed both magnetic resonance imaging (MRI and fecal biomarkers in Helicobacter- and sham-inoculated mice as methods of noninvasively detecting MUC before the predicted onset of disease. Non-contrast-enhanced MRI was able to detect lesions in 58% of mice with histologically confirmed MUC; however, serial imaging sessions produced inconsistent results. MRI was also a labor- and time-intensive technique requiring anesthesia. Alternatively, inflammatory biomarkers isolated from feces at early time points were correlated to later histologic lesions. Fecal expression of interleukin 1β, macrophage inflammatory protein 1α, and regulated on activation, normal T-cell expressed, and secreted at 3 weeks PI correlated significantly with lesion severity at 9 weeks PI. For each biomarker, receiver-operator characteristic curves were also generated, and all three biomarkers performed well at 1 to 3 weeks PI, indicating that the development of MUC can be predicted based on the early expression of certain inflammatory mediators in feces.

  8. MUC1 in human milk blocks transmission of human immunodeficiency virus from dendritic cells to T cells

    NARCIS (Netherlands)

    Saeland, E.; Jong, de M.A.W.P.; Nabatov, A.; Kalay, H.; Kooijk, van Y.; Geijtenbeek, T.B.H.

    2009-01-01

    Mother-to-child transmission of human immunodeficiency virus-1 (HIV-1) occurs frequently via breast-feeding. HIV-1 targets DC-SIGN+ dendritic cells (DCs) in mucosal areas that allow efficient transmission of the virus to T cells. Here, we demonstrate that the epithelial mucin MUC1, abundant in milk,

  9. The effect of mucA allele on biofilm architecture and the biofilm ...

    African Journals Online (AJOL)

    In this study, a unique mucA mutation (designated mucA56) was introduced, which was characterized by deletion of bases 166-333, encoding MucA56 protein with the deletion of the trans-membrane region, which then was proved to be cytoplasmic with phoA-mucA fusion method. PAOmucA56 was constructed with ...

  10. Generation and characterization of a monoclonal antibody to the cytoplasmic tail of MUC16

    DEFF Research Database (Denmark)

    Gipson, Ilene K; Mandel, Ulla; Menon, Balaraj

    2017-01-01

    of the biological relevance of the C-terminal domain of MUC16 has been limited by lack of availability of monoclonal antibodies that recognize the native CT. Here, we report the development of a novel monoclonal antibody to the CT region of the molecule that recognizes native MUC16 and its enzymatically released CT...... for the disease and it is considered a promising target for immunotherapeutic intervention. Immunodetection of the mucin has to date been through antibodies that recognize its exceptionally large ectodomain. Similar to other membrane anchored mucins, MUC16 has a short cytoplasmic tail (CT), but studies...... region. The antibody is useful for immunoprecipitation of the released CT domain as demonstrated with the OVCAR3 ovarian cancer cell line and can be used for detailed cytolocalization in cells as well as in frozen sections of ocular surface and uterine epithelium....

  11. Targeting of the MUC1-C Oncoprotein in Colitis-Associated Colorectal Cancer

    Science.gov (United States)

    2013-09-01

    effect- level isobologram analysis is shown for ED 90 (), ED 75 (+) and ED 50 (×) with the right side panel indicating the CI index for the...was generated by exposing the cells to fixed IC50 ratios of GO-203, GSK1120212 and the GO- 203/GSK1120212 combination. The multiple effect- level ...Kharbanda S, and Kufe D, MUC1 oncoprotein blocks GSK3β -mediated phosphorylation and degradation of β-catenin. Cancer Res, 2005. 65:10413-22. 11. Rajabi

  12. A bioinformatics prediction approach towards analyzing the glycosylation, co-expression and interaction patterns of epithelial membrane antigen (EMA/MUC1)

    International Nuclear Information System (INIS)

    Kalra, Rajkumar S.; Wadhwa, Renu

    2015-01-01

    Epithelial membrane antigen (EMA or MUC1) is a heavily glycosylated, type I transmembrane glycoprotein commonly expressed by epithelial cells of duct organs. It has been shown to be aberrantly glycosylated in several diseases including cancer. Protein sequence based annotation and analysis of glycosylation profile of glycoproteins by robust computational and comprehensive algorithms provides possible insights to the mechanism(s) of anomalous glycosylation. In present report, by using a number of bioinformatics applications we studied EMA/MUC1 and explored its trans-membrane structural domain sequence that is widely subjected to glycosylation. Exploration of different extracellular motifs led to prediction of N and O-linked glycosylation target sites. Based on the putative O-linked target sites, glycosylated moieties and pathways were envisaged. Furthermore, Protein network analysis demonstrated physical interaction of EMA with a number of proteins and confirmed its functional involvement in cell growth and proliferation pathways. Gene Ontology analysis suggested an involvement of EMA in a number of functions including signal transduction, protein binding, processing and transport along with glycosylation. Thus, present study explored potential of bioinformatics prediction approach in analyzing glycosylation, co-expression and interaction patterns of EMA/MUC1 glycoprotein

  13. A bioinformatics prediction approach towards analyzing the glycosylation, co-expression and interaction patterns of epithelial membrane antigen (EMA/MUC1)

    Energy Technology Data Exchange (ETDEWEB)

    Kalra, Rajkumar S., E-mail: renu-wadhwa@aist.go.jp; Wadhwa, Renu, E-mail: renu-wadhwa@aist.go.jp [Cell Proliferation Research Group and DBT-AIST International Laboratory for Advanced Biomedicine, National Institute of Advanced Industrial Science and Technology (AIST Central 4), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562 (Japan)

    2015-02-27

    Epithelial membrane antigen (EMA or MUC1) is a heavily glycosylated, type I transmembrane glycoprotein commonly expressed by epithelial cells of duct organs. It has been shown to be aberrantly glycosylated in several diseases including cancer. Protein sequence based annotation and analysis of glycosylation profile of glycoproteins by robust computational and comprehensive algorithms provides possible insights to the mechanism(s) of anomalous glycosylation. In present report, by using a number of bioinformatics applications we studied EMA/MUC1 and explored its trans-membrane structural domain sequence that is widely subjected to glycosylation. Exploration of different extracellular motifs led to prediction of N and O-linked glycosylation target sites. Based on the putative O-linked target sites, glycosylated moieties and pathways were envisaged. Furthermore, Protein network analysis demonstrated physical interaction of EMA with a number of proteins and confirmed its functional involvement in cell growth and proliferation pathways. Gene Ontology analysis suggested an involvement of EMA in a number of functions including signal transduction, protein binding, processing and transport along with glycosylation. Thus, present study explored potential of bioinformatics prediction approach in analyzing glycosylation, co-expression and interaction patterns of EMA/MUC1 glycoprotein.

  14. Factors affecting antimicrobial activity of MUC7 12-mer, a human salivary mucin-derived peptide

    Directory of Open Access Journals (Sweden)

    Bobek Libuse A

    2007-11-01

    Full Text Available Abstract Background MUC7 12-mer (RKSYKCLHKRCR, a cationic antimicrobial peptide derived from the human low-molecular-weight salivary mucin MUC7, possesses potent antimicrobial activity in vitro. In order to evaluate the potential therapeutic application of the MUC7 12-mer, we examined the effects of mono- and divalent cations, EDTA, pH, and temperature on its antimicrobial activity. Methods Minimal Inhibitory Concentrations (MICs were determined using a liquid growth inhibition assay in 96-well microtiter plates. MUC7 12-mer was added at concentrations of 1.56–50 μM. MICs were determined at three endpoints: MIC-0, MIC-1, and MIC-2 (the lowest drug concentration showing 10%, 25% and 50% of growth, respectively. To examine the effect of salts or EDTA, a checkerboard microdilution technique was used. Fractional inhibitory concentration index (FICi was calculated on the basis of MIC-0. The viability of microbial cells treated with MUC7 12-mer in the presence of sodium or potassium was also determined by killing assay or flow cytometry. Results The MICs of MUC7 12-mer against organisms tested ranged from 6.25–50 μM. For C. albicans, antagonism (FICi 4.5 was observed for the combination of MUC7 12-mer and calcium; however, there was synergism (FICi 0.22 between MUC7 12-mer and EDTA, and the synergism was retained in the presence of calcium at its physiological concentration (1–2 mM. No antagonism but additivity or indifference (FICi 0.55–2.5 was observed for the combination of MUC7 12-mer and each K+, Na+, Mg2+, or Zn2+. MUC7 12-mer peptide (at 25 μM also exerted killing activity in the presence of NaCl, (up to 25 mM for C. albicans and up to 150 mM for E. coli, a physiological concentration of sodium in the oral cavity and serum, respectively and retained candidacidal activity in the presence of KCl (up to 40 mM. The peptide exhibited higher inhibitory activity against C. albicans at pH 7, 8, and 9 than at pH 5 and 6, and temperature up to

  15. Effect of MUC8 on Airway Inflammation: A Friend or a Foe?

    Science.gov (United States)

    Cha, Hee-Jae; Song, Kyoung Seob

    2018-02-06

    In this review, we compile identifying molecular mechanisms of MUC8 gene expression and studies characterizing the physiological functions of MUC8 in the airway and analyzing how altered MUC8 gene expression in the lung is affected by negative regulators.

  16. Phase I dose escalation pharmacokinetic assessment of intravenous humanized anti-MUC1 antibody AS1402 in patients with advanced breast cancer.

    Science.gov (United States)

    Pegram, Mark D; Borges, Virginia F; Ibrahim, Nuhad; Fuloria, Jyotsna; Shapiro, Charles; Perez, Susan; Wang, Karen; Schaedli Stark, Franziska; Courtenay Luck, Nigel

    2009-01-01

    MUC1 is a cell-surface glycoprotein that establishes a molecular barrier at the epithelial surface and engages in morphogenetic signal transduction. Alterations in MUC1 glycosylation accompany the development of cancer and influence cellular growth, differentiation, transformation, adhesion, invasion, and immune surveillance. A 20-amino-acid tandem repeat that forms the core protein of MUC1 is overexpressed and aberrantly glycosylated in the majority of epithelial tumors. AS1402 (formerly R1550) is a humanized IgG1k monoclonal antibody that binds to PDTR sequences within this tandem repeat that are not exposed in normal cells. AS1402 is a potent inducer of antibody-dependent cellular cytotoxicity (ADCC), specifically against MUC1-expressing tumor cells. The objective of this study was to determine the safety, tolerability, and pharmacokinetic (PK) characteristics of AS1402 monotherapy in patients with locally advanced or metastatic MUC1-positive breast cancer that had progressed after anthracyclines- and taxane-based therapy. Patients received AS1402 over a 1- to 3-hour intravenous (i.v.) infusion at doses between 1 and 16 mg/kg, with repeated dosing every 1 to 3 weeks (based on patient-individualized PK assessment) until disease progression. Serum AS1402 levels were measured at multiple times after i.v. administration. Human anti-human antibody (HAHA) responses were measured to determine the immunogenicity of AS1402. Noncompartmental pharmacokinetic parameters were determined and were used to assess dose dependency across the dose range studied. Twenty-six patients were treated. AS1402 was generally well tolerated. Two grade 3/4 drug-related adverse events were reported, both at the 3-mg/kg dose. Neither was observed in expanded or subsequent dosing cohorts. No anti-human antibodies were detected. Plasma concentrations of AS1402 appeared to be proportional to dose within the 1- to 16-mg/kg dose range assessed, with a mean terminal half-life of 115.4 +/- 37.1 hours

  17. Tumor-associated Tn-MUC1 glycoform is internalized through the macrophage galactose-type C-type lectin and delivered to the HLA class I and II compartments in dendritic cells

    DEFF Research Database (Denmark)

    Napoletano, Chiara; Rughetti, Aurelia; Agervig Tarp, Mads P

    2007-01-01

    . This results in the expression of tumor-associated glycoforms and in MUC1 carrying the tumor-specific glycan Tn (GalNAcalpha1-O-Ser/Thr). Glycopeptides corresponding to three tandem repeats of MUC1, enzymatically glycosylated with 9 or 15 mol of GalNAc, were shown to specifically bind and to be internalized...... and ELISA done on subcellular fractions of iDCs showed that the Tn-MUC1 glycopeptides colocalized with HLA class I and II compartments after internalization. Importantly, although Tn-MUC1 recombinant protein was bound and internalized by MGL, the glycoprotein entered the HLA class II compartment......, but not the HLA class I pathway. These data indicate that MGL expressed on iDCs is an optimal receptor for the internalization of short GalNAcs carrying immunogens to be delivered into HLA class I and II compartments. Such glycopeptides therefore represent a new way of targeting the HLA class I and II pathways...

  18. Inhibition of acrolein-stimulated MUC5AC expression by Platycodon grandiflorum root-derived saponin in A549 cells.

    Science.gov (United States)

    Choi, Jae Ho; Hwang, Yong Pil; Han, Eun Hee; Kim, Hyung Gyun; Park, Bong Hwan; Lee, Hyun Sun; Park, Byung Keun; Lee, Young Chun; Chung, Young Chul; Jeong, Hye Gwang

    2011-09-01

    Mucin overproduction is a hallmark of chronic airway diseases such as chronic obstructive pulmonary disease. In this study, we investigated the inhibition of acrolein-induced expression of mucin 5, subtypes A and C (MUC5AC) by Changkil saponin (CKS) in A549 cells. Acrolein, a known toxin in tobacco smoke and an endogenous mediator of oxidative stress, increases the expression of airway MUC5AC, a major component of airway mucus. CKS, a Platycodon grandiflorum root-derived saponin, inhibited acrolein-induced MUC5AC expression and activity, through the suppression of NF-κB activation. CKS also repressed acrolein-induced phosphorylation of ERK1/2, JNK1/2, and p38MAPK, which are upstream signaling molecules that control MUC5AC expression. In addition, the MAPK inhibitors PD98059 (ERK1/2), SP600125 (JNK1/2), and SB203580 (p38 MAPK), and a PKC delta inhibitor (rottlerin; PKCδ) inhibited acrolein-induced MUC5AC expression and activity. CKS repressed acrolein-induced phosphorylation of PKCδ. Moreover, a reactive oxygen species (ROS) inhibitor, N-acetylcysteine, inhibited acrolein-induced MUC5AC expression and activity through the suppression of PKCδ and MAPK activation, and CKS repressed acrolein-induced ROS production. These results suggest that CKS suppresses acrolein-induced MUC5AC expression by inhibiting the activation of NF-κB via ROS-PKCδ-MAPK signaling. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Low-density Lipoprotein Receptor-related Protein-1 (LRP1) Mediates Autophagy and Apoptosis Caused by Helicobacter pylori VacA*

    OpenAIRE

    Yahiro, Kinnosuke; Satoh, Mamoru; Nakano, Masayuki; Hisatsune, Junzo; Isomoto, Hajime; Sap, Jan; Suzuki, Hidekazu; Nomura, Fumio; Noda, Masatoshi; Moss, Joel; Hirayama, Toshiya

    2012-01-01

    In Helicobacter pylori infection, vacuolating cytotoxin (VacA)-induced mitochondrial damage leading to apoptosis is believed to be a major cause of cell death. It has also been proposed that VacA-induced autophagy serves as a host mechanism to limit toxin-induced cellular damage. Apoptosis and autophagy are two dynamic and opposing processes that must be balanced to regulate cell death and survival. Here we identify the low-density lipoprotein receptor-related protein-1 (LRP1) as the VacA rec...

  20. Microvesicle Cargo of Tumor-Associated MUC1 to Dendritic Cells Allows Cross-presentation and Specific Carbohydrate Processing

    DEFF Research Database (Denmark)

    Rughetti, Aurelia; Rahimi, Hassan; Belleudi, Francesca

    2014-01-01

    Tumor-associated glycoproteins are a group of antigens with high immunogenic interest: The glycoforms generated by the aberrant glycosylation are tumor-specific and the novel glycoepitopes exposed can be targets of tumor-specific immune responses. The MUC1 antigen is one of the most relevant tumo...

  1. Diverse Genetic Regulon of the Virulence-Associated Transcriptional Regulator MucR in Brucella abortus 2308

    Science.gov (United States)

    Caswell, Clayton C.; Elhassanny, Ahmed E. M.; Planchin, Emilie E.; Roux, Christelle M.; Weeks-Gorospe, Jenni N.; Ficht, Thomas A.; Dunman, Paul M.

    2013-01-01

    The Ros-type regulator MucR is one of the few transcriptional regulators that have been linked to virulence in Brucella. Here, we show that a Brucella abortus in-frame mucR deletion strain exhibits a pronounced growth defect during in vitro cultivation and, more importantly, that the mucR mutant is attenuated in cultured macrophages and in mice. The genetic basis for the attenuation of Brucella mucR mutants has not been defined previously, but in the present study the genes regulated by MucR in B. abortus have been elucidated using microarray analysis and real-time reverse transcription-PCR (RT-PCR). In B. abortus 2308, MucR regulates a wide variety of genes whose products may function in establishing and maintaining cell envelope integrity, polysaccharide biosynthesis, iron homeostasis, genome plasticity, and transcriptional regulation. Particularly notable among the MucR-regulated genes identified is arsR6 (nolR), which encodes a transcriptional regulator previously linked to virulence in Brucella melitensis 16 M. Importantly, electrophoretic mobility shift assays (EMSAs) determined that a recombinant MucR protein binds directly to the promoter regions of several genes repressed by MucR (including arsR6 [nolR]), and in Brucella, as in other alphaproteobacteria, MucR binds to its own promoter to repress expression of the gene that encodes it. Overall, these studies have uncovered the diverse genetic regulon of MucR in Brucella, and in doing so this work has begun to define the MucR-controlled genetic circuitry whose misregulation contributes to the virulence defect of Brucella mucR mutants. PMID:23319565

  2. Membrane-anchored MucR mediates nitrate-dependent regulation of alginate production in Pseudomonas aeruginosa

    KAUST Repository

    Wang, Yajie

    2015-04-29

    Alginates exhibit unique material properties suitable for medical and industrial applications. However, if produced by Pseudomonas aeruginosa, it is an important virulence factor in infection of cystic fibrosis patients. The alginate biosynthesis machinery is activated by c-di-GMP imparted by the inner membrane protein, MucR. Here, it was shown that MucR impairs alginate production in response to nitrate in P. aeruginosa. Subsequent site-specific mutagenesis of MucR revealed that the second MHYT sensor motif (MHYT II, amino acids 121–124) of MucR sensor domain was involved in nitrate sensing. We also showed that both c-di-GMP synthesizing and degrading active sites of MucR were important for alginate production. Although nitrate and deletion of MucR impaired alginate promoter activity and global c-di-GMP levels, alginate yields were not directly correlated with alginate promoter activity or c-di-GMP levels, suggesting that nitrate and MucR modulate alginate production at a post-translational level through a localized pool of c-di-GMP. Nitrate increased pel promoter activity in the mucR mutant while in the same mutant the psl promoter activity was independent of nitrate. Nitrate and deletion of mucR did not impact on swarming motility but impaired attachment to solid surfaces. Nitrate and deletion of mucR promoted the formation of biofilms with increased thickness, cell density, and survival. Overall, this study provided insight into the functional role of MucR with respect to nitrate-mediated regulation of alginate biosynthesis. © 2015 Springer-Verlag Berlin Heidelberg

  3. Characterization of carbohydrate structures of bovine MUC15 and distribution of the mucin in bovine milk

    DEFF Research Database (Denmark)

    Pallesen, Lone Tjener; Pedersen, Lise Refstrup Linnebjerg; Petersen, Torben Ellebæk

    2007-01-01

    by densitometric scanning of Western blots. In raw milk, MUC15 was shown to constitute 0.08% (wt) of the protein and approximately 1.5% (wt) of the MFGM-associated proteins. Surprisingly, this study showed that in addition to the fat-containing fractions, such as MFGM and buttermilk, MUC15 was present in nonfat......The present work reports the characterization of carbohydrate structures and the distribution of the newly identified mucin MUC15, a highly glycosylated protein associated with the bovine milk fat globule membrane (MFGM). Distribution of MUC15 was investigated in various fractions of bovine milk......-containing fractions as well, such as skim milk and whey. Compositional and structural studies of the carbohydrates of bovine milk MUC15 showed that the glycans are composed of fucose, galactose, mannose, N-acetylgalactosamine, N-acetylglycosamine, and sialic acid. The carbohydrate was shown to constitute 65...

  4. MUC1 positive cutaneous metastasis with transepidermal elimination from a breast carcinoma

    Directory of Open Access Journals (Sweden)

    Luna A

    2013-11-01

    Full Text Available Amalia Luna, Maria Emilia Merino, Cecilio G Alberdi, Martin C Abba, Amada Segal-Eiras, Maria Virginia Croce Center of Basic and Applied Immunological Research, Faculty of Medical Sciences, National University of La Plata, Argentina Abstract: Breast cancer is the most common cause of cutaneous metastases from internal malignancies. Generally, the neoplastic cells are located in the dermis or hypodermis, while a finding of transepidermal elimination on cutaneous metastases is exceptional. In this report we present a patient with perforating cutaneous metastases from breast cancer with mucin 1 expression. Cutaneous, bone, lung, and hepatic lesions were detected two years after the diagnosis of the primary tumor. Keywords: breast cancer, cutaneous metastasis, transepidermal elimination, MUC1

  5. Helicobacter-negative gastritis: polymerase chain reaction for Helicobacter DNA is a valuable tool to elucidate the diagnosis.

    Science.gov (United States)

    Kiss, S; Zsikla, V; Frank, A; Willi, N; Cathomas, G

    2016-04-01

    Helicobacter-negative gastritis has been increasingly reported. Molecular techniques as the polymerase chain reaction (PCR) may detect bacterial DNA in histologically negative gastritis. To evaluate of Helicobacter PCR in gastric biopsies for the daily diagnostics of Helicobacter-negative gastritis. Over a 5-year period, routine biopsies with chronic gastritis reminiscent of Helicobacter infection, but negative by histology, were tested by using a H. pylori specific PCR. Subsequently, PCR-negative samples were re-evaluated using PCR for other Helicobacter species. Of the 9184 gastric biopsies, 339 (3.7%) with histological-negative gastritis and adequate material were forwarded to PCR analysis for H. pylori and 146 (43.1%) revealed a positive result. In 193 H. pylori DNA-negative biopsies, re-analysis using PCR primers for other Helicobacter species, revealed further 23 (11.9%) positive biopsies, including 4 (2.1%) biopsies with H. heilmannii sensu lato. PCR-positive biopsies showed a higher overall inflammatory score, more lymphoid follicles/aggregates and neutrophils (P gastritis. © 2016 John Wiley & Sons Ltd.

  6. Toll like receptors TLR1/2, TLR6 and MUC5B as binding interaction partners with cytostatic proline rich polypeptide 1 in human chondrosarcoma.

    Science.gov (United States)

    Galoian, Karina; Abrahamyan, Silva; Chailyan, Gor; Qureshi, Amir; Patel, Parthik; Metser, Gil; Moran, Alexandra; Sahakyan, Inesa; Tumasyan, Narine; Lee, Albert; Davtyan, Tigran; Chailyan, Samvel; Galoyan, Armen

    2018-01-01

    Metastatic chondrosarcoma is a bone malignancy not responsive to conventional therapies; new approaches and therapies are urgently needed. We have previously reported that mTORC1 inhibitor, antitumorigenic cytostatic proline rich polypeptide 1 (PRP-1), galarmin caused a significant upregulation of tumor suppressors including TET1/2 and SOCS3 (known to be involved in inflammatory processes), downregulation of oncoproteins and embryonic stem cell marker miR-302C and its targets Nanog, c-Myc and Bmi-1 in human chondrosarcoma. To understand better the mechanism of PRP-1 action it was very important to identify the receptor it binds to. Nuclear pathway receptor and GPCR assays indicated that PRP-1 receptors are not G protein coupled, neither do they belong to family of nuclear or orphan receptors. In the present study, we have demonstrated that PRP-1 binding interacting partners belong to innate immunity pattern recognition toll like receptors TLR1/2 and TLR6 and gel forming secreted mucin MUC5B. MUC5B was identified as PRP-1 receptor in human chondrosarcoma JJ012 cell line using Ligand-receptor capture technology. Toll like receptors TLR1/2 and TLR6 were identified as binding interaction partners with PRP-1 by western blot analysis in human chondrosarcoma JJ012 cell line lysates. Immunocytochemistry experiments confirmed the finding and indicated the localization of PRP-1 receptors in the tumor nucleus predominantly. TLR1/2, TLR6 and MUC5B were downregulated in human chondrosarcoma and upregulated in dose-response manner upon PRP-1 treatment. Experimental data indicated that in this cellular context the mentioned receptors had tumor suppressive function.

  7. The Breast Cancer-Associated Glycoforms of MUC1, MUC1-Tn and sialyl-Tn, Are Expressed in COSMC Wild-Type Cells and Bind the C-Type Lectin MGL

    DEFF Research Database (Denmark)

    Beatson, Richard; Maurstad, Gjertrud; Picco, Gianfranco

    2015-01-01

    Aberrant glycosylation occurs in the majority of human cancers and changes in mucin-type O-glycosylation are key events that play a role in the induction of invasion and metastases. These changes generate novel cancer-specific glyco-antigens that can interact with cells of the immune system through...... carbohydrate binding lectins. Two glyco-epitopes that are found expressed by many carcinomas are Tn (GalNAc-Ser/Thr) and STn (NeuAcα2,6GalNAc-Ser/Thr). These glycans can be carried on many mucin-type glycoproteins including MUC1. We show that the majority of breast cancers carry Tn within the same cell...

  8. Misidentifying helicobacters: the Helicobacter cinaedi example

    DEFF Research Database (Denmark)

    Vandamme, P.; Harrington, C.S.; Jalava, K.

    2000-01-01

    Whole-cell protein electrophoresis and biochemical examination by means of a panel of 64 tests were used to identify 14 putative helicobacters to the species level. The results were confirmed by means of DNA-DNA hybridization experiments and were used to discuss misidentification of helicobacters...

  9. Relationship between childhood asthma and Helicobacter pylori infection

    Directory of Open Access Journals (Sweden)

    Ying Wu

    2016-07-01

    Full Text Available Objective: To investigate the correlation between childhood asthma and Helicobacter pylori infection. Methods: A total of 80 children with asthma who were treated in our hospital from May 2012 to May 2015 were selected as the research subjects, and 40 cases of healthy children were selected as control group, the Helicobacter pylori infection of the two groups of patients were compared, the double antibody sandwich enzyme-linked immunosorbent assay was used to detect the serum Helicobacter pylori-IgG, Helicobacter pylori-CagAIgG, IL-4, Helicobacter pylori, IFN-γ and IL-1β, etc., and the correlation between Helicobacter pylori infection and asthma was analyzed. Results: The positive rates of Helicobacter pylori infection in asthma group and children in attack stage were significantly higher than those in control group and children in remission stage (P<0.05. The positive rates of serum Helicobacter pylori-IgG and Helicobacter pylori-CagAIgG in asthma group and children in attack stage were significantly lower than those in control group and children in remission stage (P<0.05. The serum levels of IFN-γ in asthma group and children in attack stage were significantly lower than those in control group and children in remission stage, IL-4 and IL-1β levels in the former were significantly higher than those in the latter (P<0.05. Helicobacter pylori infection positive had significant positive correlation with IL-1β concentration (r=0.75, P<0.05. Conclusions: Helicobacter pylori infection in children has significant positive correlation with the incidence of asthma, suggesting that Helicobacter pylori infection has a certain protective effect on childhood asthma, but persistent Helicobacter pylori infection in children with asthma can aggravate the immune disorder, which is the main reason for the difficulty of treatment of asthma.

  10. RNA interference suppression of mucin 5AC (MUC5AC reduces the adhesive and invasive capacity of human pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Yamada Nobuya

    2010-05-01

    Full Text Available Abstract Background MUC5AC is a secretory mucin normally expressed in the surface muconous cells of stomach and bronchial tract. It has been known that MUC5AC de novo expression occurred in the invasive ductal carcinoma and pancreatic intraepithelial neoplasm with no detectable expression in normal pancreas, however, its function remains uncertain. Here, we report the impact of MUC5AC on the adhesive and invasive ability of pancreatic cancer cells. Methods We used two MUC5AC expressing cell lines derived from human pancreatic cancer, SW1990 and BxPC3. Small-interfering (si RNA directed against MUC5AC were used to assess the effects of MUC5AC on invasion and adhesion of pancreas cancer cells in vitro and in vivo. We compared parental cells (SW1990 and BxPC3 with MUC5AC suppressed cells by si RNA (si-SW1990 and si-BxPC3. Results MUC5AC was found to express in more than 80% of pancreatic ductal carcinoma specimens. Next we observed that both of si-SW1990 and si-BxPC3 showed significantly lower adhesion and invasion to extracellular matrix components compared with parental cell lines. Expression of genes associated with adhesion and invasion including several integerins, matrix metalloproteinase (MMP -3 and vascular endothelial growth factor (VEGF were down-regulated in both MUC5AC suppressed cells. Furthermore, production of VEGF and phosphorylation of VEGFR-1 were significantly reduced by MUC5AC down regulation. Both of si-SW1990 and si-BxPC3 attenuated activation of Erk1/2. In vivo, si-SW1990 did not establish subcutaneous tumor in nude mice. Conclusions Knockdown of MUC5AC reduced the ability of pancreatic cancer cells to adhesion and invasion, suggesting that MUC5AC might contribute to the invasive motility of pancreatic cancer cells by enhancing the expression of integrins, MMP-3, VEGF and activating Erk pathway.

  11. The Use of Fluoroproline in MUC1 Antigen Enables Efficient Detection of Antibodies in Patients with Prostate Cancer

    NARCIS (Netherlands)

    Somovilla, Víctor J; Bermejo, Iris A.; Albuquerque, Inês S; Martínez-Sáez, Nuria; Castro-López, Jorge; García-Martín, Fayna; Compañón, Ismael; Hinou, Hiroshi; Nishimura, Shin-Ichiro; Jiménez-Barbero, Jesús; Asensio, Juan L.; Avenoza, Alberto; Busto, Jesús H.; Hurtado-Guerrero, Ramón; Peregrina, Jesús M.; Bernardes, Gonçalo J L; Corzana, Francisco

    2017-01-01

    A structure-based design of a new generation of tumor-associated glycopeptides with improved affinity against two anti-MUC1 antibodies is described. These unique antigens feature a fluorinated proline residue, such as a (4S)-4-fluoro-l-proline or 4,4-difluoro-l-proline, at the most immunogenic

  12. Pediatric Helicobacter pylori gastropathy demonstrates a unique pattern of gastric foveolar hyperplasia.

    Science.gov (United States)

    Saghier, Sadaf; Schwarz, Steven M; Anderson, Virginia; Gupta, Raavi; Heidarian, Amin; Rabinowitz, Simon S

    2018-04-25

    Helicobacter pylori (Hp) are the most common agents causing gastric mucosal injury worldwide. Foveolar hyperplasia is a key component of the stomach's reaction to injury. This study examines histopathologic characteristics associated with Helicobacter pylori and with non- Helicobacter pylori-associated gastropathy in children and adolescents, and compares the prevalence of foveolar hyperplasia among these disease subgroups and normal control subjects. Eighty-one gastric antral and corpus biopsies from subjects 2-19 years of age were studied. Twenty-two subjects with Helicobacter pylori gastritis were compared to 23 with non-Helicobacter pylori gastropathy and to 36 controls (normal biopsies). Foveolar length, full mucosal thickness, and the foveolar length: full mucosal thickness ratio were derived by a morphometric technique previously developed to analyze adult gastric tissue. Compared to controls, Helicobacter pylori gastritis demonstrated significant increases in antral foveolar length (P Helicobacter pylori-associated gastropathy also was characterized by increased antral foveolar length (P Helicobacter pylori gastropathy was increased, when compared to Helicobacter pylori gastritis (P Helicobacter pylori gastropathy group demonstrated increased antral foveolar length: full mucosal thickness ratios, compared with Helicobacter pylori gastritis (P Helicobacter pylori gastritis but is limited to the antrum in non-Helicobacter pylori gastropathy. © 2018 John Wiley & Sons Ltd.

  13. The silence of MUC2 mRNA induced by promoter hypermethylation associated with HBV in Hepatocellular Carcinoma

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    Ling Yang

    2013-01-01

    Full Text Available Abstract Background To evaluate the promoter methylation status of MUC2 gene and mRNA expression in patients with hepatocellular carcinoma. Methods We analyzed MUC2 methylation by MSP, and MUC2 mRNA by real-time PCR in 74 HCC. Results MUC2 mRNA were lower in HCC tissues (Mean -ΔCt = −4.70 than that in Non-HCC tissues (Mean -ΔCt = −2.98. Expression of MUC2 was elevated in only 23 (31.08% of the 74 HCC patients. MUC2 promoter was hypermethylated in 62.2% (46/74 of HCCs, and in only 18.9% (14/74 of non-tumor samples. MUC2 mRNA were lower in HCC patients with hypermethylation (Mean -ΔΔCt = −2.25 than those with demethylation (Mean -ΔΔCt = −0.22, and there is a decreased tendency for MUC2 mRNA in HCC patients with promoter hypermethylation (p = 0.011. There was a significantly correlation found between MUC2 mRNA and HBV and AFP in HCC. The loss of MUC2 mRNA and hypermethylation could be poor prognostic factors. After treated by 5-Aza-CdR and TSA, we found that MUC2 mRNA induced significantly in 7721, Huh7 and HepG2 cells. Conclusion The results suggested that MUC2 mRNA silenced by promoter hypermethylation is associated with high levels HBV in HCC.

  14. Association between the length of the MUC8-minisatellite 5 region and susceptibility to chronic obstructive pulmonary disease (COPD).

    Science.gov (United States)

    Lee, Se-Ra; Kim, Won-Tae; Kim, Tae Nam; Nam, Jong Kil; Kim, Woo Jin; Leem, Sun-Hee

    2018-01-01

    In asthma and chronic obstructive pulmonary disease (COPD), mucins display disease-related alterations caused by airway mucus obstruction. MUC5AC, MUC5B and MUC8 are known as the major secretory mucins in human airway epithelial cells. Analysis of mucin genes has identified the presence of several features with a variable number of tandem repeats (VNTR; minisatellites) in the central region of each mucin. In our previous study, six minisatellites in the region of the MUC8 gene were identified, and the MUC8-MS5 minisatellite showed the highest heterozygosity among them. In this study, we evaluated the relationship between MUC8-MS5 and susceptibility to asthma and COPD. A case-control study was performed with 229 controls, 123 COPD cases and 77 asthma cases. A significant association (OR 3.96) between short alleles (2/2 repeats) and the occurrence of COPD was observed [95% confidence interval (CI) 1.32-11.88; p = 0.008]. Hence, the increased frequency of 2/2 homo-short alleles were also found in asthma cases (3.11; CI 0.88-11.05; p = 0.066), though this association was not statistically significant. These results revealed a genetic association between MUC8 and COPD, and that the specific short minisatellite alleles (2/2) of MUC8-MS5 may be a risk factor for COPD.

  15. Single molecule real time sequencing in ADTKD-MUC1 allows complete assembly of the VNTR and exact positioning of causative mutations

    NARCIS (Netherlands)

    Wenzel, Andrea; Altmueller, Janine; Ekici, Arif B.; Popp, Bernt; Stueber, Kurt; Thiele, Holger; Pannes, Alois; Staubach, Simon; Salido, Eduardo; Nuernberg, Peter; Reinhardt, Richard; Reis, Andre; Rump, Patrick; Hanisch, Franz-Georg; Wolf, Matthias T. F.; Wiesener, Michael; Huettel, Bruno; Beck, Bodo B.

    2018-01-01

    Recently, the Mucin-1 (MUC1) gene has been identified as a causal gene of autosomal dominant tubulointerstitial kidney disease (ADTKD). Most causative mutations are buried within a GC-rich 60 basepair variable number of tandem repeat (VNTR), which escapes identification by massive parallel

  16. Purification of MUC1 from Bovine Milk-Fat Globules and Characterization of a Corresponding Full-Length cDNA Clone

    DEFF Research Database (Denmark)

    Pallesen, Lone Tjener; Andersen, Mikkel Holmen; Nielsen, Rune

    2001-01-01

    acid sequences obtained by peptide mapping. The complete amino acid sequence of MUC1 was determined by cloning and sequencing the corresponding bovine mammary gland cDNA, which was shown to encode a protein of 580 amino acid residues comprising a cleavable signal peptide of 22 residues. The deduced...

  17. A comparison of Helicobacter pylori and non-Helicobacter pylori Helicobacter spp. Binding to canine gastric mucosa with defined gastric glycophenotype.

    Science.gov (United States)

    Amorim, Irina; Freitas, Daniela P; Magalhães, Ana; Faria, Fátima; Lopes, Célia; Faustino, Augusto M; Smet, Annemieke; Haesebrouck, Freddy; Reis, Celso A; Gärtner, Fátima

    2014-08-01

    The gastric mucosa of dogs is often colonized by non-Helicobacter pylori helicobacters (NHPH), while H. pylori is the predominant gastric Helicobacter species in humans. The colonization of the human gastric mucosa by H. pylori is highly dependent on the recognition of host glycan receptors. Our goal was to define the canine gastric mucosa glycophenotype and to evaluate the capacity of different gastric Helicobacter species to adhere to the canine gastric mucosa. The glycosylation profile in body and antral compartments of the canine gastric mucosa, with focus on the expression of histo-blood group antigens was evaluated. The in vitro binding capacity of FITC-labeled H. pylori and NHPH to the canine gastric mucosa was assessed in cases representative of the canine glycosylation pattern. The canine gastric mucosa lacks expression of type 1 Lewis antigens and presents a broad expression of type 2 structures and A antigen, both in the surface and glandular epithelium. Regarding the canine antral mucosa, H. heilmannii s.s. presented the highest adhesion score whereas in the body region the SabA-positive H. pylori strain was the strain that adhered more. The canine gastric mucosa showed a glycosylation profile different from the human gastric mucosa suggesting that alternative glycan receptors may be involved in Helicobacter spp. binding. Helicobacter pylori and NHPH strains differ in their ability to adhere to canine gastric mucosa. Among the NHPH, H. heilmannii s.s. presented the highest adhesion capacity in agreement with its reported colonization of the canine stomach. © 2014 John Wiley & Sons Ltd.

  18. Autocrine Acetylcholine, Induced by IL-17A via NFκB and ERK1/2 Pathway Activation, Promotes MUC5AC and IL-8 Synthesis in Bronchial Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Angela Marina Montalbano

    2016-01-01

    Full Text Available IL-17A is overexpressed in the lung during acute neutrophilic inflammation. Acetylcholine (ACh increases IL-8 and Muc5AC production in airway epithelial cells. We aimed to characterize the involvement of nonneuronal components of cholinergic system on IL-8 and Muc5AC production in bronchial epithelial cells stimulated with IL-17A. Bronchial epithelial cells were stimulated with recombinant human IL-17A (rhIL-17A to evaluate the ChAT expression, the ACh binding and production, the IL-8 release, and the Muc5AC production. Furthermore, the effectiveness of PD098,059 (inhibitor of MAPKK activation, Bay11-7082 (inhibitor of IkBα phosphorylation, Hemicholinium-3 (HCh-3 (choline uptake blocker, and Tiotropium bromide (Spiriva® (anticholinergic drug was tested in our in vitro model. We showed that rhIL-17A increased the expression of ChAT, the levels of ACh binding and production, and the IL-8 and Muc5AC production in stimulated bronchial epithelial cells compared with untreated cells. The pretreatment of the cells with PD098,059 and Bay11-7082 decreased the ChAT expression and the ACh production/binding, while HCh-3 and Tiotropium decreased the IL-8 and Muc5AC synthesis in bronchial epithelial cells stimulated with rhIL-17A. IL-17A is involved in the IL-8 and Muc5AC production promoting, via NFκB and ERK1/2 pathway activation, the synthesis of ChAT, and the related activity of autocrine ACh in bronchial epithelial cells.

  19. Activity calibration in breath test for diagnosis of Helicobacter pylori

    International Nuclear Information System (INIS)

    Wasilewka-Radwanska, M.; Pysklak, S.; Gilewicz-Wolter, J.; Kuc, T.; Jung, A.; Niziol, J.; Kopanski, J.; Micherdzinski, J.; Cienciala, A.

    1996-01-01

    Some technical and measurement problems of the breath test for diagnosis of Helicobacter pylori are briefly discussed. Calibrated results obtained for population of 108 cases indicate difference between HP+ (infected with Helicobacter pylori) and HP- (non infected with Helicobacter pylori) in exhaled 14 C activity not less than 3.9 kBq while the lower limit for HP+ cases was set at 6.8 kBq at the detection limit: 0.9 Bq/mmol of CO 2 . It was estimated that in exhalation way up to 29% of the taken activity was removed in HP+ cases during first 35 minutes. Radiation hazard for the patient system is negligibly small - dose equipment not exceeds 0.29% of the natural (environmental) yearly exposure. (author)

  20. MUC19 expression in human ocular surface and lacrimal gland and its alteration in Sjögren syndrome patients.

    Science.gov (United States)

    Yu, D F; Chen, Y; Han, J M; Zhang, H; Chen, X P; Zou, W J; Liang, L Y; Xu, C C; Liu, Z G

    2008-02-01

    This study investigated the expression of MUC19, a newly discovered gel-forming mucin gene, in normal human lacrimal functional unit components and its alteration in Sjögren syndrome patients. Real-time PCR and immunohistochemistry were performed to determine the expression of MUC19 and MUC5AC in human cornea, conjunctiva, and lacrimal gland tissues. Conjunctival impression cytology specimens were collected from normal control subjects and Sjögren syndrome patients for Real-time PCR, PAS staining, and immunohistochemistry assays. In addition, conjunctiva biopsy specimens from both groups were examined for the expression differences of MUC19 and MUC5AC at both mRNA and protein level. The MUC19 mRNA was found to be present in cornea, conjunctiva and lacrimal gland tissues. The immunohistochemical staining of mucins showed that MUC19 was expressed in epithelial cells from corneal, conjunctival, and lacrimal gland tissues. In contrast, MUC5AC mRNA was only present in conjunctiva and lacrimal gland tissues, but not in cornea. Immunostaining demonstrates the co-staining of MUC19 and MUC5AC in conjunctival goblet cells. Consistent with the significant decrease of mucous secretion, both MUC19 and MUC5AC were decreased in conjunctiva of Sjögren syndrome patients compared to normal subjects. Considering the contribution of gel-forming mucins to the homeostasis of the ocular surface, the decreased expression of MUC19 and MUC5AC in Sjögren syndrome patients suggested that these mucins may be involved in the disruption of the ocular surface homeostasis in this disease.

  1. Mannan-MUC1-pulsed dendritic cell immunotherapy: a phase I trial in patients with adenocarcinoma.

    Science.gov (United States)

    Loveland, Bruce E; Zhao, Anne; White, Shane; Gan, Hui; Hamilton, Kate; Xing, Pei-Xiang; Pietersz, Geoffrey A; Apostolopoulos, Vasso; Vaughan, Hilary; Karanikas, Vaios; Kyriakou, Peter; McKenzie, Ian F C; Mitchell, Paul L R

    2006-02-01

    Tumor antigen-loaded dendritic cells show promise for cancer immunotherapy. This phase I study evaluated immunization with autologous dendritic cells pulsed with mannan-MUC1 fusion protein (MFP) to treat patients with advanced malignancy. Eligible patients had adenocarcinoma expressing MUC1, were of performance status 0 to 1, with no autoimmune disease. Patients underwent leukapheresis to generate dendritic cells by culture ex vivo with granulocyte macrophage colony-stimulating factor and interleukin 4 for 5 days. Dendritic cells were then pulsed overnight with MFP and harvested for reinjection. Patients underwent three cycles of leukapheresis and reinjection at monthly intervals. Patients with clinical benefit were able to continue with dendritic cell-MFP immunotherapy. Ten patients with a range of tumor types were enrolled, with median age of 60 years (range, 33-70 years); eight patients were of performance status 0 and two of performance status 1. Dendritic cell-MFP therapy led to strong T-cell IFNgamma Elispot responses to the vaccine and delayed-type hypersensitivity responses at injection sites in nine patients who completed treatments. Immune responses were sustained at 1 year in monitored patients. Antibody responses were seen in three patients only and were of low titer. Side effects were grade 1 only. Two patients with clearly progressive disease (ovarian and renal carcinoma) at entry were stable after initial therapy and went on to further leukapheresis and dendritic cell-MFP immunotherapy. These two patients have now each completed over 3 years of treatment. Immunization produced T-cell responses in all patients with evidence of tumor stabilization in 2 of the 10 advanced cancer patients treated. These data support further clinical evaluation of this dendritic cell-MFP immunotherapy.

  2. Muc5b Is the Major Polymeric Mucin in Mucus from Thoroughbred Horses With and Without Airway Mucus Accumulation

    Science.gov (United States)

    Rousseau, Karine; Cardwell, Jacqueline M.; Humphrey, Emma; Newton, Richard; Knight, David; Clegg, Peter; Thornton, David J.

    2011-01-01

    Mucus accumulation is a feature of inflammatory airway disease in the horse and has been associated with reduced performance in racehorses. In this study, we have analysed the two major airways gel-forming mucins Muc5b and Muc5ac in respect of their site of synthesis, their biochemical properties, and their amounts in mucus from healthy horses and from horses with signs of airway mucus accumulation. Polyclonal antisera directed against equine Muc5b and Muc5ac were raised and characterised. Immunohistochemical staining of normal equine trachea showed that Muc5ac and Muc5b are produced by cells in the submucosal glands, as well as surface epithelial goblet cells. Western blotting after agarose gel electrophoresis of airway mucus from healthy horses, and horses with mucus accumulation, was used to determine the amounts of these two mucins in tracheal wash samples. The results showed that in healthy horses Muc5b was the predominant mucin with small amounts of Muc5ac. The amounts of Muc5b and Muc5ac were both dramatically increased in samples collected from horses with high mucus scores as determined visually at the time of endoscopy and that this increase also correlated with increase number of bacteria present in the sample. The change in amount of Muc5b and Muc5ac indicates that Muc5b remains the most abundant mucin in mucus. In summary, we have developed mucin specific polyclonal antibodies, which have allowed us to show that there is a significant increase in Muc5b and Muc5ac in mucus accumulated in equine airways and these increases correlated with the numbers of bacteria. PMID:21602926

  3. Muc5b is the major polymeric mucin in mucus from thoroughbred horses with and without airway mucus accumulation.

    Directory of Open Access Journals (Sweden)

    Karine Rousseau

    Full Text Available Mucus accumulation is a feature of inflammatory airway disease in the horse and has been associated with reduced performance in racehorses. In this study, we have analysed the two major airways gel-forming mucins Muc5b and Muc5ac in respect of their site of synthesis, their biochemical properties, and their amounts in mucus from healthy horses and from horses with signs of airway mucus accumulation. Polyclonal antisera directed against equine Muc5b and Muc5ac were raised and characterised. Immunohistochemical staining of normal equine trachea showed that Muc5ac and Muc5b are produced by cells in the submucosal glands, as well as surface epithelial goblet cells. Western blotting after agarose gel electrophoresis of airway mucus from healthy horses, and horses with mucus accumulation, was used to determine the amounts of these two mucins in tracheal wash samples. The results showed that in healthy horses Muc5b was the predominant mucin with small amounts of Muc5ac. The amounts of Muc5b and Muc5ac were both dramatically increased in samples collected from horses with high mucus scores as determined visually at the time of endoscopy and that this increase also correlated with increase number of bacteria present in the sample. The change in amount of Muc5b and Muc5ac indicates that Muc5b remains the most abundant mucin in mucus. In summary, we have developed mucin specific polyclonal antibodies, which have allowed us to show that there is a significant increase in Muc5b and Muc5ac in mucus accumulated in equine airways and these increases correlated with the numbers of bacteria.

  4. Cholesterol-α-glucosyltransferase gene is present in most Helicobacter species including gastric non-Helicobacter pylori helicobacters obtained from Japanese patients.

    Science.gov (United States)

    Kawakubo, Masatomo; Horiuchi, Kazuki; Matsumoto, Takehisa; Nakayama, Jun; Akamatsu, Taiji; Katsuyama, Tsutomu; Ota, Hiroyoshi; Sagara, Junji

    2018-02-01

    Non-Helicobacter pylori helicobacters (NHPHs) besides H. pylori infect human stomachs and cause chronic gastritis and mucosa-associated lymphoid tissue lymphoma. Cholesteryl-α-glucosides have been identified as unique glycolipids present in H. pylori and some Helicobacter species. Cholesterol-α-glucosyltransferase (αCgT), a key enzyme for the biosynthesis of cholesteryl-α-glucosides, plays crucial roles in the pathogenicity of H. pylori. Therefore, it is important to examine αCgTs of NHPHs. Six gastric NHPHs were isolated from Japanese patients and maintained in mouse stomachs. The αCgT genes were amplified by PCR and inverse PCR. We retrieved the αCgT genes of other Helicobacter species by BLAST searches in GenBank. αCgT genes were present in most Helicobacter species and in all Japanese isolates examined. However, we could find no candidate gene for αCgT in the whole genome of Helicobacter cinaedi and several enterohepatic species. Phylogenic analysis demonstrated that the αCgT genes of all Japanese isolates show high similarities to that of a zoonotic group of gastric NHPHs including Helicobacter suis, Helicobacter heilmannii, and Helicobacter ailurogastricus. Of 6 Japanese isolates, the αCgT genes of 4 isolates were identical to that of H. suis, and that of another 2 isolates were similar to that of H. heilmannii and H. ailurogastricus. All gastric NHPHs examined showed presence of αCgT genes, indicating that αCgT may be beneficial for these helicobacters to infect human and possibly animal stomachs. Our study indicated that NHPHs could be classified into 2 groups, NHPHs with αCgT genes and NHPHs without αCgT genes. © 2017 John Wiley & Sons Ltd.

  5. Reduced sulfation of muc5b is linked to xerostomia in patients with Sjögren syndrome

    DEFF Research Database (Denmark)

    Alliende, C; Kwon, Y-J; Brito, M

    2008-01-01

    OBJECTIVES: MUC5B contains sulfated and sialylated oligosaccharides that sequester water required for moisturising the oral mucosa. Xerostomia, in patients with Sjögren syndrome, is generally associated with reduced quantities, rather than altered properties, of saliva. Here, we determined...... the amount of MUC5B (mRNA and protein) as well as sulfation levels in salivary glands of patients with normal or altered unstimulated salivary flow. Localisation of MUC5B and sulfated MUC5B, as well as total levels sulfated groups were determined and compared with acini basal lamina disorganisation. PATIENTS...... AND METHODS: In all, 18 patients with normal or altered unstimulated salivary flow and 16 controls were studied. MUC5B mRNA and protein were evaluated in salivary glands by semiquantitative RT-PCR and Western blot analysis. MUC5B sulfation was determined by Western blotting. MUC5B and sulfo-Lewis(a) antigen...

  6. UV light-induced mutability in Salmonella strains containing the umuDC or the mucAB operon

    International Nuclear Information System (INIS)

    Herrera, G.; Urios, A.; Aleixandre, V.; Blanco, M.

    1988-01-01

    Multicopy plasmids carrying either the umuDC operon of Escherichia coli or its analog mucAB operon, were introduced into Ames Salmonella strains in order to analyze the influence of UmuDC and MucAB proteins on repair and mutability after UV irradiation. It was found that in uvr + bacteria, plasmid pICV80:mucAB increased the frequency of UV-induced His + revertants whereas pSE117:umuDC caused a smaller increase in UV mutagenesis. In ΔuvrB bacteria, the protective role of pSE117 against UV killing was weak, and there was a great reduction in the mutant yield. In contrast, in these cells, pICV80 led to a large increase in both cell survival and mutation frequency. These results suggest that in Salmonella, as in E. coli, MucAB proteins mediate UV mutagenesis more efficiently than UmuDC proteins do. Plasmid pICV84:umuD + C - significantly increased UV mutagenesis of TA2659:ΔuvrB cells whereas in them, pICV77:mucA + B - had no effect on mutability indicating the presence in Salmonella TA2659 of a gene functionally homologous to umuC. 18 refs.; 1 figure; 3 tabs

  7. The MUC4 membrane-bound mucin regulates esophageal cancer cell proliferation and migration properties: Implication for S100A4 protein

    International Nuclear Information System (INIS)

    Bruyere, Emilie; Jonckheere, Nicolas; Frenois, Frederic; Mariette, Christophe; Van Seuningen, Isabelle

    2011-01-01

    Highlights: → Loss of MUC4 reduces proliferation of esophageal cancer cells. → MUC4 inhibition impairs migration of esophageal cancer cells but not their invasion. → Loss of MUC4 significantly reduces in vivo tumor growth. → Decrease of S100A4 induced by MUC4 inhibition impairs proliferation and migration. -- Abstract: MUC4 is a membrane-bound mucin known to participate in tumor progression. It has been shown that MUC4 pattern of expression is modified during esophageal carcinogenesis, with a progressive increase from metaplastic lesions to adenocarcinoma. The principal cause of development of esophageal adenocarcinoma is the gastro-esophageal reflux, and MUC4 was previously shown to be upregulated by several bile acids present in reflux. In this report, our aim was thus to determine whether MUC4 plays a role in biological properties of human esophageal cancer cells. For that stable MUC4-deficient cancer cell lines (shMUC4 cells) were established using a shRNA approach. In vitro (proliferation, migration and invasion) and in vivo (tumor growth following subcutaneous xenografts in SCID mice) biological properties of shMUC4 cells were analyzed. Our results show that shMUC4 cells were less proliferative, had decreased migration properties and did not express S100A4 protein when compared with MUC4 expressing cells. Absence of MUC4 did not impair shMUC4 invasiveness. Subcutaneous xenografts showed a significant decrease in tumor size when cells did not express MUC4. Altogether, these data indicate that MUC4 plays a key role in proliferative and migrating properties of esophageal cancer cells as well as is a tumor growth promoter. MUC4 mucin appears thus as a good therapeutic target to slow-down esophageal tumor progression.

  8. The MUC4 membrane-bound mucin regulates esophageal cancer cell proliferation and migration properties: Implication for S100A4 protein

    Energy Technology Data Exchange (ETDEWEB)

    Bruyere, Emilie; Jonckheere, Nicolas; Frenois, Frederic [Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 ' Mucins, Epithelial Differentiation and Carcinogenesis' , rue Polonovski, 59045 Lille Cedex (France); Universite Lille-Nord de France, 1 place de Verdun, 59045 Lille Cedex (France); Mariette, Christophe [Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 ' Mucins, Epithelial Differentiation and Carcinogenesis' , rue Polonovski, 59045 Lille Cedex (France); Universite Lille-Nord de France, 1 place de Verdun, 59045 Lille Cedex (France); Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, 1 place de Verdun, 59045 Lille Cedex (France); Van Seuningen, Isabelle, E-mail: isabelle.vanseuningen@inserm.fr [Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 ' Mucins, Epithelial Differentiation and Carcinogenesis' , rue Polonovski, 59045 Lille Cedex (France); Universite Lille-Nord de France, 1 place de Verdun, 59045 Lille Cedex (France)

    2011-09-23

    Highlights: {yields} Loss of MUC4 reduces proliferation of esophageal cancer cells. {yields} MUC4 inhibition impairs migration of esophageal cancer cells but not their invasion. {yields} Loss of MUC4 significantly reduces in vivo tumor growth. {yields} Decrease of S100A4 induced by MUC4 inhibition impairs proliferation and migration. -- Abstract: MUC4 is a membrane-bound mucin known to participate in tumor progression. It has been shown that MUC4 pattern of expression is modified during esophageal carcinogenesis, with a progressive increase from metaplastic lesions to adenocarcinoma. The principal cause of development of esophageal adenocarcinoma is the gastro-esophageal reflux, and MUC4 was previously shown to be upregulated by several bile acids present in reflux. In this report, our aim was thus to determine whether MUC4 plays a role in biological properties of human esophageal cancer cells. For that stable MUC4-deficient cancer cell lines (shMUC4 cells) were established using a shRNA approach. In vitro (proliferation, migration and invasion) and in vivo (tumor growth following subcutaneous xenografts in SCID mice) biological properties of shMUC4 cells were analyzed. Our results show that shMUC4 cells were less proliferative, had decreased migration properties and did not express S100A4 protein when compared with MUC4 expressing cells. Absence of MUC4 did not impair shMUC4 invasiveness. Subcutaneous xenografts showed a significant decrease in tumor size when cells did not express MUC4. Altogether, these data indicate that MUC4 plays a key role in proliferative and migrating properties of esophageal cancer cells as well as is a tumor growth promoter. MUC4 mucin appears thus as a good therapeutic target to slow-down esophageal tumor progression.

  9. Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells

    International Nuclear Information System (INIS)

    Zeng, Guo-fang; Cai, Shao-xi; Wu, Guang-Jer

    2011-01-01

    Conflicting research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM) in the Ig-like gene super-family, as both a tumor promoter and a tumor suppressor in the development of breast cancer. To resolve this, we have re-investigated the role of this CAM in the progression of human breast cancer cells. Three breast cancer cell lines were used for the tests: one luminal-like breast cancer cell line, MCF7, which did not express any METCAM/MUC18, and two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which expressed moderate levels of the protein. MCF7 cells were transfected with the human METCAM/MUC18 cDNA to obtain G418-resistant clones which expressed the protein and were used for testing effects of human METCAM/MUC18 expression on in vitro motility and invasiveness, and in vitro and in vivo tumorigenesis. Both MDA-MB-231 and MDA-MB-468 cells already expressed METCAM/MUC18. They were directly used for in vitro tests in the presence and absence of an anti-METCAM/MUC18 antibody. In MCF7 cells, enforced METCAM/MUC18 expression increased in vitro motility, invasiveness, anchorage-independent colony formation (in vitro tumorigenesis), and in vivo tumorigenesis. In both MDA-MB-231 and MDA-MB-468 cells, the anti-METCAM/MUC18 antibody inhibited both motility and invasiveness. Though both MDA-MB-231 and MDA-MB-468 cells established a disorganized growth in 3D basement membrane culture assay, the introduction of the anti-METCAM/MUC18 antibody completely destroyed their growth in the 3D culture. These findings support the notion that human METCAM/MUC18 expression promotes the progression of human breast cancer cells by increasing their motility, invasiveness and tumorigenesis

  10. Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Cai Shao-xi

    2011-03-01

    Full Text Available Abstract Background Conflicting research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM in the Ig-like gene super-family, as both a tumor promoter and a tumor suppressor in the development of breast cancer. To resolve this, we have re-investigated the role of this CAM in the progression of human breast cancer cells. Methods Three breast cancer cell lines were used for the tests: one luminal-like breast cancer cell line, MCF7, which did not express any METCAM/MUC18, and two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which expressed moderate levels of the protein. MCF7 cells were transfected with the human METCAM/MUC18 cDNA to obtain G418-resistant clones which expressed the protein and were used for testing effects of human METCAM/MUC18 expression on in vitro motility and invasiveness, and in vitro and in vivo tumorigenesis. Both MDA-MB-231 and MDA-MB-468 cells already expressed METCAM/MUC18. They were directly used for in vitro tests in the presence and absence of an anti-METCAM/MUC18 antibody. Results In MCF7 cells, enforced METCAM/MUC18 expression increased in vitro motility, invasiveness, anchorage-independent colony formation (in vitro tumorigenesis, and in vivo tumorigenesis. In both MDA-MB-231 and MDA-MB-468 cells, the anti-METCAM/MUC18 antibody inhibited both motility and invasiveness. Though both MDA-MB-231 and MDA-MB-468 cells established a disorganized growth in 3D basement membrane culture assay, the introduction of the anti-METCAM/MUC18 antibody completely destroyed their growth in the 3D culture. Conclusion These findings support the notion that human METCAM/MUC18 expression promotes the progression of human breast cancer cells by increasing their motility, invasiveness and tumorigenesis.

  11. The Importance of Urease in Acid Protection for the Gastric-colonising Bacteria Helicobacter pylori and Helicobacter felis sp. nov.

    OpenAIRE

    Ferrero, R. L.; Lee, A.

    2011-01-01

    The urease of the gastric pathogen Helicobacter pylori shares numerous characteristics with the urease of a bacterium isolated from cat gastric mucosa, Helicobacter felis sp. nov. The native enzymes have similar apparent molecular weights and, when subjected to SDS-PAGE, disassociate into active subunits of comparable relative mobilities. In contrast, a bacterium (St1) that colonises rodent ileal mucosa, and is related to Helicobacter spp., expresses a distinct urease from those of the gastri...

  12. Diversity of zoonotic enterohepatic Helicobacter species and detection of a putative novel gastric Helicobacter species in wild and wild-born captive chimpanzees and western lowland gorillas

    Czech Academy of Sciences Publication Activity Database

    Flahou, B.; Modrý, D.; Pomajbíková, K.; Petrželková, Klára Judita; Smet, A.; Ducatelle, R.; Pasmans, F.; Sá, R. M.; Todd, A.; Hashimoto, C.; Mulama, M.; Kiang, J.; Rossi, M.; Haesebrouck, F.

    2014-01-01

    Roč. 174, 1-2 (2014), s. 186-194 ISSN 0378-1135 R&D Projects: GA ČR GA206/09/0927 Institutional support: RVO:68081766 Keywords : Enterohepatic Helicobacter species * Gastric Helicobacter species * Helicobacter cinaedi * Candidatus Helicobacter homininae * Chimpanzee * Gorilla Subject RIV: EG - Zoology Impact factor: 2.511, year: 2014

  13. EVALUATION OF ENEMAS CONTAINING SUCRALFATE IN TISSUE CONTENT OF MUC-2 PROTEIN IN EXPERIMENTAL MODEL OF DIVERSION COLITIS.

    Science.gov (United States)

    Fernandez, Oscar Orlando Araya; Pereira, José Aires; Campos, Fábio Guilherme; Araya, Carolina Mardegan; Marinho, Gabriele Escocia; Novo, Rafaela de Souza; Oliveira, Thais Silva de; Franceschi, Yara Tinoco; Martinez, Carlos Augusto Real

    2017-01-01

    The effects of topical application of sucralfate (SCF) on the tissue content of MUC-2 protein have not yet been evaluated in experimental models of diversion colitis. To measure the tissue content of MUC-2 protein in the colonic mucosa diverted from fecal stream submitted to the SCF intervention. Thirty-six rats underwent derivation of intestinal transit through proximal colostomy and distal mucous fistula. The animals were divided into three groups which were submitted application of enemas with saline, SCF 1 g/kg/day and SCF 2 g/kg/day. Each group was divided into two subgroups, according to euthanasia was done after two or four weeks. The colitis diagnosis was established by histopathological study and the inflammatory intensity was evaluated by previously validated scale. The MUC-2 protein was identified by immunohistochemistry and the tissue content was measured computerized morphometry). The application of enemas with SCF in the concentration of 2 g/kg/day reduced inflammatory score of the segments that were diverted from fecal stream. The content of MUC-2 in diverted colon of the animals submitted to the intervention with SCF, independently of intervention period and the used concentration, was significantly greater than animals submitted to the application of enemas containing saline (p< 0.01). The content of MUC-2 after the intervention with SCF in the concentration of 2 g/kg/day was significantly higher when compared to the animals submitted to the application containing SCF at concentration of 1.0 g/kg/day (p<0.01). The tissue content of MUC-2 reached the highest values after intervention with SCF in the concentration of 2 g/kg/day for four weeks (p<0.01). Conclusion: The preventive application of enemas containing SCF reduces the inflammatory score and avoids the reduction of tissue content of MUC-2, suggesting that the substance is a valid therapeutic strategy to preserve the mucus layer that covers the intestinal epithelium.

  14. Diversity of zoonotic enterohepatic Helicobacter species and detection of a putative novel gastric Helicobacter species in wild and wild-born captive chimpanzees and western lowland gorillas

    Czech Academy of Sciences Publication Activity Database

    Flahou, B.; Modrý, David; Pomajbíková, Kateřina; Petrželková, Klára Judita; Smet, A.; Ducatelle, R.; Pasmans, F.; Sá, R. M.; Todd, A.; Hashimoto, C.; Mulama, M.; Kiang, J.; Rossi, M.; Haesebrouck, F.

    2014-01-01

    Roč. 174, 1-2 (2014), s. 186-194 ISSN 0378-1135 R&D Projects: GA ČR GA206/09/0927 Institutional support: RVO:60077344 Keywords : Enterohepatic Helicobacter species * Gastric Helicobacter species * Helicobacter cinaedi * 'Candidatus Helicobacter homininae' * Chimpanzee * Gorilla Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 2.511, year: 2014

  15. Helicobacter pylori infection

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007715.htm Helicobacter pylori infection To use the sharing features on this page, please enable JavaScript. Helicobacter pylori ( H pylori ) is a type of bacteria that ...

  16. Epitopes of MUC1 Tandem Repeats in Cancer as Revealed by Antibody Crystallography: Toward Glycopeptide Signature-Guided Therapy

    Directory of Open Access Journals (Sweden)

    Dapeng Zhou

    2018-05-01

    Full Text Available Abnormally O-glycosylated MUC1 tandem repeat glycopeptide epitopes expressed by multiple types of cancer have long been attractive targets for therapy in the race against genetic mutations of tumor cells. Glycopeptide signature-guided therapy might be a more promising avenue than mutation signature-guided therapy. Three O-glycosylated peptide motifs, PDTR, GSTA, and GVTS, exist in a tandem repeat HGVTSAPDTRPAPGSTAPPA, containing five O-glycosylation sites. The exact peptide and sugar residues involved in antibody binding are poorly defined. Co-crystal structures of glycopeptides and respective monoclonal antibodies are very few. Here we review 3 groups of monoclonal antibodies: antibodies which only bind to peptide portion, antibodies which only bind to sugar portion, and antibodies which bind to both peptide and sugar portions. The antigenicity of peptide and sugar portions of glyco-MUC1 tandem repeat were analyzed according to available biochemical and structural data, especially the GSTA and GVTS motifs independent from the most studied PDTR. Tn is focused as a peptide-modifying residue in vaccine design, to induce glycopeptide-binding antibodies with cross reactivity to Tn-related tumor glycans, but not glycans of healthy cells. The unique requirement for the designs of antibody in antibody-drug conjugate, bi-specific antibodies, and chimeric antigen receptors are also discussed.

  17. [Significance of MUC5B antibody in differential diagnosis between Aspergillus species and Mucorales of fungal sinusitis].

    Science.gov (United States)

    Piao, Ying-shi; Liu, Hong-gang; Liu, Xian-jun

    2008-04-01

    To differentiate between Aspergillus species and Mucorales of fungal sinusitis by immunohistochemistry. Formalin-fixed paraffin-embedded tissue blocks of 66 cases of fungal sinusitis were retrieved from the archival files of Department of Pathology of Beijing Tongren Hospital during the period from 2001 to 2006. The samples included 29 cases of fungal balls, 12 cases of allergic fungal sinusitis, 24 cases of chronic invasive fungal sinusitis and 1 case of acute invasive fungal sinusitis. The types of fungi were 44 Aspergillus species (31 cases of A. fumigatus, 7 cases of A. flavus and 6 cases of A. terreus) and 22 Mucorales (14 cases of Mucor species and 8 cases of Rhizopus species). Immunohistochemistry was performed with MUC2, MUC5AC and MUC5B antibodies. The results were compared with histochemical study for periodic acid-Schiff (PAS) and Grocott methenamine silver (GMS) stains. Immunohistochemical study for MUC5B showed that the positive rate of Aspergillus species was 90.9%, in contrast to 4.5% in Mucorales (P Mucorales in fungal sinusitis.

  18. The Drosophila melanogaster Muc68E Mucin Gene Influences Adult Size, Starvation Tolerance, and Cold Recovery.

    Science.gov (United States)

    Reis, Micael; Silva, Ana C; Vieira, Cristina P; Vieira, Jorge

    2016-07-07

    Mucins have been implicated in many different biological processes, such as protection from mechanical damage, microorganisms, and toxic molecules, as well as providing a luminal scaffold during development. Nevertheless, it is conceivable that mucins have the potential to modulate food absorption as well, and thus contribute to the definition of several important phenotypic traits. Here we show that the Drosophila melanogaster Muc68E gene is 40- to 60-million-yr old, and is present in Drosophila species of the subgenus Sophophora only. The central repeat region of this gene is fast evolving, and shows evidence for repeated expansions/contractions. This and/or frequent gene conversion events lead to the homogenization of its repeats. The amino acid pattern P[ED][ED][ST][ST][ST] is found in the repeat region of Muc68E proteins from all Drosophila species studied, and can occur multiple times within a single conserved repeat block, and thus may have functional significance. Muc68E is a nonessential gene under laboratory conditions, but Muc68E mutant flies are smaller and lighter than controls at birth. However, at 4 d of age, Muc68E mutants are heavier, recover faster from chill-coma, and are more resistant to starvation than control flies, although they have the same percentage of lipids as controls. Mutant flies have enlarged abdominal size 1 d after chill-coma recovery, which is associated with higher lipid content. These results suggest that Muc68E has a role in metabolism modulation, food absorption, and/or feeding patterns in larvae and adults, and under normal and stress conditions. Such biological function is novel for mucin genes. Copyright © 2016 Reis et al.

  19. Association of mast cells with helicobacter pylori infection in the antral mucosa

    Directory of Open Access Journals (Sweden)

    SR KC

    2011-03-01

    Full Text Available Background: Helicobacter pylori infection is associated with mixed inflammatory cell infiltrate consisting of neutrophils, eosinophils, lymphocytes and plasma cells. Helicobacter pylori lead to mast cell degranulation and release of active chemical compounds in in-vitro conditions. The objective of this study was to find out the association of mast cell density and Helicobacter pylori in the antral mucosa of the stomach. Materials and Methods: A total of 150 endoscopic biopsies were included in the study. In addition to routine Hematoxylin and Eosin stained slides, Giemsa stain was done in each case for the evaluation of Helicobacter pylori and mast cell density in the gastric mucosa. Results: Out of 150 gastric biopsies with histopathological diagnosis of chronic gastritis, 36 cases (24% were positive for Helicobacter pylori. In the antral mucosa, mast cell density was significantly higher in the Helicobacter pylori-positive group than in the Helicobacter pylori-negative group (P<0.01. Conclusion: Mast cells may play a role in the development of Helicobacter pylori gastritis. Keywords: Gastritis; Mast Cell; Helicobacter pylori DOI: 10.3126/jpn.v1i1.4448 Journal of Pathology of Nepal (2011 Vol.1, 34-36

  20. Mucin architecture behind the immune response : Design, evaluation and conformational analysis of an antitumor vaccine derived from an unnatural MUC1 fragment

    NARCIS (Netherlands)

    Martínez-Sáez, Nuria; Supekar, Nitin T.; Wolfert, Margreet A.; Bermejo, Iris A.; Hurtado-Guerrero, Ramón; Asensio, Juan L.; Jiménez-Barbero, Jesús; Busto, Jesús H.; Avenoza, Alberto; Boons, Geert Jan; Peregrina, Jesús M.; Corzana, Francisco

    2016-01-01

    A tripartite cancer vaccine candidate, containing a quaternary amino acid (α-methylserine) in the most immunogenic domain of MUC1, has been synthesized and examined for antigenic properties in transgenic mice. The vaccine which is glycosylated with GalNAc at the unnatural amino acid, was capable of

  1. Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer

    DEFF Research Database (Denmark)

    Burford, B; Gentry-Maharaj, A; Graham, R

    2013-01-01

    Autoantibodies have been detected in sera before diagnosis of cancer leading to interest in their potential as screening/early detection biomarkers. As we have found autoantibodies to MUC1 glycopeptides to be elevated in early-stage breast cancer patients, in this study we analysed these autoanti...

  2. Membrane-anchored MucR mediates nitrate-dependent regulation of alginate production in Pseudomonas aeruginosa

    KAUST Repository

    Wang, Yajie; Hay, Iain D.; Rehman, Zahid Ur; Rehm, Bernd H A

    2015-01-01

    of MucR impaired alginate promoter activity and global c-di-GMP levels, alginate yields were not directly correlated with alginate promoter activity or c-di-GMP levels, suggesting that nitrate and MucR modulate alginate production at a post

  3. Helicobacter pylori gastritis

    International Nuclear Information System (INIS)

    Urban, B.A.; Fishman, E.K.; Kuhlman, J.E.; Jones, B.

    1990-01-01

    This paper reports on the CT scans of patients with Helicobacter pylori (formerly Campylobacter pylori) infection and histologic gastritis reviewed to determine if the inflammatory changes can mimic the CT appearance of gastric neoplasm. Records were obtained of 288 consecutive cases of biopsy-confirmed. Helicobacter pylori gastritis, spanning a 21-month period from July 1988 to March 1990. Abdominal CT scans had been performed in 70 of these cases and were retrospectively reviewed. RESULTS: Seven of the 70 cases of confirmed Helicobacter pylori gastritis were suggestive of malignancy on CT

  4. Effects of the Loss of Conjunctival Muc16 on Corneal Epithelium and Stroma in Mice

    Science.gov (United States)

    Shirai, Kumi; Okada, Yuka; Cheon, Dong-Joo; Miyajima, Masayasu; Behringer, Richard R.; Yamanaka, Osamu; Saika, Shizuya

    2014-01-01

    Purpose. To examine the role of conjunctival Muc16 in the homeostasis of the ocular surface epithelium and stroma using Muc16-null knockout (KO) mice. Methods. We used KO mice (n = 58) and C57/BL6 (WT) mice (n = 58). Histology and immunohistochemistry were employed to analyze the phenotypes in the ocular surface epithelium. The expression of phospho-Stat3, AP-1 components, interleukin 6 (IL-6), and tumor necrosis factor-α (TNFα) in the cornea and conjunctiva was examined. The shape of the nuclei of corneal epithelial cells was examined to evaluate intraepithelial cell differentiation. Epithelial cell proliferation was studied using bromo-deoxyuridine labeling. Finally, the wound healing of a round defect (2-mm diameter) in the corneal epithelium was measured. The keratocyte phenotype and macrophage invasion in the stroma were evaluated after epithelial repair. Results. The loss of Muc16 activated Stat3 signal, affected JunB signal, and upregulated the expression of IL-6 in the conjunctiva. Basal-like cells were observed in the suprabasal layer of the corneal epithelium with an increase in proliferation. The loss of Muc16 accelerated the wound healing of the corneal epithelium. The incidence of myofibroblast appearance and macrophage invasion were more marked in KO stroma than in WT stroma after epithelial repair. Conclusions. The loss of Muc16 in the conjunctiva affected the homeostasis of the corneal epithelium and stroma. The mechanism might include the upregulation of the inflammatory signaling cascade (i.e., Stat3 signal, and IL-6 expression in the KO conjunctiva). Current data provides insight into the research of the pathophysiology of dry eye syndrome. PMID:24812549

  5. A Gastric Glycoform of MUC5AC Is a Biomarker of Mucinous Cysts of the Pancreas.

    Directory of Open Access Journals (Sweden)

    Jessica Sinha

    Full Text Available Molecular indicators to specify the risk posed by a pancreatic cyst would benefit patients. Previously we showed that most cancer-precursor cysts, termed mucinous cysts, produce abnormal glycoforms of the proteins MUC5AC and endorepellin. Here we sought to validate the glycoforms as a biomarker of mucinous cysts and to specify the oligosaccharide linkages that characterize MUC5AC. We hypothesized that mucinous cysts secrete MUC5AC displaying terminal N-acetylglucosamine (GlcNAc in either alpha or beta linkage. We used antibody-lectin sandwich assays to detect glycoforms of MUC5AC and endorepellin in cyst fluid samples from three independent cohorts of 49, 32, and 66 patients, and we used monoclonal antibodies to test for terminal, alpha-linked GlcNAc and the enzyme that produces it. A biomarker panel comprising the previously-identified glycoforms of MUC5AC and endorepellin gave 96%, 96%, and 87% accuracy for identifying mucinous cysts in the three cohorts with an average sensitivity of 92% and an average specificity of 94%. Glycan analysis showed that MUC5AC produced by a subset of mucinous cysts displays terminal alpha-GlcNAc, a motif expressed in stomach glands. The alpha-linked glycoform of MUC5AC was unique to intraductal papillary mucinous neoplasms (IPMN, whereas terminal beta-linked GlcNAc was increased in both IPMNs and mucinous cystic neoplasms (MCN. The enzyme that synthesizes alpha-GlcNAc, A4GNT, was expressed in the epithelia of mucinous cysts that expressed alpha-GlcNAc, especially in regions with high-grade dysplasia. Thus IPMNs secrete a gastric glycoform of MUC5AC that displays terminal alpha-GlcNAc, and the combined alpha-GlcNAc and beta-GlcNAc glycoforms form an accurate biomarker of mucinous cysts.

  6. Novel treatment option for MUC16-positive malignancies with the targeted TRAIL-based fusion protein Meso-TR3

    International Nuclear Information System (INIS)

    Garg, Gunjal; Spitzer, Dirk; Gibbs, Jesse; Belt, Brian; Powell, Matthew A; Mutch, David G; Goedegebuure, Peter; Collins, Lynne; Piwnica-Worms, David; Hawkins, William G

    2014-01-01

    The targeted delivery of cancer therapeutics represents an ongoing challenge in the field of drug development. TRAIL is a promising cancer drug but its activity profile could benefit from a cancer-selective delivery mechanism, which would reduce potential side effects and increase treatment efficiencies. We recently developed the novel TRAIL-based drug platform TR3, a genetically fused trimer with the capacity for further molecular modifications such as the addition of tumor-directed targeting moieties. MUC16 (CA125) is a well characterized biomarker in several human malignancies including ovarian, pancreatic and breast cancer. Mesothelin is known to interact with MUC16 with high affinity. In order to deliver TR3 selectively to MUC16-expressing cancers, we investigated the possibility of targeted TR3 delivery employing the high affinity mesothelin/MUC16 ligand/receptor interaction. Using genetic engineering, we designed the novel cancer drug Meso-TR3, a fusion protein between native mesothelin and TR3. The recombinant proteins were produced with mammalian HEK293T cells. Meso-TR3 was characterized for binding selectivity and killing efficacy against MUC16-positive cancer cells and controls that lack MUC16 expression. Drug efficacy experiments were performed in vitro and in vivo employing an intraperitoneal xenograft mouse model of ovarian cancer. Similar to soluble mesothelin itself, the strong MUC16 binding property was retained in the Meso-TR3 fusion protein. The high affinity ligand/receptor interaction was associated with a selective accumulation of the cancer drug on MUC16-expressing cancer targets and directly correlated with increased killing activity in vitro and in a xenograft mouse model of ovarian cancer. The relevance of the mesothelin/MUC16 interaction for attaching Meso-TR3 to the cancer cells was verified by competitive blocking experiments using soluble mesothelin. Mechanistic studies using soluble DR5-Fc and caspase blocking assays confirmed

  7. MUC5B levels in submandibular gland saliva of patients treated with radiotherapy for head-and-neck cancer: A pilot study

    International Nuclear Information System (INIS)

    Dijkema, Tim; Terhaard, Chris H J; Roesink, Judith M; Raaijmakers, Cornelis P J; Keijbus, Petra A M van den; Brand, Henk S; Veerman, Enno C I

    2012-01-01

    The salivary mucin MUC5B, present in (sero)mucous secretions including submandibular gland (SMG) saliva, plays an important role in the lubrication of the oral mucosa and is thought to be related to the feeling of dry mouth. We investigated if MUC5B levels in SMG saliva could distinguish between the presence or absence of severe dry mouth complaints 12 months after radiotherapy (RT) for head-and-neck cancer (HNC). Twenty-nine HNC patients with a residual stimulated SMG secretion rate of ≥0.2 ml/10 min at 12 months after RT were analyzed. MUC5B (in U; normalized to 1) and total protein levels (mg/ml) were measured in SMG saliva at baseline and 12 months after RT using ELISA and BCA protein assay, respectively. Overall, median MUC5B levels decreased after RT from 0.12 to 0.03 U (p = 0.47). Patients were dichotomized into none/mild xerostomia (n = 12) and severe xerostomia (n = 17) based on a questionnaire completed at 12 months. SMG and whole saliva flow rates decreased after RT but were comparable in both groups. The median MUC5B level was higher in patients with no or mild xerostomia compared to patients with severe xerostomia (0.14 vs 0.01 U, p = 0.22). Half of the patients with severe xerostomia had no detectable MUC5B at 12 months after RT. No differences in total protein levels were observed. Qualitative saliva parameters like MUC5B need further investigation in RT-induced xerostomia. This pilot study showed a trend towards lower MUC5B levels in the SMG saliva of patients with severe xerostomia 12 months after RT for HNC

  8. Rosacea is associated with Helicobacter pylori

    DEFF Research Database (Denmark)

    Jørgensen, A-H R; Egeberg, A; Gideonsson, R

    2017-01-01

    BACKGROUND: Rosacea is a common skin disease characterized by facial erythema, telangiectasia, papules and pustules. Helicobacter pylori infection has been suggested to play a role in the etiopathogenesis of rosacea. OBJECTIVE: To systematically review and meta-analyse the relationship between...... rosacea and infection with Helicobacter pylori. METHODS: A literature search was performed using PubMed, EMBASE and Web of Science. Data extraction and analyses were performed on descriptive data. Study quality was assessed using the Newcastle-Ottawa Scale. Random-effects models with Der...... in the quantitative meta-analysis, comprising a total of 928 rosacea patients and 1527 controls. The overall association between Helicobacter pylori infection and rosacea was non-significant (OR 1.68, 95% CI 1.00-2.84, P = 0.052), but analysis restricted to C-urea breath test showed a significant association (OR 3...

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

    Science.gov (United States)

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

    2016-03-15

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

  10. Incidence of Helicobacter felis and the effect of coinfection with Helicobacter pylori on the gastric mucosa in the African population

    NARCIS (Netherlands)

    Fritz, E. Lekunze; Slavik, Tomas; Delport, Wayne; Olivier, Brenda; van der Merwe, Schalk W.

    2006-01-01

    Helicobacter pylori and Helicobacter felis are two of the Helicobacter spp. that infect humans. H. pylori has been linked to significant gastric pathology. Coinfection with Helicobacter spp. may influence infectious burden, pathogenesis, and antibiotic resistance; however, this has not been studied.

  11. A graphene oxide-based fluorescent aptasensor for the turn-on detection of epithelial tumor marker mucin 1.

    Science.gov (United States)

    He, Yue; Lin, Yi; Tang, Hongwu; Pang, Daiwen

    2012-03-21

    Mucin 1 (MUC1) which presents in epithelial malignancies, is a well-known tumor biomarker. In this paper, a highly sensitive and selective fluorescent aptasensor for Mucin 1 (MUC1) detection is constructed, utilizing graphene oxide (GO) as a quencher which can quench the fluorescence of single-stranded dye-labeled MUC1 specific aptamer. In the absence of MUC1, the adsorption of the dye-labeled aptamer on GO brings the dyes in close proximity to the GO surface resulting in high efficiency quenching of dye fluorescence. Therefore, the fluorescence of the designed aptasensor is completely quenched by GO, and the system shows very low background fluorescence. Conversely, and very importantly, upon the adding of MUC1, the quenched fluorescence is recovered significantly, and MUC1 can be detected in a wide range of 0.04-10 μM with a detection limit of 28 nM and good selectivity. Moreover, the results have also been verified for real sample application by testing 2% serum containing buffer solution spiked with a series of concentrations of MUC1. This journal is © The Royal Society of Chemistry 2012

  12. Associations of genetic variants in the PSCA, MUC1 and PLCE1 genes with stomach cancer susceptibility in a Chinese population.

    Directory of Open Access Journals (Sweden)

    Hongwei Sun

    Full Text Available Several genetic variants including PSCA rs2294008 C>T and rs2976392 G>A, MUC1 rs4072037 T>C, and PLCE1 rs2274223 A>G have shown significant association with stomach cancer risk in the previous genome-wide association studies (GWASs.To evaluate associations of these SNPs in the Han Chinese, an independent hospital based case-control study was performed by genotyping these four polymorphisms in a total of 692 stomach cancer cases and 774 healthy controls acquired by using frequency matching for age and gender. False-positive report probability (FPRP analysis was also performed to validate all statistically significant findings.In the current study, significant association with stomach cancer susceptibility was observed for all the four polymorphisms of interest. Specifically, a significant increased stomach cancer risk was associated with PSCA rs2294008 (CT vs. CC: adjusted OR = 1.37, 95% CI = 1.07-1.74, and CT/TT vs.CC: adjusted OR = 1.30, 95% CI = 1.03-1.63, PSCA rs2976392 (AG vs. GG: adjusted OR = 1.30, 95% CI = 1.02-1.65, and AG/AA vs. GG: adjusted OR = 1.26, 95% CI = 1.00-1.59, or PLCE1 rs2274223 (AG vs. AA: adjusted OR = 1.48, 95% CI = 1.15-1.90, and AG/GG vs. AA: adjusted OR = 1.45, 95% CI = 1.14-1.84, respectively. In contrast, MUC1 rs4072037 was shown to decrease the cancer risk (CT vs. TT: adjusted OR = 0.77, 95% CI = 0.60-0.98. Patients with more than one risk genotypes had significant increased risk to develop stomach cancer (adjusted OR = 1.30, 95% CI = 1.03-1.64, when compared with those having 0-1 risk genotypes. Stratified analysis indicated that the increased risk was more pronounced in younger subjects, men, ever smokers, smokers with pack years ≤ 27, patients with high BMI, or non-cardia stomach cancer.This study substantiated the associations between four previous reported genetic variants and stomach cancer susceptibility in an independent Han Chinese population. Further studies with larger sample size and different

  13. Different efficiency of UmuDC and MucAB proteins in UV light induced mutagenesis in Escherichia coli

    International Nuclear Information System (INIS)

    Blanco, M.; Herrera, G.; Aleixandre, V.

    1986-01-01

    Two multicopy plasmids carrying either the umuDC or the mucAB operon were used to compare the efficiency of UmuDC and MucAB proteins in UV mutagenesis of Escherichia coli K12. It was found that in recA + uvr + bacteria, plasmid pIC80, mucAB + mediated UV mutagenesis more efficiently than did plasmid pSE 117, umuDC + . A similar result was obtained in lex A51(Def) cells, excluding the possibility that this was due to a differential regulation by LexA of the umuDC and mucAB operons. We conclude that some structural characteristic of the UmuDC and MucAB proteins determines their different efficiency in UV mutagenesis. This characteristic could be also responsible for the observation that in the recA430 mutant, pIC80 but no pSE117 can mediate UV mutagenesis. In the recAS142 mutant pIC80 also promoted UV mutagenesis more efficiently than pSE117. In this mutant, the recombination proficiency, the protease activity toward LexA and the mutation frequency were increased by the presence of adenine in the medium. In recA + uvrB5 bacteria, plasmid pSE117, umuDC caused both an increase in UV sensitivity as well as a reduction in the mutation frequency. These negative effects resulting from the overproduction of UmuDC proteins were higher in recA142 uvrB5 than in recA + uvrB5 cells. In contrast, overproduction of MucAB proteins in excision-deficient bacteria containing pIC80 led to a large increase in the mutation frequency. We suggest that the functional differences between UmuDC and MucAB proteins might be due to their different dependence on the direct role of RecA protease in UV mutagenesis. (orig.)

  14. Isolation and characterization of MUC15, a novel cell membrane-associated mucin

    DEFF Research Database (Denmark)

    Pallesen, Lone Tjener; Berglund, Lars; Rasmussen, Lone Kjær

    2002-01-01

    The present work reports isolation and characterization of a highly glycosylated protein from bovine milk fat globule membranes, known as PAS III. Partial amino-acid sequencing of the purified protein allowed construction of degenerate oligonucleotide primers, enabling isolation of a full-length c......-like protein was named MUC15 by appointment of the HUGO Gene Nomenclature Committee. The deduced amino-acid sequences of human and bovine MUC15 demonstrated structural hallmarks characteristic for other membrane-bound mucins, such as a serine, threonine, and proline-rich extracellular region with several...

  15. Mental vulnerability, Helicobacter pylori, and incidence of hospital-diagnosed peptic ulcer over 28 years in a population-based cohort.

    Science.gov (United States)

    Levenstein, Susan; Jacobsen, Rikke Kart; Rosenstock, Steffen; Jørgensen, Torben

    2017-09-01

    To examine whether mental vulnerability, an enduring personality characteristic, predicts incident hospital-diagnosed ulcer over three decades. A population-based cohort study enrolled 3365 subjects with no ulcer history, ages 30-60, in 1982-3. Mental vulnerability, Helicobacter pylori IgG antibodies, socioeconomic status, and sleep duration were determined at baseline; non-steroidal antiinflammatory drug use, smoking, leisure time physical activity, and alcohol consumption both at baseline and in 1993-4. Hospital diagnoses of incident ulcer through 2011 were detected using the Danish National Patient Registry. Ulcers were diagnosed in 166 subjects, including 83 complicated by bleeding or perforation. Age-, gender-, and socioeconomic status-adjusted associations were significant for mental vulnerability (Hazard Ratio (HR) 2.0, 95% Confidence Interval 1.4-2.8), Helicobacter pylori (HR 1.7, CI 1.2-2.3), smoking (HR 2.0, CI 1.3-3.1), heavy drinking (HR 1.6, CI 1.1-2.4), abstinence (HR 1.6, CI 1.1-2.5), non-steroidal antiinflammatory drugs (HR 2.1, CI 1.5-3.0), and sedentary lifestyle (HR 1.9, CI 1.4-2.7). Adjusted for all behavioral mediators, the HR for mental vulnerability was 1.5 (CI 1.0-2.2, p = .04). Mental vulnerability raised risk in Helicobacter pylori seropositive subjects and those exposed to neither Helicobacter pylori nor non-steroidal antiinflammatory drugs; its impact was virtually unchanged when analysis was limited to complicated ulcers. A vulnerable personality raises risk for hospital-diagnosed peptic ulcer, in part because of an association with health risk behaviors. Its impact is seen in 'idiopathic' and Helicobacter pylori-associated ulcers, and in acute surgical cases.

  16. The Detection of Helicobacter hepaticus Using Whispering-Gallery Mode Microcavity Optical Sensors

    Directory of Open Access Journals (Sweden)

    Mark E. Anderson

    2015-08-01

    Full Text Available Current bacterial detection techniques are relatively slow, require bulky instrumentation, and usually require some form of specialized training. The gold standard for bacterial detection is culture testing, which can take several days to receive a viable result. Therefore, simpler detection techniques that are both fast and sensitive could greatly improve bacterial detection and identification. Here, we present a new method for the detection of the bacteria Helicobacter hepaticus using whispering-gallery mode (WGM optical microcavity-based sensors. Due to minimal reflection losses and low material adsorption, WGM-based sensors have ultra-high quality factors, resulting in high-sensitivity sensor devices. In this study, we have shown that bacteria can be non-specifically detected using WGM optical microcavity-based sensors. The minimum detection for the device was 1 × 104 cells/mL, and the minimum time of detection was found to be 750 s. Given that a cell density as low as 1 × 103 cells/mL for Helicobacter hepaticus can cause infection, the limit of detection shown here would be useful for most levels where Helicobacter hepaticus is biologically relevant. This study suggests a new approach for H. hepaticus detection using label-free optical sensors that is faster than, and potentially as sensitive as, standard techniques.

  17. METCAM/MUC18 promoted tumorigenesis of human breast cancer SK-BR-3 cells in a dosage-specific manner.

    Science.gov (United States)

    Huang, Chang-Yu; Wu, Guang-Jer

    2016-04-01

    Overexpression of METCAM/MUC18, an immunoglobulin-like cell-adhesion molecule, promotes tumorigenesis and progression of human breast cancer cells. We also observed an intriguing phenomenon that a high-expressing SK-BR-3 clone manifested a transient tumor suppression effect in vivo. The purpose of this study was to understand if this was caused by clonal variation, METCAM/MUC18-dosage effect, or the number of cells injected. Several G418-resistant clones of SK-BR-3, expressing different levels of METCAM/MUC18, were obtained for testing effects of human METCAM/MUC18 on in vitro motility, invasiveness, and anchorage-independent colony formation (in vitro tumorigenicity) and in vivo tumorigenesis in female Balb/C athymic nude mice. Tumor sections were made for histology and immunohistochemistry analyses, and tumor lysates for Western blot analysis to determine the effects of human METCAM/MUC18 expression on levels of various downstream effectors. METCAM/MUC18 promoted in vitro motility, invasiveness, and in vitro tumorigenicity of SK-BR-3 cells in a dosage-specific manner. Overexpression of METCAM/MUC18 could promote in vivo tumorigenesis of SK-BR-3 cells even when one tenth of the previously used cell number (5 × 10(5)) was injected and in vivo tumorigenesis of SK-BR-3 cells was directly proportional to the dosage of the protein. The previously observed transient tumor suppression effect from the same clone was no longer observed. The downstream effector, such as phospho-AKT/AKT ratio, was elevated in the tumors. Transient suppression observed previously in the clone was caused by injection of a high cell number (2 × 10(6)-5 × 10(6)). METCAM/MUC18 positively promotes tumorigenesis of SK-BR-3 cells by increasing the survival and proliferation pathway. Copyright © 2016. Published by Elsevier B.V.

  18. Dual RNAseq shows the human mucosal immunity protein, MUC13, is a hallmark of Plasmodium exoerythrocytic infection

    KAUST Repository

    LaMonte, Gregory; Orjuela-Sanchez, Pamela; Wang, Lawrence; Li, Shangzhong; Swann, Justine; Cowell, Annie; Zou, Bing Yu; Abdel- Haleem Mohamed, Alyaa; Villa-Galarce, Zaira; Moreno, Marta; Tong-Rios, Carlos; Vinetz, Joseph; Lewis, Nathan; Winzeler, Elizabeth A

    2017-01-01

    The exoerythrocytic stage of Plasmodium malaria infection is a critical window for prophylactic intervention. Using a genome-wide dual RNA sequencing of flow-sorted infected and uninfected hepatoma cells we identify the human mucosal immunity gene, Mucin13 (MUC13), as strongly upregulated during Plasmodium exoerythrocytic hepatic-stage infection. We confirm that MUC13 expression is upregulated in hepatoma cell lines and primary hepatocytes. In immunofluorescence assays, host MUC13 protein expression distinguishes infected cells from adjacent uninfected cells and shows similar colocalization with parasite biomarkers such as UIS4 and HSP70. We further show that localization patterns are species independent, distinguishing both P. berghei and P. vivax infected cells, and that MUC13 can be used to identify compounds that inhibit parasite replication in hepatocytes across all Human-infecting Plasmodium species. This data presents a novel interface of host-parasite interactions in Plasmodium, in that a component of host mucosal immunity is reprogrammed to assist the progression of infection.

  19. Dual RNAseq shows the human mucosal immunity protein, MUC13, is a hallmark of Plasmodium exoerythrocytic infection

    KAUST Repository

    LaMonte, Gregory

    2017-10-03

    The exoerythrocytic stage of Plasmodium malaria infection is a critical window for prophylactic intervention. Using a genome-wide dual RNA sequencing of flow-sorted infected and uninfected hepatoma cells we identify the human mucosal immunity gene, Mucin13 (MUC13), as strongly upregulated during Plasmodium exoerythrocytic hepatic-stage infection. We confirm that MUC13 expression is upregulated in hepatoma cell lines and primary hepatocytes. In immunofluorescence assays, host MUC13 protein expression distinguishes infected cells from adjacent uninfected cells and shows similar colocalization with parasite biomarkers such as UIS4 and HSP70. We further show that localization patterns are species independent, distinguishing both P. berghei and P. vivax infected cells, and that MUC13 can be used to identify compounds that inhibit parasite replication in hepatocytes across all Human-infecting Plasmodium species. This data presents a novel interface of host-parasite interactions in Plasmodium, in that a component of host mucosal immunity is reprogrammed to assist the progression of infection.

  20. A Major Facilitator Superfamily protein encoded by TcMucK gene is not required for cuticle pigmentation, growth and development in Tribolium castaneum.

    Science.gov (United States)

    Mun, Seulgi; Noh, Mi Young; Osanai-Futahashi, Mizuko; Muthukrishnan, Subbaratnam; Kramer, Karl J; Arakane, Yasuyuki

    2014-06-01

    Insect cuticle pigmentation and sclerotization (tanning) are vital physiological processes for insect growth, development and survival. We have previously identified several colorless precursor molecules as well as enzymes involved in their biosynthesis and processing to yield the mature intensely colored body cuticle pigments. A recent study indicated that the Bombyx mori (silkmoth) gene, BmMucK, which encodes a protein orthologous to a Culex pipiens quiquefasciatus (Southern house mosquito) cis,cis, muconate transporter, is a member of the "Major Facilitator Superfamily" (MFS) of transporter proteins and is associated with the appearance of pigmented body segments of naturally occurring body color mutants of B. mori. While RNA interference of the BmMucK gene failed to result in any observable phenotype, RNAi using a dsRNA for an orthologous gene from the red flour beetle, Tribolium castaneum, was reported to result in molting defects and darkening of the cuticle and some body parts, leading to the suggestion that orthologs of MucK genes may differ in their functions among insects. To verify the role and essentiality of the ortholog of this gene in development and body pigmentation function in T. castaneum we obtained cDNAs for the orthologous gene (TcMucK) from RNA isolated from the GA-1 wild-type strain of T. castaneum. The sequence of a 1524 nucleotides-long cDNA for TcMucK which encodes the putatively full-length protein, was assembled from two overlapping RT-PCR fragments and the expression profile of this gene during development was analyzed by real-time PCR. This cDNA encodes a 55.8 kDa protein consisting of 507 amino acid residues and includes 11 putative transmembrane segments. Transcripts of TcMucK were detected throughout all of the developmental stages analyzed. The function of this gene was explored by injection of two different double-stranded RNAs targeting different regions of the TcMucK gene (dsTcMucKs) into young larvae to down

  1. Meta-analysis: Association of Helicobacter pylori infection with Parkinson's diseases.

    Science.gov (United States)

    Shen, Xiaoli; Yang, Huazhen; Wu, Yili; Zhang, Dongfeng; Jiang, Hong

    2017-10-01

    The results from observational studies on the relationship between helicobacter pylori (H. pylori) infection and Parkinson's disease remain controversial. A meta-analysis was conducted to evaluate the association between helicobacter pylori infection and Parkinson's disease. A comprehensive literature search was performed on relevant studies published from January 1983 to January 2017 in PubMed, Web of Science and EMBASE databases. The fixed or random effects model was used to pool the odds ratio with 95% confidence interval from individual studies. Publication bias was estimated by Egger's test and the funnel plot. Eight eligible studies involving 33 125 participants were included in this meta-analysis. Compared with the no helicobacter pylori infected person, the pooled odds ratio of Parkinson's disease in helicobacter pylori infected person was 1.59 (95% confidence interval: 1.37-1.85). In subgroup analyzes, the combined odds ratios were 1.96 (1.23-3.12) in Asia, 1.55 (1.32-1.82) in Europe, 1.59 (1.35-1.88) in case-control studies, 1.56 (1.01-2.39) in cross-sectional studies, 1.56 (1.32-1.85) in studies with confounders adjusted, and 1.71 (1.21-2.43) in studies with no confounder adjusted, respectively. This meta-analysis indicated that H. pylori infection might be associated with the risk of Parkinson's disease. © 2017 John Wiley & Sons Ltd.

  2. Dioscin and methylprotodioscin isolated from the root of Asparagus cochinchinensis suppressed the gene expression and production of airway MUC5AC mucin induced by phorbol ester and growth factor.

    Science.gov (United States)

    Lee, Hyun Jae; Park, Jin Sung; Yoon, Yong Pill; Shin, Ye Jin; Lee, Sang Kook; Kim, Yeong Shik; Hong, Jang-Hee; Son, Kun Ho; Lee, Choong Jae

    2015-05-15

    The root of Asparagus cochinchinensis (Lour.) Merr. has been utilized as mucoregulators and expectorants for controlling the airway inflammatory diseases in folk medicine. We investigated whether dioscin and methylprotodioscin isolated from the root of Asparagus cochinchinensis (Lour.) Merr. suppress the gene expression and production of airway MUC5AC mucin induced by phorbol ester and growth factor. Confluent NCI-H292 cells were pretreated with dioscin or methylprotodioscin for 30 min and then stimulated with EGF or PMA for 24 h. The MUC5AC mucin gene expression was measured by RT-PCR. Production of MUC5AC mucin protein was measured by ELISA. (1) Dioscin and methylprotodioscin suppressed the expression of MUC5AC mucin gene induced by EGF or PMA; (2) dioscin suppressed the production of MUC5AC mucin induced by either EGF at 10(-5) M (p Asparagus cochinchinensis suppress the gene expression and production of MUC5AC mucin, by directly acting on airway epithelial cells, and the results are consistent with the traditional use of Asparagus cochinchinensis as remedy for diverse inflammatory pulmonary diseases. Copyright © 2015 Elsevier GmbH. All rights reserved.

  3. Human milk blocks DC-SIGN - pathogen interaction via MUC1

    Directory of Open Access Journals (Sweden)

    Nathalie eKoning

    2015-03-01

    Full Text Available Beneficial effects of breastfeeding are well-recognized and include both immediate neonatal protection against pathogens, as well as long term protection against allergies and autoimmune diseases. Although several proteins have been identified to have anti-viral or anti-bacterial effects like secretory IgA or lactoferrin, the mechanisms of immune modulation are not fully understood. Recent studies identified important beneficial effects of glycans in human milk, such as those expressed in oligosaccharides or on glycoproteins. Glycans are recognized by the carbohydrate receptors C-type lectins on DC and specific tissue macrophages, which exert important functions in immune modulation and immune homeostasis. A well-characterized C-type lectin is DC-SIGN, which binds terminal fucose. The present study shows that in human milk, MUC1 is the major milk glycoprotein that binds to the lectin domain of DC-SIGN and prevents pathogen interaction through the presence of Lewis x-type oligosaccharides. Surprisingly, this was specific for human milk, as formula, bovine or camel milk did not show any presence of proteins that interacted with DC-SIGN. The expression of DC-SIGN is found in young infants along the entire gastro-intestinal tract. Our data thus suggest the importance of human milk glycoproteins for blocking pathogen interaction to DC in young children. Moreover, a potential benefit of human milk later in life in shaping the infants immune system through DC-SIGN cannot be ruled out.

  4. KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts

    International Nuclear Information System (INIS)

    Ohshimo, Shinichiro; Yokoyama, Akihito; Hattori, Noboru; Ishikawa, Nobuhisa; Hirasawa, Yutaka; Kohno, Nobuoki

    2005-01-01

    The serum level of KL-6, a MUC1 mucin, is a clinically useful marker for various interstitial lung diseases. Previous studies demonstrated that KL-6 promotes chemotaxis of human fibroblasts. However, the pathophysiological role of KL-6 remains poorly understood. Here, we further investigate the functional aspects of KL-6 in proliferation and apoptosis of lung fibroblasts. KL-6 accelerated the proliferation and inhibited the apoptosis of all human lung fibroblasts examined. An anti-KL-6 monoclonal antibody counteracted both of these effects induced by KL-6 on human lung fibroblasts. The pro-fibroproliferative and anti-apoptotic effects of KL-6 are greater than and additive to those of the maximum effective concentrations of platelet-derived growth factor, basic fibroblast growth factor, and transforming growth factor-β. These findings indicate that increased levels of KL-6 in the epithelial lining fluid may stimulate fibrotic processes in interstitial lung diseases and raise the possibility of applying an anti-KL-6 antibody to treat interstitial lung diseases

  5. Gastritis crónica antral por Helicobacter pylori en la infancia Chronic antral gastritis induced by Helicobacter pylori in children

    Directory of Open Access Journals (Sweden)

    Martha M. Gámez Escalona

    2008-03-01

    Full Text Available INTRODUCCIÓN. La investigación tiene como objetivos conocer la frecuencia de infección por Helicobacter pylori en los niños con gastritis crónica antral, estimar las diferencias en el comportamiento histológico de esta entidad en los niños con infección por Helicobacter pylori y sin ella, e identificar la posible relación entre la edad y las características histológicas de la gastritis crónica antral por Helicobacter pylori. MÉTODO. Se tomó como universo de estudio la totalidad de biopsias gástricas procesadas en el Hospital Pediátrico Provincial de Holguín, entre enero de 1991 y diciembre del 2004. Se determinó una muestra de 192 niños con diagnóstico histológico de gastritis crónica antral. Las biopsias fueron reevaluadas para detectar infección por Helicobacter pylori y su densidad de colonización junto a la actividad y la gravedad de las lesiones de la gastritis. RESULTADOS. Se encontró infección por Helicobacter pylori en el 67,7 % de los pacientes. Las formas activas predominaron en los casos con infección por Helicobacter pylori (116/130 a diferencia de quienes no tenían infección (5/62. Se identificó una relación estadísticamente significativa (p INTRODUCTION. The objective of this investigation is to know the frequency of infection caused by Helicobacter pylori in children with chronic antral gastritis, to estimate the differences in the histological behavior of this entity in children with infection due to Helicobacter pylori and without it, and to identify the possible relation existing between age and the histgological characteristics of chronic antral gastritis caused by Helicobacter pylori. METHODS. All the gastric biopsies processed in the Provincial Pediatric Hospital of Holguin from January 1991 to December 2004 were included in the study group. A sample of 192 children with histological diagnosis of chronic antral gastritis was determined. The biopsies were reevaluated to detect Helicobacter

  6. Invasive micropapillary carcinoma of the breast overexpresses MUC4 and is associated with poor outcome to adjuvant trastuzumab in HER2-positive breast cancer.

    Science.gov (United States)

    Mercogliano, María F; Inurrigarro, Gloria; De Martino, Mara; Venturutti, Leandro; Rivas, Martín A; Cordo-Russo, Rosalía; Proietti, Cecilia J; Fernández, Elmer A; Frahm, Isabel; Barchuk, Sabrina; Allemand, Daniel H; Figurelli, Silvina; Deza, Ernesto Gil; Ares, Sandra; Gercovich, Felipe G; Cortese, Eduardo; Amasino, Matías; Guzmán, Pablo; Roa, Juan C; Elizalde, Patricia V; Schillaci, Roxana

    2017-12-28

    Invasive micropapillary carcinoma of the breast (IMPC) is a histological tumor variant that occurs with low frequency characterized by an inside-out formation of tumor clusters with a pseudopapillary arrangement. IMPC is an aggressive tumor with poor clinical outcome. In addition, this histological subtype usually expresses human epidermal growth factor receptor 2 (HER2) which also correlates with a more aggressive tumor. In this work we studied the clinical significance of IMPC in HER2-positive breast cancer patients treated with adjuvant trastuzumab. We also analyzed mucin 4 (MUC4) expression as a novel biomarker to identify IMPC. We retrospectively studied 86 HER2-positive breast cancer patients treated with trastuzumab and chemotherapy in the adjuvant setting. We explored the association of the IMPC component with clinicopathological parameters at diagnosis and its prognostic value. We compared MUC4 expression in IMPC with respect to other histological breast cancer subtypes by immunohistochemistry. IMPC, either as a pure entity or associated with invasive ductal carcinoma (IDC), was present in 18.6% of HER2-positive cases. It was positively correlated with estrogen receptor expression and tumor size and inversely correlated with patient's age. Disease-free survival was significantly lower in patients with IMPC (hazard ratio = 2.6; 95%, confidence interval 1.1-6.1, P = 0.0340). MUC4, a glycoprotein associated with metastasis, was strongly expressed in all IMPC cases tested. IMPC appeared as the histological breast cancer subtype with the highest MUC4 expression compared to IDC, lobular and mucinous carcinoma. In HER2-positive breast cancer, the presence of IMPC should be carefully examined. As it is often not informed, because it is relatively difficult to identify or altogether overlooked, we propose MUC4 expression as a useful biomarker to highlight IMPC presence. Patients with MUC4-positive tumors with IMPC component should be more frequently

  7. Schistosoma mansoni mucin gene (SmPoMuc expression: epigenetic control to shape adaptation to a new host.

    Directory of Open Access Journals (Sweden)

    Cecile Perrin

    Full Text Available The digenetic trematode Schistosoma mansoni is a human parasite that uses the mollusc Biomphalaria glabrata as intermediate host. Specific S. mansoni strains can infect efficiently only certain B. glabrata strains (compatible strain while others are incompatible. Strain-specific differences in transcription of a conserved family of polymorphic mucins (SmPoMucs in S. mansoni are the principle determinants for this compatibility. In the present study, we investigated the bases of the control of SmPoMuc expression that evolved to evade B. glabrata diversified antigen recognition molecules. We compared the DNA sequences and chromatin structure of SmPoMuc promoters of two S. mansoni strains that are either compatible (C or incompatible (IC with a reference snail host. We reveal that although sequence differences are observed between active promoter regions of SmPoMuc genes, the sequences of the promoters are not diverse and are conserved between IC and C strains, suggesting that genetics alone cannot explain the evolution of compatibility polymorphism. In contrast, promoters carry epigenetic marks that are significantly different between the C and IC strains. Moreover, we show that modifications of the structure of the chromatin of the parasite modify transcription of SmPoMuc in the IC strain compared to the C strain and correlate with the presence of additional combinations of SmPoMuc transcripts only observed in the IC phenotype. Our results indicate that transcription polymorphism of a gene family that is responsible for an important adaptive trait of the parasite is epigenetically encoded. These strain-specific epigenetic marks are heritable, but can change while the underlying genetic information remains stable. This suggests that epigenetic changes may be important for the early steps in the adaptation of pathogens to new hosts, and might be an initial step in adaptive evolution in general.

  8. Characteristics of Helicobacter pylori-positive and Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma and their influence on clinical outcome.

    Science.gov (United States)

    Choi, Yoon Jin; Kim, Nayoung; Paik, Jin Ho; Kim, Jung Mogg; Lee, Sang Hyub; Park, Young Soo; Hwang, Jin-Hyeok; Kim, Jin-Wook; Jeong, Sook-Hyang; Lee, Dong Ho; Jung, Hyun Chae

    2013-06-01

    To compare clinicopathologic and molecular characteristics of low-grade gastric mucosa-associated lymphoid tissue lymphoma depending on Helicobacter pylori positivity and to find out a predictive factor for unresponsiveness to Helicobacter pylori eradication therapy in Korea. A total of 53 Helicobacter pylori-positive and 13 negative mucosa-associated lymphoid tissue lymphoma patients were enrolled, and tissues from 21 patients were investigated to examine the presence of t(11;18)(q21;q21) with fluorescence in situ hybridization. Clinicopathologic features such as the endoscopic appearance, dominant site of lesion, depth of invasion, clinical stage, and the existence of MALT1 gene rearrangement were compared between these two groups. Fifty-six patients who underwent H. pylori eradication therapy were divided into responder and nonresponder groups. The two groups were analyzed to calculate odds ratios for resistance to the eradication. Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma patients averaged a more advanced clinical stage than H. pylori-positive (p = .023) patients. The frequency of t(11;18)/API2-MALT1 did not differ between H. pylori-positive (45.5%) and H. pylori-negative cases (55.6%). Thirty-eight of 51 (74.5%) H. pylori-positive patients achieved complete regression after the eradication, while 2 of 5 (40%) H. pylori-negative patients obtained regression. Presence of lesions in both distal and proximal parts of stomach (p = .041) and bearing of t(11;18)(q21;q21) (p = .007) were predictors for nonresponsiveness for H. pylori eradication. Helicobacter pylori eradication could be performed as a primary therapy regardless of H. pylori status, and assessing t(11;18)/API2-MALT1 would be considered after failure to remission by H. pylori eradication. © 2013 John Wiley & Sons Ltd.

  9. Expression of Mucin-1 in multiple myeloma and its precursors

    DEFF Research Database (Denmark)

    Andrulis, Mindaugas; Ellert, Elena; Mandel, Ulla

    2014-01-01

    AIMS: Recent reports suggest a possible role for extracellular (MUC1N) and transmembrane (MUC1C) subunits of Mucin 1 (MUC1) in the pathogenesis of multiple myeloma (MM). Nuclear translocation of MUC1C is involved in activation of various oncogenic signalling pathways and both MUC1 subunits...

  10. Helicobacter

    DEFF Research Database (Denmark)

    Robinson, Karen; Kaneko, Kazuyo; Andersen, Leif Percival

    2017-01-01

    Helicobacter pylori is usually acquired in early childhood and the infection persists lifelong without causing symptoms. In a small of cases, the infection leads to gastric or duodenal ulcer disease, or gastric cancer. Why disease occurs in these individuals remains unclear, however the host resp...

  11. Helicobacter pylori : the causative agent of peptic ulcer ...

    African Journals Online (AJOL)

    This review examines Helicobacter pylori as an organism and as the causative agent of peptic ulcers. The review also examined the classification of ulcers, ... Elimination of Helicobacter pylori by treatment with antibiotics in peptic ulcer patients resulted in the healing of the ulcer. Prevention of Helicobacter pylori infections is ...

  12. Prevalence of Coinfection with Gastric Non-Helicobacter pylori Helicobacter (NHPH) Species in Helicobacter pylori-infected Patients Suffering from Gastric Disease in Beijing, China.

    Science.gov (United States)

    Liu, Jie; He, Lihua; Haesebrouck, Freddy; Gong, Yanan; Flahou, Bram; Cao, Qizhi; Zhang, Jianzhong

    2015-08-01

    The Helicobacter heilmannii sensu lato (H. heilmannii s.l.) group consists of long, spiral-shaped bacteria naturally colonizing the stomach of animals. Moreover, bacteria belonging to this group have been observed in 0.2-6% of human gastric biopsy specimens, and associations have been made with the development of chronic gastritis, peptic ulceration, and gastric MALT lymphoma in humans. To gain insight into the prevalence of H. heilmannii s.l. infections in patients suffering from gastric disease in China, H. heilmannii s.l. species-specific PCRs were performed on DNA extracts from rapid urease test (RUT)-positive gastric biopsies from 1517 patients followed by nucleotide sequencing. At the same time, Helicobacter pylori cultivation and specific PCR was performed to assess H. pylori infection in these patients. In total, H. heilmannii s.l. infection was detected in 11.87% (178/1499) of H. pylori-positive patients. The prevalence of H. suis, H. felis, H. bizzozeronii, H. heilmannii sensu stricto (s.s.), and H. salomonis in the patients was 6.94%, 2.20%, 0.13%, 0.07%, and 2.54%, respectively. Results revealed that all patients with H. heilmannii s.l. infection were co-infected with H. pylori, and some patients were co-infected with more than two different Helicobacter species. Helicobacter heilmannii s.l. infections are fairly common in Chinese patients. This should be kept in mind when diagnosing the cause of gastric pathologies in patients. Helicobacter suis was shown to be by far the most prevalent H. heilmannii s.l.species. © 2014 John Wiley & Sons Ltd.

  13. Relation between Helicobacter pylori infection and chronic urticaria

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    Adianez Sugrañes-Montalván

    2017-12-01

    Conclusions: In the present study, the relationship between chronic urticaria and Helicobacter pylori infection was demonstrated. Apparently, the eradicating treatment for Helicobacter pylori was effective as the patients had no symptoms after treatment. Specific immunoglobulin G and Urease Test together constitute a suitable diagnostic module for the diagnosis of Helicobacter pylori conditions.

  14. Extragastric Helicobacter species

    DEFF Research Database (Denmark)

    On, Stephen L.W.; Hynes, S.; Wadstrom, T.

    2002-01-01

    The genus Helicobacter has expanded at a rapid pace and no fewer than 31 species have been named since the proposal of the genus in 1989. Of these 31 species, 22 are principally associated with extragastric niches and there is increasing interest in the role of these taxa in diseases of humans...... and animals. Substantial evidence attests to certain species playing a role in the pathogenesis of enteric, hepatic and biliary disorders and some taxa demonstrate zoonotic potential. The importance of extragastric Helicobacters is likely to be an important topic for research in the near future. Here...

  15. Characterization of carbohydrate structures of bovine MUC15 and distribution of the mucin in bovine milk

    DEFF Research Database (Denmark)

    Pallesen, Lone Tjener; Pedersen, Lise Refstrup Linnebjerg; Petersen, Torben Ellebæk

    2007-01-01

    -containing fractions as well, such as skim milk and whey. Compositional and structural studies of the carbohydrates of bovine milk MUC15 showed that the glycans are composed of fucose, galactose, mannose, N-acetylgalactosamine, N-acetylglycosamine, and sialic acid. The carbohydrate was shown to constitute 65......% of the total molecular weight, and the molar ratios of the individual sugars to protein of the O-linked glycans were determined. The glycan structures of MUC15 were further studied by enzymatic deglycosylation experiments using different endo- and exoglycosidases as well as a panel of lectins. The N......-linked glycans. By comparing the results of peanut agglutinin lectin binding, enzymatic deglycosylation, and monosaccharide composition analysis, we concluded that bovine MUC15 also contains more complex O-glycans containing high amounts N-acetylglucosamine residues. Furthermore, a small subset of the O...

  16. II Consenso Brasileiro sobre Helicobacter pylori Second Brazilian Consensus Conference on Helicobacter pylori infection

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    Luiz Gonzaga Vaz Coelho

    2005-06-01

    Full Text Available Avanços significativos ocorridos desde o Primeiro Consenso Brasileiro sobre H. pylori realizado em 1995, em Belo Horizonte, MG, justificam este segundo consenso. O evento foi organizado pela Federação Brasileira de Gastroenterologia e pelo Núcleo Brasileiro para Estudo do Helicobacter, sendo realizado em São Paulo nos dias 19 e 20 de junho de 2004. Contou com a participação das principais autoridades nacionais na área, a partir de lista elaborada pelas duas sociedades organizadoras do evento. Assim, participaram 36 delegados provenientes de 15 estados brasileiros, incluindo gastroenterologistas, patologistas, pediatras e microbiologistas. Os participantes foram alocados em um dos cinco sub-temas a serem contemplados no encontro, a saber: Helicobacter pylori e dispepsia funcional; Helicobacter pylori e AINEs; Helicobacter pylori e doença do refluxo gastroesofágico; tratamento Helicobacter pylori e retratamento Helicobacter pylori. Foi adotado como consensual as decisões que atingissem 70% ou mais de concordância entre os participantes. Os resultados foram apresentados em outubro de 2004 durante sessão especial da VI Semana Brasileira do Aparelho Digestivo, realizada em Recife, PE, e esta publicação apresenta o sumário das principais recomendações e conclusões do evento.Significant progress has been obtained since the First Brazilian Consensus Conference on H. pylori Infection held in 1995, in Belo Horizonte, MG, and justify a second meeting to establish updated guidelines on the current management of H. pylori infection. The Second Brazilian Consensus Conference on H. pylori Infection was organized by the Brazilian Federation of Gastroenterology and Brazilian Nucleus for the Study of Helicobacter and took place on June, 19-20, 2004 in São Paulo, SP. Thirty six delegates coming from 15 different Brazilian states including gastroenterologists, pathologists, microbiologists and pediatricians undertook the meeting. The

  17. The relationship between helicobacter pylori infection and gastro-esophageal reflux disease.

    Science.gov (United States)

    Mahdi, Batool M

    2011-03-01

    Gastro-esophageal reflux disease is a common condition, affecting 25%-40% of the population. Increasing attention has been paid to the relationship between Helicobacter pylori infection and reflux esophagitis. The aim of this study was to investigate the association between CagA+ H. pylori and endoscopically proven gastro-esophageal reflux disease. The study group included 60 hospital patients with gastro-esophageal reflux disease between 2007 and 2009 as compared with 30 healthy patients from a control group that was age and sex matched. Helicobacter pylori CagA+ was identified by an immunological test (Immunochromatography test) (ACON, USA). Helicobacter pyloriCagA+ was present in 42/60 (70%) of the patients with gastro-esophageal reflux disease and in 11/30 (36.6%) patients in the control group (p=0.002). The Odds ratio = 0.8004 with 95% Confidence Interval = from 0.3188 to 2.0094. The relative risk=1.35 that indicates an association between Helicobacter pylori and disease. The presence of Helicobacter pylori is significantly increased in patients with gastro-esophageal reflux disease as compared with the control group.

  18. EKSPRESI ANTI-HELICOBACTER PYLORI PADA GASTRITIS KRONIS, LESI PRAKANKER, DAN KARSINOMA GASTER

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    Lina Damayanti

    2015-08-01

    Full Text Available Prevalence of Helicobacter pylori infection in Indonesia was 36-46%. In Jakarta and Surabaya, the prevalence were 85,7%-93,9%. Helicobacter pylori infection play role in pathogenesis of pectic ulcers, chronic gastritis, carcinoma of gaster and gastric lymphoma. Epidemiologic study showed 80% of carcinoma of gaster related with H pylori infection.This study analyzed expression of anti-Helicobacter pylori in chronic gastritis, precancer lesion , and carcinoma of gaster. This study was a observational descriptive study with case control design. Thirty (30 samples from paraffin bloc that were diagnosed with chronic gastritis, precancer lesion, and carcinoma of gaster at Dokter Kariadi hospital in 2013 was stained by hematoxylin eosin, giemsa and immunohistochemistry of anti-helicobacter pylori. Data was analyzed by descriptive analysis. Thirty (30 samples were diagnosed as gastritis chronis 13 (43,3% , pra cancer lesion(36.6%, and carcinoma(20.1%. Chronic gastritis can be occurred at all age and no distinct difference on sex, while gastric carcinoma predominant in male older than 40 years. Expresion of Helicobacter pylori on chronic gastritis was 84.6%, precancer lesion was 54.5%, and gastric carcinoma was 83.3%. The Giemsa stain gave 23.3% false positive and 20% false negative. Helicobacter pylori expression can be showed in chronic gastritis, precancer lesion, and gastric carcinoma. Keywords: Chronic gastritis, gastric carcinoma, Helicobacter pylori

  19. Efecto de la impermeabilidad del Mucílago de Nopal en bloques de tierra comprimidos

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    Yolanda Guadalupe Aranda Jiménez

    2013-01-01

    Full Text Available La arquitectura de tierra1 es conocida desde hace siglos, sin embargo, actualmente es poco utilizada comparado con los sistemas constructivos comunes. Los bloques de tierra comprimido (BTC son elementos constructivos con un potencial elevado para ser utilizado en las construcciones de vivienda en México, principalmente por su similitud con los bloques tradicionales, siendo conveniente mejorar sus características a partir de un estabilizante. Se realizó el estudio de BTC estabilizados con cemento y una sustancia proveniente de las pencas maduras de nopal. Se encontró que al añadir mucílago de nopal se observa un incremento significativo de la resistencia a la compresión húmeda y seca, lo cual estar relacionado con una disminución de la porosidad; se ofrecen algunas relaciones del efecto del mucílago en el sólido analizado.

  20. Immunohistochemical testing for Helicobacter Pylori existence in neoplasms of the colon

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    Yasar Nurgul

    2008-08-01

    Full Text Available Abstract Background Helicobacter pylori is a common pathogen, and its prevalence varies with socioeconomic conditions (10–80%. It has recently been recognized as a class I carcinogen in relation to gastric cancer. The aim of this study was to investigate the presence of Helicobacter pylori in neoplasms of the colon by immunohistochemical methods. Methods The polypectomy materials of 51 patients (19 male and 32 female who had undergone colonoscopic polypectomy were retrieved for retrospective examination. The endoscopic size and colonic localization of the polyps were recorded. Hematoxylin and eosin stains were evaluated according to histological type and grade of dysplasia. Biopsy stains were immunohistochemically treated with Helicobacter pylori antibodies by the streptavidine-biotin immunoperoxidase technique. Helicobacter pylori staining in the gastric mucosa was used as the control for the immunohistochemical method. Specimens were classified according to the presence of Helicobacter pylori under an optical microscope, and Helicobacter pylori positive specimens were stratified according to the respective staining pattern. Results Mean age was 61.88 ± 10.62 (40–82 years. Polyp sizes were 1.45 ± 0.92 (1–4 cm; and 25.5% of polyps were localized in the right colon, 68.6% in the left colon and 5.9% in the transverse colon. Presence of Helicobacter pylori was not correlated with localization (p > 0.05 or size of the polyps (p > 0.05. Eleven (21.6% of all specimens included in the study were Helicobacter pylori positive by immunohistochemical methods. Of the Helicobacter pylori positive specimens, the staining pattern was diffuse: Equivocal in 90.9%, nonspecific with a finely granular type concentrated on the luminal surface in 90.9%, dot-like granular in 54.5%, and spiral in 9.1%. Of the tubular polyps, 17.9% were H. pylori positive, and the staining pattern was equivocal in 100%, luminal in 85.7%, and dot-like granular in 57.1%. Of the

  1. Urease from Helicobacter pylori is inactivated by sulforaphane and other isothiocyanates

    Science.gov (United States)

    Fahey, Jed W.; Stephenson, Katherine K.; Wade, Kristina L.; Talalay, Paul

    2013-01-01

    Infections by Helicobacter pylori are very common, causing gastroduodenal inflammation including peptic ulcers, and increasing the risk of gastric neoplasia. The isothiocyanate (ITC) sulforaphane [SF; 1-isothiocyanato-4-(methylsulfinyl)butane] derived from edible crucifers such as broccoli is potently bactericidal against Helicobacter, including antibiotic-resistant strains, suggesting a possible dietary therapy. Gastric H. pylori infections express high urease activity which generates ammonia, neutralizes gastric acidity, and promotes inflammation. The finding that SF inhibits (inactivates) urease (jack bean and Helicobacter) raised the issue of whether these properties might be functionally related. The rates of inactivation of urease activity depend on enzyme and SF concentrations and show first order kinetics. Treatment with SF results in time-dependent increases in the ultraviolet absorption of partially purified Helicobacter urease in the 280–340 nm region. This provides direct spectroscopic evidence for the formation of dithiocarbamates between the ITC group of SF and cysteine thiols of urease. The potencies of inactivation of Helicobacter urease by isothiocyanates structurally related to SF were surprisingly variable. Natural isothiocyanates closely related to SF, previously shown to be bactericidal (berteroin, hirsutin, phenethyl isothiocyanate, alyssin, and erucin), did not inactivate urease activity. Furthermore, SF is bactericidal against both urease positive and negative H. pylori strains. In contrast, some isothiocyanates such as benzoyl-ITC, are very potent urease inactivators, but are not bactericidal. The bactericidal effects of SF and other ITC against Helicobacter are therefore not obligatorily linked to urease inactivation, but may reduce the inflammatory component of Helicobacter infections. PMID:23583386

  2. Ursodeoxycholic acid does not interfere with in vivo Helicobacter pylori colonization

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    Silva José Guilherme Nogueira da

    2000-01-01

    Full Text Available A low frequency of Helicobacter pylori in the gastric mucosa of patients with alkaline gastritis has been reported. At the same time, it can be noted that the growth of bacteria can be inhibited by bile acids. We studied 40 patients with chronic gastritis related to Helicobacter pylori in order to determine the effect of ursodeoxycholic acid on this infection. Diagnoses of the infection and the inflammatory process were obtained by histologic study of gastric biopsies collected during endoscopy. Two groups were studied: group I received ursodeoxycholic acid - 300 mg/day, and group II received the placebo, twice a day, both for 28 days. The colonization by Helicobacter pylori and the intensity of the mononuclear and polymorphonuclear inflammatory infiltrate were determined before (time 1 and after (time 2 treatment. Ursodeoxycholic acid had no effect on the Helicobacter pylori infection. A significant reduction in the intensity of the mononuclear inflammatory infiltrate of the gastric antrum mucosa was observed in patients from group I, when we compared not only times 1 and 2 but also groups I and II. However, this was not the case with the body mucosa. We concluded that ursodeoxycholic acid had no action on the colonization by Helicobacter pylori or on the polymorphonuclear inflammatory infiltrate, but it caused a significant reduction in the intensity of the mononuclear inflammatory infiltrate of the gastric antrum.

  3. Management of Helicobacter Pylori Infection

    African Journals Online (AJOL)

    Dr Olaleye

    90%, the sequential therapy seems to have a potential of becoming the standard first-line treatment for H pylori infection in the interim, while search is being made for the ideal antimicrobial monotherapy. . Keywords: Helicobacter pylori, Dyspepsia, Gastric cancer, Gastric Ulcer, Duodenal ulcer. INTRODUCTION. 1. Since the ...

  4. Helicobacter pylori infection in patients with dyspeptic symptoms having normal endoscopy

    International Nuclear Information System (INIS)

    Malik, M.F.; Hussain, T.; Khan, M.N.; Mirza, S.A.

    2010-01-01

    To find out the frequency of Helicobacter pylori infection in the local population presenting with dyspeptic symptoms but having normal upper gastrointestinal endoscopic findings. Hundred cases of dyspepsia having normal upper gastrointestinal endoscopy were taken as study population. Although the gold standard for presence or absence of Helicobacter pylori infection is culture but in this study the diagnostic method used was histopathology of gastric antrum. The male and female ratio was 2:1. Majority of the patients were either 40 years of age or less, mean age being 40.52 (sd+-13.22). The chief symptoms were pain epigastrium (46%) and upper abdominal discomfort (27%). Helicobacter pylori gastritis was found in 51% of cases. We conclude that Helicobacter pylori infection is quite common in dyspeptic patients apparently having normal endoscopic gastric mucosal findings. Eradication therapy should be instituted in positive cases to avoid its long-term complications. (author)

  5. Survey of Helicobacter infection in domestic and feral cats in Korea.

    Science.gov (United States)

    Ghil, Heh-Myung; Yoo, Jong-Hyeon; Jung, Woo-Sung; Chung, Tae-Ho; Youn, Hwa-Young; Hwang, Cheol-Yong

    2009-03-01

    Discovery of Helicobacter (H.) pylori has led to a fundamental change in our understanding of gastric diseases in humans. Previous studies have found various Helicobacter spp. in dogs and cats, and pets have been questioned as a zoonotic carrier. The present study surveyed the Helicobacter infections and investigated the presence of H. felis and H. pylori infections in domestic and feral cats in Korea. Sixty-four domestic cats and 101 feral cats were selected from an animal shelter. Saliva and feces were evaluated by Helicobacter genus-specific polymerase chain reaction (PCR). Genus-specific PCR positive samples were further evaluated for H. felis and H. pylori using specific primer pairs. Thirty-six of 64 (56.3%) samples from domestic cats and 92 of 101 (91.1%) samples from feral cats were PCR positive; the positive rate of feces samples was higher than that of saliva samples in both groups. H. felis and H. pylori species-specific PCR was uniformly negative. The prevalence of Helicobacter spp. in feral cats was approximately two-fold higher than that of domestic cats. The fecal-oral route may be more a common transmission route not only between cats but also in humans.

  6. Inflammation, immunity, and vaccines for Helicobacter pylori

    DEFF Research Database (Denmark)

    D'Elios, Mario M; Andersen, Leif P

    2009-01-01

    Helicobacter pylori infects almost half of the population worldwide and represents the major cause of gastroduodenal diseases, such as duodenal and gastric ulcer, gastric adenocarcinoma, autoimmune gastritis, and B-cell lymphoma of mucosa-associated lymphoid tissue. Helicobacter pylori induces...

  7. HELICOBACTER PYLORI

    Science.gov (United States)

    Helicobacter pylori is a pathogenic bacteria which inhabits the human stomach and upper gastrointestinal tract. This encyclopedic entry summarizes the potential role of this organism as a waterborne pathogen. Information is provided on the physiology and morphology of this bacter...

  8. Assessment of PCR-DGGE for the identification of diverse Helicobacter species, and application to faecal samples from zoo animals to determine Helicobacter prevalence

    DEFF Research Database (Denmark)

    Abu Al-Soud, W.; Bennedsen, M.; On, Stephen L.W.

    2003-01-01

    bilis and Helicobacter hepaticus in a Nile crocodile, Helicobacter cinaedi in a baboon and a red panda, and Helicobacter felis in a wolf and a Taiwan beauty snake. All of these PCR products (similar to400 bp) showed 100 % sequence similarity to 16S rDNA sequences of the mentioned species. These results...

  9. Helicobacter pylori colonization in infants and its relation to childhood morbidity

    International Nuclear Information System (INIS)

    Nizami, S.Q.; Bhutta, Z.A.; Weaver, L.

    2000-01-01

    Helicobacter pylori infection is universally reported from all over the world including both developed and developing countries. The prevalence of Helicobacter pylori infection in Pakistan is unknown. Although a few studies have been done in adults, there are no studies looking at the prevalence of Helicobacter pylori colonization especially in children. In addition, a number of symptoms such as nonspecific abdominal pain, diarrhea and malnutrition etc. are attributed to it though most cases of Helicobacter pylori colonization remain asymptomatic. The association between Helicobacter pylori and gastrointestinal symptoms however, remains controversial. Hence in order to determine the prevalence of Helicobacter pylori infection, its time of acquisition and to look at its correlation with diarrhea-associated morbidity, we proposed to do the present study. In this study we will look for the evidence of Helicobacter colonization in infants with the non-invasive techniques using 13 C urea breath test and stool ELISA for Helicobacter pylori every at three month interval in a cohort of infants from a periurban community in Karachi Pakistan. (author)

  10. Prospective study on effect of Helicobacter pylori on gastroesophageal reflux disease

    Directory of Open Access Journals (Sweden)

    Sabah Jalal Shareef

    2017-08-01

    Full Text Available Background and objective: The Helicobacter pylori infections role in etiology of peptic ulcer is well known, but its role in gastroesophageal reflux disease is one of the important issues which has to be confirmed. We tried to find out the effect of Helicobacter pylori infection on gastroesophageal reflux disease. Methods: The current study was done on 100 patients with gastroesophageal reflux disease from January 1st to June 30th, 2014 in Rizgary Teaching Hospital, Erbil city. The diagnosis was made by history, clinical examination, and endoscopy. Helicobacter pylori infection was confirmed by gastric biopsy and histopathological examination. We tried to find out the effects of Helicobacter pylori infection in gastroesophageal reflux disease patients and its eradication on their symptoms. The data was analyzed with the statistical package for the social sciences (version 18. Results: The mean age ± SD of participants was 37.13 ± 12.5 (17-75 years. The prevalence of Helicobacter pylori infection was 75%. The endoscopy showed that 50 out of 75 patients had erosive esophagitis and 25 out of 75 patients had normal appearance known as non-erosive esophagitis. The study showed no significance of its eradication on symptoms of gastroesophageal reflux disease. Conclusion: The effect of Helicobacter pylori infection in gastroesophageal reflux disease patients was significant regarding endoscopic finding while inversely related to symptoms severity. The eradication of infection did not cause improvement in symptom severity i.e. triple therapy not advised in the course of treatment.

  11. Analysis of porcine MUC4 gene as a candidate gene for prolificacy QTL on SSC13 in an Iberian × Meishan F2 population

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    Balcells Ingrid

    2011-10-01

    Full Text Available Abstract Background Reproductive traits, such as prolificacy, are of great interest to the pig industry. Better understanding of their genetic architecture should help to increase the efficiency of pig productivity through the implementation of marker assisted selection (MAS programmes. Results The Mucin 4 (MUC4 gene has been evaluated as a candidate gene for a prolificacy QTL described in an Iberian × Meishan (Ib × Me F2 intercross. For association analyses, two previously described SNPs (DQ124298:g.243A>G and DQ124298:g.344A>G were genotyped in 347 pigs from the Ib × Me population. QTL for the number of piglets born alive (NBA and for the total number of piglets born (TNB were confirmed on SSC13 at positions 44 cM and 51 cM, respectively. The MUC4 gene was successfully located within the confidence intervals of both QTL. Only DQ124298:g.344A>G MUC4 polymorphism was significantly associated with both NBA and TNB (P-value MUC4 expression level was determined in F2 sows displaying extreme phenotypes for the number of embryos (NE at 30-32 days of gestation. Differences in the uterine expression of MUC4 were found between high (NE ≥ 13 and low (NE ≤ 11 prolificacy sows. Overall, MUC4 expression in high prolificacy sows was almost two-fold increased compared with low prolificacy sows. Conclusions Our data suggest that MUC4 could play an important role in the establishment of an optimal uterine environment that would increase embryonic survival during pig gestation.

  12. 3rd Brazilian consensus on Helicobacter pylori 3º Consenso Brasileiro para Estudo do Helicobacter pylori

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    Luiz Gonzaga Coelho

    Full Text Available Significant progress has been obtained since the Second Brazilian Consensus Conference on Helicobacter pylori Infection held in 2004, in São Paulo, SP, Brazil, and justify a third meeting to establish updated guidelines on the current management of H. pylori infection. The Third Brazilian Consensus Conference on H pylori Infection was organized by the Brazilian Nucleus for the Study of Helicobacter, a Department of the Brazilian Federation of Gastroenterology and took place on April 12-15, 2011, in Bento Gonçalves, RS, Brazil. Thirty-one delegates coming from the five Brazilian regions and one international guest, including gastroenterologists, pathologists, epidemiologists, and pediatricians undertook the meeting. The participants were allocated in one of the five main topics of the meeting: H pylori, functional dyspepsia and diagnosis; H pylori and gastric cancer; H pylori and other associated disorders; H pylori treatment and retreatment; and, epidemiology of H pylori infection in Brazil. The results of each subgroup were submitted to a final consensus voting to all participants. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Seventy per cent and more votes were considered as acceptance for the final statement. This article presents the main recommendations and conclusions to guide Brazilian doctors involved in the management of H pylori infection.Os avanços significativos ocorridos desde o Segundo Consenso Brasileiro sobre H. pylori realizado em 2004, em São Paulo, justificam este terceiro consenso. O evento foi organizado pelo Núcleo Brasileiro para Estudo do Helicobacter, departamento da Federação Brasileira de Gastroenterologia, tendo sido realizado em Bento Gonçalves, RS, nos dias 12 a 15 de abril de 2011. Contou com a participação de 30 delegados provenientes das cinco regiões brasileiras e um convidado internacional, incluindo gastroenterologistas

  13. MUC2 is the prominent colonic mucin expressed in ulcerative colitis

    NARCIS (Netherlands)

    Tytgat, K. M.; Opdam, F. J.; Einerhand, A. W.; Büller, H. A.; Dekker, J.

    1996-01-01

    BACKGROUND: It has been shown that MUC2 is the prominent mucin synthesised in healthy colon. AIM: To identify the predominant mucins in ulcerative colitis (UC) and to study their biosynthesis. METHODS AND RESULTS: Mucin was purified from UC resection specimens. This mucin on sodium dodecylsulphate

  14. Inhibitory effect of green tea catechins in combination with sucralfate on Helicobacter pylori infection in Mongolian gerbils.

    Science.gov (United States)

    Takabayashi, Fumiyo; Harada, Noboru; Yamada, Masami; Murohisa, Binzaburo; Oguni, Itaro

    2004-01-01

    The occurrence of antibiotic-resistant Helicobacter pylori has been reported. It is desirable to develop an effective method to prevent the occurrence of resistant strains of Helicobacter pylori. Green tea catechins (GTCs) have been reported to have an antibacterial effect. Therefore, the possibility of eradicating Helicobacter pylori by the oral administration of GTCs was investigated. Solutions of GTCs and solutions of GTCs adsorbed to sucralfate (GTC-scf), at concentrations of 20 mg GTCs and/or 20 mg sucralfate/ml were prepared. Then 1 ml of the GTC-scf or the GTC solution was administered daily, for 10 days to Mongolian gerbils infected with Helicobacter pylori. Then the stomachs were extirpated and homogenized. The homogenate was spread on selective medium plates. After 5-day culture, colony-forming units (CFU) of Helicobacter pylori were counted. The CFU of Helicobacter pylori was significantly decreased by GTC-scf. GTC-scf may have a bactericidal effect on Helicobacter pylori infection.

  15. Helicobacter infections with rare bacteria or minimal gastritis: Expecting the unexpected.

    Science.gov (United States)

    Glickman, Jonathan N; Noffsinger, Amy; Nevin, Daniel T; Ray, Mukunda; Lash, Richard H; Genta, Robert M

    2015-07-01

    The routine use of special stains for detection of Helicobacter remains controversial. To determine the frequency of histologically atypical Helicobacter infection. All gastric biopsies received at a large pathology reference laboratory over a 6-month period were stained for Helicobacter, and the histologic and clinicopathologic parameters evaluated. Amongst 7663 Helicobacter-positive biopsies, 823 (10.7%) did not show typical chronic active gastritis with numerous Helicobacter organisms, and were therefore considered histologically atypical. Rare Helicobacter pylori organisms accounted for 58.0% of all atypical infections; the next most common atypical Helicobacter infection was that with minimal or no gastric inflammation (23.3% of atypical infections). Patients in these groups did not differ demographically from those with other forms of atypical or typical Helicobacter infection, although a small subgroup (6%) was more likely to have had a previously treated infection. In many of these atypical infections, Helicobacter would not have been suspected based on the histologic findings alone, and would have been missed without routine special stains. Performing a sensitive stain could prevent additional testing and allow prompt treatment of the affected patients, thus substantially reducing the risk for peptic ulcer and gastric cancer and preventing the transmission of the infection to family members. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  16. Interleukin-1B and Interleukin-1 Receptor Antagonist in Patients with Helicobacter pylori Associated Diseases

    Directory of Open Access Journals (Sweden)

    Elizaveta S. Ageeva, PhD

    2012-06-01

    Full Text Available The ethnic people of the Republic of Khakassia (the Khakas with ulcer disease show a significant T-cell activation and humoral immune response when compared with the Europoids. The reasons for such differences could be due to certain ethno-specific allelic variants of the interleukins, which considerably change the degree of cytokine expression. The aim was to study the peculiarities of the association of the interleukin-1 (IL-1 gene polymorphisms and interleukin-1 receptor antagonist (IL-1Ra. Patients with chronic gastritis and ulcer disease were examined using the restriction analysis method. The most wide-spread allelic variants among the Khakas were discovered to be С�� IL-1β and R4R4 IL-1Ra. In this study, we suggest the necessity to define the population’s risk and the protective genotypes that promote Helicobacter pylori-associated ulcer disease among the Khakas people.

  17. Helicobacter pylori CagA Inhibits PAR1-MARK Family Kinases by Mimicking Host Substrates

    Energy Technology Data Exchange (ETDEWEB)

    Nesic, D.; Miller, M; Quinkert, Z; Stein, M; Chait, B; Stebbins, C

    2010-01-01

    The CagA protein of Helicobacter pylori interacts with numerous cellular factors and is associated with increased virulence and risk of gastric carcinoma. We present here the cocrystal structure of a subdomain of CagA with the human kinase PAR1b/MARK2, revealing that a CagA peptide mimics substrates of this kinase family, resembling eukaryotic protein kinase inhibitors. Mutagenesis of conserved residues central to this interaction renders CagA inactive as an inhibitor of MARK2.

  18. No evidence for Helicobacter pylori in oral lichen planus.

    Science.gov (United States)

    Hulimavu, Shwetha R; Mohanty, Leeky; Tondikulam, Narayan V; Shenoy, Sadhana; Jamadar, Saleha; Bhadranna, Abhishek

    2014-09-01

    Oral lichen planus is a T-cell-mediated mucosal disease of unknown etiology. Numerous predisposing factors have been put forward in the etiology of this disease. This includes stress, drugs, genetic susceptibility, certain viruses, and bacterial infections. Recently, there have been studies published on possible role of Helicobacter pylori infection in pathogenesis of mucocutaneous diseases including oral lichen planus (OLP). The aim of this study was to detect immunohistochemically the presence of Helicobacter pylori in oral lichen planus. Paraffin-embedded tissue blocks of 50 cases of OLP and 10 cases of normal buccal mucosal biopsies and 6 endoscopic biopsies of patients with peptic ulcer (control group) were sectioned and stained by hematoxylin and eosin. Serial sections of same were stained immunohistochemically using Anti-Helicobacter pylori antibody and observed under microscope for presence or absence of Helicobacter pylori. Except for the control group, none of the cases of OLP and normal buccal mucosal biopsies showed positivity for Helicobacter pylori. As we did not detect the presence of Helicobacter pylori in any of the OLP cases, we question the role of these organisms in the pathogenesis of OLP planus if any. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Validation of a simplified carbon-14-urea breath test for routine use for detecting Helicobacter pylori noninvasively

    International Nuclear Information System (INIS)

    Henze, E.; Malfertheiner, P.; Clausen, M.; Burkhardt, H.; Adam, W.E.

    1990-01-01

    A carbon-14 ( 14 C) urea breath test for detecting Helicobacter pylori with multiple breath sampling was developed. Carbon-14-urea (110 kBq) administered orally to 18 normal subjects and to 82 patients with Helicobacter infection. The exhaled 14 C-labeled CO 2 was trapped at 10-min intervals for 90 min. The total 14 C activity exhaled over 90 min was integrated and expressed in %activity of the total dose given. In normals, a mean of 0.59% +/- 0.24% was measured, resulting in an upper limit of normal of 1.07%. In 82 patients, a sensitivity of 90.2%, a specificity of 83.8%, and a positive predictive value of 90.2% was found. The single probes at intervals of 40-60 min correlated best with the integrated result, with r ranging from 0.986 to 0.990. The test's diagnostic accuracy did not change at all when reevaluated with the 40-, 50-, or 60-min sample data alone. Thus, the 14 C-urea breath test can be applied routinely as a noninvasive, low-cost and one-sample test with high diagnostic accuracy in detecting Helicobacter pylori colonization

  20. Helicobacter pylori y dispepsia, un problema de salud comunitario

    Directory of Open Access Journals (Sweden)

    Miguel González-Carbajal Pascual

    2002-06-01

    Full Text Available Mientras la relación causal entre el Helicobacter pylori y la gastritis crónica, así como la importante conexión entre esta infección, la úlcera gastroduodenal y el cáncer gástrico han sido bien establecidas, la asociación entre la infección por Helicobacter pylori y la dispepsia "no ulcerosa" es un problema que dista mucho de estar esclarecido. Hay autores que no dudan en utilizar tratamiento de erradicación en la dispepsia "no ulcerosa" con Helicobacter pylori, pero existen enfoques alternativos a este problema. La realización de tratamiento de erradicación en los pacientes con dispepsia "no ulcerosa" pudiera beneficiar o no a los enfermos y a la comunidad, pero seguramente no puede dejar de beneficiar a las transnacionales productoras de medicamentos que cosechan cuantiosas ganancias con la comercialización de los bloqueadores de la bomba de protones y los antibióticos que se incluyen en cualquier esquema de terapia erradicadora de la infección por Helicobacter pylori. El alivio de los síntomas dispépticos como consecuencia del tratamiento de erradicación del Helicobacter pylori no ha sido comprobado. El problema de realizar tratamiento de erradicación de la infección a los pacientes con dispepsia "no ulcerosa" continúa siendo un dilema y, por tanto, no debe indicarse sistemáticamente.Although the causative relationship between Helicobacter pylori and chronic gastritis as well as the important connection of this infection with gastric-duodenal ulcer and gastric cancer are well established, the association of Helicobacter pylori infection and non-ulcer dispepsia is a problem that is still unclear. Some authors do not hesitate in using Helicobacter pylori eradication treatment in cases of non-ulcer dispepsia but there are other alternative approaches to this problem. The eradication treatment in patients with non-ulcer dispepsia may or may not benefit patients and the community, but will benefit for sure the big drug

  1. Helicobacter pylori

    DEFF Research Database (Denmark)

    Leth, Peter Mygind

    1992-01-01

    Helicobacter pylori (HP) are Gram-negative spiral bacteria which occur in the human stomach. The bacteria were cultured in vitro for the first time in 1983. It is suspected that the bacteria may cause chronic gastritis of type B and may also be a contributory cause of chronic ulceration and cancer...

  2. Structural biology studies of CagA from Helicobacter pylori and histone chaperone CIA/ASF1

    International Nuclear Information System (INIS)

    Senda, Toshiya

    2015-01-01

    Crystal structures of proteins and their complexes have become critical information for molecular-based life science. Biochemical and biological analysis based on tertiary structural information is a powerful tool to unveil complex molecular processes in the cell. Here, we present two examples of the structure-based life science study, structural biology studies of CagA, an effector protein from Helicobacter pylori, and histone chaperone CIA/ASF1, which is involved in transcription initiation. (author)

  3. Prevalence and risk factors of Helicobacter pylori infection in Chinese maritime workers.

    Science.gov (United States)

    Hu, Dongmei; Shao, Jing; Wang, Ligang; Zheng, Huichun; Xu, Yan; Song, Guirong; Liu, Qigui

    2013-01-01

    Helicobacter pylori infection is very common worldwide. To evaluate the prevalence and identify the risk factors for Helicobacter pylori infection in Chinese maritime workers. Between March 2010 and October 2010, 3995 subjects were selected in the Hospital of Dalian Port. The presence of Helicobacter pylori infection was confirmed using laboratory tests (serum IgG anti-Helicobacter pylori antibodies) and background information, family history, lifestyle and eating habits were collected using questionnaires. The prevalence of Helicobacter pylori infection was 44.9% in these Chinese maritime workers. Prevalence of Helicobacter pylori infection was associated with family income, living space, family history of gastrointestinal diseases, smoking, drinking tea, raw vegetables consumption, spicy food, pickle food, dining outside, no regular meal and dish sharing. Further analysis with multivariate logistic regression analysis indicated that raw vegetables consumption, pickle food consumption, family income and family history of gastrointestinal diseases were independent predictors for Helicobacter pylori infection. No association was found between infection and gender, marital status, education, alcohol consumption and tap water consumption. Helicobacter pylori infection is associated with raw vegetables consumption, pickle food consumption, family income and family history of gastrointestinal disease among Chinese maritime workers.

  4. The impact of Helicobacter pylori resistance on the efficacy of a short course pantoprazole based triple therapy O impacto da resistência do Helicobacter pylori na eficácia de um esquema tríplice a curto prazo com pantoprazol

    Directory of Open Access Journals (Sweden)

    Jaime Natan Eisig

    2003-03-01

    Full Text Available BACKGROUND: Many of the currently used Helicobacter pylori eradication regimens fail to cure the infection due to either antimicrobial resistance or poor patient compliance. Those patients will remain at risk of developing potentially severe complications of peptic ulcer disease. AIM: We studied the impact of the antimicrobial resistance on the efficacy of a short course pantoprazole based triple therapy in a single-center pilot study. METHODS: Forty previously untreated adult patients (age range 20 to 75 years, 14 males infected with Helicobacter pylori and with inactive or healing duodenal ulcer disease were assigned in this open cohort study to 1 week twice daily treatment with pantoprazole 40 mg, plus clarithromycin 250 mg and metronidazole 400 mg. Helicobacter pylori was assessed at entry and 50 ± 3 days after the end of treatment by rapid urease test, culture and histology of gastric biopsies. The criteria for eradication was a negative result in the tests. Susceptibility of Helicobacter pylori to clarithromycin and metronidazole was determined before treatment with the disk diffusion test. RESULTS: One week treatment and follow up were complete in all patients. Eradication of Helicobacter pylori was achieved in 35/40 patients (87.5% and was higher in patients with nitroimidazole-susceptible strains [susceptible: 20/20 (100%, resistant: 10/15 (67%]. There were six (15% mild adverse events reports. CONCLUSIONS: A short course of pantoprazole-based triple therapy is well tolerated and effective in eradicating Helicobacter pylori. The baseline metronidazole resistance may be a significant limiting factor in treatment success.OBJETIVO: Vários esquemas utilizados na erradicação do Helicobacter pylori falham por resistência ao antibiótico ou por pouca aderência ao tratamento pelo paciente. Esses pacientes permanecerão com alto risco de desenvolver complicações decorrentes da úlcera péptica. Assim, estudou-se o impacto da resist

  5. Mucin muc2 deficiency and weaning influences the expression of the innate defense genes reg3ß, reg3¿ and angiogenin-4

    NARCIS (Netherlands)

    Burger-van Paassen, N.; Loonen, L.M.P.; Witte-Bouma, J.; Korteland-van Male, A.M.; Bruijn, de A.C.; Sluis, van der M.; Lu, P.; Goudoever, van J.B.; Wells, J.; Dekker, J.; Seuningen, van I.; Renes, I.B.

    2012-01-01

    Background Mucin Muc2 is the structural component of the intestinal mucus layer. Absence of Muc2 leads to loss of this layer allowing direct bacterial-epithelial interactions. We hypothesized that absence of the mucus layer leads to increased expression of innate defense peptides. Specifically, we

  6. Rosacea and Helicobacter pylori: links and risks

    Directory of Open Access Journals (Sweden)

    Lazaridou E

    2017-08-01

    Full Text Available Elizabeth Lazaridou,1 Chrysovalantis Korfitis,2 Christina Kemanetzi,1 Elena Sotiriou,1 Zoe Apalla,1 Efstratios Vakirlis,1 Christina Fotiadou,1 Aimilios Lallas,1 Demetrios Ioannides1 1First Department of Dermatology and Venereology, Aristotle University Medical School, Thessaloniki, Greece; 2Department of Dermatology, 401 General Army Hospital, Athens, Greece Abstract: Rosacea is a chronic skin disease characterized by facial erythema and telangiectasia. Despite the fact that many hypotheses have been proposed, its etiology remains unknown. In the present review, the possible link and clinical significance of Helicobacter pylori in the pathogenesis of rosacea are being sought. A PubMed and Google Scholar search was performed using the terms “rosacea”, “H.pylori”, “gastrointestinal disorders and H.pylori”, “microorganisms and rosacea”, “pathogenesis and treatment of rosacea”, and “risk factors of rosacea”, and selected publications were studied and referenced in text. Although a possible pathogenetic link between H. pylori and rosacea is advocated by many authors, evidence is still interpreted differently by others. We conclude that further studies are needed in order to fully elucidate the pathogenesis of rosacea. Keywords: eradication, Helicobacter pylori, pathogenesis, rosacea

  7. Biological evaluation and molecular docking of baicalin and scutellarin as Helicobacter pylori urease inhibitors.

    Science.gov (United States)

    Yu, Xiao-Dan; Zheng, Rong-Bo; Xie, Jian-Hui; Su, Ji-Yan; Huang, Xiao-Qi; Wang, Yong-Hong; Zheng, Yi-Feng; Mo, Zhi-Zhun; Wu, Xiao-Li; Wu, Dian-Wei; Liang, Ye-er; Zeng, Hui-Fang; Su, Zi-Ren; Huang, Ping

    2015-03-13

    Baicalin and scutellarin are the principal bioactive components of Scutellaria baicalensis Georgi which has extensively been incorporated into heat-clearing and detoxification formulas for the treatment of Helicobacter pylori-related gastrointestinal disorders in traditional Chinese medicine. However, the mechanism of action remained to be defined. To explore the inhibitory effect, kinetics and mechanism of Helicobacter pylori urease (the vital pathogenetic factor for Helicobacter pylori infection) inhibition by baicalin and scutellarin, for their therapeutic potential. The ammonia formations, indicator of urease activity, were examined using modified spectrophotometric Berthelot (phenol-hypochlorite) method. The inhibitory effect of baicalin and scutellarin was characterized with IC50 values, compared to acetohydroxamic acid (AHA), a well known Helicobacter pylori urease inhibitor. Lineweaver-Burk and Dixon plots for the Helicobacter pylori urease inhibition of baicalin and scutellarin was constructed from the kinetic data. SH-blocking reagents and competitive active site Ni(2+) binding inhibitors were employed for mechanism study. Molecular docking technique was used to provide some information on binding conformations as well as confirm the inhibition mode. Moreover, cytotoxicity experiment using Gastric Epithelial Cells (GES-1) was evaluated. Baicalin and scutellarin effectively suppressed Helicobacter pylori urease in dose-dependent and time-independent manner with IC50 of 0.82±0.07 mM and 0.47±0.04 mM, respectively, compared to AHA (IC50=0.14±0.05 mM). Structure-activity relationship disclosed 4'-hydroxyl gave flavones an advantage to binding with Helicobacter pylori urease. Kinetic analysis revealed that the types of inhibition were non-competitive and reversible with inhibition constant Ki of 0.14±0.01 mM and 0.18±0.02 mM for baicalin and scutellarin, respectively. The mechanism of urease inhibition was considered to be blockage of the SH groups of

  8. No Helicobacter pylori, no Helicobacter pylori-associated peptic ulcer disease

    NARCIS (Netherlands)

    Tytgat, G. N.

    1995-01-01

    Virtually all duodenal ulcers (DUs) and the vast majority of gastric ulcers (GUs) are the consequence of Helicobacter pylori-associated inflammation. In DUs, the inflammation is maximal in the antrum and is associated with gastric metaplasia in the bulb. Gastrin homeostasis is disturbed by H. pylori

  9. The content of mucin MUC-2, -3 and -4 antigens in the bronchial mucosa membrane of chronic obstructive pulmonary disease patients during acute exacerbation - initial report.

    Science.gov (United States)

    Kovalenko, Svetlana; Dorofieiev, Andrey

    2017-01-01

    Changes in mucin production and dyscrinia are common features of inflammation in chronic obstructive pulmonary disease (COPD). Immunohistochemical assessment of MUC-2, MUC-3, MUC-4 expression in the integumentary epithelium, goblet cells, the epithelium of mucous glands and stroma fusiform cells of the bronchial mucosa of COPD patients during an infectious and noninfectious exacerbation was performed. 30 patients with stage III COPD were enrolled to the study. Patients were divided into 2 groups: group A - 14 patients with non-infectious acute exacerbation of COPD (AECOPD) and group B - 16 patients with infectious AECOPD. Fiberoptic bronchoscopy (FBS) and in vivo bronchial biopsy of bronchial mucosa were implemented to determine the extent and nature of bronchial inflammation. The optical density of specific color in bronchial structures was assessed using immunohistochemical staining to MUC-2, -3 and -4 antigens by means of primary monoclonal antibodies to these proteins, and visualization system Dako EnVision + System, Peroxidase (AEC). We detected that in different types of bronchial mucosa epithelial cells, during acute infectious exacerbation, a decrease of antigens MUC-2 and MUC-3 expression of a various degree may occur. This phenomenon in the stroma fusiform cells in AECOPD may be a sign of epithelial-mesenchymal transition, that may play a role in the development of an inflammatory process and progression of fibrosis in COPD.

  10. Helicobacter pylori infection: past, present and future | Jemilohun ...

    African Journals Online (AJOL)

    Helicobacter pylori infection: past, present and future. ... The discovery of Helicobacter pylori (H. pylori) by Warren and Marshall in 1982 was preceded by nearly a hundred year of inconspicuous publications in ... A major challenge is the absence of a specific antibiotic monotherapy for effective treatment of the infection.

  11. HELICOBACTER PYLORI-ASSOCIATED INFLAMMATION IN PATIENTS WITH ACUTE CORONARY SYNDROME

    Directory of Open Access Journals (Sweden)

    O. N. Pavlov

    2014-07-01

    Full Text Available The aim – assessment of the prevalence of seropositivity to Helicobacter pylori infection and laboratory comparative study of the peripheralblood in patients depending on the course of coronary heart disease (CHD.Materials and methods. Observation of 100 patients with coronary artery disease and 40 control patients is presented. Investigation indicatorsof clinical blood tests, biochemical blood analysis and determination of immunoglobulin antibody titer against Helicobacter pylori.Results. In patients with coronary artery disease signs of systemic inflammation associated with the development of acute coronary syndrome are marked with increased antibody titers to infection Helicobacter pylori.Conclusion. A history of coronary artery disease in patients with Helicobacter pylori-associated gastroduodenal pathology should be considered as a factor that increases the likelihood of unstable coronary desease course. Detected in patients with coronary artery disease signs of systemic inflammation with an increase in titer of antibodies to Helicobacter pylori infection associated with development of acute coronary syndrome.

  12. Feasibility study of Anti-MUC1 aptamer use as vector target director of 1,10 phenantrolin for radiosensitization of breast cancer cells

    International Nuclear Information System (INIS)

    Alves, Laís Nascimento

    2017-01-01

    With the rising incidence of cancer and this disease as global public health dilemma, there is an alarming need of studying new cancer therapies. To achieve the development of efficient agents is essential to understand the fundamental mechanisms of carcinogenesis and tumor progression. Overexpression of proteins in malignant tissues, in contrast to expression of the proteins found in normal tissues of the same organ, is crucially important and of great interest for the characterization of potential tumor biomarkers. Following this premise, MUC1 glycoprotein was selected as a therapeutic target in a breast cancer model. In order to determine the viability of the aptA aptamer as radiosensitizers carrier, the toxic compound 1,10 phenanthroline, complexed with Fe(II) was intercalated in the aptamers. The dissociation constant was found at a value of Kd = 30 μM. The selective binding and internalization of the compound was demonstrated. Based on these data, the aptA can be used as carrying vector of molecules such as 1,10-phenanthroline. As a next stage, the evaluation of its in vitro potential as radiosensitizers with the use of ionizing radiation will be done. (author)

  13. Correlation between Helicobacter Pylori Infection and Intra Ocular Pressure

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    Hatamizadeh

    2012-02-01

    Full Text Available Introduction: Glaucoma is one of the most common causes of blindness. It is estimated that more than 60 million people suffer from this disease of all over the world. In other hand helicobacter pylori is a gram negative bacillus that is reported in some extra-gastrointestinal system diseases recently. This study is designed to determine the association between helicobacter pylori infection and intra-ocular pressure. Methods: This was an analytical cross-sectional study that was conducted on 74 persons who were randomly selected after referring to endoscopy ward of Shohadaye Kargar hospital of Yazd in 2009. Data was analyzed by Mann-Whitney U and fisher exact tests using SPSS software (ver16. Results: Mean of intra-ocular pressure in positive helicobacter pylori group was more than negative helicobacter pylori group but there was no significant relationship (P value > 0.05, also there was no significant relationship between helicobacter pylori infection and diabetes, hypertension, hypothyroidism and hyperthyroidism (P value > 0.05. Conclusion: According to the results, more detailed studies with larger sample size are required for more reliable decisions also considering the confounder variables can help us to determine the common risk factors of these two outcomes.

  14. Helicobacter pylori Infection and Anemia in Taiwanese Adults

    Directory of Open Access Journals (Sweden)

    Hsiang-Yao Shih

    2013-01-01

    Full Text Available Background. Chronic Helicobacter pylori infection and iron-deficiency anemia (IDA are common in adults. Although the most common causes of IDA usually arise from the gastrointestinal tract, the association between chronic Helicobacter pylori infection and anemia remains unclear. Aim. To evaluate the association of chronic Helicobacter pylori infection and IDA. Materials and Methods. We enrolled 882 patients from January 2010 to April 2013. The status of Helicobacter pylori (H.p infection was confirmed and blood samples from the same participants were taken on the same day to check the level of hemoglobin, serum iron, ferritin, and total iron-binding capacity (TIBC. Results. No significant difference was noted from the demographic data. The average level of hemoglobin (Hb was not different between negative and positive groups, pos 13.57 g/dL versus neg 13.65 g/dL (P=0.699. Although the levels of serum IDA related parameters were expected in positive group (lower serum iron and ferritin and higher TIBC these differences did not reach statistical significance (P=0.824 for iron, P=0.360 for ferritin, and P=0.252 for TIBC. Conclusion. Chronic Helicobacter pylori infection is not attributed to IDA. The levels of hemoglobin, serum iron and ferritin, and TIBC remain unaffected after chronic H.p infection. Large-scale clinical studies are needed to prove the association.

  15. [Latin American contribution to the study of Helicobacter pylori].

    Science.gov (United States)

    Ramírez Ramos, Alberto; Sánchez Sánchez, Rolando

    2009-09-01

    We have reviewed Lilacs, PubMed and Google searching for original articles related to Helicobacter pylori published by Latin American investigators from 2003 to 2008. Contributions in the following fields by countries are: Molecular biology: Brasil, Chile, Colombia, Peru y Venezuela. Argentina, Brasil, Colombia, Cuba, Peru y Venezuela. Argentina, Bolivia, Brasil, Chile, Costa Rica, Colombia, Mexico, Peru y Venezuela. Helicobacter pylori and gastroduodenal diseases: Brasil, Cuba, Peru y Venezuela. Helicobacter pylori and extra digestive diseases: Brasil, Colombia and Venezuela. Pediatrics: Brasil, Cuba y Venezuela. Argentina, Brasil, Chile, Colombia, Costa Rica, Mexico, Peru y Venezuela.

  16. A Novel Assay for Easy and Rapid Quantification of Helicobacter pylori Adhesion

    DEFF Research Database (Denmark)

    Skindersoe, Mette E; Rasmussen, Lone; Andersen, Leif P

    2015-01-01

    BACKGROUND: Reducing adhesion of Helicobacter pylori to gastric epithelial cells could be a new way to counteract infections with this organism. We here present a novel method for quantification of Helicobacter pylori adhesion to cells. METHODS: Helicobacter pylori is allowed to adhere to AGS...

  17. Kyoto global consensus report on Helicobacter pylori gastritis

    NARCIS (Netherlands)

    K. Sugano (Kentaro); J. Tack (Jan); E.J. Kuipers (Ernst); D.Y. Graham (David Y.); E. El-Omar; S. Miura (Soichiro); K. Haruma (Ken); M. Asaka (Masahiro); N. Uemura (Naomi); P. Malfertheiner

    2015-01-01

    textabstractObjective To present results of the Kyoto Global Consensus Meeting, which was convened to develop global consensus on (1) classification of chronic gastritis and duodenitis, (2) clinical distinction of dyspepsia caused by Helicobacter pylori from functional dyspepsia, (3) appropriate

  18. Prevalence of Helicobacter pylori in Northern Jordan: Endoscopy based study

    International Nuclear Information System (INIS)

    Bani-Hani, Kamal E.; Hammouri, Shadi M.

    2001-01-01

    Helicobacter pylori infection is considered the most common infection worldwide and is associated with many other disorders. The aim of this study is to determine the prevalence of this infection among patients undergoing endoscopy in Northern Jordan. Between November 1998 and September 2000, all patients referred from the Gastro-esophageal Clinic to the Endoscopy Unit at Princess Basma Teaching Hospital, Irbid, Northern Jordan were enrolled in this prospective study. For each patient clinical and epidemiological data was collected and endoscopy was performed. At least 3 antral biopsies were obtained from each patient, and these were examined histologically for the presence of gastritis and stained for Helicobacter pylori using modified Giemsa stain. A total of 197 consecutive patients (113 females) with a mean age of 40.2 years (range 15-91 years) were studied. Abdominal pain was the highest presenting symptom. Gastritis 91% and esophagitis 42% were the most frequent endoscopic findings. Gastritis was documented histologically in 183 (93%) of patients. Helicobacter pylori was found in 161 patients (82%), with all of these having histological gastritis. The 11 patients with gastric ulcer, compared to the 51 out of the 59 (86%) patients with duodenal ulcer, showed Helicobacter pylori in their biopsies. The prevalence of Helicobacter pylori infection in patients subjected to an upper gastrointestinal endoscopy in Jordan is high. This study confirms that Helicobacter pylori is significantly associated with gastritis and peptic ulcer. Further studies are needed to determine the types of Helicobacter pylori strains present in Jordan. (author)

  19. Efecto del tratamiento erradicador para Helicobacter pylori en pacientes con dispepsia funcional Effect to Helicobacter pylori eradication on patients with functional dyspepsia

    Directory of Open Access Journals (Sweden)

    T. de Artaza Varasa

    2008-09-01

    Helicobacter pylori infection (27 women and 21 men, mean age 37 ± 13.5 years. Twenty-seven patients received a 10-day course of rabeprazole, amoxicillin, and clarithromycin (eradication group, followed by 20 mg of rabeprazole for 3 months. Twenty-one patients received 20 mg of rabeprazole for 3 months (control group. Patients were followed up over a 1-year period. All patients completed the Dyspepsia-Related Health Scale Questionnaire, which studies four dimensions: pain intensity, pain disability, non-pain symptoms, and satisfaction with dyspepsia-related health. Results: there was significant symptomatic improvement (p < 0.002 after 6 and 12 months, which was similar with both treatments. In the multivariate analyses, eradication therapy and less severe symptoms before treatment were the only independent factors. The symptomatic response to Helicobacter pylori eradication after 6 months was significantly greater as compared to control therapy (p = 0.01 in patients with antral gastritis and in the non-pain symptoms dimension of the questionnaire. Conclusions: both treatments proved to be clinically beneficial in patients with functional dyspepsia. We observed a tendency to greater symptomatic benefit with Helicobacter pylori eradication therapy when compared to control treatment in patients with functional dyspepsia and in a population with a high prevalence of his infection. There is a tendency to symptomatic benefit with Helicobacter pylori eradication therapy in patients with antral gastritis.

  20. Distribution of the incidence and location of the Helicobacter pylori according to age and gender in patients who undergone endoscopy

    Directory of Open Access Journals (Sweden)

    Levent Demirtas

    2014-09-01

    Full Text Available Objective:The aim of this study was to define the distribution of the incidence and location of Helicobacter pylori in terms of the age and gender in the gastritis patients undergone endoscopy. Methods:Endoscopy and pathology reports of 1,405 patients who undergone biopsy of upper gastrointestinal system endoscopy were retrospectively examined. The frequency and location of Helicobacter pylori infection were evaluated according to the locations, gender and age groups. Based on the Sydney classification, the patients were scored as none (-, low (+, medium (++ and high (+++. Results: A total of 1405 patients (58.6% females, 41.4% males who had both antrum and corpus biopsies were included. Mean age was 48.58±16.96 (15-94 years. The Helicobacter pylori positivity was significantly higher in males than in the female patients (p=0.012. Helicobacter pylori positivity both in corpus and antrum was 1,101 (78.4%, Helicobacter pylori was negative in 304 (21.6% patients. Although, females had higher positivity rate, no significant difference was found between the age and gender groups. In 1,064 patients (75.7% Helicobacter pylori was positive while it was found as negative in 341 (24.3% biopsies taken from the antrum. While in 572 (40.7% of the biopsy outcomes taken from the corpus Helicobacter pylori was found as positive, it was found as negative in 833 (59.3%. No statistically significant differences were found between the age groups in terms of the positivity of Helicobacter pylori both in antrum and in corpus. Conclusion: In our study, the frequency of the Helicobacter pylori positivity was 78.4%. This can be accepted as a serious public health problem in terms of the associated diseases.

  1. Epidemiology of Helicobacter pylori infection in dyspeptic Ghanaian patients.

    Science.gov (United States)

    Archampong, Timothy Nii Akushe; Asmah, Richard Harry; Wiredu, Edwin Kwame; Gyasi, Richard Kwasi; Nkrumah, Kofi Nyaako; Rajakumar, Kumar

    2015-01-01

    Helicobacter pylori is a gram-negative urease-producing bacterium causally linked with gastritis, peptic ulcer disease and gastric adenocarcinoma. Infection is more frequent and acquired at an earlier age in developing countries compared to European populations. The incidence of Helicobacter pylori infection in dyspeptic Ghanaian patients was 75.4%. However, epidemiological factors associated with infection vary across populations. This study used a cross-sectional design to consecutively sample dyspeptic patients at the Endoscopy Unit of the Korle-Bu Teaching Hospital, Accra between 2010 and 2012. The study questionnaire elicited their epidemiological clinical characteristics. Helicobacter pylori infection was confirmed by rapid-urease examination of antral biopsies at upper Gastro-intestinal endoscopy. The sample population of dyspeptic patients attending the Endoscopy Unit for upper GI endoscopy yielded 242 patients of which 47.5% were females. The age distribution of H. pylori-infection was even across most age - groups, ranging from 69.2% (61 - 70) years to 80% (21 - 30) years. Helicobacter pylori prevalence decreased across areas mapping to the three residential classes in accordance with increasing affluence with rural areas having the highest prevalence. The unemployed and patients in farming had relatively high Helicobacter pylori infection rates of 92.3% and 91.7% respectively. Helicobacter pylori is endemic in Ghana but the persistently high prevalence across age groups despite significant community anti-microbial use suggests likely recrudescence or re-infection from multiple sources in a developing country. Socio-cultural factors such as residential class and farming may be facilitating factors for its continued prevalence.

  2. Interleukin-13-induced MUC5AC expression is regulated by a PI3K–NFAT3 pathway in mouse tracheal epithelial cells

    International Nuclear Information System (INIS)

    Yan, Fugui; Li, Wen; Zhou, Hongbin; Wu, Yinfang; Ying, Songmin; Chen, Zhihua; Shen, Huahao

    2014-01-01

    Highlights: • IL-13 specifically induced NFAT3 activation in mouse tracheal epithelial cells. • CsA and LY294002 significantly blocked IL-13-induced MUC5AC production. • The PI3K–NFAT3 pathway is positively involved in IL-13-induced MUC5AC production. - Abstract: Interleukin-13 (IL-13) plays a critical role in asthma mucus overproduction, while the mechanisms underlying this process are not fully elucidated. Previous studies showed that nuclear factor of activated T cells (NFAT) is involved in the pathogenesis of asthma, but whether it can directly regulate IL-13-induced mucus (particularly MUC5AC) production is still not clear. Here we showed that IL-13 specifically induced NFAT3 activation through promoting its dephosphorylation in air–liquid interface (ALI) cultures of mouse tracheal epithelial cells (mTECs). Furthermore, both Cyclosporin A (CsA, a specific NFAT inhibitor) and LY294002 (a Phosphoinositide 3-kinase (PI3K) inhibitor) significantly blocked IL-13-induced MUC5AC mRNA and protein production through the inhibition of NFAT3 activity. We also confirmed that CsA could not influence the forkhead Box A2 (Foxa2) and mouse calcium dependent chloride channel 3 (mClca3) expression in IL-13-induced MUC5AC production, which both are known to be important in IL-13-stimulated mucus expression. Our study is the first to demonstrate that the PI3K–NFAT3 pathway is positively involved in IL-13-induced mucus production, and provided novel insights into the molecular mechanism of asthma mucus hypersecretion

  3. Interleukin-13-induced MUC5AC expression is regulated by a PI3K–NFAT3 pathway in mouse tracheal epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Fugui; Li, Wen; Zhou, Hongbin; Wu, Yinfang; Ying, Songmin; Chen, Zhihua [Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang (China); Shen, Huahao, E-mail: huahaoshen@163.com [Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang (China); State Key Lab. of Respiratory Disease (SKLRS) (China)

    2014-03-28

    Highlights: • IL-13 specifically induced NFAT3 activation in mouse tracheal epithelial cells. • CsA and LY294002 significantly blocked IL-13-induced MUC5AC production. • The PI3K–NFAT3 pathway is positively involved in IL-13-induced MUC5AC production. - Abstract: Interleukin-13 (IL-13) plays a critical role in asthma mucus overproduction, while the mechanisms underlying this process are not fully elucidated. Previous studies showed that nuclear factor of activated T cells (NFAT) is involved in the pathogenesis of asthma, but whether it can directly regulate IL-13-induced mucus (particularly MUC5AC) production is still not clear. Here we showed that IL-13 specifically induced NFAT3 activation through promoting its dephosphorylation in air–liquid interface (ALI) cultures of mouse tracheal epithelial cells (mTECs). Furthermore, both Cyclosporin A (CsA, a specific NFAT inhibitor) and LY294002 (a Phosphoinositide 3-kinase (PI3K) inhibitor) significantly blocked IL-13-induced MUC5AC mRNA and protein production through the inhibition of NFAT3 activity. We also confirmed that CsA could not influence the forkhead Box A2 (Foxa2) and mouse calcium dependent chloride channel 3 (mClca3) expression in IL-13-induced MUC5AC production, which both are known to be important in IL-13-stimulated mucus expression. Our study is the first to demonstrate that the PI3K–NFAT3 pathway is positively involved in IL-13-induced mucus production, and provided novel insights into the molecular mechanism of asthma mucus hypersecretion.

  4. In Vitro and In Vivo Anti-Helicobacter Activities of Eryngium foetidum (Apiaceae), Bidens pilosa (Asteraceae), and Galinsoga ciliata (Asteraceae) against Helicobacter pylori.

    Science.gov (United States)

    Kouitcheu Mabeku, Laure Brigitte; Eyoum Bille, Bertrand; Nguepi, Eveline

    2016-01-01

    This study was performed to evaluate the antimicrobial activities of extracts of Bidens pilosa, Galinsoga ciliata, and Eryngium foetidum against 6 clinical strains of Helicobacter pylori in vitro and in vivo. Broth microdilution method was used in vitro. In vivo, Swiss mice were inoculated with H. pylori and divided into 5 groups; the control group received the vehicle and the four others received 125, 250, and 500 mg/kg of methanol extract of Eryngium foetidum and ciprofloxacin (500 mg/kg) for 7 days, respectively. Helicobacter pylori colonization and number of colonies in gastric biopsies culture were assessed on days 1 and 7 after treatment. The lowest MIC value (64 μg/mL) and the best spectrum of bactericidal effect (MBC/MIC = 1) were obtained with the methanol extract of Eryngium foetidum. The number of H. pylori infected animals was 17% (plant-extract) and 0% (ciprofloxacin) compared to 100% for the infected untreated group. Plant-extract (381.9 ± 239.5 CFU) and ciprofloxacin (248 ± 153.2 CFU) significantly reduced bacterial load in gastric mucosa compared to untreated, inoculated mice (14350 ± 690 CFU). Conclusion. The present data provided evidence that methanol extract of Eryngium foetidum could be a rich source of metabolites with antimicrobial activity to fight Helicobacter pylori infections.

  5. Immediate Effect of 3% Diquafosol Ophthalmic Solution on Tear MUC5AC Concentration and Corneal Wetting Ability in Normal and Experimental Keratoconjunctivitis Sicca Rat Models.

    Science.gov (United States)

    Choi, Kwang-Eon; Song, Jong-Suk; Kang, Boram; Eom, Youngsub; Kim, Hyo-Myung

    2017-05-01

    To evaluate the immediate effect of 3% diquafosol ophthalmic solution on tear MUC5AC concentration, periodic acid-Schiff (PAS)-positive goblet cells, and tear film stability in normal and keratoconjunctivitis sicca (KCS) rat models. Rats were divided into normal and KCS groups. 3% of diquafosol solution was instilled into the right eye and normal saline into the left eye in both groups. To determine the peak time of tear MUC5AC concentration, tears were collected after 3% diquafosol instillation every 5 min up to 20 min. The tear film stability and the numbers of PAS-positive goblet cells were compared in both models. After diquafosol instillation, tear MUC5AC concentration increased steadily for 15 min, at which point the MUC5AC concentration reached its peak. In both normal and KCS groups, the MUC5AC concentration at 15 min was higher after instillation of 3% diquafosol solution (17.77 ± 2.09 ng/ml in the normal group, 9.65 ± 3.51 ng/ml in the KCS group) than that after saline instillation (13.74 ± 2.87 ng/ml in the normal group, 8.19 ± 3.99 ng/ml in the KCS group) (p = 0.018 for both). The corneal wetting ability was significantly longer after instillation of 3% diquafosol solution compared with that after instillation of normal saline in the normal group (p = 0.018). The percentage of PAS-positive goblet cells after the instillation of 3% diquafosol solution was significantly lower than that after instillation of normal saline in both models (p = 0.018 for both). Diquafosol ophthalmic solution was effective in stimulating mucin secretion in both normal and KCS rat models, and the peak time of tear MUC5AC concentration was 15 min after diquafosol instillation. The increased tear MUC5AC concentration was accompanied by improved tear film stability and a decreased percentage of PAS-positive goblet cells.

  6. Isolation and identification of Helicobacter spp, from canine and feline gastric mucosa

    DEFF Research Database (Denmark)

    Jalava, K.; On, Stephen L.W.; VanDamme, P.A.R.

    1998-01-01

    It is known that virtually all healthy adult dogs and cats harbor spiral helicobacters in their gastric mucosa, Three species, Helicobacter felis, Helicobacter bizzozeronii, and Helicobacter salomonis have been isolated in vitro from the gastric mucosa of these animals. The aims of this study were...... conventional phenotypic tests, whole-cell protein profiling, and ultrastructural analysis in identifying the different species isolated from canine and feline gastric mucose. We cultured 95 and 22 gastric mucosal biopsies from dogs and cats, respectively. Twenty-one H. bizzozeronii strains, 8 H. felis strains......, 8 H. salomonis strains, 3 mixed cultures, 2 "Flexispira rappini"-like organisms, and 3 as get uncharacterized strains were isolated from the dogs, and 3 H. felis strains were isolated from the cats. The methods used here yielded Helicobacter isolation rates of 51% from dogs and 13.6% from cats...

  7. The receptor locus for escherichia coli F4ab/F4ac in the pig maps distal to the MUC4-LMLN region

    DEFF Research Database (Denmark)

    Rampoldi, Antonio; Jacobsen, Mette Juul; Bertschinger, Hans U.

    2011-01-01

    antigenic variants, F4ab, F4ac, and F4ad, of which F4ac is the most common. Resistance to ETEC F4ab/F4ac adhesion in pigs has been shown to be inherited as an autosomal recessive trait. In previous studies the ETEC F4ab/F4ac receptor locus (F4bcR) was mapped to the q41 region on pig chromosome 13....... A polymorphism within an intron of the mucin 4 (MUC4) gene, which is one of the possible candidate genes located in this region, was shown earlier to cosegregate with the F4bcR alleles. Recently, we discovered a Large White boar from a Swiss experimental herd with a recombination between F4bcR and MUC4. A three...... a newly detected SNP in the leishmanolysin-like gene (LMLN g.15920) and SNP ALGA0072075. In this study the six SNPs ALGA0072075, ALGA0106330, MUC13-226, MUC13-813, DIA0000584, and MARC0006918 were in complete linkage disequilibrium with F4bcR. Based on this finding and earlier investigations, we suggest...

  8. Subchronic inhalation of coal dust particulate matter 10 induces bronchoalveolar hyperplasia and decreases MUC5AC expression in male Wistar rats.

    Science.gov (United States)

    Kania, Nia; Setiawan, Bambang; Widjadjanto, Edi; Nurdiana, Nurdiana; Widodo, M Aris; Kusuma, H M S Chandra

    2014-10-01

    Coal dust is a pollutant found in coal mines that are capable of inducing oxidative stress and inflammation, but the effects on lung metaplasia as an early step of carcinogenesis remain unknown. The purpose of the present study was to evaluate the effects of PM10 coal dust on lung histology, MUC5AC expression, epidermal growth factor (EGF) expression, and epidermal growth factor receptor (EGFR) expression. An experimental study was done on male Wistar rats, which were divided into the following groups: control groups exposed to coal dust for 14 days (at doses of 6.25 mg/m(3), 12.5 mg/m(3), and 25 mg/m(3)), and the groups exposed to coal dust for 28 days (at doses of 6.25 mg/m(3), 12.5 mg/m(3), and 25 mg/m(3)). EGF expressions in rat lungs were measured by ELISA. EGFR and MUC5AC were measured by a confocal laser scanning microscope. The bronchoalveolar epithelial image of the group exposed to coal dust for 14 and 28 days showed a epithelial rearrangement, hyperplastic (metaplastic) goblet cells, and scattered massive inflammatory cells. The pulmonary parenchymal image of the group of exposed to coal dust for 14 and 28 days showed scattered inflammatory cells filling up the pulmonary alveolar networks, leading to an appearance of thickened parenchymal alveoli until emphysema-like structure. There was no significant difference in MUC5AC, EGF, and EGFR expressions for 14-d exposure (p>0.05). There was no significant difference in EGF and EGFR expressions for 28-d exposure (p>0.05), but there was a significant difference in MUC5AC expression (phyperplasia and rearrangement of epithelial cells which accompanied by decrease expression MUC5AC in male rats. Copyright © 2014 Elsevier GmbH. All rights reserved.

  9. Association of Helicobacter pylori infection with peptic ulcer disease ...

    African Journals Online (AJOL)

    Background: Helicobacter pylori infection has been identified as an important risk factor for the development of peptic ulcer disease and is probably the most important cause of relapse in those previously treated for peptic ulcer disease. The aim of this study was to determine the association of Helicobacter pylori infection as ...

  10. Dyspeptic symptoms in patients with type 1 diabetes: endoscopic findings, Helicobacter pylori infection, and associations with metabolic control, mood disorders and nutritional factors.

    Science.gov (United States)

    Faria, Mariza; Pavin, Elizabeth João; Parisi, Maria Cândida Ribeiro; Nagasako, Cristiane Kibune; Mesquita, Maria Aparecida

    2015-04-01

    To evaluate, in a group of patients with long-standing type 1 diabetes (DM1), an association of dyspepsia symptoms with: changes in the gastroduodenal mucosa, infection by Helicobacter pylori, glycemic control, and psychological and nutritional factors. A total of 32 patient with DM1 were studied (age: 38 ± 9 years; females: 25; diabetes duration: 22 ± 5 years). All patients answered a standardized questionnaire for the evaluation of gastrointestinal symptoms and underwent upper gastrointestinal endoscopy, with gastric biopsies for the evaluation of Helicobacter pylori infection. The presence of anxiety and depression was evaluated by the HAD scale. Nutritional parameters were BMI, arm and waist circumference, skinfold measurement, and body fat percentage. Upper endoscopy detected lesions in the gastric mucosa in 34.4% of the patients, with similar frequency in those with (n = 21) and without dyspepsia (n = 11). The patients with dyspepsia complaints showed greater frequency of depression (60% vs. 0%; p = 0.001), higher values for HbA1c (9.6 ± 1.7 vs. 8.2 ± 1.3%; p = 0.01) and lower values for BMI (24.3 ± 4.1 vs. 27.2 ± 2.6 kg/m2; p = 0.02), body fat percentage (26.6 ± 6.2 vs. 30.8 ± 7.7%; p = 0.04), and waist circumference (78.7 ± 8 vs. 85.8 ± 8.1 cm; p = 0.02). No association was found between the symptoms and the presence of Helicobacter pylori. Dyspepsia symptoms in patients with long-standing DM1 were associated with glycemic control and depression, and they seem to negatively influence the nutritional status of these patients.

  11. Helicobacter pylori infection and atrophic gastritis | Ebule | African ...

    African Journals Online (AJOL)

    Background: Helicobacter pylori-infection associated gastritis is known to be a significant risk factor of gastric cancer. Serum levels of Gastrin-17 and Pepsinogen1which are respectively biomarkers of gastric antral and corpus mucosal activity are well known parameters of atrophic gastritis. Objectives: To determine the ...

  12. MicroRNA profiling in Muc2 knockout mice of colitis-associated cancer model reveals epigenetic alterations during chronic colitis malignant transformation.

    Directory of Open Access Journals (Sweden)

    Yonghua Bao

    Full Text Available Our previous studies have demonstrated that genetic deletion of the Muc2 gene causes colorectal cancers in mice. The current study further showed that at the early stage (3 months the mice exhibited colorectal cancer, including a unique phenotype of rectal prolapsed (rectal severe inflammation and adenocarcinoma. Thus, the age of 3 months might be the key point of the transition from chronic inflammation to cancer. To determine the mechanisms of the malignant transformation, we conducted miRNA array on the colonic epithelial cells from the 3-month Muc2-/- and +/+ mice. MicroRNA profiling showed differential expression of miRNAs (i.e. lower or higher expression enrichments in Muc2-/- mice. 15 of them were validated by quantitative PCR. Based on relevance to cytokine and cancer, 4 miRNAs (miR-138, miR-145, miR-146a, and miR-150 were validate and were found significantly downregulated in human colitis and colorectal cancer tissues. The network of the targets of these miRNAs was characterized, and interestedly, miRNA-associated cytokines were significantly increased in Muc2-/-mice. This is the first to reveal the importance of aberrant expression of miRNAs in dynamically transformation from chronic colitis to colitis-associated cancer. These findings shed light on revealing the mechanisms of chronic colitis malignant transformation.

  13. Reduced infectivity of waterborne viable but nonculturable Helicobacter pylori strain SS1 in mice.

    Science.gov (United States)

    Boehnke, Kevin F; Eaton, Kathryn A; Fontaine, Clinton; Brewster, Rebecca; Wu, Jianfeng; Eisenberg, Joseph N S; Valdivieso, Manuel; Baker, Laurence H; Xi, Chuanwu

    2017-08-01

    Helicobacter pylori infection has been consistently associated with lack of access to clean water and proper sanitation, but no studies have demonstrated that the transmission of viable but nonculturable (VBNC) H. pylori can occur from drinking contaminated water. In this study, we used a laboratory mouse model to test whether waterborne VBNCH. pylori could cause gastric infection. We performed five mouse experiments to assess the infectivity of VBNCH. pylori in various exposure scenarios. VBNC viability was examined using Live/Dead staining and Biolog phenotype metabolism arrays. High doses of VBNCH. pylori in water were chosen to test the "worst-case" scenario for different periods of time. One experiment also investigated the infectious capabilities of VBNC SS1 using gavage. Further, immunocompromised mice were exposed to examine infectivity among potentially vulnerable groups. After exposure, mice were euthanized and their stomachs were examined for H. pylori infection using culture and PCR methodology. VBNC cells were membrane intact and retained metabolic activity. Mice exposed to VBNCH. pylori via drinking water and gavage were not infected, despite the various exposure scenarios (immunocompromised, high doses) that might have permitted infection with VBNCH. pylori. The positive controls exposed to viable, culturable H. pylori did become infected. While other studies that have used viable, culturable SS1 via gavage or drinking water exposures to successfully infect mice, in our study, waterborne VBNC SS1 failed to colonize mice under all test conditions. Future studies could examine different H. pylori strains in similar exposure scenarios to compare the relative infectivity of the VBNC vs the viable, culturable state, which would help inform future risk assessments of H. pylori in water. © 2017 The Authors. Helicobacter Published by John Wiley & Sons Ltd.

  14. Specific characteristics of immunohistochemical changes of the cellular infiltrate (the content of mucins MUC 2, 3, 4 in the mucous tunic of the bronchi in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    S. V. Kovalenko

    2013-04-01

    decreases in the respiratory tract at infectious exacerbation of COPD in comparison with their expression at noninfectious exacerbation of COPD in all structures except fusiform cell of the stroma-fibroblasts. In our opinion a decrease of the mucin expression at the infectious exacerbation of COPD, most evident in the tegmental epithelium, the epithelium of the mucous glands and less in goblet cells can be explained by the influence of pathogenic microbes present in a great number on the mucous membranes and tegmental epithelium of the bronchi at infectious exacerbation of COPD. Even expression of MUC 2,3, which appears in fibroblasts of the stroma and does not depend on the variant of exacerbation of COPD is probably connected with the phenomena of an epithelial-mesenchymal transformation (EMT, when normal epithelial cells (for example, of the mucous membrane of the glands under the influence of certain factors, for instance, TGFβ1, obtain the features of miofibroblast cells. Owing to the EMT the epithelial cells are losing intercellular ties, move to the interstitium, where obtaining a complete mesenchymal fenotype, take part in the synthesis of fibrous matrix. Conclusions. The expression of antigens MUC2 and MUC3 detected in the fusiform cells of the stroma (fibroblasts during a COPD exacerbation enables to certify a fact of an epithelial-mesenchymal transformation, namely, a change of transformed epithelial cells, as a result of which they react differently than ordinary epithelial cells to molecular factors which play a certain role in the development of an inflammatory process and progression of fibrosis in COPD.

  15. Helicobacter Pylori infection of the gallbladder and the risk of chronic cholecystitis and cholelithiasis: A systematic review and meta-analysis.

    Science.gov (United States)

    Cen, Li; Pan, Jiaqi; Zhou, Boyan; Yu, Chaohui; Li, Youming; Chen, Weixing; Shen, Zhe

    2018-02-01

    Helicobacter pylori is coexisted with various diseases, including chronic gastritis, ulcer, and gastric cancer. Besides, chronic cholecystitis and cholelithiasis are extremely widespread over the world, which are considered as high health-care cost burdens of digestive diseases. Epidemiologic evidence on Helicobacter pylori infection in gallbladder increasing the risk of biliary diseases has been contradictory. Conduct a meta-analysis of overall studies and investigate an association between Helicobacter pylori infection of the gallbladder with chronic cholecystitis/cholelithiasis. We used PubMed, EMBASE, and Cochrane library databases to identify all published studies before August 2017. Pooled odds ratios (OR) and corresponding 95% confidence intervals (CIs) were obtained using the random effects model. Heterogeneity, sensitivity, and stratified analyses were also performed. Eighteen studies involving 1544 participants and 1061 biliary cases with chronic cholecystitis/cholelithiasis were included. Helicobacter pylori infection of the gallbladder was significantly associated with an increased risk of chronic cholecystitis and cholecystitis (OR = 3.022; 95% CI, 1.897-4.815; I 2  = 20.1%). In addition, country-based subgroup analysis also showed a positive association between Helicobacter pylori positivity and chronic cholecystitis/cholelithiasis risk. The ORs (95% CIs) for Asian and non-Asian region studies were 3.75 (1.83-7.71) and 2.25 (1.29-3.89), respectively. This meta-analysis suggests that infection of the gallbladder with Helicobacter pylori is closely related to an increased risk of chronic cholecystitis and cholelithiasis. © 2017 John Wiley & Sons Ltd.

  16. PREVALENCE OF HELICOBACTER PYLORI IN PATIENTS WITH DYSPEPSIA UNDERGOING UPPER GASTRO INTESTINAL ENDOSCOPY IN TERTIARY CARE HOSPITAL

    Directory of Open Access Journals (Sweden)

    Ajay Babu K

    2017-12-01

    Full Text Available BACKGROUND Acid peptic disease comprises of a wide spectrum of diseases, which cause considerable morbidity. Helicobacter pylori, a curved rod-shaped bacterium, has been consistently associated with patients suffering from acid peptic diseases, more in ulcer disease than in non-ulcer disease. Due to this high association, it is now believed that Helicobacter pylori plays an important role in the aetiopathogenesis of acid peptic disease. Several studies have revealed the association of Helicobacter pylori in 70-75 percent of patients with dyspepsia. Endoscopic studies have shown that, Helicobacter pylori is found in 80-100% of patients with duodenal ulcers and 60-75 per cent of patients with gastric ulcers. Amidst these profound variations proposed by many workers in the previous studies, we have attempted to study the prevalence of Helicobacter pylori in patients undergoing upper gastrointestinal endoscopy at our hospital and its association with acid-peptic disease. The objectives of this study were- 1. To study the prevalence of Helicobacter pylori in patients with dyspepsia undergoing upper gastrointestinal endoscopy. 2. To study the association of Helicobacter pylori with acid peptic Diseases. MATERIALS AND METHODS 344 cases of dyspepsia were studied clinically as per the proforma over a period of one and half years from July 2014 to October 2015. The inclusion and exclusion criteria were as follows; RESULTS Out of 344 patients, there were 224 male patients and 120 female patients, age ranging from 19 years to 60 years (Mean44.8. Out of 344 patients, 156 patients were diagnosed to have been infected with Helicobacter pylori (45.3%. CONCLUSION This was a prospective study conducted to determine the role of Helicobacter pylori in acid-peptic diseases. This study design was based on clinical study and endoscopic biopsy of gastric mucosa (and duodenal mucosa whenever necessary in 344 patients with a history of dyspepsia. Endoscopy confirmed the

  17. Glycosylation-related gene expression in HT29-MTX-E12 cells upon infection by Helicobacter pylori.

    Science.gov (United States)

    Cairns, Michael T; Gupta, Ananya; Naughton, Julie A; Kane, Marian; Clyne, Marguerite; Joshi, Lokesh

    2017-10-07

    To identify glycosylation-related genes in the HT29 derivative cell line, HT29-MTX-E12, showing differential expression on infection with Helicobacter pylori ( H. pylori ). Polarised HT29-MTX-E12 cells were infected for 24 h with H. pylori strain 26695. After infection RNA was isolated from both infected and non-infected host cells. Sufficient infections were carried out to provide triplicate samples for microarray analysis and for qRT-PCR analysis. RNA was isolated and hybridised to Affymetrix arrays. Analysis of microarray data identified genes significantly differentially expressed upon infection. Genes were grouped into gene ontology functional categories. Selected genes associated with host glycan structure (glycosyltransferases, hydrolases, lectins, mucins) were validated by real-time qRT-PCR analysis. Infection of host cells was confirmed by the isolation of live bacteria after 24 h incubation and by PCR amplification of bacteria-specific genes from the host cell RNA. H. pylori do not survive incubation under the adopted culture conditions unless they associate with the adherent mucus layer of the host cell. Microarray analysis identified a total of 276 genes that were significantly differentially expressed ( P < 0.05) upon H. pylori infection and where the fold change in expression was greater than 2. Six of these genes are involved in glycosylation-related processes. Real-time qRT-PCR demonstrated significant downregulation (1.8-fold, P < 0.05) of the mucin MUC20. REG4 was heavily expressed and significantly downregulated (3.1-fold, P < 0.05) upon infection. Gene ontology analysis was consistent with previous studies on H. pylori infection. Gene expression data suggest that infection with H. pylori causes a decrease in glycan synthesis, resulting in shorter and simpler glycan structures.

  18. Survey of Helicobacter infection in domestic and feral cats in Korea

    OpenAIRE

    Ghil, Heh-Myung; Yoo, Jong-Hyeon; Jung, Woo-Sung; Chung, Tae-Ho; Youn, Hwa-Young; Hwang, Cheol-Yong

    2009-01-01

    Discovery of Helicobacter (H.) pylori has led to a fundamental change in our understanding of gastric diseases in humans. Previous studies have found various Helicobacter spp. in dogs and cats, and pets have been questioned as a zoonotic carrier. The present study surveyed the Helicobacter infections and investigated the presence of H. felis and H. pylori infections in domestic and feral cats in Korea. Sixty-four domestic cats and 101 feral cats were selected from an animal shelter. Saliva an...

  19. Gastric microbiota and carcinogenesis: the role of non-Helicobacter pylori bacteria: a systematic review

    Directory of Open Access Journals (Sweden)

    Emanuel Dias-Jácome

    Full Text Available Background and aim: Helicobacter pylori is the strongest risk factor for gastric cancer. However, recent advances in DNA sequencing technology have revealed a complex microbial community in the stomach that could also contribute to the development of gastric cancer. The aim of this study was to present recent scientific evidence regarding the role of non-Helicobacter pylori bacteria in gastric carcinogenesis. Methods: A systematic review of original articles published in PubMed in the last ten years related to gastric microbiota and gastric cancer in humans was performed. Results: Thirteen original articles were included. The constitution of gastric microbiota appears to be significantly affected by gastric cancer and premalignant lesions. In fact, differences in gastric microbiota have been documented, depending on Helicobacter pylori status and gastric conditions, such as non-atrophic gastritis, intestinal metaplasia and cancer. Gastric carcinogenesis can be associated with an increase in many bacteria (such as Lactobacillus coleohominis, Klebsiella pneumoniae or Acinetobacter baumannii as well as decrease in others (such as Porphyromonas spp, Neisseria spp, Prevotella pallens or Streptococcus sinensis. However, there is no conclusive data that confirms if these changes in microbiota are a cause or consequence of the process of carcinogenesis. Conclusions: Even though there is limited evidence in humans, microbiota differences between normal individuals, pre-malignant lesions and gastric cancer could suggest a progressive shift in the constitution of gastric microbiota in carcinogenesis, possibly resulting from a complex cross-talk between gastric microbiota and Helicobacter pylori. However, further studies are needed to elucidate the specific role (if any of different microorganisms.

  20. Gastric microbiota and carcinogenesis: the role of non-Helicobacter pylori bacteria - A systematic review.

    Science.gov (United States)

    Dias-Jácome, Emanuel; Libânio, Diogo; Borges-Canha, Marta; Galaghar, Ana; Pimentel-Nunes, Pedro

    2016-09-01

    Helicobacter pylori is the strongest risk factor for gastric cancer. However, recent advances in DNA sequencing technology have revealed a complex microbial community in the stomach that could also contribute to the development of gastric cancer. The aim of this study was to present recent scientific evidence regarding the role of non-Helicobacter pylori bacteria in gastric carcinogenesis. A systematic review of original articles published in PubMed in the last ten years related to gastric microbiota and gastric cancer in humans was performed. Thirteen original articles were included. The constitution of gastric microbiota appears to be significantly affected by gastric cancer and premalignant lesions. In fact, differences in gastric microbiota have been documented, depending on Helicobacter pylori status and gastric conditions, such as non-atrophic gastritis, intestinal metaplasia and cancer. Gastric carcinogenesis can be associated with an increase in many bacteria (such as Lactobacillus coleohominis, Klebsiella pneumoniae or Acinetobacter baumannii) as well as decrease in others (such as Porphyromonas spp, Neisseria spp, Prevotella pallens or Streptococcus sinensis). However, there is no conclusive data that confirms if these changes in microbiota are a cause or consequence of the process of carcinogenesis. Even though there is limited evidence in humans, microbiota differences between normal individuals, pre-malignant lesions and gastric cancer could suggest a progressive shift in the constitution of gastric microbiota in carcinogenesis, possibly resulting from a complex cross-talk between gastric microbiota and Helicobacter pylori. However, further studies are needed to elucidate the specific role (if any) of different microorganisms.

  1. Enrichment of Probiotic Yogurt with Broccoli Sprout Extract and its Effect on Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Ali Reza Sadeghi

    2017-01-01

    Full Text Available Background and Objective: Antibiotic consumption is the main way to cure infection induced by Helicobacter pylori. On the other hand, antibiotics have side effects on human body. So, finding an efficient way to replace antibiotic consumption seems necessary. The aim of this study was to investigate the effect of broccoli sprout extract on the viability of probiotic bacteria and yogurt’s physicochemical properties, and examine the synergistic effect of this extract with probiotics on Helicobacter pylori growth inhibition.Material and Methods: Four levels of broccoli sprout extract (22.5, 45, 90 and 180 mg ml-1 were prepared and their effect on probiotic yogurt samples was examined. Moreover, their anti- Helicobacter pylori effect was determined.Results and Conclusion: The research results revealed that Broccoli sprout extract did not have any inhibitory effect on Bifidobacterium lactis and Lactobacillus acidophilus. The variations in acidity of the samples were not significant during storage. A positive correlation was observed between broccoli sprout extract concentration and syneresis. The findings showed the synergistic effect of broccoli sprout extract and probiotics on Helicobacter pylori growth inhibition. Therefore, using broccoli sprout extract and probiotic bacteria, we can produce a yogurt that is effective on the growth inhibition of Helicobacter pylori.Conflict of interest: The authors declare that there is no conflict of interest.

  2. Helicobacter pylori y enfermedad péptica ulcerosa

    Directory of Open Access Journals (Sweden)

    Noel Padrón Pérez

    1998-12-01

    Full Text Available Se realizó una revisión dirigida a los médicos de la familia sobre la relación del Helicobacter pylori y la enfermedad péptica ulcerosa. Se incluyen datos epidemiológicos y métodos diagnósticos de la infección. El papel de Helicobacter pylori en la génesis de las recidivas ulcerosas y la significativa disminución de las recurrencias posterior a la erradicación con la terapia antimicrobiana, son aspectos abordados en el presente trabajo. La inmunización como arma de prevención y tratamiento sería un importante logro que se menciona como una futura alternativa para combatir la úlcera asociada a la infecciónA review on the connection of Helicobacter pylori with peptic ulcer disease was made for the family physicians. Epidemiological data and diagnostic methods were included. The role of Helicobacter pylori in the genesis of ulcer relapses and the significant reduction of recurrences after the erradication with antimicrobial therapy are approached in the present paper. Immunization as an instrument of prevention and treatment would be an important achievement that is mentioned as a future alternative to fight ulcer associated with the infection

  3. Mucin 1-specific immunotherapy in a mouse model of spontaneous breast cancer.

    Science.gov (United States)

    Mukherjee, Pinku; Madsen, Cathy S; Ginardi, Amelia R; Tinder, Teresa L; Jacobs, Fred; Parker, Joanne; Agrawal, Babita; Longenecker, B Michael; Gendler, Sandra J

    2003-01-01

    Human mucin 1 (MUC1) is an epithelial mucin glycoprotein that is overexpressed in 90% of all adenocarcinomas including breast, lung, pancreas, prostate, stomach, colon, and ovary. MUC1 is a target for immune intervention, because, in patients with solid adenocarcinomas, low-level cellular and humoral immune responses to MUC1 have been observed, which are not sufficiently strong to eradicate the growing tumor. The hypothesis for this study is that enhancing MUC1-specific immunity will result in antitumor immunity. To test this, the authors have developed a clinically relevant breast cancer model that demonstrates peripheral and central tolerance to MUC1 and develops spontaneous tumors of the mammary gland. In these mice, the authors tested a vaccine formulation comprised of liposomal-MUC1 lipopeptide and human recombinant interleukin-2. Results indicate that when compared with untreated mice, immunized mice develop T cells that express intracellular IFN-gamma, are reactive with MHC class I H-2Db/MUC1 tetramer, and are cytotoxic against MUC1-expressing tumor cells in vitro. The presence of MUC1-specific CTL did not translate into a clinical response as measured by time of tumor onset, tumor burden, and survival. The authors demonstrate that some of the immune-evasion mechanisms used by the tumor cells include downregulation of MHC-class I molecule, expression of TGF-beta2, and decrease in IFN-gamma -expressing effector T cells as tumors progress. Finally, utilizing an injectable breast cancer model, the authors show that targeting a single tumor antigen may not be an effective antitumor treatment, but that immunization with dendritic cells fed with whole tumor lysate is effective in breaking tolerance and protecting mice from subsequent tumor challenge. A physiologically relevant spontaneous breast cancer model has been developed to test improved immunotherapeutic approaches.

  4. Review: Impact of Helicobacter pylori on Alzheimer's disease: What do we know so far?

    Science.gov (United States)

    Doulberis, Michael; Kotronis, Georgios; Thomann, Robert; Polyzos, Stergios A; Boziki, Marina; Gialamprinou, Dimitra; Deretzi, Georgia; Katsinelos, Panagiotis; Kountouras, Jannis

    2018-02-01

    Helicobacter pylori has changed radically gastroenterologic world, offering a new concept in patients' management. Over time, more medical data gave rise to diverse distant, extragastric manifestations and interactions of the "new" discovered bacterium. Special interest appeared within the field of neurodegenerative diseases and particularly Alzheimer's disease, as the latter and Helicobacter pylori infection are associated with a large public health burden and Alzheimer's disease ranks as the leading cause of disability. However, the relationship between Helicobacter pylori infection and Alzheimer's disease remains uncertain. We performed a narrative review regarding a possible connection between Helicobacter pylori and Alzheimer's disease. All accessible relevant (pre)clinical studies written in English were included. Both affected pathologies were briefly analyzed, and relevant studies are discussed, trying to focus on the possible pathogenetic role of this bacterium in Alzheimer's disease. Data stemming from both epidemiologic studies and animal experiments seem to be rather encouraging, tending to confirm the hypothesis that Helicobacter pylori infection might influence the course of Alzheimer's disease pleiotropically. Possible main mechanisms may include the bacterium's access to the brain via the oral-nasal-olfactory pathway or by circulating monocytes (infected with Helicobacter pylori due to defective autophagy) through disrupted blood-brain barrier, thereby possibly triggering neurodegeneration. Current data suggest that Helicobacter pylori infection might influence the pathophysiology of Alzheimer's disease. However, further large-scale randomized controlled trials are mandatory to clarify a possible favorable effect of Helicobacter pylori eradication on Alzheimer's disease pathophysiology, before the recommendation of short-term and cost-effective therapeutic regimens against Helicobacter pylori-related Alzheimer's disease. © 2017 John Wiley & Sons

  5. Helicobacter pylori and Peptic Ulcers

    Centers for Disease Control (CDC) Podcasts

    In this podcast, CDC's Dr. David Swerdlow discusses the relationship between Helicobacter pylori and peptic ulcer disease and trends in hospitalization rates for peptic ulcer disease in the United States between 1998 and 2005.

  6. Helicobacter Pylori Associated Gastritis Increases Risk of Colorectal Polyps: a Hospital Based-Cross-Sectional Study in Nakhon Ratchasima Province, Northeastern Thailand.

    Science.gov (United States)

    Tongtawee, Taweesak; Kaewpitoon, Soraya; Kaewpitoon, Natthawut; Dechsukhum, Chavaboon; Leeanansaksiri, Wilairat; Loyd, Ryan A; Matrakool, Likit; Panpimanmas, Sukij

    2016-01-01

    Colorectal polyps are common in Thailand, particularly in the northeastern region. The present study aimed to determine any correlation between Helicobacter pylori-associated gastritis and colorectal polyps in the Thai population. A total of 303 patients undergoing esophagogastroduodenoscopy with colonoscopy for investigation of chronic abdominal pain participated in this study from November 2014 to October 2015. A diagnosis of Helicobacter pylori associated gastritis was made if the bacteria were seen on histopathological examination and a rapid urease test was positive. Colorectal polyps were confirmed by histological examination of colorectal biopsies. Patient demographic data were analyzed for correlations. The prevalence of colorectal polyps was 77 (25.4%), lesions being found more frequently in Helicobacter pylori infected patients than non-infected subjects [38.4% vs. 12.5%; Odds Ratio (OR) (95% CI): 2.26 (1.32 - 3.86), p gastritis were at high risk of having adenomas featuring dysplasia [OR (95% CI): 1.15 (1.16 - 7.99); P = 0.02]. There was no varaition in location of polyps, age group, sex and gastric lesions with respect to Helicobacter pylori status. This study showed that Helicobacter pylori associated gastritis is associated with an increased risk of colorectal polyps, especially adenomas with dysplasia in the Thai population. Patients with Helicobacter pylori-associated gastritis may benefit from concurrent colonoscopy for diagnosis of colorectal polyps as a preventive and early treatment for colorectal cancer.

  7. Helicobacter pylori in the gastric mucosa of dead children Helicobacter pylori en la mucosa gástrica de cadáveres de niños

    Directory of Open Access Journals (Sweden)

    John Jairo Duque Alzate

    1999-03-01

    Full Text Available 23 children under the age of 12 years who died violently without receiving any treatment, had their gastric mucosa studied by means of he Warthin-Starry stain and immunohistochemistry in search for Helicobacter pylori. It was found that 60.9% (14 cases were positive; of them 64,3% belonged to a low social class and 35,7% to the middle one. Of the positive cases, 9 had acute gastritis, 1 had chronic gastritis and only 4 had normal gastric mucosa. A clear association between Helicobacter pylory and changes in gastritis was observed. En 23 niños menores de 12 años que murieron en forma violenta sin haber recibido tratamiento, se estudiaron para Helicobacter pylori las mucosas gástricas con las coloraciones de hematoxilina eosina, Warthin Starry e inmunohistoquímica. Se encontró que 14 casos (60,9% fueron positivos para esta bacteria, de los cuales 9 (64,3% pertenecían a un estrato social bajo y 5 (35,7% a uno medio. De los casos positivos para H. pylori, 9 tenían gastritis aguda, 1 gastritis crónica y sólo en 4 la mucosa gástrica era normal. Se observó una clara asociación entre H. pylori y cambios de gastritis.

  8. Relationship of Halitosis with Gastric Helicobacter Pylori Infection

    Directory of Open Access Journals (Sweden)

    Farnaz HajiFattahi

    2015-10-01

    Full Text Available Objectives: Gastric infection with Helicobacter pylori may be one of the main causes of halitosis. This study was performed to evaluate the relationship of Heli- cobacter pylori infection with halitosis.Materials and Methods: This case control study was performed on 44 dyspeptic patients with a mean age of 34.29±13.71 years (range 17 to 76 years. The case group included 22 patients with halitosis and no signs of diabetes mellitus, renal or liver failure, upper respiratory tract infection, malignancies, deep carious teeth, severe  periodontitis,  coated  tongue,  dry  mouth  or poor  oral  hygiene.  Control group included 22 patients without halitosis and the same age, sex, systemic and oral conditions as the case group. Halitosis was evaluated using organoleptic test (OLT and Helicobacter pylori infection was evaluated by Rapid Urease Test (RUT during endoscopy. The data were statistically analyzed using chi square, Mann Whitney and t-tests.Results: Helicobacter pylori infection was detected in 20 (91% out of 22 halitosis patients, and 7 control subjects (32% (P<0.001.Conclusion: Helicobacter pylori gastric infection can be a cause of bad breath. Dentists should pay more attention to this infection and refer these patients to in- ternists to prevent further gastrointestinal (GI complications and probable malig- nancies.

  9. Identification of the MUC2 Promoter as a Strong Promoter for Intestinal Gene Expression through Generation of Transgenic Quail Expressing GFP in Gut Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Rachel M. Woodfint

    2017-01-01

    Full Text Available Identification of tissue- and stage-specific gene promoters is valuable for delineating the functional roles of specific genes in genetically engineered animals. Here, through the comparison of gene expression in different tissues by analysis of a microarray database, the intestinal specificity of mucin 2 (MUC2 expression was identified in mice and humans, and further confirmed in chickens by RT-PCR (reverse transcription-PCR analysis. An analysis of cis-acting elements in avian MUC2 gene promoters revealed conservation of binding sites, within a 2.9 kb proximal promoter region, for transcription factors such as caudal type homeobox 2 (CDX2, GATA binding protein 4 (GATA4, hepatocyte nuclear factor 4 α (HNF4A, and transcription factor 4 (TCF4 that are important for maintaining intestinal homeostasis and functional integrity. By generating transgenic quail, we demonstrated that the 2.9 kb chicken MUC2 promoter could drive green fluorescent protein (GFP reporter expression exclusively in the small intestine, large intestine, and ceca. Fluorescence image analysis further revealed GFP expression in intestine epithelial cells. The GFP expression was barely detectable in the embryonic intestine, but increased during post-hatch development. The spatiotemporal expression pattern of the reporter gene confirmed that the 2.9 kb MUC2 promoter could retain the regulatory element to drive expression of target genes in intestinal tissues after hatching. This new transgene expression system, using the MUC2 promoter, will provide a new method of overexpressing target genes to study gene function in the avian intestine.

  10. The role of helicobacter pylori infection in the pathogenesis of chronic urticaria

    International Nuclear Information System (INIS)

    Ghazzawi, I.M.; Obidat, N.A.

    2004-01-01

    Objective: To determine the prevalence of H. pylori infection in patients with idiopathic chronic urticaria (ICU) and to see if eradication of the bacterium affects the course of the urticaria. Patients and Methods: One hundred patients with idiopathic chronic urticaria and 43 healthy subjects (matched for age and sex) underwent serological testing for H. pylori infection. All patients with idiopathic chronic urticaria were examined for Helicobacter pylori infection with the /sup 13/C-urea test as well as the serological testing. Gastric biopsy was obtained from 36 patients. Patients with proven Helicobacter pylori infection were given treatment for 2 weeks. Six weeks afterwards they were tested again for Helicobacter pylori infection, and their urticaria was clinically assessed. Results: There was no significant difference in the seroprevalence of H. pylori infection between : idiopathic chronic urticaria patients and healthy subjects. Helicobacter pylori was detected in 76% of patients and 69.8% of controls. Out of the 76 patients treated, only 24 showed complete remission of their urticaria after successfully eradicating Helicobacter pylori infection, the others only having some improvement in their symptoms. Conclusion: Patients with idiopathic chronic urticaria have similar high rates of H. pylori infection as healthy subjects. Bacterium eradication is associated with improvement of urticaria symptoms, suggesting a possible role of Helicobacter pylori in the pathogenesis of this skin disorder. (author)

  11. Helicobacter pylori: Beginning the Second Decade

    Directory of Open Access Journals (Sweden)

    Ann Matisko

    1995-01-01

    Full Text Available ‘Beginning the Second Decade’ - a recent international meeting on Helicobacter pylori - was held in conjunction with the VIIth International Workshop on Gastroduodenal Pathology and H pylori and with the meeting of the European Helicobacter pylori Study Group in Houston, Texas from September 30 to October 1, 1994. A menu of 476 abstracts, published in the American Journal of Gastroenterology (1994;89:8, highlighted the explosion of advances in this area. The Houston meeting was followed by the Tenth World Congresses of Gastroenterology from October 2 to 7, 1994 in Los Angeles, California, again with scores of presentations and posters on topics ranging from the epidemiology of H pylori infection to steps towards the development of a human vaccine. All this was in addition to important new work presented earlier in 1994 in New Orleans during Digestive Diseases Week. In this digest of these important meetings, the authors will not regurgitate what the informed reader already knows, but will instead focus on the recent developments in important areas, providing selected key published references for background, and referring to this new work in abstract form which is at the cutting edge of “yesterday’s tomorrow today”.

  12. Possible association between Helicobacter pylori infection and vocal fold leukoplakia.

    Science.gov (United States)

    Chen, Min; Chen, Jian; Yang, Yue; Cheng, Lei; Wu, Hai-Tao

    2018-03-06

    Several studies have indicated the larynx as possible Helicobacter pylori (H. pylori) reservoirs. This study explored the association between H. pylori and vocal fold leukoplakia. The case-control study involved 51 patients with vocal fold leukoplakia and 35 control patients with vocal polyps. Helicobacter pylori was detected in tissues by the rapid urease test, nested polymerase chain reaction (PCR), and single-step PCR. The H. pylori-specific immunoglobulin antibodies were detected in plasma by enzyme-linked immunosorbent assay (ELISA). Helicobacter pylori-positive rate of vocal fold leukoplakia and vocal polyps was 23.5% versus 11.4% (P = .157), 37.2% versus 14.3% (P = .020), 27.5% versus 8.6% (P = .031), and 70.6% versus 68.6% (P = .841) detected by rapid urease test, nested PCR, single-step PCR, and ELISA, respectively. Regression analysis indicated that H. pylori infection (P = .044) was the independent risk factor for vocal fold leukoplakia. Helicobacter pylori infection exists in the larynx and may be associated with vocal fold leukoplakia. © 2018 Wiley Periodicals, Inc.

  13. Differentiation of five enterohepatic Helicobacter species by nested PCR with high-resolution melting curve analysis.

    Science.gov (United States)

    Wu, Miaoli; Rao, Dan; Zhu, Yujun; Wang, Jing; Yuan, Wen; Zhang, Yu; Huang, Ren; Guo, Pengju

    2017-04-01

    Enterohepatic Helicobacter species (EHS) are widespread in rodent species around the world. Several studies have demonstrated that infection with EHS can interfere with the outcomes of animal experiments in cancer research and significantly influence the study results. Therefore, it is essential to establish a rapid detection and identification of EHS for biomedical research using laboratory rodents. Our study aimed to develop a rapid and sensitive method to detect and distinguish five enterohepatic Helicobacter species. Nested PCR followed by high-resolution melting curve analysis (HRM) was developed for identification of H. bilis, H. rodentium, H. muridarum, H. typhlonius, as well as H. hepaticus. To validate the accuracy of nested PCR-HRM analysis, quantitative real-time PCR methods for five different enterohepatic Helicobacter species were developed. A total of 50 cecal samples were tested using both nested PCR-HRM analysis and qPCR method. The nested PCR-HRM method could distinguish five enterohepatic Helicobacter species by different melting temperatures. The melting curve were characterized by peaks of 78.7 ± 0.12°C for H. rodentium, 80.51 ± 0.09°C for H. bilis, 81.6 ± 0.1°C for H. typhlonius, 82.11 ± 0.18°C for H. muridarum, and 82.95 ± 0.09°C for H. hepaticus. The nested PCR-HRM assay is a simple, rapid, and cost-effective assay. This assay could be a useful tool for molecular epidemiology study of enterohepatic Helicobacter infection and an attractive alternative for genotyping of enterohepatic Helicobacter species. © 2016 John Wiley & Sons Ltd.

  14. CagA, a major virulence factor of Helicobacter pylori, promotes the production and underglycosylation of IgA1 in DAKIKI cells

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Man [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Li, Fu-gang [Department of Nephrology, Affiliated Hospital of Luzhou Medical College, Luzhou City 646000 (China); Xie, Xi-sheng [Department of Nephrology, Second Clinical Medical Institution of North Sichuan Medical College (Nanchong Central Hospital), Nanchong City 637400 (China); Wang, Shao-qing [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Fan, Jun-ming, E-mail: junmingfan@163.com [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Department of Nephrology, Affiliated Hospital of Luzhou Medical College, Luzhou City 646000 (China)

    2014-02-07

    Highlights: • CagA stimulated cell proliferation and the production of IgA1 in DAKIKI cells. • CagA promoted the underglycosylation of IgA1 in DAKIKI cells. • CagA decreased the expression of C1GALT1 and its chaperone Cosmc in DAKIKI cells. • Helicobacter pylori infection may participate in the pathogenesis of IgAN via CagA. - Abstract: While Helicobacter pylori (Hp) infection is closely associated with IgA nephropathy (IgAN), the underlying molecular mechanisms remain to be elucidated. This study was to investigate the effect of cytotoxin associated gene A protein (CagA), a major virulence factor of Hp, on the production and underglycosylation of IgA1 in the B cell line DAKIKI cells. Cells were cultured and treated with recombinant CagA protein. We found that CagA stimulated cell proliferation and the production of IgA1 in a dose-dependent and time-dependent manner. Moreover, CagA promoted the underglycosylation of IgA1, which at least partly attributed to the downregulation of β1,3-galactosyltransferase (C1GALT1) and its chaperone Cosmc. In conclusion, we demonstrated that Hp infection, at least via CagA, may participate in the pathogenesis of IgAN by influencing the production and glycosylation of IgA1 in B cells.

  15. CagA, a major virulence factor of Helicobacter pylori, promotes the production and underglycosylation of IgA1 in DAKIKI cells

    International Nuclear Information System (INIS)

    Yang, Man; Li, Fu-gang; Xie, Xi-sheng; Wang, Shao-qing; Fan, Jun-ming

    2014-01-01

    Highlights: • CagA stimulated cell proliferation and the production of IgA1 in DAKIKI cells. • CagA promoted the underglycosylation of IgA1 in DAKIKI cells. • CagA decreased the expression of C1GALT1 and its chaperone Cosmc in DAKIKI cells. • Helicobacter pylori infection may participate in the pathogenesis of IgAN via CagA. - Abstract: While Helicobacter pylori (Hp) infection is closely associated with IgA nephropathy (IgAN), the underlying molecular mechanisms remain to be elucidated. This study was to investigate the effect of cytotoxin associated gene A protein (CagA), a major virulence factor of Hp, on the production and underglycosylation of IgA1 in the B cell line DAKIKI cells. Cells were cultured and treated with recombinant CagA protein. We found that CagA stimulated cell proliferation and the production of IgA1 in a dose-dependent and time-dependent manner. Moreover, CagA promoted the underglycosylation of IgA1, which at least partly attributed to the downregulation of β1,3-galactosyltransferase (C1GALT1) and its chaperone Cosmc. In conclusion, we demonstrated that Hp infection, at least via CagA, may participate in the pathogenesis of IgAN by influencing the production and glycosylation of IgA1 in B cells

  16. Evaluation of Salivary Antibodies to Detect Infection with Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Mark B Loeb

    1997-01-01

    Full Text Available Helicobacter pylori infection is an important cause of peptic ulcer disease and chronic gastritis. Infection with this bacterium stimulates the production of immunoglobulin (Ig G antibody. Salivary IgG antibody tests to detect H pylori infection offer a convenient and noninvasive method of diagnosis. To evaluate an IgG salivary antibody kit, saliva was collected from 157 out-patients with dyspepsia referred for endoscopy to a tertiary centre. A salivary IgG ELISA antibody assay was performed using the Helisal Helicobacter pylori (IgG assay kit, and at least four gastric biopsies were obtained. H pylori infection was confirmed by demonstration of the organism on Warthin-Starry silver stain (sensitivity 85%, specificity 55%. The prevalence of infection with H pylori was 30%. When the analysis was redone, excluding those treated with eradication therapy, the results were similar (sensitivity 86%, specificity 58%. The positive predictive value of the assay was 45% and the negative predictive value was 90%. Despite the ease of sampling, the assay used has limited diagnostic utility, lacking the predictive value to indicate which patients referred with dyspeptic symptoms to a tertiary care setting are infected with H pylori.

  17. Endoscopic transmission of Helicobacter pylori

    NARCIS (Netherlands)

    Tytgat, G. N.

    1995-01-01

    The contamination of endoscopes and biopsy forceps with Helicobacter pylori occurs readily after endoscopic examination of H. pylori-positive patients. Unequivocal proof of iatrogenic transmission of the organism has been provided. Estimates for transmission frequency approximate to 4 per 1000

  18. Helicobacter pylori infection in pediatrics

    DEFF Research Database (Denmark)

    Wewer, Anne Vibeke; Kalach, Nicolas

    2003-01-01

    A high prevalence and early colonization of Helicobacter pylori infection in childhood was described again this year in developing countries in contrast to developed ones. Upper gastrointestinal endoscopy including gastric biopsies remains the diagnostic gold standard method for this infection. A...

  19. The NYU System for MUC-6 or Where’s the Syntax?

    Science.gov (United States)

    1995-01-01

    34 and only in the face of compelling syntactic or semantic evidence, in a (nearly) deterministic manner . Speed was particularly an issue for MUC-6...thank BBN Systems and Technologies for providing us with this tagger. 168 Name Recognitio n The input stage is followed by several stages of pattern...Group Recognitio n The third stage of pattern matching recognizes verb groups : simple tensed verbs ("sleeps"), and verbs with auxiliaries ("will sleep

  20. Disinfectant activity against different morphological forms of Helicobacter pylori: first results

    Czech Academy of Sciences Publication Activity Database

    Gebel, J.; Vacata, V.; Sigler, Karel; Pietsch, H.; Rechenburg, A.; Exner, M.; Kistemann, T.

    2001-01-01

    Roč. 48, Suppl A (2001), s. 58-63 ISSN 0195-6701 Institutional research plan: CEZ:AV0Z5020903 Keywords : desinfection * disinfectant efficacy * Helicobacter pylori Subject RIV: EE - Microbiology, Virology Impact factor: 1.983, year: 2001

  1. A fluid model for Helicobacter pylori

    Science.gov (United States)

    Reigh, Shang-Yik; Lauga, Eric

    2015-11-01

    Swimming microorganisms and self-propelled nanomotors are often found in confined environments. The bacterium Helicobacter pylori survives in the acidic environment of the human stomach and is able to penetrate gel-like mucus layers and cause infections by locally changing the rheological properties of the mucus from gel-like to solution-like. In this talk we propose an analytical model for the locomotion of Helicobacter pylori as a confined spherical squirmer which generates its own confinement. We solve analytically the flow field around the swimmer, and derive the swimming speed and energetics. The role of the boundary condition in the outer wall is discussed. An extension of our model is also proposed for other biological and chemical swimmers. Newton Trust.

  2. Identification of Helicobacter and Wolinella spp. in Oral Cavity of Toy Breed Dogs With Periodontal Disease.

    Science.gov (United States)

    Nowroozilarki, Negar; Jamshidi, Shahram; Zahraei Salehi, Taghi; Kolahian, Saeed

    2017-09-01

    Periodontal diseases are the most common oral cavity infectious diseases in adult dogs. We aimed in this study to identify Helicobacter and Wolinella spp. in saliva and dental plaque of dogs with periodontitis. Sixty-two small-breed pet dogs, aged more than 6 years from both sexes, were categorized into healthy and periodontitis groups. Samples from saliva and dental plaques were collected, and Helicobacter and Wolinella were identified on genus and species levels using polymerase chain reaction. Our results showed significant increase in infection rate of Wolinella spp. in periodontitis compared with healthy dogs (P = .002). Furthermore, infection rate of Helicobacter genus was significantly higher in periodontitis compared with healthy dogs (P = .007). Infection with Wolinella spp. showed higher rate than Helicobacter spp. in dogs with periodontitis. According to species-specific polymerase chain reaction results, Helicobacter felis (9.76%) was the main Helicobacter spp. in dogs with periodontitis compared with healthy dogs (P dogs with periodontitis could be considered as an important source of Wolinella and Helicobacter spp. infections. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Feasibility study of Anti-MUC1 aptamer use as vector target director of 1,10 phenantrolin for radiosensitization of breast cancer cells; Estudo da viabilidade do uso do aptâmero Anti-MUC1 como vetor alvo direcionador de 1,10 fenantrolina para radio sensibilização de células de câncer de mama

    Energy Technology Data Exchange (ETDEWEB)

    Alves, Laís Nascimento

    2017-07-01

    With the rising incidence of cancer and this disease as global public health dilemma, there is an alarming need of studying new cancer therapies. To achieve the development of efficient agents is essential to understand the fundamental mechanisms of carcinogenesis and tumor progression. Overexpression of proteins in malignant tissues, in contrast to expression of the proteins found in normal tissues of the same organ, is crucially important and of great interest for the characterization of potential tumor biomarkers. Following this premise, MUC1 glycoprotein was selected as a therapeutic target in a breast cancer model. In order to determine the viability of the aptA aptamer as radiosensitizers carrier, the toxic compound 1,10 phenanthroline, complexed with Fe(II) was intercalated in the aptamers. The dissociation constant was found at a value of Kd = 30 μM. The selective binding and internalization of the compound was demonstrated. Based on these data, the aptA can be used as carrying vector of molecules such as 1,10-phenanthroline. As a next stage, the evaluation of its in vitro potential as radiosensitizers with the use of ionizing radiation will be done. (author)

  4. Halitosis and Helicobacter pylori infection

    NARCIS (Netherlands)

    Tangerman, A.; Winkel, E. G.; de Laat, L.; van Oijen, A. H.; de Boer, W. A.

    There is disagreement about a possible relationship between Helicobacter pylori (H. pylori) infection and objective halitosis, as established by volatile sulfur compounds (VSCs) in the breath. Many studies related to H. pylori used self-reported halitosis, a subjective and unreliable method to

  5. A comparative study of clinicopathological features between chronic cholecystitis patients with and without Helicobacter pylori infection in gallbladder mucosa.

    Directory of Open Access Journals (Sweden)

    Di Zhou

    Full Text Available BACKGROUND: Helicobacter pylori has been isolated from 10%-20% of human chronic cholecystitis specimens but the characteristics of "Helicobacter pylori positive cholecystitis" remains unclear. This study aims to compare the clinicopathological features between chronic cholecystitis patients with and without Helicobacter pylori infection in gallbladder mucosa. METHODS: Three hundred and twenty-six chronic cholecystitis patients were divided into two groups according to whether Helicobacter pylori could be detected by culture, staining or PCR for Helicobacter 16s rRNA gene in gallbladder mucosa. Positive samples were sequenced for Helicobacter pylori-specific identification. Clinical parameters as well as pathological characteristics including some premalignant lesions and the expression levels of iNOS and ROS in gallbladder were compared between the two groups. RESULTS: Helicobacter pylori infection in gallbladder mucosa was detected in 20.55% of cholecystitis patients. These patients had a higher prevalence of acid regurgitation symptoms (p = 0.001, more histories of chronic gastritis (p = 0.005, gastric ulcer (p = 0.042, duodenal ulcer (p = 0.026 and higher presence of Helicobacter pylori in the stomach as compared to patients without Helicobacter pylori infection in the gallbladder mucosa. Helicobacter pylori 16s rRNA in gallbladder and gastric-duodenal mucosa from the same individual patient had identical sequences. Also, higher incidences of adenomyomatosis (p = 0.012, metaplasia (p = 0.022 and higher enhanced expressions of iNOS and ROS were detected in Helicobacter pylori infected gallbladder mucosa (p<0.05. CONCLUSIONS: Helicobacter pylori infection in gallbladder mucosa is strongly associated with Helicobacter pylori existed in stomach. Helicobacter pylori is also correlated with gallbladder premalignant lesions including metaplasia and adenomyomatosis. The potential mechanism might be related with higher ROS

  6. Helicobacter species are associated with possible increase in risk of biliary lithiasis and benign biliary diseases

    Directory of Open Access Journals (Sweden)

    Pandey Manoj

    2007-08-01

    Full Text Available Abstract Background Hepato-biliary tract lithiasis is common and present either as pain or as asymptomatic on abdominal ultrasonography for other causes. Although the DNA of Helicobacter species are identified in the gallbladder bile, tissue or stones analyzed from these cases, still a causal relationship could not be established due to different results from different geographical parts. Methods A detailed search of pubmed and pubmedcentral was carried out with key words Helicobacter and gallbladder, gallstones, hepaticolithiasis, cholelithiasis and choledocholithiasis, benign biliary diseases, liver diseases. The data was entered in a data base and meta analysis was carried out. The analysis was carried out using odds ratio and a fixed effect model, 95% confidence intervals for odds ratio was calculated. Chi square test for heterogeneity was employed. The overall effect was calculated using Z test. Results A total of 12 articles were identified. One study used IgG for diagnosis while others used the PCR for Ure A gene, 16 S RNA or Cag A genes. A couple of studies used culture or histopathology besides the PCR. The cumulative results show a higher association of Helicobacter with chronic liver diseases (30.48%, and stone diseases (42.96%(OR 1.77 95% CI 1.2–2.58; Z = 2.94, p = 0.003, the effect of each could not be identified as it was difficult to isolate the effect of helicobacter due to mixing of cases in each study. Conclusion The results of present meta analysis shows that there is a slight higher risk of cholelithiasis and benign liver disease (OR 1.77, however due to inherent inability to isolate the effect of stone disease from that of other benign lesions it is not possible to say for sure that Helicobacter has a casual relationship with benign biliary disease or stone disease or both.

  7. Myeloid HIF-1 is protective in Helicobacter pylori-mediated gastritis.

    Science.gov (United States)

    Matak, Pavle; Heinis, Mylène; Mathieu, Jacques R R; Corriden, Ross; Cuvellier, Sylvain; Delga, Stéphanie; Mounier, Rémi; Rouquette, Alexandre; Raymond, Josette; Lamarque, Dominique; Emile, Jean-François; Nizet, Victor; Touati, Eliette; Peyssonnaux, Carole

    2015-04-01

    Helicobacter pylori infection triggers chronic inflammation of the gastric mucosa that may progress to gastric cancer. The hypoxia-inducible factors (HIFs) are the central mediators of cellular adaptation to low oxygen levels (hypoxia), but they have emerged recently as major transcriptional regulators of immunity and inflammation. No studies have investigated whether H. pylori affects HIF signaling in immune cells and a potential role for HIF in H. pylori-mediated gastritis. HIF-1 and HIF-2 expression was examined in human H. pylori-positive gastritis biopsies. Subsequent experiments were performed in naive and polarized bone marrow-derived macrophages from wild-type (WT) and myeloid HIF-1α-null mice (HIF-1(Δmyel)). WT and HIF-1(Δmyel) mice were inoculated with H. pylori by oral gavage and sacrificed 6 mo postinfection. HIF-1 was specifically expressed in macrophages of human H. pylori-positive gastritis biopsies. Macrophage HIF-1 strongly contributed to the induction of proinflammatory genes (IL-6, IL-1β) and inducible NO synthase in response to H. pylori. HIF-2 expression and markers of M2 macrophage differentiation were decreased in response to H. pylori. HIF-1(Δmyel) mice inoculated with H. pylori for 6 mo presented with a similar bacterial colonization than WT mice but, surprisingly, a global increase of inflammation, leading to a worsening of the gastritis, measured by an increased epithelial cell proliferation. In conclusion, myeloid HIF-1 is protective in H. pylori-mediated gastritis, pointing to the complex counterbalancing roles of innate immune and inflammatory phenotypes in driving this pathology. Copyright © 2015 by The American Association of Immunologists, Inc.

  8. DETECTION OF ENTEROHEPATIC AND GASTRIC HELICOBACTER SPP. IN WILD CHIMPANZEES (PAN TROGLODYTES) AND WESTERN LOWLAND GORILLAS (GORILLA GORILLA)

    Czech Academy of Sciences Publication Activity Database

    Flahou, B.; Modrý, David; Pomajbíková, K.; Petrželková, Klára Judita; Smet, J.; Ducatelle, R.; Pasmans, F.; Sa, R.; Haesebrouck, F.

    2011-01-01

    Roč. 16, S1 (2011), s. 141 ISSN 1083-4389. [24th International Workshop on Helicobacter and Related Bacteria in Chronic Digestive Inflammation and Gastric Cancer. 11.09.2011-13.09.2011, Dublin] Institutional research plan: CEZ:AV0Z60220518; CEZ:AV0Z60930519 Keywords : wild primates * gastric and enterohepatic helicobacters * Africa Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine

  9. The association of metabolic syndrome and Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus type 1: The Persian Gulf Healthy Heart Study

    Directory of Open Access Journals (Sweden)

    Pazoki Raha

    2006-12-01

    Full Text Available Abstract Background The metabolic syndrome together with insulin resistance and their consequences are basic factors in pathogenesis of atherosclerosis. Chronic infections with herpes simplex virus type 1 (HSV-1, cytomegalovirus (CMV, and Chlamydia pneumoniae are associated with the development of atherosclerosis and coronary heart disease. The infectious aspects of metabolic syndrome have not been investigated. Methods In a cross-sectional, population-based study, we used National Cholesterol Education Program (NCEP-Adult Treatment Panel (ATP-III criteria in 1791 subjects, aged 25 years and over, selected by cluster random sampling in three Iranian ports in the northern Persian Gulf. Sera were analyzed for IgG antibodies to Chlamydia pneumoniae, HSV-1, Helicobacter pylori (H. pylori and CMV using ELISA. Results In multiple logistic regression analysis, of the infectious agents, CMV [OR = 1.81 (1.05–3.10; p = 0.03], H. pylori [OR = 1.50 (1.12–2.00; p = 0.007] and Chlamydia pneumoniae [OR = 1.69 (1.27–2.25; p Conclusion The metabolic syndrome, which occurs very frequently in the general population, has a significant association with prior infection with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus and herpes simplex virus type 1. Hypothesis about participation of infection in pathogenesis of metabolic syndrome should be investigated.

  10. GE-CMU: Description of the Shogun System Used for MUC-5

    Science.gov (United States)

    1993-01-01

    points , anyway. In this case, the Japanese text says that the tie-up will be selling a new product called " hyu -man " . 112 70 60 — JJ V JME n JJV n JM...50 60 70 Recal l Figure 3 : GE-CMU Results for MUC-5/TIPSTER 24-month benchmar k SHOGUN correctly spots this and assumes that whatever " hyu -man...34 is will be wholesale sales with code 50 . The analyst infers from the context that " hyu -man" is an insurance product, so the actual industry type i

  11. One-week triple therapy for eradication of helicobacter pylori

    International Nuclear Information System (INIS)

    Shah, N.H.; Shah, M.S.; Khan, I.; Hameed, K.

    2002-01-01

    Objective: The optimum therapy for Helicobacter pylori infection is yet to be defined in Pakistan despite a high prevalence of helicobacter associated diseases in this community. The most popular and effective regimen was therefore chosen among the currently recommended combinations used worldwide to document its efficacy in our symptomatic Helicobacter positive dyspeptic patients. Design: It was a prospective, non-randomized study. Place and duration of Study: The study lasted from January 1998 till June 1999 at the Postgraduate Institute, Government Lady Reading Hospital and Fauji Foundation Hospital, Peshawar. Subjects and Methods: Consecutive dyspeptic patients with peptic ulcer disease as well as non ulcer dyspepsia with a positive H. pylori status on histology from the specimens obtained from the antral region of the stomach, who consented to take part in the study were enrolled. They were given omeprazole 20 mg bd, clarithromycin 500 mg bd. And amoxycillin 1 gm bd for one week. One group comprised patients with confirmed peptic ulcer disease while the second group comprised patients with macroscopic/microscopic antral gastritis. Patients with peptic ulcer disease were given additional course of omerprazol for another 4 weeks to ensure healing of their ulcers. All patients were re scoped after stopping all drugs and their H. pylori status re-assessed on histology. Results: A total of 84 patients consented to enter the study. Fifty-nine were males and twenty-five were females. Fifty-eight patients completed the study while others were lost followup. There were no dropouts due to side effects of the drugs. Sixteen patients had peptic ulcer disease while 68 had macroscopic/microscopic active antral gastric only. The Helicobacter pylori eradication has been successful in only 12 patients giving a cure rate of 20.60% as determined per protocol analysis. The eradication rates were disappointingly low in both groups. Conclusion: The results are extremely

  12. Seroprevalence of Helicobacter pylori in Korea: A multicenter, nationwide study conducted in 2015 and 2016.

    Science.gov (United States)

    Lee, Jeong Hoon; Choi, Kee Don; Jung, Hwoon-Yong; Baik, Gwang Ho; Park, Jong Kyu; Kim, Sung Soo; Kim, Byung-Wook; Hong, Su Jin; Lim, Hyun; Shin, Cheol Min; Lee, Si Hyung; Jeon, Seong Woo; Kim, Ji Hyun; Choi, Cheol Woong; Jung, Hye-Kyung; Kim, Jie-Hyun; Choi, Suck Chei; Cho, Jin Woong; Lee, Wan Sik; Na, Soo-Young; Sung, Jae Kyu; Song, Kyung Ho; Chung, Jun-Won; Yun, Sung-Cheol

    2018-04-01

    The Korean College of Helicobacter and Upper Gastrointestinal Research has studied Helicobacter pylori (H. pylori) prevalence since 1998 and found a dynamic change in its prevalence in Korea. The aim of this study was to determine the recent H. pylori prevalence rate and compare it with that of previous studies according to socioeconomic variables. We planned to enroll 4920 asymptomatic Korean adults from 21 centers according to the population distribution of seven geographic areas (Seoul, Gyeonggi, Gangwon, Chungcheong, Kyungsang, Cholla, and Jeju). We centrally collected serum and tested H. pylori serum IgG using a chemiluminescent enzyme immunoassay. We analyzed 4917 samples (4917/4920 = 99.9%) from January 2015 to December 2016. After excluding equivocal serologic results, the H. pylori seropositivity rate was 51.0% (2414/4734). We verified a decrease in H. pylori seroprevalence compared with previous studies performed in 1998, 2005, and 2011 (P pylori seroprevalence rate differed by area: Cholla (59.5%), Chungcheong (59.2%), Kyungsang (55.1%), Jeju (54.4%), Gangwon (49.1%), Seoul (47.4%), and Gyeonggi (44.6%). The rate was higher in those older than 40 years (38.1% in those aged 30-39 years and 57.7% in those aged 40-49 years) and was lower in city residents than in noncity residents at all ages. Helicobacter pylori seroprevalence in Korea is decreasing and may vary according to population characteristics. This trend should be considered to inform H. pylori-related policies. © 2018 The Authors. Helicobacter Published by John Wiley & Sons Ltd.

  13. The Construction of Chimeric T-Cell Receptor with Spacer Base of Modeling Study of VHH and MUC1 Interaction

    Directory of Open Access Journals (Sweden)

    Nazanin Pirooznia

    2011-01-01

    Full Text Available Adaptive cell immunotherapy with the use of chimeric receptors leads to the best and most specific response against tumors. Chimeric receptors consist of a signaling fragment, extracellular spacer, costimulating domain, and an antibody. Antibodies cause immunogenicity; therefore, VHH is a good replacement for ScFv in chimeric receptors. Since peptide sequences have an influence on chimeric receptors, the effect of peptide domains on each other's conformation were investigated. CD3Zeta, CD28, VHH and CD8α, and FcgIIα are used as signaling moieties, costimulating domain, antibody, and spacers, respectively. To investigate the influence of the ligation of spacers on the conformational structure of VHH, models of VHH were constructed. Molecular dynamics simulation was run to study the influence of the presence of spacers on the conformational changes in the binding sites of VHH. Root mean square deviation and root mean square fluctuation of critical segments in the binding site showed no noticeable differences with those in the native VHH. Results from molecular docking revealed that the presence of spacer FcgIIα causes an increasing effect on VHH with MUC1 interaction. Each of the constructs was transformed into the Jurkat E6.1. Expression analysis and evaluation of their functions were examined. The results showed good expression and function.

  14. Whole genome-based phylogeny of reptile-associated Helicobacter indicates independent niche adaptation followed by diversification in a poikilothermic host.

    Science.gov (United States)

    Gilbert, Maarten J; Duim, Birgitta; Timmerman, Arjen J; Zomer, Aldert L; Wagenaar, Jaap A

    2017-08-21

    Reptiles have been shown to host a significant Helicobacter diversity. In order to survive, reptile-associated Helicobacter lineages need to be adapted to the thermally dynamic environment encountered in a poikilothermic host. The whole genomes of reptile-associated Helicobacter lineages can provide insights in Helicobacter host adaptation and coevolution. These aspects were explored by comparing the genomes of reptile-, bird-, and mammal-associated Helicobacter lineages. Based on average nucleotide identity, all reptile-associated Helicobacter lineages in this study could be considered distinct species. A whole genome-based phylogeny showed two distinct clades, one associated with chelonians and one associated with lizards. The phylogeny indicates initial adaptation to an anatomical niche, which is followed by an ancient host jump and subsequent diversification. Furthermore, the ability to grow at low temperatures, which might reflect thermal adaptation to a reptilian host, originated at least twice in Helicobacter evolution. A putative tricarballylate catabolism locus was specifically present in Campylobacter and Helicobacter isolates from reptiles. The phylogeny of reptile-associated Helicobacter parallels host association, indicating a high level of host specificity. The high diversity and deep branching within these clades supports long-term coevolution with, and extensive radiation within the respective reptilian host type.

  15. The belonging of gpMuc, a glycoprotein from Mucuna pruriens seeds, to the Kunitz-type trypsin inhibitor family explains its direct anti-snake venom activity.

    Science.gov (United States)

    Scirè, Andrea; Tanfani, Fabio; Bertoli, Enrico; Furlani, Emiliano; Nadozie, Hope-Onyekwere N; Cerutti, Helena; Cortelazzo, Alessio; Bini, Luca; Guerranti, Roberto

    2011-07-15

    In Nigeria, Mucuna pruriens seeds are locally prescribed as an oral prophylactic for snake bite and it is claimed that when two seeds are swallowed they protect the individual for a year against snake bites. In order to understand the Mucuna pruriens antisnake properties, the proteins from the acqueous extract of seeds were purified by three chromatographic steps: ConA affinity chromatography, tandem anionic-cationic exchange and gel filtration, obtaining a fraction conventionally called gpMucB. This purified fraction was analysed by SDS-PAGE obtaining 3 bands with apparent masses ranging from 20 to 24 kDa, and by MALDI-TOF which showed two main peaks of 21 and 23 kDa and another small peak of 19 kDa. On the other hand, gel filtration analysis of the native protein indicated a molecular mass of about 70 kDa suggesting that in its native form, gpMucB is most likely an oligomeric multiform protein. Infrared spectroscopy of gpMucB indicated that the protein is particularly thermostable both at neutral and acidic pHs and that it is an all beta protein. All data suggest that gpMucB belongs to the Kunitz-type trypsin inhibitor family explaining the direct anti-snake venom activity of Mucuna pruriens seeds. Copyright © 2011 Elsevier GmbH. All rights reserved.

  16. Detection of Helicobacter and Campylobacter spp. from the aquatic environment of marine mammals.

    Science.gov (United States)

    Goldman, C G; Matteo, M J; Loureiro, J D; Degrossi, J; Teves, S; Heredia, S Rodriguez; Alvarez, K; González, A Beltrán; Catalano, M; Boccio, J; Cremaschi, G; Solnick, J V; Zubillaga, M B

    2009-01-13

    The mechanism by which Helicobacter species are transmitted remains unclear. To examine the possible role of environmental transmission in marine mammals, we sought the presence of Helicobacter spp. and non-Helicobacter bacteria within the order Campylobacterales in water from the aquatic environment of marine mammals, and in fish otoliths regurgitated by dolphins. Water was collected from six pools, two inhabited by dolphins and four inhabited by seals. Regurgitated otoliths were collected from the bottom of dolphins' pools. Samples were evaluated by culture, PCR and DNA sequence analysis. Sequences from dolphins' water and from regurgitated otoliths clustered with 99.8-100% homology with sequences from gastric fluids, dental plaque and saliva from dolphins living in those pools, and with 99.5% homology with H. cetorum. Sequences from seals' water clustered with 99.5% homology with a sequence amplified from a Northern sea lion (AY203900). Control PCR on source water for the pools and from otoliths dissected from feeder fish were negative. The findings of Helicobacter spp. DNA in the aquatic environment suggests that contaminated water from regurgitated fish otoliths and perhaps other tissues may play a role in Helicobacter transmission among marine mammals.

  17. Helicobacter pylori infection-induced H3Ser10 phosphorylation in stepwise gastric carcinogenesis and its clinical implications.

    Science.gov (United States)

    Yang, Tao-Tao; Cao, Na; Zhang, Hai-Hui; Wei, Jian-Bo; Song, Xiao-Xia; Yi, Dong-Min; Chao, Shuai-Heng; Zhang, Li-Da; Kong, Ling-Fei; Han, Shuang-Yin; Yang, Yu-Xiu; Ding, Song-Ze

    2018-04-15

    Our previous works have demonstrated that Helicobacter pylori (Hp) infection can alter histone H3 serine 10 phosphorylation status in gastric epithelial cells. However, whether Helicobacter pylori-induced histone H3 serine 10 phosphorylation participates in gastric carcinogenesis is unknown. We investigate the expression of histone H3 serine 10 phosphorylation in various stages of gastric disease and explore its clinical implication. Stomach biopsy samples from 129 patients were collected and stained with histone H3 serine 10 phosphorylation, Ki67, and Helicobacter pylori by immunohistochemistry staining, expressed as labeling index. They were categorized into nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, and intestinal-type gastric cancer groups. Helicobacter pylori infection was determined by either 13 C-urea breath test or immunohistochemistry staining. In Helicobacter pylori-negative patients, labeling index of histone H3 serine 10 phosphorylation was gradually increased in nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia groups, peaked at low-grade intraepithelial neoplasia, and declined in high-grade intraepithelial neoplasia and gastric cancer groups. In Helicobacter pylori-infected patients, labeling index of histone H3 serine 10 phosphorylation followed the similar pattern as above, with increased expression over the corresponding Helicobacter pylori-negative controls except in nonatrophic gastritis patient whose labeling index was decreased when compared with Helicobacter pylori-negative control. Labeling index of Ki67 in Helicobacter pylori-negative groups was higher in gastric cancer than chronic atrophic gastritis and low-grade intraepithelial neoplasia groups, and higher in intestinal metaplasia group compared with chronic atrophic gastritis group. In Helicobacter pylori-positive groups, Ki67 labeling index was increased

  18. Syntheses, structures and redox properties of some complexes containing the Os(dppe)Cp* fragment, including [{Os(dppe)Cp*}2(mu-C triple bondCC triple bond C)].

    Science.gov (United States)

    Bruce, Michael I; Costuas, Karine; Davin, Thomas; Halet, Jean-François; Kramarczuk, Kathy A; Low, Paul J; Nicholson, Brian K; Perkins, Gary J; Roberts, Rachel L; Skelton, Brian W; Smith, Mark E; White, Allan H

    2007-12-14

    The sequential conversion of [OsBr(cod)Cp*] (9) to [OsBr(dppe)Cp*] (10), [Os([=C=CH2)(dppe)Cp*]PF6 ([11]PF6), [Os(C triple bond CH)(dppe)Cp*] (12), [{Os(dppe)Cp*}2{mu-(=C=CH-CH=C=)}][PF6]2 ([13](PF6)2) and finally [{Os(dppe)Cp*}(2)(mu-C triple bond CC triple bond C)] (14) has been used to make the third member of the triad [{M(dppe)Cp*}2(mu-C triple bond CC triple bond C)] (M = Fe, Ru, Os). The molecular structures of []PF6, 12 and 14, together with those of the related osmium complexes [Os(NCMe)(dppe)Cp*]PF6 ([15]PF6) and [Os(C triple bond CPh)(dppe)Cp*] (16), have been determined by single-crystal X-ray diffraction studies. Comparison of the redox properties of 14 with those of its iron and ruthenium congeners shows that the first oxidation potential E1 varies as: Fe approximately Os < Ru. Whereas the Fe complex has been shown to undergo three sequential 1-electron oxidation processes within conventional electrochemical solvent windows, the Ru and Os compounds undergo no fewer than four sequential oxidation events giving rise to a five-membered series of redox related complexes [{M(dppe)Cp*}2(mu-C4)]n+ (n = 0, 1, 2, 3 and 4), the osmium derivatives being obtained at considerably lower potentials than the ruthenium analogues. These results are complimented by DFT and DT DFT calculations.

  19. Occurrence of Co-Infection of Helicobacter pullorum and Campylobacter spp. in Broiler and Village (Indigenous Chickens

    Directory of Open Access Journals (Sweden)

    Soe Soe Wai, A. A. Saleha*, Z. Zunita, L. Hassan and A. Jalila

    2012-10-01

    Full Text Available The reports on prevalence of Helicobacter pullorum in broiler chickens are rather limited and lacking in village chickens. This study aimed to determine the occurrence of H. pullorum in broiler and village chickens in Selangor, Malaysia and to report the detection of co-infection of H. pullorum and Campylobacter spp. in these chickens. Village (indigenous chickens were sampled in five markets and broiler chickens from six farms in different localities. Cecal contents were aseptically obtained from the chickens and subjected to three cultural methods. The isolates were identified by biochemical tests and confirmed using a species-specific PCR assay. Helicobacter pullorum were isolated from 25% village chickens and 24.6% broiler chickens, with an overall occurrence of 24.7%. Eleven (50% of these positive chickens (nine in broiler and two in village chickens showed co-infection with Campylobacter spp.

  20. Helicobacter pylori

    DEFF Research Database (Denmark)

    Leth, Peter Mygind

    1992-01-01

    Helicobacter pylori (HP) are Gram-negative spiral bacteria which occur in the human stomach. The bacteria were cultured in vitro for the first time in 1983. It is suspected that the bacteria may cause chronic gastritis of type B and may also be a contributory cause of chronic ulceration and cancer...... of the stomach. The bacteria are accompanied by characteristic inflammatory changes in the gastric mucosa. The significance for gastritis, chronic ulceration, non-ulcer dyspepsia and carcinoma of the stomach is discussed. HP occurs in a great proportion of the population of the world and the frequency increases...

  1. A Novel Assay for Easy and Rapid Quantification of Helicobacter pylori Adhesion.

    Science.gov (United States)

    Skindersoe, Mette E; Rasmussen, Lone; Andersen, Leif P; Krogfelt, Karen A

    2015-06-01

    Reducing adhesion of Helicobacter pylori to gastric epithelial cells could be a new way to counteract infections with this organism. We here present a novel method for quantification of Helicobacter pylori adhesion to cells. Helicobacter pylori is allowed to adhere to AGS or MKN45g cells in a 96-well microtiter plate. Then wells are added saponin, which lyses the cells without affecting the bacteria. After addition of alamarBlue(®) (resazurin) and 1- to 2-hour incubation, fluorescence measurements can be used to quantify the number of adherent bacteria. By use of the method, we demonstrate that adhesion of both a sabA and babA deletion mutant of H. pylori is significantly reduced compared to the wild type. The method offers a number of applications and may be used to compare the adherence potential of different strains of H. pylori to either cells or different materials or to screen for potential anti-adhesive compounds. The results presented here suggest that this easy and reproducible assay is well suited for quantitative investigation of H. pylori adhesion. © 2015 John Wiley & Sons Ltd.

  2. [The influence of Helicobacter pylori infection on the occurance of gastroesophageal reflux in patients with renal insufficiency].

    Science.gov (United States)

    Stolić, Radojica; Jovanović, Aleksandar; Perić, Vladan; Trajković, Goran; Zivić, Ziva; Stolić, Dragica; Lazarević, Tatjana; Sovtić, Sasa

    2007-12-01

    Gastric acid is a key factor in the pathophysiology of gastroesophageal reflux disease. A plausible mechanism by which the Helicobacter pylori infection might protect against reflux disease is by its propensity to produce atrophic gastritis. The aim of the study was to establish the influence of Helicobacter pylori infection on the occurrence of gastroesophageal reflux in patients with different stages of renal insufficiency. The examination was organized as a prospective, clinical study and involved 68 patients--33 patients with preterminal stage of renal failure and 35 patients with terminal renal insufficiency. Due to dyspeptic difficulties, in all the patients there was preformed upper esophagogastroscopy and Helicobacter pylori infection was found by ureasa test. The patients with preterminal renal insufficiency were significantly younger than patients with terminal renal failure (53.4 +/- 11.1 vs. 65.4 +/- 12.3 years; p = 0.014). There was found a statistically significant difference between the groups in Helicobacter pylori infection (p = 0.03), hiatal hernia (p = 0.008), gastroesophageal reflux disease (p = 0.007), and duodenal ulcer (p = 0.002). Using the multiple non-parametric correlative analysis there was confirmed a negative correlation between Helicobacter pylori infection and gastro-esophageal reflux disease (Kendal tauB = -0.523; p = 0.003) and hiatal hernia (Kendal tauB = 0.403; p = 0.021), while there was found a positive correlation between gastro-esophageal reflux disease and hiatal hernia (Kendal tauB = 0.350; p = 0.044). Helicobacter pylori infection is a significant protective parameter of the incidence of gastro-esophageal reflux disease in patients with both pre-terminal and terminal renal insufficiency.

  3. The influence of Helicobacter pylori infection on the occurrence of gastroesophageal reflux in patients with renal insufficiency

    Directory of Open Access Journals (Sweden)

    Stolić Radojica

    2007-01-01

    Full Text Available Introduction/Aim. Gastric acid is a key factor in the pathophysiology of gastroesophageal reflux disease. A plausible mechanism by which the Helicobacter pylori infection might protect against reflux disease is by its propensity to produce atrophic gastritis. The aim of the study was to establish the influence of Helicobacter pylori infection on the occurrence of gastroesophageal reflux in patients with different stages of renal insufficiency. Methods. The examination was organized as a prospective, clinical study and involved 68 patients − 33 patients with preterminal stage of renal failure and 35 patients with terminal renal insufficiency. Due to dyspeptic difficulties, in all the patients there was preformed upper esophagogastroscopy and Helicobacter pylori infection was found by ureasa test. Results. The patients with preterminal renal insufficiency were significantly younger than patients with terminal renal failure (53.4±11.1 vs. 65.4±12.3 years; p = 0.014. There was found a statistically significant difference between the groups in Helicobacter pylori infection (p = 0.03, hiatal hernia (p = 0.008, gastroesophageal reflux disease (p = 0.007, and duodenal ulcer (p = 0.002. Using the multiple non-parametric correlative analysis there was confirmed a negative correlation between Helicobacter pylori infection and gastro-esophageal reflux disease (Kendal τB = -0.523; p = 0.003 and hiatal hernia (Kendal τB = 0.403; p = 0.021, while there was found a positive correlation between gastro-esophageal reflux disease and hiatal hernia (Kendal τB = 0.350; p = 0.044. Conclusion. Helicobacter pylori infection is a significant protective parameter of the incidence of gastro-esophageal reflux disease in patients with both pre-terminal and terminal renal insufficiency.

  4. The occupational risk of Helicobacter pylori infection among gastroenterologists and their assistants

    Directory of Open Access Journals (Sweden)

    Costa José

    2011-05-01

    Full Text Available Abstract Background Helicobacter pylori is a widely spread bacterium that mainly inhabits the gastric mucosa and can lead to serious illnesses such as peptic ulcer disease, gastric carcinoma and gastric MALT lymphoma. The oral-oral route seems to be the main transmission route. The fact that endoscopes are contaminated after being used to perform a gastroscopy leads one to question whether gastroenterologists and endoscopy nurses and assistants run a higher risk of infection. Methods A systematic search for literature was conducted in the MEDLINE and EMBASE databases and further publications were found in reference lists of relevant articles. Epidemiological studies on the occupational exposure of endoscopy personnel were collected and their quality was assessed. Pooled effect estimates were identified in a meta-analysis. Results Of the 24 studies included in the analysis, 15 were considered to be methodologically good. Of these 15 studies, eight single studies showed a statistically significant increased risk of infection for gastroenterologists, and five for their assistants. Meta-analysis across all methodologically good studies found a statistically significant risk of 1.6 (95%CI 1.3-2.0 for doctors. The pooled effect estimates also indicated a statistically significant risk of Helicobacter pylori infection (RR 1.4; 95%CI 1.1-1.8 for assistants too. When studies are stratified by medical and non-medical control groups, statistically significant risks can only be recognised in the comparison with non-medical controls. Conclusions In summary, our results demonstrated an increased risk of Helicobacter pylori infection among gastroenterological personnel. However, the choice of control group is important for making a valid assessment of occupational exposure risks.

  5. MUC1 gene polymorphism in three Nelore lines selected for growth and its association with growth and carcass traits.

    Science.gov (United States)

    de Souza, Fabio Ricardo Pablos; Maione, Sandra; Sartore, Stefano; Soglia, Dominga; Spalenza, Veronica; Cauvin, Elsa; Martelli, Lucia Regina; Mercadante, Maria Eugênia Zerlotti; Sacchi, Paola; de Albuquerque, Lucia Galvão; Rasero, Roberto

    2012-02-01

    The objective of this study was to describe the VNTR polymorphism of the mucin 1 gene (MUC1) in three Nelore lines selected for yearling weight to determine whether allele and genotype frequencies of this polymorphism were affected by selection for growth. In addition, the effects of the polymorphism on growth and carcass traits were evaluated. Birth, weaning and yearling weights, rump height, Longissimus muscle area, backfat thickness, and rump fat thickness, were analyzed. A total of 295 Nelore heifers from the Beef Cattle Research Center, Instituto de Zootecnia de Sertãozinho, were used, including 41 of the control line, 102 of the selection line and 152 of the traditional. The selection and traditional lines comprise animals selected for higher yearling weight, whereas control line animals are selected for yearling weight close to the average. Five alleles were identified, with allele 1 being the most frequent in the three lines, especially in the lines selected for higher means for yearling weight. Heterozygosity was significantly higher in the control line. Association analyses showed significant effects of allele 1 on birth weight and weaning weight while the allele 3 exert significant effects on yearling weight and back fat thickness. Despite these findings, application of this marker to marker-assisted selection requires more consistent results based on the genotyping of a larger number of animals in order to increase the accuracy of the statistical analyses.

  6. Antibiotic resistance of Helicobacter pylori in Mashhad, Iran

    International Nuclear Information System (INIS)

    Zendedel, A.; Almasi, V.; Moradimoghadam, F.; Zivarifar, H.

    2013-01-01

    Objective: To evaluate Helicobacter pylori resistance to amoxicillin, clarithromycin, metronidazole and tetracycline in Mashhad, Iran. Methods: The cross-sectional study was done from January to May 2008 in Mashhad, involving 185 patients who had been indicated for endoscopy and lesions had been found. Biopsy samples were assessed with histological evaluation, rapid urease test, and culture. Antibiotic resistance was assessed by the disc diffusion method. Data was analysed with SPSS 11.5 using chi-square and Fisher exact test. P values of < 0.05 were regarded as statistically significant. Results: Of the total patients, histological evaluations were positive in 124 (67%). Compared with histology, sensitivity and specificity of rapid urease test were 96.7% and 100%, respectively. In 82 (66.1%) patients with positive cultures, antibiotic resistance was found in 14 (17.1%) for clarithromycin; 53 (64.6%) for metronidazole; and 8 (9.8%) for amoxicillin. No resistance was observed for tetracycline. Moreover, 9 (64%) patients with resistance to clarithromycin had co-resistance to metronidazole. Conclusion: Metronidazole is not recommended for treatment of Helicobacter pylori as a first-line drug. Also, considering the sensitivity and specificity of rapid urease test, we suggest this method as a suitable alternative for histology. (author)

  7. Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

    Directory of Open Access Journals (Sweden)

    Ivana Hitkova

    Full Text Available Caveolin-1 (Cav1 is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori is a major risk factor for human gastric cancer (GC where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS, infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies ("humming bird" compared to AGS cells stably transfected with Cav1 (AGS/Cav1. Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1 to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87 and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1 to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells.

  8. ( Asteraceae ) methanol extracts against Helicobacter pylori

    African Journals Online (AJOL)

    Methanol vehicle did not affect H. pylori growth. Conclusion: The observed antibacterial effect of G. glutinosum extracts may be of benefit as an adjuvant treatment of diseases caused by H. pylori. Key words: Gymnosperma glutinosum, Helicobacter pylori, methanol extract, minimal inhibitory concentration (MIC).

  9. Helicobacter pylori and early gastric cancer

    NARCIS (Netherlands)

    Craanen, M. E.; Blok, P.; Dekker, W.; Tytgat, G. N.

    1994-01-01

    The relation between Helicobacter pylori, intestinal metaplasia, and early gastric cancer was studied by examining gastrectomy specimens from 31 intestinal type and 22 diffuse type carcinomas. A total of 298 patients with antral gastritis were used as controls. Atrophic changes and intestinal

  10. Geographic pathology of Helicobacter pylori gastritis

    NARCIS (Netherlands)

    Liu, Yi; Ponsioen, Cyriel I. J.; Xiao, Shu-Dong; Tytgat, Guido N. J.; ten Kate, Fiebo J. W.

    2005-01-01

    Background and aim. Helicobacter pylori is etiologically associated with gastritis and gastric cancer. There are significant geographical differences between the clinical manifestation of H. pylori infections. The aim of this study was to compare gastric mucosal histology in relation to age among H.

  11. A Biotin Biosynthesis Gene Restricted to Helicobacter

    Science.gov (United States)

    Bi, Hongkai; Zhu, Lei; Jia, Jia; Cronan, John E.

    2016-01-01

    In most bacteria the last step in synthesis of the pimelate moiety of biotin is cleavage of the ester bond of pimeloyl-acyl carrier protein (ACP) methyl ester. The paradigm cleavage enzyme is Escherichia coli BioH which together with the BioC methyltransferase allows synthesis of the pimelate moiety by a modified fatty acid biosynthetic pathway. Analyses of the extant bacterial genomes showed that bioH is absent from many bioC-containing bacteria and is replaced by other genes. Helicobacter pylori lacks a gene encoding a homologue of the known pimeloyl-ACP methyl ester cleavage enzymes suggesting that it encodes a novel enzyme that cleaves this intermediate. We isolated the H. pylori gene encoding this enzyme, bioV, by complementation of an E. coli bioH deletion strain. Purified BioV cleaved the physiological substrate, pimeloyl-ACP methyl ester to pimeloyl-ACP by use of a catalytic triad, each member of which was essential for activity. The role of BioV in biotin biosynthesis was demonstrated using a reconstituted in vitro desthiobiotin synthesis system. BioV homologues seem the sole pimeloyl-ACP methyl ester esterase present in the Helicobacter species and their occurrence only in H. pylori and close relatives provide a target for development of drugs to specifically treat Helicobacter infections. PMID:26868423

  12. Helicobacter and Gastric Malignancies

    OpenAIRE

    Ferreira, António Carlos; Isomoto, Hajime; Moriyama, Masatsugu; Fujioka, Toshio; Machado, José Carlos; Yamaoka, Yoshio

    2008-01-01

    Individuals infected with Helicobacter pylori, a stomach colonizing bacteria, have an increased risk of developing gastric malignancies. The risk for developing cancer relates to the physiologic and histologic changes that H. pylori infection induces in the stomach. In the last year numerous studies have been conducted in order to characterize the association between H. pylori infection and gastric cancer. These studies range from epidemiologic approaches aiming at the identification of envir...

  13. Treatment for Helicobacter pylori infection and risk of Parkinson's disease in Denmark

    DEFF Research Database (Denmark)

    Nielsen, H H; Qiu, J; Friis, S

    2012-01-01

    It has been speculated that gastrointestinal infection with Helicobacter pylori (HP) contributes to the development of Parkinson's disease (PD). We used nationwide Danish registers to investigate this hypothesis.......It has been speculated that gastrointestinal infection with Helicobacter pylori (HP) contributes to the development of Parkinson's disease (PD). We used nationwide Danish registers to investigate this hypothesis....

  14. Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models

    Directory of Open Access Journals (Sweden)

    Michael D. Burkitt

    2017-02-01

    Full Text Available Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems.

  15. A novel monoclonal antibody to a defined peptide epitope in MUC16

    DEFF Research Database (Denmark)

    Marcos-Silva, Lara; Ricardo, Sara; Chen, Kowa

    2015-01-01

    with the tandem-repeat region, their epitopes appear to be conformational dependent and not definable by a short peptide. Aberrant glycoforms of MUC16 may constitute promising targets for diagnostic and immunotherapeutic intervention, and it is important to develop well-defined immunogens for induction of potent...... immunodominant linear peptide epitopes within the tandem repeat. We developed one monoclonal antibody, 5E11, reactive with a minimum epitope with the sequence FNTTER. This sequence contains potential N- and O-glycosylation sites and, interestingly, glycosylation blocked binding of 5E11. In immunochemistry...

  16. Occurrence, diversity, and host association of intestinal Campylobacter, Arcobacter, and Helicobacter in reptiles.

    Science.gov (United States)

    Gilbert, Maarten J; Kik, Marja; Timmerman, Arjen J; Severs, Tim T; Kusters, Johannes G; Duim, Birgitta; Wagenaar, Jaap A

    2014-01-01

    Campylobacter, Arcobacter, and Helicobacter species have been isolated from many vertebrate hosts, including birds, mammals, and reptiles. Multiple studies have focused on the prevalence of these Epsilonproteobacteria genera in avian and mammalian species. However, little focus has been given to the presence within reptiles, and their potential zoonotic and pathogenic roles. In this study, occurrence, diversity, and host association of intestinal Epsilonproteobacteria were determined for a large variety of reptiles. From 2011 to 2013, 444 cloacal swabs and fecal samples originating from 417 predominantly captive-held reptiles were screened for Epsilonproteobacteria. Campylobacter, Arcobacter, and Helicobacter genus specific PCRs were performed directly on all samples. All samples were also cultured on selective media and screened for the presence of Epsilonproteobacteria. Using a tiered approach of AFLP, atpA, and 16S rRNA sequencing, 432 Epsilonproteobacteria isolates were characterized at the species level. Based on PCR, Campylobacter, Arcobacter, and Helicobacter were detected in 69.3% of the reptiles; 82.5% of the chelonians, 63.8% of the lizards, and 58.0% of the snakes were positive for one or more of these genera. Epsilonproteobacteria were isolated from 22.1% of the reptiles and were isolated most frequently from chelonians (37.0%), followed by lizards (19.6%) and snakes (3.0%). The most commonly isolated taxa were Arcobacter butzleri, Arcobacter skirrowii, reptile-associated Campylobacter fetus subsp. testudinum, and a putative novel Campylobacter taxon. Furthermore, a clade of seven related putative novel Helicobacter taxa was isolated from lizards and chelonians. This study shows that reptiles carry various intestinal Epsilonproteobacteria taxa, including several putative novel taxa.

  17. Inactivation of Helicobacter pylori by Chloramination

    Science.gov (United States)

    Three strains of Helicobacter pylori (H. pylori) were studied to determine their resistance to chloramination. H. pylori is an organism listed on the U.S. Environmental Protection Agency’s (USEPA) Contaminant Control List (CCL). H. pylori was exposed to 2ppm of pre-formed monoc...

  18. Genetic diversity of the HpyC1I restriction modification system in Helicobacter pylori.

    Science.gov (United States)

    Lehours, Philippe; Dupouy, Sandrine; Chaineux, Julien; Ruskoné-Fourmestraux, Agnès; Delchier, Jean-Charles; Morgner, Andrea; Mégraud, Francis; Ménard, Armelle

    2007-04-01

    Helicobacter pylori is unique because of the unusually high number and diversity of its restriction modification (R-M) systems. HpyC1I R-M was recently characterized and contains an endonuclease which is an isoschizomer of the endonuclease BccI. This R-M is involved in adherence to gastric epithelial cells, a crucial step in bacterial pathogenesis. This observation illustrates the fact that R-M systems have other putative biological functions in addition to protecting the bacterial genome from external DNA. The genomic diversity of HpyC1I R-M was evaluated more precisely on a large collection of H. pylori strains by PCR, susceptibility to BccI digestion and sequencing. The results obtained support the mechanism of gain and loss of this R-M system in the H. pylori genome, and suggest that it is an ancestral system which gradually disappears during H. pylori evolution, following successive steps: (1) inactivation of the endonuclease gene, followed or accompanied by: (2) inactivation of the methyltransferase genes, and then: (3) definitive loss, leaving only short endonuclease remnant sequences.

  19. Helicobacter pylori and Peptic Ulcers

    Centers for Disease Control (CDC) Podcasts

    2010-08-17

    In this podcast, CDC's Dr. David Swerdlow discusses the relationship between Helicobacter pylori and peptic ulcer disease and trends in hospitalization rates for peptic ulcer disease in the United States between 1998 and 2005.  Created: 8/17/2010 by National Center for Emerging and Zoonotic Infectious Diseases.   Date Released: 8/17/2010.

  20. The rat IgGFcγBP and Muc2 C-terminal domains and TFF3 in two intestinal mucus layers bind together by covalent interaction.

    Directory of Open Access Journals (Sweden)

    Hao Yu

    Full Text Available The secreted proteins from goblet cells compose the intestinal mucus. The aims of this study were to determine how they exist in two intestinal mucus layers.The intestinal mucosa was fixed with Carnoy solution and immunostained. Mucus from the loose layer, the firm layer was gently suctioned or scraped, respectively, lysed in SDS sample buffer with or without DTT, then subjected to the western blotting of rTFF3, rIgGFcγBP or rMuc2. The non-reduced or reduced soluble mucus samples in RIPA buffer were co-immunoprecipitated to investigate their possible interactions. Polyclonal antibodies for rTFF3, the rIgGFcγBP C-terminal domain and the rMuc2 C-terminal domain confirmed their localization in the mucus layer and in the mucus collected from the rat intestinal loose layer or firm layer in both western blot and immunoprecipitation experiments. A complex of rTFF3, which was approximately 250 kDa, and a monomer of 6 kDa were present in both layers of the intestinal mucus; rIgGFcγBP was present in the complex (250-280 kDa under non-reducing conditions, but shifted to 164 kDa under reducing conditions in both of the layers. rMuc2 was found mainly in a complex of 214-270 kDa under non-reducing conditions, but it shifted to 140 kDa under reducing conditions. The co-immunoprecipitation experiments showed that binding occurs among rTFF3, rIgGFcγBP and rMuc2 in the RIPA buffer soluble intestinal mucus. Blocking the covalent interaction by 100 mM DTT in the RIPA buffer soluble intestinal mucus disassociated their binding.Rat goblet cell-secreted TFF3, IgGFcγBP and Muc2, existing in the two intestinal mucus layers, are bound together by covalent interactions in the soluble fraction of intestinal mucus and form heteropolymers to be one of the biochemical mechanisms of composing the net-like structure of mucus.

  1. Prevalência de helicobactérias e alterações na mucosa gástrica de cães saudáveis Prevalence of helicobacters and alterations in gastric mucosa of healthy dogs

    Directory of Open Access Journals (Sweden)

    F.Q. Moutinho

    2007-08-01

    Full Text Available Prevalence, distribution and density of gastric helicobacter colonization were determined in 50 healthy dogs, characterizing the macroscopic and microcospic aspects of their mucosa. Helicobacter prevalence was 96%, with greater distribution in the gastric fundus and body. Although the presence of macroscopic alterations was high (58%, it was characterized as mild due to the predominance of less severe ones (65.5%. High prevalence of mostly monoclear cell infriltate (64.7% was noted. Association between the presence of helicobacter and macro and microscopic alterations was not observed.

  2. A retrospective study of 5-year outcomes of radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication therapy

    International Nuclear Information System (INIS)

    Abe, Seiichiro; Oda, Ichiro; Inaba, Koji

    2013-01-01

    The favorable response rate of radiotherapy for localized gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication has been demonstrated. However, there are limited data available on the long-term outcomes. The aim of this retrospective study was to evaluate the long-term outcomes of radiotherapy for localized gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication. Thirty-four consecutive patients with localized gastric mucosa-associated lymphoid tissue lymphoma that were refractory to eradication were treated with radiotherapy (a total dose of 30 Gy). The response and adverse events of radiotherapy were retrospectively analyzed as short-term outcomes, and recurrence-free, overall and disease-specific survival rates were calculated as long-term outcomes. Thirty-three (97.1%) patients achieved complete remission and radiotherapy was well tolerated. One patient underwent emergency gastrectomy due to severe hematemesis. Of the 34 patients during the median follow-up period of 7.5 (1.2-13.0) years, one patient had local recurrence after 8.8 years, one patient underwent surgery for bowel obstruction secondary to small bowel metastasis after 5.1 years and one patient had pulmonary metastasis after 10.9 years. Pathologically, all three recurrences revealed mucosa-associated lymphoid tissue lymphoma without any transformation to high-grade lymphoma. None died of gastric mucosa-associated lymphoid tissue lymphoma. The 5-year recurrence-free survival rate was 97.0%. The 5-year overall survival rates and disease-specific survival rates were 97.0 and 100%, respectively. Radiotherapy in patients with localized gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication can achieve excellent overall survival. However, long-term surveillance is necessary to identify late recurrences. (author)

  3. A retrospective study of 5-year outcomes of radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication therapy.

    Science.gov (United States)

    Abe, Seiichiro; Oda, Ichiro; Inaba, Koji; Suzuki, Haruhisa; Yoshinaga, Shigetaka; Nonaka, Satoru; Morota, Madoka; Murakami, Naoya; Itami, Jun; Kobayashi, Yukio; Maeshima, Akiko Miyagi; Saito, Yutaka

    2013-09-01

    The favorable response rate of radiotherapy for localized gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication has been demonstrated. However, there are limited data available on the long-term outcomes. The aim of this retrospective study was to evaluate the long-term outcomes of radiotherapy for localized gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication. Thirty-four consecutive patients with localized gastric mucosa-associated lymphoid tissue lymphoma that were refractory to eradication were treated with radiotherapy (a total dose of 30 Gy). The response and adverse events of radiotherapy were retrospectively analyzed as short-term outcomes, and recurrence-free, overall and disease-specific survival rates were calculated as long-term outcomes. Thirty-three (97.1%) patients achieved complete remission and radiotherapy was well tolerated. One patient underwent emergency gastrectomy due to severe hematemesis. Of the 34 patients during the median follow-up period of 7.5 (1.2-13.0) years, one patient had local recurrence after 8.8 years, one patient underwent surgery for bowel obstruction secondary to small bowel metastasis after 5.1 years and one patient had pulmonary metastasis after 10.9 years. Pathologically, all three recurrences revealed mucosa-associated lymphoid tissue lymphoma without any transformation to high-grade lymphoma. None died of gastric mucosa-associated lymphoid tissue lymphoma. The 5-year recurrence-free survival rate was 97.0%. The 5-year overall survival rates and disease-specific survival rates were 97.0 and 100%, respectively. Radiotherapy in patients with localized gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication can achieve excellent overall survival. However, long-term surveillance is necessary to identify late recurrences.

  4. Validation of 14 C-urea breath test for diagnosis of Helicobacter pylori

    International Nuclear Information System (INIS)

    Mattar, Rejane; Silva, Fernando Marcuz; Alexandrino, Ana Maria; Laudanna, Antonio Atilio

    1999-01-01

    The aim of this study was to validate the 14 C-urea breath test for use in diagnosis of Helicobacter pylori infection. Thirty H. pylori positive patients, based on histologic test and thirty H. pylori negative patients by histology and anti-H pylori IgG entered the study. Fasting patients drank 5 uCi of 14 C-urea in 20 ml of water. Breath samples were collected at O, 5, 10, 15, 20 and 30 min. The difference of cpm values between the two groups was significant at all the time intervals, besides time 0 (p 14 C-urea breath test is highly accurate for Helicobacter pylori diagnosis. It is fast, simple and should be the non-invasive test used after treating Helicobacter pylori infection. (author)

  5. Nobeli auhinna tõi Helicobacter pylori / Juhan Kaldre

    Index Scriptorium Estoniae

    Kaldre, Juhan

    2005-01-01

    Nobeli meditsiiniauhind määrati sel aastal Austraalia teadlastele Robin Warrenile ja Barry Marshallile, kes avastasid, et gastriit ning peptiline haavand tekib Helicobacter pylori infektsiooni tulemusena

  6. Dietary Factors in Relation to Helicobacter pylori Infection

    Directory of Open Access Journals (Sweden)

    Seyyed Ali Mard

    2014-01-01

    Full Text Available Background and Aim. Helicobacter pylori (HP and diet are both risk factors for gastric cancer. The aim of this study was to evaluate the Helicobacter pylori infection and dietary habits common in Khuzestan province. Methods. This cross-sectional study was conducted in 2011–2013 on 374 patients. Participants were interviewed using a food frequency questionnaire and tissue sample of the antrum was sent for pathology lab. The histopathological major variables were graded on a scale of 3 (mild, moderate, and severe and data analyzed using nonparametric tests. Results. In this study, of 160 patients (43% that were determined, 8.1 percent had severe contamination. Among dietary patterns, relationship between energy intake and carbohydrate with H. pylori was significant. A direct association was found between mean daily intakes of sausage (P=0.001 and burgers (P<0.05 with HP infection. Low intake of fresh vegetables and fruits was the most significant risk factors (P<0.05. Conclusion. There is a possibility that some dietary factors such as consumption of fast foods and low intake of fresh vegetables may increase the chance of HP and severity of this infection.

  7. Helicobacter heilmannii-associated Gastritis: Clinicopathologic Findings and Comparison with Helicobacter pylori-associated Gastritis

    Science.gov (United States)

    Kwak, Ji Eun; Chang, Sun Hee; Kim, Hanseong; Chi, Je G.; Kim, Kyung-Ah; Yang, Jeon Ho; Lee, June Sung; Moon, Young-Soo; Kim, Kyoung-Mee

    2007-01-01

    The aims of this study were to evaluate the clinicopathologic features of Helicobacter heilmannii-associated gastritis and to compare H. heilmannii-associated gastritis with H. pylori-associated gastritis. We reviewed 5,985 consecutive gastric biopsy specimens. All cases of chronic gastritis with Helicobacter infection were evaluated with the Updated Sydney System, and the grades of all gastritis variables were compared between H. heilmannii-associated gastritis and H. pylori-associated gastritis groups. There were 10 cases of H. heilmannii-associated gastritis (0.17%) and 3,285 cases of H. pylori-associated gastritis (54.9%). The organisms were superficially located within the mucous layer without adhesion to epithelial cells. Interestingly, in one case many intracytoplasmic H. heilmannii organisms were observed in parietal cells with cell damage. A case of low-grade mucosa-associated lymphoid tissue (MALT) lymphoma concomitant with H. heilmannii infection was detected. Compared to H. pylori-associated gastritis, H. heilmannii-associated gastritis showed less severe neutrophilic activity (pgastritis devoid of erosion or ulcer (p=0.0309). In conclusion, we present the detailed clinicopathologic findings of H. heilmannii-associated gastritis compared to H. pylori-associated gastritis. H. heilmannii-associated gastritis is uncommon and milder than H. pylori-associated gastritis, however it may be noteworthy with respect to the development of MALT lymphoma. PMID:17297253

  8. IL10 single nucleotide polymorphisms are related to upregulation of constitutive IL-10 production and susceptibility to Helicobacter pylori infection.

    Science.gov (United States)

    Assis, Shirleide; Marques, Cintia Rodrigues; Silva, Thiago Magalhães; Costa, Ryan Santos; Alcantara-Neves, Neuza Maria; Barreto, Mauricio Lima; Barnes, Kathleen Carole; Figueiredo, Camila Alexandrina

    2014-06-01

    Helicobacter pylori infection is a strong risk factor for gastric cancer, likely due to the extensive inflammation in the stomach mucosa caused by these bacteria. Many studies have reported an association between IL10 polymorphisms, the risk of gastric cancer, and IL-10 production. The aim of the study was to evaluate the association between IL10 genetic variants, Helicobacter pylori infection, and IL-10 production by peripheral blood leukocytes in children. We genotyped a total of 12 single nucleotide polymorphisms in IL10 in 1259 children aged 4-11 years living in a poor urban area in Salvador, Brazil, using TaqMan probe based, 5' nuclease assay minor groove binder chemistry. Association tests were performed by logistic regression for Helicobacter pylori infection and linear regression for IL-10 spontaneous production (whole-blood cultures) including sex, age, and principal components for informative ancestry markers as covariates, using PLINK. Our results shown that IL10 single nucleotide polymorphisms rs1800896 (OR = 1.63; 95% CI = 1.11-2.39), rs3024491 (OR = 1.71; 95% CI = 1.14-2.57), rs1878672 (OR = 1.79; 95% CI = 1.19-2.68), and rs3024496 (OR = 1.48; 95% CI = 1.05-2.08) were positively associated with Helicobacter pylori infection. Eight single nucleotide polymorphisms were associated with spontaneous production of IL-10 in culture, of which three (rs1800896 and rs1878672, p = .04; rs3024491, p = .01) were strongly associated with infection by Helicobacter pylori. Our results indicate that IL10 variants rs1800896, rs3024491, rs1878672, and rs3024496 are more consistently associated with the presence of anti-H. pylori IgG by inducing increased production of IL-10. Further studies are underway to elucidate the role of additional genetic variants and to investigate their impact on the occurrence of gastric cancer. © 2014 John Wiley & Sons Ltd.

  9. Helicobacter Pylori eradication therapy: getting research into practice.

    LENUS (Irish Health Repository)

    McDonnell, R

    2003-01-01

    Helicobacter Pylori (H. Pylori) is the primary cause of duodenal ulcer (DU). Guidelines recommend that all patients with DU be considered for Helicobacter Pylori Eradication Therapy (HPET). However, the proportion of patients with DU on long term anti-ulcer medication receiving HPET is small. This study examined the effectiveness of the continuing medical education (CME) network of the Irish College of General Practitioners (ICGP) in promoting best practice in DU treatment among GPs in an eastern region of Ireland. Ninty eight GPs recruited from the CME network of the ICGP were randomised in two cohorts. Cohort 1 received an (early) intervention; GPs were asked to identify their patients with DU receiving long term anti-ulcer medication and prescribe HPET according to defined criteria. Cohort 2 received the intervention later. Prescribing of HPET was monitored using routine prescribing data. Twenty per cent (286\\/1,422) of patients in cohort 1 and 19.2% (127\\/661) in cohort 2 had a DU. After exclusions, 53% (152\\/286) in cohort 1 and 30.7% (39\\/127) in cohort 2, were eligible for HPET. A significantly higher proportion of patients in cohort 1 received HPET compared with cohort 2 during the early intervention period (13.8% vs 0.0%, p<0.05). Reasons for not prescribing HPET included concurrent illness in patients, failure to comply with treatment. Best practice guidelines on HPET treatment of DU can be successfully applied using CME networks. This model could be repeated in another therapeutic area where established research is not yet current practice.

  10. Helicobacter pylori virulence and cancer pathogenesis.

    Science.gov (United States)

    Yamaoka, Yoshio; Graham, David Y

    2014-06-01

    Helicobacter pylori is human gastric pathogen that causes chronic and progressive gastric mucosal inflammation and is responsible for the gastric inflammation-associated diseases, gastric cancer and peptic ulcer disease. Specific outcomes reflect the interplay between host-, environmental- and bacterial-specific factors. Progress in understanding putative virulence factors in disease pathogenesis has been limited and many false leads have consumed scarce resources. Few in vitro-in vivo correlations or translational applications have proved clinically relevant. Reported virulence factor-related outcomes reflect differences in relative risk of disease rather than specificity for any specific outcome. Studies of individual virulence factor associations have provided conflicting results. Since virulence factors are linked, studies of groups of putative virulence factors are needed to provide clinically useful information. Here, the authors discuss the progress made in understanding the role of H. pylori virulence factors CagA, vacuolating cytotoxin, OipA and DupA in disease pathogenesis and provide suggestions for future studies.

  11. [The relationship of halitosis and Helicobacter pylori].

    Science.gov (United States)

    Chen, Xi; Tao, Dan-ying; Li, Qing; Feng, Xi-ping

    2007-06-01

    The aim of the study was to investigate the relationship between halitosis and Helicobacter pylori infection in stomach. Fifty subjects without periodontal diseases and systematic disease (exclude gastrointestinal diseases) were included. Infection of H.pylori was diagnosed by biopsy and (14)C-urea breath test. SPSS11.5 software package was used to analyze the data. All the subjects were periodontal healthy according to the periodontal index. The prevalence of H.pylori infection in halitosis subjects was significantly higher than that in the normal subjects (57.1% VS 18.2%, Pperiodontal healthy subjects.

  12. Whole genome-based phylogeny of reptile-associated Helicobacter indicates independent niche adaptation followed by diversification in a poikilothermic host

    NARCIS (Netherlands)

    Gilbert, Maarten J.; Duim, Birgitta; Timmerman, Arjen J.; Zomer, Aldert L.; Wagenaar, Jaap A.

    2017-01-01

    Reptiles have been shown to host a significant Helicobacter diversity. In order to survive, reptile-associated Helicobacter lineages need to be adapted to the thermally dynamic environment encountered in a poikilothermic host. The whole genomes of reptile-associated Helicobacter lineages can

  13. Whole genome-based phylogeny of reptile-associated Helicobacter indicates independent niche adaptation followed by diversification in a poikilothermic host

    NARCIS (Netherlands)

    Gilbert, Maarten J; Duim, Birgitta; Timmerman, Arjen J; Zomer, Aldert L; Wagenaar, Jaap A

    2017-01-01

    Reptiles have been shown to host a significant Helicobacter diversity. In order to survive, reptile-associated Helicobacter lineages need to be adapted to the thermally dynamic environment encountered in a poikilothermic host. The whole genomes of reptile-associated Helicobacter lineages can provide

  14. Helicobacter pylori stool antigen test (HpSA) for the diagnosis of gastric infection

    International Nuclear Information System (INIS)

    Faruqui, A.N.; Majid, U.; Ahmed, L.; Khalil, M.; Hussan, M.U.

    2007-01-01

    To determine the accuracy of Helicobacter pylori Stool Antigen test (HpSA), compared with endoscopic histopathology for the diagnosis of gastric Helicobecter pylori infection. A total of 50 patients underwent endoscopy for gastric antral mucosal tissue biopsy for histopathology of H.pylori and advised for HpSA. Patient's information including age, gender, past history, presenting signs and symptoms, results of HpSA and histopathology were recorded. Sensitivity analysis was performed to calculate sensitivity, specificity, and predictive values of HpSA. Among 50 patients, 48% males and 52% females (M: F 1: 1.08), a total of 27 (54%) were true positive while 20 (40%) were true negative. Two patients were false negative and only one was false positive. Sensitivity of HpSA was, therefore, 93.1%, specificity 95% and positive and negative predictive values were 96.42% and 90.9% respectively. Helicobacter pylori stool antigen was an accurate and reliable test for the diagnosis of gastric H. pylori infection. (author)

  15. Helicobacter pylori as a potential target for the treatment of central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Antonio Marcelo Barbante Casella

    2012-09-01

    Full Text Available OBJECTIVES: The objective of this study was to evaluate the relationship between the treatment of Helicobacter pylori gastric infection and changes in best-corrected visual acuity and macular detachment in patients with chronic central serous chorioretinopathy. METHODS: Seventeen patients diagnosed with central serous chorioretinopathy were examined for gastric infection with Helicobacter pylori using the urease test and gastric biopsy. Helicobacter pylory-positive patients were treated with the appropriate medication. The response to therapy was monitored by evaluating the best-corrected visual acuity and optical coherence tomography. The data were analyzed using Student's t-test before and after treatment. RESULTS: Fourteen patients (15 eyes aged 30-56 years (mean 43.4 ± 8.3 years were positive for Helicobacter pylori. Most of the positive patients had gastric symptoms (78.5%; one had bilateral central serous chorioretinopathy. The mean baseline best-corrected visual acuity was 20/98 (logMAR = 0.53 ± 0.28. Three months after starting treatment with antibiotics, the serous detachment had resolved in 14 of 15 eyes, but two cases required laser treatment. The follow-up period ranged from 6 to 27 months. The mean final best-corrected visual acuity differed significantly from baseline. CONCLUSION: Our findings suggest that Helicobacter pylori infection may be present in many chronic central serous chorioretinopathy patients and that treatment for the infection may have a favorable effect on the outcome of chronic central serous chorioretinopathy. Due to the possibility of the spontaneous regression of chronic central serous chorioretinopathy and the high prevalence of the infection in the general population, prospective and masked clinical trials are necessary to confirm that treatment for Helicobacter pylori infection may benefit patients with chronic central serous chorioretinopathy.

  16. Pancreatic ductal adenocarcinoma mice lacking mucin 1 have a profound defect in tumor growth and metastasis.

    Science.gov (United States)

    Besmer, Dahlia M; Curry, Jennifer M; Roy, Lopamudra D; Tinder, Teresa L; Sahraei, Mahnaz; Schettini, Jorge; Hwang, Sun-Il; Lee, Yong Y; Gendler, Sandra J; Mukherjee, Pinku

    2011-07-01

    MUC1 is overexpressed and aberrantly glycosylated in more than 60% of pancreatic ductal adenocarcinomas. The functional role of MUC1 in pancreatic cancer has yet to be fully elucidated due to a dearth of appropriate models. In this study, we have generated mouse models that spontaneously develop pancreatic ductal adenocarcinoma (KC), which are either Muc1-null (KCKO) or express human MUC1 (KCM). We show that KCKO mice have significantly slower tumor progression and rates of secondary metastasis, compared with both KC and KCM. Cell lines derived from KCKO tumors have significantly less tumorigenic capacity compared with cells from KCM tumors. Therefore, mice with KCKO tumors had a significant survival benefit compared with mice with KCM tumors. In vitro, KCKO cells have reduced proliferation and invasion and failed to respond to epidermal growth factor, platelet-derived growth factor, or matrix metalloproteinase 9. Further, significantly less KCKO cells entered the G(2)-M phase of the cell cycle compared with the KCM cells. Proteomics and Western blotting analysis revealed a complete loss of cdc-25c expression, phosphorylation of mitogen-activated protein kinase (MAPK), as well as a significant decrease in nestin and tubulin-α2 chain expression in KCKO cells. Treatment with a MEK1/2 inhibitor, U0126, abrogated the enhanced proliferation of the KCM cells but had minimal effect on KCKO cells, suggesting that MUC1 is necessary for MAPK activity and oncogenic signaling. This is the first study to utilize a Muc1-null PDA mouse to fully elucidate the oncogenic role of MUC1, both in vivo and in vitro. ©2011 AACR

  17. Tumor necrosis factor-α and Muc2 mucin play major roles in disease onset and progression in dextran sodium sulphate-induced colitis.

    Directory of Open Access Journals (Sweden)

    Poonam Dharmani

    Full Text Available The sequential events and the inflammatory mediators that characterize disease onset and progression of ulcerative colitis (UC are not well known. In this study, we evaluated the early pathologic events in the pathogenesis of colonic ulcers in rats treated with dextran sodium sulfate (DSS. Following a lag phase, day 5 of DSS treatment was found clinically most critical as disease activity index (DAI exhibited an exponential rise with severe weight loss and rectal bleeding. Surprisingly, on days 1-2, colonic TNF-α expression (70-80-fold and tissue protein (50-fold were increased, whereas IL-1β only increased on days 7-9 (60-90-fold. Days 3-6 of DSS treatment were characterized by a prominent down regulation in the expression of regulatory cytokines (40-fold for IL-10 and TGFβ and mucin genes (15-18 fold for Muc2 and Muc3 concomitant with depletion of goblet cell and adherent mucin. Remarkably, treatment with TNF-α neutralizing antibody markedly altered DSS injury with reduced DAI, restoration of the adherent and goblet cell mucin and IL-1β and mucin gene expression. We conclude that early onset colitis is dependent on TNF-α that preceded depletion of adherent and goblet cell mucin prior to epithelial cell damage and these biomarkers can be used as therapeutic targets for UC.

  18. HELICOBACTER PYLORI: THE CAUSATIVE AGENT OF PEPTIC ...

    African Journals Online (AJOL)

    DR. AMINU

    Helicobacter pylori by treatment with antibiotics in peptic ulcer patients resulted in the healing of the ulcer. ... and gastric cancers. .... H. pyloris cause chronic active gastritis in humans and ... of the night when the stomach is empty and is.

  19. Prevalence of Helicobacter Pylori Infection Among Patients ...

    African Journals Online (AJOL)

    Conclusion: The prevalence of H. pylori infection is significantly high in rural and suburban population of Ernakulam district, Kerala. Early detection and prompt treatment are essential for prevention of serious complications. Keywords: Gastrointestinal complications, Helicobacter pylori infection, Histopathological ...

  20. Occurrence, Diversity, and Host Association of Intestinal Campylobacter, Arcobacter, and Helicobacter in Reptiles

    Science.gov (United States)

    Gilbert, Maarten J.; Kik, Marja; Timmerman, Arjen J.; Severs, Tim T.; Kusters, Johannes G.; Duim, Birgitta; Wagenaar, Jaap A.

    2014-01-01

    Campylobacter, Arcobacter, and Helicobacter species have been isolated from many vertebrate hosts, including birds, mammals, and reptiles. Multiple studies have focused on the prevalence of these Epsilonproteobacteria genera in avian and mammalian species. However, little focus has been given to the presence within reptiles, and their potential zoonotic and pathogenic roles. In this study, occurrence, diversity, and host association of intestinal Epsilonproteobacteria were determined for a large variety of reptiles. From 2011 to 2013, 444 cloacal swabs and fecal samples originating from 417 predominantly captive-held reptiles were screened for Epsilonproteobacteria. Campylobacter, Arcobacter, and Helicobacter genus specific PCRs were performed directly on all samples. All samples were also cultured on selective media and screened for the presence of Epsilonproteobacteria. Using a tiered approach of AFLP, atpA, and 16S rRNA sequencing, 432 Epsilonproteobacteria isolates were characterized at the species level. Based on PCR, Campylobacter, Arcobacter, and Helicobacter were detected in 69.3% of the reptiles; 82.5% of the chelonians, 63.8% of the lizards, and 58.0% of the snakes were positive for one or more of these genera. Epsilonproteobacteria were isolated from 22.1% of the reptiles and were isolated most frequently from chelonians (37.0%), followed by lizards (19.6%) and snakes (3.0%). The most commonly isolated taxa were Arcobacter butzleri, Arcobacter skirrowii, reptile-associated Campylobacter fetus subsp. testudinum, and a putative novel Campylobacter taxon. Furthermore, a clade of seven related putative novel Helicobacter taxa was isolated from lizards and chelonians. This study shows that reptiles carry various intestinal Epsilonproteobacteria taxa, including several putative novel taxa. PMID:24988130

  1. Occurrence, diversity, and host association of intestinal Campylobacter, Arcobacter, and Helicobacter in reptiles.

    Directory of Open Access Journals (Sweden)

    Maarten J Gilbert

    Full Text Available Campylobacter, Arcobacter, and Helicobacter species have been isolated from many vertebrate hosts, including birds, mammals, and reptiles. Multiple studies have focused on the prevalence of these Epsilonproteobacteria genera in avian and mammalian species. However, little focus has been given to the presence within reptiles, and their potential zoonotic and pathogenic roles. In this study, occurrence, diversity, and host association of intestinal Epsilonproteobacteria were determined for a large variety of reptiles. From 2011 to 2013, 444 cloacal swabs and fecal samples originating from 417 predominantly captive-held reptiles were screened for Epsilonproteobacteria. Campylobacter, Arcobacter, and Helicobacter genus specific PCRs were performed directly on all samples. All samples were also cultured on selective media and screened for the presence of Epsilonproteobacteria. Using a tiered approach of AFLP, atpA, and 16S rRNA sequencing, 432 Epsilonproteobacteria isolates were characterized at the species level. Based on PCR, Campylobacter, Arcobacter, and Helicobacter were detected in 69.3% of the reptiles; 82.5% of the chelonians, 63.8% of the lizards, and 58.0% of the snakes were positive for one or more of these genera. Epsilonproteobacteria were isolated from 22.1% of the reptiles and were isolated most frequently from chelonians (37.0%, followed by lizards (19.6% and snakes (3.0%. The most commonly isolated taxa were Arcobacter butzleri, Arcobacter skirrowii, reptile-associated Campylobacter fetus subsp. testudinum, and a putative novel Campylobacter taxon. Furthermore, a clade of seven related putative novel Helicobacter taxa was isolated from lizards and chelonians. This study shows that reptiles carry various intestinal Epsilonproteobacteria taxa, including several putative novel taxa.

  2. Characterization in Helicobacter pylori of a Nickel Transporter Essential for Colonization That Was Acquired during Evolution by Gastric Helicobacter Species

    Science.gov (United States)

    Turlin, Evelyne; Mancuso, Francesco; Michel, Valérie; Richaud, Pierre; Veyrier, Frédéric J.; De Reuse, Hilde; Vinella, Daniel

    2016-01-01

    Metal acquisition is crucial for all cells and for the virulence of many bacterial pathogens. In particular, nickel is a virulence determinant for the human gastric pathogen Helicobacter pylori as it is the cofactor of two enzymes essential for in vivo colonization, urease and a [NiFe] hydrogenase. To import nickel despite its scarcity in the human body, H. pylori requires efficient uptake mechanisms that are only partially defined. Indeed, alternative ways of nickel entry were predicted to exist in addition to the well-described NixA permease. Using a genetic screen, we identified an ABC transporter, that we designated NiuBDE, as a novel H. pylori nickel transport system. Unmarked mutants carrying deletions of nixA, niuD and/or niuB, were constructed and used to measure (i) tolerance to toxic nickel exposure, (ii) intracellular nickel content by ICP-OES, (iii) transport of radioactive nickel and (iv) expression of a reporter gene controlled by nickel concentration. We demonstrated that NiuBDE and NixA function separately and are the sole nickel transporters in H. pylori. NiuBDE, but not NixA, also transports cobalt and bismuth, a metal currently used in H. pylori eradication therapy. Both NiuBDE and NixA participate in nickel-dependent urease activation at pH 5 and survival under acidic conditions mimicking those encountered in the stomach. However, only NiuBDE is able to carry out this activity at neutral pH and is essential for colonization of the mouse stomach. Phylogenomic analyses indicated that both nixA and niuBDE genes have been acquired via horizontal gene transfer by the last common ancestor of the gastric Helicobacter species. Our work highlights the importance of this evolutionary event for the emergence of Helicobacter gastric species that are adapted to the hostile environment of the stomach where the capacity of Helicobacter to import nickel and thereby activate urease needs to be optimized. PMID:27923069

  3. Prevalence of Helicobacter Pylori Infection Among Patients ...

    African Journals Online (AJOL)

    was seen. Conclusion: The prevalence of H. pylori infection is significantly high in rural and suburban population of Ernakulam district, Kerala. Early detection and prompt treatment are essential for prevention of serious complications. Keywords: Gastrointestinal complications, Helicobacter pylori infection, Histopathological ...

  4. Mucin dynamics in intestinal bacterial infection.

    Directory of Open Access Journals (Sweden)

    Sara K Lindén

    Full Text Available Bacterial gastroenteritis causes morbidity and mortality in humans worldwide. Murine Citrobacter rodentium infection is a model for gastroenteritis caused by the human pathogens enteropathogenic Escherichia coli and enterohaemorrhagic E. coli. Mucin glycoproteins are the main component of the first barrier that bacteria encounter in the intestinal tract.Using Immunohistochemistry, we investigated intestinal expression of mucins (Alcian blue/PAS, Muc1, Muc2, Muc4, Muc5AC, Muc13 and Muc3/17 in healthy and C. rodentium infected mice. The majority of the C. rodentium infected mice developed systemic infection and colitis in the mid and distal colon by day 12. C. rodentium bound to the major secreted mucin, Muc2, in vitro, and high numbers of bacteria were found in secreted MUC2 in infected animals in vivo, indicating that mucins may limit bacterial access to the epithelial surface. In the small intestine, caecum and proximal colon, the mucin expression was similar in infected and non-infected animals. In the distal colonic epithelium, all secreted and cell surface mucins decreased with the exception of the Muc1 cell surface mucin which increased after infection (p<0.05. Similarly, during human infection Salmonella St Paul, Campylobacter jejuni and Clostridium difficile induced MUC1 in the colon.Major changes in both the cell-surface and secreted mucins occur in response to intestinal infection.

  5. Pancreatic Ductal Adenocarcinoma (PDA) mice lacking Mucin 1 have a profound defect in tumor growth and metastasis

    Science.gov (United States)

    Besmer, Dahlia M.; Curry, Jennifer M.; Roy, Lopamudra D.; Tinder, Teresa L.; Sahraei, Mahnaz; Schettini, Jorge; Hwang, Sun-Il; Lee, Yong Y.; Gendler, Sandra J.; Mukherjee, Pinku

    2011-01-01

    MUC1 is over expressed and aberrantly glycosolated in >60% of pancreatic ductal adenocarcinomas. The functional role of MUC1 in pancreatic cancer has yet to be fully elucidated due to a dearth of appropriate models. In the present study, we have generated mouse models that spontaneously develop pancreatic ductal adenocarcinoma (KC), which are either Muc1-null (KCKO) or express human MUC1 (KCM). We show that KCKO mice have significantly slower tumor progression and rates of secondary metastasis, compared to both KC and KCM. Cell lines derived from KCKO tumors have significantly lower tumorigenic capacity compared to cells from KCM tumors. Therefore, mice with KCKO tumors had a significant survival benefit compared to mice with KCM tumors. In vitro, KCKO cells have reduced proliferation and invasion and failed to respond to epidermal growth factor (EGF), platelet-derived growth factor (PDGF), or matrix metalloproteinase-9 (MMP9). Further, significantly fewer KCKO cells entered the G2M phase of the cell cycle compared to the KCM cells. Proteomics and western blotting analysis revealed a complete loss of cdc-25c expression, phosphorylation of MAPK, as well as a significant decrease in Nestin and Tubulin α-2 chain expression in KCKO cells. Treatment with a MEK1/2 inhibitor, U0126, abrogated the enhanced proliferation of the KCM cells but had minimal effect on KCKO cells, suggesting that MUC1 is necessary for MAPK activity and oncogenic signaling. This is the first study to utilize a Muc1-null PDA mouse in order to fully elucidate the oncogenic role of MUC1, both in vivo and in vitro. PMID:21558393

  6. Autoimmune gastritis: relationships with anemia and Helicobacter pylori status.

    Science.gov (United States)

    Villanacci, Vincenzo; Casella, Giovanni; Lanzarotto, Francesco; Di Bella, Camillo; Sidoni, Angelo; Cadei, Moris; Salviato, Tiziana; Dore, Maria Pina; Bassotti, Gabrio

    Autoimmune gastritis (AIG) is a gastric pathologic condition affecting the mucosa of the fundus and the body and eventually leading to hypo-achlorhydria. We report our clinical and pathological experience with AIG. Data from patients with a diagnosis of AIG seen in the period January 2002-December 2012 were retrieved. Only patients with complete sets of biopsies were analyzed. Data from 138 patients were available for analysis. Pernicious anemia was present in 25% of patients, iron deficiency anemia was found in 29.7% of patients, hypothyroidism in 23% of patients, type 1 diabetes in 7.9% of patients, and vitiligo in 2.8% of patients. Parietal cell antibodies were positive in 65% of patients, and no patient had serology positive for celiac disease. All gastric biopsies showed glandular atrophy associated with enterochromaffin-like (ECL)-cells hyperplasia, features limited to the mucosa of the fundus and body, and focal glandular intestinal metaplasia. Helicobacter pylori was negative in all cases. AIG was strongly associated with anemia; atrophy, intestinal metaplasia and ECL hyperplasia in the gastric fundus and body are hallmarks of this condition.

  7. Randomized Controlled Trial for Helicobacter pylori Eradication in a Naive Portuguese Population: Is Sequential Treatment Superior to Triple Therapy in Real World Clinical Setting?

    Science.gov (United States)

    Boal Carvalho, Pedro; Magalhães, Joana; Dias de Castro, Francisca; Rosa, Bruno; Cotter, José

    2017-03-31

    Helicobacter pylori eradication has become increasingly difficult as resistances to several antibiotics develop. We aimed to compare Helicobacter pylori eradication rates between triple therapy and sequential therapy in a naive Portuguese population. Prospective randomized trial including consecutive patients referred for first-line Helicobacter pylori eradication treatment. previous gastric surgery/neoplasia, pregnancy/lactancy, allergy to any of the drugs. The compared eradication regimens were triple therapy (pantoprazol, amoxicillin and clarithromycin 12/12 hours, 14 days) and sequential therapy (pantoprazol 12/12 hours for 10 days, amoxicillin 12/12 hours for days 1 - 5 and clarithromycin plus metronidazol 12/12 hours during days 6 - 10). Eradication success was confirmed with urea breath test. Statistical analysis was performed with SPSS v21.0 and a p-value population, we found a satisfactory global Helicobacter pylori eradication rate of 82%, with no statistical differences observed in the efficacy of the treatment between triple and sequential regimens. These results support the use of either therapy for the first-line eradication of Helicobacter pylori.

  8. Effect of helicobacter pylori L-form infection on proliferation, apoptosis and invasion molecule expression in gastric cancer tissue

    Directory of Open Access Journals (Sweden)

    Hua Xin

    2017-05-01

    Full Text Available Objective: To study the effect of Helicobacter pylori L-form infection on proliferation, apoptosis and invasion molecule expression in gastric cancer tissue. Methods: The gastric cancer tissues surgically removed in our hospital between May 2013 and October 2016 were collected and divided into Hp negative, Hp-L negative and Hp-L positive according to the condition of helicobacter pylori infection. The proliferation, apoptosis and invasion gene expression were detected. Results: LOXL2, PCNA, CyclinD1, Rab1A, Bcl-2, Snail, N-cadherin, UHRF1 and AnnexinII mRNA expression in Hp-L-positive gastric cancer tissues were significantly higher than those in Hp-L-negative and Hp-negative gastric cancer tissues while ING5, PTPN13, Beclin1 and Mst1 mRNA expression were significantly lower than those in Hp-L-negative and Hp-negative gastric cancer tissues; LOXL2, PCNA, CyclinD1, Rab1A, Bcl-2, ING5, PTPN13, Beclin1, Mst1, Snail, N-cadherin, UHRF1 and AnnexinII mRNA expression in Hp-L-negative gastric cancer tissues were not different from those in Hpnegative gastric cancer tissues. Conclusion: Helicobacter pylori L-form infection can influence the proliferation, apoptosis and invasion gene expression to promote cell proliferation and invasion, and inhibit cell apoptosis.

  9. Helicobacter Pylori: Vías de transmisión

    Directory of Open Access Journals (Sweden)

    Martín Alonso Bayona Rojas

    2017-09-01

    Full Text Available La importancia de Helicobacter pylori como agente etiológico en diversas patologías se asocia con una alta tasa de morbimortalidad y genera un fuerte impacto en nuestra sociedad y en los sistemas de salud. En ese sentido, la presente revisión de literatura pretende analizar y comprender la ruta de transmisión de este patógeno con el objeto de prevenir su propagación. El conocimiento de la epidemiología y el modo de transmisión permite prevenir la propagación e identificar poblaciones de alto riesgo, especialmente en áreas que tienen altas tasas de linfoma gástrico, cáncer gástrico y úlcera gástrica. Helicobacter Pylori: Transmission RoutesAbstractThe importance of Helicobacter pylori as an etiological agent in several pathologies is associated with a high rate of morbi mortality, which generates a strong impact in our society and in the health systems. The present literature review sought to analize and understand the route of transmission of this pathogen to prevent its spread. Knowledge of the epidemiology and mode of transmission of this pathogen is important to prevent its spread and be useful in identifying high-risk populations, especially in areas with high rates of gastric lymphoma, gastric cancer, and gastric ulcer

  10. Interaction between Helicobacter pylori and latent toxoplasmosis and demographic variables on cognitive function in young to middle-aged adults.

    Science.gov (United States)

    Gale, Shawn D; Erickson, Lance D; Brown, Bruce L; Hedges, Dawson W

    2015-01-01

    Helicobacter pylori and latent toxoplasmosis are widespread diseases that have been associated with cognitive deficits and Alzheimer's disease. We sought to determine whether interactions between Helicobacter pylori and latent toxoplasmosis, age, race-ethnicity, educational attainment, economic status, and general health predict cognitive function in young and middle-aged adults. To do so, we used multivariable regression and multivariate models to analyze data obtained from the United States' National Health and Nutrition Examination Survey from the Centers for Disease Control and Prevention, which can be weighted to represent the US population. In this sample, we found that 31.6 percent of women and 36.2 percent of men of the overall sample had IgG Antibodies against Helicobacter pylori, although the seroprevalence of Helicobacter pylori varied with sociodemographic variables. There were no main effects for Helicobacter pylori or latent toxoplasmosis for any of the cognitive measures in models adjusting for age, sex, race-ethnicity, educational attainment, economic standing, and self-rated health predicting cognitive function. However, interactions between Helicobacter pylori and race-ethnicity, educational attainment, latent toxoplasmosis in the fully adjusted models predicted cognitive function. People seropositive for both Helicobacter pylori and latent toxoplasmosis - both of which appear to be common in the general population - appear to be more susceptible to cognitive deficits than are people seropositive for either Helicobacter pylori and or latent toxoplasmosis alone, suggesting a synergistic effect between these two infectious diseases on cognition in young to middle-aged adults.

  11. Interaction between Helicobacter pylori and latent toxoplasmosis and demographic variables on cognitive function in young to middle-aged adults.

    Directory of Open Access Journals (Sweden)

    Shawn D Gale

    Full Text Available Helicobacter pylori and latent toxoplasmosis are widespread diseases that have been associated with cognitive deficits and Alzheimer's disease. We sought to determine whether interactions between Helicobacter pylori and latent toxoplasmosis, age, race-ethnicity, educational attainment, economic status, and general health predict cognitive function in young and middle-aged adults. To do so, we used multivariable regression and multivariate models to analyze data obtained from the United States' National Health and Nutrition Examination Survey from the Centers for Disease Control and Prevention, which can be weighted to represent the US population. In this sample, we found that 31.6 percent of women and 36.2 percent of men of the overall sample had IgG Antibodies against Helicobacter pylori, although the seroprevalence of Helicobacter pylori varied with sociodemographic variables. There were no main effects for Helicobacter pylori or latent toxoplasmosis for any of the cognitive measures in models adjusting for age, sex, race-ethnicity, educational attainment, economic standing, and self-rated health predicting cognitive function. However, interactions between Helicobacter pylori and race-ethnicity, educational attainment, latent toxoplasmosis in the fully adjusted models predicted cognitive function. People seropositive for both Helicobacter pylori and latent toxoplasmosis - both of which appear to be common in the general population - appear to be more susceptible to cognitive deficits than are people seropositive for either Helicobacter pylori and or latent toxoplasmosis alone, suggesting a synergistic effect between these two infectious diseases on cognition in young to middle-aged adults.

  12. Aplicación de películas comestibles a base de quitosano y mucílago de nopal en fresa (Fragaria ananassa) almacenada en refrigeración

    OpenAIRE

    Ruiz Hernández, Fabiola

    2009-01-01

    El objetivo del presente trabajo fue realizar un estudio para evaluar la aplicación de películas comestibles a base de quitosano y mucílago de nopal (Opuntia ficus indica) en la calidad de fresas (Fragaria ananassa) variedad "Festival", almacenadas en recipientes plásticos, listas para consumir y almacenadas en refrigeración. La primera etapa del estudio consistió en estandarizar una técnica para la extracción de mucílago de nopal. Se evaluaron varias técnicas reportadas...

  13. HO-1 inhibits IL-13-induced goblet cell hyperplasia associated with CLCA1 suppression in normal human bronchial epithelial cells.

    Science.gov (United States)

    Mishina, Kei; Shinkai, Masaharu; Shimokawaji, Tadasuke; Nagashima, Akimichi; Hashimoto, Yusuke; Inoue, Yoriko; Inayama, Yoshiaki; Rubin, Bruce K; Ishigatsubo, Yoshiaki; Kaneko, Takeshi

    2015-12-01

    Mucus hypersecretion and goblet cell hyperplasia are common features that characterize asthma. IL-13 increases mucin (MUC) 5AC, the major component of airway mucus, in airway epithelial cells. According to the literature, IL-13 receptor activation leads to STAT6 activation and consequent induction of chloride channel accessory 1 (CLCA1) gene expression, associated with the induction of MUC5AC. Heme oxygenase-1 (HO-1) is an enzyme that catalyzes oxidation of heme to biliverdin, and has anti-inflammatory and anti-oxidant properties. We examined the effects of HO-1 on mucin production and goblet cell hyperplasia induced by IL-13. Moreover, we assessed the cell signaling intermediates that appear to be responsible for mucin production. Normal human bronchial epithelial (NHBE) cells were grown at air liquid interface (ALI) in the presence or absence of IL-13 and hemin, a HO-1 inducer, for 14 days. Protein concentration was analyzed using ELISA, and mRNA expression was examined by real-time PCR. Histochemical analysis was performed using HE staining, andWestern blotting was performed to evaluate signaling transduction pathway. Hemin (4 μM) significantly increased HO-1 protein expression (p b 0.01) and HO-1 mRNA expression (p b 0.001). IL-13 significantly increased goblet cells, MUC5AC protein secretion (p b 0.01) and MUC5AC mRNA (p b 0.001), and these were decreased by hemin by way of HO-1. Tin protoporphyrin (SnPP)-IX, a HO-1 inhibitor, blocked the effect of hemin restoring MUC5AC protein secretion (p b 0.05) and goblet cell hyperplasia. Hemin decreased the expression of CLCA1 mRNA (p b 0.05) and it was reversed by SnPP-IX, but could not suppress IL-13-induced phosphorylation of STAT6 or SAM pointed domain-containing ETS transcription factor (SPDEF) and Forkhead box A2 (FOXA2) mRNA expression. In summary, HO-1 overexpression suppressed IL-13-induced goblet cell hyperplasia and MUC5AC production, and involvement of CLCA1 in the mechanism was suggested.

  14. 14C-urea breath test for the detection of Helicobacter pylori

    International Nuclear Information System (INIS)

    Veldhuyzen van Zanten, S.J.; Tytgat, K.M.; Hollingsworth, J.; Jalali, S.; Rshid, F.A.; Bowen, B.M.; Goldie, J.; Goodacre, R.L.; Riddell, R.H.; Hunt, R.H.

    1990-01-01

    The high urease activity of Helicobacter pylori can be used to detect this bacterium by noninvasive breath tests. We have developed a 14 C-urea breath test which uses 5 microCi 14 C with 50 mg nonradioactive urea. Breath samples are collected at baseline and every 30 min for 2 h. Our study compared the outcome of the breath test to the results of histology and culture of endoscopically obtained gastric biopsies in 84 patients. The breath test discriminated well between the 50 positive patients and the 34 patients negative for Helicobacter pylori: the calculated sensitivity was 100%, specificity 88%, positive predictive value 93%, and negative predictive value 100%. Treatment with bismuth subsalicylate and/or ampicillin resulted in lower counts of exhaled 14 CO 2 which correlated with histological improvement in gastritis. The 14 C-urea breath test is a better gold standard for the detection of Helicobacter pylori than histology and/or culture

  15. Functional dyspepsia and dyspepsia associated with Helicobacter pylori infection: Do they have different clinical characteristics?

    Directory of Open Access Journals (Sweden)

    J.L. Rodríguez-García

    2016-07-01

    Conclusions: The patients with dyspepsia infected with Helicobacter pylori had similar clinical characteristics to the non-infected patients and could not be differentiated a priori. The prevalence of Helicobacter pylori infection in patients with functional dyspepsia was 58% and increased with age.

  16. SRS-sensor 13C/12C isotops measurements for detecting Helicobacter Pylori

    Science.gov (United States)

    Grishkanich, Aleksandr; Chubchenko, Yan; Elizarov, Valentin; Zhevlakov, Aleksandr; Konopelko, Leonid

    2018-02-01

    We developed SRS-sensor 13C/12C isotops measurements detecting Helicobacter Pylori for medical diagnostics of human health. Measuring of absolute 13C/12C isotope amount ratios allows to explore the topical problems of the modern world, alcoholic beverages and tobacco, medical diagnostics of human health. SRS method is used to measure the ratio of carbon isotopes in the exhaled carbon dioxide, which is used to diagnose the human infection of Helicobacter pylori and the influence of the Helicobacter pylori bacterium on the occurrence of gastritis, gastric and duodenal ulcers. A method for the analysis of human infection with Helicobacter pylori was developed on the basis of measurements of the ratio of 13C / 12C carbon isotopes in human exhaled air with a high level of measurement accuracy. The article reviews the work in the field of provision comparability of absolute 13C/12C isotope amount ratios in the environment and food. The analysis of the technical and metrological characteristics of traditional and perspective instruments for measuring isotope ratios is presented. The provision of comparability of absolute 13C/12C isotope amount ratios is carried by gravimetrically prepared reference standards. The key features and emerging issues are discussed.

  17. A novel aptamer functionalized CuInS2 quantum dots probe for daunorubicin sensing and near infrared imaging of prostate cancer cells

    International Nuclear Information System (INIS)

    Lin, Zihan; Ma, Qiang; Fei, Xiaofang; Zhang, Hao; Su, Xingguang

    2014-01-01

    Graphical abstract: - Highlights: • The daunorubicin (DNR)-loaded MUC1 aptamer-NIR CuInS 2 QDs conjugates were developed. • DNR can intercalate into the double-stranded CG sequence of the MUC1 (CGA) 7 –QDs. The aptamer-QDs can sense DNR by the change of photoluminescence intensity of QDs. • The probe can image and sense the delivery of DNR to targeted prostate tumor cell. - Abstract: In this paper, a novel daunorubicin (DNR)-loaded MUC1 aptamer-near infrared (NIR) CuInS 2 quantum dot (DNR–MUC1–QDs) conjugates were developed, which can be used as a targeted cancer imaging and sensing system. After the NIR CuInS 2 QDs conjugated with the MUC1 aptamer–(CGA) 7 , DNR can intercalate into the double-stranded CG sequence of the MUC1–QDs. The incorporation of multiple CG sequences within the stem of the aptamers may further increase the loading efficiency of DNR on these conjugates. DNR–MUC1–QDs can be used to target prostate cancer cells. We evaluated the capacity of MUC1–CuInS 2 QDs for delivering DNR to cancer cells in vitro, and its binding affinity to MUC1-positive and MUC1-negative cells. This novel aptamer functionalized QDs bio-nano-system can not only deliver DNR to the targeted prostate cancer cells, but also can sense DNR by the change of photoluminescence intensity of CuInS 2 QDs, which concurrently images the cancer cells. The quenched fluorescence intensity of MUC1–QDs was proportional to the concentration of DNR in the concentration ranges of 33–88 nmol L −1 . The detection limit (LOD) for DNR was 19 nmol L −1 . We demonstrate the specificity and sensitivity of this DNR–MUC1–QDs probe as a cancer cell imaging, therapy and sensing system in vitro

  18. IRAK-M expression limits dendritic cell activation and proinflammatory cytokine production in response to Helicobacter pylori.

    Directory of Open Access Journals (Sweden)

    Jessica Shiu

    Full Text Available Helicobacter pylori (H. pylori infects the gastric mucosa and persists for the life of the host. Bacterial persistence may be due to the induction of regulatory T cells (Tregs whichmay have protective effects against other diseases such as asthma. It has been shown that H. pylori modulates the T cell response through dendritic cell reprogramming but the molecular pathways involved are relatively unknown. The goal of this study was to identify critical elements of dendritic cell (DC activation and evaluate potential influence on immune activation. Microarray analysis was used to demonstrate limited gene expression changes in H. pylori stimulated bone marrow derived DCs (BMDCs compared to the BMDCs stimulated with E. coli. IRAK-M, a negative regulator of TLR signaling, was upregulated and we selectedit for investigation of its role in modulating the DC and T cell responses. IRAK-M(-/- and wild type BMDC were compared for their response to H. pylori. Cells lacking IRAK-M produced significantly greater amounts of proinflammatory MIP-2 and reduced amounts of immunomodulatory IL-10 than wild type BMDC. IRAK-M(-/- cells also demonstrated increased MHC II expression upon activation. However, IRAK-M(-/- BMDCs were comparable to wild type BMDCs in inducing T-helper 17 (TH17 and Treg responses as demonstrated in vitro using BMDC CD4+ T cells co-culture assays,and in vivo though the adoptive transfer of CD4(+ FoxP3-GFP T cells into H. pylori infected IRAK-M(-/- mice. These results suggest that H. pylori infection leads to the upregulation of anti-inflammatory molecules like IRAK-M and that IRAK-M has a direct impact on innate functions in DCs such as cytokine and costimulation molecule upregulation but may not affect T cell skewing.

  19. Helicobacter pylori Infection in Children: Nutritional Status and Associations with Serum Leptin, Ghrelin, and IGF-1 Levels.

    Science.gov (United States)

    Erdemir, Gulin; Ozkan, Tanju Basarir; Ozgur, Taner; Altay, Derya; Cavun, Sinan; Goral, Guher

    2016-08-01

    Helicobacter pylori is associated with gastrointestinal diseases such as gastritis, peptic ulcers, malignancy and lymphoma, and extra-gastrointestinal conditions. H. pylori infection is negatively associated with children's growth. Chronic inflammation of the stomach that results in the loss of appetite and, dysregulation of neuroendocrine hormones such as leptin, and ghrelin are the probable reasons of this negative association. The objective of this study is to determine the serum levels of leptin, ghrelin, and IGF-1 in H. pylori-infected children and their relations with growth. A hundred and sixty-one school children aged between 6 and 14 years were selected randomly from five primary schools representing a cross section of population. Demographic and sociocultural characteristics, and anthropometric measurements were recorded. Serum H. pylori IgG, insulin-like growth factor-1, leptin, and ghrelin levels were measured in all children. The children were grouped according to the nutritional status and Helicobacter pylori seropositivity. Nutritional indices were compared among groups in association with serum leptin, ghrelin, and insulin-like growth factor-1 levels. H. pylori IgG positivity was found in 34.2%, and 14.9% of children were malnourished. H. pylori seropositivity was significantly higher in older ages (10.32 ± 2.26 vs 9.53 ± 2.36 years, p = .036), and body weight and height Z scores were significantly lower in H. pylori-seropositive children (-0.33 ± 1.08 vs 0.04 ± 1.26, p = .044 and 0.13 ± 0.92 vs 0.23 ± 0.91, p = .018 respectively). H. pylori seropositivity was found to be an independent risk factor for shorter body height (p = .01). Serum leptin, ghrelin, and IGF-1 levels were not associated with H. pylori IgG seropositivity (0.35 vs 0.55 ng/mL, p = .3; 3267.4 ± 753.0 vs 2808.3 ± 911.4 pg/mL, p = .06; 470 ± 176 vs 521 ± 179 ng/mL, p = .32, respectively). Children infected with H. pylori are prone to short stature. This effect seems to be

  20. "Helicobacter Pylori" Infection in Five Inpatient Units for People with Intellectual Disability and Psychiatric Disorder

    Science.gov (United States)

    Clarke, David; Vemuri, Murali; Gunatilake, Deepthi; Tewari, Sidhartha

    2008-01-01

    Background: A high prevalence of "Helicobacter pylori" infection has been reported among people with intellectual disability, especially those residing in hospital and similar settings. Surveys of inpatients have found unusually high rates of gastrointestinal malignancy, to which "H. pylori" infection predisposes. Methods: "Helicobacter pylori"…

  1. Cure of Helicobacter pylori-positive active duodenal ulcer patients: a double-blind, multicentre, 12-month study comparing a two-week dual vs a one-week triple therapy. GISU (Interdisciplinary Group for Ulcer Study).

    Science.gov (United States)

    Di Mario, F; Battaglia, F; Dal Bò, N; Leandro, G; Benedetti, E; Bottona, E; Caroli, A; Costan-Biedo, F; De Bastiani, R; Germanà, B; Andrea Grassi, S; Madia, D; Marcon, V; Marin, R; Monica, F; Olivieri, P; Orzes, N; Pilotto, A; Ronzani, G; Saggioro, A; Tafner, G

    2000-03-01

    To compare a two-week dual therapy to a one-week triple therapy for the healing of duodenal ulcer and the eradication of the Helicobacter pylori infection. A total of 165 patients with active duodenal ulcer were enrolled in the study. At entry, endoscopy, clinical examination and laboratory tests were performed. Histology and the rapid urease test were used to diagnose Helicobacter pylori infection. Patients received either lansoprazole 30 mg plus amoxycillin 1 g bid for two weeks (two-week, dual therapy) or lansoprazole 30 mg plus amoxycillin 1 g plus tinidazole 500 mg bid for one week plus lansoprazole qd for an additional week (one-week, triple therapy). Two and twelve months after cessation of therapy, endoscopy and clinical assessments were repeated. Duodenal ulcer healing and Helicobacter pylori eradication were both significantly greater (pcure rate: 72.6%) than in the dual therapy group (healing: 77.3%; Helicobacter pylori cure rate: 33.3%). Ulcers healed more frequently in Helicobacter pyloricured than in Helicobacter pylori-not cured patients (94.9% vs. 77.2%; pulcer relapses were observed throughout follow-up: all were in Helicobacter pylori-not cured patients. Triple therapy was more effective than dual both in curing Helicobacter pylori infection and healing active duodenal ulcers. The speed of ulcer healing obtained after only 7 days of antibiotics and 14 days of proton pump inhibitors confirmed that longer periods of anti ulcer therapy were not necessary. Helicobacter pylori -not cured patients had more slowly healing ulcers which were more apt to relapse when left untreated.

  2. Seroprevalence of Helicobacter pylori in human immunodeficiency ...

    African Journals Online (AJOL)

    Background: This study assessed the seroprevalence of Helicobacter pylori antibodies among Iranian patients with human immunodeficiency virus (HIV) infection. It also examines whether anti H. pylori seroprevalence was associated with the severity of the HIV infection or the antiretroviral treatment. Material and Methods: ...

  3. BLEEDING PEPTIC ULCER, NONSTEROIDAL ANTIINFLAMMATORY DRUGS AND HELICOBACTER PYLORI INFECTION – A PROSPECTIVE, CONTROLLED, RANDOMIZED STUDY

    Directory of Open Access Journals (Sweden)

    Pavel Skok

    2002-06-01

    Full Text Available Background. The explanation of peptic ulcer etiology has changed significantly in the past decade after the clarification of the significance of Helicobacter pylori infection.Aim. To evaluate the effectiveness of Helicobacter pylori eradication in patients with hemorrhaging peptic ulcer and patients with peptic ulcer without complications.Study ethics. The study was approved in 1998 by the Medical Ethics Committee of the Republic of Slovenia (No. 90/09/98.Type of study. Prospective, controlled and randomized study, carried out between 1998–2000.Patients and methods. The study included 80 patients (50 male and 30 female, av.age 57.5 years, SD ± 17.1, range 22– 80 in which endoscopy confirmed hemorrhage from peptic ulcer of stomach or duodenum and Helicobacter pylori infection. In all cases endoscopic hemostasis was performed: injection sclerotherapy with diluted adrenalin 1:10,000 and 1% polidocanol or argon plasma coagulation. The control group was made up of 80 patients (50 male and 30 female, av.age 56.8 years, SD ± 16.8, range 19–80 with peptic ulcer of stomach or duodenum and Helicobacter pylori infection. Infection was confirmed by a rapid urease test and histologic investigation of the gastric mucosa. In all cases the recommended drug combinations were used in the treatment of the infection: a proton pump inhibitor, omeprazol (4 weeks, and combination of antibiotics, claritromycin and metronidazole or with regard to the antibiogram (1 week. The therapeutic success was ascertained endoscopically four weeks after inclusion in the study. Infection eradication was confirmed by the rapid urease test and histologic investigation of the gastric mucosa.Results. Four weeks after inclusion in the study the success of infection eradication was 92.5% in the study group, in the control group it was 91.3% (p > 0.05. In 6 patients (7.5%, 6/ 80 from the study group and in 7 (8.8%, 7/80 from the control group we introduced a replacement treatment

  4. Sero-prevalence and associated factors of Helicobacter pylori ...

    African Journals Online (AJOL)

    Department of Internal medicine, Weill Bugando School of Medicine, P.O.Box 1464, Mwanza, Tanzania. 2. Department of .... Data was entered in the computer using excel software ..... study of Helicobacter pylori infection in Mexico. Journal.

  5. Investigation of the N-terminal coding region of MUC7 alterations in dentistry students with and without caries

    Directory of Open Access Journals (Sweden)

    Koç Öztürk L

    2016-06-01

    Full Text Available Human low-molecular weight salivary mucin (MUC7 is a small, secreted glycoprotein coded by MUC7. In the oral cavity, they inhibit the colonization of oral bacteria, including cariogenic ones, by masking their surface adhesions, thus helping saliva to avoid dental caries. The N-terminal domain is important for low-molecular weight (MG2 mucins to contact with oral microorganisms. In this study, we aimed to identify the N-terminal coding region of the MUC7 gene between individuals with and without caries. Forty-four healthy dental students were enrolled in this study; 24 of them were classified to have caries [decayed, missing, filled-teeth (DMFT = 5.6] according to the World Health Organization (WHO criteria, and 20 of them were caries-free (DMFT = 0. Simplified oral hygiene index (OHI-S and gingival index (GI were used to determine the oral hygiene and gingival conditions. Total protein levels and salivary total protein levels and salivary buffer capacity (SBC were determined by Lowry and Ericsson methods. DNA was extracted from peripheral blood cells of all the participants and genotyping was carried out by a polymerase chain reaction (PCR-sequencing method. No statistical differences were found between two groups in the terms of salivary parameters, oral hygiene and gingival conditions. We detected one common single nucleotide polymorphism (SNP that leads to a change of asparagine to lysine at codon 80. This substitution was found in 29.0 and 40.0%, respectively, of the groups with and without caries. No other sequence variations were detected. The SNP found in this study may be a specific polymorphism affecting the Turkish population. Further studies with extended numbers are necessary in order to clarify this finding.

  6. Helicobacter pylori infection in apparently healthy South Indian children

    International Nuclear Information System (INIS)

    Kurpad, A.V.; Caszo, B.; Raj, T.; Vaz, M.

    2000-01-01

    Helicobacter pylori infection has been established as a major cause of chronic gastritis in adults, and it has been implicated in the genesis of gastric carcinomas and the development of gastric and duodenal ulcers. It is now postulated that neatly 90% of the adult population in developing countries may be affected with the infection since childhood. Earlier studies on Indians using serology and endoscopic biopsy have shown a high incidence of H. pylori infection in small numbers of patients. The 13 C-urea breath test, which is simple, specific and non-invasive, is also increasingly being used to determine the presence of Helicobacter pylori infection. Preliminary data from India has shown a high prevalence in the urban Indian environment, and there is an urgent need to quantify the prevalence of H. pylori infections on an epidemiological basis in both urban and rural settings. It is also important to study the possible impact of this infection on growth in children, particularly in environments with low sanitation and high crowding. In this paper, we outline a proposal to study the prevalence of Helicobacter pylori infections in children from the following different environments: urban middle socio-economic class, urban slum, rural middle socio-economic class and rural village. (author)

  7. ANTIMICROBIAL ACTIVITY OF GYMNOSPERMA GLUTINOSUM (SPRENG.) LESS. (ASTERACEAE) METHANOL EXTRACTS AGAINST HELICOBACTER PYLORI

    OpenAIRE

    Gomez-Flores, Ricardo; Espinosa-Ramos, David; Quintanilla-Licea, Ramiro; Barr?n-Gonzalez, Mar?a Porfiria; Tamez-Guerra, Patricia; Tamez-Guerra, Reyes; Rodriguez-Padilla, Cristina

    2016-01-01

    Background: Prolonged use of antibiotics may lead to the selection of drug-resistant bacteria; as a result, efforts are being made to identify new and effective antimicrobial agents, particularly, from medicinal plants, against bacterial infections. Antimicrobial activity of Gymnosperma glutinosum against Helicobacter pylori has not yet been reported. Materials and methods: The antibacterial in vitro effect of Gymnosperma glutinosum methanol leaf extracts against Helicobacter pylori (ATCC 435...

  8. Differential expression of CK20, β-catenin, and MUC2/5AC/6 in Lynch syndrome and familial colorectal cancer type X.

    Science.gov (United States)

    Haraldsson, Stefan; Klarskov, Louise; Nilbert, Mef; Bernstein, Inge; Bonde, Jesper; Holck, Susanne

    2017-01-01

    Hereditary non-polyposis colorectal cancer comprises Lynch syndrome and familial colorectal cancer type X (FCCTX). Differences in genetics, demographics and histopathology have been extensively studied. The purpose of this study is to characterize their immunoprofile of markers other than MMR proteins. We compared the expression patterns of cytokeratins (CK7 and CK20), mucins (MUC2/5 AC/6), CDX2 and β-catenin in Lynch syndrome and FCCTX. Differences were identified for CK20 and nuclear β-catenin, which were significantly more often expressed in FCCTX than in Lynch syndrome ( p  Lynch syndrome tumors compared with FCCTX tumors ( p  = 0.001, Lynch syndrome with a more sporadic-like profile in the former group and a more distinct profile with frequent MUC6 positivity in the latter group.

  9. [Changing prevalence of Helicobacter pylori infection in the 9th district of Budapest. A retrospective endoscopic study, 1997-2012].

    Science.gov (United States)

    Buzás, György Miklós; Lotz, Gábor; Schneider, Ferenc; Józan, Jolán

    2013-06-09

    The prevalence of Helicobacter pylori infection in developed countries is decreasing. The time-frame of this process is largely unknown. The aim of the authors was to evaluate the changes in the prevalence of Helicobacter pylori infection in their endoscopic centre. This retrospective study included 4647 patients examined between 1997 and 2012. Helicobacter pylori was determined from antral and corpus biopsies by the modified Giemsa stain and rapid urease test. The prevalence of the infection was calculated yearly for the period studied, for age decades from 18 to 85 years, birth cohorts of 10 years from 1920 to 1994 and according to diagnosis. The overall prevalence of Helicobacter pylori infection was 54.7%, which decreased from 71.3% in 1997 to 32.76% in 2011. Functional dyspepsia was found in 37.9%, duodenal ulcer in 25.3%, gastric ulcer in 3.8% and reflux disease in 24.2% of the patients. The mean prevalence of infection was 62.5% in birth cohorts of 10 years between 1920 and 1959, 57.4% in those between 1960 and 1969, and decreased to 39.0% and 26.7% in birth cohorts between 1970 and 1979) and between 1980 and 1989, respectively. According to age cohorts, the prevalence was 21.8% 34.9%, 46.5%, 63.7%, 63.2% and 59.2% in patients aged 18-19 years, 20-29 years, 30-39 years, 40-49 years, 50-59 years and 60-69 years, respectively. The proportion of H. pylori positive duodenal ulcers decreased from 95.9% in 1998 to 59.1% in 2011 (p = 0.001). The prevalence of Helicobacter pylori infection in the 9th district of Budapest is decreasing, especially in cohorts born in the late 1960s and 1970s, nearly 1.5 decades before the discovery of the bacterium.

  10. Helicobacter pylori Stool Antigen test: a reliable non-invasive test for the diagnosis of Helicobacter pylori infection in children

    NARCIS (Netherlands)

    van Doorn, O. J.; Bosman, D. K.; van't Hoff, B. W.; Taminiau, J. A.; ten Kate, F. J.; van der Ende, A.

    2001-01-01

    OBJECTIVE: To evaluate the Helicobacter pylori Stool Antigen (HpSA) test for the diagnosis of H. pylori infection in children. DESIGN AND SETTING: Prospective cohort study in an academic medical centre. PATIENTS AND METHODS: A total of 106 consecutive children who underwent gastroscopy were

  11. Helicobacter Pylori : Serological Testing and Treatment in ...

    African Journals Online (AJOL)

    Purpose: Helicobacter pylori has been strongly associated with dyspepsia and eradication of H. pylori after a non-invasive testing is an integral part of most management guidelines. This study evaluated the benefit of serological testing and treatment of H. pylori in Nigerian patients presenting with uninvestigated dyspepsia.

  12. Magnitude of Helicobacter pylori among Dyspeptic patients ...

    African Journals Online (AJOL)

    Background: Helicobacter pylori (H.pylori) infection is predominantly acquired in childhood from family members. The infection can cause dypepepsia, chronic and acute gastritis and gastric cancer. Dyspepsia is the most common illness in the Ethiopian population visiting outpatient department of health facilities, and it has ...

  13. Fisiopatología molecular en la infección por Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Franklin Torres Jiménez

    2016-01-01

    Full Text Available La infección por Helicobacter pylori es el proceso de colonización bacteriana más común a nivel mundial. En 1994 la Agencia Internacional para la Investigación en Cáncer ( IARC catalogó al Helicobacter Pylori como un carcinógeno tipo I. La infección por esta bacteria incrementa el riesgo de padecer cáncer gástrico hasta 6 veces más que los individuos que no presentan la infección. Colombia tiene una prevalencia de infección por Helicobacter pylori del 86 % en adultos mayores de 20 años y del 80% en niños mayores de 8 años. La infección persistente y recidivante de la mucosa gástrica puede generar una respuesta inflamatoria, o procesos silentes, que en el peor de los casos puede progresar a un adenocarcinoma gástrico tipo difuso o intestinal. Existen múltiples factores que influyen en las consecuencias clínicas de la infección por Helicobacter pylori: en mención: predisposición genética del huésped, inmunorregulación genética del paciente infectado, factores ambientales y heterogeneidad de los factores de virulencia de las diversas cepas. Por lo anterior se infiere que las patolo - gías gástricas, en especial la gastritis y el adenocarcinoma, son padecimientos de etiología multifactorial que pueden originarse por diversas causas o condiciones. En esta revisión se analizarán los principales aspectos relacionados con la fisiopatología molecular en la infección por Helicobacter pylori , en particular tópicos correspondientes a los factores de virulencia.

  14. Helicobacter pylori vaccine: from past to future.

    Science.gov (United States)

    Agarwal, Kanishtha; Agarwal, Shvetank

    2008-02-01

    Helicobacter pylori infection is highly prevalent worldwide and is an important cause of gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma (MALToma), and gastric adenocarcinoma. Infection is usually acquired during childhood and tends to persist unless treated. Because eradication requires treatment with multidrug regimens, prevention of initial infection by a suitable vaccine is attractive. Although immunization with H pylori protein subunits has been encouraging in animals, similar vaccine trials in humans have shown adjuvant-related adverse effects and only moderate effectiveness. Newer immunization approaches (use of DNA, live vectors, bacterial ghosts, and microspheres) are being developed. Several questions about when and whom to vaccinate will need to be appropriately answered, and a cost-effective vaccine production and delivery strategy will have to be useful for developing countries. For this review, we searched MEDLINE using the Medical Subject Heading (MeSH) terms Helicobacter pylori and vaccines for articles in English from 1990 to 2007.

  15. Vitamin B12 status and its association with Helicobacter pylori infection in alcohol dependent patients

    NARCIS (Netherlands)

    van Oijen, Martijn G. H.; Laheij, Robert J. F.; de Jong, Cor A. J.; Peters, Wilbert H. M.; Jansen, Jan B. M. J.

    2004-01-01

    Both infection with Helicobacter pylori and alcohol abuse have been associated with low vitamin B12 serum levels. The interaction between both risk factors is unknown. The aim of this study was to determine whether Helicobacter pylori infection is associated with low vitamin B12 levels in alcohol

  16. [Helicobacter pylori in the development of dental caries].

    Science.gov (United States)

    Moseeva, M V; Belova, E V; Vakhrushev, Ia M

    2010-01-01

    It is shown, that in patients with erosive and ulcer defects of gastroduodenal zone at settling Helicobacter pylori (Hp) in an oral cavity in 100% of cases caries develops at intensity 13.6 +/- 1.4 teeth. Produced Hp protease and ammonia cause disintegration connected to protein silica acids and reduce activity lysocim, worsening, thus, fluid and protective properties of a saliva. In the subsequent infringement of autopurification of a teeth results in accumulation of a dental strike where protease activity conditionally pathogenic microflora conducts to depolymerization and demineralization enamels of a teeth.

  17. Role of Helicobacter pylori in stomach cancer after partial gastrectomy for benign ulcer disease Papel del Helicobacter pylori en el cáncer gástrico tras gastrectomía parcial por úlcera benigna

    Directory of Open Access Journals (Sweden)

    A. Seoane

    2005-11-01

    Full Text Available Objective: to determine the prevalence of Helicobacter pylori infection in patients having undergone gastrectomy for non-neoplastic disease who later developed gastric stump cancer. Material and methods: retrospective study of all patients with partial gastrectomy for non-malignant peptic disease who were submitted to an endoscopic exploration between 1995 and 2001. A comparison was made of major clinical and histological characteristics, and the presence of Helicobacter pylori among patients with and without gastric cancer in the stomach remnant. Results: a total of 73 patients were studied in this period. Fifteen patients (20.5% had remnant-stump gastric cancer. All but one were adenocarcinomas (71% intestinal and 29% diffuse, respectively. The average time between diagnosis of gastric cancer and previous gastrectomy was 32 (14-48 years. There was a higher detection rate of Helicobacter pylori in patients with cancer in the gastric remnant (100 vs. 81.5%, respectively, p Objetivo: determinar la prevalencia de la infección por Helicobacter pylori en pacientes gastrectomizados por enfermedad no neoplásica, y que han desarrollado posteriormente cáncer gástrico. Material y métodos: estudio retrospectivo con reclutamiento de todos los pacientes con gastrectomía parcial por enfermedad péptica benigna que han sido sometidos a una exploración endoscópica entre 1995-2001. Se ha realizado una comparación de las principales características clínicas e histológicas y de la presencia de Helicobacter pylori en los pacientes con y sin cáncer del remanente gástrico. Resultados: se han estudiado un total de 73 pacientes en este periodo. Se han encontrado 15 pacientes (20,5% con cáncer en el remanente gástrico, 14 adenocarcinomas (71% tipo intestinal y 29% tipo difuso y un linfoma. El tiempo transcurrido entre el diagnóstico de cáncer gástrico y la gastrectomía previa ha sido de 32 (14-48 años. Se ha detectado un alto porcentaje de infecci

  18. Characteristics of clinical Helicobacter pylori strains from Ecuador.

    Science.gov (United States)

    Debets-Ossenkopp, Yvette J; Reyes, Germán; Mulder, Janet; aan de Stegge, Birgit M; Peters, José T A M; Savelkoul, Paul H M; Tanca, J; Peña, Amado S; Vandenbroucke-Grauls, Christina M J E

    2003-01-01

    In Ecuador, Helicobacter pylori infections are highly prevalent. A total of 42 H. pylori clinical isolates from 86 patients attending the outpatient clinic of the gastroenterology department of the university hospital of Guayaquil in Ecuador were characterized. Their susceptibility, and cagA and vacA status were determined. Resistance to metronidazole and clarithromycin was found in 80.9% and 9.5% of strains, respectively. Neither amoxicillin- nor tetracycline-resistant strains were found. The most prevalent genotype was the cagA(+), vacA s1b,m1 type. This genotype was associated with gastric cancer and peptic ulcer. Typing by random amplified polymorphic DNA showed no genetic relationship among the strains.

  19. Helicobacter pylori and upper digestive diseases - diagnosis ...

    African Journals Online (AJOL)

    Results: The prevalence of Helicobacter pylori in patients with various upper gastrointestinal problems was 84.7%. The use of medication that can reduce the H. pylori density was common among the infected patients, as history of antibiotics use, acid suppressant use and medications for eradication treatment were ...

  20. Prevalence of Helicobacter pylori in children by noninvasive stool ...

    African Journals Online (AJOL)

    Prevalence of Helicobacter pylori in children by noninvasive stool Antigen Enzyme Immunoassay. Augustine O. Ebonyi, Emeka Ejeliogu, Stanley T. Odigbo, Martha Omoo Ochoga, Stephen Oguche, Anejo-Okopi A. Joseph ...

  1. Pretargeting of human mammary carcinoma xenografts with bispecific anti-MUC1/anti-Ga chelate antibodies and immunoscintigraphy with PET

    International Nuclear Information System (INIS)

    Schuhmacher, Jochen; Klivenyi, Gabor; Kaul, Sepp; Henze, Marcus; Matys, Ronald; Hauser, Harald; Clorius, John

    2001-01-01

    We recently demonstrated the feasibility of combining enhanced tumor-to-tissue contrast and PET imaging for immunoscintigraphic tumor localization in pancreas and colon carcinoma bearing nude mice. Contrast enhancement was obtained with a multistep targeting technique that consists of the sequential administration of an antitumor/antihapten bispecific antibody (BS-MAb), a blocker to saturate the antihapten binding sites of the BS-MAb that remains in circulation, and a low molecular weight Ga chelate, labeled with the positron emitter 68 Ga, which serves as the hapten. To evaluate the efficacy of this pretargeting technique for breast cancer localization, we synthesized a BS-MAb from the F(ab') 2 fragments of the anti-MUC1 MAb 12H12 which reacts with the vast majority of human breast carcinomas, and the F(ab') fragment of an anti-Ga chelate MAb using a bifunctional chemical linker. The BS-MAb was tested for its affinity and its biokinetics in nude mice bearing a human mammary carcinoma. Equilibrium binding of the BS-MAb for mammary carcinoma cells was low (1.2 x 10 7 M -1 ) while the binding capacity of cells was high (8.4 x 10 6 BS-MAbs per cell). Tumor uptake of the 67 Ga labeled chelate in pretargeted animals was to 5.8 ± 0.8% iD/g resulting in a tumor-to-blood ratio of 2.6 at 1h postinjection. This compares with a ratio of 0.65 and 0.85 obtained with 125 I-labeled native 12H12 at 24h and 48h postinjection. No difference in the tumor uptake of both the 68 Ga and 67 Ga labeled chelate was observed. PET imaging of mice, started 1h postinjection of the 68 Ga chelate, clearly visualized all tumors

  2. Pretargeting of human mammary carcinoma xenografts with bispecific anti-MUC1/anti-Ga chelate antibodies and immunoscintigraphy with PET

    Energy Technology Data Exchange (ETDEWEB)

    Schuhmacher, Jochen; Klivenyi, Gabor; Kaul, Sepp; Henze, Marcus; Matys, Ronald; Hauser, Harald; Clorius, John

    2001-10-01

    We recently demonstrated the feasibility of combining enhanced tumor-to-tissue contrast and PET imaging for immunoscintigraphic tumor localization in pancreas and colon carcinoma bearing nude mice. Contrast enhancement was obtained with a multistep targeting technique that consists of the sequential administration of an antitumor/antihapten bispecific antibody (BS-MAb), a blocker to saturate the antihapten binding sites of the BS-MAb that remains in circulation, and a low molecular weight Ga chelate, labeled with the positron emitter {sup 68}Ga, which serves as the hapten. To evaluate the efficacy of this pretargeting technique for breast cancer localization, we synthesized a BS-MAb from the F(ab'){sub 2} fragments of the anti-MUC1 MAb 12H12 which reacts with the vast majority of human breast carcinomas, and the F(ab') fragment of an anti-Ga chelate MAb using a bifunctional chemical linker. The BS-MAb was tested for its affinity and its biokinetics in nude mice bearing a human mammary carcinoma. Equilibrium binding of the BS-MAb for mammary carcinoma cells was low (1.2 x 10{sup 7} M{sup -1}) while the binding capacity of cells was high (8.4 x 10{sup 6} BS-MAbs per cell). Tumor uptake of the {sup 67}Ga labeled chelate in pretargeted animals was to 5.8 {+-} 0.8% iD/g resulting in a tumor-to-blood ratio of 2.6 at 1h postinjection. This compares with a ratio of 0.65 and 0.85 obtained with {sup 125}I-labeled native 12H12 at 24h and 48h postinjection. No difference in the tumor uptake of both the {sup 68}Ga and {sup 67}Ga labeled chelate was observed. PET imaging of mice, started 1h postinjection of the {sup 68}Ga chelate, clearly visualized all tumors.

  3. The 13carbon urea breath test for the diagnosis of Helicobacter pylori infection in subjects with atrophic gastritis: evaluation in a primary care setting

    NARCIS (Netherlands)

    Korstanje, A.; van Eeden, S.; Offerhaus, G. J. A.; Sabbe, L. J. M.; den Hartog, G.; Biemond, I.; Lamers, C. B. H. W.

    2006-01-01

    BACKGROUND: (13)Carbon urea breath testing is reliable to detect current infection with Helicobacter pylori but has been reported to be of limited value in selected patients with atrophic body gastritis or acid-lowering medication. AIM: To evaluate the accuracy of (13)carbon urea breath testing for

  4. Estado actual de la resistencia de Helicobacter pylori a tetraciclina: revisión sistemática de la literatura

    Directory of Open Access Journals (Sweden)

    Marcela Mercado-Reyes

    2012-08-01

    Full Text Available Current status of Helicobacter pylori resistance to tetracycline: a systematic review of the literature. Objective. To determinethe prevalence of Helicobacter pylori resistance to and the possible mutations that generate this worldwide resistance. Materials andmethods. A systematic search for literature was performed in the databases Medline, Science Direct (Elsevier, Ovid, PubMed, Lilacsand MedicLatina using relevant key words. Data extraction was independent and checklists were prepared to assess the methodologicalquality of the studies. Analysis of information was done with RevMan 5®. Results. We found Helicobacter pylori resistance prevalencerates of 1% for North America, 8% for Central and South America, 5% for Asia, and 2% for Europe. The mutation associated to thisresistance is in the 16S rDNA gene at nucleotide position 967TTC to AGA965 responsible of high resistance to tetracycline. Conclusions.Antibiotic resistance is one of the causes most associated to treatment failure in the eradication of Helicobacter pylori, as well as pooradherence to treatment and indiscriminate use of antibiotics. We also evidenced that the rate of tetracycline resistance is higher whenit is used in a second treatment scheme. The distribution of resistance is variable in different areas and it is important to know these resistances to avoid treatment failures.

  5. empiric treatment based on helicobacter pylori serology cannot ...

    African Journals Online (AJOL)

    EMPIRIC TREATMENT BASED ON. HELICOBACTER PYLORI SEROLOGY. CANNOT SUBSTITUTE FOR EARLY. ENDOSCOPY IN THE. MANAGEMENT OF DYSPEPTIC. RURAL BLACK AFRICANS. Stephen JD O'Keefe, B Salvador, J Nainkin, S Majikir H. Stevens, A Atherstone. Background_ Evidence that chronic gastric ...

  6. Molecular Mechanisms of Antibiotic Resistance in Helicobacter pylori

    NARCIS (Netherlands)

    M.M. Gerrits (Monique)

    2004-01-01

    textabstractAn estimated 4 to 5 million individuals in the Netherlands are actively infected with Helicobacter pylori. Eradication of this bacterium becomes more difficult as the prevalence of antibiotic resistance is increasing worldwide. Most H. pylori infections are now diagnosed by

  7. Alcohol consumption and Helicobacter pylori infection

    DEFF Research Database (Denmark)

    Brenner, H; Berg, Gabriele; Lappus, N

    1999-01-01

    Alcohol has strong antimicrobial activity and stimulates gastric acid secretion. Alcohol consumption may therefore compromise the living conditions of Helicobacter pylori in the stomach. We assessed the relation of alcohol consumption with H. pylori infection among 1,785 participants ages 18...... prevalence of H. pylori infection was 39.2%. There was a clear inverse dose-response-relation between reported alcohol consumption and H. pylori infection. The relation persisted after control for potential confounding factors. The adjusted prevalence ratios (95% confidence intervals) for H. pylori infection...... among persons who consumed up to 10, 10 to 20, and more than 20 gm of alcohol per day compared with non-drinkers were 0.93 (0.77-1.13), 0.82 (0.65-1.04), and 0.71 (0.55-0.92). The inverse relation between alcohol consumption and H. pylori infection was even stronger when individuals with an indication...

  8. In vitro anti-Helicobacter pylori action of 30 Chinese herbal medicines used to treat ulcer diseases.

    Science.gov (United States)

    Li, Yang; Xu, Chen; Zhang, Qiang; Liu, Jun Yan; Tan, Ren Xiang

    2005-04-26

    Infection by Helicobacter pylori has been ascertained to be an important etiologic impetus leading usually to chronic active gastritis and gastric ulcer with growing incidences worldwide. Utilizing as the test pathogen a standard and five clinic strains of Helicobacter pylori, the antibacterial action was assessed in vitro with ethanol extracts of 30 Chinese herbal medicines which have been frequently prescribed since ancient times for treating gastritis-like disorders. Among the 30 tested materials, the ethanol extracts of Abrus cantoniensis (Fabaceae), Saussurea lappa (Asteraceae) and Eugenia caryophyllata (Myrtaceae) were strongly inhibitory to all test strains (MICs: approximately 40 microg/ml), and Hippophae rhamnoides (Elaeagnaceae), Fritillaria thunbergii (Liliaceae), Magnolia officinalis and Schisandra chinensis (Magnoliaceae), Corydalis yanhusuo (Papaveraceae), Citrus reticulata (Rutaceae), Bupleurum chinense and Ligusticum chuanxiong (Apiaceae) substantially active with MICs close to 60.0 microg/ml. As to antibacterial actions of the aqueous extracts of the same drugs, those derived from Cassia obtusifolia (Fabaceae), Fritillaria thunbergii and Eugenia caryophyllata were remarkably inhibitory against all the six Helicobacter pylori strains (MICs: approximately 60 microg/ml). The work compared almost quantitatively the magnitude of the anti-Helicobacter pylori actions of the 30 most prescribed gastritis-treating Chinese herbal drugs, and located as well some source plants where potent anti-Helicobacter pylori phytochemicals could be characterized.

  9. Systematic review: Helicobacter pylori infection and impaired drug absorption.

    Science.gov (United States)

    Lahner, E; Annibale, B; Delle Fave, G

    2009-02-15

    Impaired acid secretion may affect drug absorption and may be consequent to corporal Helicobacter pylori-gastritis, which may affect the absorption of orally administered drugs. To focus on the evidence of impaired drug absorption associated with H. pylori infection. Data sources were the systematic search of MEDLINE/EMBASE/SCOPUS databases (1980-April 2008) for English articles using the keywords: drug malabsorption/absorption, stomach, Helicobacter pylori, gastritis, gastric acid, gastric pH, hypochlorhydria, gastric hypoacidity. Study selection was made from 2099 retrieved articles, five studies were identified. Data were extracted from selected papers, investigated drugs, study type, main features of subjects, study design, intervention type and results were extracted. In all, five studies investigated impaired absorption of l-dopa, thyroxine and delavirdine in H. pylori infection. Eradication treatment led to 21-54% increase in l-dopa in Parkinson's disease. Thyroxine requirement was higher in hypochlorhydric goitre with H. pylori-gastritis and thyrotropin levels decreased by 94% after treatment. In H. pylori- and HIV-positive hypochlorhydric subjects, delavirdine absorption increased by 57% with orange juice administration and by 150% after eradication. A plausible mechanism of impaired drug absorption is decreased acid secretion in H. pylori-gastritis patients. Helicobacter pylori infection and hypochlorhydria should be considered in prescribing drugs the absorption of which is potentially affected by intragastric pH.

  10. Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

    International Nuclear Information System (INIS)

    Zhao, Hangyong; Zhu, Huanghuang; Lin, Zhou; Lin, Gang; Lv, Guoqiang

    2015-01-01

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK–HO–1 signaling. - Highlights: • We synthesized compound 13 (C13), a α1-selective small molecule AMPK activator. • C13-induced AMPK activation requires α1 subunit in gastric epithelial cells (GECs). • C13 enhances Helicobacter pylori-induced pro-survival AMPK activation to inhibit GEC apoptosis. • C13 inhibits H. pylori-induced reactive oxygen species (ROS) production in GECs. • AMPK-heme oxygenase (HO-1) activation is required for C13-mediated anti-oxidant activity

  11. Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Hangyong; Zhu, Huanghuang; Lin, Zhou; Lin, Gang; Lv, Guoqiang, E-mail: lvguoqiangwuxivip@163.com

    2015-08-07

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK–HO–1 signaling. - Highlights: • We synthesized compound 13 (C13), a α1-selective small molecule AMPK activator. • C13-induced AMPK activation requires α1 subunit in gastric epithelial cells (GECs). • C13 enhances Helicobacter pylori-induced pro-survival AMPK activation to inhibit GEC apoptosis. • C13 inhibits H. pylori-induced reactive oxygen species (ROS) production in GECs. • AMPK-heme oxygenase (HO-1) activation is required for C13-mediated anti-oxidant activity.

  12. MGMT and MLH1 methylation in Helicobacter pylori-infected children and adults.

    Science.gov (United States)

    Alvarez, Marisa C; Santos, Juliana C; Maniezzo, Nathália; Ladeira, Marcelo S; da Silva, Artur L C; Scaletsky, Isabel C A; Pedrazzoli, José; Ribeiro, Marcelo L

    2013-05-28

    To evaluate the association between Helicobacter pylori (H. pylori) infection and MLH1 and MGMT methylation and its relationship with microsatellite instability (MSI). The methylation status of the MLH1 and MGMT promoter region was analysed by methylation specific methylation-polymerase chain reaction (MSP-PCR) in gastric biopsy samples from uninfected or H. pylori-infected children (n = 50), from adults with chronic gastritis (n = 97) and from adults with gastric cancer (n = 92). MLH1 and MGMT mRNA expression were measured by real-time PCR and normalised to a constitutive gene (β actin). MSI analysis was performed by screening MSI markers at 4 loci (Bat-25, Bat-26, D17S250 and D2S123) with PCR; PCR products were analysed by single strand conformation polymorphism followed by silver staining. Statistical analyses were performed with either the χ(2) test with Yates continuity correction or Fisher's exact test, and statistical significance for expression analysis was assessed using an unpaired Student's t-test. Methylation was not detected in the promoter regions of MLH1 and MGMT in gastric biopsy samples from children, regardless of H. pylori infection status. The MGMT promoter was methylated in 51% of chronic gastritis adult patients and was associated with H. pylori infection (P MLH1 methylation frequencies among H. pylori-infected and non-infected chronic gastritis adult patients were 13% and 7%, respectively. We observed methylation of the MLH1 promoter (39%) and increased MSI levels (68%) in samples from gastric cancer patients in comparison to samples from H. pylori-infected adult chronic gastritis patients (P MLH1 and MGMT mRNA were significantly reduced in chronic gastritis samples that were also hypermethylated (P MLH1 methylation did not occur in earlier-stage H. pylori infections and thus might depend on the duration of infection.

  13. Association between Helicobacter pylori seropositivity and Hepatic Encephalopathy

    International Nuclear Information System (INIS)

    Behroozian, R.; Faramarzpur, M.; Rahimi, E.

    2010-01-01

    Objective: The knowledge on Helicobacter pylori (H. pylori) contribution in the pathology of the liver and biliary tract diseases in human is very limited. The aim of this study was to assess the probable association between H. pylori seropositivity and hepatic encephalopathy. Methodology: This is a case control study conducted through three groups, cirrhotics with hepatic encephalopathy (HE), cirrhotics without HE and healthy controls. All subjects were examined serologically for determination of IgG class antibodies to H. pylori based on ELISA technique. Results: H. pylori seropositivity was present in 88% cirrhotic patients with hepatic encephalopathy, 86% cirrhotics without hepatic encephalopathy and 66% healthy controls. Conclusion: According to our results, H. pylori seropositivity rate in cirrhotic patients with or without hepatic encephalopathy was higher than healthy controls. But H. pylori seropositivity rate was not significantly different among cirrhotics with hepatic encephalopathy and those without it.

  14. Site-specific O-Glycosylation on the MUC2 Mucin Protein Inhibits Cleavage by the Porphyromonas gingivalis Secreted Cysteine Protease (RgpB)

    DEFF Research Database (Denmark)

    van der Post, Sjoerd; Subramani, Durai B; Bäckström, Malin

    2013-01-01

    that are protease-resistant and has cysteine-rich N and C termini responsible for polymerization. Culture supernatants of Porphyromonas gingivalis, a bacterium that secretes proteases responsible for periodontitis, cleaved the MUC2 C-terminal region, whereas the N-terminal region was unaffected. The active enzyme...

  15. Acute perforated duodenal ulcer in Maiduguri: experience with simple closure and Helicobacter pylori eradication.

    Science.gov (United States)

    Nuhu, A; Madziga, A G; Gali, B M

    2009-01-01

    Effective medical management of peptic ulcer disease (PUD) has reduced the incidence of gastric outlet obstruction (GOO) as a complication, but perforation especially in the elderly remains unchanged and is in fact on the increase. There is a changing trend in emergency surgery for perforated duodenal ulcer (PDU) from definitive anti ulcer surgery to simple closure followed by Helicobacter pylori eradication. To present our experience in managing PDU with simple closure followed by Helicobacter pylori eradication. This was a chart review of patients managed for PDU over a nine year period (Jan 1999 to Dec 2007) using information obtained from ward admission registers, theatre operation registers, and patients case files from the medical records department. The patients biodata, clinical, and operative findings as well as treatment outcome were extracted for analysis. Of 55 patients eligible for analysis, 44 (80%) were males and 11(20%) females (M to F, 4:1). Their ages ranged between 18 and 65 years with a mean(SD) of 39.9 (13.5) years. Most of the patients, 34 (61.8%), were below 40 years of age and majority 39(71.0%) had a history suggestive of chronic peptic ulcer disease. Twenty six (47.3%) patients presented within 24 hours of perforation, while nine (16.4%) presented more than 72 hours afterwards. The latter group accounted for most, five(55.6%), of the mortality. All the perforations were anterior pyloroduodenal and all except one had simple closure with omental patch followed by a course of a proton pump inhibitor and Helicobacter pylori eradication therapy. Simple closure with omental patch followed by Helicobacter pylori eradication is effective in managing PDU with low morbidity and mortality despite patients late presentation in our center. This technique is recommended in place of a definitive ulcer surgery.

  16. [Helicobacter pylori -- 2010].

    Science.gov (United States)

    Buzás, György Miklós

    2010-12-05

    Helicobacter pylori, discovered 27 years ago, has remained the most prevalent infectious agent in the world. In the author's hypothesis, the increase of peptic ulcer prevalence in the 19-20th century could be attributable to the extended worldwide use of gastric tubes for secretory testing which led to the iatrogenic transmission of pathogenic strains. Helicobacter pylori outer membrane proteins (OMP), and duodenal ulcer promoting (dupA) proteins were identified as novel virulence factors, leading to the production of pro-inflammatory cytokines, which could be future targets of therapy. There is no ideal first-line eradication of the infection and according to expert's opinion, the efficiency of these regimens has fallen gradually in recent years to unacceptably low levels; however, in the author's opinion this is a multifactorial phenomenon which can not be generalized. As alternative drugs, the efficiency of levofloxacin, furazolidone and rifabutin has been proven by meta-analyses. Sequential and bismuth-free quadruple therapies, although highly efficient, are not yet used on a large scale. The recurrence of the infection is 2.27%/year in developed and of 13.0%/year in developing countries. Spontaneous eradication occurred in 8-20% of the children and 5-11% of adults. The prevalence of clarithromycin resistance is increasing worldwide. In Hungary, it has reached 10.9% in county cities, according to a national survey. In a district of Budapest called Ferencváros, the prevalence between 2005 and 2009 was 16-22%, with no increasing trend. The development of enzymatic inhibitors (urease, carbonic anhydrase and gamma-glutamyl transpeptidase), modified antibiotics and efflux pump inhibitors seem promising ways because these compounds do not lead to resistance; however, none have yet been used in humans.

  17. Gastritis Induced by the Helicobacter ‘Gastrospirillum Hominis’

    OpenAIRE

    Veldhuyzen van Zanten, Sander JO; Malatjalian, Dickran A; Desormeau, Leon M; Pereira, Leo V

    1994-01-01

    A patient with a ‘Gastrospirillum hominis’ infection in the stomach is described. ‘Gastrospirillum hominis’ belongs to the genus Helicobacter and is a rare cause of gastritis in the human stomach. It can be recognized by its distinctive morphological appearance on histology.

  18. The presence of Helicobacter pylori in oral cavities of patients with leukoplakia and oral lichen planus

    Directory of Open Access Journals (Sweden)

    Magdalena Kazanowska-Dygdała

    2016-02-01

    Full Text Available ABSTRACT Objective Helicobacter pylori infection is one of the most common bacterial infections in men. This gastrointestinal pathogen is closely related to gastritis, peptic ulcers, and the increased risk of gastric cancer. Numerous studies have indicated oral cavities as possible Helicobacter pylori reservoirs. Helicobacter pylori has been detected both in supragingival and subgingival plaques, and also in saliva. In addition, the relationship between lesions of oral mucosa and the presence of H. pylori has been evaluated and described in some studies. The aim of this study was to assess the presence of Helicobacter pylori DNA in the oral cavity of patients with oral leukoplakia and oral lichen planus. Material and Methods The study included 54 patients with oral leukoplakia, 72 with oral lichen planus lesions, and 40 healthy controls. The presence of Helicobacter pylori in oral cavity samples was analyzed using a single-step Polymerase Chain Reaction (PCR method. All patients underwent a periodontal examination and the following clinical parameters were collected: pocket depth, bleeding, and plaque indexes. The periodontal status was assessed using the Offenbacher classification. Results In most patients, pathological lesions were in typical sites on the buccal mucosa (leukoplakia in 88%, and oral lichen planus in 93% of patients. The DNA of the Helicobacter pylori was present in 20% of patients with leukoplakia and 23% of patients with lichen planus. We did not find the DNA of H. pylori in healthy controls. The periodontal status described by periodontal indices was worse in the investigated group than in the control group. Conclusion These findings suggest that the H. pylori presence in oral cavities may be related with leukoplakia and lichen planus oral lesions.

  19. The presence of Helicobacter pylori in oral cavities of patients with leukoplakia and oral lichen planus.

    Science.gov (United States)

    Kazanowska-Dygdała, Magdalena; Duś, Irena; Radwan-Oczko, Małgorzata

    2016-01-01

    Helicobacter pylori infection is one of the most common bacterial infections in men. This gastrointestinal pathogen is closely related to gastritis, peptic ulcers, and the increased risk of gastric cancer. Numerous studies have indicated oral cavities as possible Helicobacter pylori reservoirs. Helicobacter pylori has been detected both in supragingival and subgingival plaques, and also in saliva. In addition, the relationship between lesions of oral mucosa and the presence of H. pylori has been evaluated and described in some studies. The aim of this study was to assess the presence of Helicobacter pylori DNA in the oral cavity of patients with oral leukoplakia and oral lichen planus. The study included 54 patients with oral leukoplakia, 72 with oral lichen planus lesions, and 40 healthy controls. The presence of Helicobacter pylori in oral cavity samples was analyzed using a single-step Polymerase Chain Reaction (PCR) method. All patients underwent a periodontal examination and the following clinical parameters were collected: pocket depth, bleeding, and plaque indexes. The periodontal status was assessed using the Offenbacher classification. In most patients, pathological lesions were in typical sites on the buccal mucosa (leukoplakia in 88%, and oral lichen planus in 93% of patients). The DNA of the Helicobacter pylori was present in 20% of patients with leukoplakia and 23% of patients with lichen planus. We did not find the DNA of H. pylori in healthy controls. The periodontal status described by periodontal indices was worse in the investigated group than in the control group. These findings suggest that the H. pylori presence in oral cavities may be related with leukoplakia and lichen planus oral lesions.

  20. Helicobacter Pylori – A Moving Target | Lambiotte | South African ...

    African Journals Online (AJOL)

    Pylori) continues to grow. Testing is also now advised for patients with immune thrombocytopenia purpura, unexplained vitamin B12 or iron deficiency anemia. Despite the indications for treatment of Helicobacter pylori infection widening, definitive ...

  1. Empiric treatment based on Helicobacter Pylori serology cannont ...

    African Journals Online (AJOL)

    Background: Evidence that chronic gastric Helicobacter pylori (HP) infection is an aetiological factor in dyspepsia, peptic ulcer disease, gastric carcinoma and lymphoma has led to the suggestion that all serologically positive dyspeptic patients should be treated empirically with antibiotics to eradicate the infection, without ...

  2. Indigenous Greenlanders have a higher sero-prevalence of IgG antibodies to Helicobacter pylori than Danes

    DEFF Research Database (Denmark)

    Milman, Nils; Byg, Keld-Erik; Andersen, Leif P

    2003-01-01

    To assess the sero-prevalence of IgG antibodies to Helicobacter pylori (H. pylori) in Greenlanders and compare with the sero-prevalence in Caucasian Danes.......To assess the sero-prevalence of IgG antibodies to Helicobacter pylori (H. pylori) in Greenlanders and compare with the sero-prevalence in Caucasian Danes....

  3. Animal models for the study of Helicobacter pylori infection

    Directory of Open Access Journals (Sweden)

    Eliza Miszczyk

    2014-05-01

    Full Text Available The Gram-negative bacillus Helicobacter pylori is widely recognized as a major etiologic agent responsible for chronic active gastritis, peptic ulcers, the development of gastric cancer and mucosa-associated lymphoid tissue (MALT lymphoma. Still, little is known about the natural history of H. pylori infection, since patients usually after many years of not suffering from symptoms of the infection are simply asymptomatic. Since the research investigators carried out on human models has many limitations, there is an urgent need for the development of an animal model optimal and suitable for the monitoring of H. pylori infections. This review summarizes the recent findings on the suitability of animal models used in H. pylori research. Several animal models are useful for the assessment of pathological, microbiological and immunological consequences of infection, which makes it possible to monitor the natural

  4. DNA sequences from two SSRs (CIR316 and MUCS088) linked to root-knot nematode resistance genes from diverse cottons (Gossypium spp).

    Science.gov (United States)

    We investigated DNA sequencing information from alleles (DNA amplified fragments) of two previously reported SSR markers (CIR316 and MUCS088) linked to root-knot nematode (RKN) resistance genes. Markers based on electrophoretic differences, including RFLPs, AFLPs and SSRs can sometimes mask underlyi...

  5. Assessment of Helicobacter pylori eradication by virgin olive oil.

    Science.gov (United States)

    Castro, Manuel; Romero, Concepción; de Castro, Antonio; Vargas, Julio; Medina, Eduardo; Millán, Raquel; Brenes, Manuel

    2012-08-01

     A recent study conducted by Medina et al. disclosed that virgin olive oil has a bactericidal effect in vitro against Helicobacter pylori because of its contents of certain phenolic compounds with dialdehydic structures. We carried out two clinical trials to evaluate the effect of virgin olive oil on H. pylori-infected individuals.  Two different pilot studies were performed with 60 H. pylori-infected adults. In the first study, thirty subjects who tested positive for H. pylori received 30 g of washed virgin olive oil for 14 days, and after 1 month, the patients took 30 g of unwashed virgin olive oil for another 14 days. In a second study, a group of 30 subjects received 30 g of a different virgin olive oil for 14 days. Helicobacter pylori-infection status was checked by the urea breath test.  Helicobacter pylori was eradicated in 8 of 30 individuals when microorganism status was checked after 4-6 weeks from the first clinical intervention although 12 of 30 individuals did not show H. pylori infection at 24-72 hour of the last oil dose. Eradication rates were 27 and 40% by intention to treat and per protocol, respectively. Moreover, only 3 of 30 individuals were H. pylori negative after 4-6 weeks from the second clinical intervention but 5 of 30 were negative at 24-72 hour of the last oil dose. Eradication rates were 10 and 11% by intention to treat and per protocol, respectively. It must also be noted that 13 subjects withdrew from the studies because of taste and nausea drawbacks.  The administration of virgin olive oil showed moderate effectiveness in eradicating H. pylori. Further studies are needed to confirm these findings, especially with longer periods, different administration conditions, and several types of olive oils. © 2012 Blackwell Publishing Ltd.

  6. High prevalence of Helicobacter pylori infection in Malaysian Parkinson's disease patients

    Directory of Open Access Journals (Sweden)

    Nafisah WY

    2013-11-01

    Full Text Available WY Nafisah,1 A Hamdi Najman,1 R Hamizah,1 S Azmin,1 R Rabani,1 SA Shah,2 MI Norlinah11Department of Medicine, 2Department of Community Health, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, MalaysiaBackground: Studies have reported a higher prevalence of Helicobacter pylori (H. pylori infection in Parkinson's disease.Objectives: To determine the frequency of H. pylori in patients with Parkinson's disease compared to controls and its effect on symptom severity and quality of life.Methods: A cross-sectional comparative study involving 29 Parkinson's disease patients and 23 controls. The 13C-urea breath test was used to diagnose H. pylori. Symptom severity and quality of life were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS and 39-item Parkinson's Disease Questionnaire (PDQ-39, respectively.Results: The frequency of H. pylori infection was 48.3% in the Parkinson's disease group and 21.7% in controls (P=0.048. This became more significant (P=0.012 when we excluded relatives of H. pylori-positive patients from the control group. There was no association between Hoehn and Yahr stages, UPDRS and PDQ-39 scores, and H. pylori.Conclusion: H. pylori infection is more prevalent in the Malaysian Parkinson's disease population compared to controls (48.3% versus 21.7%. However, symptom severity and quality of life was not related to H. pylori infection.Keywords: Parkinson's disease, Helicobacter pylori, prevalence, 13C-urea breath test

  7. Utilization of urea micro dose with 14 C in breath test to detect the Helicobacter pylori

    International Nuclear Information System (INIS)

    Chausson, Yvon; Coelho, Luiz Gonzaga V.; Passos, Maria do Carmo F.; Andrade, Angela A.M.; Simal, Carlos J.R.; Paula Castro, Luiz de; Fernandes, M.L.; Yazaki, F.R.

    1995-01-01

    A lower dose is used in the 14 C-urea breath test to detect the Helicobacter pylori (Hp). Such dose produce trivial radiation doses. The results shown that the use of this desirable dose is possible. (author). 4 refs., 1 fig

  8. Prevalence of Helicobacter pylori and risk factors among dyspepsia ...

    African Journals Online (AJOL)

    Helicobacter pylori antibody conjugated with colloid gold nitrocellulose membrane strip and a structured face-to-face interview was also administered to assess risk factors for H. pylori infection. Data were analyzed using SPSS version 20. Logistic ...

  9. Virulence factors and treatment of Helicobacter pylori infections

    NARCIS (Netherlands)

    Talebibezminabadi, A.

    2013-01-01

    Helicobacter pylori is a Gram-negative, spiral shaped bacterium that colonizes the epithelial mucosa of the human stomach of more than 50% of the worlds population. Colonization typically occurs during early childhood, and if left untreated it usually lasts for life. The long-term persistence of H.

  10. Gastritis Induced by the Helicobacter ‘Gastrospirillum Hominis’

    Directory of Open Access Journals (Sweden)

    Sander JO Veldhuyzen van Zanten

    1994-01-01

    Full Text Available A patient with a ‘Gastrospirillum hominis’ infection in the stomach is described. ‘Gastrospirillum hominis’ belongs to the genus Helicobacter and is a rare cause of gastritis in the human stomach. It can be recognized by its distinctive morphological appearance on histology.

  11. Lactoferrin Adsorbed onto Biomimetic Hydroxyapatite Nanocrystals Controlling - In Vivo - the Helicobacter pylori Infection

    Science.gov (United States)

    Fulgione, Andrea; Nocerino, Nunzia; Iannaccone, Marco; Roperto, Sante; Capuano, Federico; Roveri, Norberto; Lelli, Marco; Crasto, Antonio; Calogero, Armando; Pilloni, Argenia Paola; Capparelli, Rosanna

    2016-01-01

    Background The resistance of Helicobacter pylori to the antibiotic therapy poses the problem to discover new therapeutic approaches. Recently it has been stated that antibacterial, immunomodulatory, and antioxidant properties of lactoferrin are increased when this protein is surface-linked to biomimetic hydroxyapatite nanocrystals. Objective Based on these knowledge, the aim of the study was to investigate the efficacy of lactoferrin delivered by biomimetic hydroxyapatite nanoparticles with cell free supernatant from probiotic Lactobacillus paracasei as an alternative therapy against Helicobacter pylori infection. Methods Antibacterial and antinflammatory properties, humoral antibody induction, histopathological analysis and absence of side effects were evaluated in both in vitro and in vivo studies. Results The tests carried out have been demonstrated better performance of lactoferrin delivered by biomimetic hydroxyapatite nanoparticles combined with cell free supernatant from probiotic Lactobacillus paracasei compared to both lactoferrin and probiotic alone or pooled. Conclusion These findings indicate the effectiveness and safety of our proposed therapy as alternative treatment for Helicobacter pylori infection. PMID:27384186

  12. Validation of {sup 14} C-urea breath test for diagnosis of Helicobacter pylori

    Energy Technology Data Exchange (ETDEWEB)

    Mattar, Rejane; Silva, Fernando Marcuz; Alexandrino, Ana Maria; Laudanna, Antonio Atilio [Sao Paulo Univ., SP (Brazil). Hospital das Clinicas. Dept. de Gastroenterologia]. E-mail: shiroineko@uol.com.br

    1999-02-01

    The aim of this study was to validate the {sup 14} C-urea breath test for use in diagnosis of Helicobacter pylori infection. Thirty H. pylori positive patients, based on histologic test and thirty H. pylori negative patients by histology and anti-H pylori IgG entered the study. Fasting patients drank 5 uCi of {sup 14} C-urea in 20 ml of water. Breath samples were collected at O, 5, 10, 15, 20 and 30 min. The difference of cpm values between the two groups was significant at all the time intervals, besides time 0 (p < 0.0001). At 20 min, the test gave 100% sensitivity and specificity with a cut-off value of 562 cpm. Females were higher expirers than males (p=0.005). {sup 14} C-urea breath test is highly accurate for Helicobacter pylori diagnosis. It is fast, simple and should be the non-invasive test used after treating Helicobacter pylori infection. (author)

  13. Helicobacter pylori in out-patients of a general practitioner

    DEFF Research Database (Denmark)

    Rothenbacher, D; Bode, G; Winz, T

    1997-01-01

    Data on prevalence and determinants of Helicobacter pylori infection in well-defined populations are scarce. We investigated the prevalence and determinants of active H. pylori infection in a population of out-patients attending a general practitioner in Southern Germany. Infection status.......4%). Prevalence of H. pylori infection increased with age from 10.8% (95% CI 5.7-18.1%) in the age group 15-29 years to 30.8% (95% CI 22.1-40.6%) in the age group 60-79 years and was 20.3%, 30.4% and 28.2% for the age groups 30-39, 40-49 and 50-59 years, respectively. Education and childhood living conditions...

  14. Saccharomyces boulardii administration can inhibit the formation of gastric lymphoid follicles induced by Helicobacter suis infection.

    Science.gov (United States)

    Yang, Lin; Tian, Zi-Bin; Yu, Ya-Nan; Zhang, Cui-Ping; Li, Xiao-Yu; Mao, Tao; Jing, Xue; Zhao, Wen-Jun; Ding, Xue-Li; Yang, Ruo-Ming; Zhang, Shuai-Qing

    2017-01-01

    Helicobacter suis has a greater tendency to induce gastric mucosa-associated lymphoid tissue lymphoma compared with other Helicobacter species in humans and animals. Saccharomyces boulardii has been established as an adjunct to H. pylori eradication treatment, but the effect of S. boulardii administration alone on Helicobacter infection remains unclear. Here, we found that S. boulardii administration effectively decreased the bacterial load of H. suis and inhibited the formation of lymphoid follicles in the stomach post-infection. The levels of H. suis-specific immunoglobulin A (IgA) and secretory IgA in the gastric juice and small intestinal secretions and the production of mouse β-defensin-3 in the small intestinal secretions were significantly increased by S. boulardii administration at 12 weeks after H. suis infection. In addition, feeding with S. boulardii inhibited the expression of inflammatory cytokines and lymphoid follicle formation-related factors after H. suis infection. These results suggested that S. boulardii may be useful for the prevention and treatment of Helicobacter infection-related diseases in humans. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Effect of specimen collection techniques, transport media, and incubation of cultures on the detection rate of Helicobacter pylori

    NARCIS (Netherlands)

    van der Hulst, R. W.; Verheul, S. B.; Weel, J. F.; Gerrits, Y.; ten Kate, F. J.; Dankert, J.; Tytgat, G. N.

    1996-01-01

    Culture and histologic examination are considered "gold standard" methods for the detection of Helicobacter pylori, but discrepancies may occur with either method. Failure to detect Helicobacter pylori may be due to sampling error, inappropriate transport or culture media, or insufficient duration

  16. Helicobacter pylori and histopathological changes of gastric mucosa ...

    African Journals Online (AJOL)

    Helicobacter pylori and histopathological changes of gastric mucosa in Uganda population with varying prevalence of stomach cancer. ... Results: The severity of gastritis correlated with the presence of H. pylori in Ganda and Nyarwanda but not in Nkole. Intestinal metaplasia (IM) was observed in Nyarwanda and Nkole and ...

  17. Implications of Antibiotic Resistance in the Management of Helicobacter pylori Infection: Canadian Helicobacter Study Group

    Directory of Open Access Journals (Sweden)

    RH Hunt

    2000-01-01

    Full Text Available Eradication of Helicobacter pylori from the gastric and duodenal mucosa is an important clinical goal in the treatment of infected patients with peptic ulcer disease and other H pylori-associated conditions. Although several oral drug combination regimens are associated with eradication rates of approximately 85% in controlled trials, the success rate in patients infected with a resistant strain of H pylori is closer to 75%. Resistance to metronidazole and clarithromycin, which are common components of combination treatment regimens, is of greatest concern. Reported rates of H pylori resistance to various antibiotics vary considerably. In Canada, the data documenting H pylori susceptibility are limited but suggest that resistance to these antibiotics varies geographically and within specific treatment groups. Although susceptibility testing is not a prerequisite for initial treatment of individual patients infected with H pylori, formal efforts to identify and monitor both the causes and prevalence of antibiotic resistance across Canada are a much needed step in the ongoing management of this important infection. Recommended treatment regimens may be useful, even for treating apparently resistant H pylori strains. However, it is important to understand the mechanisms of the development of resistant strains to manage patients with treatment failure better.

  18. SURVIVAL OF HELICOBACTER PYLORI IN A NATURAL FRESHWATER ENVIRONMENT

    Science.gov (United States)

    The mode by which Helicobacter pylori, the causative agent of most gastric ulcers, is transmitted remains undetermined. Epidemiological evidence suggests these organisms are waterborne; however, H. pylori has rarely been grown from potential water sources. This may be due to th...

  19. Integrin Subunit CD18 Is the T-Lymphocyte Receptor for the Helicobacter pylori Vacuolating Cytotoxin

    Czech Academy of Sciences Publication Activity Database

    Sewald, X.; Gebert-Vogl, B.; Prassl, S.; Barwig, I.; Weiss, E.; Fabbri, M.; Osička, Radim; Schiemann, M.; Busch, D. H.; Semmrich, M.; Holzmann, B.; Šebo, Peter; Haas, R.

    2008-01-01

    Roč. 3, č. 1 (2008), s. 20-29 ISSN 1931-3128 R&D Projects: GA ČR GP204/07/P105 Institutional research plan: CEZ:AV0Z50200510 Keywords : helicobacter pylori * vacuolating cytotoxin * adenocarcinoma Subject RIV: EE - Microbiology, Virology Impact factor: 7.436, year: 2008

  20. Co-infection with Helicobacter pylori and Epstein-Barr virus in benign upper digestive diseases: An endoscopic and serologic pilot study.

    Science.gov (United States)

    Buzás, György M; Konderák, Judith

    2016-06-01

    Some gastric cancers are Epstein-Barr virus associated. To assess the prevalence of Helicobacter pylori and viral co-infection in benign upper digestive diseases. One hundred and four outpatients were included in a prospective endoscopic-serologic study. Epstein-Barr virus immunoglobulin G (IgG), immunoglobulin M and viral capsid antigen titres were assayed with an ELISA test. Helicobacter pylori was determined by the modified Giemsa stain and by IgG-chemiluminescence. The overall prevalence of Helicobacter pylori was 56.7%. Duodenal ulcer patients were infected in 72.5 % of the cases, with the prevalence being 33.3% in functional dyspepsia (p = 0.0008) and 25.8% in reflux patients (p = 0.0001). Epstein-Barr virus IgG was detected in 70.1% of the whole group, 75% of duodenal ulcer patients, 51.2% of functional dyspepsia patients (p = 0.04) and 51.6% of the reflux disease cases (p = 0.04). Co-infection with both agents was detected in 60% of duodenal ulcer patients, 18.1% of functional dyspepsia (p = 0.00014) and 12.9% of reflux disease patients (p = 0.00012). Anti-viral IgG titre displayed a 31.7 ± 3.0 cut-off index in duodenal ulcer, 20.5 ± 3.5 in functional dyspepsia (p = 0.01) and 21.4 ± 3.6 in reflux cases (p = 0.03). Both Helicobacter pylori and Epstein-Barr virus, and co-infection with these agents, were significantly more prevalent in duodenal ulcer patients than in dyspeptic/reflux patients.

  1. Treatment of Helicobacter pylori infections: Mitigating factors and ...

    African Journals Online (AJOL)

    Helicobacter pylori is a Gram-negative, microaerophilic spiral or motile rod that infects about half the world's population with a very high prevalence in the developing world. It is an important aetiological factor in the development of gastritis, peptic ulcer disease, gastric atrophy and B cell mucosa associated lymphoid tissue ...

  2. An evaluation of the Oxoid Biochemical Identification System Campy rapid screening test for Campylobacteraceae and Helicobacter spp.

    Science.gov (United States)

    Hoosain, N; Lastovica, A J

    2009-06-01

    To evaluate the Oxoid Biochemical Identification System (OBIS) Campy test (ID0800M) against Campylobacter; Arcobacter; and other micro-organisms, with similar colonial morphology, for the detection of l-alanine aminopeptidase (l-ALA). The KOH and l-ALA (OBIS and Fluka) tests were carried out on every isolate. The procedures were followed as indicated in the OBIS and Fluka kit instructions. A total of 146 strains of 19 species of Campylobacter, seven strains of Arcobacter butzleri, four Arcobacter butzleri-like strains, 42 strains of 10 species of Helicobacter, 96 Gram-negative and 49 Gram-positive clinical isolates were tested. As expected, Campylobacter and Arcobacter strains were negative, while other Gram-negative bacteria were positive for the l-ALA test. An unexpected finding was that Helicobacter strains, although Gram-negative, were all negative for the l-ALA tests suggesting the absence of l-ALA within this genus. This is a novel finding. The absence of l-ALA was confirmed upon comparison with the available full genomic sequences of Helicobacter on the NCBI database. The OBIS Campy (ID0800M) test kit proved to be rapid and accurate for the presumptive characterization of Campylobacter and Arcobacter. A novel finding was that Helicobacter species also did not have the l-ALA enzyme. The OBIS kit will be useful in diagnostic laboratories for the presumptive diagnosis of Campylobacter, Arcobacter and Helicobacter strains.

  3. Helicobacter pylori infection and typhoid fever in Jakarta, Indonesia.

    NARCIS (Netherlands)

    Vollaard, A.M.; Verspaget, H.W.; Ali, S.; Visser, L.G.; Veenendaal, R.A.; Asten, H.A.G.H. van; Widjaja, S.; Surjadi, C.; Dissel, J.T. van

    2006-01-01

    We evaluated the association between typhoid fever and Helicobacter pylori infection, as the latter microorganism may influence gastric acid secretion and consequently increase susceptibility to Salmonella typhi infection. Anti-H. pylori IgG and IgA antibody titres (ELISA) and gastrin concentration

  4. Association between helicobacter pylori and gastrointestinal symptoms in children

    NARCIS (Netherlands)

    Spee, Leo A A; Madderom, Marieke B; Pijpers, Maaike; van Leeuwen, Yvonne; Berger, Marjolein Y

    OBJECTIVE: Recurrent abdominal pain (RAP) and other gastrointestinal (GI) symptoms are common complaints among children. The role of Helicobacter pylori in the cause of these complaints remains controversial. Nevertheless, there is an increasing pressure on primary care clinicians to screen for H

  5. Helicobacter pylori infection generates genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel; Figueiredo, C.; Seruca, R.

    2010-01-01

    The discovery that Helicobacter pylori is associated with gastric cancer has led to numerous studies that investigate the mechanisms by which H. pylori induces carcinogenesis. Gastric cancer shows genetic instability both in nuclear and mitochondrial DNA, besides impairment of important DNA repai...

  6. Association of specific haplotype of TNFα with Helicobacter pylori ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 87; Issue 3. Association of specific haplotype of TNF with Helicobacter pylori-mediated duodenal ulcer in eastern Indian population. Meenakshi Chakravorty Dipanjana Datta De Abhijit Choudhury Amal Santra Susanta Roychoudhury. Research Note Volume 87 Issue 3 ...

  7. Genotyping of vacA alleles of Helicobacter pylori strains recovered ...

    African Journals Online (AJOL)

    commonly detected genotypes in the meat-based foods, viz, vegetable sandwich and ready to eat fish, were vacA ... Keywords: Helicobacter pylori, VacA genotypes, Genotyping, Food items ..... Microbiology and Quality Control, Islamic Azad.

  8. Helicobacter canis bacteremia in a renal transplant patient

    NARCIS (Netherlands)

    van der Vusse, M. L.; van Son, W. J.; Ott, A.; Manson, W.

    Here we present a case report of a 41-year-old woman suffering from high fever and bacteremia due to Helicobacter canis, 11months after kidney transplantation. Identification of H.canis was achieved by 16s rDNA sequence analysis of a positive blood culture. The patient was restored fully to health

  9. Seroprevalence of Helicobacter pylori in Hispanics living in Puerto Rico: A population-based study.

    Science.gov (United States)

    González-Pons, María; Soto-Salgado, Marievelisse; Sevilla, Javier; Márquez-Lespier, Juan M; Morgan, Douglas; Pérez, Cynthia M; Cruz-Correa, Marcia

    2018-02-01

    Helicobacter pylori is an important etiologic factor for peptic ulcers and gastric cancer, one of the top ten leading causes of cancer death in Puerto Rico. However, the prevalence of H. pylori infections in this population was previously unknown. The aim of this study was to examine the seroprevalence of H. pylori and its associated risk factors in Puerto Rico. A cross-sectional study was designed using an existing population-based biorepository. Seropositivity was determined using the Premier ™ H. pylori immunoassay. Helicobacter pylori seroprevalence was estimated with 95% confidence using marginal standardization following logistic regression. To assess the risk factors associated with H. pylori seropositivity, a multivariable log-binomial model was fitted to estimate the prevalence ratio (PR) and its 95% confidence interval (95% CI). A total of 528 population-based serum samples were analyzed. The mean age of the study population was 41 ± 12 years, of whom 55.3% were females. The overall seroprevalence of H. pylori was 33.0% (95% CI = 28.3%-38.1%). Increasing age and having Puerto Rico. The H. pylori seroprevalence observed in Puerto Rico is similar to the seroprevalence reported in the overall population of the United States. The association between H. pylori seroprevalence and the risk factors analyzed offers insight into the epidemiology of gastric cancer in Puerto Rico and warrants further investigation. © 2017 The Authors. Helicobacter Published by John Wiley & Sons Ltd.

  10. Medicinal plants in the treatment of Helicobacter pylori infections.

    Science.gov (United States)

    Safavi, Maliheh; Shams-Ardakani, Mohammadreza; Foroumadi, Alireza

    2015-07-01

    Helicobacter pylori is a small, spiral, Gram-negative bacillus that plays a role in the pathogenesis of a number of diseases ranging from asymptomatic gastritis to gastric cancer. Schedule compliance, antibiotic drug resistance, and side-effects of triple or quadruple therapy have led to research for novel candidates from plants. The purpose of this paper is to review the most potent medicinal plants of recently published literature with anti-H. pylori activity. For centuries, herbals have been used by traditional healers around the world to treat various gastrointestinal tract disorders such as dyspepsia, gastritis, and peptic ulcer disease. The mechanism of action by which these botanicals exert their therapeutic properties has not been completely and clearly elucidated. Anti-H. pylori properties may be one of the possible mechanisms by which gastroprotective herbs treat gastrointestinal tract disorders. Electronic databases such as PubMed, Google scholar, EBSCO, and local databases were explored for medicinal plants with anti-H. pylori properties between 1984 and 2013 using key words "medicinal plants" and "Helicobacter pylori" or "anti-Helicobacter pylori". A total of 43 medicinal plant species belonging to 27 families including Amaryllidaceae, Anacardiaceae, Apiaceae, Apocynaceae, Asclepiadoideae, Asteraceae, Bignoniaceae, Clusiaceae, Chancapiedra, Combretaceae, Cyperaceae, Euphorbiaceae, Fabaceae, Geraniaceae, Lamiaceae, Lauraceae, Lythraceae, Menispermaceae, Myristicaceae, Myrtaceae, Oleaceae, Papaveraceae, Plumbaginaceae, Poaceae, Ranunculaceae, Rosaceae, and Theaceae were studied as herbs with potent anti-H. pylori effects. Traditional folk medicinal use of some of these plants to treat gastric infections is substantiated by the antibacterial activity of their extracts against H. pylori.

  11. Data on gut metagenomes of the patients with Helicobacter pylori infection before and after the antibiotic therapy

    Directory of Open Access Journals (Sweden)

    Oksana E. Glushchenko

    2017-04-01

    Full Text Available Antibiotic therapy can lead to the disruption of gut microbiota community with possible negative outcomes for human health. One of the diseases for which the treatment scheme commonly included antibiotic intake is Helicobacter pylori infection. The changes in taxonomic and functional composition of microbiota in patients can be assessed using “shotgun” metagenomic sequencing. Ten stool samples were collected from 4 patients with Helicobacter pylori infection before and directly after the H. pylori eradication course. Additionally, for two of the subjects, the samples were collected 1 month after the end of the treatment. The samples were subject to “shotgun” (whole-genome metagenomic sequencing using Illumina HiSeq platform. The reads are deposited in the ENA (project ID: PRJEB18265.

  12. Critical roles of mucin-1 in sensitivity of lung cancer cells to tumor necrosis factor-alpha and dexamethasone.

    Science.gov (United States)

    Xu, Menglin; Wang, Xiangdong

    2017-08-01

    Lung cancer is the leading cause of death from cancer. Mucins are glycoproteins with high molecular weight, responsible for cell growth, differentiation, and signaling, and were proposed to be correlated with gene heterogeneity of lung cancer. Here, we report aberrant expression of mucin genes and tumor necrosis factor receptors in lung adenocarcinoma tissues compared with normal tissues in GEO datasets. Mucin-1 (MUC1) gene was selected and considered as the target gene; furthermore, the expression pattern of adenocarcinomic cells (A549, H1650, or H1299 cells) was validated under the stimulation with tumor necrosis factor-alpha (TNFα) or dexamethasone (DEX), separately. MUC1 gene interference was done to A549 cells to show its role in sensitivity of lung cancer cells to TNFα and DEX. Results of our experiments indicate that MUC1 may regulate the influence of inflammatory mediators in effects of glucocorticoids (GCs), as a regulatory target to improve therapeutics. It shows the potential effect of MUC1 and GCs in lung adenocarcinoma (LADC), which may help in LADC treatment in the future.

  13. Apigenin has anti-atrophic gastritis and anti-gastric cancer progression effects in Helicobacter pylori-infected Mongolian gerbils.

    Science.gov (United States)

    Kuo, Chao-Hung; Weng, Bi-Chuang; Wu, Chun-Chieh; Yang, Sheau-Fang; Wu, Deng-Chang; Wang, Yuan-Chuen

    2014-02-12

    Apigenin, one of the most common flavonoids, is abundant in celery, parsley, chamomile, passionflower, and other vegetables and fruits. Celery is recognized as a medicinal vegetable in Oriental countries to traditionally treat inflammation, swelling, blood pressure, serum lipid, and toothache. In this study, we investigated apigenin treatment effects on Helicobacter pylori-induced atrophic gastritis and gastric cancer progression in Mongolian gerbils. Five to eight-week-old Mongolian gerbils were inoculated with Helicobacter pylori for four weeks without (atrophic gastritis group) or with N'-methyl-N'-nitro-N-nitroso-guanidine (MNNG) (gastric cancer group) in drinking water, and were then rested for two weeks. During the 7th-32th (atrophic gastritis group) or the 7th-52th (gastric cancer group) weeks, they were given various doses (0-60 mg/kgbw/day) of apigenin. At the end of the 32th (atrophic gastritis group) or the 52th (atrophic gastritis group) week, all Mongolian gerbils were sacrificed using the CO2 asphyxia method. The histological changes of Helicobacter pylori colonization, neutrophil and monocyte infiltrations, and atrophic gastritis in both atrophic gastritis and gastric cancer Mongolian gerbils were examined using immunohistochemistry stain and Sydney System scoring. Apigenin treatments (30-60 mg/kgbw/day) effectively decreased atrophic gastritis (atrophic gastritis group) and dysplasia/gastric cancer (gastric cancer group) rates in Mongolian gerbils. Apigenin treatment (60 mg/kgbw/day) significantly decreased Helicobacter pylori colonization and Helicobacter pylori-induced histological changes of neutrophil and monocyte infiltrations and atrophic gastritis in both atrophic gastritis and gastric cancer Mongolian gerbils. Apigenin has the remarkable ability to inhibit Helicobacter pylori-induced atrophic gastritis and gastric cancer progression as well as possessing potent anti-gastric cancer activity. Copyright © 2013 Elsevier Ireland Ltd. All rights

  14. Efficacy and safety of sequential versus quadruple therapy as second-line treatment for helicobacter pylori infection-A randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Daniela Munteanu

    Full Text Available Quadruple therapy is recommended as second-line treatment for Helicobacter pylori eradication failure. However, high cost, multiple side effects, and low adherence rates are major drawbacks to its routine use. Our aim was to compare the efficacy and safety of sequential versus quadruple regimens as second line treatment for persistent Helicobacter pylori infection.Prospective, randomized, open label trial was conducted at a large academic, tertiary care center in Israel. Patients who previously failed a standard triple treatment eradication course were randomly assigned (1:1 to receive a 10-day sequential therapy course, or a 14-day quadruple regimen. Compliance and adverse events were evaluated by telephone questionnaires. The primary endpoint for analysis was the rate of Helicobacter pylori eradication as defined by either a negative 13C-urea breath-test, or stool antigen test, 4-16 weeks after treatment assessed under the non-inferiority hypothesis. The trial was terminated prematurely due to low recruitment rates. See S1 Checklist for CONSORT checklist.One hundred and one patients were randomized. Per modified intention-to-treat analysis, eradication rate was 49% in the sequential versus 42.5% in the quadruple regimen group (p-value for non-inferiority 0.02. Forty-two (84.0% versus 33 (64.7% patients completed treatment in the sequential and quadruple groups respectively (p 0.027. Gastrointestinal side effects were more common in the quadruple regimen group.Sequential treatment when used as a second line regimen, was non-inferior to the standard of care quadruple regimen in achieving Helicobacter pylori eradication, and was associated with better compliance and fewer adverse effects. Both treatment protocols failed to show an adequate eradication rate in the population of Southern Israel.ClinicalTrials.gov NCT01481844.

  15. Linezolid susceptibility in Helicobacter pylori, including strains with multidrug resistance.

    Science.gov (United States)

    Boyanova, Lyudmila; Evstatiev, Ivailo; Gergova, Galina; Yaneva, Penka; Mitov, Ivan

    2015-12-01

    Only a few studies have evaluated Helicobacter pylori susceptibility to linezolid. The aim of the present study was to assess linezolid susceptibility in H. pylori, including strains with double/multidrug resistance. The susceptibility of 53 H. pylori strains was evaluated by Etest and a breakpoint susceptibility testing method. Helicobacter pylori resistance rates were as follows: amoxicillin, 1.9%; metronidazole, 37.7%; clarithromycin, 17.0%; tetracycline, 1.9%; levofloxacin, 24.5%; and linezolid (>4 mg/L), 39.6%. The linezolid MIC50 value was 31.2-fold higher than that of clarithromycin and 10.5-fold higher than that of levofloxacin; however, 4 of 11 strains with double/multidrug resistance were linezolid-susceptible. The MIC range of the oxazolidinone agent was larger (0.125-64 mg/L) compared with those in the previous two reports. The linezolid resistance rate was 2.2-fold higher in metronidazole-resistant strains and in strains resistant to at least one antibiotic compared with the remaining strains. Briefly, linezolid was less active against H. pylori compared with clarithromycin and levofloxacin, and linezolid resistance was linked to resistance to metronidazole as well as to resistance to at least one antibiotic. However, linezolid activity against some strains with double/multidrug resistance may render the agent appropriate to treat some associated H. pylori infections following in vitro susceptibility testing of the strains. Clinical trials are required to confirm this suggestion. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  16. Helicobacter bilis Infection Alters Mucosal Bacteria and Modulates Colitis Development in Defined Microbiota Mice.

    Science.gov (United States)

    Atherly, Todd; Mosher, Curtis; Wang, Chong; Hostetter, Jesse; Proctor, Alexandra; Brand, Meghan W; Phillips, Gregory J; Wannemuehler, Michael; Jergens, Albert E

    2016-11-01

    Helicobacter bilis infection of C3H/HeN mice harboring the altered Schaedler flora (ASF) triggers progressive immune responsiveness and the development of colitis. We sought to investigate temporal alterations in community structure of a defined (ASF-colonized) microbiota in normal and inflamed murine intestines and to correlate microbiota changes to histopathologic lesions. The colonic mucosal microbiota of healthy mice and ASF mice colonized with H. bilis for 3, 6, or 12 weeks were investigated by fluorescence in situ hybridization targeting the 16S ribosomal RNA genes of total bacteria, group-specific organisms, and individual ASF bacterial species. Microbial profiling of ASF and H. bilis abundance was performed on cecal contents. Helicobacter bilis-colonized mice developed colitis associated with temporal changes in composition and spatial distribution of the mucosal microbiota. The number of total bacteria, ASF519, and helicobacter-positive bacteria were increased (P attachment, or by invasion, and this interaction is differentially expressed over time.

  17. Almagate interference in breath test results for the diagnosis of Helicobacter pylori infection

    Directory of Open Access Journals (Sweden)

    Carles Pons

    2014-08-01

    Full Text Available Background: Infection by Helicobacter pylori is common and affects both genders at any age. The 13C-urea breath test is a widely used test for the diagnosis of this infection. However, multiple drugs used for the treatment of Helicobacter pylori infection symptoms have interactions with this breath test that generate false negative results. This observational study was to assess the potential interaction between almagate and the breath test. Methods: Thirty subjects on almagate therapy who underwent a breath test were included. If the result was negative, almagate was withdrawn for a month and the breath test was then repeated. Results: In general, 51.9 % of assessed subjects had a negative result after the first test, and 100 % of these also had a negative result after the second test. Conclusions: It was concluded that the use of almagate does not interfere in breath test results. These results provide a drug therapy option for the treatment of symptoms associated with Helicobacter pylori infection during the diagnostic process.

  18. Are clinical features able to predict Helicobacter pylori gastritis patterns? Evidence from tertiary centers.

    Science.gov (United States)

    Carabotti, Marilia; Lahner, Edith; Porowska, Barbara; Colacci, Enzo; Trentino, Paolo; Annibale, Bruno; Severi, Carola

    2014-12-01

    Outcome of Helicobacter pylori infection is different according to gastritis extension (i.e. antrum-restricted gastritis or pangastritis). The aim of this study is to evaluate whether different gastritis patterns are associated with specific gastrointestinal symptoms or clinical signs that could be suggestive of the topography of gastritis. 236 consecutive symptomatic outpatients were recruited in two tertiary centers. They filled in a validated and self-administered Rome III modular symptomatic questionnaire, and underwent gastroscopy with histological sampling. 154 patients with Helicobacter pylori infection were included. Clinical presentation did not differ between antrum-restricted gastritis and pangastritis, gastro-esophageal reflux disease being present in 48.2 and 54.1 % of patients and dyspepsia in 51.8 and 45.9 %, respectively. However, pangastritis statistically differed from antrum-restricted gastritis in that the presence of clinical signs (p gastritis pattern whereas their association with signs, accurately detected, is indicative for the presence of pangastritis.

  19. Helicobacter pylori prevalence in dyspeptic patients in the Eastern ...

    African Journals Online (AJOL)

    Helicobacter pylori prevalence in dyspeptic patients in the Eastern Cape province – race and disease status. ... Fisher's exact test was used to assess the univariate association between H. pylori infection and the possible risk factors. ... Gender, antibiotic treatment and alcohol consumption may be risk factors for infection.

  20. The efficacy of sequential therapy in eradication of Helicobacter ...

    African Journals Online (AJOL)

    ... the Helicobacter pylori (H. pylori) eradication rates of standard triple, sequential and quadruple therapies including claritromycin regimes in this study. Materials and Methods: A total of 160 patients with dyspeptic symptoms were enrolled to the study. The patients were randomized to four groups of treatment protocols.

  1. Helicobacter pylori eradication therapy: A review of current trends ...

    African Journals Online (AJOL)

    Helicobacter pylori has been implicated in the formation of chronic gastritis, peptic ulcer disease, mucosa‑associated lymphoid tissue lymphoma and gastric cancer. Eradication of H. Pylori has been recommended as treatment and prevention for these complications. This review is based on a search of Medline, the ...

  2. 49 Marked susceptibility of South African Helicobacter pylori strains ...

    African Journals Online (AJOL)

    Objectives. Helicobacter pylori-associated infection is common in South Africa, as in other developing countries. Antibiotic resistance is recognised as a major cause of treatment failure. We studied the susceptibility and resistance patterns of H. pylori to guide empiric treatment and prevent the emergence of resistance.

  3. Pattern of gastritis and Helicobacter pylori colonization of the ...

    African Journals Online (AJOL)

    Objective: Helicobacter pylori infection of the stomach causes chronic active gastritis. The pattern of gastritis is related to the disease outcome. This study aimed to determine the predominant gastritis pattern in Nigerian dyspeptic patients with a view to predicting gastroduodenal disease outcomes. Methods: Patients referred ...

  4. Helicobacter hepaticus HHGI1 is a pathogenicity island associated with typhlocolitis in B6.129-IL10tm1Cgn mice

    Science.gov (United States)

    Ge, Zhongming; Sterzenbach, Torsten; Whary, Mark; Rickman, Barry; Rogers, Arlin; Shen, Zeli; Taylor, Nancy S.; Schauer, David B.; Josenhans, Christine; Suerbaum, Sebastian; Fox, James G.

    2008-01-01

    Helicobacter hepaticus strain 3B1 (H. hepaticus) contains a genomic island of ∼71 kb, HHGI1, with some of the common features shared among known bacterial pathogenicity islands. In this study, we characterized the pathogenic potential of HHGI1 by infecting B6.129-IL10tm1Cgn (IL10-/-) mice with an isogenic mutant (namely HhPAId1) lacking 19 predicted genes within HHGI1. In contrast to H. hepaticus (P < 0.001), HhPAId1did not cause typhlocolitis and hyperplasia in IL10-/- mice. Colonization levels of HhPAId1 were significantly higher in the cecum (P <0.007) and similar in the colon (P=0.27) when compared to H. hepaticus by 13 or 16 weeks post inoculation (WPI). The magnitude of the Th1-associated IgG2c response against HhPAId1 was less than that against H. hepaticus (P < 0.004). There was no significant difference in Th2-associated IgG1 responses against these two strains. Cecal and colonic mRNA levels of proinflammatory cytokines IFN-γ, TNF-α and IL-17a in the HhPAId1-infected mice were significantly lower than those in the H. hepaticus-infected mice (P <0.05) at 13 WPI. These results demonstrate that genes in the HHGI1 contribute to the pathogenicity of H. hepaticus, at least in part via up-regulation of proinflammatory mediators IFN-γ, TNF-α and IL-17a. PMID:18538610

  5. Helicobacter pylori-coccoid forms and biofilm formation

    DEFF Research Database (Denmark)

    Andersen, Leif Percival; Rasmussen, Lone

    2009-01-01

    be detected by PCR in water supplies. There is no substantial evidence for viable H. pylori persisting in water supplies. Epidemiological studies suggest that environmental water is a risk factor for H. pylori infection when compared with tap water, and formation of H. pylori biofilm cannot be excluded....... Helicobacter pylori does not seem to take part in biofilm formation in the oral cavity even though the bacterium may be detected....

  6. (Nutmeg) on Helicobacter pylori induced gastritis in albino rats

    African Journals Online (AJOL)

    The anti-Helicobacter pylori (H. pylori) activities of dichloromethane and methanol extracts of Myristica fragrans Houtt. seed (nutmeg) was studied to authenticate ... Analysis of variance (ANOVA) tested the effect of the groups on the treatment days and revealed a significant difference between the treatments at p< 0.05.

  7. Prevalência de infecção por Helicobacter pylori em uma comunidade indígena em São Paulo e fatores associados: estudo transversal

    Directory of Open Access Journals (Sweden)

    Juliana Rejane da Silva Roque

    Full Text Available ABSTRACT CONTEXT AND OBJECTIVE: The prevalence of Helicobacter pylori infection is unevenly distributed among different populations. The aim here was to evaluate the factors associated with Helicobacter pylori infection among children up to five years of age living in a high-risk community. DESIGN AND SETTING: Cross-sectional study in an indigenous community of Guarani Mbya ethnicity, Tekoa Ytu and Tekoa Pyau villages, Jaraguá district, city of São Paulo (SP, Brazil. METHODS: 74 children aged 0.4 to 4.9 years (mean 2.9 ± 1.3 years; median 3.1, and 145 family members (86 siblings, 43 mothers and 16 fathers were evaluated for Helicobacter pylori infection using the validated 13C-urea breath test. Clinical and demographic data were collected. RESULTS: The prevalence was 8.3% among children aged 1-2 years and reached 64.3% among those aged 4-5 years (P = 0.018; overall 31.1%. The prevalence was 76.7% among siblings and 89.8% among parents. There was a negative association with previous use of antibiotics in multivariate analysis adjusted for age (odds ratio, OR: 0.07; 95% confidence interval, CI: 0.01 to 0.66; P = 0.02. The prevalence was higher among males (OR: 1.55, and was associated with maternal infection (OR: 1.81, infection of both parents (OR: 1.5, vomiting (OR: 1.28, intestinal parasitosis (OR: 2.25, previous hospitalization (OR: 0.69 and breastfeeding (OR: 1.87. CONCLUSIONS: The prevalence was high among subjects older than three years of age, thus suggesting that the incidence of infection was higher over the first three years of life. Previous use of antibiotics was inversely associated with current Helicobacter pylori infection.

  8. Prevalence of Helicobacter Pylori in Gastric Fluid in the Surgical Patient

    National Research Council Canada - National Science Library

    Mc

    1998-01-01

    Helicobacter pylori is a bacterium that infects the human gastric mucosa. It is well established as a primary factor in peptic ulcer disease and has been implicated in the pathogenesis of gastric adenocarcinoma...

  9. Comparison of the clinical and microbiological characteristics of Campylobacter and Helicobacter bacteremia: the importance of time to blood culture positivity using the BACTEC blood culture systems.

    Science.gov (United States)

    Yamamoto, Kei; Hayakawa, Kayoko; Nagashima, Maki; Shimada, Kayo; Kutsuna, Satoshi; Takeshita, Nozomi; Kato, Yasuyuki; Kanagawa, Shuzo; Yamada, Koji; Mezaki, Kazuhisa; Kirikae, Teruo; Ohmagari, Norio

    2017-11-28

    Campylobacter spp. and Helicobacter spp. are rare but important causes of bacteremia in humans. Distinguishing these bacteria is complicated because of their similar phenotypic profiles. We conducted clinical and microbiological investigations of Campylobacter spp. or Helicobacter spp. bacteremia. Patients diagnosed with bacteremia from 2008 to 2014 were included. The clinical and microbiological characteristics of Campylobacter spp. and Helicobacter spp. bacteremia were compared. The BACTEC system was used in blood cultures. A receiver operating characteristic curve was plotted based on the time to blood culture positivity. Sixteen cases of Helicobacter spp. bacteremia (patient age: 61 ± 18 years) and 14 cases of Campylobacter spp. bacteremia (patient age: 49 ± 21 years) were identified. Median time to blood culture positivity was longer for the Helicobacter spp. cases than the Campylobacter spp. cases (91.4 h vs 55.3 h, p culture positivity > 75 h predicted Helicobacter spp. bacteremia with a sensitivity of 0.88 and a specificity of 0.93 (area under the receiver operating characteristic curve of 0.90). In conclusion, a time to blood culture positivity was useful in distinguishing Helicobacter spp. bacteremia from Campylobacter spp. bacteremia.

  10. Enhanced M1 macrophage polarization in human helicobacter pylori-associated atrophic gastritis and in vaccinated mice.

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    Marianne Quiding-Järbrink

    Full Text Available BACKGROUND: Infection with Helicobacter pylori triggers a chronic gastric inflammation that can progress to atrophy and gastric adenocarcinoma. Polarization of macrophages is a characteristic of both cancer and infection, and may promote progression or resolution of disease. However, the role of macrophages and their polarization during H. pylori infection has not been well defined. METHODOLOGY/PRINCIPAL FINDINGS: By using a mouse model of infection and gastric biopsies from 29 individuals, we have analyzed macrophage recruitment and polarization during H. pylori infection by flow cytometry and real-time PCR. We found a sequential recruitment of neutrophils, eosinophils and macrophages to the gastric mucosa of infected mice. Gene expression analysis of stomach tissue and sorted macrophages revealed that gastric macrophages were polarized to M1 after H. pylori infection, and this process was substantially accelerated by prior vaccination. Human H. pylori infection was characterized by a mixed M1/M2 polarization of macrophages. However, in H. pylori-associated atrophic gastritis, the expression of inducible nitric oxide synthase was markedly increased compared to uncomplicated gastritis, indicative of an enhanced M1 macrophage polarization in this pre-malignant lesion. CONCLUSIONS/SIGNIFICANCE: These results show that vaccination of mice against H. pylori amplifies M1 polarization of gastric macrophages, and that a similar enhanced M1 polarization is present in human H. pylori-induced atrophic gastritis.

  11. Correlation of Serum Anti- Helicobacter pylori Immunoglobulin A (IGA)

    African Journals Online (AJOL)

    Background: The seroprevalence of anti-H. pylori IgA antibodies has been reported to vary among populations and in relation to strains of Helicobacter pylori bacterium. However, there has been conflicting reports on the association between IgA serological status and the histological variables of chronic gastritis. This study ...

  12. Helicobacter Pylori –Infected Patients | Eltayeb | Sudan Journal of ...

    African Journals Online (AJOL)

    Background: The role of Helicobacter pylori on gastric carcinogenesis is still unclear but it is considered to predispose carriers to gastric cancer. Objective: The aim of this study is to investigate the relationship between the extent of DNA damage of normal gastric epithelial cells and H. Pylori positive & negative gastritis ...

  13. Comportamiento higiénico-sanitario de pacientes con diagnóstico de úlcera gastroduodenal por Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Javier Jesús Suárez Rivera

    Full Text Available Introducción: actualmente la infección por Helicobacter pylori constituye la infección crónica más extensamente difundida en la especie humana, la cual puede cursar como síndrome dispéptico funcional u orgánico, gastritis, úlcera gastroduodenal y con síntomas subjetivos de cáncer gástrico. Diferentes estudios epidemiológicos cifran prácticamente en el 95 % de los casos la asociación entre úlcera duodenal e infección por Helicobacter pylori. Objetivo: describir el comportamiento de algunas variables higiénicas-sanitarias en pacientes con úlceras gastroduodenales por Helicobacter pylori. Métodos: se realizó un estudio descriptivo y prospectivo de corte transversal a 908 pacientes con diagnóstico de úlcera péptica y positiva al test rápido de ureasa, en el período comprendido desde enero de 2007 hasta diciembre de 2008, en el Centro de Diagnóstico Integral del municipio «Rafael Urdaneta», estado Miranda, República Bolivariana de Venezuela. Resultados: predominaron los pacientes que mantenían una higiene alimentaria inadecuada; los que no hervían el agua para tomar; y los que compartían los cubiertos sin previo lavado, elementos que pueden favorecer la infección por Helicobacter pylori. Conclusiones: hay estrecha relación entre la infección por Helicobacter pylori y el hábito higiénico, siendo más frecuente en los pacientes con hábito higiénico inadecuado.

  14. ANTIBIOTIC RESISTANCE OF HELICOBACTER PYLORI AMONG CHILDREN AND THERAPY SELECTION

    Directory of Open Access Journals (Sweden)

    Ye.A. Kornienko

    2006-01-01

    Full Text Available The reason for the low therapy efficiency of many gastrobduodenal diseases is the increasing resistance to the antibiotics helicobacter pylori (Н. pylori, which is conditioned by the mutations of its various genes. The most practical importance is attributed to the 23s RRNA mutations, underlying resistance to claritromicin. According to the international consensus maastrichtb3, the scheme of treatment with the inhibitor of the proton pump, claritromicin and metronidasol is recommended as the 1st line therapy. The present work assesses the resistance of Н. pylori to claritromicin aided by pcrbdiagnostics of the 23s RRNA mutation of rna in the biopsy material of the mucous coat of stomach and standard treatment scheme efficiency if compared with the onebantibiotic scheme – amoxicillin, bismuth and inhibitor of the proton pump. 68 children with Н. pylori bassociated diseases have been examined. The frequency of resistance of Н. pylori to claritromicin made up 28%. The standard 10bday long scheme of treatment was efficient among 14% of the patients, the 7bday long schemes with amoxicillin, bismuth and omeprazole were efficient among 40% of the patients, the 10bday long schemes with amoxicillin, bismuth and omeprazole were efficient among 75% of the patients; with omeprazole replaced by esomeprazole the efficiency was observed among 83% of the patients along with the good treatment tolerance.Key words: helicobacter pylori, antibiotic resistance, eradication.

  15. Spanish scientific output on Helicobacter pylori. A study through Medline.

    Science.gov (United States)

    Trapero-Marugán, M; Gisbert, J P; Pajares, J M

    2006-04-01

    to analyze scientific output from Spanish hospitals in relation to Helicobacter pylori infection. papers collected from the Medline database between January 1988 and December 2003 were selected. Our search strategy was: "Helicobacter pylori" [MeSH] AND ((Spain [AD] OR Espana [AD] OR Spanien [AD] OR Espagne [AD] OR Espanha [AD]) OR (Spanish [LA]) OR Spain). The following was analyzed: geographic area, Spanish or foreign publication, topic, and year of publication. Output and impact bibliometric markers were evaluated. in all, 691 papers were identified, of which 241 were excluded. Number of papers went from 2 in 1988 to 47 in 2002 and 13 in 2003. There were more reports in Spanish versus foreign journals (58 vs. 42%). In the first 5 years the areas with greater output were associated with diagnosis and microbiology (33 and 20%), whereas therapy was the predominating subject during the last 5 years (27%). Original papers were most common among publications (69%). Hospitals with highest output included La Princesa (24%) and Ramón y Cajal (17.6%) in Madrid, and Parc Taulí in Barcelona (6.4%). Mean impact factor progressively increased from 1.826 in 1988 to 2.142 in 2002 and 2.493 in 2003. the production and impact of documents published by Spanish scientists regarding H. pylori infection considerably increased during the past two decades.

  16. Greater than 95% success with 14-day bismuth quadruple anti- Helicobacter pylori therapy: a pilot study in US Hispanics.

    Science.gov (United States)

    Salazar, Cesar O; Cardenas, Victor M; Reddy, Rita K; Dominguez, Delfina C; Snyder, Lindsey K; Graham, David Y

    2012-10-01

    A combination capsule of bismuth, metronidazole, and tetracycline plus omeprazole given as 10-day therapy has an overall effectiveness of 92-93% in per-protocol analysis (Grade B) with eradication of 86-91% of metronidazole-resistant Helicobacter pylori. This study aimed to explore whether extending the duration to 14 days would improve overall effectiveness per protocol to ≥95% (Grade A) in a population in which metronidazole resistance was anticipated to exist. A one-arm, open-label pilot study of H. pylori-infected, asymptomatic/mildly dyspeptic adults, Hispanic residents of El Paso, Texas, received a 14-day course of omeprazole, plus the combination capsule. We cultured and Gram-stained specimens obtained using a minimally invasive orogastric brush. Helicobacter pylori status was determined by (13)C-urea breath test at 4 or more weeks post-therapy. Forty-seven subjects (7 men and 40 women, average age 42 years) were entered. The per-protocol effectiveness was 97.1% (33/34) (95% mid-P CI: 86.3, 99.9); 100% of metronidazole-resistant strains were eradicated. Side effects were mild and self-limited but contributed to nonadherence. Therapy taken for failure (p forms in all specimens. This pilot study supports the concept that 14-day OBMT therapy is likely to be more efficacious for H. pylori eradication (Grade A, PP basis) than a 10-day course where metronidazole resistance is suspected. If confirmed, 14 days should be recommended in populations where metronidazole resistance is common. © 2012 Blackwell Publishing Ltd.

  17. The interaction of hepatitis A virus (HAV with soluble forms of its cellular receptor 1 (HAVCR1 share the physiological requirements of infectivity in cell culture

    Directory of Open Access Journals (Sweden)

    Kaplan Gerardo G

    2009-10-01

    Full Text Available Abstract Background Hepatitis A virus (HAV, an atypical Picornaviridae that causes acute hepatitis in humans, usurps the HAV cellular receptor 1 (HAVCR1 to infect cells. HAVCR1 is a class 1 integral membrane glycoprotein that contains two extracellular domains: a virus-binding immunoglobulin-like (IgV domain and a mucin-like domain that extends the IgV from the cell membrane. Soluble forms of HAVCR1 bind, alter, and neutralize cell culture-adapted HAV, which is attenuated for humans. However, the requirements of the HAV-HAVCR1 interaction have not been fully characterized, and it has not been determined whether HAVCR1 also serves as a receptor for wild-type (wt HAV. Here, we used HAV soluble receptor neutralization and alteration assays to study the requirements of the HAV-HAVCR1 interaction and to determine whether HAVCR1 is also a receptor for wt HAV. Results Treatment of HAV with a soluble form of HAVCR1 that contained the IgV and two-thirds of the mucin domain fused to the Fc fragment of human IgG1 (D1 muc-Fc, altered particles at 37°C but left a residual level of unaltered particles at 4°C. The kinetics of neutralization of HAV by D1 muc-Fc was faster at 37°C than at 4°C. Alteration of HAV particles by D1 muc-Fc required Ca, which could not be replaced by Li, Na, Mg, Mn, or Zn. Neutralization of HAV by D1 muc-Fc occurred at pH 5 to 8 but was more efficient at pH 6 to 7. D1 muc-Fc neutralized wt HAV as determined by a cell culture system that allows the growth of wt HAV. Conclusion The interaction of HAV with soluble forms of HAVCR1 shares the temperature, Ca, and pH requirements for infectivity in cell culture and therefore mimics the cell entry process of HAV. Since soluble forms of HAVCR1 also neutralized wt HAV, this receptor may play a significant role in pathogenesis of HAV.

  18. The Efficacy of Eradication of Helicobacter pylori Infection in Primary Prevention of NSAID-induced Gastropathy

    Directory of Open Access Journals (Sweden)

    S.M. Tkach

    2015-09-01

    Full Text Available With the aim of clarifying the efficacy of eradication therapy for Helicobacter pylori (Hp infection in primary prevention of NSAID-induced gastropathy, we have examined 39 Hp-positive patients, in whom we planned to administer non-steroidal anti-inflammatory drugs (NSAIDs for various arthritis. In group I, non-steroidal anti-inflammatory drugs were prescribed after anti-helicobacter therapy, in group II eradication was not carried out, and the patients immediately received diclofenac. In both groups the incidence of peptic ulcers has been compared in 1 month after receiving diclofenac. In group I, peptic ulcers occurred in 2 patients (10.5 %, in group II — in 5 patients (26.3 %, ie in the group of eradication therapy they occurred significantly less frequently (χ2 = 0.5221. It is concluded that eradication of Hp-infection can be considered as an effective strategy for primary prevention of NSAID-induced gastropathy.

  19. Prevalence Of Helicobacter pylori In Gastric Biopsies Of Patients ...

    African Journals Online (AJOL)

    The prevalence of Helicobacter pylori infection as seen at the University of Benin Teaching Hospital (UBTH) Benin City Nigeria was 16% which was significant using the students T-test (P<0.05). Eighty one gastric biopsy specimens received in the microbiology laboratory were cultured on chocolate agar. Of the H. pylori ...

  20. Comparative Genomics of H. pylori and Non-Pylori Helicobacter Species to Identify New Regions Associated with Its Pathogenicity and Adaptability

    Directory of Open Access Journals (Sweden)

    De-Min Cao

    2016-01-01

    Full Text Available The genus Helicobacter is a group of Gram-negative, helical-shaped pathogens consisting of at least 36 bacterial species. Helicobacter pylori (H. pylori, infecting more than 50% of the human population, is considered as the major cause of gastritis, peptic ulcer, and gastric cancer. However, the genetic underpinnings of H. pylori that are responsible for its large scale epidemic and gastrointestinal environment adaption within human beings remain unclear. Core-pan genome analysis was performed among 75 representative H. pylori and 24 non-pylori Helicobacter genomes. There were 1173 conserved protein families of H. pylori and 673 of all 99 Helicobacter genus strains. We found 79 genome unique regions, a total of 202,359bp, shared by at least 80% of the H. pylori but lacked in non-pylori Helicobacter species. The operons, genes, and sRNAs within the H. pylori unique regions were considered as potential ones associated with its pathogenicity and adaptability, and the relativity among them has been partially confirmed by functional annotation analysis. However, functions of at least 54 genes and 10 sRNAs were still unclear. Our analysis of protein-protein interaction showed that 30 genes within them may have the cooperation relationship.

  1. Prevalence of Helicobacter spp in chronic cholecystitis and correlation with changes on the histological pattern of the gallbladder Prevalência do Helicobacter spp na colecistite crônica calculosa e correlação com as alterações histológicas da vesícula biliar

    Directory of Open Access Journals (Sweden)

    André de Moricz

    2010-06-01

    Full Text Available PURPOSE: Establish the prevalence of Helicobacter spp in chronic cholecystitis and its correlation with the gallbladder's histological findings. METHODS: 100 patients were operated for chronic cholecystitis with cholecystolithiasis. In pathological examination of the gallbladder, were evaluated the presence of metaplasia, dysplasia, lymphoid follicles, anaplasia and tumors that might be related to the presence of Helicobacter plus the presence of the bacilli Giemsa? by optical microscopy. From the DNA extracted from the gallbladder's bile, PCR was performed by using specific primers for the identification of Helicobacter spp with amplification of the 400bp segment of rRNA gene16S, with positive control DNA from Helicobacter pylori. All the cases negative for isolation of genetic material were excluded. The cases of PCRΘ and GiemsaΘ were used as negative control group. The histological findings were compared to the presence of bacilli and PCR data using a chi-square and Fisher's Exact test (CI = 95.0%, p OBJETIVO: Estabelecer a prevalência do Helicobacter spp nos doentes com colecistopatia crônica calculosa e correlacioná-la com as alterações histológicas da vesícula biliar. MÉTODOS: Foram operados 100 doentes portadores de colecistite crônica calculosa. No anátomo-patológico foram avaliadas a presença de, metaplasias, displasias, folículos linfóides, anaplasias e tumores que pudessem se relacionar à presença do helicobacter e a presença de bacilos Giemsa ? à microscopia. A partir do DNA extraído da bile foi realizada PCR utilizando-se primers específicos para identificação de Helicobacter spp com amplificação de segmento de 400bp do gene16S rRNA, com controle positivo de DNA de Helicobacter Pylori. Os casos negativos para isolamento de material genético na bile foram excluídos. Os casos de PCR e Giemsa negativos foram utilizados como grupo controle. Os achados histológicos foram comparados ao Giemsa e à PCR

  2. Effect of Pretreatment with Lactobacillus delbrueckii and Streptococcus thermophillus on Tailored Triple Therapy for Helicobacter pylori Eradication: A Prospective Randomized Controlled Clinical Trial.

    Science.gov (United States)

    Tongtawee, Taweesak; Dechsukhum, Chavaboon; Leeanansaksiri, Wilairat; Kaewpitoon, Soraya; Kaewpitoon, Natthawut; Loyd, Ryan A; Matrakool, Likit; Panpimanmas, Sukij

    2015-01-01

    Helicobacter pylori plays an important role in gastric cancer and typical eradication regimens are no longer effective in many countries, including Thailand. The aim of our study was to compare the effect of Lactobacillus delbrueckii and Streptococcus thermophillus on tailored triple therapy for Helicobacter pylori eradication. This prospective single-center study was conducted in Thailand. Helicobacter pylori associated gastritis patients were randomized to 2 groups: group 1 (n=100) was tailored triple therapy with placebo (esomeprazole 20 mg bid, clarithromycin 500 mg bid or metronidazole 400 mg tid if clarithromycin resistance and amoxicillin 1000 mg bid), and group 2 was tailored triple therapy plus pretreatment with probiotic containing yogurt. Successful eradication was defined as both negative histology and negative rapid urease test at four weeks after treatment. A total of 200 infected patients were enrolled. PP analysis involved 194 patients: 96 in the tailored triple therapy with placebo group (group 1) and 98 the in tailored triple therapy plus pretreatment with probiotic containing yogurt group (group 2). Successful eradication was observed in 170 (87.6%) patients; by PP analysis, the eradication rate was significantly higher in group 2 (P=0.04, 95%CI; 0.02-0.13) than in group 1. ITT analysis also showed that the value was significantly higher in the tailored triple threapy plus pretreatment with probiotic containing yogurt group (group 2) (89/100; 89%) than in the tailored triple therapy with placebo group (group 1) (P=0.01, 95%CI; 0.04-0.15). In terms of adverse events, there was no significant difference between the two groups. Pretreatment with probiotic containing yogurt can improve Helicobacter pylori eradication rates with tailored triple therapy. Adding probiotics does not reduce adverse effects of the medication.

  3. Effect of Helicobacter pylori Eradication on Functional Dyspepsia

    Science.gov (United States)

    Kim, Sung Eun; Park, Young Soo; Kim, Min Soo; Jo, Hyun Jin; Shin, Cheol Min; Lee, Sang Hyub; Hwang, Jin-Hyeok; Kim, Jin-Wook; Jeong, Sook-Hyang; Lee, Dong Ho; Jung, Hyun Chae

    2013-01-01

    Background/Aims This study evaluated the effect of Helicobacter pylori eradication on functional dyspepsia (FD), and the relationship between the changes of histological gastritis and FD symptom responses. Methods A total of 213 FD patients diagnosed by Rome III criteria were consecutively enrolled. H. pylori tests and gastritis grade by the Sydney system were performed before and 1 year after the proton pump based-eradication therapy for 7 days. Serum levels of pepsinogen, and genetic polymorphisms IL-6, IL-8 and IL-10 were investigated. Results Total of 91 patients completed the 1 year follow-up. When the response rate of dyspepsia was compared at 1 year between the non-eradicated group (n = 24) and eradicated group (n = 67), each group showed complete response of 62.5% and 62.7%; satisfactory response (≥ 50%) of 0.0% and 19.4%; partial response (gastritis at 1 year, suggesting that inflammation mediates FD. PMID:23667755

  4. Association of the Helicobacter pylori cagA, vacA, and iceA genotypes with chronic follicular gastritis in a Colombian population at high risk for gastric cancer.

    Science.gov (United States)

    Carlosama-Rosero, Y H; Bolaños-Bravo, H; Sierra-Tórres, C H; Rosero, E A

    2018-05-16

    Follicular gastritis is associated with Helicobacter pylori infection, but little is known of its relation to bacterial genotypes. Our aim was to establish the relation between follicular gastritis and different H. pylori strains. An analytic case-control study was conducted that included 36 patients with follicular gastritis (cases) and 83 with nonatrophic gastritis (controls). The sociodemographic information was obtained through a questionnaire. Biopsies were evaluated according to the Sydney System and the Wotherspoon scoring system. Helicobacter pylori genotyping was performed using the polymerase chain reaction technique. The quantitative variables were presented as mean and standard deviation and the qualitative variables as proportions and absolute frequency. The effect of each variable on outcome (follicular gastritis) was evaluated through the odds ratio and its 95% confidence interval. Statistical significance was set at a P<.05. Follicular gastritis was associated with Helicobacter pylori infection (OR: 13.41, CI: 1.7-103, P=.01). The CagA+ genotype was present in 56.5% of the cases and 58% of the controls. The cytotoxic VacAs1m1strain was present in 82% of the isolates in both groups. IceA1 frequency was 34.8% in the cases and 26% in the controls and the difference was not statistically significant. The population studied had elevated frequencies of cytotoxic Helicobacter pylori strains and the iceA1 genotype was more frequent in follicular gastritis. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  5. Helicobacter pylori: focus on CagA and VacA major virulence factors Helicobacter pylori: enfoque sobre los factores de virulencia CagA y VacA

    Directory of Open Access Journals (Sweden)

    Gonzalo Castillo-Rojas

    2004-12-01

    Full Text Available After colonizing the human gastric mucosa, Helicobacter pylori can remain within the host for years and even decades, and is associated with several, highly significant gastric pathologies. In Mexico, the seroprevalence at 1 year of age is 20% and the estimated increment in seropositivity per year is 5% for children aged 1-10 years. More than 80% of adults are infected by the time they are 18-20 years old. Bacterial virulence factors have been proposed for H. pylori, such as urease, flagella, heat-shock protein, lipopolysaccharide, adhesions, vacuolating cytotoxin, cag pathogenicity island and the cytotoxin-associated protein, the latter being the most studied mechanism to date.Después de colonizar la mucosa gástrica humana, Helicobacter pylori puede permanecer por años e incluso décadas en el humano, y se asocia a varias patologías gástricas. En México, la seroprevalencia estimada es de 20% en niños de un año de edad, con una tasa de incremento en seropositividad de 5% anual durante los primeros 10 años de vida hasta alcanzar 80% en adultos jóvenes entre los 18 y 20 años de edad. Los factores bacterianos de virulencia propuestos para H. pylori son ureasa, flagelos, proteínas de choque térmico, lipopolisacárido, adhesinas, citotoxina vacuolizante, isla de patogenicidad y la proteína asociada a la citoxina; este último factor es el más estudiado hasta la fecha.

  6. Efficacy of a triple therapy for Helicobacter pylori eradication in a well-developed urban area in Brazil

    Directory of Open Access Journals (Sweden)

    Patrick Bellelis

    Full Text Available CONTEXT: Helicobacter pylori eradication has become the standard treatment for peptic ulcer disease. Triple therapy with omeprazole plus two antibiotics has been used. Due to the lack of ideal treatment and the high rates of primary resistance to nitroimidazoles, the use of clarithromycin has been adopted. OBJECTIVE: To determine the Helicobacter pylori eradication rates using lansoprazole, amoxicillin and clarithromycin for seven days, in patients with peptic ulcer disease in a well developed urban area in Brazil. METHODS: This was a retrospective, open-label study carried out at the School of Medicine of the Fundação ABC. It included 130 patients with peptic ulcer disease (upper endoscopy who had been tested positive for Helicobacter pylori infection (urease test, histology or breath test, without previous treatment. Patients were treated with lansoprazole 30 mg, amoxicillin 1,000 mg and clarithromycin 500 mg b.i.d., for seven days. Eradication was verified after 90 days. RESULTS: Follow-up data were available for 94 patients. Their mean age was 52.23 years; 51.54% were woman, 84.31% white, 37.69% smokers, 20.77% using nonsteroidal anti-inflammatory drugs and 8.46% alcoholics. Upper endoscopy revealed that 78.46% had duodenal ulcers and 21.53% had gastric ulcers (a 4:1 DU:GU ratio. The eradication rates were 85.11% per protocol and 61.54% by intention to treat; 97% had no adverse effects. CONCLUSION: Triple therapy using lansoprazole, amoxicillin and clarithromycin is well tolerated with high eradication rates and forms a good alternative for developing countries.

  7. Frequency of helicobacter pylori antibodies in porto-systemic encephalopathy,

    International Nuclear Information System (INIS)

    Sethar, G.H.; Ahmed, R.; Afsar, S.; Zuberi, B.F.

    2004-01-01

    Objective: To study the frequency of Helicobacter pylori antibodies in patients presenting with porto-systemic encephalopathy due to liver disease. Patients and Methods: During the study period, seventy-six patients of porto-systemic encephalopathy due to liver diseases was selected. These subjects were evaluated for hepatic encephalopathy grade, modified Child-Pugh classification and were managed according to the standard practices. These patients were evaluated for Helicobacter (H. pylori) antibody status by ELlSA (Abbott Laboratories) method. Results: Out of 76 patients studied and tested for H. pylori antibodies, 48(63.2%) were males and 28(36.8%) were females with age ranging between 17 and 85 years. Out of 76 patients who presented with porto-systemic encephalopathy, 59(77.6%) had a positive H. pylori antibody test. Thirty-five of these were males and 24 were females. A significant number of patients who presented with higher grade of encephalopathy were H. pylori antibody positive (p<0.001). Conclusion: In this study, frequency of H. pylori antibodies was significantly high in patients of porto-systematic encephalopathy. (author)

  8. [Seroprevalence of Helicobacter pylori among the child population of Ecuador].

    Science.gov (United States)

    Gómez, Nestor A; Salvador, Alexandra; Vargas, Paola E; Zapatier, Jorge A; Alvarez, José

    2004-01-01

    To determine the prevalence of anti-Helicobacter pylori IgG antibodies among the children population of Ecuador and the possible relation with the presence of recurring gastrointestinal symptoms. Children randomly selected from different geographical areas were included and the presence of serum antibodies was tested using the enzyme-linked immunosorbent assay (ELISA). The gastrointestinal symptoms between patients with serum antibodies and those without serum antibodies were analyzed, excluding children who had not been treated for intestinal parasites before. A total of 257 children was studied, with a mean age of 8.3 years (age range between 6 months and 16 years). A seroprevalence of 63.03% was found, the most affected being the children from the Andes mountains, in the range 0 to 4 years old. A significant relation was found between the presence of anti-Hp antibodies and symptoms (p=0.001). There is a high prevalence of anti-Helicobacter pylori IgG antibodies among the Ecuadorian children, related with the presence of recurring gastrointestinal symptoms.

  9. Relationship of interleukin-1B gene promoter region polymorphism with Helicobacter pylori infection and gastritis.

    Science.gov (United States)

    Ramis, Ivy Bastos; Vianna, Júlia Silveira; Halicki, Priscila Cristina Bartolomeu; Lara, Caroline; Tadiotto, Thássia Fernanda; da Silva Maciel, João Batista; Gonçalves, Carla Vitola; von Groll, Andrea; Dellagostin, Odir Antônio; da Silva, Pedro Eduardo Almeida

    2015-09-29

    Helicobacter pylori infection is associated with gastritis, peptic ulcer disease and gastric carcinoma. The severity of damage is determined by the interplay between environmental/behavioral factors, bacterial pathogenicity genes and host genetic polymorphisms that can influence the secretion levels of inflammatory cytokines. Accordingly, this study aimed to identify polymorphisms in the IL-1B and IL-1RN genes and their associations with H. pylori infection, cagA gene of H. pylori, and gastroduodenal diseases. Gastric biopsy samples from 151 patients infected with H. pylori and 76 uninfected individuals were analyzed. H. pylori infection was diagnosed by histology and PCR. Polymorphisms at positions -511, -31 and +3954 of the IL-1B gene were detected by PCR-RFLP, and an analysis of the VNTR polymorphism of the IL-1RN gene was performed by PCR. It was observed that the presence of the T/T genotype at position -511 and the C/C genotype at position -31 were associated with H. pylori infection and with an increased risk of gastritis in H. pylori-positive patients. Additionally, strains from patients H. pylori-positive carrying the cagA gene was significantly related with the T/T genotype at position -511 of IL-1B.  No association of polymorphisms at position +3954 of IL-1B and in the IL-1RN with H. pylori infection and with risk of severe gastric diseases was found. We demonstrated that polymorphisms in the promoter region of the IL-1B gene (at positions -511 and -31) are associated with an enhanced risk of H. pylori infection as well as gastritis in H. pylori-positive patients.

  10. Epithelial cell kinetics of the gastric mucosa during Helicobacter pylori infection

    DEFF Research Database (Denmark)

    Holck, Susanne; Holm, I.L.; Holck, P.P.

    2007-01-01

    Helicobacter pylori is an important pathogen in major gastroduodenal diseases, including inflammation with ulceration and gastric malignancies. Alterations in H. pylori associated cell turnover in gastric epithelial cells are examined in relation to inflammatory activity, bacteria load and cytoki...

  11. Natural Gastric Infection with Helicobacter pylori in Monkeys: A Model for Spiral Bacteria Infection in Humans

    Science.gov (United States)

    1994-01-01

    Methods: Infection and gastritis were have facilitated larger epidemiological studies. Another graded blindly by histological analysis and culture of...infec- with both types of bacteria by histological analysis and tion. Gastritis scores began to decrease 1 month after culture of H. pylori. In these 3...indicated that monkeys were not Infected. Gastritis score was :1.5 this organism belongs in the Helicobacter genus, and it in animals uninfected or

  12. 3rd BRAZILIAN CONSENSUS ON Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Luiz Gonzaga Coelho

    2013-04-01

    Full Text Available Significant progress has been obtained since the Second Brazilian Consensus Conference on Helicobacter pylori Infection held in 2004, in São Paulo, SP, Brazil, and justify a third meeting to establish updated guidelines on the current management of H. pylori infection. The Third Brazilian Consensus Conference on H pylori Infection was organized by the Brazilian Nucleus for the Study of Helicobacter, a Department of the Brazilian Federation of Gastroenterology and took place on April 12-15, 2011, in Bento Gonçalves, RS, Brazil. Thirty-one delegates coming from the five Brazilian regions and one international guest, including gastroenterologists, pathologists, epidemiologists, and pediatricians undertook the meeting. The participants were allocated in one of the five main topics of the meeting: H pylori, functional dyspepsia and diagnosis; H pylori and gastric cancer; H pylori and other associated disorders; H pylori treatment and retreatment; and, epidemiology of H pylori infection in Brazil. The results of each subgroup were submitted to a final consensus voting to all participants. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Seventy per cent and more votes were considered as acceptance for the final statement. This article presents the main recommendations and conclusions to guide Brazilian doctors involved in the management of H pylori infection.

  13. Genotyping of vacA alleles of Helicobacter pylori strains recovered ...

    African Journals Online (AJOL)

    Genotyping of vacA alleles of Helicobacter pylori strains recovered from some Iranian food items. ... Tropical Journal of Pharmaceutical Research ... Conclusion: The presence of similar genotypes in H. pylori strains of foods and those of human clinical samples suggest that contaminated foods may be the source of bacteria ...

  14. Optical Aptamer Probes of Fluorescent Imaging to Rapid Monitoring of Circulating Tumor Cell

    Directory of Open Access Journals (Sweden)

    Ji Yeon Hwang

    2016-11-01

    Full Text Available Fluorescence detecting of exogenous EpCAM (epithelial cell adhesion molecule or muc1 (mucin1 expression correlated to cancer metastasis using nanoparticles provides pivotal information on CTC (circulating tumor cell occurrence in a noninvasive tool. In this study, we study a new skill to detect extracellular EpCAM/muc1 using quantum dot-based aptamer beacon (QD-EpCAM/muc1 ALB (aptamer linker beacon. The QD-EpCAM/muc1 ALB was designed using QDs (quantum dots and probe. The EpCAM/muc1-targeting aptamer contains a Ep-CAM/muc1 binding sequence and BHQ1 (black hole quencher 1 or BHQ2 (black hole quencher2. In the absence of target EpCAM/muc1, the QD-EpCAM/muc1 ALB forms a partial duplex loop-like aptamer beacon and remained in quenched state because the BHQ1/2 quenches the fluorescence signal-on of the QD-EpCAM/muc1 ALB. The binding of EpCAM/muc1 of CTC to the EpCAM/muc1 binding aptamer sequence of the EpCAM/muc1-targeting oligonucleotide triggered the dissociation of the BHQ1/2 quencher and subsequent signal-on of a green/red fluorescence signal. Furthermore, acute inflammation was stimulated by trigger such as caerulein in vivo, which resulted in increased fluorescent signal of the cy5.5-EpCAM/muc1 ALB during cancer metastasis due to exogenous expression of EpCAM/muc1 in Panc02-implanted mouse model.

  15. Outer membrane biogenesis in Helicobacter pylori: A deviation from the paradigm

    Directory of Open Access Journals (Sweden)

    George W. Liechti

    2012-04-01

    Full Text Available The bacterial pathogen Helicobacter pylori is capable of colonizing the gastric mucosa of the human stomach using a variety of factors associated with or secreted from its outer membrane (OM. Lipopolysaccharide (LPS and numerous outer membrane proteins have been shown to be involved in adhesion and immune stimulation/evasion. Many of these factors are essential for colonization and/or pathogenesis in a variety of animal models. Despite this wide array of potential targets present on the bacterial surface, the ability of H. pylori to vary its outer membrane profile limits the effectiveness of vaccines that use any single one of these components. However, it has become evident that the proteins comprising the complexes that transport the majority of these molecules to the OM are highly conserved and often essential. The field of membrane biogenesis has progressed remarkably in the last few years, and the possibility now exists for targeting the mechanisms by which β-barrel proteins, lipoproteins, and LPS are transported to the OM, resulting in loss of bacterial fitness and significant altering of membrane permeability. In this review, the OM transport machinery for LPS, lipoproteins, and outer membrane proteins are discussed. While the principal investigations of these transport mechanisms have been conducted in Escherichia coli and Neisseria meningitidis, here these systems will be presented in the genetic context of ε- proteobacteria. Bioinformatic analysis reveals that minimalist genomes, such as that of Helicobacter pylori, offer insight into the smallest number of components required for these essential pathways to function. Interestingly, in the majority of ε-proteobacteria, while the inner and outer membrane associated apparatus of LPS, lipoprotein, and OM protein transport pathways appear to all be intact, most of the components associated with the periplasmic compartment are either missing or are almost unrecognizable when compared to

  16. Lactotetraosylceramide, a novel glycosphingolipid receptor for Helicobacter pylori, present in human gastric epithelium

    OpenAIRE

    Teneberg, Susann; Leonardsson, Iréne; Karlsson, Hasse; Jovall, Per-Åke; Ångström, Jonas; Danielsson, Dan; Näslund, Ingmar; Ljungh, Åsa; Wadström, Torkel; Karlsson, Karl-Anders

    2002-01-01

    The binding of Helicobacter pylori to glycosphingolipids was examined by binding of 35S-labeled bacteria to glycosphingolipids on thin-layer chromatograms. In addition to previously reported binding specificities, a selective binding to a non-acid tetraglycosylceramide of human meconium was found. This H. pylori binding glycosphingolipid was isolated and, on the basis of mass spectrometry, proton NMR spectroscopy, and degradation studies, were identified as Gal3GlcNAc3Gal4Glc1Cer (lactotetrao...

  17. Genetic Polymorphism of MDM2 SNP309 in Patients with Helicobacter Pylori-Associated Gastritis.

    Science.gov (United States)

    Tongtawee, Taweesak; Dechsukhum, Chavaboon; Leeanansaksiri, Wilairat; Kaewpitoon, Soraya; Kaewpitoon, Natthawut; Loyd, Ryan A; Matrakool, Likit; Panpimanmas, Sukij

    2015-01-01

    Helicobacter pylori plays an important role in gastric cancer, which has a relatively low inciduence in Thailand. MDM2 is a major negative regulator of p53, the key tumor suppressor involved in tumorigenesis of the majority of human cancers. Whether its expression might explain the relative lack of gastric cancer in Thailand was assessed here. This single-center study was conducted in the northeast region of Thailand. Gastric mucosa from 100 patients with Helicobacter pylori associated gastritis was analyzed for MDM2 SNP309 using real-time PCR hybridization (light-cycler) probes. In the total 100 Helicobacter pylori associated gastritis cases the incidence of SNP 309 T/T homozygous was 78 % with SNP309 G/T heterozygous found in 19% and SNP309 G/G homozygous in 3%. The result show SNP 309 T/T and SNP 309 G/T to be rather common in the Thai population. Our study indicates that the MDM2 SNP309 G/G homozygous genotype might be a risk factor for gastric cancer in Thailand and the fact that it is infrequent could explain to some extent the low incidence of gastric cancer in the Thai population.

  18. 13C-urea breath test analyzed with infrared isotope spectrometry for the diagnosis of Helicobacter pylori

    International Nuclear Information System (INIS)

    Dahlberg, M.; Schoensby, H.

    1998-01-01

    The authors have evaluated a 13 C-urea breath test for the diagnosis of Helicobacter pylori infection. The 13 C-test was analyzed with isotope-selective non-dispersive infrared spectrometry and compared with a 14 C-urea breath test and the urease test in gastric mucosal biopsies. 46 patients were analyzed with breath tests, 23 patients were negative and 22 patients were positive with both methods. One patients was positive with 14 C-method and negative with the 13 C-urea breath test. 61 patients were analyzed with the 13 C-urea breath test and the urease test. 30 patients were negative and 30 patients were positive with both methods, whereas one patient with a negative urease test had a positive breath test. 13 C-urea breath test analyzed with isotope-selective non-dispersive infrared spectrometry is a fast, simple, non-radioactive, non-invasive, convenient and reliable method for the diagnosis of Helicobacter pylori infection. 12 refs., 2 figs., 1 tab

  19. Treatment of Helicobacter pylori infection favourably affects gastric mucosal superoxide dismutases

    NARCIS (Netherlands)

    Götz, J. M.; Thio, J. L.; Verspaget, H. W.; Offerhaus, G. J.; Biemond, I.; Lamers, C. B.; Veenendaal, R. A.

    1997-01-01

    Excessive production of reactive oxygen metabolites (ROMs) by phagocytic cells is thought to contribute to the mucosal pathology of Helicobacter pylori infection. Previously, H pylori infection was shown to have a differential effect on some gastric mucosal scavenger enzymes of ROMs-namely,

  20. Helicobacter pylori HP1034 (ylxH) is required for motility

    NARCIS (Netherlands)

    van Amsterdam, Karin; van der Ende, Arie

    2004-01-01

    Background. Helicobacter pylori motility is essential for the colonization and persistence in the human gastric mucosa. So far, more than 50 genes have been described to play a role in flagellar biosynthesis. H. pylori YlxH (HP1034) is annotated as an ATP-binding protein. However, H. pylori YlxH

  1. Implications of Helicobacter pylori infection for stomach cancer prevention

    Directory of Open Access Journals (Sweden)

    Goodman Karen J.

    1997-01-01

    Full Text Available Accumulating evidence has implicated Helicobacter pylori, an established cause of chronic gastritis and peptic ulcer, in the etiology of gastric cancer. Control of this infection would reduce the occurrence of chronic gastritis and peptic ulcer and might substantially lower the risk of stomach cancer as well. The public health impact of this infectious agent warrants efforts to identify preventive measures. This paper reviews the evidence linking H. pylori infection to gastric cancer and evaluates the potential for control in high-risk populations. Current obstacles to H. pylori control are discussed, including the link to poor socioeconomic conditions, difficulty in identifying incident cases, lack of natural immunity to reinfection, limited effectiveness of antibiotic therapy in high-prevalence populations, and incomplete knowledge regarding the reservoir of infection, mode of transmission, host susceptibility factors, and the potential for developing an effective vaccine. Worthwhile avenues of research include studies designed to identify modifiable risk factors for acquisition of the infection, modifiable host factors that may increase resistance to chronic infection, more effective antibiotic therapies, and effective vaccines.

  2. Primary antibiotic resistance of Helicobacter pylori strains among adults and children in a tertiary referral centre in Lithuania

    DEFF Research Database (Denmark)

    Dargiene, Gintare; Kupcinskas, Juozas; Jonaitis, Laimas

    2018-01-01

    The study evaluated primary antibiotic resistance of Helicobacter pylori within the period 2013-2015 and trends of antibiotic consumption over the last decade in Lithuania; 242 adults and 55 children were included in the study. E-tests were performed for amoxicillin, metronidazole, clarithromycin......, ciprofloxacin, rifampicin and tetracycline. The presence of H. pylori and clarithromycin resistance was additionally tested by PCR. Helicobacter pylori culture was positive in 67 of 242 (28%) adult and in 12 of 55 (21.8%) children samples. Resistance rates among adults by E-tests were as follows: metronidazole......, while it has doubled from 1.10 to 2.22 DDD/1000/children/day in children within 2003-2015. There are no significant changes in the susceptibility of H. pylori to the most widely used antibiotics in adults over the last years in Lithuania; however, clarithromycin resistance among children exceeds 15...

  3. Antibacterial activity of ethanolic extracts of some Vietnamese medicinal plants against Helicobacter pylori

    Science.gov (United States)

    Ngan, Luong Thi My; Dung, Pham Phuong; Nhi, Nguyen Vang Thi Yen; Hoang, Nguyen van Minh; Hieu, Tran Trung

    2017-09-01

    Helicobacter pylori is one of the most common human infectious bacteria. The infection is highly associated with a number of the most important disease of the upper gastrointestinal tract, including gastritis, duodenitis, peptic ulceration, and gastric cancer. In addition, widespread use of antimicrobial agents has resulted in the development of antibiotic resistance. Metabolites of plants, particularly higher plants, have been suggested as alternative potential sources for antibacterial products due to their safe. This study aimed to evaluate antibacterial activities of crude ethanolic extracts of seventeen Vietnamese medicinal plants toward one reference strain and three clinical isolates of Helicobacter pylori using broth micro-dilution bioassay. The antibacterial activities of these extracts were also compared with those of seven antibiotics, amoxicillin, clarithromycin, erythromycin, levofloxacin, azithromycin, tetracycline, and metronidazole. The extracts of Ampelopsis cantoniensis and Cleistocalyx operculatus showed highest antibacterial activity with MIC (MBC) values of 0.31 - 0.97 (2.5 - 5) mg/mL, followed by the extracts of Hedyotis diffusa and Ardisia silvestris with MIC (MBC) values of 1.04 - 1.94 (7.5 - 10) mg/mL. The remaining plant extracts exhibited moderate, low and very low or no active to the H. pylori strains. Further studies are needed to determine the active compounds from the extracts that showed high antibacterial activity against H. pylori.

  4. Evaluation of brushing cytology in the diagnosis of Helicobacter pylori gastritis

    Directory of Open Access Journals (Sweden)

    Amir Ahmad Mostaghni

    2008-02-01

    Full Text Available Background: Helicobacter pylori (HP is the cause of the most common infection in the world. It has been recognized as the major cause of peptic ulcer and an important risk factor for gastric malignancy. A variety of reliable methods are available for detecting HP during upper gastrointestinal endoscopy. Rapid urease test (RUT is the cheapest method and histology is the most expensive brush cytology is faster and cheaper than histology. Methods: The brushing cytology materials were obtained from the antrum of the stomach in 109 patients who suffered from dyspepsia and were candidates for endoscopy. The RUT and histology with hematoxylin-eosin staining were also performed on each patient separately. The infection status for each patient was established by a concordance of two test results. Results: Seventy-eight of 100 patients (78% were diagnosed as positive for Helicobacter pylori organisms using brushing cytology. The sensitivity and specificity of brushing cytology were 96% and 72% respectively. Sensitivity of brush cytology (96% was higher than RUT (77.4%, and RUT was more specific than histology (100% vs 90%. Conclusion: Gastric brushing cytology provides an accurate, inexpensive and easy technique in the rapid detection of Helicobacter pylori infection. When additional information about the severity of mucosal damage or the presence of cell atypias is not necessary, histologic examination can be omitted, and a cost effective strategy for assessing HP status might consist of taking antral biopsies, the former for RUT and performing brush cytology slide, which should be stained and examined only when the RUT result is negative.

  5. Association between Virulence Factors and TRAF1/4-1BB/Bcl-xL Expression in Gastric Mucosa Infected with Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Fen Wang

    2015-01-01

    Full Text Available Objective. CagA+/vacAs1+/vacAm1+ Helicobacter pylori upregulates the expression of tumor necrosis factor receptor–associated factor 1 (TRAF1, tumor necrosis factor receptor superfamily member 9 (4-1BB, and B-cell lymphoma-extra large (Bcl-xL in human gastric epithelial cells. We investigated the correlation between cagA/vacAs1/vacAm1 and TRAF1/4-1BB/Bcl-xL expression in gastric mucosal tissue of patients with gastric disorders. Methods. We collected gastric mucosa samples from 35 chronic, nonatrophic gastritis (CG patients, 41 atrophic gastritis patients, 44 intestinal metaplasia with atypical hyperplasia (IM patients, and 28 gastric carcinoma (Ca patients. The expression of  TRAF1, 4-1BB, and Bcl-xL was determined using western blotting. The expression of cagA, vacAs1, and vacAm1 in H. pylori was examined with polymerase chain reaction. Results. The expression of TRAF1, 4-1BB, and Bcl-xL was significantly upregulated in IM and Ca patients (P<0.05 compared with CG. There were more cases of cagA+/vacAs1+/vacAm1+ H. pylori infection in samples with elevated TRAF1, 4-1BB, or Bcl-xL expression (P<0.05. Additionally, there were a remarkably large number of samples with upregulated TRAF1/4-1BB/Bcl-xL expression in cases of cagA+/vacAs1+/vacAm1+ H. pylori infection (44 cases, 67.7%; P<0.05. Conclusions. The pathogenesis of IM and Ca may be promoted by cagA+/vacAs1+/vacAm1+ H. pylori, possibly via upregulated TRAF1, 4-1BB, and Bcl-xL in gastric mucosal tissue.

  6. Oxyntic gastric atrophy in Helicobacter pylori gastritis is distinct from autoimmune gastritis.

    Science.gov (United States)

    Venerito, Marino; Varbanova, Mariya; Röhl, Friedrich-Wilhelm; Reinhold, Dirk; Frauenschläger, Katrin; Jechorek, Doerthe; Weigt, Jochen; Link, Alexander; Malfertheiner, Peter

    2016-08-01

    To assess characteristics of oxyntic gastric atrophy (OGA) in autoimmune gastritis (AIG) compared with OGA as a consequence of Helicobacter pylori infection. Patients undergoing oesophagogastroduodenoscopy from July 2011 to October 2014 were prospectively included (N=452). Gastric biopsies were obtained for histology and H. pylori testing. Serum gastrin-17 (G17), pepsinogen (PG) I, PGII and antibodies against H. pylori and cytotoxin-associated gene A protein were determined in all patients. Antibodies against parietal cells and intrinsic factor were determined in patients with advanced (moderate to severe) OGA. Areas under the receiver operating characteristic curves (AUCs) were calculated for serum biomarkers and compared with histology. Overall, 34 patients (8.9%) had advanced OGA by histology (22 women, age 61±15 years). Current or past H. pylori infection and AIG were present in 14/34 and 22/34 patients, respectively. H. pylori-negative AIG patients (N=18) were more likely to have another autoimmune disease (OR 6.3; 95% CI 1.3 to 29.8), severe corpus atrophy (OR 10.1; 95% CI 1.9 to 54.1) and corpus intestinal metaplasia (OR 26.9; 95% CI 5.3 to 136.5) compared with H. pylori-positive patients with advanced OGA. Antrum atrophy was present in 39% of H. pylori-negative AIG patients. The diagnostic performance of G17, PG I and PGI/II was excellent for AIG patients (AUC=0.83, 0.95 and 0.97, respectively), but limited for H. pylori-positive patients with advanced OGA (AUC=0.62, 0.75 and 0.67, respectively). H. pylori-negative AIG has a distinct clinical, morphological and serological phenotype compared with advanced OGA in H. pylori gastritis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  7. A Helicobacter pylori TolC efflux pump confers resistance to metronidazole

    NARCIS (Netherlands)

    van Amsterdam, Karin; Bart, Aldert; van der Ende, Arie

    2005-01-01

    In Helicobacter pylori, the contribution of efflux proteins to antibiotic resistance is not well established. As translocases that act in parallel may have overlapping substrate specificities, the loss of function of one such translocase may be compensated for by that of another translocase with no

  8. CagA and VacA Helicobacter Pylori Antibodies in Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Renzo Suriani

    2008-01-01

    Full Text Available BACKGROUND: Infection with different genotypes of virulent Helicobacter pylori strains (cytotoxin-associated gene A [CagA]-and/or vacuolating cytotoxin A [VacA]-positive can play a role in the development of atrophic gastritis, duodenal ulcer (DU and gastric cancer (GC.

  9. Did transmission of Helicobacter pylori from humans cause a disease outbreak in a colony of Stripe-faced Dunnarts (Sminthopsis macroura?

    Directory of Open Access Journals (Sweden)

    Every Alison L

    2011-02-01

    Full Text Available Abstract Since the discovery that Helicobacter pylori causes a range of pathologies in the stomachs of infected humans, it has become apparent that Helicobacters are found in a diverse range of animal species where they are frequently associated with disease. In 2003 and 2004, there were two outbreaks of increased mortality associated with gastric bleeding and weight-loss in a captive colony of the Australian marsupial, the Stripe-faced Dunnart (Sminthopsis macroura. The presence of gastric pathology led to an investigation of potential Helicobacter pathogenesis in these animals. Histological examination revealed the presence of gastritis, and PCR analysis confirmed the presence of Helicobacter infection in the stomachs of these marsupials. Surprisingly, sequencing of 16S rRNA from these bacteria identified the species as H. pylori and PCR confirmed the strain to be positive for the important pathogenesis factor, cagA. We therefore describe, for the first time, an apparent reverse zoonotic infection of Stripe-faced Dunnarts with H. pylori. Already prone to pathological effects of stress (as experienced during breeding season, concomitant H. pylori infection appears to be a possible essential but not sufficient co-factor in prototypic gastric bleeding and weight loss in these marsupials. The Stripe-faced Dunnart could represent a new model for investigating Helicobacter-driven gastric pathology. Infections from their human handlers, specifically of H. pylori, may be a potential risk to captive colonies of marsupials.

  10. Characterization of Helicobacter pylori dapE and construction of a conditionally lethal dapE mutant.

    OpenAIRE

    Karita, M; Etterbeek, M L; Forsyth, M H; Tummuru, M K; Blaser, M J

    1997-01-01

    Helicobacter pylori colonizes the human gastric mucosa and causes gastritis, ulceration, or gastric cancer. A previously uncharacterized region of the H. pylori genome was identified and sequenced. This region includes a putative operon containing three open reading frames termed gidA (1,866 bp), dapE (1,167 bp), and orf2 (753 bp); the gidA and dapE products are highly homologous to other bacterial proteins. In E. coli, dapE encodes N-succinyl-L-diaminopimelic acid desuccinylase, which cataly...

  11. Helicobacter Catalase Devoid of Catalytic Activity Protects the Bacterium against Oxidative Stress.

    Science.gov (United States)

    Benoit, Stéphane L; Maier, Robert J

    2016-11-04

    Catalase, a conserved and abundant enzyme found in all domains of life, dissipates the oxidant hydrogen peroxide (H 2 O 2 ). The gastric pathogen Helicobacter pylori undergoes host-mediated oxidant stress exposure, and its catalase contains oxidizable methionine (Met) residues. We hypothesized catalase may play a large stress-combating role independent of its classical catalytic one, namely quenching harmful oxidants through its recyclable Met residues, resulting in oxidant protection to the bacterium. Two Helicobacter mutant strains ( katA H56A and katA Y339A ) containing catalase without enzyme activity but that retain all Met residues were created. These strains were much more resistant to oxidants than a catalase-deletion mutant strain. The quenching ability of the altered versions was shown, whereby oxidant-stressed (HOCl-exposed) Helicobacter retained viability even upon extracellular addition of the inactive versions of catalase, in contrast to cells receiving HOCl alone. The importance of the methionine-mediated quenching to the pathogen residing in the oxidant-rich gastric mucus was studied. In contrast to a catalase-null strain, both site-change mutants proficiently colonized the murine gastric mucosa, suggesting that the amino acid composition-dependent oxidant-quenching role of catalase is more important than the well described H 2 O 2 -dissipating catalytic role. Over 100 years after the discovery of catalase, these findings reveal a new non-enzymatic protective mechanism of action for the ubiquitous enzyme. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Systematic review, meta-analysis, and meta-regression: Successful second-line treatment for Helicobacter pylori.

    Science.gov (United States)

    Muñoz, Neus; Sánchez-Delgado, Jordi; Baylina, Mireia; Puig, Ignasi; López-Góngora, Sheila; Suarez, David; Calvet, Xavier

    2018-06-01

    Multiple Helicobacter pylori second-line schedules have been described as potentially useful. It remains unclear, however, which are the best combinations, and which features of second-line treatments are related to better cure rates. The aim of this study was to determine that second-line treatments achieved excellent (>90%) cure rates by performing a systematic review and when possible a meta-analysis. A meta-regression was planned to determine the characteristics of treatments achieving excellent cure rates. A systematic review for studies evaluating second-line Helicobacter pylori treatment was carried out in multiple databases. A formal meta-analysis was performed when an adequate number of comparative studies was found, using RevMan5.3. A meta-regression for evaluating factors predicting cure rates >90% was performed using Stata Statistical Software. The systematic review identified 115 eligible studies, including 203 evaluable treatment arms. The results were extremely heterogeneous, with 61 treatment arms (30%) achieving optimal (>90%) cure rates. The meta-analysis favored quadruple therapies over triple (83.2% vs 76.1%, OR: 0.59:0.38-0.93; P = .02) and 14-day quadruple treatments over 7-day treatments (91.2% vs 81.5%, OR; 95% CI: 0.42:0.24-0.73; P = .002), although the differences were significant only in the per-protocol analysis. The meta-regression did not find any particular characteristics of the studies to be associated with excellent cure rates. Second-line Helicobacter pylori treatments achieving>90% cure rates are extremely heterogeneous. Quadruple therapy and 14-day treatments seem better than triple therapies and 7-day ones. No single characteristic of the treatments was related to excellent cure rates. Future approaches suitable for infectious diseases-thus considering antibiotic resistances-are needed to design rescue treatments that consistently achieve excellent cure rates. © 2018 John Wiley & Sons Ltd.

  13. Association between TNF-α and IL-1β genotypes vs Helicobacter pylori infection in Indonesia

    Science.gov (United States)

    Zhao, Yang; Wang, Jing-Wen; Tanaka, Tsutomu; Hosono, Akihiro; Ando, Ryosuke; Tokudome, Shinkan; Soeripto; Triningsih, FX Ediati; Triono, Tegu; Sumoharjo, Suwignyo; Achwan, EY Wenny Astuti; Gunawan, Stephanus; Li, Yu-Min

    2013-01-01

    AIM: To investigate the correlation between the Helicobacter pylori (H. pylori) infection and host genetic background of healthy populations in Indonesia. METHODS: In March 2007, epidemiological studies were undertaken on the general population of a city in Indonesia (Mataram, Lombok). The participants included 107 men and 187 women, whose ages ranged from 6 to 74 years old, with an average age of 34.0 (± 14.4) (± SD). The H. pylori of subject by UBT method determination, and through the polymerase chain reaction with confronting two-pair primers (PCR-CTPP) method parsing the single nucleotide polymorphism of interleukin (IL)-8, IL-4, IL-1β, CD14, tumor necrosis factor (TNF-α) and tyrosine-protein phosphates non-receptor type 11 (PTPN11) genotypes. The experimental data were analyzed by the statistical software SAS. RESULTS: The H. pylori infection rates in the healthy Indonesian population studied were 8.4% for men and 12.8% for women; no obvious differences were noted for H. pylori infection rates by sex or age. TC genotypes of IL-4, TC and CC genotypes of TNF-α, and GA genotypes of PTPN11, were higher in frequency. Both CC and TC genotype of TNF-α T-1031C loci featured higher expressions in the healthy Indonesian population Indonesia studied of (OR = 1.99; 95%CI: 0.67-5.89) and (OR = 1.66; 95%CI: 0.73-3.76), respectively. C allele of IL-1β T-31C gene locus was at a higher risk (OR = 1.11; 95%CI: 0.70-1.73) of H. pylori infection, but no statistical significance was found in our study. CONCLUSION: We reveal that the association between the TNF-α and IL-1β genotypes may be the susceptibility of H. pylori in the studied population. PMID:24379597

  14. Transcriptional Regulation of the Nickel and Iron Metabolism in Helicobacter pylori

    NARCIS (Netherlands)

    F.D.J. Ernst (Florian)

    2005-01-01

    textabstractUp to 50 % of the world's population is infected with Helicobacter pylori. Colonization of the mucus layer of the human stomach by H. pylori, is lifelong unless treated with antibiotics (26). H. pylori, which is a neutralophilic bacterium, survives in the mucus layer of the human

  15. Re-annotation of the genome sequence of Helicobacter pylori 26695

    Directory of Open Access Journals (Sweden)

    Resende Tiago

    2013-12-01

    Full Text Available Helicobacter pylori is a pathogenic bacterium that colonizes the human epithelia, causing duodenal and gastric ulcers, and gastric cancer. The genome of H. pylori 26695 has been previously sequenced and annotated. In addition, two genome-scale metabolic models have been developed. In order to maintain accurate and relevant information on coding sequences (CDS and to retrieve new information, the assignment of new functions to Helicobacter pylori 26695s genes was performed in this work. The use of software tools, on-line databases and an annotation pipeline for inspecting each gene allowed the attribution of validated EC numbers and TC numbers to metabolic genes encoding enzymes and transport proteins, respectively. 1212 genes encoding proteins were identified in this annotation, being 712 metabolic genes and 500 non-metabolic, while 191 new functions were assignment to the CDS of this bacterium. This information provides relevant biological information for the scientific community dealing with this organism and can be used as the basis for a new metabolic model reconstruction.

  16. [NSAID-gastropathy and Helicobacter pylori: more questions than answers].

    Science.gov (United States)

    Shirinskaia, N V; Akhmedov, V A

    2010-01-01

    NSAID-gastropathy is a very serious problem as for gastroenterology, so for cardiology and rheumatology. On a present moment the influence of a Helicobacter pylori in ulcerogenesis in patients taking NSAID for a long period is a very unclear especially treatment position. For the analysis of this problem was made a systemic literature search from 1966 till 2009 years and all randomizes, meta-analysis was reviewed.

  17. The Association of Helicobacter pylori Infection with Hashimoto's Thyroiditis

    Directory of Open Access Journals (Sweden)

    Maryam Alsadat Salami

    2013-05-01

    Full Text Available Autoimmune thyroid diseases (ATD are multifactorial conditions that result from genetic predisposition in combination with environmental risk factors. Helicobacter pylori infection as an environmental risk factor has been proposed to imitate the antigenic components of the thyroid cell membrane and may play a leading role in the onset of the autoimmune diseases, such as Hashimoto thyroiditis. The aim of this study was to investigate the association between Helicobacter pylori (HP infection and Hashimoto's thyroiditis (HT. The participants in this case-control study included 43 patients affected by Hashimoto's thyroiditis, and 40 healthy individuals without history of autoimmune disease as the control group. Anti HP IgG and anti-TPO antibodies were determined using ELISA method. Results were considered positive when the IgG anti-HP value was higher than 30 IU/ml and the anti-TPO autoantibody value was higher than 75 IU/ml. The mean TSH level was 18.3±16.8 IU/ml for patients and 2.8±1.2 IU/ml for the control group (P<0.001. 46.5% of the patient group and 10.8% of the control group were infected with HP. The association between HP and Hashimoto's thyroiditis was statistically significant (Odds Ratio=7.2, 95%, Confidence Interval: 2.0- 28.8, P<0.001. The findings show that, there is an association between HP and Hashimoto's thyroiditis. To establish a definite correlation between them, more detailed studies with a more specialized examination and precise consideration regarding species of HP, genetic polymorphism of the host and investigation of environmental factors are needed.

  18. Dealing with uncertainty in the treatment of Helicobacter pylori.

    Science.gov (United States)

    Calvet, Xavier

    2018-04-01

    Helicobacter pylori treatment may be viewed as an uncertain situation, where current knowledge is insufficient to provide evidence-based recommendations for all possible scenarios. Evidence suggests that, under uncertainty conditions, a few simple rules of thumb tend to work better than complex algorithms. Overall, five evidence-based rules of thumb are suggested: (1) Use four drugs; (2) Use maximal acid inhibition; (3) Treat for 2 weeks; (4) Do not repeat antibiotics after treatment failure; and (5) If your treatment works locally, keep using it. These simple rules of thumb may help the reader to select the best alternative for a given patient, choosing between the heterogeneous recommendations provided by the many different consensus conferences on H. pylori treatment recently published.

  19. Randomised controlled trial of effects of Helicobacter pylori infection and its eradication on heartburn and gastro-oesophageal reflux: Bristol helicobacter project

    Science.gov (United States)

    Harvey, Richard F; Lane, J Athene; Murray, Liam J; Harvey, Ian M; Donovan, Jenny L; Nair, Prakash

    2004-01-01

    Objectives To investigate the effects of Helicobacter pylori infection and its eradication on heartburn and gastro-oesophageal reflux. Design Cross sectional study, followed by a randomised placebo controlled trial. Setting Seven general practices in Bristol, England. Participants 10 537 people, aged 20-59 years, with and without H pylori infection (determined by the 13C-urea breath test). Main outcome measures Prevalence of heartburn and gastro-oesophageal acid reflux at baseline and two years after treatment to eradicate H pylori infection. Results At baseline, H pylori infection was associated with increased prevalence of heartburn (odds ratio 1.14, 95% confidence interval 1.05 to 1.23) but not reflux (1.05, 0.97 to 1.14). In participants with H pylori infection, active treatment had no effect on the overall prevalence of heartburn (0.99, 0.88 to 1.12) or reflux (1.04, 0.91 to 1.19) and did not improve pre-existing symptoms of heartburn or reflux. Conclusions H pylori infection is associated with a slightly increased prevalence of heartburn but not reflux. Treatment to eradicate H pylori has no net benefit in patients with heartburn or gastro-oesophageal reflux. PMID:15126313

  20. The diagnosis and treatment of Helicobacter pylori infection in Arctic regions with a high prevalence of infection

    DEFF Research Database (Denmark)

    McMAHON, B J; Bruce, M G; Koch, A

    2016-01-01

    Helicobacter pylori infection is a major cause of peptic ulcer and is also associated with chronic gastritis, mucosa-associated lymphoid tissue (MALT) lymphoma, and adenocarcinoma of the stomach. Guidelines have been developed in the United States and Europe (areas with low prevalence) for the di......Helicobacter pylori infection is a major cause of peptic ulcer and is also associated with chronic gastritis, mucosa-associated lymphoid tissue (MALT) lymphoma, and adenocarcinoma of the stomach. Guidelines have been developed in the United States and Europe (areas with low prevalence...