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Sample records for human gastrointestinal cells

  1. Cancer stem cells in human gastrointestinal cancer.

    Science.gov (United States)

    Taniguchi, Hiroaki; Moriya, Chiharu; Igarashi, Hisayoshi; Saitoh, Anri; Yamamoto, Hiroyuki; Adachi, Yasushi; Imai, Kohzoh

    2016-11-01

    Cancer stem cells (CSCs) are thought to be responsible for tumor initiation, drug and radiation resistance, invasive growth, metastasis, and tumor relapse, which are the main causes of cancer-related deaths. Gastrointestinal cancers are the most common malignancies and still the most frequent cause of cancer-related mortality worldwide. Because gastrointestinal CSCs are also thought to be resistant to conventional therapies, an effective and novel cancer treatment is imperative. The first reported CSCs in a gastrointestinal tumor were found in colorectal cancer in 2007. Subsequently, CSCs were reported in other gastrointestinal cancers, such as esophagus, stomach, liver, and pancreas. Specific phenotypes could be used to distinguish CSCs from non-CSCs. For example, gastrointestinal CSCs express unique surface markers, exist in a side-population fraction, show high aldehyde dehydrogenase-1 activity, form tumorspheres when cultured in non-adherent conditions, and demonstrate high tumorigenic potential in immunocompromised mice. The signal transduction pathways in gastrointestinal CSCs are similar to those involved in normal embryonic development. Moreover, CSCs are modified by the aberrant expression of several microRNAs. Thus, it is very difficult to target gastrointestinal CSCs. This review focuses on the current research on gastrointestinal CSCs and future strategies to abolish the gastrointestinal CSC phenotype.

  2. Human Nanog pseudogene8 promotes the proliferation of gastrointestinal cancer cells

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    Uchino, Keita, E-mail: uchino13@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Hirano, Gen [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Hirahashi, Minako [Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Isobe, Taichi; Shirakawa, Tsuyoshi; Kusaba, Hitoshi; Baba, Eishi [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Tsuneyoshi, Masazumi [Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Akashi, Koichi [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

    2012-09-10

    There is emerging evidence that human solid tumor cells originate from cancer stem cells (CSCs). In cancer cell lines, tumor-initiating CSCs are mainly found in the side population (SP) that has the capacity to extrude dyes such as Hoechst 33342. We found that Nanog is expressed specifically in SP cells of human gastrointestinal (GI) cancer cells. Nucleotide sequencing revealed that NanogP8 but not Nanog was expressed in GI cancer cells. Transfection of NanogP8 into GI cancer cell lines promoted cell proliferation, while its inhibition by anti-Nanog siRNA suppressed the proliferation. Immunohistochemical staining of primary GI cancer tissues revealed NanogP8 protein to be strongly expressed in 3 out of 60 cases. In these cases, NanogP8 was found especially in an infiltrative part of the tumor, in proliferating cells with Ki67 expression. These data suggest that NanogP8 is involved in GI cancer development in a fraction of patients, in whom it presumably acts by supporting CSC proliferation. -- Highlights: Black-Right-Pointing-Pointer Nanog maintains pluripotency by regulating embryonic stem cells differentiation. Black-Right-Pointing-Pointer Nanog is expressed in cancer stem cells of human gastrointestinal cancer cells. Black-Right-Pointing-Pointer Nucleotide sequencing revealed that Nanog pseudogene8 but not Nanog was expressed. Black-Right-Pointing-Pointer Nanog pseudogene8 promotes cancer stem cells proliferation. Black-Right-Pointing-Pointer Nanog pseudogene8 is involved in gastrointestinal cancer development.

  3. Interstitial cells of Cajal in human gut and gastrointestinal disease

    DEFF Research Database (Denmark)

    Vanderwinden, J M; Rumessen, J J

    1999-01-01

    of their functional significance. Alterations of ICC reported in achalasia of cardia, infantile hypertrophic pyloric stenosis, chronic intestinal pseudoobstruction, Hirschsprung's disease, inflammatory bowel diseases, slow transit constipation, and some other disorders of GI motility as well as in gastrointestinal...... stromal tumors are reviewed, with emphasis on the place of ICC in the pathophysiology of disease....

  4. CD34 immunoreactivity and interstitial cells of Cajal in the human and mouse gastrointestinal tract

    DEFF Research Database (Denmark)

    Vanderwinden, J M; Rumessen, J J; De Laet, M H;

    2000-01-01

    Immunoreactivity for the tyrosine kinase receptor Kit (Kit-ir) is an established marker for the interstitial cells of Cajal (ICC) of the gut. Recently, the presence of CD34 immunoreactivity (CD34-ir) has been reported in Kit-ir ICC around the myenteric plexus in human small intestine. Conversely,......-localization. The ontogeny and function of CD34-ir cells in the gut, as well as the origin of gastrointestinal stromal tumors, remain unclear....

  5. Gastrointestinal stem cells in health and disease: from flies to humans

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    Hongjie Li

    2016-05-01

    Full Text Available The gastrointestinal tract of complex metazoans is highly compartmentalized. It is lined by a series of specialized epithelia that are regenerated by specific populations of stem cells. To maintain tissue homeostasis, the proliferative activity of stem and/or progenitor cells has to be carefully controlled and coordinated with regionally distinct programs of differentiation. Metaplasias and dysplasias, precancerous lesions that commonly occur in the human gastrointestinal tract, are often associated with the aberrant proliferation and differentiation of stem and/or progenitor cells. The increasingly sophisticated characterization of stem cells in the gastrointestinal tract of mammals and of the fruit fly Drosophila has provided important new insights into these processes and into the mechanisms that drive epithelial dysfunction. In this Review, we discuss recent advances in our understanding of the establishment, maintenance and regulation of diverse intestinal stem cell lineages in the gastrointestinal tract of Drosophila and mice. We also discuss the field's current understanding of the pathogenesis of epithelial dysfunctions.

  6. Gastrointestinal stem cells in health and disease: from flies to humans

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    Li, Hongjie; Jasper, Heinrich

    2016-01-01

    ABSTRACT The gastrointestinal tract of complex metazoans is highly compartmentalized. It is lined by a series of specialized epithelia that are regenerated by specific populations of stem cells. To maintain tissue homeostasis, the proliferative activity of stem and/or progenitor cells has to be carefully controlled and coordinated with regionally distinct programs of differentiation. Metaplasias and dysplasias, precancerous lesions that commonly occur in the human gastrointestinal tract, are often associated with the aberrant proliferation and differentiation of stem and/or progenitor cells. The increasingly sophisticated characterization of stem cells in the gastrointestinal tract of mammals and of the fruit fly Drosophila has provided important new insights into these processes and into the mechanisms that drive epithelial dysfunction. In this Review, we discuss recent advances in our understanding of the establishment, maintenance and regulation of diverse intestinal stem cell lineages in the gastrointestinal tract of Drosophila and mice. We also discuss the field's current understanding of the pathogenesis of epithelial dysfunctions. PMID:27112333

  7. Cell proliferation in gastrointestinal mucosa.

    OpenAIRE

    Wong, W M; Wright, N A

    1999-01-01

    Gastrointestinal cell proliferation plays an important role in the maintenance of the integrity of the gastrointestinal system. The study of gastrointestinal proliferation kinetics allows a better understanding of the complexity of the system, and also has important implications for the study of gastrointestinal carcinogenesis. Gastrointestinal stem cells are shown to be pluripotential and to give rise to all cell lineages in the epithelium. Carcinogenesis in the colon occurs through sequenti...

  8. Sangre de grado Croton palanostigma induces apoptosis in human gastrointestinal cancer cells.

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    Sandoval, Manuel; Okuhama, Nataly N; Clark, Melinda; Angeles, Fausto M; Lao, Juan; Bustamante, Sergio; Miller, Mark J S

    2002-05-01

    Sangre de grado is an ethnomedicinal red tree sap obtained from Croton spp. that is used to treat gastrointestinal ulcers, cancer and to promote wound healing. To evaluate the potential role of sangre de grado (SdG) in cancer we examined its effects on human cancer cells, AGS (stomach), HT29 and T84 (colon). Viability of cells treated with SdG (10-200 microg/ml) decreased (P100 microg/ml). When cells in suspension were treated with SdG (100 microg/ml) cell adherence was severely compromised (>85%). Cells treated with SdG (100 microg/ml) underwent apoptosis as detected by nucleus condensation and DNA fragmentation determined by ELISA, and flow cytometry. Morphological changes as assessed by acridine orange. These effects were similar to that observed with Taxol (30 microM). A significant alteration of microtubular architecture was equally observed in both stomach and colon cancer cells exposed to SdG (100 microg/ml). The induction of apoptosis and microtubule damage in AGS, HT29 and T84 cells suggest that sangre de grado should be evaluated further as a potential source of anti-cancer agents.

  9. Tumor-initiating label-retaining cancer cells in human gastrointestinal cancers undergo asymmetric cell division.

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    Xin, Hong-Wu; Hari, Danielle M; Mullinax, John E; Ambe, Chenwi M; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J; Wiegand, Gordon W; Garfield, Susan H; Thorgeirsson, Snorri S; Avital, Itzhak

    2012-04-01

    Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment. Copyright © 2012 AlphaMed Press.

  10. Specific expression of human intelectin-1 in malignant pleural mesothelioma and gastrointestinal goblet cells.

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    Kota Washimi

    Full Text Available Malignant pleural mesothelioma (MPM is a fatal tumor. It is often hard to discriminate MPM from metastatic tumors of other types because currently, there are no reliable immunopathological markers for MPM. MPM is differentially diagnosed by some immunohistochemical tests on pathology specimens. In the present study, we investigated the expression of intelectin-1, a new mesothelioma marker, in normal tissues in the whole body and in many cancers, including MPM, by immunohistochemical analysis. We found that in normal tissues, human intelectin-1 was mainly secreted from gastrointestinal goblet cells along with mucus into the intestinal lumen, and it was also expressed, to a lesser extent, in mesothelial cells and urinary epithelial cells. Eighty-eight percent of epithelioid-type MPMs expressed intelectin-1, whereas sarcomatoid-type MPMs, biphasic MPMs, and poorly differentiated MPMs were rarely positive for intelectin-1. Intelectin-1 was not expressed in other cancers, except in mucus-producing adenocarcinoma. These results suggest that intelectin-1 is a better marker for epithelioid-type MPM than other mesothelioma markers because of its specificity and the simplicity of pathological assessment. Pleural intelectin-1 could be a useful diagnostic marker for MPM with applications in histopathological identification of MPM.

  11. Neuropilin-2 mediated β-catenin signaling and survival in human gastro-intestinal cancer cell lines.

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    Shaija Samuel

    Full Text Available NRP-2 is a high-affinity kinase-deficient receptor for ligands belonging to the class 3 semaphorin and vascular endothelial growth factor families. NRP-2 has been detected on the surface of several types of human cancer cells, but its expression and function in gastrointestinal (GI cancer cells remains to be determined. We sought to determine the function of NRP-2 in mediating downstream signals regulating the growth and survival of human gastrointestinal cancer cells. In human gastric cancer specimens, NRP-2 expression was detected in tumor tissues but not in adjacent normal mucosa. In CNDT 2.5 cells, shRNA mediated knockdown NRP-2 expression led to decreased migration and invasion in vitro (p<0.01. Focused gene-array analysis demonstrated that loss of NRP-2 reduced the expression of a critical metastasis mediator gene, S100A4. Steady-state levels and function of β-catenin, a known regulator of S100A4, were also decreased in the shNRP-2 clones. Furthermore, knockdown of NRP-2 sensitized CNDT 2.5 cells in vitro to 5FU toxicity. This effect was associated with activation of caspases 3 and 7, cleavage of PARP, and downregulation of Bcl-2. In vivo growth of CNDT 2.5 cells in the livers of nude mice was significantly decreased in the shNRP-2 group (p<0.05. Intraperitoneal administration of NRP-2 siRNA-DOPC decreased the tumor burden in mice (p = 0.01. Collectively, our results demonstrate that tumor cell-derived NRP-2 mediates critical survival signaling in gastrointestinal cancer cells.

  12. Ghrelin Cells in the Gastrointestinal Tract

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    Ichiro Sakata

    2010-01-01

    Full Text Available Ghrelin is 28-amino-acid peptide that was discovered from the rat and human stomach in 1999. Since the discovery of ghrelin, various functions of ghrelin, including growth hormone release, feeding behavior, glucose metabolism, memory, and also antidepressant effects, have been studied. It has also been reported that ghrelin in the gastrointestinal tract has an important physiological effect on gastric acid secretion and gastrointestinal motility. Ghrelin has a unique structure that is modified by O-acylation with n-octanoic acid at third serine residues, and this modification enzyme has recently been identified and named ghrelin O-acyl transferase (GOAT. Ghrelin is considered to be a gut-brain peptide and is abundantly produced from endocrine cells in the gastrointestinal mucosa. In the gastrointestinal tract, ghrelin cells are most abundant in the stomach and are localized in gastric mucosal layers. Ghrelin cells are also widely distributed throughout the gastrointestinal tract. In addition, abundance of ghrelin cells in the gastric mucosa is evolutionally conserved from mammals to lower vertebrates, indicating that gastric ghrelin plays important roles for fundamental physiological functions. Ghrelin cells in the gastrointestinal tract are a major source of circulating plasma ghrelin, and thus understanding the physiology of these cells would reveal the biological significance of ghrelin.

  13. [GASTROINTESTINAL INVOLVEMENT IN HUMAN BARTONELLOSIS

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    Maguiña, Ciro; Gotuzzo, Eduardo; Carcelén, Amador; Salinas, César; Cok, Jaime; Recavarren, Sixto; Bussalleu, Alejandro

    1997-01-01

    We present a prospective study of 68 patients with the acute phase of human bartonellosis, admitted to Cayetano Heredia National Hospital.Gastrointestinal symptoms were reported as follows: abdominal pain 46,3%, coluria 44,4%, vomiting 40,3%, jaundice 38,5%, diarrhea 29,9%, constipation 8,9%. The more common signs were pallor 97%, hepatomegaly 82%, fever 79,1%, malnutrition 75,2%, systolic heart murmur 77,9%, jaundice 71,6%, lymph node enlargement 70,1%.Signs observed during the hospital course were 29,4% lower extremities edema, 22,6% myalgia, 16,4% pericardial effusion, 16,4% generalized edema. The more common gastrointestinal signs were hepatomegaly 82%(52/68), jaundice 71,6% (48/68) and splenomegaly 29,4%(20/68).The -lower liver border was found between 1 to 4 below the lower rib border in 71,6%(48/67) and below 5 cm b. l. r. b. in 11,9%(8/67).60% had abnormal liver function tests, 54,6% had mainly direct bilirrubin elevationand 45,4% mainly indirect.SGOT was elevated in 28,5% and SGPT in 25%, 28,3% had elevated alkaline phosphatase. The bilirrubin media was 3,5 mg/dI (range 0,6-21), the indirect bilirrubin media was 1,6 mg/dI (range 0,5-11,5), the direct bilirrubin media was 1,9 mg/dI (range 0,3-18), The SGOT media 73,9 U/L (range 9-1250), SGPT media 65,5U/L (range 6-1596). Alkaline phosphatase 5,9 mui/ml (range 3-497). Albumin media 3,09 (range 2-4,2).Patients with bacterial coinfection (salmonella, staphilococcus, enterobacter, shigella) had a higher increase in bilirrubin and transaminases.Three patients had liver biopsies, two revealed Küpffer cells hyperplasia (moderate to severe), one revealed intracellular hyperplasia, one patient coinfected with diseminated hystoplasmosis had granulomas in the liver.Mortality(8,8%) was associated to hepatocellular involvement (SGOT media 330U/L, SGPT media 207 U/L, alkaline phosphatase media 183 mui/ml), hypoalbuminemia media = 2,4 gr/1) and generalized edema.

  14. Intracellular gold nanoparticles enhance non-invasive radiofrequency thermal destruction of human gastrointestinal cancer cells

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    Mukherjee Priyabrata

    2008-01-01

    Full Text Available Abstract Background Novel approaches to treat human cancer that are effective with minimal toxicity profiles are needed. We evaluated gold nanoparticles (GNPs in human hepatocellular and pancreatic cancer cells to determine: 1 absence of intrinsic cytotoxicity of the GNPs and 2 external radiofrequency (RF field-induced heating of intracellular GNPs to produce thermal destruction of malignant cells. GNPs (5 nm diameter were added to 2 human cancer cell lines (Panc-1, Hep3B. 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and propidium iodide-fluorescence associated cell sorting (PI-FACS assessed cell proliferation and GNP-related cytotoxicity. Other GNP-treated cells were exposed to a 13.56 MHz RF field for 1, 2, or 5 minutes, and then incubated for 24 hours. PI-FACS measured RF-induced cytotoxicity. Results GNPs had no impact on cellular proliferation by MTT assay. PI-FACS confirmed that GNPs alone produced no cytotoxicity. A GNP dose-dependent RF-induced cytotoxicity was observed. For Hep3B cells treated with a 67 μM/L dose of GNPs, cytotoxicity at 1, 2 and 5 minutes of RF was 99.0%, 98.5%, and 99.8%. For Panc-1 cells treated at the 67 μM/L dose, cytotoxicity at 1, 2, and 5 minutes of RF was 98.5%, 98.7%, and 96.5%. Lower doses of GNPs were associated with significantly lower rates of RF-induced thermal cytotoxicity for each cell line (P Conclusion We demonstrate that GNPs 1 have no intrinsic cytotoxicity or anti-proliferative effects in two human cancer cell lines in vitro and 2 GNPs release heat in a focused external RF field. This RF-induced heat release is lethal to cancer cells bearing intracellular GNPs in vitro.

  15. [Influence of human gastrointestinal tract bacterial pathogens on host cell apoptosis].

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    Wronowska, Weronika; Godlewska, Renata; Jagusztyn-Krynicka, Elzbieta Katarzyna

    2005-01-01

    Several pathogenic bacteria are able to trigger apoptosis in the host cell, but the mechanisms by which it occurs differ, and the resulting pathology can take different courses. Induction and/or blockage of programmed cell death upon infection is a result of complex interaction of bacterial proteins with cellular proteins involved in signal transduction and apoptosis. In this review we focus on pro/anti-apoptotic activities exhibited by two enteric pathogens Salmonella enterica, Yersinia spp. and gastric pathogen Helicobacter pylori. We present current knowledge on how interaction between mammalian and bacterial cell relates to the molecular pathways of apoptosis, and what is the role of apoptosis in pathogenesis.

  16. Altered global gene expression profiles in human gastrointestinal epithelial Caco2 cells exposed to nanosilver

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    Saura C. Sahu

    2016-01-01

    Full Text Available Extensive consumer exposure to food- and cosmetics-related consumer products containing nanosilver is of public safety concern. Therefore, there is a need for suitable in vitro models and sensitive predictive rapid screening methods to assess their toxicity. Toxicogenomic profile showing subtle changes in gene expressions following nanosilver exposure is a sensitive toxicological endpoint for this purpose. We evaluated the Caco2 cells and global gene expression profiles as tools for predictive rapid toxicity screening of nanosilver. We evaluated and compared the gene expression profiles of Caco-2 cells exposed to 20 nm and 50 nm nanosilver at a concentration 2.5 μg/ml. The global gene expression analysis of Caco2 cells exposed to 20 nm nanosilver showed that a total of 93 genes were altered at 4 h exposure, out of which 90 genes were up-regulated and 3 genes were down-regulated. The 24 h exposure of 20 nm silver altered 15 genes in Caco2 cells, out of which 14 were up-regulated and one was down-regulated. The most pronounced changes in gene expression were detected at 4 h. The greater size (50 nm nanosilver at 4 h exposure altered more genes by more different pathways than the smaller (20 nm one. Metallothioneins and heat shock proteins were highly up-regulated as a result of exposure to both the nanosilvers. The cellular pathways affected by the nanosilver exposure is likely to lead to increased toxicity. The results of our study presented here suggest that the toxicogenomic characterization of Caco2 cells is a valuable in vitro tool for assessing toxicity of nanomaterials such as nanosilver.

  17. Molecular characterization of bacterial communities in the human gastrointestinal tract

    NARCIS (Netherlands)

    Zoetendal, E.G.

    2001-01-01

    The human gastrointestinal (GI) tract is a complex ecosystem in which host and microbial cells live in close contact with each other. The microbial community in the human GI tract has an important nutritional and protective function and mainly consists of anaerobic bacteria. After birth, the germ-fr

  18. Toxicity profiling of water contextual zinc oxide, silver, and titanium dioxide nanoparticles in human oral and gastrointestinal cell systems.

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    Giovanni, Marcella; Tay, Chor Yong; Setyawati, Magdiel Inggrid; Xie, Jianping; Ong, Choon Nam; Fan, Rongli; Yue, Junqi; Zhang, Lifeng; Leong, David Tai

    2015-12-01

    Engineered nanoparticles (ENPs) are increasingly detected in water supply due to environmental release of ENPs as the by-products contained within the effluent of domestic and industrial run-off. The partial recycling of water laden with ENPs, albeit at ultra-low concentrations, may pose an uncharacterized threat to human health. In this study, we investigated the toxicity of three prevalent ENPs: zinc oxide, silver, and titanium dioxide over a wide range of concentrations that encompasses drinking water-relevant concentrations, to cellular systems representing oral and gastrointestinal tissues. Based on published in silico-predicted water-relevant ENPs concentration range from 100 pg/L to 100 µg/L, we detected no cytotoxicity to all the cellular systems. Significant cytotoxicity due to the NPs set in around 100 mg/L with decreasing extent of toxicity from zinc oxide to silver to titanium dioxide NPs. We also found that noncytotoxic zinc oxide NPs level of 10 mg/L could elevate the intracellular oxidative stress. The threshold concentrations of NPs that induced cytotoxic effect are at least two to five orders of magnitude higher than the permissible concentrations of the respective metals and metal oxides in drinking water. Based on these findings, the current estimated levels of NPs in potable water pose little cytotoxic threat to the human oral and gastrointestinal systems within our experimental boundaries.

  19. Distribution of obestatin and ghrelin in human tissues: immunoreactive cells in the gastrointestinal tract, pancreas, and mammary glands

    DEFF Research Database (Denmark)

    Grönberg, Malin; Tsolakis, Apostolos V; Magnusson, Linda

    2008-01-01

    Obestatin and ghrelin are two peptides derived from the same prohormone. It is well established that ghrelin is produced by endocrine cells in the gastric mucosa. However, the distribution of human obestatin immunoreactive cells is not thoroughly characterized. A polyclonal antibody...... that specifically recognizes human obestatin was produced. Using this antibody and a commercial antibody vs ghrelin, the distribution of obestatin and ghrelin immunoreactive cells was determined in a panel of human tissues using immunohistochemistry. The two peptides were detected in the mucosa...

  20. Sensory testing of the human gastrointestinal tract.

    NARCIS (Netherlands)

    Brock, C.; Arendt-Nielsen, L.; Wilder-Smith, O.H.G.; Drewes, A.M.

    2009-01-01

    The objective of this appraisal is to shed light on the various approaches to screen sensory information in the human gut. Understanding and characterization of sensory symptoms in gastrointestinal disorders is poor. Experimental methods allowing the investigator to control stimulus intensity and mo

  1. Down-regulation of human leukocyte antigens class I on peripheral T lymphocytes and NK cells from subjects in region of high-incidence gastrointestinal tumor

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    ZHANG Zhi-mian; LI Ying-jie; GUAN Xiao; YANG Xiao-yun; GAO Xi-mei; YANG Xiao-jing; WANG Li-shui; ZOU Xiong

    2011-01-01

    Background Many types of human tumors can suppress the immune system to enhance their survival. Loss or down-regulation of human leukocyte antigens (HLA) class I on tumors is considered to be a major mechanism of tumor immune escape. Our previous studies found that HLA class I on peripheral-blood mononuclear cells was significantly lower in gastric cancer patients. The present study made an analysis of HLA class I expression on peripheral-blood T lymphocytes and NK cells from subjects of Lijiadian village, a village with high-incidence gastrointestinal tumor. Methods A total of 181 villagers from Lijiadian village and 153 normal controls from the Department of Health Examination Center were enrolled in this study. Using a multi-tumor markers detection system, these villagers were divided into two groups: high-risk group (tumor markers positive group) and low-risk group (tumor markers negative group). The percentage of T lymphocytes and NK cells and levels of HLA class I on their surface were determined in these subjects by flow cytometry.Results Percentages of T lymphocytes and NK cells in peripheral-blood mononuclear cells did not vary with age. The expression level of HLA class I on peripheral T lymphocytes and NK cells was not affected by age or gender, but was significantly down-regulated in Lijiadian villagers (P<0.05), especially on the surface of NK cells (P<0.01). Compared with the low-risk group, there was a significant reduction of HLA class I on peripheral T lymphocytes (P <0.05) and NK cells (P <0.05) in the high-risk group.Conclusions HLA class I on peripheral T lymphocytes and NK cells may be involved in tumorigenesis and development of gastrointestinal tumor, and understanding their changes in expression may provide new insights into the mechanism of tumor immunity.

  2. Gastrointestinal stem cell up-to-date.

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    Pirvulet, V

    2015-01-01

    Cellular and tissue regeneration in the gastrointestinal tract depends on stem cells with properties of self-renewal, clonogenicity, and multipotency. Progress in stem cell research and the identification of potential gastric, intestinal, colonic stem cells new markers and the signaling pathways provide hope for the use of stem cells in regenerative medicine and treatments for disease. This review provides an overview of the different types of stem cells, focusing on tissue-restricted adult stem cells.

  3. [Gastrointestinal human myiasis caused by Eristalis tenax].

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    Kun, M; Kreiter, A; Semenas, L

    1998-08-01

    The myiasis observed in Bariloche are characterized and the probable conditions under which the infestations took place established. The larvae obtained from faeces of 2 patients were identified as Eristalis tenax (Diptera: Syrphidae) according to Hartley (1961) and Organización Panamericana de la Salud keys (1962). These 2 cases of human gastrointestinal myiasis were the first to be registered in Bariloche (Patagonia, Argentina) and their characteristics were similar to those described for this species in other parts of the world. The lack of specific control measures in the domestic water supply system was the most probable cause of the infestation. This event extends the distribution of E. tenax and human gastrointestinal myiasis in South America to 41 degrees 03' S.

  4. Cytotoxic effects of bromelain in human gastrointestinal carcinoma cell lines (MKN45, KATO-III, HT29-5F12, and HT29-5M21

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    Amini A

    2013-04-01

    Full Text Available Afshin Amini, Anahid Ehteda, Samar Masoumi Moghaddam, Javed Akhter, Krishna Pillai, David Lawson Morris Department of Surgery, St George Hospital, University of New South Wales, Sydney, NSW, Australia Background: Bromelain is a pineapple stem extract with a variety of therapeutic benefits arising from interaction with a number of different biological processes. Several preclinical studies and anecdotal clinical observations have reported the anticancer properties of bromelain. In the present study, we investigated the cytotoxic effects of bromelain in four human cancer cell lines of gastrointestinal origin and the mechanisms involved. Methods: The gastric carcinoma cell lines (KATO-III and MKN45 and two chemoresistant subpopulations of the HT29 colon adenocarcinoma cell line (HT29-5M21 and HT29-5F12 were treated with a range of concentrations of bromelain, as well as with cisplatin as a positive control. The effect of bromelain on the growth and proliferation of cancer cells was determined using a sulforhodamine B assay after 72 hours of treatment. Expression of apoptosis-associated proteins in MKN45 cells treated with bromelain was analyzed by Western blotting. Results: Data from our sulforhodamine B assay showed that bromelain inhibited proliferation of HT29-5F12, HT29-5M21, MKN45, and KATO-III cells, with respective half maximal inhibitory concentration values of 29, 34, 94, and 142 µg/mL. Analyzing the expression of proapoptotic and antiapoptotic proteins in bromelain-treated MKN45 cells, we observed activation of the caspase system, cleavage of PARP and p53, overexpression of cytochrome C, attenuation of phospho-Akt and Bcl2, and removal of MUC1. Apart from the caspase-dependent apoptosis observed, emergence of cleaved p53 supports a direct, extranuclear apoptotic function of p53. Moreover, interrupted Akt signaling and attenuation of Bcl2 and MUC1 oncoproteins suggest impaired survival of cancer cells. Conclusion: Our findings

  5. Neural Crest Cell Implantation Restores Enteric Nervous System Function and Alters the Gastrointestinal Transcriptome in Human Tissue-Engineered Small Intestine

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    Christopher R. Schlieve

    2017-09-01

    Full Text Available Acquired or congenital disruption in enteric nervous system (ENS development or function can lead to significant mechanical dysmotility. ENS restoration through cellular transplantation may provide a cure for enteric neuropathies. We have previously generated human pluripotent stem cell (hPSC-derived tissue-engineered small intestine (TESI from human intestinal organoids (HIOs. However, HIO-TESI fails to develop an ENS. The purpose of our study is to restore ENS components derived exclusively from hPSCs in HIO-TESI. hPSC-derived enteric neural crest cell (ENCC supplementation of HIO-TESI establishes submucosal and myenteric ganglia, repopulates various subclasses of neurons, and restores neuroepithelial connections and neuron-dependent contractility and relaxation in ENCC-HIO-TESI. RNA sequencing identified differentially expressed genes involved in neurogenesis, gliogenesis, gastrointestinal tract development, and differentiated epithelial cell types when ENS elements are restored during in vivo development of HIO-TESI. Our findings validate an effective approach to restoring hPSC-derived ENS components in HIO-TESI and may implicate their potential for the treatment of enteric neuropathies.

  6. Investigation of Genipin Cross-Linked Microcapsule for Oral Delivery of Live Bacterial Cells and Other Biotherapeutics: Preparation and In Vitro Analysis in Simulated Human Gastrointestinal Model

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    Hongmei Chen

    2010-01-01

    Full Text Available Oral therapy utilizing engineered microorganisms has shown promise in the treatment of many diseases. By microencapsulation, viable cells can overcome the harsh gastrointestinal (GI environment and secrete needed therapeutics into the gut. These engineered cells should be encased without escaping into the GI tract for safety concerns, thus robust microcapsule membrane is requisite. This paper examined the GI performance of a novel microcapsule membrane using a dynamic simulated human GI model. Results showed that the genipin cross-linked alginate-chitosan (GCAC microcapsules possessed strong resistance to structural disintegration in the simulated GI environment. Leakage of encapsulated high molecular weight dextran, a model material to be protected during the simulated GI transit, was negligible over 72 h of exposure, in contrast to considerable leakage of dextran from the non-cross-linked counterparts. These microcapsules did not alter the microflora and enzymatic activities in the simulated human colonic media. This study suggested the potential of the GCAC microcapsules for oral delivery of live microorganisms and other biotherapeutics.

  7. Human papillomavirus and gastrointestinal cancer: A review

    Science.gov (United States)

    Bucchi, Dania; Stracci, Fabrizio; Buonora, Nicola; Masanotti, Giuseppe

    2016-01-01

    Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Exposure to HPV is very common, and an estimated 65%-100% of sexually active adults are exposed to HPV in their lifetime. The majority of HPV infections are asymptomatic, but there is a 10% chance that individuals will develop a persistent infection and have an increased risk of developing a carcinoma. The International Agency for Research on Cancer has found that the following cancer sites have a strong causal relationship with HPV: cervix uteri, penis, vulva, vagina, anus and oropharynx, including the base of the tongue and the tonsils. However, studies of the aetiological role of HPV in colorectal and esophageal malignancies have conflicting results. The aim of this review was to organize recent evidence and issues about the association between HPV infection and gastrointestinal tumours with a focus on esophageal, colorectal and anal cancers. The ultimate goal was to highlight possible implications for prognosis and prevention. PMID:27672265

  8. Development of Eimeria bovis in vitro: suitability of several bovine, human and porcine endothelial cell lines, bovine fetal gastrointestinal, Madin-Darby bovine kidney (MDBK) and African green monkey kidney (VERO) cells.

    Science.gov (United States)

    Hermosilla, C; Barbisch, B; Heise, A; Kowalik, S; Zahner, H

    2002-04-01

    Several bovine, human and porcine endothelial cell lines, bovine fetal gastrointestinal cells (BFGC), Madin-Darby bovine kidney (MDBK) and African green monkey kidney (VERO) cells were exposed in vitro to sporozoites of Eimeria bovis. Parasites invaded all cells used and changed their shape to more stumpy forms within 12 h. Sporozoites left their host cells and invaded new ones frequently within the first 12 h post-infection. Further development took place only in bovine cells, although parasites survived in the other cells for at least 3 weeks. Within the non-bovine cells, conspicuously enlarged parasitophorous vacuoles developed in VERO cells and reached a diameter of 15-20 microm. The best development to first generation schizonts with regard both to time required to mature, to schizont size and to merozoite yields was observed in BFGC, followed by bovine umbilical vein and bovine spleen lymphatic endothelial cells. MDBK cells were less suitable. The life cycle was completed (development of oocysts) only occasionally in BFGC. Results are considered under several aspects. Thus, infected VERO cells may represent a suitable tool for studying the parasitophorous vacuole, while infected endothelial cells represent a system quite narrow to the in vivo situation and should allow basic studies on parasite/host cell interactions and BFGC can be used for the mass production of E. bovis first generation merozoites.

  9. Sensory testing of the human gastrointestinal tract

    Institute of Scientific and Technical Information of China (English)

    Christina Brock; Lars Arendt-Nielsen; Oliver Wilder-Smith; Asbjφrn Mohr Drewes

    2009-01-01

    The objective of this appraisal is to shed light on the various approaches to screen sensory information in the human gut. Understanding and characterization of sensory symptoms in gastrointestinal disorders is poor. Experimental methods allowing the investigator to control stimulus intensity and modality, as well as using validated methods for assessing sensory response have contributed to the understanding of pain mechanisms. Mechanical stimulation based on impedance planimetry allows direct recordings of luminal cross-sectional areas, and combined with ultrasound and magnetic resonance imaging, the contribution of different gut layers can be estimated. Electrical stimulation depolarizes free nerve endings non-selectively. Consequently, the stimulation paradigm (single, train, tetanic) influences the involved sensory nerves. Visual controlled electrical stimulation combines the probes with an endoscopic approach, which allows the investigator to inspect and obtain small biopsies from the stimulation site. Thermal stimulation (cold or warm) activates selectively mucosal receptors, and chemical substances such as acid and capsaicin (either alone or in combination) are used to evoke pain and sensitization. The possibility of multimodal (e.g. mechanical, electrical, thermal and chemical) stimulation in different gut segments has developed visceral pain research. The major advantage is involvement of distinctive receptors, various sensory nerves and different pain pathways mimicking clinical pain that favors investigation of central pain mechanisms involved in allodynia, hyperalgesia and referred pain. As impairment of descending control mechanisms partly underlies the pathogenesis in chronic pain, a cold pressor test that indirectly stimulates such control mechanisms can be added. Hence, the methods undoubtedly represent a major step forward in the future characterization and treatment of patients with various diseases of the gut, which provides knowledge to

  10. Computer aided classification of cell nuclei in the gastrointestinal tract by volume and principal axis

    Science.gov (United States)

    Sagstetter, Ann M.; Camp, Jon J.; Lurken, Matthew S.; Szurszewski, Joseph H.; Farrugia, Gianrico; Gibbons, Simon J.; Robb, Richard A.

    2007-03-01

    Normal function of the gastrointestinal tract involves the coordinated activity of several cell types Human disorders of motor function of the gastrointestinal tract are often associated with changes in the number of these cells. For example, in diabetic patients, abnormalities in gastrointestinal transit are associated with changes in nerves and interstitial cells of Cajal (ICC), two key cells that generate and regulate motility. ICC are cells of mesenchymal origin that function as pacemakers and amplify neuronal signals in the gastrointestinal tract. Quantifying the changes in number of specific cell types in tissues from patients with motility disorders is challenging and requires immunolabeling for specific antigens. The shape of nuclei differs between the cell types in the wall of the gastrointestinal tract. Therefore the objective of this study was to determine whether cell nuclei can be classified by analyzing the 3D morphology of the nuclei. Furthermore, the orientation of the long axis of nuclei changes within and between the muscle layers. These features can be used to classify and differentially label the nuclei in confocal volume images of the tissue by computing the principal axis of the coordinates of the set of voxels forming each nucleus and thereby to identify cells by their nuclear morphology. Using this approach, we were able to separate and quantify nuclei in the smooth muscle layers of the tissue. Therefore we conclude that computer-aided classification of cell nuclei can be used to identify changes in the cell types expressed in gastrointestinal smooth muscle.

  11. Gastrointestinal-active oligosaccharides from human milk and functional foods

    NARCIS (Netherlands)

    Albrecht, S.A.

    2011-01-01

    Keywords: human milk oligosaccharides (HMOs), galacto-oligosaccharides (GOS), konjac glucomannan (KGM), breast milk, baby feces, gastrointestinal metabolization, blood-group specific conjugates, CE-LIF-MSn   Oligosaccharides, as present in human milk or supplemented to food, are renowned for

  12. Viability of Lactobacillus delbrueckii Under Human Gastrointestinal Conditions Simulated In Vitro

    Directory of Open Access Journals (Sweden)

    Karina C. Pacheco

    2010-01-01

    Full Text Available Problem statement: Lactobacillus delbrueckii subsp. bulgaricus is a lactic bacteria mostly used in the production of yoghurt and it has an important probiotic activity that brings benefits to the human body. However, the gastrointestinal tract has aggressive conditions, such as the acid pH in the stomach and the bile in the duodenum, that reduce the viability of this bacteria. Approach: In order to evaluate the effect of the human gastrointestinal conditions on Lactobacillus delbrueckiis viability, a simulated in vitro gastrointestinal system was designed, which consisted of two reactors where stomach and human small intestine conditions were simulated. Results: Lactobacillus delbrueckii cells were treated in human gastric conditions simulated in vitro (gastric juice adjusted to pH 2, 37°C, 90 min and 50 rpm and in intestinal conditions simulated in vitro (pancreatic juice adjusted to pH 6.8, 37°C, 150 min and 50 rpm and in presence of a sample of food or beverages. A sample of typical Mexican food was added and at the end of the treatment 73% of the cells remained viable. This means 36.5 times more viability with respect to the cells treated under the same conditions in presence of a sample of milk with 8% starch. At the end of the treatment, the viability of cells treated in simulated in vitro gastrointestinal juices without sample of food or beverage (blank was 1%. Conclusion: The results indicated that the in vitro simulated human gastrointestinal conditions were aggressive to the Lactobacillus delbrueckiis viability. To minimize this negative effect it is suggested that probiotics be consumed with some food because this could increase the probability that the bacteria reach the human colon in a large number and carry out their probiotic effect.

  13. Gastrointestinal and hepatic complications of hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Hande H Tuncer; Naveed Rana; Cannon Milani; Angela Darko; Samer A Al-Homsi

    2012-01-01

    Recognition and management of gastrointestinal and hepatic complications of hematopoietic stem cell transplantation has gained increasing importance as indications and techniques of transplantation have expanded in the last few years.The transplant recipient is at risk for several complications including conditioning chemotherapy related toxicities,infections,bleeding,sinusoidal obstruction syndrome,acute and chronic graftversus-host disease (GVHD) as well as other long-term problems.The severity and the incidence of many complications have improved in the past several years as the intensity of conditioning regimens has diminished and better supportive care and GVHD prevention strategies have been implemented.Transplant clinicians,however,continue to be challenged with problems arising from human leukocyte antigen-mismatched and unrelated donor transplants,expanding transplant indications and age-limit.This review describes the most commonly seen transplant related complications,focusing on their pathogenesis,differential diagnosis and management.

  14. Gastrointestinal metabolization of human milk oligosaccharides

    NARCIS (Netherlands)

    Albrecht, S.A.; Heuvel, van den E.G.H.M.; Gruppen, H.; Schols, H.A.

    2013-01-01

    Breast feeding has a great impact on the growth of infants both physically and psychologically. Human breast milk is beneficial to infant health because it contains the necessary macro- and micro-nutrients for tissue accretion, repair and behavioural developments. The production of milk is a complex

  15. Wnt and the cancer niche: paracrine interactions with gastrointestinal cancer cells undergoing asymmetric cell division.

    Science.gov (United States)

    Xin, Hong-Wu; Ambe, Chenwi M; Ray, Satyajit; Kim, Bo-Kyu; Koizumi, Tomotake; Wiegand, Gordon W; Hari, Danielle; Mullinax, John E; Jaiswal, Kshama R; Garfield, Susan H; Stojadinovic, Alexander; Rudloff, Udo; Thorgeirsson, Snorri S; Avital, Itzhak

    2013-01-01

    Stem-like cancer cells contribute to cancer initiation and maintenance. Stem cells can self-renew by asymmetric cell division (ACD). ACD with non-random chromosomal cosegregation (ACD-NRCC) is one possible self-renewal mechanism. There is a paucity of evidence supporting ACD-NRCC in human cancer. Our aim was to investigate ACD-NRCC and its potential interactions with the cancer niche (microenvironment) in gastrointestinal cancers. We used DNA double and single labeling approaches with FACS to isolate live cells undergoing ACD-NRCC. Gastrointestinal cancers contain rare subpopulations of cells capable of ACD-NRCC. ACD-NRCC was detected preferentially in subpopulations of cells previously suggested to be stem-like/tumor-initiating cancer cells. ACD-NRCC was independent of cell-to-cell contact, and was regulated by the cancer niche in a heat-sensitive paracrine fashion. Wnt pathway genes and proteins are differentially expressed in cells undergoing ACD-NRCC vs. symmetric cell division. Blocking the Wnt pathway with IWP2 (WNT antagonist) or siRNA-TCF4 resulted in suppression of ACD-NRCC. However, using a Wnt-agonist did not increase the relative proportion of cells undergoing ACD-NRCC. Gastrointestinal cancers contain subpopulations of cells capable of ACD-NRCC. Here we show for the first time that ACD-NRCC can be regulated by the Wnt pathway, and by the cancer niche in a paracrine fashion. However, whether ACD-NRCC is exclusively associated with stem-like cancer cells remains to be determined. Further study of these findings might generate novel insights into stem cell and cancer biology. Targeting the mechanism of ACD-NRCC might engender novel approaches for cancer therapy.

  16. Gastrointestinal Complications Following Hematopoietic Stem Cell Transplantation in Children

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Hye; Lim, Gye Yeon; Im, Soo Ah; Chung, Nak Gyun; Hahn, Seung Tae [St. Mary' s Hospital, The Catholic University of Korea, Seoul (Korea, Republic of)

    2008-10-15

    Gastrointestinal system involvement is one of the principal complications seen in the recipients of hematopoietic stem cell transplantation (HSCT), and it is also a major cause of morbidity and death in these patients. The major gastrointestinal complications include typhlitis (neutropenic enterocolitis), pseudomembranous enterocolitis, viral enteritis, graft-versus-host disease, benign pneumatosis intestinalis, intestinal thrombotic microangiopathy, and post-transplantation lymphoproliferative disease. As these patients present with nonspecific abdominal symptoms, evaluation with using such imaging modalities as ultrasonography and CT is essential in order to assess the extent of gastrointestinal involvement and to diagnose these complications. We present here a pictorial review of the imaging features and other factors involved in the diagnosis of these gastrointestinal complications in pediatric HSCT recipients.

  17. Human breast milk and the gastrointestinal innate immune system.

    Science.gov (United States)

    Jakaitis, Brett M; Denning, Patricia W

    2014-06-01

    The gastrointestinal (GI) tract is a large potential portal for multiple infectious agents to enter the human body. The GI system performs multiple functions as part of the neonate's innate immune system, providing critical defense during a vulnerable period. Multiple mechanisms and actions are enhanced by the presence of human breast milk. Bioactive factors found in human milk work together to create and maintain an optimal and healthy environment, allowing the intestines to deliver ideal nutrition to the host and afford protection by a variety of mechanisms.

  18. Myiasis gastrointestinal humana por Eristalis tenax Gastrointestinal human myiasis for Eristalis tenax

    Directory of Open Access Journals (Sweden)

    Marcelo Kun

    1998-08-01

    Full Text Available Son caracterizadas las myiasis registradas en Bariloche y establecidas las condiciones probables bajo las cuales se produjeron las infestaciones. Las larvas obtenidas a partir de heces de 2 pacientes fueron identificadas como Eristalis tenax (Diptera: Syrphidae de acuerdo a las claves de Hartley (1961 y Organización Panamericana de la Salud (1962. Estos 2 casos de myiasis gastrointestinal humana constituyen los primeros registrados en Bariloche (Patagonia, Argentina y sus características responden a las registradas para esta especie de Díptera en otras partes del mundo. La falta de control específico en el sistema domiciliario de suministro de agua ha sido la causa más probable de la infestación. Este registro extiende la distribución de E. tenax y de las myiasis gastrointestinales humanas en América del Sur hasta los 41º 03' S.Foram caracterizadas as miasis registradas em Bariloche (Patagonia, Argentina e estabelecidas as prováveis condições sob as quais são produzidas as infestações. As larvas obtidas a partir das fezes de dois pacientes foram identificadas como Eristalis tenax (Diptera: Syrphdae. Esses dois casos de miasis gastrointestinal humana foram os primeiros registrados em Bariloche, Argentina, e suas características respondem às registradas para esta espécie de Diptera em outras partes do mundo. A falta de controle específico no sistema domiciliário de abastecimento de água tem sido a causa mais provável de infestação. Este registro amplia a distribuição de E. tenax e das miasis gastrointestinais humanas em América do Sul até os 41º 03's.The myiasis observed in Bariloche are characterized and the probable conditions under which the infestations took place established. The larvae obtained from faeces of 2 patients were identified as Eristalis tenax (Diptera: Syrphidae according to Hartley (1961 and Organización Panamericana de la Salud keys (1962. These 2 cases of human gastrointestinal myiasis were the

  19. Mast cells and gastrointestinal dysmotility in the cystic fibrosis mouse.

    Directory of Open Access Journals (Sweden)

    Robert C De Lisle

    Full Text Available BACKGROUND: Cystic fibrosis (CF has many effects on the gastrointestinal tract and a common problem in this disease is poor nutrition. In the CF mouse there is an innate immune response with a large influx of mast cells into the muscularis externa of the small intestine and gastrointestinal dysmotility. The aim of this study was to evaluate the potential role of mast cells in gastrointestinal dysmotility using the CF mouse (Cftr(tm1UNC, Cftr knockout. METHODOLOGY: Wild type (WT and CF mice were treated for 3 weeks with mast cell stabilizing drugs (ketotifen, cromolyn, doxantrazole or were treated acutely with a mast cell activator (compound 48/80. Gastrointestinal transit was measured using gavage of a fluorescent tracer. RESULTS: In CF mice gastric emptying at 20 min post-gavage did not differ from WT, but was significantly less than in WT at 90 min post-gavage. Gastric emptying was significantly increased in WT mice by doxantrazole, but none of the mast cell stabilizers had any significant effect on gastric emptying in CF mice. Mast cell activation significantly enhanced gastric emptying in WT mice but not in CF mice. Small intestinal transit was significantly less in CF mice as compared to WT. Of the mast cell stabilizers, only doxantrazole significantly affected small intestinal transit in WT mice and none had any effect in CF mice. Mast cell activation resulted in a small but significant increase in small intestinal transit in CF mice but not WT mice. CONCLUSIONS: The results indicate that mast cells are not involved in gastrointestinal dysmotility but their activation can stimulate small intestinal transit in cystic fibrosis.

  20. The effect of selected factors on the survival of Bacillus cereus in the human gastrointestinal tract.

    Science.gov (United States)

    Berthold-Pluta, Anna; Pluta, Antoni; Garbowska, Monika

    2015-05-01

    Bacillus cereus is a Gram-positive bacterium widely distributed in soil and vegetation. This bacterial species can also contaminate raw or processed foods. Pathogenic B. cereus strains can cause a range of infections in humans, as well as food poisoning of an emetic (intoxication) or diarrheal type (toxico-infection). Toxico-infections are due to the action of the Hbl toxin, Nhe toxin, and cytotoxin K produced by the microorganism in the gastrointestinal tract. This occurs once the spores or vegetative B. cereus cells survive the pH barrier of the stomach and reach the small intestine where they produce toxins in sufficient amounts. This article discusses the effect of various factors on the survival of B. cereus in the gastrointestinal tract, including low pH and the presence of digestive enzymes in the stomach, bile salts in the small intestine, and indigenous microflora in the lower parts of the gastrointestinal tract. Additional aspects also reported to affect B. cereus survival and virulence in the gastrointestinal tract include the interaction of the spores and vegetative cells with enterocytes. In vitro studies revealed that both vegetative B. cereus and spores can survive in the gastrointestinal tract suggesting that the biological form of the microorganism may have less influence on the occurrence of the symptoms of infection than was once believed. It is most likely the interaction between the pathogen and enterocytes that is necessary for the diarrheal form of B. cereus food poisoning to develop. The adhesion of B. cereus to the intestinal epithelium allows the bacterium to grow and produce enterotoxins in the proximity of the epithelium. Recent studies suggest that the human intestinal microbiota inhibits the growth of vegetative B. cereus cells considerably.

  1. Interstitial cells in the musculature of the gastrointestinal tract

    DEFF Research Database (Denmark)

    Rumessen, Jüri J; Vanderwinden, Jean-Marie

    2003-01-01

    Expression of the receptor tyrosine kinase KIT on cells referred to as interstitial cells of Cajal (ICC) has been instrumental during the past decade in the tremendous interest in cells in the interstitium of the smooth muscle layers of the digestive tract. ICC generate the pacemaker component...... "non-Cajal" (including the FLC and possibly also other cell types) cell types in the interstitium of the smooth musculature of the gastrointestinal tract, is proposed. Furthermore, evidence is accumulating to suggest that, as postulated by Santiago Ramon y Cajal, the concept of interstitial cells...

  2. Raman spectra of single cell from gastrointestinal cancer patients

    Institute of Scientific and Technical Information of China (English)

    Xun-Ling Yan; Rui-Xin Dong; Lei Zhang; Xue-Jun Zhang; Zong-Wang Zhang

    2005-01-01

    AIM: To explore the difference between cancer cells and normal cells, we investigated the Raman spectra of singlecells from gastrointestinal cancer patients. METHODS: All samples were obtained from 30 diagnosed as gastrointestinal cancer patients. The flesh tumor specimen is located in the center of tumor tissue, while the normal ones were 5 cm away from the outside tumor section. The imprint was put under the microscope and a single cell was chosen for Raman measurement. All spectra were collected at confocal Raman micro-spectroscopy (British Renishaw) with NIR 780 nm laser.RESULTS: We measured the Raman spectra of several cells from gastrointestinal cancer patients. The result shows that there exists the strong line at 1 002/cm with less half-width assigned to the phenylalanine in several cells. The Raman lines of white cell were lower and less, while those of red cell were not only higher in intensity and more abundant, but also had a parti cular C-N breathing stretching band of pyrrole ring at 1 620-1 540/cm. The line at 1 084/cm assigned to phosphate backbone of DNA became obviously weaker in cancer cell. The Raman spectra of stomach cancer cells were similar to those of normal cells, but the Raman intensity of cancer cells was much lower than that of normal cells, and even some lines disappear. The lines of enteric cancer cells became weaker than spectra above and many lines disappeared, and the cancer cells in different position had different fluorescence intensity.CONCLUSION: The Raman spectra of several cells from cancer patients show that the structural changes of cancer cells happen and many bonds rupture so that the biological function of cells are lost. The results indicate that Raman spectra can offer the experiment basis for the cancer diagnosis and treatment.

  3. Impact of Oat-Based Products on Human Gastrointestinal Tract

    Directory of Open Access Journals (Sweden)

    Staka Aiga

    2015-09-01

    Full Text Available Oat is rich in valuable nutrients. In comparison to other cereals, oat contains more total proteins, carbohydrate, fat, non-starch fibre, as well as unique antioxidants (one of them - avenanthramides, vitamins, and minerals. One of the most often studied components of oats is β-glucan - a type of soluble dietary fibre located throughout the starch endosperm, but with highest concentration in the bran. Many studies have shown the beneficial health effects of oat β-glucan as a soluble dietary fibre. Until now, most of the studies on this nutrient have been conducted in the cardiovascular and diabetology field. This article aimed to review the literature on studies that investigated the effects of oat-based products on human gastrointestinal tract - gastrointestinal microflora, irritable bowel syndrome, inflammatory bowel disease as well as prevention/treatment of colorectal cancer. A literature search was conducted using PubMed database. More than 80 potential articles were identified, which were selected afterwards according to aims of our study. Studies done on human were preferred. A long-term dietary intake of oat-based products improves human intestinal microflora, could have benefits in irritable bowel syndrome, and probable effects were seen in patients with ulcerative colitis, but this remains to be proven. There are few studies regarding prevention/treatment of colorectal cancer and they do not show clear benefit nor provide recommendations.

  4. Pacemaker cells in the gastrointestinal tract

    DEFF Research Database (Denmark)

    Rumessen, J J; Thuneberg, L

    1996-01-01

    patterns; characteristic patterns of contact with smooth muscle cells) and ultrastructure (myoid features: basal lamina, caveolae, rich in sER and mitochondria, often prominent filament bundles and dense bands/bodies) has allowed the identification of ICC in the GI musculature of all species investigated......Interstitial cells of Cajal (ICC) were described a century ago as primitive neurons in the intestines. Through the years, ICC have been mistaken for neurons, glial cells, fibroblasts, smooth muscle cells, and macrophages. We identified ICC in the musculature of mouse small intestine...

  5. A heptameric peptide purified from Spirulina sp. gastrointestinal hydrolysate inhibits angiotensin I-converting enzyme- and angiotensin II-induced vascular dysfunction in human endothelial cells.

    Science.gov (United States)

    Heo, Seong-Yeong; Ko, Seok-Chun; Kim, Chang Su; Oh, Gun-Woo; Ryu, Bomi; Qian, Zhong-Ji; Kim, Geunhyung; Park, Won Sun; Choi, Il-Whan; Phan, Thi Tuong Vy; Heo, Soo-Jin; Kang, Do-Hyung; Yi, Myunggi; Jung, Won-Kyo

    2017-05-01

    In this study, a marine microalga Spirulina sp.-derived protein was hydrolyzed using gastrointestinal enzymes to produce an angiotensin I (Ang I)-converting enzyme (ACE) inhibitory peptide. Following consecutive purification, the potent ACE inhibitory peptide was composed of 7 amino acids, Thr-Met‑Glu‑Pro‑Gly‑Lys-Pro (molecular weight, 759 Da). Analysis using the Lineweaver-Burk plot and molecular modeling suggested that the purified peptide acted as a mixed non-competitive inhibitor of ACE. The inhibitory effects of the peptide against the cellular production of vascular dysfunction-related factors induced by Ang II were also investigated. In human endothelial cells, the Ang II-induced production of nitric oxide and reactive oxygen species was inhibited, and the expression of inducible nitric oxide synthase (iNOS) and endothelin-1 (ET-1) was downregulated when the cells were cultured with the purified peptide. Moreover, the peptide blocked the activation of p38 mitogen‑activated protein kinase. These results indicated that this Spirulina sp.-derived peptide warrants further investigation as a potential pharmacological inhibitor of ACE and vascular dysfunction.

  6. PCR Expression Analysis Of the Estrogeninducible Gene Bcei in Gastrointestinal and Other Human Tumors

    Directory of Open Access Journals (Sweden)

    Iris Wundrack

    1994-01-01

    Full Text Available A polymerase chain reaction (PCR assay was developed to test for tumor cell specific expression of the BCEI gene. This new marker gene, reported at first for human breast cancer, was found specifically active in various gastrointestinal carcinomas by previously applying immunohistochemistry and RNA (Northern blot analysis. Presently, by using reverse transcription -PCR analysis, a series of primary tumor tissues and established tumor cell lines were testcd for BCEI transcription. This approach was compared to immunostaining achieved by an antibody directed against the BCEI gene’s product. The result demonstrate the superior sensitivity of PCR by indicating the gene’ s expression in cases where immunohistochemical testing remained negative.

  7. Stem cells in gastrointestinal cancers: The road less travelled

    Institute of Scientific and Technical Information of China (English)

    Sameh; Mikhail; Amer; Zeidan

    2014-01-01

    Cancer stem cells(CSC) are thought to be malignant cells that have the capacity to initiate and maintain tumor growth and survival. Studies have described CSC in various gastrointestinal neoplasms such as colon, pancreas and liver and gastroesophageal tumors. The mechanism by which CSC develop remains unclear. Several studies have explored the role of dysregulation of the Wnt/β-catenin, transformation growth factor-beta and hedhog pathways in generation of CSC. In this review, we discuss the various molecular abnormalities that may be related to formation of CSC in gastrointestinal malignancies, strategies to identify CSC and therapeutic strategies that are based on these concepts. Identification and targeting CSC is an intriguing area and may provide a new therapeutic option for patients with cancer including gastrointestinal malignancies. Although great progress has been made, many issues need to be addressed. Precise targeting of CSC will require precise isolation and characterization of those cells. This field is also evolving but further research is needed to identify markers that are specific for CSC.Although the application of this field has not entered the clinic yet, there continues to be significant optimism about its potential utility in overcoming cancer resistance and curing patients with cancer.

  8. Hepatic metabolism of toluene after gastrointestinal uptake in humans

    DEFF Research Database (Denmark)

    Bælum, Jesper; Mølhave, Lars; Honoré Hansen, S

    1993-01-01

    The metabolism of toluene and the influence of small doses of ethanol were measured in eight male volunteers after gastrointestinal uptake, the toluene concentration in alveolar air and the urinary excretion of hippuric acid and ortho-cresol being used as the measures of metabolism. During toluene...... exposure to 2 mg.min-1 for 3 h the alveolar toluene concentration was 0.07 (range 0-0.11) mg.m-3; exposure to 6 mg.min-1 for 30 min increased the alveolar concentration to 0.9 (range 0.03-2.6) mg.m-3. Ingestion of 0.08, 0.16, and 0.32 g of ethanol per kilogram of body weight during toluene exposure of 2 mg...... doses of ethanol inhibit toluene metabolism, and the procedure is sensitive enough to measure metabolic interactions between solvents and other xenobiotics in humans....

  9. Gastrointestinal Fibroblasts Have Specialized, Diverse Transcriptional Phenotypes: A Comprehensive Gene Expression Analysis of Human Fibroblasts.

    Directory of Open Access Journals (Sweden)

    Youichi Higuchi

    Full Text Available Fibroblasts are the principal stromal cells that exist in whole organs and play vital roles in many biological processes. Although the functional diversity of fibroblasts has been estimated, a comprehensive analysis of fibroblasts from the whole body has not been performed and their transcriptional diversity has not been sufficiently explored. The aim of this study was to elucidate the transcriptional diversity of human fibroblasts within the whole body.Global gene expression analysis was performed on 63 human primary fibroblasts from 13 organs. Of these, 32 fibroblasts from gastrointestinal organs (gastrointestinal fibroblasts: GIFs were obtained from a pair of 2 anatomical sites: the submucosal layer (submucosal fibroblasts: SMFs and the subperitoneal layer (subperitoneal fibroblasts: SPFs. Using hierarchical clustering analysis, we elucidated identifiable subgroups of fibroblasts and analyzed the transcriptional character of each subgroup.In unsupervised clustering, 2 major clusters that separate GIFs and non-GIFs were observed. Organ- and anatomical site-dependent clusters within GIFs were also observed. The signature genes that discriminated GIFs from non-GIFs, SMFs from SPFs, and the fibroblasts of one organ from another organ consisted of genes associated with transcriptional regulation, signaling ligands, and extracellular matrix remodeling.GIFs are characteristic fibroblasts with specific gene expressions from transcriptional regulation, signaling ligands, and extracellular matrix remodeling related genes. In addition, the anatomical site- and organ-dependent diversity of GIFs was also discovered. These features of GIFs contribute to their specific physiological function and homeostatic maintenance, and create a functional diversity of the gastrointestinal tract.

  10. Immunohistochemical study on gastrointestinal endocrine cells of four reptiles

    Institute of Scientific and Technical Information of China (English)

    Xu-Gen Huang; Xiao-Bing Wu

    2005-01-01

    AIM: To darify the types, regional distributions and distribution densities as well as morphological features of gastrointestinal (GI) endocrine cells in various parts of the gastrointestinal track (GIT) of four reptiles, Gekko japonicus, Eumeces chinensis, Sphenomorphus indicus and Eumeces elegans.METHODS: Paraffin-embedded sections (5 μm) of seven parts (cardia, fundus, pylorus, duodenum, jejunum, ileum,rectum) of GIT dissected from the four reptiles were prepared. GI endocrine cells were revealed by using immunohistochemical techniques of streptavidin-peroxidase (S-P) method. Seven types of antisera against 5-hydroxytryptamine (5-HT), somatostatin (SS), gastrin (GAS),glucagon (GLU), substance P (SP), insulin and pancreatic polypeptide were identified and then GI endocrine cells were photomicrographed and counted.RESULTS: The GI endocrine system of four reptiles was a complex structure containing many endocrine cell types similar in morphology to those found in higher vertebrates.Five types of GI endocrine cells, namely 5-HT, SS, GAS,SP and GLU immunoreactive (IR) cells were identified in the GIT of G. japonicus, E. chinensis and S. indicus, while in the GIT of E. elegans only the former three types of endocrine cells were observed. No PP- and INS- IR cells were found in all four reptiles. 5-HT-IR cells, which were most commonly found in the pylorus or duodenum, distributed throughout the whole GIT of four reptiles. However, their distribution patterns varied from each other. SS-IR cells,which were mainly found in the stomach especially in the pylorus and/or fundus, were demonstrated in the whole GIT of E. chinensis, only showed restricted distribution in the other three species. GAS-IR cells, with a much restricted distribution, were mainly demonstrated in the pylorus and/or the proximal small intestine of four reptiles. GLU-IR cells exhibited a limited and species-dependent variant distribution in the GIT of four reptiles. SP-IR cells were found throughout the

  11. Epithelial cell adhesion and gastrointestinal colonization of Lactobacillus in poultry.

    Science.gov (United States)

    Spivey, Megan A; Dunn-Horrocks, Sadie L; Duong, Tri

    2014-11-01

    Administration of probiotic Lactobacillus cultures is an important alternative to the use of antibiotic growth promoters and has been demonstrated to improve animal health, growth performance, and preharvest food safety in poultry production. Whereas gastrointestinal colonization is thought to be critical to their probiotic functionality, factors important to Lactobacillus colonization in chickens are not well understood. In this study we investigate epithelial cell adhesion in vitro and colonization of Lactobacillusin vivo in broiler chickens. Adhesion of Lactobacillus cultures to epithelial cells was evaluated using the chicken LMH cell line. Lactobacillus cultures were able adhere effectively to LMH cells relative to Bacillus subtilis and Salmonella Typhimurium. Epithelial cell adhesion was similar for Lactobacillus crispatus TDCC 75, L. cristpatus TDCC 76, and Lactobacillus gallinarum TDCC 77, and all 3 were more adherent than L. gallinarum TDCC 78. However, when colonization was evaluated in the ileum and cecum of broiler chicks, L. crispatus TDCC 75 and L. gallinarum TDCC 77 were more persistent than L. crispatus TDCC 76 and L. gallinarum TDCC 78. The reduction of growth in medium supplemented with oxgal was greater for L. gallinarum TDCC 78 than L. gallinarum TDCC 77, suggesting that whereas adhesion was similar for the 2 strains, the difference in colonization between L. gallinarum strains may be due in part to their bile sensitivity. This study demonstrates that whereas adhesion to epithelial cells may be important in predicting gastrointestinal colonization, other factors including bile tolerance may also contribute to the colonization of Lactobacillus in poultry. Additionally, the chicken LMH cell line is expected to provide a platform for investigating mechanisms of Lactobacillus adhesion to epithelial tissue and evaluating the probiotic potential Lactobacillus in poultry.

  12. Functional Development of the Human Gastrointestinal Tract: Hormone- and Growth Factor-Mediated Regulatory Mechanisms

    Directory of Open Access Journals (Sweden)

    Daniel Ménard

    2004-01-01

    Full Text Available The present review focuses on the control of gastrointestinal (GI tract development. The first section addresses the differences in general mechanisms of GI development in humans versus rodents, highlighting that morphogenesis of specific digestive organs and the differentiation of digestive epithelia occur not only at different stages of ontogeny but also at different rates. The second section provides an overview of studies from the author's laboratory at the Université de Sherbrooke pertaining to the development of the human fetal small intestine and colon. While both segments share similar morphological and functional characteristics, they are nevertheless modulated by distinct regulatory mechanisms. Using the organ culture approach, the author and colleagues were able to establish that hormones and growth factors, such as glucocorticoids, epidermal growth factor, insulin and keratinocyte growth factor, not only exert differential effects within these two segments, they can also trigger opposite responses in comparison with animal models. In the third section, emphasis is placed on the functional development of human fetal stomach and its various epithelial cell types; in particular, the glandular chief cells responsible for the synthesis and secretion of gastric enzymes such as pepsinogen-5 and gastric lipase. Bearing in mind that limitations of available cell models have, until now, greatly impeded the comprehension of molecular mechanisms regulating human gastric epithelial cell functions, the last section focuses on new human gastric epithelial cell models recently developed in the author's laboratory. These models comprise a novel primary culture system of human fetal gastric epithelium including, for the first time, functional chief cells, and human gastric epithelium cell lines cloned from the parental NCI-N87 strain. These new cells lines could serve important applications in the study of pathogenic action and epithelial

  13. Gastrointestinal opportunistic infections in human immunodeficiency virus disease

    Directory of Open Access Journals (Sweden)

    Al Anazi Awadh

    2009-01-01

    Full Text Available Gastrointestinal (GI opportunistic infections (OIs are commonly encountered at various stages of human immunodeficiency virus (HIV disease. In view of the suppressive nature of the virus and the direct contact with the environment, the GI tract is readily accessible and is a common site for clinical expression of HIV. The subject is presented based on information obtained by electronic searches of peer-reviewed articles in medical journals, Cochrane reviews and PubMed sources. The spectrum of GI OIs ranges from oral lesions of Candidiasis, various lesions of viral infections, hepatobiliary lesions, pancreatitis and anorectal lesions. The manifestations of the disease depend on the level of immunosuppression, as determined by the CD4 counts. The advent of highly active antiretroviral therapy has altered the pattern of presentation, resorting mainly to features of antimicrobial-associated colitis and side effects of antiretroviral drugs. The diagnosis of GI OIs in HIV/ acquired immunodeficiency syndrome patients is usually straightforward. However, subtle presentations require that the physicians should have a high index of suspicion when given the setting of HIV infection.

  14. The use of BLT humanized mice to investigate the immune reconstitution of the gastrointestinal tract.

    Science.gov (United States)

    Wahl, Angela; Victor Garcia, J

    2014-08-01

    The gastrointestinal (GI) track represents an important battlefield where pathogens first try to gain entry into a host. It is also a universe where highly diverse and ever changing inhabitants co-exist in an exceptional equilibrium without parallel in any other organ system of the body. The gut as an organ has its own well-developed and fully functional immune organization that is similar and yet different in many important ways to the rest of the immune system. Both a compromised and an overactive immune system in the gut can have dire and severe consequences to human health. It has therefore been of great interest to develop animal models that recapitulate key aspects of the human condition to better understand the interplay of the host immune system with its friends and its foes. However, reconstitution of the GI tract in humanized mice has been difficult and highly variable in different systems. A better molecular understanding of the development of the gut immune system in mice has provided critical cues that have been recently used to develop novel humanized mouse models that fully recapitulate the genesis and key functions of the gut immune system of humans. Of particular interest is the presence of human gut-associated lymphoid tissue (GALT) aggregates in the gut of NOD/SCID BLT humanized mice that demonstrate the faithful development of bona fide human plasma cells capable of migrating to the lamina propria and producing human IgA1 and IgA2.

  15. Enteric glial cells and their role in gastrointestinal motor abnormalities: Introducing the neuro-gliopathies

    Institute of Scientific and Technical Information of China (English)

    Gabrio Bassotti; Vincenzo Villanacci; Simona Fisogni; Elisa Rossi; Paola Baronio; Carlo Clerici; Christoph A Maurer; Gieri Cathomas; Elisabetta Antonelli

    2007-01-01

    The role of enteric glial cells has somewhat changed from that of mere mechanical support elements, gluing together the various components of the enteric nervous system, to that of active participants in the complex interrelationships of the gut motor and inflammatory events. Due to their multiple functions, spanning from supporting elements in the myenteric plexuses to neurotransmitters, to neuronal homeostasis, to antigen presenting cells, this cell population has probably more intriguing abilities than previously thought. Recently,some evidence has been accumulating that shows how these cells may be involved in the pathophysiological aspects of some diseases. This review will deal with the properties of the enteric glial cells more strictly related to gastrointestinal motor function and the human pathological conditions in which these cells may play a role, suggesting the possibility of enteric neurogliopathies.

  16. Synergistic anti-proliferative effects of gambogic acid with docetaxel in gastrointestinal cancer cell lines

    Directory of Open Access Journals (Sweden)

    Zou Zhengyun

    2012-04-01

    Full Text Available Summary Background Gambogic acid has a marked anti-tumor effect for gastric and colorectal cancers in vitro and in vivo. However, recent investigations on gambogic acid have focused mainly on mono-drug therapy, and its potential role in cancer therapy has not been comprehensively illustrated. This study aimed to assess the interaction between gambogic acid and docetaxel on human gastrointestinal cancer cells and to investigate the mechanism of gambogic acid plus docetaxel treatment-induced apoptotic cell death. Methods MTT assay was used to determine IC50 values in BGC-823, MKN-28, LOVO and SW-116 cells after gambogic acid and docetaxel administration. Median effect analysis was applied for determination of synergism and antagonism. Synergistic interaction between gambogic acid and docetaxel was evaluated using the combination index (CI method. Furthermore, cellular apoptosis was analyzed by Annexin-V and propidium iodide (PI double staining. Additionally, mRNA expression of drug-associated genes, i.e., β-tublin III and tau, and the apoptosis-related gene survivin, were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR. Results Gambogic acid provided a synergistic effect on the cytotoxicity induced by docetaxel in all four cell lines. The combined application of gambogic acid and docetaxel enhanced apoptosis in gastrointestinal cancer cells. Moreover, gambogic acid markedly decreased the mRNA expression of docetaxel-related genes, including β-tubulin III, tau and survivin, in BGC-823 cells. Conclusions Gambogic acid plus docetaxel produced a synergistic anti-tumor effect in gastrointestinal cancer cells, suggesting that the drug combination may offer a novel treatment option for patients with gastric and colorectal cancers.

  17. Human in vivo and in vitro studies on gastrointestinal absorption of titanium dioxide nanoparticles.

    Science.gov (United States)

    Jones, Kate; Morton, Jackie; Smith, Ian; Jurkschat, Kerstin; Harding, Anne-Helen; Evans, Gareth

    2015-03-04

    The study was designed to conduct human in vivo and in vitro studies on the gastrointestinal absorption of nanoparticles, using titanium dioxide as a model compound, and to compare nanoparticle behaviour with that of larger particles. A supplier's characterisation data may not fully describe a particle formulation. Most particles tested agreed with their supplied characterisation when assessed by particle number but significant proportions of 'nanoparticle formulations' were particles >100nm when assessed by particle weight. Oral doses are measured by weight and it is therefore important that the weight characterisation is taken into consideration. The human volunteer studies demonstrated that very little titanium dioxide is absorbed gastrointestinally after an oral challenge. There was no demonstrable difference in absorption for any of the three particle sizes tested. All tested formulations were shown to agglomerate in simulated gastric fluid, particularly in the smaller particle formulations. Further agglomeration was observed when dispersing formulations in polymeric or elemental foods. Virtually no translocation of titanium dioxide particles across the cell layer was demonstrated. This study found no evidence that nanoparticulate titanium dioxide is more likely to be absorbed in the gut than micron-sized particles.

  18. The possible role of gastrointestinal endocrine cells in the pathophysiology of irritable bowel syndrome.

    Science.gov (United States)

    El-Salhy, Magdy; Hausken, Trygve; Gilja, Odd Helge; Hatlebakk, Jan Gunnar

    2017-02-01

    The etiology of irritable bowel syndrome (IBS) is unknown, but several factors appear to play a role in its pathophysiology, including abnormalities of the gastrointestinal endocrine cells. The present review illuminates the possible role of gastrointestinal hormones in the pathophysiology of IBS and the possibility of utilizing the current knowledge in treating the disease. Areas covered: Research into the intestinal endocrine cells and their possible role in the pathophysiology of IBS is discussed. Furthermore, the mechanisms underlying the abnormalities in the gastrointestinal endocrine cells in IBS patients are revealed. Expert commentary: The abnormalities observed in the gastrointestinal endocrine cells in IBS patients explains their visceral hypersensitivity, gastrointestinal dysmotility, and abnormal intestinal secretion, as well as the interchangeability of symptoms over time. Clarifying the role of the intestinal stem cells in the pathophysiology of IBS may lead to new treatment methods for IBS.

  19. Gastrointestinal osmoreceptors and renal sodium excretion in humans

    DEFF Research Database (Denmark)

    Andersen, L J; Skram, Thomas Ulrik; Bestle, M H;

    2000-01-01

    The hypothesis that natriuresis can be induced by stimulation of gastrointestinal osmoreceptors was tested in eight supine subjects on constant sodium intake (150 mmol NaCl/day). A sodium load equivalent to the amount contained in 10% of measured extracellular volume was administered by a nasogas......The hypothesis that natriuresis can be induced by stimulation of gastrointestinal osmoreceptors was tested in eight supine subjects on constant sodium intake (150 mmol NaCl/day). A sodium load equivalent to the amount contained in 10% of measured extracellular volume was administered......-angiotensin system....

  20. The human gastrointestinal microbiota - An unexplored frontier for pharmaceutical discovery

    NARCIS (Netherlands)

    Roeselers, G.; Bouwman, J.; Venema, K.; Montijn, R.

    2012-01-01

    The mammalian gastrointestinal tract (GIT) harbors microorganisms (the microbiota) of vast phylogentic, genomic, and metabolic diversity, and recent years have seen a rapid development in the techniques for studying these complex microbial ecosystems. It is increasingly apparent that the GIT microbi

  1. Incidental detection of a bleeding gastrointestinal stromal tumor on Tc-99m red blood cell scintigraphy.

    Science.gov (United States)

    Santhosh, Sampath; Bhattacharya, Anish; Gupta, Vikas; Singh, Rajinder; Radotra, Bishan Dass; Mittal, Bhagwant Rai

    2012-10-01

    The role of 99m-technetium labeled red blood cell (RBC) scintigraphy in acute gastro-intestinal bleed is well-established. The authors report a case of a bleeding gastrointestinal stromal tumor (GIST) incidentally discovered on Tc-99m RBC scintigraphy.

  2. Pancreatic Perivascular Epithelioid Cell Tumour Presenting with Upper Gastrointestinal Bleeding

    Directory of Open Access Journals (Sweden)

    Christos Petrides

    2015-01-01

    Full Text Available PEComa is a family of rare mesenchymal tumours which can occur in any part of the human body. Primary PEComas of the pancreas are extremely rare tumours with uncertain malignant potential. A 17-year-old female was admitted to the hospital due to melena. She required several transfusions. CT scan demonstrated a mass at the head of the pancreas measuring 4.2 cm in maximum diameter. An endoscopic ultrasound showed an ulcerating malignant looking mass infiltrating 50% of the wall of the second part of the duodenum in the region of the ampulla. Multiple biopsies taken showed extensive ulceration with granulation tissue formation and underlying large macrophages without being able to establish a definite diagnosis. We proceeded with pylorus-preserving pancreaticoduodenectomy. The postoperative course of the patient was unremarkable, and she was discharged on the 8th postoperative day. Histology examination of the specimen showed a PEComa of pancreas. Eighteen months after resection the patient is disease free. To the best of our knowledge this is the first time we describe a case of a pancreatic PEComa presenting with massive gastrointestinal bleeding.

  3. MicroRNAs dynamically remodel gastrointestinal smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Chanjae Park

    Full Text Available Smooth muscle cells (SMCs express a unique set of microRNAs (miRNAs which regulate and maintain the differentiation state of SMCs. The goal of this study was to investigate the role of miRNAs during the development of gastrointestinal (GI SMCs in a transgenic animal model. We generated SMC-specific Dicer null animals that express the reporter, green fluorescence protein, in a SMC-specific manner. SMC-specific knockout of Dicer prevented SMC miRNA biogenesis, causing dramatic changes in phenotype, function, and global gene expression in SMCs: the mutant mice developed severe dilation of the intestinal tract associated with the thinning and destruction of the smooth muscle (SM layers; contractile motility in the mutant intestine was dramatically decreased; and SM contractile genes and transcriptional regulators were extensively down-regulated in the mutant SMCs. Profiling and bioinformatic analyses showed that SMC phenotype is regulated by a complex network of positive and negative feedback by SMC miRNAs, serum response factor (SRF, and other transcriptional factors. Taken together, our data suggest that SMC miRNAs are required for the development and survival of SMCs in the GI tract.

  4. C-kit gene mutation in human gastrointestinal stromal tumors

    Institute of Scientific and Technical Information of China (English)

    Ying-Yong Hou; Ai-Hua Zheng; Tai-Ming Zhang; Wen-Zhong Hou; Jian Wang; Xiang Du; Xiong-Zeng Zhu; Yun-Shan Tan; Meng-Hong Sun; Yong-Kun Wei; Jian-Fang Xu; Shao-Hua Lu; Su-Jie A-Ke-Su; Yan-Nan Zhou; Feng Gao

    2004-01-01

    AIM: To investigate the significance of c-kit gene mutation in gastrointestinal stromal tumors (GIST).METHODS: Fifty two cases of GIST and 28 cases of other tumors were examined. DNA samples were extracted from paraffin sections and fresh blocks. Exons 11, 9 and 13 of the c-kit gene were amplified by PCR and sequenced.RESULTS: Mutations of exon 11 were found in 14 of 25 malignant GISTs (56%), mutations of exon 11 of the c-kit gene were revealed in 2 of 19 borderline GISTs (10.5%),and no mutation was found in benign tumors. The mutation rate showed significant difference (X2=14.39, P<0.01)between malignant and benign GISTs. Most of mutations consisted of the in-frame deletion or replication from 3 to 48 bp in heterozygous and homozygous fashions, None of the mutations disrupted the downstream reading frame of the gene. Point mutations and frame deletions were most frequently observed at codons 550-560, but duplications were most concentrated at codons 570-585. No mutations of exons 9 and 13 were revealed in GISTs, Neither c-kit gene expression nor gene mutations were found in 3 leiomyomas, 8 leiomyosarcomas, 2 schwannomas, 2malignant peripheral nerve sheath tumors, 2 intraabdominal fibromatoses, 2 malignant fibrous histiocytomas and 9 adenocarcinomas.CONCLUSION: C-kit gene mutations occur preferentially in malignant GISTs and might be a clinically useful adjunct marker in the evaluation of GISTs and can help to differentiate GISTs from other mesenchymal tumors of gastrointestinal tract, such as smooth muscle tumors,schwannomas, etc.

  5. Analyzing global gene expression of Lactobacillus plantarum in the human gastrointestinal tract

    NARCIS (Netherlands)

    Vries, de M.C.

    2006-01-01

    The human gastrointestinal (GI)-tract represents a dynamic ecosystem comprising various habitats each with niche-specific microbial communites, collectively called microbiota. Lactic acid bacteria (LAB) are considered to be a large group of the microbiota in the upper GI-tract that is involved in he

  6. Behaviour of silver nanoparticles and silver ions in an in vitro human gastrointestinal digestion model

    NARCIS (Netherlands)

    Walczak, A.P.; Fokkink, R.G.; Peters, R.J.B.; Tromp, P.; Herrera Rivera, Z.E.; Rietjens, I.M.C.M.; Hendriksen, P.J.M.; Bouwmeester, H.

    2013-01-01

    Oral ingestion is an important exposure route for silver nanoparticles (AgNPs), but their fate during gastrointestinal digestion is unknown. This was studied for 60 nm AgNPs and silver ions (AgNO3) using in vitro human digestion model. Samples after saliva, gastric and intestinal digestion were

  7. Measurement of Gastrointestinal and Colonic Motor Functions in Humans and Animals

    OpenAIRE

    Camilleri, Michael; Linden, David R

    2016-01-01

    Accurately measuring the complex motor behaviors of the gastrointestinal tract has tremendous value for the understanding, diagnosis and treatment of digestive diseases. This review synthesizes the literature regarding current tests that are used in both humans and animals. There remains further opportunity to enhance such tests, especially when such tests are able to provide value in both the preclinical and the clinical settings.

  8. Isolation of DNA from bacterial samples of the human gastrointestinal tract

    NARCIS (Netherlands)

    Zoetendal, E.G.; Heilig, G.H.J.; Klaassens, E.S.; Booijink, C.C.G.M.; Kleerebezem, M.; Smidt, H.; Vos, de W.M.

    2006-01-01

    The human gastrointestinal (GI) tract contains a complex microbial community that develops in time and space. The most widely used approaches to study microbial diversity and activity are all based on the analysis of nucleic acids, DNA, rRNA and mRNA. Here, we present a DNA isolation protocol that i

  9. Analyzing global gene expression of Lactobacillus plantarum in the human gastrointestinal tract

    NARCIS (Netherlands)

    Vries, de M.C.

    2006-01-01

    The human gastrointestinal (GI)-tract represents a dynamic ecosystem comprising various habitats each with niche-specific microbial communites, collectively called microbiota. Lactic acid bacteria (LAB) are considered to be a large group of the microbiota in the upper GI-tract that is involved in he

  10. Gastrointestinal Physiology During Head Down Tilt Bedrest in Human Subjects

    Science.gov (United States)

    Vaksman, Z.; Guthienz, J.; Putcha, L.

    2008-01-01

    Introduction: Gastrointestinal (GI) motility plays a key role in the physiology and function of the GI tract. It directly affects absorption of medications and nutrients taken by mouth, in addition to indirectly altering GI physiology by way of changes in the microfloral composition and biochemistry of the GI tract. Astronauts have reported nausea, loss of appetite and constipation during space flight all of which indicate a reduction in GI motility and function similar to the one seen in chronic bed rest patients. The purpose of this study is to determine GI motility and bacterial proliferation during -6 degree head down tilt bed rest (HTD). Methods: Healthy male and female subjects between the ages of 25-40 participated in a 60 day HTD study protocol. GI transit time (GITT) was determined using lactulose breath hydrogen test and bacterial overgrowth was measured using glucose breath hydrogen test. H. Pylori colonization was determined using C13-urea breath test (UBIT#). All three tests were conducted on 9 days before HDT, and repeated on HDT days 2, 28, 58, and again on day 7 after HDT. Results: GITT increased during HTD compared to the respective ambulatory control values; GITT was significantly lower on day 7 after HTD. A concomitant increase in bacterial colonization was also noticed during HDT starting after approximately 28 days of HDT. However, H. Pylori proliferation was not recorded during HDT as indicated by UBIT#. Conclusion: GITT significantly decreased during HDT with a concomitant increase in the proliferation of GI bacterial flora but not H. pylori.

  11. A piglet model for studying Candida albicans colonization of the human oro-gastrointestinal tract.

    Science.gov (United States)

    Hoeflinger, Jennifer L; Coleman, David A; Oh, Soon-Hwan; Miller, Michael J; Hoyer, Lois L

    2014-08-01

    Pigs from a variety of sources were surveyed for oro-gastrointestinal (oro-GIT) carriage of Candida albicans. Candida albicans-positive animals were readily located, but we also identified C. albicans-free pigs. We hypothesized that pigs could be stably colonized with a C. albicans strain of choice, simply by feeding yeast cells. Piglets were farrowed routinely and remained with the sow for 4 days to acquire a normal microbiota. Piglets were then placed in an artificial rearing environment and fed sow milk replacer. Piglets were inoculated orally with one of three different C. albicans strains. Piglets were weighed daily, and culture swabs were collected to detect C. albicans orally, rectally and in the piglet's environment. Stable C. albicans colonization over the course of the study did not affect piglet growth. Necropsy revealed mucosally associated C. albicans throughout the oro-GIT with the highest abundance in the esophagus. Uninoculated control piglets remained C. albicans-negative. These data establish the piglet as a model to study C. albicans colonization of the human oro-GIT. Similarities between oro-GIT colonization in humans and pigs, as well as the ease of working with the piglet model, suggest its adaptability for use among investigators interested in understanding C. albicans-host commensal interactions.

  12. Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humans

    DEFF Research Database (Denmark)

    Falkén, Y; Hellström, P M; Sanger, G J

    2010-01-01

    Ghrelin is produced by enteroendocrine cells in the gastric mucosa and stimulates gastric emptying in healthy volunteers and patients with gastroparesis in short-term studies. The aim of this study was to evaluate effects of intravenous ghrelin on gastrointestinal motility and glucose homeostasis...

  13. Orthotopic transplantation model of human gastrointestinal cancer and detection of micrometastases

    Institute of Scientific and Technical Information of China (English)

    Jun Hui Cui; Uwe Krueger; Doris Henne-Bruns; Bernd Kremer; Holger Kalthoff

    2001-01-01

    AIM To establish a relevant animal model ofhuman gastrointestinal cancer, which can beused for repetitive investigations, so as toimprove our understanding and management ofcarcinogenesis and cancer metastasis.METHODS Intact tissues of human colorectaland pancreatic cancers were transplanted innude mice. The biological characteristics of theoriginal and the corresponding transplantedtumors were investigated by HE staining, PASstaining and immunostaining. The metastases inthe livers and lungs of nude mice wereinvestigated by immunostaining withbiotinylated mab KL-1 and by RT-PCR using CK20specific primers.RESULTS There were totally 9 of 16 surgicalspecimens growing in nude mice subcutaneouslyand/.or orthotopically (4 of 6 colorectal and 5 of10 pancreatic cancer). Tumor cell content of thespecimens and freezing of tissue specimens areimportant factors influencing the growth oftransplanted tumor. In the group of fresh tumortissues with greater than 50% tumor cellcontent, the success rate of the transplantationwas 100% (3 cases of pancreatic cancer and 3cases of colorectal cancer). The orthotopicallytransplanted tumors resemble the original tumormorphologically and biologically, including TAAexpression such as CEA byimmunohistochemistry, and CEA level in theserum of mice. Ki-67 labeling index and theexpression of TAA especially K-ras, 17-lA andRA-96, are associated with the potential of tumorgrowth in nude mice. Micrometastases in thelungs and livers of tumor bearing mice can bedetected by immunostaining with biotinylatedmab KL-1 and CK20-specific RT-PCR.CONCLUSION An orthotopic transplantationmodel for human colon and pancreatic cancer innude mice has been set up. We have alsoestablished sensitive detection methods withCK-immunohistochemistry and CK20-RT-PCR tostudy xenotransplanted human cancer and itsmetastatic cancer cells in the liver and lung ofnude mice. This study may be helpful inunderstanding the mechanism of cancermetastasis and in developing new

  14. Human milk glycobiome and its impact on the infant gastrointestinal microbiota

    OpenAIRE

    Zivkovic, Angela M.; German, J. Bruce; Lebrilla, Carlito B.; David A. Mills

    2010-01-01

    Human milk contains an unexpected abundance and diversity of complex oligosaccharides apparently indigestible by the developing infant and instead targeted to its cognate gastrointestinal microbiota. Recent advances in mass spectrometry-based tools have provided a view of the oligosaccharide structures produced in milk across stages of lactation and among human mothers. One postulated function for these oligosaccharides is to enrich a specific “healthy” microbiota containing bifidobacteria, a...

  15. Innate lymphoid cells and natural killer T cells in the gastrointestinal tract immune system

    Directory of Open Access Journals (Sweden)

    Enrique Montalvillo

    2014-05-01

    Full Text Available The gastrointestinal tract is equipped with a highly specialized intrinsic immune system. However, the intestine is exposed to a high antigenic burden that requires a fast, nonspecific response -so-called innate immunity- to maintain homeostasis and protect the body from incoming pathogens. In the last decade multiple studies helped to unravel the particular developmental requirements and specific functions of the cells that play a role in innate immunity. In this review we shall focus on innate lymphoid cells, a newly discovered, heterogeneous set of cells that derive from an Id2-dependent lymphoid progenitor cell population. These cells have been categorized on the basis of the pattern of cytokines that they secrete, and the transcription factors that regulate their development and functions. Innate lymphoid cells play a role in the early response to pathogens, the anatomical contention of the commensal flora, and the maintenance of epithelial integrity. Amongst the various innate lymphoid cells we shall lay emphasis on a subpopulation with several peculiarities, namely that of natural killer T cells, a subset of T lymphocytes that express both T-cell and NK-cell receptors. The most numerous fraction of the NKT population are the so-called invariant NKT or iNKT cells. These iNKT cells have an invariant TCR and recognize the glycolipidic structures presented by the CD1d molecule, a homolog of class-I MHC molecules. Following activation they rapidly acquire cytotoxic activity and secrete both Th1 and Th2 cytokines, including IL-17. While their specific role is not yet established, iNKT cells take part in a great variety of intestinal immune responses ranging from oral tolerance to involvement in a number of gastrointestinal conditions.

  16. Innate lymphoid cells and natural killer T cells in the gastrointestinal tract immune system.

    Science.gov (United States)

    Montalvillo, Enrique; Garrote, José Antonio; Bernardo, David; Arranz, Eduardo

    2014-05-01

    The gastrointestinal tract is equipped with a highly specialized intrinsic immune system. However, the intestine is exposed to a high antigenic burden that requires a fast, nonspecific response -so-called innate immunity- to maintain homeostasis and protect the body from incoming pathogens. In the last decade multiple studies helped to unravel the particular developmental requirements and specific functions of the cells that play a role in innate immunity. In this review we shall focus on innate lymphoid cells, a newly discovered, heterogeneous set of cells that derive from an Id2-dependent lymphoid progenitor cell population. These cells have been categorized on the basis of the pattern of cytokines that they secrete, and the transcription factors that regulate their development and functions. Innate lymphoid cells play a role in the early response to pathogens, the anatomical contention of the commensal flora, and the maintenance of epithelial integrity.Amongst the various innate lymphoid cells we shall lay emphasis on a subpopulation with several peculiarities, namely that of natural killer T cells, a subset of T lymphocytes that express both T-cell and NK-cell receptors. The most numerous fraction of the NKT population are the so-called invariant NKT or iNKT cells. These iNKT cells have an invariant TCR and recognize the glycolipidic structures presented by the CD1d molecule, a homolog of class-I MHC molecules. Following activation they rapidly acquire cytotoxic activity and secrete both Th1 and Th2 cytokines, including IL-17. While their specific role is not yet established, iNKT cells take part in a great variety of intestinal immune responses ranging from oral tolerance to involvement in a number of gastrointestinal conditions.

  17. EFFECTS OF PERIOPERATIVE CIMETIDINE ADMINISTRATION ON NATURAL KILLER CELLS IN PATIENTS WITH GASTROINTESTINAL CANCER

    Institute of Scientific and Technical Information of China (English)

    LI Yan; BAI De-jiao; WANG Kun; YANG Guo-liang; YUAN Hong-yin; SHAO Hua

    1999-01-01

    Objective: To study the effects of perioperative use of cimetidine on natural killer (NK) cells in gastrointestinal (GI) cancer patients. Methods: 49 GI cancer patients were randomized into treatment group which took cimetidine in the perioperative period, and control group which did not take the drug. NK cells were measured by immunocytochemical method, using mouse-anti-human CD57 monoclonal antibody as the primary antibody. Blood samples from 20 healthy volunteers were treated in the same way as normal control. Comparisons were made within and between groups. Results: The NK cell percentage of normal control was 18.50±2.31. Both groups of patients had significantly lower than normal NK percentages before treatment (P<0.05). NK cell percentages at admission,before operation, on the 2nd and the 10th postoperative days were 14.60±3.91, 15.64±3.61, 17.40±3.28, 20.68±4.13, respectively, for the treatment group, and 14.88±2.76, 13.17±2.93, 14.50±2.77, 15.67±2.55, respectively,for control group. The difference between the two groups was statistically significant. Conclusion: Perioperative cimetidine application can help restore NK cells. The drug may be useful to reverse postoperative immuno-depression in GI cancer patients.

  18. Transcriptional silencing of Dickkopf gene family by CpG island hypermethylation in human gastrointestinal cancer

    Institute of Scientific and Technical Information of China (English)

    Tadateru Maehata; Fumio Itoh; Hiroaki Taniguchi; Hiroyuki Yamamoto; Katsuhiko Nosho; Yasushi Adachi; Nobuki Miyamoto; Chic Miyamoto; Noriyuki Akutsu; Satoshi Yamaoka

    2008-01-01

    AIM:To clarify alterations of Dickkopfs (Dkks) and Kremen2 (Krm2) in gastrointestinal cancer.METHODS:We investigated the expression profiles and epigenetic alterations of Dkks and Krm2 genes in gastrointestinal cancer using RT-PCR,tissue microarray analysis,and methylation specific PCR (MSP).Cancer cells were treated with the demethylating agent and/or histone deacetylase inhibitor.WST-8 assays and in vitro invasion assays after treatment with specific siRNA for those genes were performed.RESULTS:Dkks and Krm2 expression levels were reduced in a certain subset of the gastrointestinal cancer cell lines and cancer tissues.This was correlated with promoter hypermethylation.There were significant correlations between Dkks over-expression levels and beta-catenin over-expression in colorectal cancer.In colorectal cancers with beta-catenin over-expression,Dkk-1 expression levels were significantly lower in those with lymph node metastases than in those without.Down-regulation of Dkks expression by siRNA resulted in a significant increase in cancer cell growth and invasiveness in vitro.CONCLUSION:Down-regulation of the Dkks associated to promoter hypermethylation appears to be frequently involved in gastrointestinal tumorigenesis.

  19. Relevance of Bifidobacterium animalis subsp. lactis Plasminogen Binding Activity in the Human Gastrointestinal Microenvironment ▿

    Science.gov (United States)

    Candela, Marco; Turroni, Silvia; Centanni, Manuela; Fiori, Jessica; Bergmann, Simone; Hammerschmidt, Sven; Brigidi, Patrizia

    2011-01-01

    Human plasmin(ogen) is regarded as a component of the molecular cross talk between the probiotic species Bifidobacterium animalis subsp. lactis and the human host. However, up to now, only in vitro studies have been reported. Here, we demonstrate that the probiotic strain B. animalis subsp. lactis BI07 is capable of recruiting plasmin(ogen) present at physiological concentrations in crude extracts from human feces. Our results provide evidence that supports the significance of the B. lactis-plasmin(ogen) interaction in the human gastrointestinal tract. PMID:21821753

  20. Relevance of Bifidobacterium animalis subsp. lactis plasminogen binding activity in the human gastrointestinal microenvironment.

    Science.gov (United States)

    Candela, Marco; Turroni, Silvia; Centanni, Manuela; Fiori, Jessica; Bergmann, Simone; Hammerschmidt, Sven; Brigidi, Patrizia

    2011-10-01

    Human plasmin(ogen) is regarded as a component of the molecular cross talk between the probiotic species Bifidobacterium animalis subsp. lactis and the human host. However, up to now, only in vitro studies have been reported. Here, we demonstrate that the probiotic strain B. animalis subsp. lactis BI07 is capable of recruiting plasmin(ogen) present at physiological concentrations in crude extracts from human feces. Our results provide evidence that supports the significance of the B. lactis-plasmin(ogen) interaction in the human gastrointestinal tract.

  1. Interstitial cells of Cajal as targets for pharmacological intervention in gastrointestinal motor disorders

    DEFF Research Database (Denmark)

    Huizinga, J D; Thuneberg, L; Vanderwinden, J M

    1997-01-01

    Interstitial cells of Cajal (ICCs) have recently been identified as the pacemaker cells for contractile activity of the gastrointestinal tract. These cells generate the electrical 'slow-wave' activity that determines the characteristic frequency of phasic contractions of the stomach, intestine an...... through the gut organs. Here Jan Huizinga, Lars Thuneberg, Jean-Marie Vanderwinden and Jüri Rumessen, suggest that, as ICCs are unique to the gut, they might be ideal targets for pharmacological intervention in gastrointestinal motility disorders, which are very common and costly....

  2. Study of orthotopic transplantation model of human gastrointestinal cancerand detection of micrometastases

    Institute of Scientific and Technical Information of China (English)

    Jun Hui Cui; Uwe Krueger; Doris Henne-Bruns; Bernd Kremer; Holger Kalthoff

    2000-01-01

    AIM To establish a relevant animal model of human gastrointestinal cancer, which can be used forrepetitive investigations and may improve our understanding of carcinogenesis and cancer metastasis.METHODS Intact tissue of human colorectal and pancreatic cancers was transplanted in nude mice. Thebiological characteristics of the original and corresponding transplanted tumors were investigated by HEstaining, PAS staining and immunostaining. The metastases in livers and lungs of the nude mice wereinvestigated by immunostaining with biotinylated mab KL-1 and by RT-PCR using CK20 specific primers.RESULTS Nine of 16 surgical specimens grew in the nude mice subcutaneously and/or orthotopically (4 of6 colorectal and 5 of 10 pancreatic cancer). Tumor cell content of the specimens and freezing of tissuespecimens are important factors influencing the growth of transplanted tumor. In the group of fresh tumortissues with greater than 50% tumor cell content, transplantation rate was 100% (3 cases of pancreatic cancerand 3 cases of colorectal cancer). The orthotopically transplanted tumors resembled the original tumormorphologically and biologically, including TAA expression such as CEA by immunohistochemistry, andCEA level in the serum of mice. Ki-67 labeling index and the expression of TAA especially K-ras, 17-1A and RA-96, were associated with the potential of tumor growth in nude mice. Micrometastases in the lungs andlivers of tumor bearing mice could be detected by immunostaining with biotinylated mab KL-1 and CK20-sepcific RT-PCR.CONCLUSION An orthotopic transplantation model for human colon and pancreatic cancer in nude micehas been established. The sensitive detection methods with CK-immunohistochemistry and CK20-RT-PCRwere also established to study xenotransplanted human cancer and its metastatic cancer cells in the liver andlung of nude mice. This study may be helpful in understanding the mechanism of cancer metastasis and indeveloping new diagnostic methods and

  3. The role of KCNQ1 in mouse and human gastrointestinal cancers.

    Science.gov (United States)

    Than, B L N; Goos, J A C M; Sarver, A L; O'Sullivan, M G; Rod, A; Starr, T K; Fijneman, R J A; Meijer, G A; Zhao, L; Zhang, Y; Largaespada, D A; Scott, P M; Cormier, R T

    2014-07-17

    Kcnq1, which encodes for the pore-forming α-subunit of a voltage-gated potassium channel, was identified as a gastrointestinal (GI) tract cancer susceptibility gene in multiple Sleeping Beauty DNA transposon-based forward genetic screens in mice. To confirm that Kcnq1 has a functional role in GI tract cancer, we created Apc(Min) mice that carried a targeted deletion mutation in Kcnq1. Results demonstrated that Kcnq1 is a tumor suppressor gene as Kcnq1 mutant mice developed significantly more intestinal tumors, especially in the proximal small intestine and colon, and some of these tumors progressed to become aggressive adenocarcinomas. Gross tissue abnormalities were also observed in the rectum, pancreas and stomach. Colon organoid formation was significantly increased in organoids created from Kcnq1 mutant mice compared with wild-type littermate controls, suggesting a role for Kcnq1 in the regulation of the intestinal crypt stem cell compartment. To identify gene expression changes due to loss of Kcnq1, we carried out microarray studies in the colon and proximal small intestine. We identified altered genes involved in innate immune responses, goblet and Paneth cell function, ion channels, intestinal stem cells, epidermal growth factor receptor and other growth regulatory signaling pathways. We also found genes implicated in inflammation and in cellular detoxification. Pathway analysis using Ingenuity Pathway Analysis and Gene Set Enrichment Analysis confirmed the importance of these gene clusters and further identified significant overlap with genes regulated by MUC2 and CFTR, two important regulators of intestinal homeostasis. To investigate the role of KCNQ1 in human colorectal cancer (CRC), we measured protein levels of KCNQ1 by immunohistochemistry in tissue microarrays containing samples from CRC patients with liver metastases who had undergone hepatic resection. Results showed that low expression of KCNQ1 expression was significantly associated with poor

  4. Impact of pasteurization of human milk on preterm newborn in vitro digestion: Gastrointestinal disintegration, lipolysis and proteolysis.

    Science.gov (United States)

    de Oliveira, Samira C; Bourlieu, Claire; Ménard, Olivia; Bellanger, Amandine; Henry, Gwénaële; Rousseau, Florence; Dirson, Emelyne; Carrière, Frédéric; Dupont, Didier; Deglaire, Amélie

    2016-11-15

    Human milk feeding is an important recommendation for preterm newborns considering their vulnerability and digestive immaturity. Holder pasteurization (62.5°C, 30min) applied in milk banks modifies its biological quality and its microstructure. We investigated the impact of pasteurization of preterm human milk on its gastrointestinal kinetics of lipolysis, proteolysis and structural disintegration. An in vitro dynamic system was set up to simulate the gastrointestinal digestion of preterm newborns. A pool of preterm human milk was digested as raw or after Holder pasteurization. Pasteurization impacted the microstructure of undigested human milk, its gastrointestinal disintegration and tended to limit the intestinal lipolysis. Furthermore, the gastrointestinal bioaccessibility of some fatty acids was decreased by pasteurization, while the intestinal bioaccessibility of some amino acids was selectively modulated. The impact of pasteurization on the digestion of human milk may have nutritional relevance in vivo and potentially modulates preterm development and growth. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Identification and localization of soluble sulfotransferases in the human gastrointestinal tract

    OpenAIRE

    Teubner, Wera; Meinl, Walter; Florian, Simone; Kretzschmar, Michael; Glatt, Hansruedi

    2007-01-01

    Abstract Soluble sulfotransferases (SULTs) are important in the regulation of messenger molecules and the elimination of xenobiotics. However, sulfo-conjugation of various substrates can also lead to the formation of reactive metabolites that may induce cancer and cause other damage. Our aim was to identify the SULT forms expressed in the human gastrointestinal tract, especially colon and rectum (common sites for cancer) and to determine their cellular localization. Normal colonic ...

  6. Campylobacter hominis sp nov., from the human gastrointestinal tract

    DEFF Research Database (Denmark)

    Lawson, A.J.; On, Stephen L.W.; Logan, J.M.J.

    2001-01-01

    Sequences of 16S rDNA of a novel campylobacter from faeces of healthy humans were previously shown to originate from a new taxon, 'Candidatus Campylobacter hominis', which could not be cultured. Since phylogenetic analysis suggested that anaerobic conditions might be required for growth......, an isolation strategy was developed employing initial non-selective membrane filtration onto fastidious anaerobe agar. Campylobacters were then isolated from the resulting mixed microbial flora by a dilution strategy and/or by immunomagnetic separation with genus-specific polyclonal antibody. Isolates were...... identified by a genus and taxon-specific PCR assay, and 16S rDNA nucleotide sequence analysis was carried out. All isolates exhibited the typical Campylobacter characteristics of being non-fermentative, oxidase-positive, catalase-negative and Gram-negative. Unusually, however, they were straight rods lacking...

  7. Gastrointestinal Hormone Cholecystokinin Increases P-Glycoprotein Membrane Localization and Transport Activity in Caco-2 Cells.

    Science.gov (United States)

    Yano, Kentaro; Shimizu, Saori; Tomono, Takumi; Ogihara, Takuo

    2017-09-01

    It was reported that stimulation of taste receptor type 2 member 38 by a bitter substance, phenylthiocarbamide (PTC), increased P-glycoprotein (P-gp) mRNA level and transport activity via release of the gastrointestinal hormone cholecystokinin-8 (CCK-8) at 9 h. Therefore, we hypothesized that CCK-8 and PTC might also regulate P-gp activity more rapidly via a different mechanism. As a result, we found that the pretreatment of human colon adenocarcinoma (Caco-2) cells with 10-mM PTC significantly decreased the intracellular accumulation of P-gp substrate rhodamine 123 (Rho123) compared with the control after 90-min incubation. Moreover, CCK-8 treatments significantly reduced the accumulation of Rho123 within 30 min, compared with the control. On the other hand, when Caco-2 cells were pretreated with PTC, the efflux ratio of Rho123 was significantly increased compared with control. The efflux ratio of Rho123 in CCK-8 treatment cells was also significantly increased compared with control. Furthermore, CCK-8 increased the phosphorylation of the scaffold proteins ezrin, radixin, and moesin, which regulate translocation of P-gp to the plasma membrane. Therefore, our results indicate that PTC induced release of CCK-8, which in turn induced the phosphorylation of ezrin, radixin, and moesin proteins, leading to upregulation of P-gp transport activity via increased membrane localization of P-gp. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  8. Reactive oxygen species and antioxidant defense in human gastrointestinal diseases

    Directory of Open Access Journals (Sweden)

    Peter Patlevič

    2016-12-01

    Full Text Available Crohn's disease and ulcerative colitis, known together as inflammatory bowel diseases (IBDs, and celiac disease are the most common disorders affecting not only adults but also children. Both IBDs and celiac disease are associated with oxidative stress, which may play a significant role in their etiologies. Reactive oxygen species (ROS such as superoxide radicals (O2·−, hydroxyl radicals (·−OH, hydrogen peroxide (H2O2, and singlet oxygen (1O2 are responsible for cell death via oxidation of DNA, proteins, lipids, and almost any other cellular constituent. To protect biological systems from free radical toxicity, several cellular antioxidant defense mechanisms exist to regulate the production of ROS, including enzymatic and nonenzymatic pathways. Superoxide dismutase catalyzes the dismutation of O2·− to H2O2 and oxygen. The glutathione redox cycle involves two enzymes: glutathione peroxidase, which uses glutathione to reduce organic peroxides and H2O2; and glutathione reductase, which reduces the oxidized form of glutathione with concomitant oxidation of nicotinamide adenine dinucleotide phosphate. In addition to this cycle, GSH can react directly with free radicals. Studies into the effects of free radicals and antioxidant status in patients with IBDs and celiac disease are scarce, especially in pediatric patients. It is therefore very necessary to conduct additional research studies to confirm previous data about ROS status and antioxidant activities in patients with IBDs and celiac disease, especially in children.

  9. Unusual Upper Gastrointestinal Bleeding due to Late Metastasis from Renal Cell Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Wen-Tsan Chang

    2004-03-01

    Full Text Available A case of recurrent massive upper gastrointestinal bleeding originating from metastatic renal cell carcinoma is reported. A 63-year-old woman underwent right nephrectomy 9 years previously and experienced no recurrence during follow-up. A gradually enlarging ulcerative tumor over the bulb of the duodenum and four subsequent episodes of massive bleeding from this tumor occurred between June 2001 and March 2002. The patient underwent surgery in April 2002 for intractable bleeding from the tumor. Renal cell carcinoma metastasis to the duodenum was confirmed from the surgical specimen. Upper gastrointestinal bleeding due to malignancy is very rare and the duodenum is the least frequently involved site. Furthermore, a solitary late renal cell carcinoma metastasis 9 years after a nephrectomy is extremely uncommon. This case suggests that life-long follow-up of renal cell carcinoma patients is necessary, owing to unpredictable behavior and the possibility of long disease-free intervals. In nephrectomized patients suffering from gastrointestinal bleeding, complete evaluation, especially endoscopic examination, is indicated. The possibility of late recurrent renal cell carcinoma metastasis to the gastrointestinal tract should be kept in mind, although it is rare. If the patient is fit for surgery, metastatectomy is the first choice of treatment.

  10. Gastrointestinal toxicity, systemic inflammation, and liver biochemistry in allogeneic hematopoietic stem cell transplantation

    Science.gov (United States)

    Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between liver toxicity, gastrointestinal toxicity, and levels of immune-r...

  11. Gastrointestinal toxicity, systemic inflammation, and liver biochemistry in allogeneic hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Jordan, Karina; Pontoppidan, Peter; Uhlving, Hilde Hylland

    2017-01-01

    Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between liver toxicity, gastrointestinal toxicity, and levels of immun...

  12. Perivascular epithelioid cell tumor of gastrointestinal tract: case report and review of the literature

    NARCIS (Netherlands)

    Lu, B.; Wang, C.; Zhang, Junxiao; Kuiper, R.P.; Song, M.; Zhang, X.; Song, S.; Geurts van Kessel, A.; Iwamoto, A.; Wang, J; Liu, H.

    2015-01-01

    Perivascular epithelioid cell tumors of gastrointestinal tract (GI PEComas) are exceedingly rare, with only a limited number of published reports worldwide. Given the scarcity of GI PEComas and their relatively short follow-up periods, our current knowledge of their biologic behavior, molecular gene

  13. Investigation of T-cell receptor-γ gene rearrangement in gastrointestinal lymphomas by PCR-SSCP analysis

    Institute of Scientific and Technical Information of China (English)

    Xi-Qun Han; Li He; Lan-Ying Shong; Hui-Yong Jiang; Mei-Gang Zhu; Tong Zhao

    2004-01-01

    AIM: To analyze the characterization of T-cell receptor-γ (TCR-γ) gene rearrangement in the gastrointestinal lymphomas and evaluate the value of PCR-SSCP analysis in gastrointestinal lymphomas investigation.METHODS: TCR-γgene rearrangement segments of gastrointestinal lymphomas were cloned and sequenced.Single clone plasmid and mixed clone plsamids were subsequently submitted to PCR-SSCP analysis to investigate the relationship between the number of amplified clones and band patterns of the amplified products. The PCR products of TCR-γgene rearrangement of 40 gastrointestinal lymphomas were electrophoresed on agarose gels and the positive cases on agarose gels were studied by SSCP analysis.RESULTS: The sequencing showed that TCR-γ gene rearrangement of the gastrointestinal lymphomas included functional gene and pseudogene with extensive variety in the junctional regions. In SSCP analysis, the number of the single-stranded bands was about two times of the number of amplified clones, and double-stranded band became broad with the increased number of the amplified clones. Thirteen of the 25 B-cell gastrointestinal lymphomas and 14 of the 15 gastrointestinal T-cell lymphomas were positive detected on agarose gel electrophoresis. Of the positive cases detected by SSCP analysis, 3 B-cell lymphomas and 13 T-cell lymphomas showed positive bands. The other cases showed only smears. The rearranged pattern included 13 monoallelic gene rearrangements and 3 biallelic or oligoclonal gene rearrangements.CONCLUSION: The pattern of TCR-γ, gene rearrangement in gastrointestinal lymphomas are similar to that of the nodular lymphomas. PCR-SSCP analysis for TCR-γ gene rearrangement can be applied both for adjuvant diagnosis of gastrointestinal lymphomas and analysis of the gene rearrangement pattern. The ratio of TCR-γ gene rearrangements occurred in T-cell gastrointestinal lymphomas is significantly higher than that in B-cell gastrointestinal lymphomas. The gene rearrangement

  14. Reactivating effect of levamisole on cell-mediated immunity in gastrointestinal cancer patients

    Directory of Open Access Journals (Sweden)

    Miwa,Hiroaki

    1977-10-01

    Full Text Available Cell-mediated immunity was studied in 23 cases of advanced gastrointestinal cancer. The patients received levamisole at 150 mg/day for three consecutive days each week for four weeks. In cases at the terminal stage of gastrointestinal cancer, the blastformation rate of peripheral blood lymphocytes against phytohemagglutinin (PHA after the administration of levamisole showed a slight increase, but cases with blastformation rates over 40% increased markedly three or four weeks after the initial administration of levamisole. The peripheral blood lymphocyte count showed little change in these cases.

  15. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract.

    Science.gov (United States)

    Brenchley, Jason M; Schacker, Timothy W; Ruff, Laura E; Price, David A; Taylor, Jodie H; Beilman, Gregory J; Nguyen, Phuong L; Khoruts, Alexander; Larson, Matthew; Haase, Ashley T; Douek, Daniel C

    2004-09-20

    The mechanisms underlying CD4(+) T cell depletion in human immunodeficiency virus (HIV) infection are not well understood. Comparative studies of lymphoid tissues, where the vast majority of T cells reside, and peripheral blood can potentially illuminate the pathogenesis of HIV-associated disease. Here, we studied the effect of HIV infection on the activation and depletion of defined subsets of CD4(+) and CD8(+) T cells in the blood, gastrointestinal (GI) tract, and lymph node (LN). We also measured HIV-specific T cell frequencies in LNs and blood, and LN collagen deposition to define architectural changes associated with chronic inflammation. The major findings to emerge are the following: the GI tract has the most substantial CD4(+) T cell depletion at all stages of HIV disease; this depletion occurs preferentially within CCR5(+) CD4(+) T cells; HIV-associated immune activation results in abnormal accumulation of effector-type T cells within LNs; HIV-specific T cells in LNs do not account for all effector T cells; and T cell activation in LNs is associated with abnormal collagen deposition. Taken together, these findings define the nature and extent of CD4(+) T cell depletion in lymphoid tissue and point to mechanisms of profound depletion of specific T cell subsets related to elimination of CCR5(+) CD4(+) T cell targets and disruption of T cell homeostasis that accompanies chronic immune activation.

  16. Interstitial cells in the musculature of the gastrointestinal tract: Cajal and beyond

    DEFF Research Database (Denmark)

    Rumessen, Jüri J; Vanderwinden, Jean-Marie

    2003-01-01

    Expression of the receptor tyrosine kinase KIT on cells referred to as interstitial cells of Cajal (ICC) has been instrumental during the past decade in the tremendous interest in cells in the interstitium of the smooth muscle layers of the digestive tract. ICC generate the pacemaker component...... "non-Cajal" (including the FLC and possibly also other cell types) cell types in the interstitium of the smooth musculature of the gastrointestinal tract, is proposed. Furthermore, evidence is accumulating to suggest that, as postulated by Santiago Ramon y Cajal, the concept of interstitial cells...

  17. Human development index is associated with mortality-to-incidence ratios of gastrointestinal cancers.

    Science.gov (United States)

    Hu, Qi-Da; Zhang, Qi; Chen, Wei; Bai, Xue-Li; Liang, Ting-Bo

    2013-08-28

    To identify the role of human development in the incidence and mortality rates of gastrointestinal cancers worldwide. The age-standardized incidence and mortality rates for gastrointestinal cancers, including cancers of the esophagus, stomach, pancreas, liver, gallbladder, and colorectum, were obtained from the GLOBOCAN 2008 database and United States Cancer Statistics (USCS) report. The human development index (HDI) data were calculated according to the 2011 Human Development Report. We estimated the mortality-to-incidence ratios (MIRs) at the regional and national levels, and explored the association of the MIR with development levels as measured by the HDI using a modified "drug dose to inhibition response" model. Furthermore, countries were divided into four groups according to the HDI distribution, and the MIRs of the four HDI groups were compared by one-way ANOVA followed by the Tukey-Kramer post-hoc test. State-specific MIRs in the United States were predicted from the estimated HDI using the fitted non-linear model, and were compared with the actual MIRs calculated from data in the USCS report. The worldwide incidence and mortality rates of gastrointestinal cancers were as high as 39.4 and 54.9 cases per 100000 individuals, respectively. Linear and non-linear regression analyses revealed an inverse correlation between the MIR of gastrointestinal cancers and the HDI at the regional and national levels (β < 0; P = 0.0028 for regional level and < 0.0001 for national level, ANOVA). The MIR differed significantly among the four HDI areas (very high HDI, 0.620 ± 0.033; high HDI, 0.807 ± 0.018; medium HDI, 0.857 ± 0.021; low HDI, 0.953 ± 0.011; P < 0.001, one-way ANOVA). Prediction of the MIRs for individual United States states using best-fitted non-linear models showed little deviation from the actual MIRs in the United States. Except for 28 data points (9.93% of 282), the actual MIRs of all gastrointestinal cancers were mostly located in the prediction

  18. In Vitro Culture Conditions for Maintaining a Complex Population of Human Gastrointestinal Tract Microbiota

    Directory of Open Access Journals (Sweden)

    Bong-Soo Kim

    2011-01-01

    Full Text Available A stable intestinal microbiota is important in maintaining human physiology and health. Although there have been a number of studies using in vitro and in vivo approaches to determine the impact of diet and xenobiotics on intestinal microbiota, there is no consensus for the best in vitro culture conditions for growth of the human gastrointestinal microbiota. To investigate the dynamics and activities of intestinal microbiota, it is important for the culture conditions to support the growth of a wide range of intestinal bacteria and maintain a complex microbial community representative of the human gastrointestinal tract. Here, we compared the bacterial community in three culture media: brain heart infusion broth and high- and low-carbohydrate medium with different growth supplements. The bacterial community was analyzed using denaturing gradient gel electrophoresis (DGGE, pyrosequencing and real-time PCR. Based on the molecular analysis, this study indicated that the 3% fecal inoculum in low-concentration carbohydrate medium with 1% autoclaved fecal supernatant provided enhanced growth conditions to conduct in vitro studies representative of the human intestinal microbiota.

  19. Human epididymis protein 4 immunostaining of malignant ascites differentiates cancer of Müllerian origin from gastrointestinal cancer.

    Science.gov (United States)

    Stiekema, Anna; Van de Vijver, Koen K; Boot, Henk; Broeks, Annegien; Korse, Catharina M; van Driel, Willemien J; Kenter, Gemma G; Lok, Christianne A R

    2017-03-01

    An accurate diagnosis of cancer of Müllerian origin is required before the initiation of treatment. An overlap in clinical presentation and cytological, histological, or imaging studies with other nongynecological tumors does occur. Therefore, immunocytochemistry markers are used to determine tumor origin. Human epididymis protein 4 (HE4) is overexpressed in tissue of epithelial ovarian cancer (EOC). It has shown to be a sensitive and specific serum marker for EOC and to be of value for the differentiation between EOC and ovarian metastases of gastrointestinal origin. The objective of the current study was to evaluate HE4 immunocytochemistry in malignant ascites for differentiation between cancer of Müllerian origin, including EOC, and adenocarcinomas of the gastrointestinal tract. Cytological specimens of 115 different adenocarcinomas (45 EOCs, 46 cases of gastric cancer, and 24 cases of colorectal cancer) were stained for HE4, paired box 8 (PAX8), and other specific markers. 91% of the ascites samples from patients with EOC stained for both HE4 and PAX8. The 4 samples without HE4 staining were a clear cell carcinoma, a low-grade serous adenocarcinoma, an undifferentiated adenocarcinoma, and a neuroendocrine carcinoma. All high-grade serous adenocarcinomas (n = 37, 100%) stained with HE4, compared with 94% that stained positively for PAX8. In cases of gastric or colorectal cancer, 25% and 21% of cases, respectively, stained positive for HE4. No PAX8 staining was observed in colorectal or gastric adenocarcinomas. HE4 staining in ascites is feasible and appears to have a high sensitivity for high-grade serous ovarian cancer. HE4 is a useful addition to the current panel of immunocytochemistry markers for the diagnosis of EOC and for differentiation with gastrointestinal adenocarcinomas. Cancer Cytopathol 2017;125:197-204. © 2016 American Cancer Society. © 2017 American Cancer Society.

  20. Human papillomavirus and gastrointestinal cancer in Iranian population: A systematic review and meta-analysis.

    Science.gov (United States)

    Omrani-Navai, Versa; Alizadeh-Navaei, Reza; Yahyapour, Yousef; Hedayatizadeh-Omran, Akbar; Abediankenari, Saeid; Janbabaei, Ghasem; Toghani, Fatima

    2017-01-01

    Gastrointestinal (GI) malignancies are the most common cancers and account for nearly half of all cancer-related deaths in Iran. There was a strong association between human papillomavirus (HPV) infection and urogenital cancers, in particular the cervix. However, there is no clear causal relationship in all types of cancers, including gastrointestinal cancers. Therefore, the present study as a systematic review and meta-analysis was designed to evaluate the prevalence and relation of HPV in GI cancers. This systematic review and meta-analysis study assess the prevalence of human papillomavirus in GI cancers in Iran. Data were collected by searching electronic databases, including PubMed, Google Scholar, Scopus, SID and Iranmedex by English and Persian key words up to August 2016. Key words included: Human Papillomavirus, HPV, Cancer, Neoplasm, Carcinoma, Esophageal, colorectal, Gastrointestinal and Iran articles were entered in the EndNote software and duplicate papers were excluded. Data were extracted and analyzed by comprehensive meta-analysis software, Version 2 (CMA.V2) and random effects model. Finally, we included 17 studies in this meta-analysis. The prevalence of HPV in Iranian patients with GI cancers was 16.4% (CI95%: 10.4-24.9). Considering all HPV types, the odds ratio of GI cancers in positive patients was 3.03 (CI95%: 1.42-6.45) while in patients with HPV-16 was 3.62 (CI: 1.43-4.82). The results show a strong relationship between HPV infection especially high-risk HPV type 16 and GI cancers in Iranian population.

  1. Horizontal gene transfer in the human gastrointestinal tract: potential spread of antibiotic resistance genes

    Directory of Open Access Journals (Sweden)

    Huddleston JR

    2014-06-01

    Full Text Available Jennifer R HuddlestonBiology Department, Abilene Christian University, Abilene, TX, USAAbstract: Bacterial infections are becoming increasingly difficult to treat due to widespread antibiotic resistance among pathogens. This review aims to give an overview of the major horizontal transfer mechanisms and their evolution and then demonstrate the human lower gastrointestinal tract as an environment in which horizontal gene transfer of resistance determinants occurs. Finally, implications for antibiotic usage and the development of resistant infections and persistence of antibiotic resistance genes in populations as a result of horizontal gene transfer in the large intestine will be discussed.Keywords: gut microbiome, conjugation, natural transformation, transduction

  2. Human milk glycobiome and its impact on the infant gastrointestinal microbiota.

    Science.gov (United States)

    Zivkovic, Angela M; German, J Bruce; Lebrilla, Carlito B; Mills, David A

    2011-03-15

    Human milk contains an unexpected abundance and diversity of complex oligosaccharides apparently indigestible by the developing infant and instead targeted to its cognate gastrointestinal microbiota. Recent advances in mass spectrometry-based tools have provided a view of the oligosaccharide structures produced in milk across stages of lactation and among human mothers. One postulated function for these oligosaccharides is to enrich a specific "healthy" microbiota containing bifidobacteria, a genus commonly observed in the feces of breast-fed infants. Isolated culture studies indeed show selective growth of infant-borne bifidobacteria on milk oligosaccharides or core components therein. Parallel glycoprofiling documented that numerous Bifidobacterium longum subsp. infantis strains preferentially consume small mass oligosaccharides that are abundant early in the lactation cycle. Genome sequencing of numerous B. longum subsp. infantis strains shows a bias toward genes required to use mammalian-derived carbohydrates by comparison with adult-borne bifidobacteria. This intriguing strategy of mammalian lactation to selectively nourish genetically compatible bacteria in infants with a complex array of free oligosaccharides serves as a model of how to influence the human supraorganismal system, which includes the gastrointestinal microbiota.

  3. The fingerprint of the human gastrointestinal tract microbiota: a hypothesis of molecular mapping.

    Science.gov (United States)

    Tomasello, G; Mazzola, M; Jurjus, A; Cappello, F; Carini, F; Damiani, P; Gerges Geagea, A; Zeenny, M N; Leone, A

    2017-01-01

    The precise etiology of Inflammatory Bowel Disease (IDB) remains unclear and several factors are believed to play a role in its development and progression, including the composition of microbial communities resident in the gastrointestinal tract. Human intestinal microbiota are extensive with at least 15,000-36,000 bacterial species. However, thanks to the new development in sequencing and molecular taxonomic methodologies, our understanding of the microbiota population composition, dynamics, and ecology has greatly increased. Intestinal microbiota play a critical role in the maintenance of the host intestinal barrier homeostasis, while dysbiosis, which involves reduction in the microbiome diversity, can lead to progression of inflammatory disorders, such as IBD and colorectal cancer. It is hypothesized that fingerprinting characterization of the microbiota community composition is the first step in the study of this complex bacterial ecosystem and a crucial step in the targeted therapy. Molecular fingerprinting of human gastrointestinal tract microbiota could be performed by different techniques including the semi quantitation, 16SrRNA, the DNA- microarray as well as other relatively new methods which were developed to study many complex bacterial ecosystems. These techniques provide individual data and profiles, using fast and sensitive tools for the high taxonomic level fingerprint of the human intestinal microbiota and provide estimation of the relative presence of the microbial target groups within each individual. Such personalized information serves as a remarkable and unprecedented opportunity to improve targeted medical treatment and probably develop strategies to prevent disease.

  4. Th9 Cells Drive Host Immunity against Gastrointestinal Worm Infection.

    Science.gov (United States)

    Licona-Limón, Paula; Henao-Mejia, Jorge; Temann, Angela U; Gagliani, Nicola; Licona-Limón, Ileana; Ishigame, Harumichi; Hao, Liming; Herbert, De'broski R; Flavell, Richard A

    2013-10-17

    Type 2 inflammatory cytokines, including interleukin-4 (IL-4), IL-5, IL-9, and IL-13, drive the characteristic features of immunity against parasitic worms and allergens. Whether IL-9 serves an essential role in the initiation of host-protective responses is controversial, and the importance of IL-9- versus IL-4-producing CD4⁺ effector T cells in type 2 immunity is incompletely defined. Herein, we generated IL-9-deficient and IL-9-fluorescent reporter mice that demonstrated an essential role for this cytokine in the early type 2 immunity against Nippostrongylus brasiliensis. Whereas T helper 9 (Th9) cells and type 2 innate lymphoid cells (ILC2s) were major sources of infection-induced IL-9 production, the adoptive transfer of Th9 cells, but not Th2 cells, caused rapid worm expulsion, marked basophilia, and increased mast cell numbers in Rag2-deficient hosts. Taken together, our data show a critical and nonredundant role for Th9 cells and IL-9 in host-protective type 2 immunity against parasitic worm infection. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Zoonotic gastrointestinal parasite burden of local dogs in Zaria, Northern Nigeria: Implications for human health

    Directory of Open Access Journals (Sweden)

    Christopher I. Ogbaje

    2015-10-01

    Full Text Available Background: Zoonotic gastrointestinal parasites of dogs are of the global problem particularly in the developing countries. Dogs are the most common pet animals worldwide and have been reported to be hosts of many intestinal parasites of zoonotic importance globally. In Nigeria, gastrointestinal helminthes of dogs is currently endemic in 20 of the 36 states. Aim: In general, dogs are the closest animals to humans and for that reason we decided to carry out a survey study to check the incidence of these parasites in dogs and to ascertain the level of environmental contamination in the study area. Materials and Methods: Fecal samples were collected from dog patients presented to small animal clinic of Veterinary Teaching Hospital of Faculty of Veterinary Medicine, Ahmadu Bello University Zaria, dog’s fecal droppings from the streets, and residential Quarters of the University and gastrointestinal tracts (GIT of dogs from dogs slaughtering house at Basawa Barrack, Zaria. Three methods were used in the analysis of the samples; simple flotation, sedimentation, and GIT processing methods within 48 h of collection. Results: Out of 224 samples analyzed 76(33.9% were positive of at least one of the parasites. Of the 101 samples from streets and residential quarters of ABU, Zaria, Isospora spp. 12(11.9% recorded the highest prevalence rate followed by Taenia spp. 6(5.9%, then Toxocara canis, Ancylostoma caninum, and Dipylidium caninum were 5.0%, 4.0%, and 1.0%, respectively. Isospora spp. (19.0% recorded the highest prevalence rate for the 100 samples collected from small animal clinic. Other parasites encountered were T. canis (8.0%, A. caninum (8.0% and Taenia spp. (5.0%. Parasites observed from the 23 gastrointestinal contents from “dog slaughtered houses” were T. canis (17.3%, Isospora spp.(13.1% and A. caninum (4.3. Conclusion: The study revealed that zoonotic gastrointestinal parasites of dogs are endemic in Zaria and the general public in the

  6. Ruminant Gastrointestinal Cell Proliferation and Clearance of Escherichia coli O157:H7

    OpenAIRE

    Magnuson, Bernadene A.; Davis, Margaret; Hubele, Suzanna; Austin, Paula R.; Kudva, Indira T.; Christopher J Williams; Hunt, Carl W.; Hovde, Carolyn J.

    2000-01-01

    Human infections with Escherichia coli O157:H7 cause hemorrhagic colitis that can progress to a life-threatening sequelae. The most common mode of disease transmission is ingestion of contaminated bovine food products, and it is well established that E. coli O157:H7 is a transient member of the bovine microbiota. However, the conditions that induce acquisition and subsequent clearance of this bacterium from the ruminant gastrointestinal tract (GIT) are not understood. Evidence that the rates ...

  7. Hedgehog signaling pathway and gastrointestinal stem cell signaling network (review).

    Science.gov (United States)

    Katoh, Yuriko; Katoh, Masaru

    2006-12-01

    Hedgehog, BMP/TGFbeta, FGF, WNT and Notch signaling pathways constitute the stem cell signaling network, which plays a key role in a variety of processes, such as embryogenesis, maintenance of adult tissue homeostasis, tissue repair during chronic persistent inflammation, and carcinogenesis. Sonic hedgehog (SHH), Indian hedgehog (IHH) and Desert hedgehog (DHH) bind to PTCH1/PTCH or PTCH2 receptor to release Smoothened (SMO) signal transducer from Patched-dependent suppression. SMO then activates STK36 serine/threonine kinase to stabilize GLI family members and to phosphorylate SUFU for nuclear accumulation of GLI. Hedgehog signaling activation leads to GLI-dependent transcriptional activation of target genes, such as GLI1, PTCH1, CCND2, FOXL1, JAG2 and SFRP1. GLI1-dependent positive feedback loop combined with PTCH1-dependent negative feedback loop gives rise to transient proliferation of Hedgehog target cells. Iguana homologs (DZIP1 and DZIP1L) and Costal-2 homologs (KIF7 and KIF27) are identified by comparative integromics. SHH-dependent parietal cell proliferation is implicated in gastric mucosal repair during chronic Helicobacter pylori infection. BMP-RUNX3 signaling induces IHH expression in surface differentiated epithelial cells of stomach and intestine. Hedgehog signals from epithelial cells then induces FOXL1-mediated BMP4 upregulation in mesenchymal cells. Hedgehog signaling is frequently activated in esophageal cancer, gastric cancer and pancreatic cancer due to transcriptional upregulation of Hedgehog ligands and epigenetic silencing of HHIP1/HHIP gene, encoding the Hedgehog inhibitor. However, Hedgehog signaling is rarely activated in colorectal cancer due to negative regulation by the canonical WNT signaling pathway. Hedgehog signaling molecules or targets, such as SHH, IHH, HHIP1, PTCH1 and GLI1, are applied as biomarkers for cancer diagnostics, prognostics and therapeutics. Small-molecule inhibitors for SMO or STK36 are suitable to be used for

  8. A predominant pelvic gastrointestinal stromal tumor (GIST) mass observed on Tc-99m red blood cell gastrointestinal bleeding scintigraphy.

    Science.gov (United States)

    Sood, Ravi; Tee, Shang Ian

    2011-08-01

    A 51-year-old woman presented with recurrent bleeding per rectum. Her earlier endoscopies were negative. Tc-99m RBC GI bleeding scintigraphy was performed. It demonstrated an apparent hypervascular pelvic mass, and active small bowel bleeding. Based on scintigraphic finding of a predominant pelvic mass indicating tumor, CT of the abdomen and pelvis was performed for further gastrointestinal bleeding localization work up instead of an invasive angiography or endoscopy, which detected a small bowel tumor in the pelvis. A small bowel gastrointestinal stromal tumor was resected subsequently.

  9. Comparison of five in vitro digestion models to in vivo experimental results: Lead bioaccessibility in the human gastrointestinal tract

    NARCIS (Netherlands)

    Wiele, T.R. van de; Oomen, A.G.; Wragg, J.; Cave, M.; Minekus, M.; Hack, A.; Cornelis, C.; Rompelberg, C.J.M.; Zwart, L.L. de; Klinck, B.; Wijnen, J. van; Verstraete, W.; Sips, A.J.A.M.

    2007-01-01

    This paper presents a multi-laboratory comparison study of in vitro models assessing bioaccessibility of soil-bound lead in the human gastrointestinal tract under simulated fasted and fed conditions. Oral bioavailability data from a previous human in vivo study on the same soil served as a reference

  10. Novel endoscopic imaging techniques toward in vivo observation of living cancer cells in the gastrointestinal tract.

    Science.gov (United States)

    Inoue, Haruhiro; Kudo, Shin-ei; Shiokawa, Akira

    2005-07-01

    It is now possible to perform microscopic imaging of living cells from both normal mucosa and malignant tissue in the gastrointestinal tract. Endocytoscopy is a catheter-type contact endoscope that has more than 1000-fold magnifying power and can pass through the working channel of the straight-view endoscope. In esophageal cells, the nucleus, cell body, and even the nucleolus were clearly distinguished with high-resolution images comparable with those of conventional cytology. This novel technology has the potential to provide histologic diagnoses during endoscopic examinations, similar to those obtained currently by conventional histology techniques.

  11. Massive Upper Gastrointestinal Bleeding Caused by Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    O. Telci Caklili

    2016-01-01

    Full Text Available Massive upper gastrointestinal bleeding is a life-threatening emergency which needs urgent intervention. Hematological malignancies are very rare causes of this type of bleeding and they usually originate from duodenum. In this case we present a gastric diffuse large B-cell lymphoma (DLBCL causing massive upper gastrointestinal system bleeding. A 77-year-old male patient was admitted to emergency clinic with hematemesis and hematochezia. In physical examination patient was pale and sweaty; his vitals were unstable with a heart rate of 110 per minute and a blood pressure of 90/50 mmHg. His hemoglobin level was found 7.5 g/dL and he was transfused with one unit of packed red blood cells. After his vitals were normalized, gastroscopy was performed showing mosaic pattern in corpus and antrum mucosa and multiple ulcers in various sizes, largest being approximately 2 cm in diameter, higher than mucosa covered with exude mostly on corpus and large curvature. Biopsy results were reported as DLBCL. Gastric mucosa is involved in most of the DLBCL cases. Although not listed as a common cause of massive gastrointestinal bleeding DLBCL can cause life-threatening situations mostly because of its malignant nature.

  12. Upper Gastrointestinal Bleed as a Manifestation of Poorly Differentiated Metastatic Squamous Cell Carcinoma of the Lung.

    Science.gov (United States)

    Bhardwaj, Richa; Bhardwaj, Gaurav; Gautam, Arun; Karagozian, Raffi

    2017-06-01

    Gastrointestinal (GI) metastasis from primary lung cancer is a rare clinical finding. Lung cancer most often metastasizes to the brain, bone, liver, and adrenal glands; with gastrointestinal involvement being very rare. We report a case of a 39-year-old female with a diagnosis of poorly differentiated Squamous Cell Carcinoma (SCC) of the lung presenting with dizziness and melena. Esophagogastroduodenoscopy (EGD) showed a bleeding mass in the stomach. Final biopsy report and Immunohistochemistry (IHC) of the specimen were consistent with SCC lung metastasis. While it is imperative to have a high clinical suspicion for GI metastasis in patients with primary lung cancer presenting with GI symptoms, it may be challenging to establish diagnosis. Endoscopy along with pathology and immunohistochemistry play a crucial role in differentiating primary GI malignancies from metastasis.

  13. Perivascular epithelioid cell tumor of the liver coexisting with a gastrointestinal stromal tumor

    DEFF Research Database (Denmark)

    Paiva, Carlos Eduardo; Moraes Neto, Francisco Alves; Agaimy, Abbas

    2008-01-01

    Approximately 10% of patients with gastrointestinal stromal tumors (GIST) develop other neoplasms, either synchronously or metachronously. In this report we describe coexistence of a gastrointestinal stromal tumor and a hepatic perivascular epithelioid cell tumor (PEComa) in a 51-year-old woman...... with no evidence of tuberous sclerosis. A subcapsular hepatic nodule (0.8 cm in diameter) was found during surgery for symptomatic gastric neoplasm (15 cm in diameter) arising from the lesser curvature. Both tumors revealed histomorphological and immunohistochemical features confirming a diagnosis of a small...... incidental hepatic PEComa and a high risky extramural gastric GIST, respectively. The patient remained disease-free 25 mo after surgery with no evidence of tumor recurrence or new neoplasms. To our knowledge, this is the first report of PEComa in a patient with GIST. Hepatic lesions detected synchronously...

  14. Small cell carcinomas of the gastrointestinal tract: clinicopathological features and treatment approach.

    Science.gov (United States)

    Brenner, Baruch; Tang, Laura H; Shia, Jinruh; Klimstra, David S; Kelsen, David P

    2007-02-01

    Small cell undifferentiated carcinoma (SmCC) of the gastrointestinal tract (GIT) is a rare and highly aggressive malignancy. To date, fewer than 1,000 cases have been reported, with an estimated prevalence of 0.1% to 1% of all gastrointestinal (GI) tumors. Data on the disease are scarce due to its rarity and the fact that most authors have focused on one site within the GIT. In light of the limited data and its perceived similarity to SmCC of the lung, the disease has usually been treated as the latter. Nevertheless, recent clinicopathologic and molecular data imply several differences between the two entities, questioning the extent to which extrapolations from one to the other can be made. We review the available data on GI SmCC with emphasis on outlining its clinicopathologic features and the recommended treatment approach.

  15. Animal Farm: Considerations in Animal Gastrointestinal Physiology and Relevance to Drug Delivery in Humans.

    Science.gov (United States)

    Hatton, Grace B; Yadav, Vipul; Basit, Abdul W; Merchant, Hamid A

    2015-09-01

    "All animals are equal, but some are more equal than others" was the illustrious quote derived from British writer George Orwell's famed work, Animal Farm. Extending beyond the remit of political allegory, however, this statement would appear to hold true for the selection of appropriate animal models to simulate human physiology in preclinical studies. There remain definite gaps in our current knowledge with respect to animal physiology, notably those of intra- and inter-species differences in gastrointestinal (GI) function, which may affect oral drug delivery and absorption. Factors such as cost and availability have often influenced the choice of animal species without clear justification for their similarity to humans, and lack of standardization in techniques employed in past studies using various animals may also have contributed to the generation of contradictory results. As it stands, attempts to identify a single animal species as appropriately representative of human physiology and which may able to adequately simulate human in vivo conditions are limited. In this review, we have compiled and critically reviewed data from numerous studies of GI anatomy and physiology of various animal species commonly used in drug delivery modeling, commenting on the appropriateness of these animals for in vivo comparison and extrapolation to humans.

  16. Granule proteinases define mast cell heterogeneity in the serosa and the gastrointestinal mucosa of the mouse.

    Science.gov (United States)

    Miller, H R; Huntley, J F; Newlands, G F; Mackellar, A; Lammas, D A; Wakelin, D

    1988-12-01

    In order to define further mast cell heterogeneity in the mouse, affinity-purified antibodies against a 28,000 MW serine proteinase from mouse intestinal mast cells (IMCP) and against rat mast cell proteinase I (RMCPI) were used to characterize mast cell cytoplasmic granules immunohistochemically. On Western blot, anti-IMCP cross-reacted with RMCPI and with a 25,000 MW antigen from isolated mouse serosal mast cells (SMC). Anti-RMCPI did not react with IMCP, although it identified the same 25,000 MW antigen from SMC. Isolated SMC (85-90% pure) lacked the 28,000 MW IMCP on Western blot, even though, immunohistochemically, the cells were stained with both anti-RMCPI and anti-IMCP. Anti-IMCP stained the granules of more than 85% of all mast cells detected with toluidine blue in the tongue or gastrointestinal mucosa. The specificity of anti-RMCPI which, in the rat, detects very few mucosal mast cells was almost identical to that of anti-IMCP for murine tongue and gastric and large intestinal mucosae, but a significant proportion of cells in distal jejunal, ileal and caecal mucosae were not stained with this antibody. The immunohistochemistry of the large numbers of mast cells recruited to jejunum following infection 10 days previously with 300 Trichinella spiralis muscle larvae was similar to that of uninfected control mice. The results show that considerable mast cell heterogeneity exists within the gastrointestinal mucosa of the mouse and indicate that there are both similarities and differences between mouse and rat in the distribution of mast cells and of their granule proteinases.

  17. Human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Abdallah, Basem; Kassem, Moustapha

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of clonogenic cells present among the bone marrow stroma and capable of multilineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. Due to their ease of isolation and their differentiation potential, MSC are being...... introduced into clinical medicine in variety of applications and through different ways of administration. Here, we discuss approaches for isolation, characterization and directing differentiation of human mesenchymal stem cells (hMSC). An update of the current clinical use of the cells is also provided....

  18. Enrichment of Bifidobacterium longum subsp. infantis ATCC 15697 within the human gut microbiota using alginate-poly-L-lysine-alginate microencapsulation oral delivery system: an in vitro analysis using a computer-controlled dynamic human gastrointestinal model.

    Science.gov (United States)

    Rodes, Laetitia; Tomaro-Duchesneau, Catherine; Saha, Shyamali; Paul, Arghya; Malhotra, Meenakshi; Marinescu, Daniel; Shao, Wei; Kahouli, Imen; Prakash, Satya

    2014-01-01

    This study evaluates alginate-poly-L-lysine-alginate Bifidobacterium longum subsp. infantis ATCC 15697-loaded microcapsules to enrich the human gut microbiota. The cell survival of alginate-poly-L-lysine-alginate microencapsulated B. infantis ATCC 15697 in gastric acid, bile, and through human gastrointestinal transit was investigated, as well as the formulation's effect on the gut microbiota. Results show that microencapsulation increases B. infantis ATCC 15697 cell survival at pH1.0 (33.54 ± 2.80% versus  0.05) colonic microbiota.

  19. Anti-infective activities of lactobacillus strains in the human intestinal microbiota: from probiotics to gastrointestinal anti-infectious biotherapeutic agents.

    Science.gov (United States)

    Liévin-Le Moal, Vanessa; Servin, Alain L

    2014-04-01

    A vast and diverse array of microbial species displaying great phylogenic, genomic, and metabolic diversity have colonized the gastrointestinal tract. Resident microbes play a beneficial role by regulating the intestinal immune system, stimulating the maturation of host tissues, and playing a variety of roles in nutrition and in host resistance to gastric and enteric bacterial pathogens. The mechanisms by which the resident microbial species combat gastrointestinal pathogens are complex and include competitive metabolic interactions and the production of antimicrobial molecules. The human intestinal microbiota is a source from which Lactobacillus probiotic strains have often been isolated. Only six probiotic Lactobacillus strains isolated from human intestinal microbiota, i.e., L. rhamnosus GG, L. casei Shirota YIT9029, L. casei DN-114 001, L. johnsonii NCC 533, L. acidophilus LB, and L. reuteri DSM 17938, have been well characterized with regard to their potential antimicrobial effects against the major gastric and enteric bacterial pathogens and rotavirus. In this review, we describe the current knowledge concerning the experimental antibacterial activities, including antibiotic-like and cell-regulating activities, and therapeutic effects demonstrated in well-conducted, placebo-controlled, randomized clinical trials of these probiotic Lactobacillus strains. What is known about the antimicrobial activities supported by the molecules secreted by such probiotic Lactobacillus strains suggests that they constitute a promising new source for the development of innovative anti-infectious agents that act luminally and intracellularly in the gastrointestinal tract.

  20. A Double-Blind, Placebo-Controlled Trial of Oral Human Immunoglobulin for Gastrointestinal Dysfunction in Children with Autistic Disorder

    Science.gov (United States)

    Handen, Benjamin L.; Melmed, Raun D.; Hansen, Robin L.; Aman, Michael G.; Burnham, David L.; Bruss, Jon B.; McDougle, Christopher J.

    2009-01-01

    Controversy exists regarding the extent and possible causal relationship between gastrointestinal symptoms and autism. A randomized, double-blind, placebo-controlled, parallel groups, dose-ranging study of oral, human immunoglobulin (IGOH 140, 420, or 840 mg/day) was utilized with 125 children (ages 2-17 years) with autism and persistent GI…

  1. Three-Dimensional Gastrointestinal Organoid Culture in Combination with Nerves or Fibroblasts: A Method to Characterize the Gastrointestinal Stem Cell Niche.

    Science.gov (United States)

    Pastuła, Agnieszka; Middelhoff, Moritz; Brandtner, Anna; Tobiasch, Moritz; Höhl, Bettina; Nuber, Andreas H; Demir, Ihsan Ekin; Neupert, Steffi; Kollmann, Patrick; Mazzuoli-Weber, Gemma; Quante, Michael

    2016-01-01

    The gastrointestinal epithelium is characterized by a high turnover of cells and intestinal stem cells predominantly reside at the bottom of crypts and their progeny serve to maintain normal intestinal homeostasis. Accumulating evidence demonstrates the pivotal role of a niche surrounding intestinal stem cells in crypts, which consists of cellular and soluble components and creates an environment constantly influencing the fate of stem cells. Here we describe different 3D culture systems to culture gastrointestinal epithelium that should enable us to study the stem cell niche in vitro in the future: organoid culture and multilayered systems such as organotypic cell culture and culture of intestinal tissue fragments ex vivo. These methods mimic the in vivo situation in vitro by creating 3D culture conditions that reflect the physiological situation of intestinal crypts. Modifications of the composition of the culture media as well as coculturing epithelial organoids with previously described cellular components such as myofibroblasts, collagen, and neurons show the impact of the methods applied to investigate niche interactions in vitro. We further present a novel method to isolate labeled nerves from the enteric nervous system using Dclk1-CreGFP mice.

  2. Cell Aging of Mouse Gastrointestinal Tract Observed by Light and Electron Microscopic Radioautography

    Science.gov (United States)

    Nagata, Tetsuji

    2014-01-01

    The term “cell aging” initially means how the cells change due to their aging. There are two meanings, i.e. how a cell changes when it is isolated from original animals such as in vitro cells in cell culture, otherwise how all the cells of an animal change in vivo due to the aging of the individual animal. We have been studying the latter changes from the viewpoint of the cell nutrients, the precursors for the macromolecular synthesis such as deoxyribonucleic acid (DNA), ribonucleic acid (RNA), proteins, glucides and lipids, which are incorporated and synthesized into various cells of individual animals. Therefore, this article deals with only the cell aging of animal cells in vivo, how the metabolism, i.e. incorporations and syntheses of respective nutrient precursors in various kinds of cells change due to the aging of individual experimental animals such as mice by means of microscopic radioautography to localize the RI-labeled precursors. The incorporations and syntheses of various precursors for macromolecules such as DNA, RNA, proteins, glucides, lipids and others in various kinds of cells of various organs in the gastrointestinal tract such as the mouth, esophagus, stomach and intestines are reviewed referring many original papers already published from our laboratory during these 60 years since the late 20th century. PMID:27785275

  3. MAPKs and Signal Transduction in the Control of Gastrointestinal Epithelial Cell Proliferation and Differentiation

    Directory of Open Access Journals (Sweden)

    Luciana H. Osaki

    2013-05-01

    Full Text Available Mitogen-activated protein kinase (MAPK pathways are activated by several stimuli and transduce the signal inside cells, generating diverse responses including cell proliferation, differentiation, migration and apoptosis. Each MAPK cascade comprises a series of molecules, and regulation takes place at different levels. They communicate with each other and with additional pathways, creating a signaling network that is important for cell fate determination. In this review, we focus on ERK, JNK, p38 and ERK5, the major MAPKs, and their interactions with PI3K-Akt, TGFβ/Smad and Wnt/β-catenin pathways. More importantly, we describe how MAPKs regulate cell proliferation and differentiation in the rapidly renewing epithelia that lines the gastrointestinal tract and, finally, we highlight the recent findings on nutritional aspects that affect MAPK transduction cascades.

  4. Characterization of PrPc-immunoreactive cells in monkey (Macaca fascicularis) gastrointestinal tract.

    Science.gov (United States)

    Marcos, Z; Bodegas, M E; Sesma, M P; Guembe, L

    2005-04-01

    The gastrointestinal tract (GIT) is one of the most likely entry sites for the pathological isoform of prions (PrP(sc)). To understand how PrP(sc) crosses the digestive mucosa, it is crucial to characterize the cells expressing normal prion protein (PrP(c)). By means of double immunofluorescence applied to sections of the monkey GIT, we demonstrated that, in the stomach, PrP(c) immunostaining occurs in subsets of histamine, somatostatin (Som), ghrelin (Ghr), gastrin (G), and serotonin (5HT) cells. In the small and large bowels, PrP(c) cells were found in subpopulations of cells immunolabeled for 5HT, Som, G, and peptide YY (PYY).

  5. The use of formulation technology to assess regional gastrointestinal drug absorption in humans.

    Science.gov (United States)

    Basit, Abdul W; Podczeck, Fridrun; Newton, J Michael; Waddington, Wendy A; Ell, Peter J; Lacey, Larry F

    2004-02-01

    The aim of this study was to assess the feasibility of using oral modified-release formulations for the purposes of site-specific targeting and regional drug absorption assessment in man. An immediate release pellet formulation containing ranitidine as the model drug of choice for the study was fabricated by extrusion-spheronisation, and then film coated with either the enteric polymer polyvinyl acetate phthalate or the bacteria-degradable polymer amylose, in combination with ethylcellulose, to effect drug release within the small intestine and colon, respectively. Optimised formulations were evaluated in vivo in ten healthy volunteers, who each received, on four separate occasions, the immediate release, small intestinal release and colonic release formulations (each equivalent to 150mg ranitidine), and an intravenous injection of ranitidine (equivalent to 50mg ranitidine). Blood samples were collected and assessed for ranitidine concentration, and radiolabelled placebo pellets were co-administered with the coated ranitidine pellets to monitor their gastrointestinal transit using a gamma camera. Ranitidine was rapidly released and absorbed from the immediate release formulation, whereas the enteric formulation (10% coat weight gain) delayed drug release until some or all of the pellets had emptied into the small intestine. The amylose-ethylcellulose coated formulation (coat ratio 1:3, coat weight gain 25%) retarded ranitidine release until the pellets had reached the colon. The mean absolute bioavailability of ranitidine from the immediate release, small intestinal release and colonic release formulations were 50.6, 46.1 and 5.5%, respectively. These data are in general agreement to those obtained from a previous regional intubation study. The present study therefore demonstrates the practical potential of utilising a non-invasive, formulation-based approach to assess drug absorption from different regions of the human gastrointestinal tract.

  6. Bone marrow stromal cell transplantation mitigates radiation-induced gastrointestinal syndrome in mice.

    Directory of Open Access Journals (Sweden)

    Subhrajit Saha

    Full Text Available BACKGROUND: Nuclear accidents and terrorism presents a serious threat for mass casualty. While bone-marrow transplantation might mitigate hematopoietic syndrome, currently there are no approved medical countermeasures to alleviate radiation-induced gastrointestinal syndrome (RIGS, resulting from direct cytocidal effects on intestinal stem cells (ISC and crypt stromal cells. We examined whether bone marrow-derived adherent stromal cell transplantation (BMSCT could restitute irradiated intestinal stem cells niche and mitigate radiation-induced gastrointestinal syndrome. METHODOLOGY/PRINCIPAL FINDINGS: Autologous bone marrow was cultured in mesenchymal basal medium and adherent cells were harvested for transplantation to C57Bl6 mice, 24 and 72 hours after lethal whole body irradiation (10.4 Gy or abdominal irradiation (16-20 Gy in a single fraction. Mesenchymal, endothelial and myeloid population were characterized by flow cytometry. Intestinal crypt regeneration and absorptive function was assessed by histopathology and xylose absorption assay, respectively. In contrast to 100% mortality in irradiated controls, BMSCT mitigated RIGS and rescued mice from radiation lethality after 18 Gy of abdominal irradiation or 10.4 Gy whole body irradiation with 100% survival (p<0.0007 and p<0.0009 respectively beyond 25 days. Transplantation of enriched myeloid and non-myeloid fractions failed to improve survival. BMASCT induced ISC regeneration, restitution of the ISC niche and xylose absorption. Serum levels of intestinal radioprotective factors, such as, R-Spondin1, KGF, PDGF and FGF2, and anti-inflammatory cytokines were elevated, while inflammatory cytokines were down regulated. CONCLUSION/SIGNIFICANCE: Mitigation of lethal intestinal injury, following high doses of irradiation, can be achieved by intravenous transplantation of marrow-derived stromal cells, including mesenchymal, endothelial and macrophage cell population. BMASCT increases blood levels of

  7. [Carbon monoxide in human physiology--its role in the gastrointestinal tract].

    Science.gov (United States)

    Jasnos, Katarzyna; Magierowski, Marcin; Kwiecień, Sławomir; Brzozowski, Tomasz

    2014-01-30

    Carbon monoxide (CO) is produced endogenously in the body as a byproduct of heme degradation catalyzed by the action of heme oxygenase (HO) enzymes. An inducible form, HO-1, responds to many factors such as oxidative stress, hypoxia, heme, bacterial endotoxins, proinflammatory cytokines and heavy metals. HO-2 is constitutively expressed under basal conditions in most human tissues including brain and gonads. Recent data show that CO is a gaseous mediator with multidirectional biological activity. It is involved in maintaining cellular homeostasis and many physiological and pathophysiological processes. CO shares many properties with another established vasodilatator and neurotransmitter - nitric oxide (NO). Both CO and NO are involved in neural transmission, modulation of blood vessel function and inhibition of platelet aggregation. The binding to guanylate cyclase, stimulation of the production of cGMP, activation of Ca2+-dependent potassium channels and stimulation of mitogen-activated protein kinases are well known cellular targets of CO action. Since CO is nowadays a subject of extensive investigation in many centers worldwide, the aim of the present study was to present the role of CO in various aspects of human physiology with special focus on its activity in the gastrointestinal tract.

  8. A wireless capsule system with ASIC for monitoring the physiological signals of the human gastrointestinal tract.

    Science.gov (United States)

    Xu, Fei; Yan, Guozheng; Zhao, Kai; Lu, Li; Gao, Jinyang; Liu, Gang

    2014-12-01

    This paper presents the design of a wireless capsule system for monitoring the physiological signals of the human gastrointestinal (GI) tract. The primary components of the system include a wireless capsule, a portable data recorder, and a workstation. Temperature, pH, and pressure sensors; an RF transceiver; a controlling and processing application specific integrated circuit (ASIC); and batteries were applied in a wireless capsule. Decreasing capsule size, improving sensor precision, and reducing power needs were the primary challenges; these were resolved by employing micro sensors, optimized architecture, and an ASIC design that include power management, clock management, a programmable gain amplifier (PGA), an A/D converter (ADC), and a serial peripheral interface (SPI) communication unit. The ASIC has been fabricated in 0.18- μm CMOS technology with a die area of 5.0 mm × 5.0 mm. The wireless capsule integrating the ASIC controller measures Φ 11 mm × 26 mm. A data recorder and a workstation were developed, and 20 cases of human experiments were conducted in hospitals. Preprocessing in the workstation can significantly improve the quality of the data, and 76 original features were determined by mathematical statistics. Based on the 13 optimal features achieved in the evaluation of the features, the clustering algorithm can identify the patients who lack GI motility with a recognition rate reaching 83.3%.

  9. Bone marrow-derived cells may not be the original cells for carcinogen-induced mouse gastrointestinal carcinomas.

    Directory of Open Access Journals (Sweden)

    Chen Yang

    Full Text Available AIM: It has been reported that bone marrow-derived cells (BMDC can be original cells of mouse gastric cancers induced by Helicobacter felis (H. felis infection. However, it is unknown whether BMDCs are also the original cells of mouse gastrointestinal cancers induced by gastric carcinogens N-nitroso-N-methylurea (NMU and H. felis infection. METHODS: C57BL/6 recipient mice were initially irradiated with 10Gy X-ray, reconstituted with bone marrow cells from the C57BL/6-Tg (CAG-EGFP donor mice to label BMDCs with green fluorescence protein (GFP. After 4 weeks of recovery, the bone marrow-transplanted mice were given NMU in drinking water (240 ppm and subsequently infected with H. felis by gavage. Eighty weeks later, all mice were euthanized for pathological examination. The BMDCs expressing GFP were detected in tissues using direct GFP fluorescence confocal microscopy analysis and immunohistochemistry staining (IHC assays. RESULTS: Neoplastic lesions were induced by NMU treatment and/or H. felis infection at the antrum of the glandular stomach and small intestine. In the direct GFP fluorescence confocal assay, GFP(+ epithelial cell cluster or glands were not observed in these gastrointestinal tumors, however, most GFP(+ BMDCs sporadically located in the tumor stromal tissues. Some of these GFP(+ stromal BMDCs co-expressed the hematopoietic marker CD45 or myofibroblasts markers αSMA and SRF. In the indirect GFP IHC assay, similar results were observed among 11 gastric intraepithelial neoplasia lesions and 2 small intestine tumors. CONCLUSION: These results demonstrated that BMDCs might not be the source of gastrointestinal tumor cells induced by NMU and/or H. felis infection.

  10. Preliminary study of the role of gastrointestinal endocrine cells in the maintenance of villous structure following X-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Wyatt, M.G.; Hume, S.P.; Carr, K.E.; Marigold, J.C.

    1987-03-01

    The mechanism of gastrointestinal villous damage following ionizing irradiation is complex. Various compartments within the gastrointestinal tract have in turn been considered important for the maintenance of normal villous structure. To date, however, evidence for a single overriding regulator of epithelial well-being is lacking. In this study, the role of the gastro-intestinal (enteroendocrine) cells is explored and comparison made between endocrine cell number and villous structure. Experiments were organized using both control and irradiated groups of mice. Two time points (1 and 3 days) and three radiation doses (6, 10 and 18Gy) were employed. A simple method for endocrine cell identification and subsequent quantification is described. Endocrine cell number was then compared with villous surface detail, as seen with a scanning electron microscope (SEM). Results indicated a decrease in the endocrine cell number at all three radiation doses. Whereas at low doses endocrine cell recovery occurred between 1 and 3 days, at medium and high doses further decline was noticed. A similar pattern was seen when considering villous surface structure. It is suggested that both scanning electron microscopy and endocrine cell number provide a more sensitive indicator of gastrointestinal radiation damage than do current crypt counting techniques. In addition, a link between endocrine cell number and villous structure is proposed.

  11. Molecular Cloning of Ghrelin and Characteristics of Ghrelin-Producing Cells in the Gastrointestinal Tract of the Common Marmoset (Callithrix jacchus).

    Science.gov (United States)

    Takemi, Shota; Sakata, Ichiro; Apu, Auvijit Saha; Tsukahara, Shinji; Yahashi, Satowa; Katsuura, Goro; Iwashige, Fumihiro; Akune, Atsushi; Inui, Akio; Sakai, Takafumi

    2016-10-01

    Ghrelin was first isolated from human and rat as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R). In the present study, we determined the ghrelin cDNA sequence of the common marmoset (Callithrix jacchus), a small-bodied New World monkey, and investigated the distribution of ghrelin-producing cells in the gastrointestinal tract and localization profiles with somatostatin-producing cells. The marmoset ghrelin cDNA coding region was 354 base pairs, and showed high homology to that in human, rhesus monkey, and mouse. Marmoset ghrelin consists of 28 amino acids, and the N-terminal region is highly conserved as found in other mammalian species. Marmoset preproghrelin and mature ghrelin have 86.3% and 92.9% homology, respectively, to their human counterparts. Quantitative RT-PCR analysis showed that marmoset ghrelin mRNA is highly expressed in the stomach, but it is not detected in other tissues of the gastrointestinal tract. In addition, a large number of ghrelin mRNA-expressing cells and ghrelin-immunopositive cells were detected in the mucosal layer of the stomach, but not in the myenteric plexus. Moreover, all the ghrelin cells examined in the stomach were observed to be closed-type. Double staining showed that somatostatin-immunopositive cells were not co-localized with ghrelin-producing cells; however, a subset of somatostatin-immunopositive cells is directly adjacent to ghrelin-immunopositive cells. These findings suggest that the distribution of ghrelin cells in marmoset differs from that in rodents, and thus the marmoset may be a more useful model for the translational study of ghrelin in primates. In conclusion, we have clarified the expression and cell distribution of ghrelin in marmoset, which may represent a useful model in translational study.

  12. Chemical coding and chemosensory properties of cholinergic brush cells in the mouse gastrointestinal and biliary tract

    Directory of Open Access Journals (Sweden)

    Burkhard eSchütz

    2015-03-01

    Full Text Available The mouse gastro-intestinal and biliary tract mucosal epithelia harbor choline acetyltransferase (ChAT-positive brush cells with taste cell-like traits. With the aid of two transgenic mouse lines that express green fluorescent protein (EGFP under the control of the ChAT promoter (EGFPChAT and by using in situ hybridization and immunohistochemistry we found that EGFPChAT cells were clustered in the epithelium lining the gastric groove. EGFPChAT cells were numerous in the gall bladder and bile duct, and found scattered as solitary cells along the small and large intestine. While all EGFPChAT cells were also ChAT-positive, expression of the high-affinity choline transporter (ChT1 was never detected. Except for the proximal colon, EGFPChAT cells also lacked detectable expression of the vesicular acetylcholine transporter (VAChT. EGFPChAT cells were found to be separate from enteroendocrine cells, however they were all immunoreactive for cytokeratin 18 (CK18, transient receptor potential melastatin-like subtype 5 channel (TRPM5, and for cyclooxygenases 1 (COX1 and 2 (COX2. The ex vivo stimulation of colonic EGFPChAT cells with the bitter substance denatonium resulted in a strong increase in intracellular calcium, while in other epithelial cells such an increase was significantly weaker and also timely delayed. Subsequent stimulation with cycloheximide was ineffective in both cell populations. Given their chemical coding and chemosensory properties, EGFPChAT brush cells thus may have integrative functions and participate in induction of protective reflexes and inflammatory events by utilizing ACh and prostaglandins for paracrine signaling.

  13. [Gastrointestinal bezoars].

    Science.gov (United States)

    Espinoza González, Ricardo

    2016-08-01

    Gastrointestinal bezoars are a concretion of indigested material that can be found in the gastrointestinal tract of humans and some animals. This material forms an intraluminal mass, more commonly located in the stomach. During a large period of history animal bezoars were considered antidotes to poisons and diseases. We report a historical overview since bezoars stones were thought to have medicinal properties. This magic conception was introduced in South America by Spanish conquerors. In Chile, bezoars are commonly found in a camelid named guanaco (Lama guanicoe). People at Central Chile and the Patagonia believed that bezoar stones had magical properties and they were traded at very high prices. In Santiago, during the eighteenth century the Jesuit apothecary sold preparations of bezoar stones. The human bezoars may be formed by non-digestible material like cellulose (phytobezoar), hair (trichobezoar), conglomerations of medications or his vehicles (pharmacobezoar or medication bezoar), milk and mucus component (lactobezoar) or other varieties of substances. This condition may be asymptomatic or can produce abdominal pain, ulceration, gastrointestinal bleeding, gastric outlet obstruction, perforation and mechanical intestinal obstruction. We report their classification, diagnostic modalities and treatment.

  14. Cellular prion protein is expressed in a subset of neuroendocrine cells of the rat gastrointestinal tract.

    Science.gov (United States)

    Marcos, Zuberoa; Pffeifer, Kristine; Bodegas, María E; Sesma, María P; Guembe, Laura

    2004-10-01

    Prion diseases are believed to develop from the conformational change of normal cellular prion protein (PrPc) to a pathogenic isoform (PrPsc). PrPc is present in both the central nervous system and many peripheral tissues, although protein concentration is significantly lower in non-neuronal tissues. PrPc expression is essential for internalization and replication of the infectious agent. Several works have pointed to the gastrointestinal (GI) tract as the principal site of entry of PrPsc, but how passage through the GI mucosa occurs is not yet known. Here we studied PrPc expression using Western blot, RT-PCR, and immunohistochemistry in rat GI tract. PrPc mRNA and protein were detected in corpus, antrum, duodenum, and colon. Immunoreactivity was found in scattered cells of the GI epithelium. With double immunofluorescence, these cells have been identified as neuroendocrine cells. PrPc immunostaining was found in subsets of histamine, somatostatin (Som), ghrelin, gastrin (G), and serotonin (5HT) cells in stomach. In small and large bowel, PrPc cells co-localized with subpopulations of 5HT-, Som-, G-, and peptide YY-immunolabeled cells. Our results provide evidence for a possible and important role of endocrine cells in the internalization of PrPsc from gut lumen.

  15. Effects of Genetically Modified Milk Containing Human Beta-Defensin-3 on Gastrointestinal Health of Mice.

    Directory of Open Access Journals (Sweden)

    Xin Chen

    Full Text Available This study was performed to investigate the effects of genetically modified (GM milk containing human beta-defensin-3 (HBD3 on mice by a 90-day feeding study. The examined parameters included the digestibility of GM milk, general physical examination, gastric emptying function, intestinal permeability, intestinal microflora composition of mice, and the possibility of horizontal gene transfer (HGT. The emphasis was placed on the effects on gastrointestinal (GI tract due to the fact that GI tract was the first site contacting with food and played crucial roles in metabolic reactions, nutrition absorption and immunity regulation in the host. However, the traditional methods for analyzing the potential toxicological risk of GM product pay little attention on GI health. In this study, the results showed GM milk was easy to be digested in simulated gastric fluid, and it did not have adverse effects on general and GI health compared to conventional milk. And there is little possibility of HGT. This study may enrich the safety assessment of GM product on GI health.

  16. Behaviour of silver nanoparticles and silver ions in an in vitro human gastrointestinal digestion model.

    Science.gov (United States)

    Walczak, Agata P; Fokkink, Remco; Peters, Ruud; Tromp, Peter; Herrera Rivera, Zahira E; Rietjens, Ivonne M C M; Hendriksen, Peter J M; Bouwmeester, Hans

    2013-11-01

    Oral ingestion is an important exposure route for silver nanoparticles (AgNPs), but their fate during gastrointestinal digestion is unknown. This was studied for 60 nm AgNPs and silver ions (AgNO₃) using in vitro human digestion model. Samples after saliva, gastric and intestinal digestion were analysed with SP-ICPMS, DLS and SEM-EDX. In presence of proteins, after gastric digestion the number of particles dropped significantly, to rise back to original values after the intestinal digestion. SEM-EDX revealed that reduction in number of particles was caused by their clustering. These clusters were composed of AgNPs and chlorine. During intestinal digestion, these clusters disintegrated back into single 60 nm AgNPs. The authors conclude that these AgNPs under physiological conditions can reach the intestinal wall in their initial size and composition. Importantly, intestinal digestion of AgNO₃ in presence of proteins resulted in particle formation. These nanoparticles (of 20-30 nm) were composed of silver, sulphur and chlorine.

  17. A New High-Throughput Approach to Genotype Ancient Human Gastrointestinal Parasites.

    Science.gov (United States)

    Côté, Nathalie M L; Daligault, Julien; Pruvost, Mélanie; Bennett, E Andrew; Gorgé, Olivier; Guimaraes, Silvia; Capelli, Nicolas; Le Bailly, Matthieu; Geigl, Eva-Maria; Grange, Thierry

    2016-01-01

    Human gastrointestinal parasites are good indicators for hygienic conditions and health status of past and present individuals and communities. While microscopic analysis of eggs in sediments of archeological sites often allows their taxonomic identification, this method is rarely effective at the species level, and requires both the survival of intact eggs and their proper identification. Genotyping via PCR-based approaches has the potential to achieve a precise species-level taxonomic determination. However, so far it has mostly been applied to individual eggs isolated from archeological samples. To increase the throughput and taxonomic accuracy, as well as reduce costs of genotyping methods, we adapted a PCR-based approach coupled with next-generation sequencing to perform precise taxonomic identification of parasitic helminths directly from archeological sediments. Our study of twenty-five 100 to 7,200 year-old archeological samples proved this to be a powerful, reliable and efficient approach for species determination even in the absence of preserved eggs, either as a stand-alone method or as a complement to microscopic studies.

  18. Role of CCK/gastrin receptors in gastrointestinal/metabolic diseases and results of human studies using gastrin/CCK receptor agonists/antagonists in these diseases

    Science.gov (United States)

    Berna, Marc J.; Jensen, Robert T.

    2009-01-01

    In this paper, the estabished and possible roles of CCK1 and CCK2 receptors in gastrointestinal (GI) and metabolic diseases are reviewed and available results from human agonist/antagonist studies are discussed. While there is evidence for the involvement of CCK1R in numerous diseases including pancreatic disorders, motility disorders, tumor growth, regulation of satiety and a number of CCK-deficient states, the role of CCK1R in these conditions is not clearly defined. There are encouraging data from several clinical studies of CCK1R antagonists in some of these conditions, but their role as therapeutic agents remains unclear. The role of CCK2R in physiological (atrophic gastritis, pernicious anemia) and pathological (Zollinger-Ellison syndrome) hypergastrinemic states, its effects on the gastric mucosa (ECL cell hyperplasia, carcinoids, parietal cell mass) and its role in acid-peptic disorders are clearly defined. Furthermore, recent studies point to a possible role for CCK2R in a number of GI malignancies. Current data from human studies of CCK2R antagonists are presented and their potential role in the treatment of these conditions reviewed. Furthermore, the role of CCK2 receptors as targets for medical imaging is discussed. Even though cholecystokinin (CCK) and gastrin were among the first gastrointestinal hormones discovered [1,2], both their physiological roles as well as their roles in clinically relevant gastrointestinal diseases remain unclear and even controversial in many cases [3–6]. The structural characterization of CCK and gastrin [7,8], pharmacological identification [9–13] and cloning [14,15] of CCK and gastrin receptors (CCK1R, CCK2R), characterization of receptor location, peptide and receptor genes, development of receptor antagonists and receptor/agonist knockout animals [16–21] have led to important advancements in our understanding of the physiological and pathophysiological role of CCK and gastrin signaling [3]. Most of these topics

  19. Perivascular epithelioid cell tumor of the liver coexisting with a gastrointestinal stromal tumor

    Institute of Scientific and Technical Information of China (English)

    Carlos Eduardo Paiva; Francisco Alves Moraes Neto; Abbas Agaimy; Maria Aparecida Custódio Domingues; Silvia Regina Rogatto

    2008-01-01

    Approximately 10% of patients with gastrointestinal stromal tumors (GIST) develop other neoplasms,either synchronously or metachronously.In this report we describe coexistence of a gastrointestinal stromal tumor and a hepatic perivascular epithelioid cell tumor (PEComa) in a 51-year-old woman with no evidence of tuberous sclerosis.A subcapsular hepatic nodule (0.8 cm in diameter) was found during surgery for symptomatic gastric neoplasm (15 cm in diameter) arising from the lesser curvature.Both tumors revealed histomorphological and immunohistochemical features confirming a diagnosis of a small incidental hepatic PEComa and a high risky extramural gastric GIST,respectively.The patient remained disease-free 25 mo after surgery with no evidence of tumor recurrence or new neoplasms.To our knowledge,this is the first report of PEComa in a patient with GIST.Hepatic lesions detected synchronously or metachronously in patients with GISTs may represent histogenetically distinct lesions and should be sampled to confirm or exclude metastatic GISTs.

  20. Identification of calgranulin B interacting proteins and network analysis in gastrointestinal cancer cells

    Science.gov (United States)

    Yoo, Byong Chul

    2017-01-01

    Calgranulin B is known to be involved in tumor development, but the underlying molecular mechanism is not clear. To gain insight into possible roles of calgranulin B, we screened for calgranulin B-interacting molecules in the SNU-484 gastric cancer and the SNU-81 colon cancer cells. Calgranulin B-interacting partners were identified by yeast two-hybrid and functional information was obtained by computational analysis. Most of the calgranulin B-interacting partners were involved in metabolic and cellular processes, and found to have molecular function of binding and catalytic activities. Interestingly, 46 molecules in the network of the calgranulin B-interacting proteins are known to be associated with cancer and FKBP2 was found to interact with calgranulin B in both SNU-484 and SNU-81 cells. Polyubiquitin-C encoded by UBC, which exhibited an interaction with calgranulin B, has been associated with various molecules of the extracellular space and plasma membrane identified in our screening, including Na-K-Cl cotransporter 1 and dystonin in SNU-484 cells, and ATPase subunit beta-1 in SNU-81 cells. Our data provide novel insight into the roles of calgranulin B of gastrointestinal cancer cells, and offer new clues suggesting calgranulin B acts as an effector molecule through which the cell can communicate with the tumor microenvironment via polyubiquitin-C. PMID:28152021

  1. An obscure cause of gastrointestinal bleeding: Renal cell carcinoma metastasis to the small bowel

    Directory of Open Access Journals (Sweden)

    Robyn L. Gorski

    2015-01-01

    Full Text Available Renal cell carcinoma metastasis to the small intestine is a rare condition. It usually results in gastrointestinal bleeding and it could happen many years after the diagnosis with renal cell cancer. Treatment includes surgery as well as targeted agents such as tyrosine kinases. We report here the case of an 82-year-old man with a past medical history of high-grade renal cell carcinoma and right nephrectomy 6 years earlier, who presented with recurrent episodes of syncope and black stools. He underwent esophagogastroduodenoscopy (EGD and colonoscopy without evident source of bleeding. Video capsule endoscopy (VCE showed three bleeding lesions in the jejunum and ileum. Push enteroscopy revealed a proximal jejunum bleeding mass that was suspicious for malignancy. Histopathology demonstrated poorly differentiated carcinoma. Given the patient’s history of high-grade renal cell carcinoma, and similarity of histologic changes to the old renal cell cancer specimen, metastatic renal cell carcinoma was felt to be the responsible etiology.

  2. Age and gender affect the composition of fungal population of the human gastrointestinal tract

    Directory of Open Access Journals (Sweden)

    Francesco Strati

    2016-08-01

    Full Text Available The fungal component of the human gut microbiota has been neglected for long time due to the low relative abundance of fungi with respect to bacteria, and only recently few reports have explored its composition and dynamics in health or disease. The application of metagenomics methods to the full understanding of fungal communities is currently limited by the under representation of fungal DNA with respect to the bacterial one, as well as by the limited ability to discriminate passengers from colonizers. Here we investigated the gut mycobiota of a cohort of healthy subjects in order to reduce the gap of knowledge concerning fungal intestinal communities in the healthy status further screening for phenotypical traits that could reflect fungi adaptation to the host. We studied the fecal fungal populations of 111 healthy subjects by means of cultivation on fungal selective media and by amplicon-based ITS1 metagenomics analysis on a subset of 57 individuals. We then characterized the isolated fungi for their tolerance to gastrointestinal tract-like challenges and their susceptibility to antifungals. A total of 34 different fungal species were isolated showing several phenotypic characteristics associated with intestinal environment such as tolerance to body temperature (37°C, to acidic and oxidative stress and to bile salts exposure. We found a high frequency of azoles resistance in fungal isolates, with potential and significant clinical impact. Analyses of fungal communities revealed that the human gut mycobiota differs in function of individuals’ life stage in a gender-related fashion. The combination of metagenomics and fungal cultivation allowed an in-depth understanding of the fungal intestinal community structure associated to the healthy status and the commensalism-related traits of isolated fungi. We further discussed comparatively the results of sequencing and cultivation to critically evaluate the application of metagenomics

  3. Anti-inflammatory properties of fruit juices enriched with pine bark extract in an in vitro model of inflamed human intestinal epithelium: the effect of gastrointestinal digestion.

    Science.gov (United States)

    Frontela-Saseta, Carmen; López-Nicolás, Rubén; González-Bermúdez, Carlos A; Martínez-Graciá, Carmen; Ros-Berruezo, Gaspar

    2013-03-01

    Enrichment of fruit juices with pine bark extract (PBE) could be a strategy to compensate for phenolic losses during the gastrointestinal digestion. A coculture system with Caco-2 cells and RAW 264.7 macrophages was established as an in vitro model of inflamed human intestinal epithelium for evaluating the anti-inflammatory capacity of fruit juices enriched with PBE (0.5 g L(-1)) before and after in vitro digestion. The digestion of both PBE-enriched pineapple and red fruit juice led to significant changes in most of the analysed phenolic compounds. The in vitro inflammatory state showed cell barrier dysfunction and overproduction of IL-8, nitric oxide (NO) and reactive oxygen species (ROS). In the inflamed cells, incubation with nondigested samples reduced (Pproperties of PBE-enriched fruit juices decreased after digestion; further research on the bioavailability of the assayed compounds is needed to properly assess their usefulness for the treatment of gut inflammation.

  4. Cell-block procedure in endoscopic ultrasound-guided-fine-needle-aspiration of gastrointestinal solid neoplastic lesions

    Institute of Scientific and Technical Information of China (English)

    Antonio; Ieni; Valeria; Barresi; Paolo; Todaro; Rosario; Alberto; Caruso; Giovanni; Tuccari

    2015-01-01

    In the present review we have analyzed the clinical applications of endoscopic ultrasound-guided-fineneedle-aspiration(EUS-FNA) and the methodological aspects obtained by cell-block procedure(CBP) in the diagnostic approach to the gastrointestinal neoplastic pathology. CBP showed numerous advantages in comparison to the cytologic routine smears; in particular, better preservation of cell architecture, achievement of routine haematoxylin-eosin staining equivalent to histological slides and possibility to perform immunohistochemistry or molecular analyses represented the most evident reasons to choose this method. Moreover, by this approach, the differential diagnosis of solid gastrointestinal neoplasias may be more easily achieved and the background of contaminant nonneoplastic gastrointestinal avoided. Finally, biological samples collected by EUS-FNA CBP-assisted should be investigated in order to identify and quantify further potential molecular markers.

  5. Cell encoding recombinant human erythropoietin

    Energy Technology Data Exchange (ETDEWEB)

    Beck, A.K.; Withy, R.M.; Zabrecky, J.R.; Masiello, N.C.

    1990-09-04

    This patent describes a C127 cell transformed with a recombinant DNA vector. It comprises: a DNA sequence encoding human erythropoietin, the transformed cell being capable of producing N-linked and O-linked glycosylated human erythropoietin.

  6. In vitro approaches to assess bioavailability and human gastrointestinal mobilization of food-borne polychlorinated biphenyls (PCBs).

    Science.gov (United States)

    Adenugba, Adeola A; McMartin, Dena W; Beck, Angus J

    2008-06-01

    This study reports on the potential for gastrointestinal (GI) mobilization and bioavailability of food-borne PCBs in humans. The development and validation of a GI simulator and operational protocols, developed in compliance with the requirements of German DIN 19738 risk assessment test procedure, are presented. Food, naturally contaminated with PCBs, was homogenized with simulated saliva fluid and shaken in the GI simulator with simulated gastric fluids (containing pepsin, mucine) for 2 h at 37 degrees C. Afterwards, the simulated intestinal fluids (containing pepsin, mucine, trypsin, pancreatin, bile) were added and the mixture shaken for a further 6 h prior to centrifugation and filtration using Buchner funnels to separate the undigested GI residues from GI fluids. PCBs were recovered from GI residues and fluids by Soxhlet and liquid-liquid extraction respectively, cleaned up using silica-SFE, and analyzed by gas chromatography mass spectrometry detection (GC-MSD). Detailed studies with fish indicate variations in mobilization and bioavailability of Sigma PCBs (28, 52, 101, 118, 153, 138 and 180). For example, the bioavailable fractions (fractions mobilized) in mackerel, salmon, crab and prawn were 0.77, 0.60, 0.54, and 0.72 respectively of the Sigma PCBs initially present in these food samples. The bioavailable fraction was dependent on the physicochemical characteristics of the PCBs. In mackerel bioavailable fractions for individual PCB congeners ranged from 0.47-0.82, from 0.30-0.70 in salmon, 0.44-0.64 in crab and in prawn from 0.47-0.77. Future studies will focus on understanding better, the variability in bioavailable fractions to be expected for different foodstuffs, in addition to tissue culture techniques using human gut cell lines to investigate a simultaneous mobilization and absorption of food-borne PCBs.

  7. Nestin in gastrointestinal and other cancers: Effects on cells and tumor angiogenesis

    Institute of Scientific and Technical Information of China (English)

    Toshiyuki Ishiwata; Yoko Matsuda; Zenya Naito

    2011-01-01

    Nestin is a class Ⅵ intermediate filament protein that was originally described as a neuronal stem cell marker during central nervous system (CNS) development, and is currently widely used in that capacity. Nestin is also expressed in non-neuronal immature or progenitor cells in normal tissues. Under pathological conditions, nestin is expressed in repair processes in the CNS, muscle, liver, and infarcted myocardium. Furthermore, increased nestin expression has been reported in various tumor cells, including CNS tumors, gastrointestinal stromal tumors, pancreatic cancer, prostate cancer, breast cancer, malignant melanoma, dermatofibrosarcoma protuberances, and thyroid tumors. Nestin is reported to correlate with aggressive growth, metastasis, and poor prognosis in some tumors; however, the roles of nestin in cancer cells have not been well characterized. Furthermore, nestin is more specifically expressed in proliferating small-sized tumor vessels in glioblastoma and gastric, colorectal, and prostate cancers than are other tumor vessel markers. These findings indicate that nestin may be a marker for newly synthesized tumor vessels and a therapeutic target for tumor angiogenesis. It has received a lot of attention recently as a cancer stem cell marker in various cancer cells including brain tumors, malignant rhabdoid tumors, and uterine, cervical, prostate, bladder, head and neck, ovarian, testicular, and pancreatic cancers. The purpose of this review is to clarify the roles of nestin in cancer cells and in tumor angiogenesis, and to examine the association between nestin and cancer stem cells. Nestin has the potential to serve as a molecular target for cancers with nestin-positive cancer cells and nestin-positive tumor vasculature.

  8. The Role of Cell Surface Architecture of Lactobacilli in Host-Microbe Interactions in the Gastrointestinal Tract

    Directory of Open Access Journals (Sweden)

    Ranjita Sengupta

    2013-01-01

    Full Text Available Lactobacillus species can exert health promoting effects in the gastrointestinal tract (GIT through many mechanisms, which include pathogen inhibition, maintenance of microbial balance, immunomodulation, and enhancement of the epithelial barrier function. Different species of the genus Lactobacillus can evoke different responses in the host, and not all strains of the same species can be considered beneficial. Strain variations may be related to diversity of the cell surface architecture of lactobacilli and the bacteria's ability to express certain surface components or secrete specific compounds in response to the host environment. Lactobacilli are known to modify their surface structures in response to stress factors such as bile and low pH, and these adaptations may help their survival in the face of harsh environmental conditions encountered in the GIT. In recent years, multiple cell surface-associated molecules have been implicated in the adherence of lactobacilli to the GIT lining, immunomodulation, and protective effects on intestinal epithelial barrier function. Identification of the relevant bacterial ligands and their host receptors is imperative for a better understanding of the mechanisms through which lactobacilli exert their beneficial effects on human health.

  9. Influence of gastrointestinal system conditions on adhesion of exopolysaccharide-producing Lactobacillus delbrueckii subsp. bulgaricus strains to caco-2 cells

    Directory of Open Access Journals (Sweden)

    Derya Onal Darilmaz

    2011-10-01

    Full Text Available This study aimed to assess the transit tolerance of potential probiotic dairy Lactobacillus strains in human uppergastrointestinal tract in vitro, and to evaluate the effect of EPS production on the viability and adhesion of these strains. Survival and adhesion of two exopolysaccharide (EPS-producing L. delbrueckii subsp. bulgaricus strains (B3 and B2 and E. coli ATCC11229 were assessed after the exposure of different pH (gastric juice and gastric plus pancreatic juice challenges. In the artificial gastric juice (pH 2, both the viability of the strain B3 and B2 was decreased. Artificial juice treatments significantly reduced the adhesion to caco-2 cells (P< 0.05. High EPS-producing B3 survived better in the adverse gastrointestinal conditions and showed better ability of adhesion to Caco-2 cells when assessed for competition with E. coli ATCC 11229 compared to low EPS-producing B2. This investigation showed that EPS production could be affected or be involved in the viability, adherence and competition of L. delbrueckii subsp. bulgaricus strains and support the potential of B3 strain for development of new probiotic products.

  10. A rare case of langerhans cell histiocytosis of the gastrointestinal tract

    Institute of Scientific and Technical Information of China (English)

    Uday Shankar; Monika Prasad; Om P Chaurasia

    2012-01-01

    Langerhans cell histiocytosis (LCH) is a group of idiopathic disorders characterized by the proliferation of specialized,bone marrow-derived langerhans cells and mature eosinophils.The clinical spectrum ranges from an acute,fulminant,disseminated disease called LettererSiwe disease to solitary or few,indolent and chronic lesions of the bone or other organs called eosinophilic granuloma.Involvement of the gastrointestinal tract is very rare in LCH.We present the case of a 53-year-old woman referred by her primary care physician for a screening colonoscopy.A single sessile polyp,measuring 4 mm in size,was found in the rectum.Histopathological examination revealed that the lesion was relatively well circumscribed and comprised mainly a mixture of polygonal cells with moderate-to-abundant pink slightly granular cytoplasm.The nuclei within these cells had frequent grooves and were occasionally folded.Immunohistochemical staining was positive for CD-1a which confirmed the diagnosis of LCH.On further workup,there was no evidence of involvement of any other organ.On follow up colonoscopy one year later,there was no evidence of disease recurrence.Review of the published literature revealed that LCH presenting as solitary colonic polyp is rare.However,with the increasing rates of screening colonoscopy,more colonic polyps may be identified as LCH on histopathology.This underscores the importance of recognizing this rare condition and ensuring proper follow-up to rule out systemic disease.

  11. Gene therapy for type 1 diabetes mellitus in rats by gastrointestinal administration of chitosan nanoparticles containing human insulin gene

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To study the expression of human insulin gene in gastrointestinal tracts of diabetic rats. METHODS: pCHV.Ins, an expression plasmid of the human insulin gene, wrapped with chitosan nanoparticles, was transfected to the diabetic rats through lavage and coloclysis, respectively. Fasting blood glucose and plasma insulin levels were measured for 7 d. Reverse transcription polymerase chain reaction (RT-PCR) analysis and Western blot analysis were performed to confirm the expression of human insulin gene. RESULTS: Compared with the control group, the fasting blood glucose levels in the lavage and coloclysis groups were decreased significantly in 4 d (5.63 ± 0.48 mmol/L and 5.07 ± 0.37 mmol/L vs 22.12± 1.31 mmol/L, respectively, P < 0.01), while the plasma insulin levels were much higher (32.26±1.81 μIU/mL and 32.79 ± 1.84 μIU/mL vs 14.23 ± 1.38 μIU/mL, respectively, P<0.01). The human insulin gene mRNA and human insulin were only detected in the lavage and coloclysis groups. CONCLUSION: Human insulin gene wrapped with chitosan nanoparticles can be successfully transfected to rats through gastrointestinal tract, indicating that chitosan is a promising non-viral vector.

  12. A review of duodenal metastases from squamous cell carcinoma of the cervix presenting as an upper gastrointestinal bleed.

    Science.gov (United States)

    Kanthan, Rani; Senger, Jenna-Lynn; Diudea, Dana; Kanthan, Selliah

    2011-09-29

    Upper gastrointestinal bleeding due to duodenal metastases is extremely uncommon. Extra-pelvic spread of squamous cell carcinoma (SCC) of the cervix to the small bowel is rare with only 6 reported cases in the English literature since 1981(PubMed, Medline).We report the case of a 49-year-old woman who presented with upper-gastrointestinal bleeding two years after the diagnosis of SCC of the cervix. At esophagogastroduodenoscopy, there was a stricture in the second part of the duodenum which was biopsied for a suspected neoplastic lesion. Histologic and immunohistochemical examination showed a malignant lesion with characteristics identical to her original tumor in the cervix confirming the duodenal metastases.The clinical presentation of a 'malignant' upper-gastrointestinal bleed due to duodenal metastases from SCC of the cervix is unusual. Awareness of such infrequent patterns of metastases in cervical cancer confirmed by histopathological diagnosis is important for best practice therapeutic decisions in these patients.

  13. A review of duodenal metastases from squamous cell carcinoma of the cervix presenting as an upper gastrointestinal bleed

    Directory of Open Access Journals (Sweden)

    Diudea Dana

    2011-09-01

    Full Text Available Abstract Upper gastrointestinal bleeding due to duodenal metastases is extremely uncommon. Extra-pelvic spread of squamous cell carcinoma (SCC of the cervix to the small bowel is rare with only 6 reported cases in the English literature since 1981(PubMed, Medline. We report the case of a 49-year-old woman who presented with upper-gastrointestinal bleeding two years after the diagnosis of SCC of the cervix. At esophagogastroduodenoscopy, there was a stricture in the second part of the duodenum which was biopsied for a suspected neoplastic lesion. Histologic and immunohistochemical examination showed a malignant lesion with characteristics identical to her original tumor in the cervix confirming the duodenal metastases. The clinical presentation of a 'malignant' upper-gastrointestinal bleed due to duodenal metastases from SCC of the cervix is unusual. Awareness of such infrequent patterns of metastases in cervical cancer confirmed by histopathological diagnosis is important for best practice therapeutic decisions in these patients.

  14. GASTROINTESTINAL EOSINOPHILIA

    Science.gov (United States)

    Zuo, Li; Rothenberg, Marc E.

    2007-01-01

    SYNOPSIS Gastrointestinal eosinophilia, as a broad term for abnormal eosinophil accumulation in the GI tract, involves many different disease identities. These diseases include primary eosinophil associated gastrointestinal diseases, gastrointestinal eosinophilia in HES and all gastrointestinal eosinophilic states associated with known causes. Each of these diseases has its unique features but there is no absolute boundary between them. All three groups of GI eosinophila are described in this chapter although the focus is on primary gastrointestinal eosinophilia, i.e. EGID. PMID:17868858

  15. Red blood cell transfusion is associated with increased rebleeding in patients with nonvariceal upper gastrointestinal bleeding.

    Science.gov (United States)

    Restellini, S; Kherad, O; Jairath, V; Martel, M; Barkun, A N

    2013-02-01

    There exists considerable practice variation and little evidence to guide red blood cell (RBC) transfusion in patients with nonvariceal upper gastrointestinal bleeding (NVUGIB). Studies in other critically ill cohorts suggest associations between transfusions and adverse patient outcomes. To characterise any possible clinically-relevant association between RBC transfusion following NVUGIB with rebleeding and mortality. Observational study utilising the Canadian Registry of patients with Upper Gastrointestinal Bleeding and Endoscopy (RUGBE). Multivariable logistic regression models were used to examine and quantify independent associations between RBC transfusion and clinical outcomes. Overall, 1677 patients were included (66.2 ± 16.8 years, 61.7% male, 2.5 ± 1.7 comorbid conditions, initial haemoglobin, 96.8 ± 27.2 g/L); 53.7% received RBC transfusions (2.9 ± 1.6 units of blood), 31.6% had haemodynamic instability, 5.1% fresh blood on rectal examination and 8.6% in the nasogastric tube aspirate. Endoscopic haemostasis was performed in 35.2%. Overall rebleeding (defined as continuous bleeding, rebleeding or surgery) and mortality rates were 17.9% and 5.4%, respectively. After adjusting for potential confounders, transfusion of RBC within 24 h of presentation was significantly and independently associated with an increased risk of rebleeding (OR: 1.0, 95% CI: 0.6-1.8), but not death (OR: 1.5, 95% CI: 0.94-2.23). This study suggests an association between RBC transfusion following NVUGIB and subsequent rebleeding, after appropriate and extensive adjustment for confounding. Prospective randomised trial evidence is needed to identify the most efficacious and cost-effective transfusional strategies in these patients. © 2012 Blackwell Publishing Ltd.

  16. Efficient Inhibition of HIV Replication in the Gastrointestinal and Female Reproductive Tracts of Humanized BLT Mice by EFdA.

    Directory of Open Access Journals (Sweden)

    Uma Shanmugasundaram

    Full Text Available The nucleoside reverse transcriptase inhibitor (NRTI 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA in preclinical development exhibits improved safety and antiviral activity profiles with minimal drug resistance compared to approved NRTIs. However, the systemic antiviral efficacy of EFdA has not been fully evaluated. In this study, we utilized bone marrow/liver/thymus (BLT humanized mice to investigate the systemic effect of EFdA treatment on HIV replication and CD4+ T cell depletion in the peripheral blood (PB and tissues. In particular, we performed a comprehensive analysis of the female reproductive tract (FRT and gastrointestinal (GI tract, major sites of transmission, viral replication, and CD4+ T cell depletion and where some current antiretroviral drugs have a sub-optimal effect.EFdA treatment resulted in reduction of HIV-RNA in PB to undetectable levels in the majority of treated mice by 3 weeks post-treatment. HIV-RNA levels in cervicovaginal lavage of EFdA-treated BLT mice also declined to undetectable levels demonstrating strong penetration of EFdA into the FRT. Our results also demonstrate a strong systemic suppression of HIV replication in all tissues analyzed. In particular, we observed more than a 2-log difference in HIV-RNA levels in the GI tract and FRT of EFdA-treated BLT mice compared to untreated HIV-infected control mice. In addition, HIV-RNA was also significantly lower in the lymph nodes, liver, lung, spleen of EFdA-treated BLT mice compared to untreated HIV-infected control mice. Furthermore, EFdA treatment prevented the depletion of CD4+ T cells in the PB, mucosal tissues and lymphoid tissues.Our findings indicate that EFdA is highly effective in controlling viral replication and preserving CD4+ T cells in particular with high efficiency in the GI and FRT tract. Thus, EFdA represents a strong potential candidate for further development as a part of antiretroviral therapy regimens.

  17. Functional consequences of microbial shifts in the human gastrointestinal tract linked to antibiotic treatment and obesity

    NARCIS (Netherlands)

    Hernandez, E.; Bargiela, R.; Suarez Diez, M.; Friedrichs, A.; Pérez-Cobas, A.E.; Gosalbes, M.J.; Knecht, H.; Martinez-Martinez, M.; Seifert, J.; Bergen, von M.; Martins Dos Santos, V.A.P.

    2013-01-01

    The microbiomes in the gastrointestinal tract (GIT) of individuals receiving antibiotics and those in obese subjects undergo compositional shifts, the metabolic effects and linkages of which are not clearly understood. Herein, we set to gain insight into these effects, particularly with regard to ca

  18. Oral Human Immunoglobulin for Children with Autism and Gastrointestinal Dysfunction: A Prospective, Open-Label Study

    Science.gov (United States)

    Schneider, Cindy K.; Melmed, Raun D.; Barstow, Leon E.; Enriquez, F. Javier; Ranger-Moore, James; Ostrem, James A.

    2006-01-01

    Immunoglobulin secretion onto mucosal surfaces is a major component of the mucosal immune system. We hypothesized that chronic gastrointestinal (GI) disturbances associated with autistic disorder (AD) may be due to an underlying deficiency in mucosal immunity, and that orally administered immunoglobulin would be effective in alleviating chronic GI…

  19. Functional consequences of microbial shifts in the human gastrointestinal tract linked to antibiotic treatment and obesity

    NARCIS (Netherlands)

    Hernandez, E.; Bargiela, R.; Suarez Diez, M.; Friedrichs, A.; Pérez-Cobas, A.E.; Gosalbes, M.J.; Knecht, H.; Martinez-Martinez, M.; Seifert, J.; Bergen, von M.; Martins Dos Santos, V.A.P.

    2013-01-01

    The microbiomes in the gastrointestinal tract (GIT) of individuals receiving antibiotics and those in obese subjects undergo compositional shifts, the metabolic effects and linkages of which are not clearly understood. Herein, we set to gain insight into these effects, particularly with regard to

  20. Treatment of Feline Gastrointestinal Small-Cell Lymphoma With Chlorambucil and Glucocorticoids

    Science.gov (United States)

    Stein, Timothy J.; Pellin, MacKenzie; Steinberg, Howard; Chun, Ruthanne

    2011-01-01

    Gastrointestinal (GI) lymphoma is the most frequently diagnosed form of lymphoma in the cat and is categorized into two distinct forms based on the size of neoplastic lymphocytes. Treatments for both large- and small-cell GI lymphoma have been described previously; however, multiple chemotherapy protocols were used, a minimal amount of histopathological characterization was provided, and, in most studies, the majority of diagnoses were obtained via endoscopic pinch biopsies. Twenty-eight cats (24 with full-thickness intestinal biopsies) were diagnosed with small-cell GI lymphoma and treated with a combination of chlorambucil and glucocorticoids. The majority of cases were strongly CD3+, and many displayed epitheliotropism. The overall clinical response rate was 96%, with a median clinical remission duration of 786 days. Follow-up identified seven cats with relapsed disease—all of which were treated with a rescue protocol of cyclophosphamide and glucocorticoids; the response rate was 100%, and four of the 28 cats were diagnosed with a second malignancy. PMID:21041334

  1. Events at the host-microbial interface of the gastrointestinal tract III. Cell-to-cell signaling among microbial flora, host, and pathogens: there is a whole lot of talking going on.

    Science.gov (United States)

    Clarke, Marcie B; Sperandio, Vanessa

    2005-06-01

    Humans have an important association with their intestinal microbial flora. The microbial flora helps to shape the mammalian innate immune system, absorbs nutrients, and plays an intricate role on intestinal development. Microbes and mammals communicate with each other through an array of hormone and hormonelike chemical compounds. These "signals," however, are hijacked by bacterial pathogens, such as enterohemorrhagic Eschrichia coli (EHEC), to activate its virulence genes, colonize the host, and start the disease process. This review explores the cell-to-cell signaling events in the gastrointestinal tract that lead EHEC to regulate its virulence genes in a coordinate manner.

  2. Gastrointestinal fistula

    Science.gov (United States)

    Entero-enteral fistula; Enterocutaneous fistula; Fistula - gastrointestinal ... Most gastrointestinal fistulas occur after surgery. Other causes include: Blockage in the intestine Infection Crohn disease Radiation to the abdomen (most ...

  3. Wild Raspberry Subjected to Simulated Gastrointestinal Digestion Improves the Protective Capacity against Ethyl Carbamate-Induced Oxidative Damage in Caco-2 Cells.

    Science.gov (United States)

    Chen, Wei; Xu, Yang; Zhang, Lingxia; Li, Ya; Zheng, Xiaodong

    2016-01-01

    Ethyl carbamate (EC), a probable human carcinogen, occurs widely in many fermented foods. Previous studies indicated that EC-induced cytotoxicity was associated with oxidative stress. Wild raspberries are rich in polyphenolic compounds, which possess potent antioxidant activity. This study was conducted to investigate the protective effect of wild raspberry extracts produced before (RE) and after in vitro simulated gastrointestinal digestion (RD) on EC-induced oxidative damage in Caco-2 cells. Our primary data showed that ethyl carbamate could result in cytotoxicity and genotoxicity in Caco-2 cells and raspberry extract after digestion (RD) may be more effective than that before digestion (RE) in attenuating toxicity caused by ethyl carbamate. Further investigation by fluorescence microscope revealed that RD may significantly ameliorate EC-induced oxidative damage by scavenging the overproduction of intracellular reactive oxygen species (ROS), maintaining mitochondrial function and preventing glutathione (GSH) depletion. In addition, HPLC-ESI-MS results showed that the contents of identified polyphenolic compounds (esculin, kaempferol O-hexoside, and pelargonidin O-hexoside) were remarkably increased after digestion, which might be related to the better protective effect of RD. Overall, our results demonstrated that raspberry extract undergoing simulated gastrointestinal digestion may improve the protective effect against EC-induced oxidative damage in Caco-2 cells.

  4. Genome engineering in human cells.

    Science.gov (United States)

    Song, Minjung; Kim, Young-Hoon; Kim, Jin-Soo; Kim, Hyongbum

    2014-01-01

    Genome editing in human cells is of great value in research, medicine, and biotechnology. Programmable nucleases including zinc-finger nucleases, transcription activator-like effector nucleases, and RNA-guided engineered nucleases recognize a specific target sequence and make a double-strand break at that site, which can result in gene disruption, gene insertion, gene correction, or chromosomal rearrangements. The target sequence complexities of these programmable nucleases are higher than 3.2 mega base pairs, the size of the haploid human genome. Here, we briefly introduce the structure of the human genome and the characteristics of each programmable nuclease, and review their applications in human cells including pluripotent stem cells. In addition, we discuss various delivery methods for nucleases, programmable nickases, and enrichment of gene-edited human cells, all of which facilitate efficient and precise genome editing in human cells.

  5. Limited stage small cell carcinoma of the gastrointestinal tract: a clinicopathologic and prognostic analysis of 27 cases

    Directory of Open Access Journals (Sweden)

    Xiaoping Zou

    2013-02-01

    Full Text Available Small cell carcinoma of the gastrointestinal tract is a rare and aggressive neuroendocrine tumor. This study aims to analyze the clinical characteristics and potential prognostic factors for patients with limited stage small cell carcinoma of the gastrointestinal tract. The records of 27 patients with limited stage small cell carcinoma of the gastrointestinal tract, who all received surgery with lymphadenectomy, were retrieved and analyzed retrospectively. The median age of patients was 60 years old (range 38-79. The primary locations of tumor were the esophagus (74.1% and stomach (14.8%. The rate of preoperative accurate diagnosis (16.7% was low for small cell carcinoma of the esophagus and stomach. 40.7% of all the patients had regional lymph node metastases. Five patients underwent surgery alone, and the other 22 were treated with surgery + postoperative chemotherapy. All patients had disease progression or recurrence. The overall median survival time was 10 months and the 1-year survival rate was 37.0%. Patients who received postoperative chemotherapy had a median survival time of 12 months, which was superior to the 5-month survival of for those who only had surgery (P<0.0001. TNM stage (P=0.02 and postoperative chemotherapy (P<0.0001 were considered as two prognostic factors in univariate analysis. Postoperative chemotherapy was a significant independent prognostic factor in multivariate analysis (P=0.01. The prognosis for patients with limited stage small cell carcinoma of the gastrointestinal tract remains dismal, however, postoperative chemotherapy may have the potential to improve the outcome for these patients.

  6. Gastrointestinal involvement of recurrent renal cell carcinoma: CT findings and clinicpathologic features

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyo Jung; Kim, Hyun Jin; Park, Seung Ho; Lee, Jong Seok; Kim, Ah Young [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Ha, Hyun Kwon [Dept. of Radiology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung (Korea, Republic of)

    2017-06-15

    To retrospectively evaluate the CT findings and clinicopathologic features in patients with gastrointestinal (GI) involvement of recurrent renal cell carcinoma (RCC). The medical records were reviewed for 15 patients with 19 pathologically proven GI tract metastases of RCC. The CT findings were analyzed to determine the involved sites and type of involvement; lesion size, morphology, and contrast enhancement pattern; and occurrence of lymphadenopathy, ascites and other complications. The most common presentation was GI bleeding (66.7%). The average interval between nephrectomy and the detection of GI involvement was 30.4 ± 37.4 months. GI lesions were most commonly found in the ileum (36.8%) and duodenum (31.6%). A distant metastasis (80%) was more common than a direct invasion from metastatic lesions. The mean lesion size was 34.1 ± 15.0 mm. Intraluminal polypoid masses (63.2%) with hyperenhancement (78.9%) and heterogeneous enhancement (63.2%) were the most common findings. No patients had regional lymphadenopathy. Complications occurred in four patients, with one each of bowel obstruction, intussusception, bile duct dilatation, and pancreatic duct dilatation. GI involvement of recurrent RCC could be included in the differential diagnosis of patients with heterogeneous, hyperenhanced intraluminal polypoid masses in the small bowel on CT scans along with a relative paucity of lymphadenopathy.

  7. Alpha-Synuclein to the Rescue: Immune Cell Recruitment by Alpha-Synuclein during Gastrointestinal Infection.

    Science.gov (United States)

    Labrie, Viviane; Brundin, Patrik

    2017-09-02

    Intraneuronal accumulation of misfolded alpha-synuclein in the central and peripheral nervous systems is strongly linked to Parkinson disease (PD) and other related synucleinopathies. In rare inherited forms of PD, point mutations or gene multiplications mediate the formation of alpha-synuclein protein aggregates. However, in most PD cases it is presumed that the combined effects of ageing and environmental factors drive the formation of alpha-synuclein aggregates. Despite advances regarding alpha-synuclein pathobiology, the normal functions of this protein and factors that regulate its expression are not well understood. We discuss a recent study reporting that viral infection induces alpha-synuclein expression in neurons of the gastrointestinal tract. Alpha-synuclein levels increased during norovirus infection in the duodenum of children. In an in vitro paradigm, monomeric and oligomeric alpha-synuclein acted as chemoattractants for neutrophils and monocytes, and promoted the maturation of dendritic cells. This suggests that alpha-synuclein facilitates immune responses to infection. We explore the possibility that intestinal infections, and associated inflammation, place individuals at increased risk of PD by increasing alpha-synuclein levels and promoting the formation of alpha-synuclein aggregates that propagate in a prion-like fashion via the vagal nerve to the brainstem. © 2017 S. Karger AG, Basel.

  8. Massive Upper Gastrointestinal Bleeding Secondary to Duodenal Metastasis of Transitional Cell Carcinoma of the Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Carlos H.F. Chan

    2011-04-01

    Full Text Available Acute upper gastrointestinal (UGI bleeding is a common problem in our clinical practice and is often due to peptic ulcer diseases. Occasionally, malignancy may be implicated in these situations. Here we report a rare case of UGI bleeding secondary to metastatic transitional cell carcinoma (TCC of the urinary bladder. A 62-year-old man with a history of stage IIIb TCC of the urinary bladder presented with hematemesis. Endoscopy showed a large tumor in the second stage of the duodenum that occupied 40% of the duodenal circumference, over 7 cm in length. Biopsies revealed a poorly differentiated malignant neoplasm consistent with metastasis from urothelial carcinoma that was identical to the previous surgical specimen of the urinary bladder. He was treated with supportive therapy and intravenous proton pump inhibitor and was discharged home 2 weeks later. Two weeks after discharge, the patient returned to the hospital with a painful swelling of the floor of his mouth. Biopsy again showed the same cancer type. He had unremitting bleeding from his mouth requiring multiple transfusions and a course of palliative radiation therapy. He progressively deteriorated in his cardiopulmonary and neurological functions and expired with cardiopulmonary arrest one month later.

  9. Modulation of Ingestive Behavior and Gastrointestinal Motility by Ghrelin in Diabetic Animals and Humans

    Directory of Open Access Journals (Sweden)

    Chih-Yen Chen

    2010-05-01

    Full Text Available Acyl ghrelin, a 28-amino acid peptide hormone, is the endogenous cognate ligand for the growth hormone secretagogue receptor. Ghrelin is involved in stimulating growth hormone release, eliciting feeding behavior, inducing adiposity and stimulating gastrointestinal motility. Ghrelin is unique for its post-translational modification of O-n-octanoylation at serine 3 through ghrelin O-acyltransferase, and is the only peripheral signal to enhance food intake. Plasma ghrelin levels manifest “biphasic changes” in diabetes mellitus (DM. In the early stage of DM, the stomach significantly increases the secretion of ghrelin into the plasma, and elevated plasma ghrelin levels are correlated with diabetic hyperphagic feeding and accelerated gastrointestinal motility. In the late stage of DM, plasma ghrelin levels may be lower, which might be linked with anorexia/muscle wasting, delayed gastrointestinal transit, and even gastroparesis. Therefore, the unique ghrelin system may be the most important player compared to the other hindgut hormones participating in the “entero-insular axis”. Further studies using either knockdown or knockout of ghrelin gene products and ghrelin O-acyltransferase may unravel the pathogenesis of DM, and show benefits in combating this disease and metabolic syndrome.

  10. Immunocytochemical Identification and Localization of Diffuse Neuroendocrine System (DNES) Cells in Gastrointestinal Tract of Channel Catfish (Ictalurus punctatus)

    Institute of Scientific and Technical Information of China (English)

    HE Min; WANG Kai-yu; ZHANG Yu

    2009-01-01

    To detect distribution and relative frequency of diffuse neuroendocrine system (DNES) cells in the gastrointestinal tract of channel catfish (Ictalurus punctatus), the intestinal tract of channel catfish was divided into seven portions from proximal to distal: the enlarged area after oesophagus, cardia, fundus, pylorus, and anterior, middle, and posterior intestine. Immunohistochemical method using the strept avidin-biotin-complex (SABC) was employed. All antisera between seven portions of the channel catfish were compared statistically using statistical package for the social science (SPSS). Five types of DNES cells were determined: neuropeptide Y-immunoreactive (NPY-IR) cells were demonstrated in both anterior and middle intestine; serotonin (5-HT) immunoreactive cells were detected throughout the whole gastrointestinal tract; vasoactive intestinal peptide (VIP) positive cells were at the highest frequency in pylorus; glucagon-immunoreactive (GLU-IR) cells were moderate in number in the fundus and anterior, middle intestine, and no immunoreactivity was determined in the other portions; somatostatin (SOM) positive cells were more abundant in the anterior and middle intestine. The regional distribution and relative frequency of immunoreactive cells in the channel catfish, Ictalurus punctatus, are essentially similar to those of other fish. However, some characteristics are observed in this species, which further proved that the diversity of the physiological function of DNES cells was based on their morphology.

  11. [Neoplasms of the disseminated neuroendocrine cell system of the gastrointestinal tract].

    Science.gov (United States)

    Klöppel, G

    2015-05-01

    The classification of neuroendocrine neoplasms (NEN) of the gastrointestinal tract and also the pancreas is based on the World Health Organization (WHO) classification from 2010, the site-related TNM stage classification and the clinicopathological characterization. This allows a classification of NEN that is adapted to the individual patient, is of high prognostic relevance and serves the needs of an adequate treatment. This article summarizes the current knowledge on the clinical pathology of gastrointestinal NEN, in order to enable a rapid diagnostic orientation.

  12. Viral suppression and immune restoration in the gastrointestinal mucosa of human immunodeficiency virus type 1-infected patients initiating therapy during primary or chronic infection.

    Science.gov (United States)

    Guadalupe, Moraima; Sankaran, Sumathi; George, Michael D; Reay, Elizabeth; Verhoeven, David; Shacklett, Barbara L; Flamm, Jason; Wegelin, Jacob; Prindiville, Thomas; Dandekar, Satya

    2006-08-01

    Although the gut-associated lymphoid tissue (GALT) is an important early site for human immunodeficiency virus (HIV) replication and severe CD4+ T-cell depletion, our understanding is limited about the restoration of the gut mucosal immune system during highly active antiretroviral therapy (HAART). We evaluated the kinetics of viral suppression, CD4+ T-cell restoration, gene expression, and HIV-specific CD8+ T-cell responses in longitudinal gastrointestinal biopsy and peripheral blood samples from patients initiating HAART during primary HIV infection (PHI) or chronic HIV infection (CHI) using flow cytometry, real-time PCR, and DNA microarray analysis. Viral suppression was more effective in GALT of PHI patients than CHI patients during HAART. Mucosal CD4+ T-cell restoration was delayed compared to peripheral blood and independent of the time of HAART initiation. Immunophenotypic analysis showed that repopulating mucosal CD4+ T cells were predominantly of a memory phenotype and expressed CD11 alpha, alpha(E)beta 7, CCR5, and CXCR4. Incomplete suppression of viral replication in GALT during HAART correlated with increased HIV-specific CD8+ T-cell responses. DNA microarray analysis revealed that genes involved in inflammation and cell activation were up regulated in patients who did not replenish mucosal CD4+ T cells efficiently, while expression of genes involved in growth and repair was increased in patients with efficient mucosal CD4+ T-cell restoration. Our findings suggest that the discordance in CD4+ T-cell restoration between GALT and peripheral blood during therapy can be attributed to the incomplete viral suppression and increased immune activation and inflammation that may prevent restoration of CD4+ T cells and the gut microenvironment.

  13. Immunohistochemical study on localization of serotonin immunoreactive cells in the gastrointestinal tract of the European catfish (Silurus glanis, L.).

    Science.gov (United States)

    Köprücü, S; Yaman, M

    2015-02-01

    In this study, it was aimed to identify the distribution of serotonin immunoreactive cells within the gastrointestinal tract (GIT) of European catfish (Silurus glanis). For this purpose, the tissue samples were taken from the stomach (cardia, fundus and pylorus region) and intestine (anterior, middle and posterior region). They were examined by applying the avidin-biotin-immunoperoxidase method. The serotonin containing immunoreactive cells are presented in all regions of the GIT. It was determined to be localized generally in different distribution within the stomachs and intestines of S. glanis. It was found that the most intensive regions of immunoreactive cells were the cardia stomach and posterior of intestine.

  14. Efeito protetor da lactoferrina humana no trato gastrintestinal Efecto protector de la lactoferrina humana en el sistema gastrointestinal Protective effect of human lactoferrin in the gastrointestinal tract

    Directory of Open Access Journals (Sweden)

    Valterlinda Alves de O. Queiroz

    2013-03-01

    ón de morbilidades gastrointestinales. FUENTES DE DATOS: Revisión no sistemática de la literatura utilizando como estrategia de búsqueda investigación bibliográfica en bases de datos, que incluyeron SciELO, Lilacs y MedLine entre 1990 y 2011. Los descriptores utilizados fueron: lactoferrina, leche materna/humana, gastrointestinal e inmunidad, en los idiomas portugués e inglés. SÍNTESIS DE LOS DATOS: La lactoferrina es la segunda proteína predominante en la leche humana, con concentraciones más elevadas en el calostro (5,0 a 6,7mg/mL respecto a la leche madura (0,2 a 2,6mg/mL. En contraste, la leche de vaca contiene tenores inferiores, 0,83mg/mL en el calostro y 0,09mg/mL en la leche madura. La lactoferrina desempeña diversas funciones fisiológicas en la protección del sistema gastrointestinal. La actividad antimicrobiana está relacionada a la capacidad de secuestrar hierro de los fluidos biológicos y/o de desestructurar la membrana de microorganismos. La lactoferrina posee además la capacidad de estimular la proliferación celular. La acción antiinflamatoria desempeñada por la lactoferrina está asociada a la capacidad de penetrar en el núcleo del leucocito y bloquear la transcripción del nuclear factor Kappa B. Frente a la importancia de la lactoferrina en la prevención de enfermedades infecciosas en niños amamantados al pecho, la industria viene, por medio de ingeniería genética, desarrollando tecnologías para expresar esta proteína recombinante humana en plantas y animales en el intento de adecuar la composición de las fórmulas infantiles a aquella de la leche humana. CONCLUSIONES: La lactoferrina humana es un péptido con potencial para prevenir morbilidades, especialmente las gastrointestinales. Evidencias científicas de los efectos protectores de la lactoferrina humana fortalecen todavía más la recomendación para la práctica de la lactancia materna.OBJECTIVE: To describe mechanisms of action of human lactoferrin to protect

  15. Cellular and Molecular Mechanisms of 3,3′-Diindolylmethane in Gastrointestinal Cancer

    Directory of Open Access Journals (Sweden)

    Soo Mi Kim

    2016-07-01

    Full Text Available Studies in humans have shown that 3,3′-diindolylmethane (DIM, which is found in cruciferous vegetables, such as cabbage and broccoli, is effective in the attenuation of gastrointestinal cancers. This review presents the latest findings on the use, targets, and modes of action of DIM for the treatment of human gastrointestinal cancers. DIM acts upon several cellular and molecular processes in gastrointestinal cancer cells, including apoptosis, autophagy, invasion, cell cycle regulation, metastasis, angiogenesis, and endoplasmic reticulum (ER stress. In addition, DIM increases the efficacy of other drugs or therapeutic chemicals when used in combinatorial treatment for gastrointestinal cancer. The studies to date offer strong evidence to support the use of DIM as an anticancer and therapeutic agent for gastrointestinal cancer. Therefore, this review provides a comprehensive understanding of the preventive and therapeutic properties of DIM in addition to its different perspective on the safety of DIM in clinical applications for the treatment of gastrointestinal cancers.

  16. Arcobacter in Lake Erie beach waters: an emerging gastrointestinal pathogen linked with human-associated fecal contamination.

    Science.gov (United States)

    Lee, Cheonghoon; Agidi, Senyo; Marion, Jason W; Lee, Jiyoung

    2012-08-01

    The genus Arcobacter has been associated with human illness and fecal contamination by humans and animals. To better characterize the health risk posed by this emerging waterborne pathogen, we investigated the occurrence of Arcobacter spp. in Lake Erie beach waters. During the summer of 2010, water samples were collected 35 times from the Euclid, Villa Angela, and Headlands (East and West) beaches, located along Ohio's Lake Erie coast. After sample concentration, Arcobacter was quantified by real-time PCR targeting the Arcobacter 23S rRNA gene. Other fecal genetic markers (Bacteroides 16S rRNA gene [HuBac], Escherichia coli uidA gene, Enterococcus 23S rRNA gene, and tetracycline resistance genes) were also assessed. Arcobacter was detected frequently at all beaches, and both the occurrence and densities of Arcobacter spp. were higher at the Euclid and Villa Angela beaches (with higher levels of fecal contamination) than at the East and West Headlands beaches. The Arcobacter density in Lake Erie beach water was significantly correlated with the human-specific fecal marker HuBac according to Spearman's correlation analysis (r = 0.592; P Arcobacter sequences were closely related to Arcobacter cryaerophilus, which is known to cause gastrointestinal diseases in humans. Since human-pathogenic Arcobacter spp. are linked to human-associated fecal sources, it is important to identify and manage the human-associated contamination sources for the prevention of Arcobacter-associated public health risks at Lake Erie beaches.

  17. Impaired Lymphocytes Development and Xenotransplantation of Gastrointestinal Tumor Cells in Prkdc-Null SCID Zebrafish Model

    Directory of Open Access Journals (Sweden)

    In Hye Jung

    2016-08-01

    Full Text Available Severe combined immunodeficiency (SCID mice have widely been used as hosts for human tumor cell xenograft study. This animal model, however, is labor intensive. As zebrafish is largely emerging as a promising model system for studying human diseases including cancer, developing efficient immunocompromised strains for tumor xenograft study are also demanded in zebrafish. Here, we have created the Prkdc-null SCID zebrafish model which provides the stable immune-deficient background required for xenotransplantation of tumor cell. In this study, the two transcription activator-like effector nucleases that specifically target the exon3 of the zebrafish Prkdc gene were used to induce a frame shift mutation, causing a complete knockout of the gene function. The SCID zebrafish showed susceptibility to spontaneous infection, a well-known phenotype found in the SCID mutation. Further characterization revealed that the SCID zebrafish contained no functional T and B lymphocytes which reflected the phenotypes identified in the mice SCID model. Intraperitoneal injection of human cancer cells into the adult SCID zebrafish clearly showed tumor cell growth forming into a solid mass. Our present data show the suitability of using the SCID zebrafish strain for xenotransplantation experiments, and in vivo monitoring of the tumor cell growth in the zebrafish demonstrates use of the animal model as a new platform of tumor xenograft study.

  18. Primary gastrointestinal lymphoma

    Institute of Scientific and Technical Information of China (English)

    Prasanna Ghimire; Guang-Yao Wu; Ling Zhu

    2011-01-01

    Gastrointestinal tract is the most common extranodal site involved by lymphoma with the majority being non-Hodgkin type. Although lymphoma can involve any part of the gastrointestinal tract, the most frequent sites in order of its occurrence are the stomach followed by small intestine and ileocecal region. Gastrointestinal tract lymphoma is usually secondary to the widespread nodal diseases and primary gastrointestinal tract lymphoma is relatively rare. Gastrointestinal lymphomas are usually not clinically specific and indistinguishable from other benign and malignant conditions. Diffuse large B-cell lymphoma is the most common pathological type of gastrointestinal lymphoma in essentially all sites of the gastrointestinal tract, although recently the frequency of other forms has also increased in certain regions of the world. Although some radiological features such as bulky lymph nodes and maintenance of fat plane are more suggestive of lymphoma, they are not specific,thus mandating histopathological analysis for its definitive diagnosis. There has been a tremendous leap in the diagnosis, staging and management of gastrointestinal lymphoma in the last two decades attributed to a better insight into its etiology and molecular aspect as well as the knowledge about its critical signaling pathways.

  19. EFFECTS OF PERIOPERATIVE CIMETIDINE ADMINISTRATION ON TUMOR CELL NUCLEAR MORPHOMETRY AND DNA CONTENT IN PATIENTS WITH GASTROINTESTINAL CANCER

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To explore the effects of perioperative cimetidine administration on tumor cell nuclear morphometric parameters and DNA content in patients with gastrointestinal adenocarcinoma. Methods: 49 patients with pathologically confirmed gastrointestinal adenocarcinoma were randomized into test group (n=25) and control group (n=24). The test group started oral cimetidine intake 400 mg, tid, 7-10d before operation, followed by standard curative operation. The control group did not receive cimetidine. Tumor specimens were paraffin embedded for microsection and stained with hematoxylin and eosin (HE) and Feulgen stain. Morphometric studies and DNA content of tumor nuclei were performed on IBAS Image Analyzer. Results: The tumor cell nuclear area (m m2), nuclear perimeter (m m), maximal nuclear diameter (m m) for test group/control group were 23.54 ± 5.08/34.69± 10.08 (Pquintuple ploidy tumor cells for test group/control group were 16.64± 2.58/5.33± 2.14 (P0.50), 12.42± 5.00/14.48± 0.74 (P>0.20), 31.11± 6.86/ 45.97± 3.82 (P<0.005), respectively. Conclusion: Perioperative administration of cimetidine in gasgtrointestinal cancer patients could decrease the nuclear size and raise the percentage of diploid tumor cells, and convert high aneuploid tumor cells into low-aneuploid tumor cells, which might help reduce the invasiveness of tumor cells.

  20. Stem cell factor-mediated wild-type KIT receptor activation is critical for gastrointestinal stromal tumor cell growth

    Institute of Scientific and Technical Information of China (English)

    Chen-Guang Bai; Xiao-Wei Hou; Feng Wang; Cen Qiu; Yan Zhu; Ling Huang; Jing Zhao

    2012-01-01

    AIM:To clarify the biological role of stem cell factor (SCF)-mediated wild-type KIT receptor activation in gastrointestinal stromal tumor (GIST) growth.METHODS:The co-expression of wild-type KIT receptor and SCF was evaluated in 51 GIST samples using mutation analysis and immunohistochemistry,and the results were correlated with clinicopathological parameters,including the mitotic count,proliferative index (Ki-67 immunohistochemical staining),mitotic index (phospho-histone H3 immunohistochemical staining)and apoptotic index (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling).Using primary cultured GIST cells,the effect of SCF-mediated wild-type KIT receptor activation was determined by western blotting,methyl thiazolyl tetrazolium (MTT),and apoptosis assays.RESULTS:We found that wild-type KIT receptor and SCF protein were expressed in 100% and 76.5% of the 51 GIST samples,respectively,and the co-expression of wild-type KIT receptor and SCF was associated with known indicators of poor prognosis,including larger tumor size (P =0.0118),higher mitotic count (P =0.0058),higher proliferative index (P =0.0012),higher mitotic index (P =0.0282),lower apoptosis index (P =0.0484),and increased National Institutes of Health risk level (P =0.0012).We also found that the introduction of exogenous SCF potently increased KIT kinase activity,stimulated cell proliferation (P < 0.01) and inhibited apoptosis (P < 0.01) induced by serum starvation,while a KIT immunoblocking antibody suppressed proliferation (P =0.01) and promoted apoptosis (P < 0.01)in cultured GIST cells.CONCLUSION:SCF-mediated wild-type KIT receptor activation plays an important role in GIST cell growth.The inhibition of SCF-mediated wild-type KIT receptor activation may prove to be particularly important for GIST therapy.

  1. Terpinen-4-ol: A Novel and Promising Therapeutic Agent for Human Gastrointestinal Cancers.

    Directory of Open Access Journals (Sweden)

    Shiran Shapira

    Full Text Available Terpinen-4-ol, a naturally occurring monoterpene is the main bioactive component of tea-tree oil and has been shown to have many biological activities.To study the antitumor effects of terpinen-4-ol and its mechanism of action in prostate and GI malignancies, alone and in combination with chemotherapeutic and biological agents.Terpinen-4-ol was administrated alone or combined with standard chemotherapy (Oxaliplatin, Fluorouracil, Gemcitabine, Tarceva and biological agent (Cetuximab. It was also combined with humanized anti-CD24 mAbs (was developed by us. Killing effects were measured qualitatively by light microscopy and quantitatively using the MTT and FACS analysis, following treatment of colorectal, pancreatic, gastric and prostate cancer cells. Terpinen-4-ol effect on tumor development was evaluated in xenograft model.Terpinen-4-ol induces a significant growth inhibition of colorectal, pancreatic, prostate and gastric cancer cells in a dose-dependent manner (10-90% in 0.005-0.1%. Terpinen-4-ol and various anti-cancer agents (0.2μM oxaliplatin and 0.5μM fluorouracil demonstrated a synergistic inhibitory effect (83% and 91%, respectively on cancer cell proliferation. In KRAS mutated colorectal cancer cells, which are resistant to anti-EGFR therapy, combining of terpinen-4-ol with cetuximab (1 μM resulted in impressive efficacy of 80-90% growth inhibition. Sub-toxic concentrations of terpinen-4-ol potentiate anti-CD24 mAb (150μg/ml-induced growth inhibition (90%. Considerable reduction in tumor volume was seen following terpinen-4-ol (0.2% treatment alone and with cetuximab (10mg/kg (40% and 63%, respectively as compare to the control group.Terpinen-4-ol significantly enhances the effect of several chemotherapeutic and biological agents. The possible molecular mechanism for its activity involves induction of cell-death rendering this compound as a potential anti-cancer drug alone and in combination in the treatment of numerous malignancies

  2. High adhesion of tumor cells to mesothelial monolayers derived from peritoneal wash of disseminated gastrointestinal cancers.

    Directory of Open Access Journals (Sweden)

    Danilo Ranieri

    Full Text Available The role of the mesothelial layer in the peritoneal spreading of cancer cells is only partially clarified. Here we attempted to better define the mesothelial contribution to the tumor cell adhesion using a direct adhesion test applied to human primary cultures of mesothelial cells (HPMCs derived from the peritoneal washes of patients with gastric and colorectal cancers. Gastric and colon carcinoma cells were seeded on different mesothelial monolayers and quantitative fluorescence analysis was performed to analyze their growth and adhesive properties. The adhesion of the cancer cells was not affected by the origin of the HPMCs when derived from patients with different cancers or with benign disease. In contrast, the high levels of ICAM1 expression and ROS production, which characterize these senescent mesothelial cells, enhanced the tumor cell adhesion. These results suggest that the mesothelial adhesive properties are dependent on the cell senescence, while are not affected by the tumor environment. The use of peritoneal washes as a source to isolate HPMCs provides a practical and reliable tool for the in vitro analysis of the mesothelial conditions affecting the peritoneal carcinomatosis.

  3. Cytotoxic Effects of Newly Synthesized Palladium(II Complexes of Diethyldithiocarbamate on Gastrointestinal Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Shahram Hadizadeh

    2014-01-01

    Full Text Available As a part of a drug development program to discover novel therapeutic and more effective palladium (Pd based anticancer drugs, a series of water-soluble Pd complexes have been synthesized by interaction between [Pd (phen(H2O2(NO32] and alkylenebisdithiocarbamate(al-bis-dtc disodium salts. This study was undertaken to examine the possible cytotoxic effect of three novel complexes (0.125–64 µg/mL on human gastric carcinoma (AGS, esophageal squamous cell carcinoma (Kyse-30, and hepatocellular carcinoma (HepG2 cell lines. The cytotoxicity was examined using cell proliferation and acridine orange/ethidium bromide (AO/EB assay. In order to examine the effects of new Pd(II complexes on cell cycle status, we performed cell cycle analysis. The complexes were found to have completely lethal effects on the cell lines, and the half maximal inhibitory concentration (IC50 values obtained for the cell lines were much lower in comparison with cisplatin. We demonstrated that the three new Pd(II complexes are able to induce G2/M phase arrest in AGS and HepG2; in addition, the Pd(II complexes caused an S phase arrest in Kyse-30 cell line. Our results indicate that newly synthesized Pd(II complexes may provide a novel class of chemopreventive compounds for anticancer therapy.

  4. Doxorubicin delivery enhanced by electroporation to gastrointestinal adenocarcinoma cells with P-gp overexpression.

    Science.gov (United States)

    Kulbacka, Julita; Daczewska, Małgorzata; Dubińska-Magiera, Magda; Choromańska, Anna; Rembiałkowska, Nina; Surowiak, Paweł; Kulbacki, Marek; Kotulska, Małgorzata; Saczko, Jolanta

    2014-12-01

    Electroporation (EP) can effectively support the penetration of macromolecules from the extracellular space into cells. Electropores induced by the influence of electromagnetic field generate additional paths of transport for macromolecules. The aim of this study was evaluation of the electroporation effect on doxorubicin transport efficiency to human colon (LoVo and LoVo/DX) and gastric (EPG85-257/P and EPG85-257/RDB) adenocarcinoma cells with overexpression of P-glycoprotein and murine macrophage cell line (P388/D1). In our EP experiments cells were placed into a cuvette with aluminum electrodes and pulsed with five square electric pulses of 1300 V/cm and duration of 50 μs each. Cells were also treated with low doxorubicin concentration ([DOX]=1.7 μM). The ultrastructure (TEM) and changes of P-glycoprotein expression of tumor cells subjected to electric field were monitored. The mitochondrial cell function and trypan blue staining were evaluated after 24h. Our results indicate the most pronounced effect of EP with DOX and disturbed ultrastructure in resistant gastric and colon cells with decrease of P-gp expression. Electroporation may be an attractive delivery method of cytostatic drugs in chemotherapy, enabling reduction of drug dose, exposure time and side effects.

  5. Diffusion inside living human cells

    DEFF Research Database (Denmark)

    Leijnse, N.; Jeon, J. -H.; Loft, Steffen

    2012-01-01

    Naturally occurring lipid granules diffuse in the cytoplasm and can be used as tracers to map out the viscoelastic landscape inside living cells. Using optical trapping and single particle tracking we found that lipid granules exhibit anomalous diffusion inside human umbilical vein endothelial...... cells. For these cells the exact diffusional pattern of a particular granule depends on the physiological state of the cell and on the localization of the granule within the cytoplasm. Granules located close to the actin rich periphery of the cell move less than those located towards to the center...... of the cell or within the nucleus. Also, granules in cells which are stressed by intense laser illumination or which have attached to a surface for a long period of time move in a more restricted fashion than those within healthy cells. For granules diffusing in healthy cells, in regions away from the cell...

  6. Identification of orexin A- and orexin type 2 receptor-positive cells in the gastrointestinal tract of neonatal dogs

    Directory of Open Access Journals (Sweden)

    C Dall’Aglio

    2009-08-01

    Full Text Available The presence and distribution of cells positive to orexin A (OXA and to orexin type 2 receptor (OX2R were investigated in the gastrointestinal tract of neonatal dogs by means of immunohistochemical techniques. The orexin A-positive cells were identified with some of the endocrine cells in the stomach and in the duodenum; they were both of the open and closed type and were lacking in the large intestine. In the stomach, a large subset of orexin A-positive cells also showed gastrin-like immunoreactivity while, in the duodenum, many of them seemed to store serotonin. The orexin type 2 receptor-positive cells were evidenced all along the gastrointestinal tract examined, also in the large intestine, and they showed the same morphological characteristics as those positive to orexin A. Moreover, the immunohistochemical techniques revealed intense positivity for both orexin A and orexin type 2 receptor in the neurons and fibers of the enteric nervous system. A large subset of orexin A-positive neurons seemed to store substance P.

  7. The Role of Costimulatory Molecules in the Development of Memory and Effector T Helper 2 Cells During an in vivo Immune Response to the Murine Gastrointestinal Parasite Heligmosomoides polygyrus

    Science.gov (United States)

    2007-11-02

    not well understood. One model used to study the Th immune response involves oral infection of mice with the gastrointestinal nematode parasite...the development of the Th2 response to the gastrointestinal nematode parasite Heligmosomoides polygyrus.” Discussion...4-producing effector and memory Th2 cells following priming with the murine gastrointestinal nematode parasite H. polygyrus. Previous studies

  8. Recurrent Renal Cell Carcinoma with Synchronous Tumor Growth in Azygoesophageal Recess and Duodenum: A Rare Cause of Anemia and Upper Gastrointestinal Bleeding

    Directory of Open Access Journals (Sweden)

    Vamshidhar R. Vootla

    2015-01-01

    Full Text Available Renal cell carcinoma (RCC has potential to present with distant metastasis several years after complete resection. The common sites of metastases include the lungs, bones, liver, renal fossa, and brain. RCCs metastasize rarely to the duodenum, and duodenal metastasis presenting with acute gastrointestinal bleed is infrequently reported in literature. We present a case of synchronous presentation of duodenal and azygoesophageal metastasis manifesting as acute upper gastrointestinal bleeding, four years after undergoing nephrectomy for RCC. The patient underwent further workup and was treated with radiation. The synchronous presentation is rare and stresses the importance of searching for recurrence of RCC in patients presenting with acute gastrointestinal bleeding.

  9. Neonatal lethality of neural crest cell-specific Rest knockout mice is associated with gastrointestinal distension caused by aberrations of myenteric plexus.

    Science.gov (United States)

    Aoki, Hitomi; Hara, Akira; Oomori, Yoshiyuki; Shimizu, Yasutake; Yamada, Yasuhiro; Kunisada, Takahiro

    2014-10-01

    RE1-silencing transcription factor (REST), also known as NRSF (neuron-restrictive silencer factor), is a well-known transcriptional repressor of neural genes. Rest null mice have embryonic lethality which prevents further investigations of the functions of the Rest gene in vivo. We studied neonatal but not embryonic lethality that was characterized by gastrointestinal tract dilation in the neural crest cell (NCC)-specific Rest conditional knockout (CKO) mice. While no histological abnormalities except the thinning of the digestive tract as a consequence of the gas accumulation were found in the digestive tract of the mutant mice, they do not have proper gastric retention after oral dye administration and the reduction of acetylcholinesterase (AChE) activity in NCC-derived myenteric plexus in the stomach was detected. High CO2 concentration in the dilated digestive tract of the Rest CKO mice indicates a failure of gut function by underdeveloped cholinergic transmission in the enteric nervous system. The observed gastrointestinal distension phenotype provides a model for understanding the genetic and molecular basis of NCC defects in humans.

  10. Human stromal (mesenchymal) stem cells

    DEFF Research Database (Denmark)

    Aldahmash, Abdullah; Zaher, Walid; Al-Nbaheen, May

    2012-01-01

    Human stromal (mesenchymal) stem cells (hMSC) represent a group of non-hematopoietic stem cells present in the bone marrow stroma and the stroma of other organs including subcutaneous adipose tissue, placenta, and muscles. They exhibit the characteristics of somatic stem cells of self-renewal and......Human stromal (mesenchymal) stem cells (hMSC) represent a group of non-hematopoietic stem cells present in the bone marrow stroma and the stroma of other organs including subcutaneous adipose tissue, placenta, and muscles. They exhibit the characteristics of somatic stem cells of self...... of clinical applications, e.g., non-healing bone fractures and defects and also non-skeletal degenerative diseases like heart failure. Currently, the numbers of clinical trials that employ MSC are increasing. However, several biological and biotechnological challenges need to be overcome to benefit from...

  11. Detection of Clostridium botulinum type C cells in the gastrointestinal tracts of Mozambique tilapia (Oreochromis mossambicus) by polymerase chain reaction

    Science.gov (United States)

    Nol, P.; Williamson, J.L.; Rocke, T.E.; Yuill, Thomas M.

    2004-01-01

    We established a method of directly detecting Clostridium botulinum type C cells, while minimizing spore detection, in the intestinal contents of Mozambique tilapia (Oreochromis mossambicus). This technique involved extraction of predominantly cellular DNA from tilapia intestinal tracts and used a polymerase chain reaction assay to detect presence of type C1 toxin gene. We consistently detected C. botulinum type C cells in tilapia gastrointestinal contents at a level of 7.5×104 cells per 0.25 g material or 1.9×103 cells. This technique is useful for determining prevalence of the potentially active organisms within a given population of fish and may be adapted to other types of C. botulinum and vertebrate populations as well.

  12. Genome sequence of Victivallis vadensis ATCC BAA-548, an anaerobic bacterium from the phylum Lentisphaerae, isolated from the human gastro-intestinal tract

    Energy Technology Data Exchange (ETDEWEB)

    Van Passel, Mark W.J. [Wageningen University and Research Centre, The Netherlands; Kant, Ravi [University of Helsinki; Palva, Airi [University of Helsinki; Lucas, Susan [U.S. Department of Energy, Joint Genome Institute; Copeland, A [U.S. Department of Energy, Joint Genome Institute; Lapidus, Alla L. [U.S. Department of Energy, Joint Genome Institute; Glavina Del Rio, Tijana [U.S. Department of Energy, Joint Genome Institute; Dalin, Eileen [U.S. Department of Energy, Joint Genome Institute; Tice, Hope [U.S. Department of Energy, Joint Genome Institute; Bruce, David [Los Alamos National Laboratory (LANL); Goodwin, Lynne A. [Los Alamos National Laboratory (LANL); Pitluck, Sam [U.S. Department of Energy, Joint Genome Institute; Davenport, Karen W. [Los Alamos National Laboratory (LANL); Sims, David [Los Alamos National Laboratory (LANL); Detter, J. Chris [U.S. Department of Energy, Joint Genome Institute; Han, Cliff [Los Alamos National Laboratory (LANL); Larimer, Frank W [ORNL; Land, Miriam L [ORNL; Hauser, Loren John [ORNL; Kyrpides, Nikos C [U.S. Department of Energy, Joint Genome Institute; Ovchinnikova, Galina [U.S. Department of Energy, Joint Genome Institute; Richardson, Paul [U.S. Department of Energy, Joint Genome Institute; De Vos, Willem M. [Wageningen University and Research Centre, The Netherlands; Smidt, Hauke [Wageningen University and Research Centre, The Netherlands; Zoetendal, Erwin G. [Wageningen University and Research Centre, The Netherlands

    2011-01-01

    Victivallis vadensis ATCC BAA-548 represents the first cultured representative from the novel phylum Lentisphaerae, a deep-branching bacterial lineage. Few cultured bacteria from this phylum are known, and V. vadensis therefore represents an important organism for evolutionary studies. V. vadensis is a strictly anaerobic sugar-fermenting isolate from the human gastro-intestinal tract.

  13. Early impairment of gut function and gut flora supporting a role for alteration of gastrointestinal mucosa in human immunodeficiency virus pathogenesis

    NARCIS (Netherlands)

    Gori, Andrea; Tincati, Camilla; Rizzardini, Giuliano; Torti, Carlo; Quirino, Tiziana; Haarman, Monique; Ben Amor, Kaouther; van Schaik, Jacqueline; Vriesema, Aldwin; Knol, Jan; Marchetti, Giulia; Welling, Gjalt; Clerici, Mario

    Our results show that impairment of the gastrointestinal tracts in human immunodeficiency virus (HIV)-positive patients is present in the early phases of HIV disease. This impairment is associated with alterations in gut microbiota and intestinal inflammatory parameters. These findings support the

  14. Early impairment of gut function and gut flora supporting a role for alteration of gastrointestinal mucosa in human immunodeficiency virus pathogenesis

    NARCIS (Netherlands)

    Gori, Andrea; Tincati, Camilla; Rizzardini, Giuliano; Torti, Carlo; Quirino, Tiziana; Haarman, Monique; Ben Amor, Kaouther; van Schaik, Jacqueline; Vriesema, Aldwin; Knol, Jan; Marchetti, Giulia; Welling, Gjalt; Clerici, Mario

    2008-01-01

    Our results show that impairment of the gastrointestinal tracts in human immunodeficiency virus (HIV)-positive patients is present in the early phases of HIV disease. This impairment is associated with alterations in gut microbiota and intestinal inflammatory parameters. These findings support the h

  15. Comparison of the gastrointestinal absorption and bioavailability of fenofibrate and fenofibric acid in humans.

    Science.gov (United States)

    Zhu, Tong; Ansquer, Jean-Claude; Kelly, Maureen T; Sleep, Darryl J; Pradhan, Rajendra S

    2010-08-01

    This study compared the gastrointestinal (GI) absorption characteristics and absolute bioavailability of fenofibric acid and fenofibrate (which is converted to fenofibric acid in vivo) in healthy volunteers. Treatments were delivered to the proximal small bowel, distal small bowel, and colon using a site-specific delivery system (Enterion capsule) and to the stomach by oral administration of equimolar doses. Serial blood samples were collected for 120 hours postdose and assayed for plasma fenofibric acid concentrations. The absolute bioavailability of each treatment was determined relative to 50 mg of fenofibric acid administered intravenously. Plasma exposure to fenofibric acid following fenofibric acid administration was approximately 1.5 times higher than that following fenofibrate administration for delivery to the proximal and distal small bowel and following oral administration, and it was approximately 5 times higher following colon delivery. The absolute bioavailability in the stomach, proximal small bowel, distal small bowel, and colon was approximately 81%, 88%, 84%, and 78%, respectively, for fenofibric acid and 69%, 73%, 66%, and 22%, respectively, for fenofibrate (P fenofibric acid vs fenofibrate in the colon and distal small bowel, respectively). In conclusion, fenofibric acid is well absorbed throughout the GI tract and has greater bioavailability than fenofibrate in all GI regions.

  16. Obesity and gastrointestinal neoplasms

    Directory of Open Access Journals (Sweden)

    Izabela Binkowska-Borgosz

    2014-10-01

    Full Text Available Being overweight or obese is a significant public health problem in the 21st century due to its scale, common existence and its cause-effect association with multiple diseases. Excessive accumulation of adipose tissue in humans is regarded as a major risk factor for development of cardiovascular and skeletal diseases. However, data from recent years have revealed that obesity is also strongly associated with increased risk of the majority of cancers in humans, including those originating from the gastrointestinal tract. During the last few year this association has been thoroughly proven and supported by several epidemiological analyses. The authors present i the current state of knowledge regarding key (pathomechanisms that link metabolism of human adipose tissue to development/progression of neoplasms (especially in the gastrointestinal tract, as well as ii the results of selected clinical studies in which the influence of obesity on risk of gastrointestinal cancer development has been addressed.

  17. Obesity and gastrointestinal neoplasms

    Directory of Open Access Journals (Sweden)

    Izabela Binkowska-Borgosz

    2014-10-01

    Full Text Available Being overweight or obese is a significant public health problem in the 21st century due to its scale, common existence and its cause-effect association with multiple diseases. Excessive accumulation of adipose tissue in humans is regarded as a major risk factor for development of cardiovascular and skeletal diseases. However, data from recent years have revealed that obesity is also strongly associated with increased risk of the majority of cancers in humans, including those originating from the gastrointestinal tract. During the last few year this association has been thoroughly proven and supported by several epidemiological analyses. The authors present i the current state of knowledge regarding key (pathomechanisms that link metabolism of human adipose tissue to development/progression of neoplasms (especially in the gastrointestinal tract, as well as ii the results of selected clinical studies in which the influence of obesity on risk of gastrointestinal cancer development has been addressed.

  18. Gastrointestinal tract spindle cell lesions--just like real estate, it's all about location.

    Science.gov (United States)

    Voltaggio, Lysandra; Montgomery, Elizabeth A

    2015-01-01

    Interpretation of gastrointestinal tract mesenchymal lesions is simplified merely by knowing in which anatomic layer they are usually found. For example, Kaposi sarcoma is detected on mucosal biopsies, whereas inflammatory fibroid polyp is nearly always in the submucosa. Gastrointestinal stromal tumors (GISTs) are generally centered in the muscularis propria. Schwannomas are essentially always in the muscularis propria. Mesenteric lesions are usually found in the small bowel mesentery. Knowledge of the favored layer is even most important in interpreting colon biopsies, as many mesenschymal polyps are encountered in the colon. Although GISTs are among the most common mesenchymal lesions, we will concentrate our discussion on other mesenchymal lesions, some of which are in the differential diagnosis of GIST, and point out some diagnostic pitfalls, particularly in immunolabeling.

  19. Mantle cell lymphoma of the gastrointestinal tract presenting with multiple intussusceptions – case report and review of literature

    Directory of Open Access Journals (Sweden)

    Abo Stephen M

    2009-07-01

    Full Text Available Abstract Background Mantle cell lymphoma (MCL is an aggressive type of B-cell non-Hodgkin's lymphoma that originates from small to medium sized lymphocytes located in the mantle zone of the lymph node. Extra nodal involvement is present in the majority of cases, with a peculiar tendency to invade the gastro-intestinal tract in the form of multiple lymphomatous polyposis. MCL can be accurately diagnosed with the use of the highly specific marker Cyclin D1. Few cases of mantle cell lymphoma presenting with intussuception have been reported. Here we present a rare case of multiple intussusceptions caused by mantle cell lymphoma and review the literature of this disease. Case presentation A 68-year-old male presented with pain, tenderness in the right lower abdomen, associated with nausea and non-bilious vomiting. CT scan of abdomen revealed ileo-colic intussusception. Laparoscopy confirmed multiple intussusceptions involving ileo-colic and ileo-ileal segments of gastrointestinal tract. A laparoscopically assisted right hemicolectomy and extended ileal resection was performed. Postoperative recovery was uneventful. The histology and immuno-histochemistry of the excised small and large bowel revealed mantle cell lymphoma with multiple lymphomatous polyposis and positivity to Cyclin D1 marker. The patient was successfully treated with Rituximab-CHOP chemotherapy and remains in complete remission at one-year follow-up. Conclusion This is a rare case of intestinal lymphomatous polyposis due to mantle cell lymphoma presenting with multiple small bowel intussusceptions. Our case highlights laparoscopic-assisted bowel resection as a potential and feasible option in the multi-disciplinary treatment of mantle cell lymphoma.

  20. The peripheral chimerism of bone marrow-derived stem cells after transplantation: regeneration of gastrointestinal tissues in lethally irradiated mice.

    Science.gov (United States)

    Filip, Stanislav; Mokrý, Jaroslav; Vávrová, Jiřina; Sinkorová, Zuzana; Mičuda, Stanislav; Sponer, Pavel; Filipová, Alžběta; Hrebíková, Hana; Dayanithi, Govindan

    2014-05-01

    Bone marrow-derived cells represent a heterogeneous cell population containing haematopoietic stem and progenitor cells. These cells have been identified as potential candidates for use in cell therapy for the regeneration of damaged tissues caused by trauma, degenerative diseases, ischaemia and inflammation or cancer treatment. In our study, we examined a model using whole-body irradiation and the transplantation of bone marrow (BM) or haematopoietic stem cells (HSCs) to study the repair of haematopoiesis, extramedullary haematopoiesis and the migration of green fluorescent protein (GFP(+)) transplanted cells into non-haematopoietic tissues. We investigated the repair of damage to the BM, peripheral blood, spleen and thymus and assessed the ability of this treatment to induce the entry of BM cells or GFP(+) lin(-) Sca-1(+) cells into non-haematopoietic tissues. The transplantation of BM cells or GFP(+) lin(-) Sca-1(+) cells from GFP transgenic mice successfully repopulated haematopoiesis and the haematopoietic niche in haematopoietic tissues, specifically the BM, spleen and thymus. The transplanted GFP(+) cells also entered the gastrointestinal tract (GIT) following whole-body irradiation. Our results demonstrate that whole-body irradiation does not significantly alter the integrity of tissues such as those in the small intestine and liver. Whole-body irradiation also induced myeloablation and chimerism in tissues, and induced the entry of transplanted cells into the small intestine and liver. This result demonstrates that grafted BM cells or GFP(+) lin(-) Sca-1(+) cells are not transient in the GIT. Thus, these transplanted cells could be used for the long-term treatment of various pathologies or as a one-time treatment option if myeloablation-induced chimerism alone is not sufficient to induce the entry of transplanted cells into non-haematopoietic tissues.

  1. Functional consequences of microbial shifts in the human gastrointestinal tract linked to antibiotic treatment and obesity.

    Science.gov (United States)

    Hernández, Ester; Bargiela, Rafael; Diez, María Suárez; Friedrichs, Anette; Pérez-Cobas, Ana Elena; Gosalbes, María José; Knecht, Henrik; Martínez-Martínez, Mónica; Seifert, Jana; von Bergen, Martin; Artacho, Alejandro; Ruiz, Alicia; Campoy, Cristina; Latorre, Amparo; Ott, Stephan J; Moya, Andrés; Suárez, Antonio; Martins dos Santos, Vitor A P; Ferrer, Manuel

    2013-01-01

    The microbiomes in the gastrointestinal tract (GIT) of individuals receiving antibiotics and those in obese subjects undergo compositional shifts, the metabolic effects and linkages of which are not clearly understood. Herein, we set to gain insight into these effects, particularly with regard to carbohydrate metabolism, and to contribute to unravel the underlying mechanisms and consequences for health conditions. We measured the activity level of GIT carbohydrate-active enzymes toward 23 distinct sugars in adults patients (n = 2) receiving 14-d β-lactam therapy and in obese (n = 7) and lean (n = 5) adolescents. We observed that both 14 d antibiotic-treated and obese subjects showed higher and less balanced sugar anabolic capacities, with 40% carbohydrates being preferentially processed as compared with non-treated and lean patients. Metaproteome-wide metabolic reconstructions confirmed that the impaired utilization of sugars propagated throughout the pentose phosphate metabolism, which had adverse consequences for the metabolic status of the GIT microbiota. The results point to an age-independent positive association between GIT glycosidase activity and the body mass index, fasting blood glucose and insulin resistance (r ( 2) ≥ 0.95). Moreover, antibiotics altered the active fraction of enzymes controlling the thickness, composition and consistency of the mucin glycans. Our data and analyses provide biochemical insights into the effects of antibiotic usage on the dynamics of the GIT microbiota and pin-point presumptive links to obesity. The knowledge and the hypotheses generated herein lay a foundation for subsequent, systematic research that will be paramount for the design of "smart" dietary and therapeutic interventions to modulate host-microbe metabolic co-regulation in intestinal homeostasis.

  2. Effect of bread gluten content on gastrointestinal function: a crossover MRI study on healthy humans.

    Science.gov (United States)

    Coletta, Marina; Gates, Fred K; Marciani, Luca; Shiwani, Henna; Major, Giles; Hoad, Caroline L; Chaddock, Gemma; Gowland, Penny A; Spiller, Robin C

    2016-01-14

    Gluten is a crucial functional component of bread, but the effect of increasing gluten content on gastrointestinal (GI) function remains uncertain. Our aim was to investigate the effect of increasing gluten content on GI function and symptoms in healthy participants using the unique capabilities of MRI. A total of twelve healthy participants completed this randomised, mechanistic, open-label, three-way crossover study. On days 1 and 2 they consumed either gluten-free bread (GFB), or normal gluten content bread (NGCB) or added gluten content bread (AGCB). The same bread was consumed on day 3, and MRI scans were performed every 60 min from fasting baseline up to 360 min after eating. The appearance of the gastric chime in the images was assessed using a visual heterogeneity score. Gastric volumes, the small bowel water content (SBWC), colonic volumes and colonic gas content and GI symptoms were measured. Fasting transverse colonic volume after the 2-d preload was significantly higher after GFB compared with NGCB and AGCB with a dose-dependent response (289 (SEM 96) v. 212 (SEM 74) v. 179 (SEM 87) ml, respectively; P=0·02). The intragastric chyme heterogeneity score was higher for the bread with increased gluten (AGCB 6 (interquartile range (IQR) 0·5) compared with GFB 3 (IQR 0·5); P=0·003). However, gastric half-emptying time was not different between breads nor were study day GI symptoms, postprandial SBWC, colonic volume and gas content. This MRI study showed novel mechanistic insights in the GI responses to different breads, which are poorly understood notwithstanding the importance of this staple food.

  3. Evidence That the Enterotoxin Gene Can Be Episomal in Clostridium perfringens Isolates Associated with Non-Food-Borne Human Gastrointestinal Diseases

    OpenAIRE

    1998-01-01

    Clostridium perfringens enterotoxin (CPE) is responsible for the diarrheal and cramping symptoms of human C. perfringens type A food poisoning. CPE-producing C. perfringens isolates have also recently been associated with several non-food-borne human gastrointestinal (GI) illnesses, including antibiotic-associated diarrhea and sporadic diarrhea. The current study has used restriction fragment length polymorphism (RFLP) and pulsed-field gel electrophoresis (PFGE) analyses to compare the genoty...

  4. Characterization of various types of mast cells derived from model mice of familial gastrointestinal stromal tumors with KIT-Asp818Tyr mutation.

    Science.gov (United States)

    Kajimoto, Noriko; Nakai, Norihiro; Ohkouchi, Mizuka; Hashikura, Yuka; Liu-Kimura, Ning-Ning; Isozaki, Koji; Hirota, Seiichi

    2015-01-01

    Sporadic mast cell neoplasms and gastrointestinal stromal tumors (GISTs) often have various types of somatic gain-of-function mutations of the c-kit gene which encodes a receptor tyrosine kinase, KIT. Several types of germline gain-of-function mutations of the c-kit gene have been detected in families with multiple GISTs. All three types of model mice for the familial GISTs with germline c-kit gene mutations at exon 11, 13 or 17 show development of GIST, while they are different from each other in skin mast cell number. Skin mast cell number in the model mice with exon 17 mutation was unchanged compared to the corresponding wild-type mice. In the present study, we characterized various types of mast cells derived from the model mice with exon 17 mutation (KIT-Asp818Tyr) corresponding to human familial GIST case with human KIT-Asp820Tyr to clarify the role of the c-kit gene mutation in mast cells. Bone marrow-derived cultured mast cells (BMMCs) derived from wild-type mice, heterozygotes and homozygotes were used for the experiments. Immortalized BMMCs, designated as IMC-G4 cells, derived from BMMCs of a homozygote during long-term culture were also used. Ultrastructure, histamine contents, proliferation profiles and phosphorylation of various signaling molecules in those cells were examined. In IMC-G4 cells, presence of additional mutation(s) of the c-kit gene and effect of KIT inhibitors on both KIT autophosphorylation and cell proliferation were also analyzed. We demonstrated that KIT-Asp818Tyr did not affect ultrastructure and proliferation profiles but did histamine contents in BMMCs. IMC-G4 cells had an additional novel c-kit gene mutation of KIT-Tyr421Cys which is considered to induce neoplastic transformation of mouse mast cells and the mutation appeared to be resistant to a KIT inhibitor of imatinib but sensitive to another KIT inhibitor of nilotinib. IMC-G4 cells might be a useful mast cell line to investigate mast cell biology.

  5. Gastrointestinal bleeding.

    Science.gov (United States)

    Marek, T A

    2011-11-01

    Gastrointestinal bleeding remains one of the most important emergencies in gastroenterology. Despite this, only about 100 abstracts concerning gastrointestinal bleeding (excluding bleeding complicating endoscopic procedures) were presented at this year's Digestive Disease Week (DDW; 7-10 May 2011; Chicago, Illinois, USA), accounting for less than 2% of all presented lectures and posters. It seems that the number of such abstracts has been decreasing over recent years. This may be due in part to the high level of medical care already achieved, especially in the areas of pharmacotherapy and endoscopic treatment of gastrointestinal bleeding. In this review of gastrointestinal bleeding, priority has been given to large epidemiological studies reflecting "real life," and abstracts dealing more or less directly with endoscopic management. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Gastrointestinal bleeding

    Science.gov (United States)

    ... Sigmoidoscopy Alternative Names Lower GI bleeding; GI bleeding; Upper GI bleeding; Hematochezia Images GI bleeding - series Fecal occult blood test References Kovacs TO, Jensen DM. Gastrointestinal hemorrhage. In: Goldman L, Schafer AI, eds. Goldman-Cecil ...

  7. Gastrointestinal tattoos.

    Science.gov (United States)

    Snider, T E; Goodell, W M; Pulitzer, D R

    1994-06-01

    Tattooing of the gastrointestinal tract is used to facilitate the relocation of biopsy sites or other sites of interest at the time of subsequent biopsy or surgery. Submucosal injection of sterile india ink produces a zone of blue-black coloration that is grossly visible from both the mucosal and serosal surfaces. The pathology of gastrointestinal tattoos has only been briefly mentioned previously in the medical literature. We report two cases of gastrointestinal tattooing: one that was done to mark the margin of resection in a patient with gastric lymphoma, and the second that occurred unintentionally following the administration of activated charcoal for drug overdosage in a patient with undiagnosed active inflammatory bowel disease. Unintentional tattooing of the gastrointestinal tract has, therefore, not been reported.

  8. Gastrointestinal manifestations.

    Science.gov (United States)

    Tanowitz, H B; Simon, D; Weiss, L M; Noyer, C; Coyle, C; Wittner, M

    1996-11-01

    Gastrointestinal disease is a common problem in the setting of HIV-1 infection. As patients live longer and other opportunistic pathogens are suppressed, these problems are becoming even more important in the quality of life.

  9. The effect of forced expression of mutated K-RAS gene on gastrointestinal cancer cell lines and the IGF-1R targeting therapy.

    Science.gov (United States)

    Matsunaga, Yasutaka; Adachi, Yasushi; Sasaki, Yasushi; Koide, Hideyuki; Motoya, Masayo; Nosho, Katsuhiko; Takagi, Hideyasu; Yamamoto, Hiroyuki; Sasaki, Shigeru; Arimura, Yoshiaki; Tokino, Takashi; Carbone, David P; Imai, Kohzoh; Shinomura, Yasuhisa

    2017-02-01

    Mutation in K-RAS (K-RAS-MT) plays important roles in both cancer progression and resistance to anti-epidermal growth factor receptor (EGFR) therapy in gastrointestinal tumors. Insulin-like growth factor-1 receptor (IGF-1R) signaling is required for carcinogenicity and progression of many tumors as well. We have previously shown successful therapy for gastrointestinal cancer cell lines bearing a K-RAS mutation using an anti-IGF-1R monoclonal antibody. In this study, we sought to evaluate effects of forced K-RAS-MT expression on gastrointestinal cancer cell lines representing a possible second resistance mechanism for anti-EGFR therapy and IGF-1R-targeted therapy for these transfectants. We made stable transfectants of K-RAS-MT in two gastrointestinal cancer cell lines, colorectal RKO and pancreatic BxPC-3. We assessed the effect of forced expression of K-RAS-MT on proliferation, apoptosis, migration, and invasion in gastrointestinal cancer cells. Then we assessed anti-tumor effects of dominant negative IGF-1R (IGF-1R/dn) and an IGF-1R inhibitor, picropodophyllin, on the K-RAS-MT transfectants. Overexpression of K-RAS-MT in gastrointestinal cancer cell lines led to more aggressive phenotypes, with increased proliferation, decreased apoptosis, and increased motility and invasion. IGF-1R blockade suppressed cell growth, colony formation, migration, and invasion, and up-regulated chemotherapy-induced apoptosis of gastrointestinal cancer cells, even when K-RAS-MT was over-expressed. IGF-1R blockade inhibited the Akt pathway more than the extracellular signal-regulated kinase (ERK) pathway in the K-RAS-MT transfectants. IGF-1R/dn, moreover, inhibited the growth of murine xenografts expressing K-RAS-MT. Thus, K-RAS-MT might be important for progressive phonotype observed in gastrointestinal cancers. IGF-1R decoy is a candidate molecular therapeutic approach for gastrointestinal cancers even if K-RAS is mutated. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals

  10. Human embryonic stem cells handbook

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2013-03-01

    Full Text Available After the Nobel prize in physiology or medicine was awarded jointly to Sir John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent it became imperative to write down the review for a book entirely devoted to human embryonic stem cells (hES, those cells that are a urgent need for researchers, those cells that rekindle the ethical debates and finally, last but not least, those cells whose study paved the way to obtain induced pluripotent stem cells by the OSKC’s Yamanaka method (the OSKC acronim refers, for those not familiar with the topic, to the four stemness genes used to transfect somatic fibroblasts: Oct4, Sox2, Klf4 and c-Myc....

  11. Coupling in vitro gastrointestinal lipolysis and Caco-2 cell cultures for testing the absorption of different food emulsions.

    Science.gov (United States)

    Vors, Cécile; Capolino, Perrine; Guérin, Clémence; Meugnier, Emmanuelle; Pesenti, Sandra; Chauvin, Marie-Agnès; Monteil, Julien; Peretti, Noël; Cansell, Maud; Carrière, Frédéric; Michalski, Marie-Caroline

    2012-05-01

    There is a growing interest in the optimization of dietary emulsions for monitoring postprandial lipid metabolism in the frame of preventing metabolic diseases. Using various emulsions, we investigated in a systematic scheme the combination of (i) in vitro gastrointestinal lipolysis and (ii) absorption and metabolism of lipolysis media in Caco-2 cells. Four emulsions based on either milk fat olein (OL) or rapeseed oil (RA) as the dispersed phase and either lecithin (LE) or sodium caseinate (CA) as the emulsifier were tested. After a sequential incubation of these emulsions with gastric and pancreatic enzymes, lipolysis media were incubated with Caco-2 cells, after dilution (1 : 20) to maintain the barrier integrity. Both gastric and duodenal lipolysis levels were similar to values reported in vivo and the rates of lipolysis were higher with LE-stabilized emulsions than with CA-stabilized emulsions (P < 0.05). TAG secretion by Caco-2 cells was found to be higher using (i) duodenal vs. gastric media (P < 0.001) and (ii) emulsions stabilized with CA vs. LE (P < 0.01). Consistently, gene expression of both FABP2 and FATP4 induced by the duodenal media was (i) higher than that with gastric media (P < 0.001) and (ii) faster than that with model mixed micelles. Using gastric media, TAG secretion of Caco-2 cells after 12 h was higher with RA than with OL (P < 0.001). Moreover, the RA-CA emulsion increased the size of secreted lipoprotein particles (514 nm vs. 61 to 130 nm; P < 0.01). In conclusion, it was possible to observe distinct responses in the lipid metabolism of Caco-2 cells incubated with lipolysis media obtained from different dietary emulsions digested by gastrointestinal lipases in vitro.

  12. Hypertensive crisis during wide excision of gastrointestinal stromal cell tumor (GIST): Undiagnosed paraganglioma -A case report-.

    Science.gov (United States)

    Shinn, Helen Ki; Jung, Jong Kwon; Park, Jay Kim; Kim, Jong Hoon; Jung, In Young; Lee, Hong Sik

    2012-03-01

    Although paraganglioma (PGL), an extra-adrenal retroperitoneal pheochromocytoma (PHEO), is a rare catecholamine-secreting neuroendocrine tumor, it can cause severe hypertensive crisis during anesthesia or surgery if undiagnosed preoperatively. Extraluminal perigastric masses may be presumed to be gastrointestinal stromal tumors (GISTs) or soft tissue sarcomas even when histologic confirmation is not possible. Therefore, without a histologic diagnosis or symptoms of excessive catecholamine secretion, PGL may be mistaken for GIST. We report a case of preoperatively undiagnosed PGL which caused hypertensive crisis during anesthesia for retroperitoneal mass excision.

  13. Comparison of Nitrogen Bioaccessibility from Salmon and Whey Protein Hydrolysates using a Human Gastrointestinal Model (TIM-1

    Directory of Open Access Journals (Sweden)

    Bomi Framroze

    2014-05-01

    Full Text Available Background: The TIM-1 system is a computer-controlled multi-compartmental dynamic model that closely simulates in vivo gastrointestinal tract digestion in humans. During digestion, the compounds released from meal matrix by gastric and intestinal secretions (enzymes are progressively absorbed through semipermeable membranes depending on their molecular weight. These absorbed (dialysed compounds are considered as bioaccessible, which means that they can be theoretically absorbed by the small intestine in the body. Methods: Salmon protein hydrolysate (SPH, whey protein hydrolysates extensively (WPHHigh or weakly (WPH-Low hydrolysed, non-hydrolysed whey protein isolate (WPI and mixtures of WPI:SPH (90:10, 80:20 were digested in TIM-1 using the conditions for a fast gastrointestinal transit that simulate the digestion of a liquid meal in human adults. During digestion (2 hours, samples were collected in intestinal compartments (duodenum, jejunum, and ileum and in both jejunal and ileal dialysates to determine their nitrogen content. All the products were compared in terms of kinetics of nitrogen absorption through the semipermeable membranes (bioaccessible nitrogen and nitrogen distribution throughout the intestinal compartments at the end of the 2 hour digestion. Results: After a 2 h-digestion in TIM-1, SPH was the protein substrate from which the highest amount of nitrogen (67.0% becomes available for the small intestine absorption. WPH-High had the second highest amount (56.0% of bioaccessible nitrogen while this amount decreased to 38.5–42.2% for the other protein substrates. The high nitrogen bioaccessibility of SPH is consistent with its richness in low molecular weight peptides (50% < 1000 Da. Conclusions: The results of this study indicate that SPH provides a higher proportion of bioaccessible nitrogen to a healthy adult compared to all forms of whey proteins, including extensively hydrolysed whey protein hydrolysate. The substitution of

  14. The dose-response relation in human volunteers for gastro-intestinal pathogens

    NARCIS (Netherlands)

    Teunis PFM; Heijden OG van der; Giessen JWB van der; Havelaar AH; MGB

    1996-01-01

    Published data on infection of human hosts with various protozoa, bacteria, and viruses causing gastro-enteritis are used to establish a quantitative relationship between ingested dose and the risk of infection. For all data sets analysed, this relationship is determined by fitting either an exponen

  15. The dose-response relation in human volunteers for gastro-intestinal pathogens

    NARCIS (Netherlands)

    Teunis PFM; van der Heijden OG; van der Giessen JWB; Havelaar AH; MGB

    1996-01-01

    Gepubliceerde gegevens omtrent infectie van humane proefpersonen met pathogene micro-organismen die gastro-enteritis veroorzaken (protozoa, bacterien en virussen), worden gebruikt om een kwantitatieve relatie vast te stellen tussen de ingenomen dosis en het risico op infectie. Voor alle bestudeerde

  16. N-nitrosation of medicinal drugs catalysed by bacteria from human saliva and gastro-intestinal tract, including Helicobacter pylori.

    Science.gov (United States)

    Ziebarth, D; Spiegelhalder, B; Bartsch, H

    1997-02-01

    Micro-organisms commonly present in human saliva and three DSM strains (Helicobacter pylori, Campylobacter jejuni and Neisseria cinerea), which can be isolated from the human gastro-intestinal tract, were assayed in vitro for their capacity to catalyse N-nitrosation of a series of medicinal drugs and other compounds. Following incubation at pH 7.2 in the presence of nitrate (or nitrite) for up to 24 (48) h, the yield of N-nitroso compounds (NOC) was quantified by HPLC equipped with a post-column derivatization device, allowing the sensitive detection of acid-labile and acid-stable NOC. Eleven out of the 23 test compounds underwent bacteria-catalysed nitrosation by salivary bacteria, the yield of the respective nitrosation products varying 800-fold. 4-(Methylamino)antipyrine exhibited the highest rate of nitrosation, followed by dichlofenac > metamizole > piperazine > five other drugs, whilst L-proline and L-thioproline had the lowest nitrosation rate. Ten drugs including aminophenazone, cimetidine and nicotine, did not inhibit bacterial growth, allowing transitory nitrite to be formed, but no N-nitroso derivatives were detected. Three drugs inhibited the proliferation of bacteria and neither nitrite nor any NOC were formed. Using metamizole as an easily nitrosatable precursor, two strains, Campylobacter jejuni and Helicobacter pylori, were shown to catalyse nitrosation in the presence of nitrite at pH 7.2. As compared to Neisseria cinerea used as a nitrosation-proficient control strain, H. pylori was 30-100 times less effective, whilst C. jejuni had intermediary activity. The results of our sensitive nitrosation assay further confirm that bacteria isolated from human sources, possessing nitrate reductase and/or nitrosating enzymes such as cytochrome cd1-nitrite reductase (Calmels et al., Carcinogenesis, 17, 533-536, 1996), can contribute to intragastric nitrosamine formation in the anacidic stomach when nitrosatable precursors from exogenous and endogenous sources

  17. Research Progress of Leucine-Rich Repeat Containing G Protein Coupled Receptor 5 Positive Cells in Gastrointestinal Mucosa%胃肠黏膜G蛋白偶联受体5阳性细胞研究进展

    Institute of Scientific and Technical Information of China (English)

    李毅; 孙涛

    2013-01-01

      干细胞和再生医学的研究已成为自然科学中最为引人注目的领,人类已在胚胎干细胞、部分成体干细胞如骨髓造血干细胞方面取得进展,但在其他成体干细胞研究,特别是胃肠黏膜干细胞研究领进展甚少.富含亮氨酸重复序列的 G 蛋白偶联受体5(LGR5)是 G 蛋白偶联受体超家族的成,在胃肠黏膜隐窝基底有少量表达,其阳性细胞可在体内分化为胃肠黏膜所有类型的细胞,被认为是可能的胃肠黏膜成体干细胞.LGR5阳性细胞的研究,对组织工程、消化道疾病发病机制研究、干细胞治疗、肿瘤治疗等方面有重要意义.%Stem cell researchs and regenerative medicine have become the most spectacular areas of natural sci⁃ences. Research progresses of human embryonic stem cells, as well as part of adult stem cells such as bone mar⁃row hematopoietic stem-cell has developed obviously. But little progress in the field of other adult stem cell, espe⁃cially the gastrointestinal mucosa stem cell has been made. Leucine-rich repeat sequences of G-protein coupled re⁃ceptor 5(LGR5) is a member of the G-protein coupled receptor superfamily. They are expressed by a small amount of cells in the crypt base of gastrointestinal mucosa. LGR5 positive cells are considered as possible gastro⁃intestinal mucosa stem cells, because they can differente into all cell types of the gastrointestinal mucosa. Re⁃searchs on LGR5 positive cells are important for researchs of tissue engineering, pathogenesis of gastrointestinal disease, stem cell therapy, cancer treatment.

  18. Colonizing the embryonic zebrafish gut with anaerobic bacteria derived from the human gastrointestinal tract.

    Science.gov (United States)

    Toh, Michael C; Goodyear, Mara; Daigneault, Michelle; Allen-Vercoe, Emma; Van Raay, Terence J

    2013-06-01

    The zebrafish has become increasingly popular for microbiological research. It has been used as an infection model for a variety of pathogens, and is also emerging as a tool for studying interactions between a host and its resident microbial communities. The mouse microbiota has been transplanted into the zebrafish gut, but to our knowledge, there has been no attempt to introduce a bacterial community derived from the human gut. We explored two methods for colonizing the developing gut of 5-day-old germ-free zebrafish larvae with a defined anaerobic microbial community derived from a single human fecal sample. Both environmental exposure (static immersion) and direct microinjection into the gut resulted in the establishment of two species-Lactobacillus paracasei and Eubacterium limosum-from a community of 30 strains consisting of 22 anaerobic species. Of particular interest is E. limosum, which, as a strict anaerobe, represents a group of bacteria which until now have not been shown to colonize the developing zebrafish gut. Our success here indicates that further investigation of zebrafish as a tool for studying human gut microbial communities is warranted.

  19. In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract

    Science.gov (United States)

    Piyawattanametha, Wibool; Ra, Hyejun; Qiu, Zhen; Friedland, Shai; Liu, Jonathan T. C.; Loewke, Kevin; Kino, Gordon S.; Solgaard, Olav; Wang, Thomas D.; Mandella, Michael J.; Contag, Christopher H.

    2012-02-01

    Near-infrared confocal microendoscopy is a promising technique for deep in vivo imaging of tissues and can generate high-resolution cross-sectional images at the micron-scale. We demonstrate the use of a dual-axis confocal (DAC) near-infrared fluorescence microendoscope with a 5.5-mm outer diameter for obtaining clinical images of human colorectal mucosa. High-speed two-dimensional en face scanning was achieved through a microelectromechanical systems (MEMS) scanner while a micromotor was used for adjusting the axial focus. In vivo images of human patients are collected at 5 frames/sec with a field of view of 362×212 μm2 and a maximum imaging depth of 140 μm. During routine endoscopy, indocyanine green (ICG) was topically applied a nonspecific optical contrasting agent to regions of the human colon. The DAC microendoscope was then used to obtain microanatomic images of the mucosa by detecting near-infrared fluorescence from ICG. These results suggest that DAC microendoscopy may have utility for visualizing the anatomical and, perhaps, functional changes associated with colorectal pathology for the early detection of colorectal cancer.

  20. Human intestinal dendritic cells as controllers of mucosal immunity

    Directory of Open Access Journals (Sweden)

    David Bernardo

    2013-06-01

    Full Text Available Dendritic cells are the most potent, professional antigen-presenting cells in the body; following antigen presentation they control the type (proinflammatory/regulatory of immune response that will take place, as well as its location. Given their high plasticity and maturation ability in response to local danger signals derived from innate immunity, dendritic cells are key actors in the connection between innate immunity and adaptive immunity responses. In the gut dendritic cells control immune tolerance mechanisms against food and/or commensal flora antigens, and are also capable of initiating an active immune response in the presence of invading pathogens. Dendritic cells are thus highly efficient in controlling the delicate balance between tolerance and immunity in an environment so rich in antigens as the gut, and any factor involving these cells may impact their function, ultimately leading to the development of bowel conditions such as celiac disease or inflammatory bowel disease. In this review we shall summarize our understanding of human intestinal dendritic cells, their ability to express and induce migration markers, the various environmental factors modulating their properties, their subsets in the gut, and the problems entailed by their study, including identification strategies, differences between humans and murine models, and phenotypical variations along the gastrointestinal tract.

  1. Lineage-specific expression of bestrophin-2 and bestrophin-4 in human intestinal epithelial cells

    DEFF Research Database (Denmark)

    Ito, Go; Okamoto, Ryuichi; Murano, Tatsuro

    2013-01-01

    Intestinal epithelial cells (IECs) regulate the absorption and secretion of anions, such as HCO3(-) or Cl(-). Bestrophin genes represent a newly identified group of calcium-activated Cl(-) channels (CaCCs). Studies have suggested that, among the four human bestrophin-family genes, bestrophin-2...... (BEST2) and bestrophin-4 (BEST4) might be expressed within the intestinal tissue. Consistently, a study showed that BEST2 is expressed by human colonic goblet cells. However, their precise expression pattern along the gastrointestinal tract, or the lineage specificity of the cells expressing these genes...

  2. Presence of gastrointestinal parasites in swine and human of four swine production farms in Cundinamarca- Colombia

    Directory of Open Access Journals (Sweden)

    María F Mendoza-Gómez

    2015-11-01

    Full Text Available Objectives. Determine the presence and the type of endoparasites with zoonotic potential in swine and human of two technified and two semi-technified farms in the department of Cundinamarca, Colombia. Materials and methods. Three serial samplings of feces were taken in a pen row within intervals of 15 days, in two technified and two semi-technified farms in different age groups distributed as follows: pregnant-sows, nursing-females, boars, weaners, suckling-piglets, and growing-pig. By means of informed consent thirty-three people agreed to enter the study. Thirty-three samples from men and women of different ages were received. The pool and individual samples of fecal were evaluated by direct analysis, qualitative flotation and sedimentation techniques and modified ZiehlNeelsen stain. Results. For the porcine population, on the average, the results obtained from both technified farms showed that Balantidium coli (42%, Endolimax nana (21.9% and Iodamoeba bütschlii (7.8% were the most common parasites. In semi-technified farms they were: Entamoeba coli (40%, Endolimax nana (35%, Iodamoeba bütschlii (25% and Balantidium coli (5%. By means of the test chi2 it is possible to conclude that there is a significant difference between the parasites species and the type of farm. The results obtained in human showed the presence of parasites as: E. coli (42.2%, Entamoeba hystolitica/dispar (12.1%, E. nana (9.1%, B. coli (9.1%, I. bütschlii (3.0% and Blastocystis hominis (3.0%. Conclusions. The presence of parasites such as Balantidium coli, Endolimax nana, Iodamoeba bütschlii and Entamoeba coli in swine and human suggests a possible rotation of parasitic species between hosts.

  3. Aspects of gastrointestinal immunology and nutrition in human immunodeficiency virus-1 infection in Brazil

    Directory of Open Access Journals (Sweden)

    Castello-Branco Luiz RR

    2000-01-01

    Full Text Available Mucosal surfaces have a fundamental participation in many aspects of the human immunodeficiency virus (HIV infection pathogenesis. In Brazilian HIV-1 infected subjects, loss of weight and appetite are among the most debilitating symptoms. In this review we describe a defined mucosal immunogen that has profound but transient effects on HIV viral load, and we suggest that gut associated lymphoid tissue under constant immunostimulation is likely to provide a major contribution to the total levels of HIV. We also show that hypermetabolism appears to play a role in the wasting process in Brazilian patients coinfected with HIV and tuberculosis.

  4. How do they stick together? Bacterial adhesins implicated in the binding of bacteria to the human gastrointestinal mucins.

    Science.gov (United States)

    Ringot-Destrez, Bélinda; Kalach, Nicolas; Mihalache, Adriana; Gosset, Pierre; Michalski, Jean-Claude; Léonard, Renaud; Robbe-Masselot, Catherine

    2017-04-15

    The gastrointestinal mucosal surface is the primary interface between internal host tissues and the vast microbiota. Mucins, key components of mucus, are high-molecular-weight glycoproteins characterized by the presence of many O-linked oligosaccharides to the core polypeptide. They play many biological functions, helping to maintain cellular homeostasis and to establish symbiotic relationships with complex microbiota. Mucin O-glycans exhibit a huge variety of peripheral sequences implicated in the binding of bacteria to the mucosal tissues, thereby playing a key role in the selection of specific species and in the tissue tropism displayed by commensal and pathogenic bacteria. Bacteria have evolved numerous strategies to colonize host mucosae, and among these are modulation of expression of cell surface adhesins which allow bacteria to bind to mucins. However, despite well structurally characterized adhesins and lectins, information on the nature and structure of oligosaccharides recognized by bacteria is still disparate. This review summarizes the current knowledge on the structure of epithelial mucin O-glycans and the interaction between host and commensal or pathogenic bacteria mediated by mucins. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  5. Human fetal mesenchymal stem cells.

    Science.gov (United States)

    O'Donoghue, Keelin; Chan, Jerry

    2006-09-01

    Stem cells have been isolated at all stages of development from the early developing embryo to the post-reproductive adult organism. However, the fetal environment is unique as it is the only time in ontogeny that there is migration of stem cells in large numbers into different organ compartments. While fetal neural and haemopoietic stem cells (HSC) have been well characterised, only recently have mesenchymal stem cells from the human fetus been isolated and evaluated. Our group have characterised in human fetal blood, liver and bone marrow a population of non-haemopoietic, non-endothelial cells with an immunophenotype similar to adult bone marrow-derived mesenchymal stem cells (MSC). These cells, human fetal mesenchymal stem cells (hfMSC), are true multipotent stem cells with greater self-renewal and differentiation capacity than their adult counterparts. They circulate in first trimester fetal blood and have been found to traffic into the maternal circulation, engrafting in bone marrow, where they remain microchimeric for decades after pregnancy. Though fetal microchimerism has been implicated in the pathogenesis of autoimmune disease, the biological role of hfMSC microchimerism is unknown. Potential downstream applications of hfMSC include their use as a target cell for non-invasive pre-natal diagnosis from maternal blood, and for fetal cellular and gene therapy. Using hfMSC in fetal therapy offers the theoretical advantages of avoidance of immune rejection, increased engraftment, and treatment before disease pathology sets in. Aside from allogeneic hfMSC in utero transplantation, the use of autologous hfMSC has been brought a step forward with the development of early blood sampling techniques, efficient viral transduction and clonal expansion. Work is ongoing to determine hfMSC fate post-transplantation in murine models of genetic disease. In this review we will examine what is known about hfMSC biology, as well as discussing areas for future research. The

  6. Risk factors for gastrointestinal parasite infections of dogs living around protected areas of the Atlantic Forest: implications for human and wildlife health

    OpenAIRE

    N. H. A. Curi; Paschoal,A. M. O.; Massara,R. L.; SANTOS, H. A.; Guimarães,M.P.; M. Passamani; Chiarello,A.G.

    2016-01-01

    Abstract Despite the ubiquity of domestic dogs, their role as zoonotic reservoirs and the large number of studies concerning parasites in urban dogs, rural areas in Brazil, especially those at the wildlife-domestic animal-human interface, have received little attention from scientists and public health managers. This paper reports a cross-sectional epidemiological survey of gastrointestinal parasites of rural dogs living in farms around Atlantic Forest fragments. Through standard parasitologi...

  7. Differentiated human stem cells resemble fetal, not adult, β cells.

    Science.gov (United States)

    Hrvatin, Sinisa; O'Donnell, Charles W; Deng, Francis; Millman, Jeffrey R; Pagliuca, Felicia Walton; DiIorio, Philip; Rezania, Alireza; Gifford, David K; Melton, Douglas A

    2014-02-25

    Human pluripotent stem cells (hPSCs) have the potential to generate any human cell type, and one widely recognized goal is to make pancreatic β cells. To this end, comparisons between differentiated cell types produced in vitro and their in vivo counterparts are essential to validate hPSC-derived cells. Genome-wide transcriptional analysis of sorted insulin-expressing (INS(+)) cells derived from three independent hPSC lines, human fetal pancreata, and adult human islets points to two major conclusions: (i) Different hPSC lines produce highly similar INS(+) cells and (ii) hPSC-derived INS(+) (hPSC-INS(+)) cells more closely resemble human fetal β cells than adult β cells. This study provides a direct comparison of transcriptional programs between pure hPSC-INS(+) cells and true β cells and provides a catalog of genes whose manipulation may convert hPSC-INS(+) cells into functional β cells.

  8. Kit K641E oncogene up-regulates Sprouty homolog 4 and Trophoblast glycoprotein in interstitial cells of Cajal in a murine model of gastrointestinal stromal tumours

    Science.gov (United States)

    Gromova, Petra; Ralea, Sebastian; Lefort, Anne; Libert, Frédérick; Rubin, Brian P; Erneux, Christophe; Vanderwinden, Jean-Marie

    2009-01-01

    Gastrointestinal stromal tumours (GIST) are thought to derive from the interstitial cells of Cajal (ICC) or an ICC precursor. Oncogenic mutations of the receptor tyrosine kinase KIT are present in most GIST. KIT K642E was originally identified in sporadic GIST and later found in the germ line of a familial GIST cohort. A mouse model harbouring a germline Kit K641E mutant was created to model familial GIST. The expression profile was investigated in the gastric antrum of the KitK641E murine GIST model by microarray, quantitative PCR and immunofluorescence. Gja1/Cx43, Gpc6, Gpr133, Pacrg, Pde3a, Prkar2b, Prkcq/Pkce, Rasd2, Spry4 and Tpbg/5T4 were found to be up-regulated. The proteins encoded by Gja1/Cx43, Pde3a, Prkcq/Pkce were localized in Kit-ir ICC in wild-type and KitK641E animals while Spry4 and Tpbg/5T4 were detected in Kit-ir cells only in KitK641E, but not in KitWT/WT animals. Most up-regulated genes in this mouse model belong to the gene expression profile of human GIST but also to the profile of normal Kit+ ICC in the mouse small intestine. Spry4 and Tpbg/5T4 may represent candidates for targeted therapeutic approaches in GIST with oncogenic KIT mutations. PMID:19453770

  9. Correlation of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase with sensitivity of gastrointestinal cancer cells to 5-fluorouracil and 5-fluoro-2'-deoxyuridine

    Institute of Scientific and Technical Information of China (English)

    Tao Ma; Zheng-Gang Zhu; Yu-Bao Ji; Yi Zhang; Ying-Yan Yu; Bing-Ya Liu; Hao-Ran Yin; Yan-Zhen Lin

    2004-01-01

    AIM: To determine the expression levels of three metabolic enzymes of fluoropyrimidines: thymidylate synthase (TS),thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) in seven human gastrointestinal cancer cell lines, and to compare the enzyme levels with the sensitivity to 5-fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd).METHODS: TS, TP and DPD mRNA levels were assessed by semi-quantitative RT-PCR, TP and DPD protein contents were measured by ELISA. Fifty percent inhibitory concentrations of growth (IC50), representing the sensitivityto drugs, were determined by MTT assay.RESULTS: IC50 values ranged from 1.28 to 12.26 uM for 5-FU, and from 5.02 to 24.21 uM for FdUrd, respectively.Cell lines with lower DPD mRNA and protein levels tended to be more sensitive to 5-FU (P<0.05), but neither TS nor TP correlated with 5-FU IC50 (P>0.05). Only TS mRNA level was sharply related with FdUrd sensitivity (P<0.05), but TP and DPD were not (P>0.05). A correlation was found between mRNA and protein levels of DPD (P<0.05), but not TP (P<0.05).CONCLUSION: DPD and TS enzyme levels may be useful indicators in predicting the antitumor activity of 5-FU or FdUrd, respectively.

  10. Characteristic features of ghrelin cells in the gastrointestinal tract and the regulation of stomach ghrelin expression and production

    Institute of Scientific and Technical Information of China (English)

    Zheng Zhao; Takafumi Sakai

    2008-01-01

    Ghrelin was isolated as an endogenous ligand for the GH secretagogue receptor from the rat stomach. Although physiological effects of ghrelin have been revealed by numerous studies, the regulation of stomach ghrelin remains obscure, and the factor that directly regulates ghrelin expression and production has not been identified. Here, we show some data regarding the characteristic features of ghrelin cells and the regulation of stomach ghrelin. In the gastrointestinal tract, ghrelin cells were identified as opened- and closed-type cells, and it was found that the number of ghrelin cells decreased from the stomach to the colon. The postnatal change in number of ghrelin cells in the stomach showed a sexually dimorphic pattern, indicating a role of estrogen in the regulation of stomach ghrelin. In vitro studies revealed that estrogen stimulated both ghrelin expression and production and that treatment with formestane, an aromatase (estrogen synthetase) inhibitor, decreased ghrelin expression level. On the other hand, leptin was found to inhibit both basal and estrogen-stimulated ghrelin expression. Moreover, both aromatase mRNA-expressing cells and leptin cells were found to be located close to ghrelin cells in the gastric mucosa. Furthermore, we found an inverse relationship between gastric ghrelin and leptin levels in a fasting state, and we revealed relative changes in expression of gastric ghrelin, estrogen and leptin in the postnatal rats. We propose that gastric estrogen and leptin directly regulate stomach ghrelin and that the balance control through gastric estrogen and leptin contributes to the altered ghrelin expression level in some physiological states.

  11. Gastrointestinal System

    NARCIS (Netherlands)

    Jepson, Mark A.; Bouwmeester, Hans

    2017-01-01

    The epithelial lining of the gastrointestinal tract (GIT) acts as a barrier to uptake of potentially dangerous material while allowing absorption of processed food. The gut may be exposed to a diverse range of engineered nanomaterials due to their deliberate addition to food and consumer products

  12. Emergency Pancreatoduodenectomy with Preservation of Gastroduodenal Artery for Massive Gastrointestinal Bleeding due to Duodenal Metastasis by Clear Cell Renal Cell Carcinoma in a Patient with Celiac Artery Stenosis

    Directory of Open Access Journals (Sweden)

    Kyriakos Neofytou

    2014-01-01

    Full Text Available Duodenal metastasis from renal cell carcinoma is rare, and even rarer is a massive gastrointestinal bleeding from such tumours. Coeliac occlusive disease, although rarely symptomatic, can lead to ischaemic changes with anastomotic dehiscence and leaks when a patient undergoes pancreatoduodenectomy. A 41-year-old man with known metastasis to the adrenal glands and the second part of the duodenum close to the ampulla of Vater from clear cell renal cell carcinoma was admitted to our department due to massive gastrointestinal bleeding from the duodenal metastasis. Endoscopic control of the bleed was not possible, while the bleeding vessel embolization was able to control the haemorrhage only temporarily. An angiography during the embolization demonstrated the presence of stenosis of the coeliac artery and also hypertrophic inferior pancreaticoduodenal arteries supplying the proper hepatic artery via the gastroduodenal artery (GDA. The patient underwent emergency pancreatoduodenectomy with preservation of the gastroduodenal artery. The patient had an uneventful recovery and did not experience further bleeding. Also the blood flow to the liver was compromised as shown by the normal liver function tests (LFTs postoperatively. To the best of our knowledge, this is the first report of a preservation of the GDA during an emergency pancreatoduodenectomy.

  13. Effect of encapsulation of selected probiotic cell on survival in simulated gastrointestinal tract condition

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    Hasiah Ayama

    2014-06-01

    Full Text Available The health benefits of probiotic bacteria have been led to their increasing use in foods. Encapsulation has been investigated to improve their survival. In this study, the selection, encapsulation and viability of lactic acid bacteria (LAB with probiotic properties in simulated gastrointestinal tract (GIT condition were investigated. One hundred and fifty isolates of LAB were obtained from 30 samples of raw cow and goat milk and some fermented foods. Nine isolates could survive under GIT condition and only 3 isolates exhibited an antimicrobial activity against all food-borne pathogenic bacteria. Among them, 2 isolates (CM21 and CM53 exhibited bile salt hydrolase activity on glycocholate and glycodeoxycholate agar plates and were identified as Lactobacillus plantarum. CM53 was selected for encapsulation using 1-3% alginate and 2% Hi-maize resistant starch by emulsion system. Viability and releasing ability of encapsulated CM53 in simulated GIT condition was increased in accordance to the alginate concentration and incubation time, respectively.

  14. Associations between gastrointestinal toxicity, micro RNA and cytokine production in patients undergoing myeloablative allogeneic stem cell transplantation.

    Science.gov (United States)

    Pontoppidan, Peter L; Jordan, Karina; Carlsen, Anting Liu; Uhlving, Hilde Hylland; Kielsen, Katrine; Christensen, Mette; Ifversen, Marianne; Nielsen, Claus Henrik; Sangild, Per; Heegaard, Niels Henrik Helweg; Heilmann, Carsten; Sengeløv, Henrik; Müller, Klaus

    2015-03-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a procedure with a high risk of treatment related mortality. The primary aim of the present study was to examine associations between markers of gastrointestinal toxicity, markers of systemic inflammation, and plasma levels of microRNA (miRNA) -155 and -146a during the first month after HSCT. The secondary aim was to characterize the impact of the toxic-inflammatory response on the function of circulating leukocytes during immune recovery. Thirty HSCT patients were included. Gastrointestinal injury was monitored by toxicity scores, lactulose-mannitol test and plasma citrulline, as a measure of the enterocyte population. Nadir of citrulline and maximum of oral toxicity scores, intestinal permeability, CRP and plasma levels of IL-6 and IL-10 was seen at day +7 post-HSCT. miRNA-155 and mi-RNA-146a showed an inverse relation with significantly elevated miRNA-155 and decreased miRNA-146a levels, from day 0 to day +28 compared with pre-conditioning levels. Citrulline levels below the median at day +7 were associated with higher spontaneous production of IL-6 and TNF-α as well as higher in vitro stimulated production of IL-17A at day +21. This study is the first to demonstrate that toxic responses to chemotherapy are accompanied by differential regulation of miRNAs with opposing effects on immune regulation. We find that a proinflammatory miRNA profile is sustained during the first three weeks after the transplantation, indicating that these miRNAs may play a role in the regulation of the inflammatory environment during immune reconstitution after HSCT. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. The potency of human testicular stem cells

    NARCIS (Netherlands)

    Chikhovskaya, J.V.

    2013-01-01

    In this thesis, we evaluate the stem cell state of cells present in primary human testicular cell cultures as well as their origin and relation to germ or somatic lineages within testicular tissue. We conclude that human testis-derived embryonic stem cell-like (htES-like) colonies arising in primary

  16. Stem cell differentiation and human liver disease

    Institute of Scientific and Technical Information of China (English)

    Wen-Li Zhou; Claire N Medine; Liang Zhu; David C Hay

    2012-01-01

    Human stem cells are scalable cell populations capable of cellular differentiation.This makes them a very attractive in vitro cellular resource and in theory provides unlimited amounts of primary cells.Such an approach has the potential to improve our understanding of human biology and treating disease.In the future it may be possible to deploy novel stem cell-based approaches to treat human liver diseases.In recent years,efficient hepatic differentiation from human stem cells has been achieved by several research groups including our own.In this review we provide an overview of the field and discuss the future potential and limitations of stem cell technology.

  17. Connexin 26 facilitates gastrointestinal bacterial infection in vitro.

    Science.gov (United States)

    Simpson, Charlotte; Kelsell, David P; Marchès, Olivier

    2013-01-01

    Escherichia coli, including enteropathogenic E. coli (EPEC), represents the most common cause of diarrhoea worldwide and is therefore a serious public health burden. Treatment for gastrointestinal pathogens is hindered by the emergence of multiple antibiotic resistance, leading to the requirement for the development of new therapies. A variety of mechanisms act in combination to mediate gastrointestinal-bacterial-associated diarrhoea development. For example, EPEC infection of enterocytes induces attaching and effacing lesion formation and the disruption of tight junctions. An alternative enteric pathogen, Shigella flexneri, manipulates the expression of Connexin 26 (Cx26), a gap junction protein. S. flexneri can open Cx26 hemichannels allowing the release of ATP, whereas HeLa cells expressing mutant gap-junction-associated Cx26 are less susceptible to cellular invasion by S. flexneri than cells expressing wild-type (WT) Cx26. We have investigated further the link between Cx26 expression and gastrointestinal infection by using EPEC and S. flexneri as in vitro models of infection. In this study, a significant reduction in EPEC adherence was observed in cells expressing mutant Cx26 compared with WT Cx26. Furthermore, a significant reduction in both cellular invasion by S. flexneri and adherence by EPEC was demonstrated in human intestinal cell lines following treatment with Cx26 short interfering RNA. These in vitro results suggest that the loss of functional Cx26 expression provides improved protection against gastrointestinal bacterial pathogens. Thus, Cx26 represents a potential therapeutic target for gastrointestinal bacterial infection.

  18. The human airway epithelial basal cell transcriptome.

    Directory of Open Access Journals (Sweden)

    Neil R Hackett

    Full Text Available BACKGROUND: The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population. METHODOLOGY/PRINCIPAL FINDINGS: Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the "human airway basal cell signature" as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels. CONCLUSION/SIGNIFICANCE: The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of

  19. Prevalence of gastrointestinal parasites in captive non-human primates of twenty-four zoological gardens in China.

    Science.gov (United States)

    Li, Mei; Zhao, Bo; Li, Bo; Wang, Qiang; Niu, Lili; Deng, Jiabo; Gu, Xiaobin; Peng, Xuerong; Wang, Tao; Yang, Guangyou

    2015-06-01

    Captive primates are susceptible to gastrointestinal (GIT) parasitic infections, which are often zoonotic and can contribute to morbidity and mortality. Fecal samples were examined by the means of direct smear, fecal flotation, fecal sedimentation, and fecal cultures. Of 26.51% (317/1196) of the captive primates were diagnosed gastrointestinal parasitic infections. Trichuris spp. were the most predominant in the primates, while Entamoeba spp. were the most prevalent in Old World monkeys (P primates and the safety of animal keepers and visitors.

  20. The distribution of mucous secreting cells in the gastrointestinal tracts of three small rodents from Saudi Arabia: Acomys dimidiatus, Meriones rex and Meriones libycus.

    Science.gov (United States)

    Johnson, Olga; Marais, Sumine; Walters, Jacklynn; van der Merwe, Elizabeth L; Alagaili, Abdulaziz N; Mohammed, Osama B; Bennett, Nigel C; Kotzé, Sanet H

    2016-03-01

    The proportion of mucin phenotypes (which form the protective biofilm of the gastrointestinal tract) differs between intestinal regions. This study examines the distribution of mucin secreting cells in the gastrointestinal tracts of the Eastern spiny mouse (Acomys dimidiatus), King jird (Meriones rex) and Libyan jird (Meriones libycus), which inhabit the dry and hot deserts of Saudi Arabia. Intestinal tract samples were processed to wax and tissue sections stained with Alcian Blue-Periodic Acid Schiff (AB-PAS) and High Iron Diamine-Alcian Blue (HID-AB) in order to determine different mucin phenotypes by quantitative analysis. Mixed mucin secreting cells (combined neutral and acid) was the predominant mucin secreting cell type observed throughout the gastrointestinal tract in all species. Acid mucin secreting goblet cells were mainly located in the colon. A. dimidiatus presented with significantly more total sialo than sulfomucin secreting cells while the opposite was true for both Meriones species. The distribution of mucin secreting cells is therefore similar to previously reported results for small mammals not living under arid conditions.

  1. Microarray analysis of human epithelial cell responses to bacterial interaction.

    Science.gov (United States)

    Mans, Jeffrey J; Lamont, Richard J; Handfield, Martin

    2006-09-01

    Host-pathogen interactions are inherently complex and dynamic. The recent use of human microarrays has been invaluable to monitor the effects of various bacterial and viral pathogens upon host cell gene expression programs. This methodology has allowed the host response transcriptome of several cell lines to be studied on a global scale. To this point, the great majority of reports have focused on the response of immune cells, including macrophages and dendritic cells. These studies revealed that the immune response to microbial pathogens is tailored to different microbial challenges. Conversely, the paradigm for epithelial cells has--until recently--held that the epithelium mostly served as a relatively passive physical barrier to infection. It is now generally accepted that the epithelial barrier contributes more actively to signaling events in the immune response. In light of this shift, this review will compare transcriptional profiling data from studies that involved host-pathogen interactions occurring with epithelial cells. Experiments that defined both a common core response, as well as pathogen-specific host responses will be discussed. This review will also summarize the contributions that transcriptional profiling analysis has made to our understanding of bacterial physio-pathogensis of infection. This will include a discussion of how host transcriptional responses can be used to infer the function of virulence determinants from bacterial pathogens interacting with epithelial mucosa. In particular, we will expand upon the lessons that have been learned from gastro-intestinal and oral pathogens, as well as from members of the commensal flora.

  2. Intestinal epithelial cell secretion of RELM-beta protects against gastrointestinal worm infection

    Science.gov (United States)

    IL-4 and IL-13 protect against parasitic helminths, but little is known about the mechanism of host protection. We show that IL-4/IL-13 confer immunity against worms by inducing intestinal epithelial cells (IEC) to differentiate into goblet cells that secrete resistin-like molecule beta (RELMB). R...

  3. Implications of occult metastatic cells for systemic cancer treatment in patients with breast or gastrointestinal cancer.

    Science.gov (United States)

    Braun, S; Rosenberg, R; Thorban, S; Harbeck, N

    2001-06-01

    The early and clinically occult spread of viable tumour cells to the organism is becoming acknowledged as a hallmark in cancer progression, since abundant clinical and experimental data suggest that these cells are precursors of subsequent distant relapse. Using monoclonal antibodies against epithelial cytokeratins or tumour-associated cell membrane glycoproteins, individual carcinoma cells can be detected in cytological bone marrow preparations at frequencies of 10(-5) to 10(-6). Prospective clinical studies have shown that the presence of such immunostained cells in bone marrow is prognostically relevant with regard to relapse-free and overall survival, even in malignancies that do not preferentially metastasise to bone. As current treatment strategies have resulted in a substantial improvement of cancer mortality rates, it is noteworthy to consider the intriguing options of immunocytochemical screening of bone marrow aspirates for occult metastatic cells. Besides improved tumour staging, such screening offers opportunities for guiding patient stratification for adjuvant therapy trials, monitoring response to adjuvant therapies (which, at present, can only be assessed retrospectively after an extended period of clinical follow-up), and specifically targeting tumour-biological therapies against disseminated tumour cells. The present review summarises the current data on the clinical significance of occult metastatic cancer cells in bone marrow.

  4. Gastrointestinal tract modelling in health and disease

    Institute of Scientific and Technical Information of China (English)

    Dong-Hua Liao; Jing-Bo Zhao; Hans Gregersen

    2009-01-01

    The gastrointestinal (GI) tract is the system of organs within multi-cellular animals that takes in food, digests it to extract energy and nutrients, and expels the remaining waste. The various patterns of GI tract function are generated by the integrated behaviour of multiple tissues and cell types. A thorough study of the GI tract requires understanding of the interactions between cells, tissues and gastrointestinal organs in health and disease. This depends on knowledge, not only of numerous cellular ionic current mechanisms and signal transduction pathways, but also of large scale GI tissue structures and the special distribution of the nervous network. A unique way of coping with this explosion in complexity is mathematical and computational modelling; providing a computational framework for the multilevel modelling and simulation of the human gastrointestinal anatomy and physiology. The aim of this review is to describe the current status of biomechanical modelling work of the GI tract in humans and animals, which can be further used to integrate the physiological, anatomical and medical knowledge of the GI system. Such modelling will aid research and ensure that medical professionals benefit, through the provision of relevant and precise information about the patient's condition and GI remodelling in animal disease models. It will also improve the accuracy and efficiency of medical procedures, which could result in reduced cost for diagnosis and treatment.

  5. Campylobacter-induced interleukin-8 responses in human intestinal epithelial cells and primary intestinal chick cells.

    Science.gov (United States)

    Borrmann, Erika; Berndt, Angela; Hänel, Ingrid; Köhler, Heike

    2007-09-20

    Campylobacter (C.) jejuni and C. coli can cause gastrointestinal disorders in humans characterized by acute inflammation. Inflammatory signals are initiated during interaction between these pathogens and human intestinal cells, but nothing is known about the stimulation of avian intestinal cells by Campylobacter. Interleukin-8 (IL-8) as a proinflammatory chemokine plays an important role in mobilizing cellular defence mechanism. IL-8 mRNA expression in both human intestinal cells (INT 407) and primary intestinal chick cells (PIC) was determined by quantitative real-time RT-PCR. The secretion of IL-8 protein by INT407 was measured using ELISA. Although C. jejuni and C. coli are considered to be harmless commensals in the gut of birds, the avian Campylobacter isolates investigated were able to induce the proinflammatory IL-8 in PIC as well as in INT407. In an in vitro system, C. jejuni as well as C. coli were able to induce IL-8 mRNA in PIC. Relation between the virulence properties like toxin production, the ability to invade and to survive in Caco-2 cells and the level of IL-8 mRNA produced by INT 407 and PIC after infection with Campylobacter strains was also investigated.

  6. Angiotensin I-Converting Enzyme (ACE Inhibitory Activity and ACE Inhibitory Peptides of Salmon (Salmo salar Protein Hydrolysates Obtained by Human and Porcine Gastrointestinal Enzymes

    Directory of Open Access Journals (Sweden)

    Małgorzata Darewicz

    2014-08-01

    Full Text Available The objectives of the present study were two-fold: first, to detect whether salmon protein fractions possess angiotensin I-converting enzyme (ACE inhibitory properties and whether salmon proteins can release ACE inhibitory peptides during a sequential in vitro hydrolysis (with commercial porcine enzymes and ex vivo digestion (with human gastrointestinal enzymes. Secondly, to evaluate the ACE inhibitory activity of generated hydrolysates. A two-step ex vivo and in vitro model digestion was performed to simulate the human digestion process. Salmon proteins were degraded more efficiently by porcine enzymes than by human gastrointestinal juices and sarcoplasmic proteins were digested/hydrolyzed more easily than myofibrillar proteins. The ex vivo digested myofibrillar and sarcoplasmic duodenal samples showed IC50 values (concentration required to decrease the ACE activity by 50% of 1.06 and 2.16 mg/mL, respectively. The in vitro hydrolyzed myofibrillar and sarcoplasmic samples showed IC50 values of 0.91 and 1.04 mg/mL, respectively. Based on the results of in silico studies, it was possible to identify 9 peptides of the ex vivo hydrolysates and 7 peptides of the in vitro hydrolysates of salmon proteins of 11 selected peptides. In both types of salmon hydrolysates, ACE-inhibitory peptides IW, IY, TVY and VW were identified. In the in vitro salmon protein hydrolysates an ACE-inhibitory peptides VPW and VY were also detected, while ACE-inhibitory peptides ALPHA, IVY and IWHHT were identified in the hydrolysates generated with ex vivo digestion. In our studies, we documented ACE inhibitory in vitro effects of salmon protein hydrolysates obtained by human and as well as porcine gastrointestinal enzymes.

  7. Endocannabinoids and Human Sperm Cells

    Directory of Open Access Journals (Sweden)

    Giovanna Zolese

    2010-10-01

    Full Text Available N-acylethanolamides (NAEs are naturally occurring signaling lipids consisting of amides and esters of long-chain polyunsaturated fatty acids. Usually they are present in a very small amounts in many mammalian tissues and cells, including human reproductive tracts and fluids. Recently, the presence of N-arachidonoylethanolamide (anandamide, AEA, the most characterised member of endocannabinoids, and its congeners palmitoylethanolamide (PEA and oleylethanolamide (OEA in seminal plasma, oviductal fluid, and follicular fluids was demonstrated. AEA has been shown to bind not only type-1 (CB1 and type-2 (CB2 cannabinoid receptors, but also type-1 vanilloid receptor (TRPV1, while PEA and OEA are inactive with respect to classical cannabinoid CB1 and CB2 but activate TRPV1 or peroxisome proliferator activate receptors (PPARs. This review concerns the most recent experimental data on PEA and OEA, endocannabinoid-like molecules which appear to exert their action exclusively on sperm cells with altered features, such as membrane characteristics and kinematic parameters. Their beneficial effects on these cells could suggest a possible pharmacological use of PEA and OEA on patients affected by some forms of idiopathic infertility.

  8. Analysis of the human intestinal epithelial cell transcriptional response to Lactobacillus acidophilus, Lactobacillus salivarius, Bifidobacterium lactis and Escherichia coli

    DEFF Research Database (Denmark)

    Putaala, H; Barrangou, R; Leyer, G J

    2010-01-01

    The complex microbial population residing in the human gastrointestinal tract consists of commensal, potential pathogenic and beneficial species, which are probably perceived differently by the host and consequently could be expected to trigger specific transcriptional responses. Here, we provide...... insights into the relationship between probiotics and human intestinal epithelial cells, notably with regard to strain-specific responses, and highlight the differences between transcriptional responses to pathogenic and probiotic bacteria.......The complex microbial population residing in the human gastrointestinal tract consists of commensal, potential pathogenic and beneficial species, which are probably perceived differently by the host and consequently could be expected to trigger specific transcriptional responses. Here, we provide...... a comparative analysis of the global in vitro transcriptional response of human intestinal epithelial cells to Lactobacillus acidophilus NCFM™, Lactobacillus salivarius Ls-33, Bifidobacterium animalis subsp. lactis 420, and enterohaemorrhagic Escherichia coli O157:H7 (EHEC). Interestingly, L. salivarius Ls-33...

  9. Identification and Phylogeny of the First T Cell Epitope Identified from a Human Gut Bacteroides Species.

    Science.gov (United States)

    Perez-Muñoz, Maria Elisa; Joglekar, Payal; Shen, Yi-Ju; Shen, Yi-Ji; Chang, Kuan Y; Peterson, Daniel A

    2015-01-01

    Host T cell reactivity toward gut bacterial epitopes has been recognized as part of disease pathogenesis. However, the specificity of T cells that recognize this vast number of epitopes has not yet been well described. After colonizing a C57BL/6J germ-free mouse with the human gut symbiotic bacteria Bacteroides thetaiotaomicron, we isolated a T cell that recognized these bacteria in vitro. Using this T cell, we mapped the first known non-carbohydrate T cell epitope within the phylum Bacteroidetes. The T cell also reacted to two other additional Bacteroides species. We identified the peptide that stimulated the T cell by using a genetic approach. Genomic data from the epitope-positive and epitope-negative bacteria explain the cross-reactivity of the T cell to multiple species. This epitope degeneracy should shape our understanding of the T cell repertoire stimulated by the complex microbiome residing in the gastrointestinal tract in both healthy and disease states.

  10. Human regulatory B cells control the TFH cell response.

    Science.gov (United States)

    Achour, Achouak; Simon, Quentin; Mohr, Audrey; Séité, Jean-François; Youinou, Pierre; Bendaoud, Boutahar; Ghedira, Ibtissem; Pers, Jacques-Olivier; Jamin, Christophe

    2017-07-01

    Follicular helper T (TFH) cells support terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses, but their control of TFH cell-dependent humoral immune responses is unknown. We sought to assess the role of Breg cells on TFH cell development and function. Human T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate TFH cells. They were cocultured with B cells to induce their terminal differentiation. Breg cells were included in these cultures, and their effects were evaluated by using flow cytometry and ELISA. B-cell lymphoma 6, IL-21, inducible costimulator, CXCR5, and programmed cell death protein 1 (PD-1) expressions increased on stimulated human T cells, characterizing TFH cell maturation. In cocultures they differentiated B cells into CD138(+) plasma and IgD(-)CD27(+) memory cells and triggered immunoglobulin secretions. Breg cells obtained by Toll-like receptor 9 and CD40 activation of B cells prevented TFH cell development. Added to TFH cell and B-cell cocultures, they inhibited B-cell differentiation, impeded immunoglobulin secretions, and expanded Foxp3(+)CXCR5(+)PD-1(+) follicular regulatory T cells. Breg cells modulated IL-21 receptor expressions on TFH cells and B cells, and their suppressive activities involved CD40, CD80, CD86, and intercellular adhesion molecule interactions and required production of IL-10 and TGF-β. Human Breg cells control TFH cell maturation, expand follicular regulatory T cells, and inhibit the TFH cell-mediated antibody secretion. These novel observations demonstrate a role for the Breg cell in germinal center reactions and suggest that deficient activities might impair the TFH cell-dependent control of humoral immunity and might lead to the development of aberrant autoimmune responses. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  11. gastrointestinal tract

    Directory of Open Access Journals (Sweden)

    Rolandas Vaicekauskas

    2016-07-01

    Full Text Available Introduction : Accurate diagnosis of subepithelial lesions (SELs in the gastrointestinal tract depends on a variety of methods: endoscopy, endoscopic ultrasound and different types of biopsy. Making an error-free diagnosis is vital for the subsequent application of an appropriate treatment. Aim: To evaluate the efficacy of deep biopsy via the endoscopic submucosal dissection (ESD technique for SELs in the upper gastrointestinal tract. Material and methods: It was a case series study. Deep biopsy via the ESD technique was completed in 38 patients between November 2012 and October 2014. Thirty-eight SELs in the upper gastrointestinal tract of varying size (very small ≤ 1 cm, small 1–2 cm and large ≥ 2 cm by means of the ESD technique after an incision with an electrosurgical knife of the overlying layers and revealing a small part of the lesion were biopsied under direct endoscopic view. Results: Deep biopsy via the ESD technique was diagnostic in 28 of 38 patients (73.3%; 95% CI: 59.7–89.7%. The diagnostic yield for SELs with a clear endophytic shape increased to 91.3%. An evident endophytic appearance of a subepithelial lesion, the mean number of biopsied samples (6.65 ±1.36 and the total size in length of all samples per case (19.88 ±8.07 mm were the main criteria influencing the positiveness of deep biopsy in the diagnostic group compared to the nondiagnostic one (p = 0.001; p = 0.025; p = 0.008. Conclusions : Deep biopsy via the ESD technique is an effective and safe method for the diagnosis of SELs especially with a clear endophytic appearance in a large number of biopsied samples.

  12. In-vitro bioaccessibility of five pyrethroids after human ingestion and the corresponding gastrointestinal digestion parameters: A contribution for human exposure assessments.

    Science.gov (United States)

    Shi, Yan-Hong; Xiao, Jin-Jing; Feng, Rong-Peng; Liu, Yu-Ying; Liao, Min; Wu, Xiang-Wei; Hua, Ri-Mao; Cao, Hai-Qun

    2017-09-01

    Bioaccessibility is a crucial parameter in assessing the absorption of contaminants during the human digestive process, but few studies have involved the differences in the bioaccessibilities of pesticides. To investigate the mode of using the in vitro bioaccessibility to refine estimates of dietary exposure to pesticide residues, this study measured the bioaccessibilities of five pyrethroids in apples, and then, it modelled physicochemical predictors (gastrointestinal pH, digestive times, and the solid-liquid (S/L) ratio) of the bioaccessibilities of pyrethroids. Apple samples of gastric and intestinal phase digestive juices were obtained from an in vitro simulated digestion model. Our survey of in vitro digestion models found that the bioaccessibilities ranged from 4.42% to 31.22% and 10.58%-35.63% in the gastric and intestinal phases, respectively. A sharp trend similar to a normal distribution was observed between the bioaccessibilities and pH values. The bioaccessibility reached its highest value at a pH of 1.91 in the simulated gastric juice and did not significantly change with an increase of the digestive time. A significant negative correlation occurred between the bioaccessibility and S/L ratio, which followed a logarithmic equation. The correlation coefficients (R(2)) ranged from 0.9259 to 0.9831 and 0.9077 to 0.9960 in the simulated gastric and intestinal juice, respectively, suggested that both the pH value and S/L ratio were the main factors affecting the bioaccessibility. Furthermore, a combination of the acceptable daily intake (ADI) and bioaccessibility for human exposure assessments indicated the implication that traditional risk assessment using ADI may seriously overestimate the actual risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Cancer immunoediting by GITR (glucocorticoid-induced TNF-related protein) ligand in humans: NK cell/tumor cell interactions.

    Science.gov (United States)

    Baltz, Katrin M; Krusch, Matthias; Bringmann, Anita; Brossart, Peter; Mayer, Frank; Kloss, Mercedes; Baessler, Tina; Kumbier, Ingrid; Peterfi, Andrea; Kupka, Susan; Kroeber, Stefan; Menzel, Dagmar; Radsak, Markus P; Rammensee, Hans-Georg; Salih, Helmut R

    2007-08-01

    Glucocorticoid-induced TNF-related protein (GITR) has been shown to stimulate T cell-mediated antitumor immunity in mice. However, the functional relevance of GITR and its ligand (GITRL) for non-T cells has yet to be fully explored. In addition, recent evidence suggests that GITR plays different roles in mice and humans. We studied the role of GITR-GITRL interaction in human tumor immunology and report for the first time that primary gastrointestinal cancers and tumor cell lines of different histological origin express substantial levels of GITRL. Signaling through GITRL down-regulated the expression of the immunostimulatory molecules CD40 and CD54 and the adhesion molecule EpCAM, and induced production of the immunosuppressive cytokine TGF-beta by tumor cells. On NK cells, GITR is constitutively expressed and up-regulated following activation. Blocking GITR-GITRL interaction in cocultures of tumor cells and NK cells substantially increased cytotoxicity and IFN-gamma production of NK cells demonstrating that constitutive expression of GITRL by tumor cells diminishes NK cell antitumor immunity. GITRL-Ig fusion protein or cell surface-expressed GITRL did not induce apoptosis in NK cells, but diminished nuclear localized c-Rel and RelB, indicating that GITR might negatively modulate NK cell NF-kappaB activity. Taken together, our data indicate that tumor-expressed GITRL mediates immunosubversion in humans.

  14. Satellite cells in human skeletal muscle plasticity.

    Science.gov (United States)

    Snijders, Tim; Nederveen, Joshua P; McKay, Bryon R; Joanisse, Sophie; Verdijk, Lex B; van Loon, Luc J C; Parise, Gianni

    2015-01-01

    Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodeling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodeling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodeling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

  15. Enzyme activity of β-galactosidase from Kluyveromyces lactis and Aspergillus oryzae on simulated conditions of human gastrointestinal system

    Directory of Open Access Journals (Sweden)

    Alessandra Bosso

    2015-09-01

    Full Text Available An alternative to relieve the symptoms of lactose intolerance is the intake of the enzyme β-galactosidase in pharmaceutical dosage forms. The ability of β-galactosidase produced by Kluyveromyces lactis and Aspergillus oryzae to hydrolyze lactose in simulated conditions of the human gastrointestinal tract was investigated. The experiment was carried out in the optimum temperature for each enzyme activity, 40 and 55°C, respectively, and at the normal human body temperature (37°C at concentrations of 1.5, 3.0, and 5.0 g/L (enzyme from A. oryzae or mL/L (enzyme from K. lactis. Both enzymes were completely inactivated under simulated gastric conditions (pH 2. When the enzymes were subjected to simulated small intestine conditions (pH 7.4, lactose hydrolysis has occurred, but at 37°C the percentage was lower than that under the optimal temperatures. At concentrations of 1.5, 3.0, and 5.0 mL/L the enzyme from K. lactis hydrolyzed 76.63%, 88.91% and 94.80% of lactose at 40°C, and 55.99%, 80.91% and 81.53% at 37°C, respectively. In contrast, the enzyme from A. oryzae hydrolyzed 7.11%, 16.18% and 21.29% at 55°C, and 8.4%, 11.85% and 16.43% at 37°C. It was observed that under simulated intestinal conditions, the enzyme from K. lactis was more effective on lactose hydrolysis as compared to the enzyme from A. oryzae. Considering the findings of this study, it is extremely necessary to use an enteric coating on β-galactosidase capsules so that this enzyme is released only in the small intestine, which is its site of action, thus not suffering the action of the stomach pH.Keywords: Lactase. Hydrolysis. Lactose intolerance. Gastrointestinal tract. RESUMOAtividade de β-galactosidase de Kluyveromyces lactis e Aspergillus oryzae, em condições simuladas do sistema gastrintestinal humanoUma das alternativas para amenizar os sintomas da intolerância à lactose é a ingestão de β-galactosidase em formas farmacêuticas. Neste trabalho avaliou-se a

  16. Two cases of gastrointestinal perforation after radiotherapy in patients receiving tyrosine kinase inhibitor for advanced renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Inoue Takaaki

    2012-08-01

    Full Text Available Abstract We report two cases of gastrointestinal perforation (GIP after radiotherapy in patients receiving tyrosine kinase inhibitor (TKI for advanced renal cell carcinoma (RCC. Case 1 was a 61-year-old woman with lung metastases after a radical nephrectomy for a right RCC (cT3aN0M0 treated with interferon-alpha (OIF, 5 MIU, three times per week. She developed lytic metastases of the left femur and the left acetabulum. She was treated with palliative radiotherapy to the metastatic portion (3 Gy × 10 fractions, and 400 mg sorafenib twice per day plus continuing interferon alpha. She experienced sudden left lower abdominal pain after four weeks of treatment, and was diagnosed with a perforation of the sigmoid colon with fecal peritonitis. Case 2 was a 48-year-old man with lung, lymph node, and bone metastases after a radical nephrectomy for a right RCC (cT2N0M0, and was treated with 400 mg sorafenib twice per day. He developed lytic bone metastases of the lumbar vertebrae, which was treated with palliative radiotherapy to L2-4 (3 Gy × 10 fractions. He experienced sudden abdominal pain after two months of radiation treatment, and was diagnosed with a perforation of the sigmoid colon with fecal peritonitis. These cases underwent radiotherapy, and therefore this may be related to the radiosensitivity of TKI.

  17. Circulating levels of cell adhesion molecule L1 as a prognostic marker in gastrointestinal stromal tumor patients

    Directory of Open Access Journals (Sweden)

    Schachner Melitta

    2011-05-01

    Full Text Available Abstract Background L1 cell adhesion molecule (CD171 is expressed in many malignant tumors and its expression correlates with unfavourable outcome. It thus represents a target for tumor diagnosis and therapy. An earlier study conducted by our group identified L1 expression levels in primary gastrointestinal stromal tumors (GIST as a prognostic marker. The aim of the current study was to compare L1 serum levels of GIST patients with those of healthy controls and to determine whether levels of soluble L1 in sera could serve as a prognostic marker. Methods Using a sensitive enzyme-linked immunosorbent assay (ELISA, soluble L1 was measured in sera of 93 GIST patients und 151 healthy controls. Soluble L1 levels were then correlated with clinicopathological data. Results Median levels of soluble L1 were significantly higher (p p Conclusion These results suggest that high soluble L1 levels predict poor prognosis and may thus be a promising tumor marker that can contribute to individualise therapy.

  18. IMMUNORESPONSES OF HUMANIZED SCID MICE TO HUMAN LUNG CANCER CELLS

    Institute of Scientific and Technical Information of China (English)

    陈力真; 王树蕙; 张云; 王世真

    1996-01-01

    HuPBL-SCID mice were used to explore how they would response to human ttmoor cells of 801/MLC.Living 801/MLC cells appeared to be fetal to the the mice due to the production of human TNF. The huP-BL-SCID rniee did not generate any noticeable amotmt of specific human immunoglobttlin either by single immunization with living 801/MLC cells or by repeated immunization with irradiated 801/MLC cells. Our preliminary experiments with huPBL-SCID mice showed that such chimeras would he a very useful models for tumor immunological researches.

  19. Search for naive human pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    Simone Aparecida Siqueira Fonseca; Roberta Montero Costas; Lygia Veiga Pereira

    2015-01-01

    Normal mouse pluripotent stem cells were originallyderived from the inner cell mass (ICM) of blastocystsand shown to be the in vitro equivalent of those preimplantationembryonic cells, and thus were calledembryonic stem cells (ESCs). More than a decade later,pluripotent cells were isolated from the ICM of humanblastocysts. Despite being called human ESCs, thesecells differ significantly from mouse ESCs, includingdifferent morphology and mechanisms of control ofpluripotency, suggesting distinct embryonic originsof ESCs from the two species. Subsequently, mousepluripotent stem cells were established from the ICMderivedepiblast of post-implantation embryos. Thesemouse epiblast stem cells (EpiSCs) are morphologicaland epigenetically more similar to human ESCs. Thisraised the question of whether cells from the humanICM are in a more advanced differentiation stage thantheir murine counterpart, or whether the availableculture conditions were not adequate to maintain thosehuman cells in their in vivo state, leading to a transitioninto EpiSC-like cells in vitro . More recently, novel cultureconditions allowed the conversion of human ESCs intomouse ESC-like cells called naive (or ground state)human ESCs, and the derivation of naive human ESCsfrom blastocysts. Here we will review the characteristicsof each type of pluripotent stem cells, how (andwhether) these relate to different stages of embryonicdevelopment, and discuss the potential implications ofnaive human ESCs in research and therapy.

  20. Dynamic In Vitro Models of the Human Gastrointestinal Tract as Relevant Tools to Assess the Survival of Probiotic Strains and Their Interactions with Gut Microbiota

    Directory of Open Access Journals (Sweden)

    Charlotte Cordonnier

    2015-10-01

    Full Text Available The beneficial effects of probiotics are conditioned by their survival during passage through the human gastrointestinal tract and their ability to favorably influence gut microbiota. The main objective of this study was to use dynamic in vitro models of the human digestive tract to investigate the effect of fasted or fed state on the survival kinetics of the new probiotic Saccharomyces cerevisiae strain CNCM I-3856 and to assess its influence on intestinal microbiota composition and activity. The probiotic yeast showed a high survival rate in the upper gastrointestinal tract whatever the route of admistration, i.e., within a glass of water or a Western-type meal. S. cerevisiae CNCM I-3856 was more sensitive to colonic conditions, as the strain was not able to colonize within the bioreactor despite a twice daily administration. The main bacterial populations of the gut microbiota, as well as the production of short chain fatty acids were not influenced by the probiotic treatment. However, the effect of the probiotic on the gut microbiota was found to be individual dependent. This study shows that dynamic in vitro models can be advantageously used to provide useful insight into the behavior of probiotic strains in the human digestive environment.

  1. Gastrointestinal stem cells. III. Emergent themes of liver stem cell biology: niche, quiescence, self-renewal, and plasticity.

    Science.gov (United States)

    Theise, Neil D

    2006-02-01

    This essay will address areas of liver stem/progenitor cell studies in which consensus has emerged and in which controversy still prevails over consensus, but it will also highlight important themes that inevitably should be a focus of liver stem/progenitor cell investigations in coming years. Thus concepts regarding cell plasticity, the existence of a physiological/anatomic stem cell niche, and whether intrahepatic liver stem/progenitor cells comprise true stem cells or progenitor cells (or both) will be approached in some detail.

  2. Endothelial cells derived from human embryonic stem cells

    Science.gov (United States)

    Levenberg, Shulamit; Golub, Justin S.; Amit, Michal; Itskovitz-Eldor, Joseph; Langer, Robert

    2002-04-01

    Human embryonic stem cells have the potential to differentiate into various cell types and, thus, may be useful as a source of cells for transplantation or tissue engineering. We describe here the differentiation steps of human embryonic stem cells into endothelial cells forming vascular-like structures. The human embryonic-derived endothelial cells were isolated by using platelet endothelial cell-adhesion molecule-1 (PECAM1) antibodies, their behavior was characterized in vitro and in vivo, and their potential in tissue engineering was examined. We show that the isolated embryonic PECAM1+ cells, grown in culture, display characteristics similar to vessel endothelium. The cells express endothelial cell markers in a pattern similar to human umbilical vein endothelial cells, their junctions are correctly organized, and they have high metabolism of acetylated low-density lipoprotein. In addition, the cells are able to differentiate and form tube-like structures when cultured on matrigel. In vivo, when transplanted into SCID mice, the cells appeared to form microvessels containing mouse blood cells. With further studies, these cells could provide a source of human endothelial cells that could be beneficial for potential applications such as engineering new blood vessels, endothelial cell transplantation into the heart for myocardial regeneration, and induction of angiogenesis for treatment of regional ischemia.

  3. Identification of TRPM7 channels in human intestinal interstitial cells of Cajal

    Institute of Scientific and Technical Information of China (English)

    Byung Joo Kim; Kyu Joo Park; Hyung Woo Kim; Seok Choi; Jae Yeoul Jun; In Youb Chang; Ju-Hong Jeon; Insuk So; Seon Jeong Kim

    2009-01-01

    AIM: To investigate the characteristics of slow electrical waves and the presence of transient receptor potential melastatin-type 7 (TRPM7) in the human gastrointestinal (GI) tract. METHODS: Conventional microelectrode techniques were used to record intracellular electrical responses from human GI smooth muscle tissue. Immunohistochemistry was used to identify TRPM7 channels in interstitial cells of Cajal (ICCs). RESULTS: The human GI tract generated slow electrical waves and had ICCs which functioned as pacemaker cells. Flufenamic acid, a nonselective cation channel blocker, and 2-APB (2-aminoethoxydiphenyl borate) and La3~+, TRPM7 channel blockers, inhibited the slow waves. Also, TRPM7 channels were expressed in ICCs in human tissue. CONCLUSION: These results suggest that the human GI tract generates slow waves and that TRPM7 channels expressed in the ICCs may be involved in the generation of the slow waves.

  4. Rebamipide attenuates nonsteroidal anti-inflammatory drugs (NSAID) induced lipid peroxidation by the manganese superoxide dismutase (MnSOD) overexpression in gastrointestinal epithelial cells.

    Science.gov (United States)

    Nagano, Y; Matsui, H; Shimokawa, O; Hirayama, A; Tamura, M; Nakamura, Y; Kaneko, T; Rai, K; Indo, H P; Majima, H J; Hyodo, I

    2012-04-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) often cause gastrointestinal complications such as gastric ulcers and erosions. Recent studies on the pathogenesis have revealed that NSAIDs induce lipid peroxidation in gastric epithelial cells by generating superoxide anion in mitochondria, independently with cyclooxygenase-inhibition and the subsequent prostaglandin deficiency. Although not clearly elucidated, the impairment of mitochondrial oxidative phosphorylation, or uncoupling, by NSAIDs is associated with the generation of superoxide anion. Physiologically, superoxide is immediately transformed into hydrogen peroxide and diatomic oxygen with manganese superoxide dismutase (MnSOD). Rebamipide is an antiulcer agent that showed protective effects against NSAID-induced lipid peroxidation in gastrointestinal tracts. We hypothesized that rebamipide may attenuate lipid peroxidation by increasing the expression of MnSOD protein in mitochondria and decreasing the leakage of superoxide anion in NSAID-treated gastric and small intestinal epithelial cells. Firstly, to examine rebamipide increases the expression of MnSOD proteins in mitochondria of gastrointestinal epithelial cells, we underwent Western blotting analysis against anti-MnSOD antibody in gastric RGM1 cells and small intestinal IEC6 cells. Secondly, to examine whether the pretreatment of rebamipide decreases NSAID-induced mitochondrial impairment and lipid peroxidation, we treated these cells with NSAIDs with or without rebamipide pretreatment, and examined with specific fluorescent indicators. Finally, to examine whether pretreatment of rebamipide attenuates NSAID-induced superoxide anion leakage from mitochondria, we examined the mitochondria from indomethacin-treated RGM1 cells with electron spin resonance (ESR) spectroscopy using a specific spin-trapping reagent, CYPMPO. Rebamipide increased the expression of MnSOD protein, and attenuated NSAID-induced mitochondrial impairment and lipid peroxidation in RGM1

  5. Induced pluripotent stem cell lines derived from human somatic cells.

    Science.gov (United States)

    Yu, Junying; Vodyanik, Maxim A; Smuga-Otto, Kim; Antosiewicz-Bourget, Jessica; Frane, Jennifer L; Tian, Shulan; Nie, Jeff; Jonsdottir, Gudrun A; Ruotti, Victor; Stewart, Ron; Slukvin, Igor I; Thomson, James A

    2007-12-21

    Somatic cell nuclear transfer allows trans-acting factors present in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. We show that four factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells. These induced pluripotent human stem cells have normal karyotypes, express telomerase activity, express cell surface markers and genes that characterize human ES cells, and maintain the developmental potential to differentiate into advanced derivatives of all three primary germ layers. Such induced pluripotent human cell lines should be useful in the production of new disease models and in drug development, as well as for applications in transplantation medicine, once technical limitations (for example, mutation through viral integration) are eliminated.

  6. Microbiota alterations in acute and chronic gastrointestinal inflammation of cats and dogs

    National Research Council Canada - National Science Library

    Julia B Honneffer Yasushi Minamoto Jan S Suchodolski

    2014-01-01

    ...) inhabiting the gastrointestinal tract. Novel bacterial identification approaches have revealed that the gastrointestinal microbiota of dogs and cats is, similarly to humans, a highly complex ecosystem...

  7. Comparative in vitro effects of closantel and selected beta-ketoamide anthelmintics on a gastrointestinal nematode and vertebrate liver cells.

    Science.gov (United States)

    Bacon, J A; Ulrich, R G; Davis, J P; Thomas, E M; Johnson, S S; Conder, G A; Sangster, N C; Rothwell, J T; McCracken, R O; Lee, B H; Clothier, M F; Geary, T G; Thompson, D P

    1998-06-01

    PNU-87407 and PNU-88509, beta-ketoamide anthelmintics that are structurally related to each other and to the salicylanilide anthelmintic closantel, exhibit different anthelmintic spectra and apparent toxicity in mammals. The basis for this differential pharmacology was examined in experiments that measured motility and adenosine triphosphate (ATP) levels in larval and adult stages of the gastrointestinal nematode, Haemonchus contortus, and in a vertebrate liver cell line and mitochondria. PNU-87407 and PNU-88509 both exhibited functional cross-resistance with closantel in larval migration assays using closantel-resistant and -sensitive isolates of H. contortus. Each compound reduced motility and ATP levels in cultured adult H. contortus in a concentration- and time-dependent manner; however, motility was reduced more rapidly by PNU-88509, and ATP levels were reduced by lower concentrations of closantel than the beta-ketoamides. Tension recordings from segments of adult H. contortus showed that PNU-88509 induces spastic paralysis, while PNU-87407 and closantel induce flaccid paralysis of the somatic musculature. Marked differences in the actions of these compounds were also observed in the mammalian preparations. In Chang liver cells, ATP levels were reduced after 3 h exposures to > or = 0.25 microM PNU-87407, > or = 1 microM closantel or > or = 10 microM PNU-88509. Reductions in ATP caused by PNU-88509 were completely reversible, while the effects of closantel and PNU-87407 were irreversible. PNU-87407, closantel and PNU-88509 uncoupled oxidative phosphorylation in isolated rat liver mitochondria, inhibiting the respiratory control index (with glutamate or succinate as substrate) by 50% at concentrations of 0.14, 0.9 and 7.6 microM, respectively.

  8. Kit signaling is essential for development and maintenance of interstitial cells of Cajal and electrical rhythmicity in the embryonic gastrointestinal tract.

    Science.gov (United States)

    Beckett, Elizabeth A H; Ro, Seungil; Bayguinov, Yulia; Sanders, Kenton M; Ward, Sean M

    2007-01-01

    Interstitial cells of Cajal (ICC) are specialized cells in smooth muscle organs that generate and propagate pacemaker activity, receive inputs from motor neurons, and serve as mechanosensors. In the gastrointestinal tract, development and maintenance of the ICC phenotype have been linked to intracellular signaling via Kit, but its role in development of ICC during embryogenesis is controversial. Here we have studied the development of functional ICC-MY during the late gestational period in mice. Blocking Kit with a neutralizing antibody before and after development of spontaneous electrical activity (E17 to P0) caused loss of ICC-MY networks and pacemaker activity. ICC-MY and pacemaker activity developed normally in W/+ and W(V)/+ heterozygotes, but failed to develop between E17 to P0 in W/W(V) embryos with compromised Kit function. Muscles treated with Kit neutralizing antibody or the tyrosine kinase inhibitor, imatinib mesylate (STI571), from E17-P0 for 3 days caused loss of functionally developed ICC-MY networks, but ICC-MY and pacemaker activity recovered within 9 days after discontinuing treatment with neutralizing antibody or imatinib mesylate. These data suggest that Kit signaling is an important factor in lineage decision and in the development of functional ICC in late gestation. ICC-MY demonstrate significant plasticity in gastrointestinal tissues. Manipulation of the ICC phenotype might provide useful therapies in gastrointestinal disease where the Kit-positive cell population is either lost or amplified.

  9. Trophoblast lineage cells derived from human induced pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ying, E-mail: ying.chen@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Wang, Kai; Chandramouli, Gadisetti V.R. [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Knott, Jason G. [Developmental Epigenetics Laboratory, Department of Animal Science, Michigan State University (United States); Leach, Richard, E-mail: Richard.leach@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Department of Obstetrics, Gynecology and Women’s Health, Spectrum Health Medical Group (United States)

    2013-07-12

    Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro.

  10. Protective role of R-spondin1, an intestinal stem cell growth factor, against radiation-induced gastrointestinal syndrome in mice.

    Directory of Open Access Journals (Sweden)

    Payel Bhanja

    Full Text Available BACKGROUND: Radiation-induced gastrointestinal syndrome (RIGS results from a combination of direct cytocidal effects on intestinal crypt and endothelial cells and subsequent loss of the mucosal barrier, resulting in electrolyte imbalance, diarrhea, weight loss, infection and mortality. Because R-spondin1 (Rspo1 acts as a mitogenic factor for intestinal stem cells, we hypothesized that systemic administration of Rspo1 would amplify the intestinal crypt cells and accelerate the regeneration of the irradiated intestine, thereby, ameliorating RIGS. METHODS AND FINDINGS: Male C57Bl/6 mice received recombinant adenovirus expressing human R-spondin1 (AdRspo1 or E.coli Lacz (AdLacz, 1-3 days before whole body irradiation (WBI or abdominal irradiation (AIR. Post-irradiation survival was assessed by Kaplan Meier analysis. RIGS was assessed by histological examination of intestine after hematoxilin and eosin staining, immunohistochemical staining of BrdU incorporation, Lgr5 and beta-catenin expression and TUNEL staining. The xylose absorption test (XAT was performed to evaluate the functional integrity of the intestinal mucosal barrier. In order to examine the effect of R-spondin1 on tumor growth, AdRspo1 and AdLacZ was administered in the animals having palpable tumor and then exposed to AIR. There was a significant increase in survival in AdRspo1 cohorts compared to AdLacZ (p<0.003 controls, following WBI (10.4 Gy. Significant delay in tumor growth was observed after AIR in both cohorts AdRspo1 and AdLacZ but AdRspo1 treated animals showed improved survival compared to AdLacZ. Histological analysis and XAT demonstrated significant structural and functional regeneration of the intestine in irradiated animals following AdRspo1 treatment. Immunohistochemical analysis demonstrated an increase in Lgr5+ve crypt cells and the translocation of beta-catenin from the cytosol to nucleus and upregulation of beta-catenin target genes in AdRspo1-treated mice, as

  11. Human Neural Cell-Based Biosensor

    Science.gov (United States)

    2013-05-28

    including incubation with factors such as SHH ) and proceed to Human Neural Progenitor Cells Dopaminergic Differentiation β-III Tubulin/TH...exposure in human embryonic stem cells. J Recept Signal Transduct Res. 2011 Jun;31(3):206-13. Gerwe BA, Angel PM, West FD, Hasneen K, Young A

  12. Hedgehog signaling and gastrointestinal cancer

    Science.gov (United States)

    Saqui-Salces, Milena; Merchant, Juanita L.

    2017-01-01

    Hedgehog (Hh) signaling is critical for embryonic development and in differentiation, proliferation, and maintenance of multiple adult tissues. De-regulation of the Hh pathway is associated with birth defects and cancer. In the gastrointestinal tract, Hh ligands Sonic (Shh) and Indian (Ihh), as well as the receptor Patched (Ptch1), and transcription factors of Glioblastoma family (Gli) are all expressed during development. In the adult, Shh expression is restricted to the stomach and colon, while Ihh expression occurs throughout the luminal gastrointestinal tract, its expression being highest in the proximal duodenum. Several studies have demonstrated a requirement for Hh signaling during gastrointestinal tract development. However to date, the specific role of the Hh pathway in the adult stomach and intestine is not completely understood. The current review will place into context the implications of recent published data related to the biochemistry and cell biology of Hh signaling on the luminal gastrointestinal tract during development, normal physiology and subsequently carcinogenesis. PMID:20307590

  13. Erlotinib Hydrochloride and Cetuximab in Treating Patients With Advanced Gastrointestinal Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer

    Science.gov (United States)

    2015-09-28

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Gastrointestinal Stromal Tumor; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Intestine Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Anal Cancer; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Gastric Cancer

  14. The protective effects of total phenols in magnolia officinalix rehd. et wils on gastrointestinal tract dysmotility is mainly based on its influence on interstitial cells of cajal.

    Science.gov (United States)

    Tian, Hui; Huang, Dazhi; Li, Tao; Huang, Lihua; Zheng, Xingguang; Tang, Danxia; Zhang, Lu; Wang, Jian

    2015-01-01

    Magnolia officinalix Rehd. et Wils is a kind of herb which is widely used for gastrointestinal tract mobility disorder in Asian countries. In this study, we investigated whether the total phenols of Magnolia officinalix Rehd. et Wils (TPM) treatment improves gastrointestinal tract dysmobility induced by intraperitoneal injection of atropine (5 mg/kg) in rats. Rats were randomly grouped into three units: TPM-pretreated/atropine-treated group, atropinetreated group and control group. TPM were administrated for 7 days. Gastric residual rate and intestinal transit were measured 20 min after atropine injected, and gastrointestinal hormones (including: gastrin (GAS), motilin (MTL), somatostatin (SS) and p substance (PS) levels in serum were also measured by ELISA kits. The number and distribution of interstitial cells of Cajal (ICCs) in stomach were detected by immunohistochemistry analysis, while c-kit and stem cell factor (SCF) expressions in stomach were also measured by western blotting. We found that TPM pretreatment significantly improved atropine-induced gastric residual rate increase, while had no significantly effects on intestinal transit; it also significantly normalized GAS, MTL and PS serum levels. Atropine-induced ICCs numbers decreased in both sinuses ventriculi and body of stomach, which is improved by TPM pretreatment. Western blotting results showed the expressions of c-kit and SCF were down-regulated after atropine injection, which can be reversed with TPM pretreatment. These results above indicates that TPM treatment can significantly protected atropine-induced gastric dysmoblility, which may owed to its regulation on c-kit/SCF signing pathway.

  15. Integrated meta-omic analyses of the gastrointestinal tract microbiome in patients undergoing allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Kaysen, Anne; Heintz-Buschart, Anna; Muller, Emilie E L; Narayanasamy, Shaman; Wampach, Linda; Laczny, Cédric C; Graf, Norbert; Simon, Arne; Franke, Katharina; Bittenbring, Jörg; Wilmes, Paul; Schneider, Jochen G

    2017-08-01

    In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), treatment-induced changes to the gastrointestinal tract (GIT) microbiome have been linked to adverse outcomes, most notably graft-versus-host disease (GvHD). However, it is presently unknown whether this relationship is causal or consequential. Here, we performed an integrated meta-omic analysis to probe deeper into the GIT microbiome changes during allo-HSCT and its accompanying treatments. We used 16S and 18S rRNA gene amplicon sequencing to resolve archaea, bacteria, and eukaryotes within the GIT microbiomes of 16 patients undergoing allo-HSCT for the treatment of hematologic malignancies. These results revealed a major shift in the GIT microbiome after allo-HSCT including a marked reduction in bacterial diversity, accompanied by only limited changes in eukaryotes and archaea. An integrated analysis of metagenomic and metatranscriptomic data was performed on samples collected from a patient before and after allo-HSCT for acute myeloid leukemia. This patient developed severe GvHD, leading to death 9 months after allo-HSCT. In addition to drastically decreased bacterial diversity, the post-treatment microbiome showed a higher overall number and higher expression levels of antibiotic resistance genes (ARGs). One specific Escherichia coli strain causing a paravertebral abscess was linked to GIT dysbiosis, suggesting loss of intestinal barrier integrity. The apparent selection for bacteria expressing ARGs suggests that prophylactic antibiotic administration may adversely affect the overall treatment outcome. We therefore assert that such analyses including information about the selection of pathogenic bacteria expressing ARGs may assist clinicians in "personalizing" regimens for individual patients to improve overall outcomes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Cortical network from human embryonic stem cells

    OpenAIRE

    2010-01-01

    Abstract The connection of embryonic stem cell technology and developmental biology provides valuable tools to decipher the mechanisms underlying human brain development and diseases, especially among neuronal populations, that are not readily available in primary cultures. It is obviously the case of neurons forming the human cerebral cortex. In the images that are presented, the neurons were generated in vitro from human embryonic stem cells via forebrain-like progenitors. Maintained in cul...

  17. Effect of lumiracoxib on proliferation and apoptosis of human nonsmall cell lung cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    HAO Ji-qing; LI Qi; XU Shu-ping; SHEN Yu-xian; SUN Gen-yun

    2008-01-01

    Background Lumiracoxib is a highly selective cyclooxygenase-2(COX-2)inhibitor with antiinflammatory,analgesic and antipyretic activities comparable with class specific drugs,but with much improved gastrointestinal safety.No studies have examined lumiracoxib for antitumorigenic activity on human nonsmall cell lung cancer cell lines in vitro or its possible molecular mechanisms.Methods The antiproliferative effect of lumiracoxib alone or combined with docetaxol on A549 and NCI-H460 lines was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Drug-drug interactions were analyzed using the coefficient of drug interaction(CDI)to characterize the interactions as synergism,additivity or antagonism.Morphological changes were observed by acridine orange fluorescent staining.Extent of apoptosis was determined by flow cytometry.Results Lumiracoxib(15-240 μmol/L)has an inhibitory effect on the proliferation of A549 and NCI-H460 celllines in concentration- and time-dependent manners with the IC50 values of 2597 μmol/L and 833 pmol/L,respectively.The synergistic effect was prominent when lumiracoxib(15-240 μmol/L)was combined with docetaxol(0.2-2 μmol/L)(CDI <1).Fluorescent staining showed that lumiracoxib could induce apoptosis in A549 and NCI-H460 cells.Lumiracoxib treatment also caused an increase of the sub-G1 fraction in each cell line and resulted in an increase of G0/G1-phase cells and a decrease of S-phase cells.Conclusions Lumiracoxib had antiproliferative effect on the human nonsmall cell lung cancer cell lines A549 and NCI-H460 and had a significant synergy with docetaxol,which may be related to apoptotic induction and cell cycle arrest.

  18. Nutrition, anthropometry, gastrointestinal dysfunction, and circulating levels of tumour necrosis factor alpha receptor I and interleukin-1 receptor antagonist in children during stem cell transplantation

    DEFF Research Database (Denmark)

    Andreassen, B. U.; Pærregaard, Anders; Michaelsen, Kim F.

    2008-01-01

    To evaluate anthropometry, nutrition and gastrointestinal dysfunction, and to characterize the relation between these parameters and the inflammatory activity evaluated by plasma levels of soluble tumour necrosis factor alpha receptor I (sTNFRI) and interleukin-1 receptor antagonist (IL-1Ra) levels...... during stem cell transplantation (SCT) in children. Clinical assessments and blood sampling were performed on days -3, 0, +7, +15 and +31 in eight children undergoing SCT. Energy intake, anthropometry, gastrointestinal dysfunction (WHO toxicity score) and sTNFRI and IL-1Ra were evaluated. The energy...... if the use of conditioning regimens with limited proinflammatory cytokine inducing activity, anti-inflammatory agents, or more optimised nutritional support can reduce the burden of such posttransplant complications....

  19. Secreted Human Adipose Leptin Decreases Mitochondrial Respiration in HCT116 Colon Cancer Cells

    Science.gov (United States)

    Yehuda-Shnaidman, Einav; Nimri, Lili; Tarnovscki, Tanya; Kirshtein, Boris; Rudich, Assaf; Schwartz, Betty

    2013-01-01

    Obesity is a key risk factor for the development of colon cancer; however, the endocrine/paracrine/metabolic networks mediating this connection are poorly understood. Here we hypothesize that obesity results in secreted products from adipose tissue that induce malignancy-related metabolic alterations in colon cancer cells. Human HCT116 colon cancer cells, were exposed to conditioned media from cultured human adipose tissue fragments of obese vs. non-obese subjects. Oxygen consumption rate (OCR, mostly mitochondrial respiration) and extracellular acidification rate (ECAR, mostly lactate production via glycolysis) were examined vis-à-vis cell viability and expression of related genes and proteins. Our results show that conditioned media from obese (vs. non-obese) subjects decreased basal (40%, prespiration and function in HCT116 colon cancer cells, an effect that is at least partly mediated by leptin. These results highlight a putative novel mechanism for obesity-associated risk of gastrointestinal malignancies, and suggest potential new therapeutic avenues. PMID:24073224

  20. Human hematopoietic cell culture, transduction, and analyses

    DEFF Research Database (Denmark)

    Bonde, Jesper; Wirthlin, Louisa; Kohn, Donald B;

    2008-01-01

    This unit provides methods for introducing genes into human hematopoietic progenitor cells. The Basic Protocol describes isolation of CD34(+) cells, transduction of these cells with a retroviral vector on fibronectin-coated plates, assaying the efficiency of transduction, and establishing long...

  1. Human embryonic stem cells derived by somatic cell nuclear transfer.

    Science.gov (United States)

    Tachibana, Masahito; Amato, Paula; Sparman, Michelle; Gutierrez, Nuria Marti; Tippner-Hedges, Rebecca; Ma, Hong; Kang, Eunju; Fulati, Alimujiang; Lee, Hyo-Sang; Sritanaudomchai, Hathaitip; Masterson, Keith; Larson, Janine; Eaton, Deborah; Sadler-Fredd, Karen; Battaglia, David; Lee, David; Wu, Diana; Jensen, Jeffrey; Patton, Phillip; Gokhale, Sumita; Stouffer, Richard L; Wolf, Don; Mitalipov, Shoukhrat

    2013-06-06

    Reprogramming somatic cells into pluripotent embryonic stem cells (ESCs) by somatic cell nuclear transfer (SCNT) has been envisioned as an approach for generating patient-matched nuclear transfer (NT)-ESCs for studies of disease mechanisms and for developing specific therapies. Past attempts to produce human NT-ESCs have failed secondary to early embryonic arrest of SCNT embryos. Here, we identified premature exit from meiosis in human oocytes and suboptimal activation as key factors that are responsible for these outcomes. Optimized SCNT approaches designed to circumvent these limitations allowed derivation of human NT-ESCs. When applied to premium quality human oocytes, NT-ESC lines were derived from as few as two oocytes. NT-ESCs displayed normal diploid karyotypes and inherited their nuclear genome exclusively from parental somatic cells. Gene expression and differentiation profiles in human NT-ESCs were similar to embryo-derived ESCs, suggesting efficient reprogramming of somatic cells to a pluripotent state.

  2. Gastrointestinal behavior of itraconazole in humans - Part 1: Supersaturation from a solid dispersion and a cyclodextrin-based solution.

    Science.gov (United States)

    Brouwers, Joachim; Geboers, Sophie; Mols, Raf; Tack, Jan; Augustijns, Patrick

    2017-06-15

    This study evaluated the fasted state gastrointestinal behavior of the lipophilic drug itraconazole, orally administered to healthy volunteers as either a solid dispersion (Sporanox(®) capsules) or a cyclodextrin-based solution (Sporanox(®) solution). Following intake of the drug products, gastric and duodenal fluids were aspirated and analyzed for itraconazole concentration, total content and solubilizing capacity. Release of itraconazole from the solid dispersion generated high and metastable supersaturated levels in the stomach, but the dissolved fraction in the duodenum remained extremely low (median 2.5%). After intake of the itraconazole solution, precipitation was limited in the stomach but pronounced in the small intestine. Still, the dissolved fraction of itraconazole in the duodenum (median 38%) appeared much higher than after intake of the solid dispersion, possibly explaining the improved absorption of itraconazole from the solution. As for the solid dispersion, the absorption-enabling ability of the solution appeared mainly related to increased intraluminal concentrations by means of supersaturation. Cyclodextrin-based solubilization of itraconazole occurred only in the case of limited intraluminal dilution, but did not further enhance itraconazole absorption. The obtained data will help to understand critical aspects of supersaturating drug delivery systems and act as direct reference for the optimization of in vitro simulation tools for gastrointestinal drug behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. E3B1/ABI-1 Isoforms Are Down-Regulated in Cancers of Human Gastrointestinal Tract

    Directory of Open Access Journals (Sweden)

    Rafia A. Baba

    2012-01-01

    Full Text Available The expression of E3B1/ABI-1 protein and its role in cancer progression and prognosis are largely unknown in the majority of solid tumors. In this study, we examined the expression pattern of E3B1/ABI-1 protein in histologically confirmed cases of esophageal (squamous cell carcinoma and adenocarcinoma, gastro-esophageal junction, colorectal cancers and corresponding normal tissues freshly resected from a cohort of 135 patients, by Western Blotting and Immunofluorescence Staining. The protein is present in its phosphorylated form in cells and tissues. Depending on the extent of phosphorylation it is either present in hyper-phosphorylated (M. Wt. 72 kDa form or in hypo-phosphorylated form (M. Wt. 68 kDa and 65 kDa. A thorough analysis revealed that expression of E3B1/ABI-1 protein is significantly decreased in esophageal, gastro-esophageal junction and colorectal carcinomas irrespective of age, gender, dietary and smoking habits of the patients. The decrease in expression of E3B1/ABI-1 was consistently observed for all the three isoforms. However, the decrease in the expression of isoforms varied with different forms of cancers. Down-regulation of E3B1/ABI-1 expression in human carcinomas may play a critical role in tumor progression and in determining disease prognosis.

  4. Irisin immunohistochemistry in gastrointestinal system cancers.

    Science.gov (United States)

    Aydin, S; Kuloglu, T; Ozercan, M R; Albayrak, S; Aydin, S; Bakal, U; Yilmaz, M; Kalayci, M; Yardim, M; Sarac, M; Kazez, A; Kocdor, H; Kanat, B; Ozercan, İ H; Gonen, M; Bilgen, M; Balgetir, F

    2016-01-01

    Cancer is the leading cause of morbidity and mortality worldwide. Some studies have shown that high heat kills cancer cells. Irisin is a protein involved in heat production by converting white into brown adipose tissue, but there is no information about how its expression changes in cancerous tissues. We used irisin antibody immunohistochemistry to investigate changes in irisin expression in gastrointestinal cancers compared to normal tissues. Irisin was found in human brain neuroglial cells, esophageal epithelial cells, esophageal epidermoid carcinoma, esophageal adenocarcinoma and neuroendocrine esophageal carcinoma, gastric glands, gastric adenosquamous carcinoma, gastric neuroendocrine carcinoma, gastric signet ring cell carcinoma, neutrophils in vascular tissues, intestinal glands of colon, colon adenocarcinoma, mucinous colon adenocarcinoma, hepatocytes, hepatocellular carcinoma, islets of Langerhans, exocrine pancreas, acinar cells and interlobular and interlobular ducts of normal pancreas, pancreatic ductal adenocarcinoma, and intra- and interlobular ducts of cancerous pancreatic tissue. Histoscores (area × intensity) indicated that irisin was increased significantly in gastrointestinal cancer tissues, except liver cancers. Our findings suggest that the relation of irisin to cancer warrants further investigation.

  5. Gastrointestinal lipoma and malignancies.

    Science.gov (United States)

    Siegal, A; Witz, M

    1991-07-01

    Twenty gastrointestinal lipomata in 18 patients are reviewed: 15 located in the colon, 3 in the distal ileum, one in the duodenum, and one in the stomach. They were found most frequently in European-born, elderly women and presented with variable abdominal symptomatology. Four lipomata were removed during endoscopy, the remainder at laparotomy, partial colectomy being performed in 10 cases. All, except 2 subserosal types, were located in the submucosa, and their average size was 2.7 cm diameter. Microscopically, none showed true encapsulation, and all were composed of mature fat cells without cellular atypia. In spite of nonspecific changes at endoscopy, one-half of the cases showed, on microscopic examination, atrophy of the overlying glands and a prominent eosinophilic and/or lymphoplasmocytic infiltration of the lamina propria. Two large subserosal lipomata were associated with Crohn's disease. In addition, in 39% of cases, malignant tumours, either single or double, were present in the gastrointestinal tract or elsewhere. Gastrointestinal "lipomata" are located in the sites of normal fatty infiltration in the elderly; these growths could be a local aging or reactive process of the intestinal wall rather than true neoplasms without any potential malignancy. However, coexistent malignancies should be carefully searched for in elderly patients with colonic lipoma.

  6. Human Neuroepithelial Cells Express NMDA Receptors

    Directory of Open Access Journals (Sweden)

    Cappell B

    2003-11-01

    Full Text Available Abstract L-glutamate, an excitatory neurotransmitter, binds to both ionotropic and metabotropic glutamate receptors. In certain parts of the brain the BBB contains two normally impermeable barriers: 1 cerebral endothelial barrier and 2 cerebral epithelial barrier. Human cerebral endothelial cells express NMDA receptors; however, to date, human cerebral epithelial cells (neuroepithelial cells have not been shown to express NMDA receptor message or protein. In this study, human hypothalamic sections were examined for NMDA receptors (NMDAR expression via immunohistochemistry and murine neuroepithelial cell line (V1 were examined for NMDAR via RT-PCR and Western analysis. We found that human cerebral epithelium express protein and cultured mouse neuroepithelial cells express both mRNA and protein for the NMDA receptor. These findings may have important consequences for neuroepithelial responses during excitotoxicity and in disease.

  7. Polyclonal B cell differentiation and loss of gastrointestinal tract germinal centers in the earliest stages of HIV-1 infection.

    Science.gov (United States)

    Levesque, Marc C; Moody, M Anthony; Hwang, Kwan-Ki; Marshall, Dawn J; Whitesides, John F; Amos, Joshua D; Gurley, Thaddeus C; Allgood, Sallie; Haynes, Benjamin B; Vandergrift, Nathan A; Plonk, Steven; Parker, Daniel C; Cohen, Myron S; Tomaras, Georgia D; Goepfert, Paul A; Shaw, George M; Schmitz, Jörn E; Eron, Joseph J; Shaheen, Nicholas J; Hicks, Charles B; Liao, Hua-Xin; Markowitz, Martin; Kelsoe, Garnett; Margolis, David M; Haynes, Barton F

    2009-07-07

    The antibody response to HIV-1 does not appear in the plasma until approximately 2-5 weeks after transmission, and neutralizing antibodies to autologous HIV-1 generally do not become detectable until 12 weeks or more after transmission. Moreover, levels of HIV-1-specific antibodies decline on antiretroviral treatment. The mechanisms of this delay in the appearance of anti-HIV-1 antibodies and of their subsequent rapid decline are not known. While the effect of HIV-1 on depletion of gut CD4(+) T cells in acute HIV-1 infection is well described, we studied blood and tissue B cells soon after infection to determine the effect of early HIV-1 on these cells. In human participants, we analyzed B cells in blood as early as 17 days after HIV-1 infection, and in terminal ileum inductive and effector microenvironments beginning at 47 days after infection. We found that HIV-1 infection rapidly induced polyclonal activation and terminal differentiation of B cells in blood and in gut-associated lymphoid tissue (GALT) B cells. The specificities of antibodies produced by GALT memory B cells in acute HIV-1 infection (AHI) included not only HIV-1-specific antibodies, but also influenza-specific and autoreactive antibodies, indicating very early onset of HIV-1-induced polyclonal B cell activation. Follicular damage or germinal center loss in terminal ileum Peyer's patches was seen with 88% of follicles exhibiting B or T cell apoptosis and follicular lysis. Early induction of polyclonal B cell differentiation, coupled with follicular damage and germinal center loss soon after HIV-1 infection, may explain both the high rate of decline in HIV-1-induced antibody responses and the delay in plasma antibody responses to HIV-1. Please see later in the article for Editors' Summary.

  8. Polyclonal B cell differentiation and loss of gastrointestinal tract germinal centers in the earliest stages of HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Marc C Levesque

    2009-07-01

    Full Text Available The antibody response to HIV-1 does not appear in the plasma until approximately 2-5 weeks after transmission, and neutralizing antibodies to autologous HIV-1 generally do not become detectable until 12 weeks or more after transmission. Moreover, levels of HIV-1-specific antibodies decline on antiretroviral treatment. The mechanisms of this delay in the appearance of anti-HIV-1 antibodies and of their subsequent rapid decline are not known. While the effect of HIV-1 on depletion of gut CD4(+ T cells in acute HIV-1 infection is well described, we studied blood and tissue B cells soon after infection to determine the effect of early HIV-1 on these cells.In human participants, we analyzed B cells in blood as early as 17 days after HIV-1 infection, and in terminal ileum inductive and effector microenvironments beginning at 47 days after infection. We found that HIV-1 infection rapidly induced polyclonal activation and terminal differentiation of B cells in blood and in gut-associated lymphoid tissue (GALT B cells. The specificities of antibodies produced by GALT memory B cells in acute HIV-1 infection (AHI included not only HIV-1-specific antibodies, but also influenza-specific and autoreactive antibodies, indicating very early onset of HIV-1-induced polyclonal B cell activation. Follicular damage or germinal center loss in terminal ileum Peyer's patches was seen with 88% of follicles exhibiting B or T cell apoptosis and follicular lysis.Early induction of polyclonal B cell differentiation, coupled with follicular damage and germinal center loss soon after HIV-1 infection, may explain both the high rate of decline in HIV-1-induced antibody responses and the delay in plasma antibody responses to HIV-1. Please see later in the article for Editors' Summary.

  9. Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts.

    Science.gov (United States)

    Ding, Xinxin; Kaminsky, Laurence S

    2003-01-01

    Cytochrome P450 (CYP) enzymes in extrahepatic tissues often play a dominant role in target tissue metabolic activation of xenobiotic compounds. They may also determine drug efficacy and influence the tissue burden of foreign chemicals or bioavailability of therapeutic agents. This review focuses on xenobiotic-metabolizing CYPs of the human respiratory and gastrointestinal tracts, including the lung, trachea, nasal respiratory and olfactory mucosa, esophagus, stomach, small intestine, and colon. Many CYPs are expressed in one or more of these organs, including CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2A13, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP2F1, CYP2J2, CYP2S1, CYP3A4, CYP3A5, and CYP4B1. Of particular interest are the preferential expression of certain CYPs in the respiratory tract and the regional differences in CYP expression profile in different parts of the gastrointestinal tract. Current research activities on the characterization of CYP expression, function, and regulation in these tissues, as well as future research needs, are discussed.

  10. HER-2 status in gastrointestinal stromal tumor.

    Science.gov (United States)

    Lopes, Lisandro Ferreira; Bacchi, Carlos E

    2008-08-01

    Human epidermal growth factor receptor-2 (HER-2) encodes for the transmembrane glycoprotein HER-2 that is involved in activation of intracellular signal transduction pathways that control cell growth and differentiation. HER-2 is overexpressed in approximately 20% of patients with breast cancer and has been associated with poorer prognosis. Since 1998, the anti-HER-2 antibody trastuzumab has been used for the treatment of patients with HER-2-positive breast cancers. However, little information is available about the relationship between HER-2 and gastrointestinal stromal tumors. This study's purpose was to determine the HER-2 status in gastrointestinal stromal tumors. We found that all 477 cases included in this study were negative (score 0) by immunohistochemistry using HercepTest, and no HER-2 gene amplification was detected in 71 cases submitted to fluorescence in situ hybridization. These results show that HER-2 may not have any role in gastrointestinal stromal tumor pathogenesis and that the neoplasm may not be suitable for treatment with trastuzumab.

  11. Lipomas of the gastrointestinal system.

    Science.gov (United States)

    Dolai, Matilda; Andrejić, Bojana; Ivanov, Dejan

    2012-01-01

    Lipomas are rare benign tumors in the gastrointestinal system. Within the gastrointestinal system, 65% of the lipomas are located in the colon (sigmoid part of the colon or rectum) and rarely in the stomach and esophagus. The paper presents two gastrointestinal lipomas. First is the case of lipoma of the sigmoid colon and the other one is gastric lipoma. In both cases the material was sent for histopathological analysis due to suspicion of malignancy of the lesions. In both cases, the histopathologic analysis showed tumor made of mature adipocytes, localized in the submucosa both of the stomach and intestine. Hypercellularity and/or atypia of the cell was found in neither case. Lipomas are shown because of its atypical localization and clinically suspicious malignancy in the stomach and sigmoid colon. These cases show that the applied methods of preoperative diagnosis of tumors in the gastrointestinal system are not sufficient to determine the origin and biological behavior of tumors. Histopathological diagnosis provides a correct insight into the nature of tumors and determine the course of treatment. This paper presents a rare localization of lipomas in the gastrointestinal system. The preoperative diagnosis of lesions in the gastrointestinal system may not be sufficient to determine the origin and biological behavior of the lesions, hence the histopathological diagnosis gives an accurate insight into the nature of the change, preventing the possibility of further aggressive therapy.

  12. Cell Cycle Progression of Human Cells Cultured in Rotating Bioreactor

    Science.gov (United States)

    Parks, Kelsey

    2009-01-01

    Space flight has been shown to alter the astronauts immune systems. Because immune performance is complex and reflects the influence of multiple organ systems within the host, scientists sought to understand the potential impact of microgravity alone on the cellular mechanisms critical to immunity. Lymphocytes and their differentiated immature form, lymphoblasts, play an important and integral role in the body's defense system. T cells, one of the three major types of lymphocytes, play a central role in cell-mediated immunity. They can be distinguished from other lymphocyte types, such as B cells and natural killer cells by the presence of a special receptor on their cell surface called T cell receptors. Reported studies have shown that spaceflight can affect the expression of cell surface markers. Cell surface markers play an important role in the ability of cells to interact and to pass signals between different cells of the same phenotype and cells of different phenotypes. Recent evidence suggests that cell-cycle regulators are essential for T-cell function. To trigger an effective immune response, lymphocytes must proliferate. The objective of this project is to investigate the changes in growth of human cells cultured in rotating bioreactors and to measure the growth rate and the cell cycle distribution for different human cell types. Human lymphocytes and lymphoblasts will be cultured in a bioreactor to simulate aspects of microgravity. The bioreactor is a cylindrical culture vessel that incorporates the aspects of clinostatic rotation of a solid fluid body around a horizontal axis at a constant speed, and compensates gravity by rotation and places cells within the fluid body into a sustained free-fall. Cell cycle progression and cell proliferation of the lymphocytes will be measured for a number of days. In addition, RNA from the cells will be isolated for expression of genes related in cell cycle regulations.

  13. Cell Cycle Progression of Human Cells Cultured in Rotating Bioreactor

    Science.gov (United States)

    Parks, Kelsey

    2009-01-01

    Space flight has been shown to alter the astronauts immune systems. Because immune performance is complex and reflects the influence of multiple organ systems within the host, scientists sought to understand the potential impact of microgravity alone on the cellular mechanisms critical to immunity. Lymphocytes and their differentiated immature form, lymphoblasts, play an important and integral role in the body's defense system. T cells, one of the three major types of lymphocytes, play a central role in cell-mediated immunity. They can be distinguished from other lymphocyte types, such as B cells and natural killer cells by the presence of a special receptor on their cell surface called T cell receptors. Reported studies have shown that spaceflight can affect the expression of cell surface markers. Cell surface markers play an important role in the ability of cells to interact and to pass signals between different cells of the same phenotype and cells of different phenotypes. Recent evidence suggests that cell-cycle regulators are essential for T-cell function. To trigger an effective immune response, lymphocytes must proliferate. The objective of this project is to investigate the changes in growth of human cells cultured in rotating bioreactors and to measure the growth rate and the cell cycle distribution for different human cell types. Human lymphocytes and lymphoblasts will be cultured in a bioreactor to simulate aspects of microgravity. The bioreactor is a cylindrical culture vessel that incorporates the aspects of clinostatic rotation of a solid fluid body around a horizontal axis at a constant speed, and compensates gravity by rotation and places cells within the fluid body into a sustained free-fall. Cell cycle progression and cell proliferation of the lymphocytes will be measured for a number of days. In addition, RNA from the cells will be isolated for expression of genes related in cell cycle regulations.

  14. Derivation of naive human embryonic stem cells.

    Science.gov (United States)

    Ware, Carol B; Nelson, Angelique M; Mecham, Brigham; Hesson, Jennifer; Zhou, Wenyu; Jonlin, Erica C; Jimenez-Caliani, Antonio J; Deng, Xinxian; Cavanaugh, Christopher; Cook, Savannah; Tesar, Paul J; Okada, Jeffrey; Margaretha, Lilyana; Sperber, Henrik; Choi, Michael; Blau, C Anthony; Treuting, Piper M; Hawkins, R David; Cirulli, Vincenzo; Ruohola-Baker, Hannele

    2014-03-25

    The naïve pluripotent state has been shown in mice to lead to broad and more robust developmental potential relative to primed mouse epiblast cells. The human naïve ES cell state has eluded derivation without the use of transgenes, and forced expression of OCT4, KLF4, and KLF2 allows maintenance of human cells in a naïve state [Hanna J, et al. (2010) Proc Natl Acad Sci USA 107(20):9222-9227]. We describe two routes to generate nontransgenic naïve human ES cells (hESCs). The first is by reverse toggling of preexisting primed hESC lines by preculture in the histone deacetylase inhibitors butyrate and suberoylanilide hydroxamic acid, followed by culture in MEK/ERK and GSK3 inhibitors (2i) with FGF2. The second route is by direct derivation from a human embryo in 2i with FGF2. We show that human naïve cells meet mouse criteria for the naïve state by growth characteristics, antibody labeling profile, gene expression, X-inactivation profile, mitochondrial morphology, microRNA profile and development in the context of teratomas. hESCs can exist in a naïve state without the need for transgenes. Direct derivation is an elusive, but attainable, process, leading to cells at the earliest stage of in vitro pluripotency described for humans. Reverse toggling of primed cells to naïve is efficient and reproducible.

  15. Regulatory T Cells in Human Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Dong-Jun Peng

    2012-01-01

    Full Text Available Multiple layers of suppressive components including regulatory T (TReg cells, suppressive antigen-presenting cells, and inhibitory cytokines form suppressive networks in the ovarian cancer microenvironment. It has been demonstrated that as a major suppressive element, TReg cells infiltrate tumor, interact with several types of immune cells, and mediate immune suppression through different molecular and cellular mechanisms. In this paper, we focus on human ovarian cancer and will discuss the nature of TReg cells including their subsets, trafficking, expansion, and function. We will briefly review the development of manipulation of TReg cells in preclinical and clinical settings.

  16. Generation of pancreatic islet cells from human embryonic stem cells

    Institute of Scientific and Technical Information of China (English)

    ZHANG DongHui; JIANG Wei; SHI Yan; DENG HongKui

    2009-01-01

    Efficiently obtaining functional pancreaUc islet cells derived from human embryonic stem (hES) cells not only provides great potential to solve the shortage of islets sources for type I diabetes cell therapy,but also benefits the study of the development of the human pancreas and diabetes pathology. In 2001,hES cells were reported to have the capacity to generate insulin-producing cells by spontaneous differentiation in vitro. Since then, many strategies (such as overexpression of key transcription factors,delivery of key proteins for pancreatic development, co-transplantation of differentiated hES cells along with fetal pancreas, stepwise differentiation by mimicking in vivo pancreatic development) have been employed in order to induce the differentiation of pancreatic islet cells from hES cells. Moreover, patient-specific induced pluripotent stem (iPS) cells can be generated by reprogramming somatic cells.iPS cells have characteristics similar to those of ES cells and offer a new cell source for type I diabetes cell therapy that reduces the risk of immunologic rejection. In this review, we summarize the recent progress made in the differentiation of hES and iPS cells into functional pancreatic islet cells and discuss the challenges for their future study.

  17. Generation of pancreatic islet cells from human embryonic stem cells

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Efficiently obtaining functional pancreatic islet cells derived from human embryonic stem(hES) cells not only provides great potential to solve the shortage of islets sources for type I diabetes cell therapy,but also benefits the study of the development of the human pancreas and diabetes pathology.In 2001,hES cells were reported to have the capacity to generate insulin-producing cells by spontaneous differentiation in vitro.Since then,many strategies(such as overexpression of key transcription factors,delivery of key proteins for pancreatic development,co-transplantation of differentiated hES cells along with fetal pancreas,stepwise differentiation by mimicking in vivo pancreatic development) have been employed in order to induce the differentiation of pancreatic islet cells from hES cells.Moreover,patient-specific induced pluripotent stem(iPS) cells can be generated by reprogramming somatic cells.iPS cells have characteristics similar to those of ES cells and offer a new cell source for type I diabetes cell therapy that reduces the risk of immunologic rejection.In this review,we summarize the recent progress made in the differentiation of hES and iPS cells into functional pancreatic islet cells and discuss the challenges for their future study.

  18. PPARs Signaling and Cancer in the Gastrointestinal System

    Directory of Open Access Journals (Sweden)

    Valerio Pazienza

    2012-01-01

    Full Text Available Nowadays, the study of the peroxisome proliferators activated receptors (PPARs as potential targets for cancer prevention and therapy has gained a strong interest. From a biological point of view, the overall responsibility of PPARs in cancer development and progression is still controversial since several studies report both antiproliferative and tumor-promoting actions for these signaling molecules in human cancer cells and animal models. In this paper, we discuss PPARs functions in the context of different types of gastrointestinal cancer.

  19. Plasma membrane proteomics of human embryonic stem cells and human embryonal carcinoma cells.

    NARCIS (Netherlands)

    Dormeyer, W.; van Hoof, D.; Braam, S.R.; Heck, A.J.R.; Mummery, C.L.; Krijgsveld, J.

    2008-01-01

    Human embryonic stem cells (hESCs) are of immense interest in regenerative medicine as they can self-renew indefinitely and can give rise to any adult cell type. Human embryonal carcinoma cells (hECCs) are the malignant counterparts of hESCs found in testis tumors. hESCs that have acquired chromosom

  20. An atlas of B-cell clonal distribution in the human body.

    Science.gov (United States)

    Meng, Wenzhao; Zhang, Bochao; Schwartz, Gregory W; Rosenfeld, Aaron M; Ren, Daqiu; Thome, Joseph J C; Carpenter, Dustin J; Matsuoka, Nobuhide; Lerner, Harvey; Friedman, Amy L; Granot, Tomer; Farber, Donna L; Shlomchik, Mark J; Hershberg, Uri; Luning Prak, Eline T

    2017-09-01

    B-cell responses result in clonal expansion, and can occur in a variety of tissues. To define how B-cell clones are distributed in the body, we sequenced 933,427 B-cell clonal lineages and mapped them to eight different anatomic compartments in six human organ donors. We show that large B-cell clones partition into two broad networks-one spans the blood, bone marrow, spleen and lung, while the other is restricted to tissues within the gastrointestinal (GI) tract (jejunum, ileum and colon). Notably, GI tract clones display extensive sharing of sequence variants among different portions of the tract and have higher frequencies of somatic hypermutation, suggesting extensive and serial rounds of clonal expansion and selection. Our findings provide an anatomic atlas of B-cell clonal lineages, their properties and tissue connections. This resource serves as a foundation for studies of tissue-based immunity, including vaccine responses, infections, autoimmunity and cancer.

  1. Gastrointestinal helminth parasites of pet and stray dogs as a potential risk for human health in Bahir Dar town, north-western Ethiopia

    Directory of Open Access Journals (Sweden)

    Tadiwos Abere

    Full Text Available Aim: A cross-sectional study was carried out from November 2011 to April 2012 to determine the prevalence and species of gastrointestinal (GI helminth parasites in pet and stray dogs as a potential risk for human health in Bahir Dar town, northwestern Ethiopia. Materials and Methods: A total of 384 and 46 faecal samples were collected from pet and stray dogs, respectively and xamined by using standard coprologic techniques. Results: The overall prevalence of GI helminth infection in pet and stray dogs was 75.26 and 84.78%, respectively. The detected parasites with their frequencies in pet dogs were Ancylostoma caninum (78.89%, Toxocara canis (39.79%, Dipylidium caninum (29.75%, Strongyloides stercoralis (29.06%, Taeniidae (23.87% and Trichuris vulpis (7.95%. Stray dogs were found more likely to be polyparasitized and presented higher prevalence of A. caninum, T. canis, S. stercoralis, Trichuris vulpis and Taeniidae (P < 0.05 than domiciled ones. Diphyllobothrium latum was detected only in 10.25% of stray dogs. Toxocara canis and A. caninum (P < 0.05 were detected more frequently in dogs with less than 6 months of age (P <0.05 than old age dogs. The sex or breed groups didn't significantly affect the prevalence of parasites. A significant variation was recorded (P < 0.05 between different feeding systems where higher prevalence was observed in uncontrolled feeding group (82.18% compared to controlled feeding (32.08%. Conclusion: Different gastrointestinal parasites in pet and stray dogs were identified in the study area that can potentially infect humans and cause serious public-health problems. Thus, concerted efforts should therefore be made to educate dog owners to embrace modern dog disease control programs and measures have to be taken on stray dogs. [Vet World 2013; 6(7.000: 388-392

  2. Derivation of Human Skin Fibroblast Lines for Feeder Cells of Human Embryonic Stem Cells.

    Science.gov (United States)

    Unger, Christian; Felldin, Ulrika; Rodin, Sergey; Nordenskjöld, Agneta; Dilber, Sirac; Hovatta, Outi

    2016-02-03

    After the first derivations of human embryonic stem cell (hESC) lines on fetal mouse feeder cell layers, the idea of using human cells instead of mouse cells as feeder cells soon arose. Mouse cells bear a risk of microbial contamination, and nonhuman immunogenic proteins are absorbed from the feeders to hESCs. Human skin fibroblasts can be effectively used as feeder cells for hESCs. The same primary cell line, which can be safely used for up to 15 passages after stock preparations, can be expanded and used for large numbers of hESC derivations and cultures. These cells are relatively easy to handle and maintain. No animal facilities or animal work is needed. Here, we describe the derivation, culture, and cryopreservation procedures for research-grade human skin fibroblast lines. We also describe how to make feeder layers for hESCs using these fibroblasts.

  3. Variations of very low-density lipoprotein receptor subtype expression in gastrointestinal adenocarcinoma cells with various differentiations

    Institute of Scientific and Technical Information of China (English)

    Tao Chen; Fan Wu; Feng-Ming Chen; Jun Tian; Shen Qu

    2005-01-01

    AIM: This study is aimed at investigating the expression and possible significances of very low-density lipoprotein receptor (VLDLR) subtypes in gastroenteric adenocarcinoma tissues and cells with various differentiations. METHODS: Thirty-one cases of gastroenteric carcinoma/ adjacent normal tissues were enrolled in the study, which were diagnosed and classified by the clinicopathological diagnosis. The expression of VLDLR subtypes was detected in gastroenteric carcinoma/adjacent normal tissues and three various differentiated human gastric adenocarcinoma cell lines (MKN28, SGC7901 and MKN45) by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis.RE,SULTS: Two VLDLR subtypes, namely, type Ⅱ VLDLR and type Ⅰ VLDLR, were found to express changes in gastroenteric carcinoma tissues, their adjacent normal tissue, and gastric adenocarcinoma cell lines as well. Type Ⅱ VLDLR is predominantly expressed in poorly- or moderately-differentiated gastroenteric carcinoma tissues and gastric adenocarcinoma cell lines, whereas type ⅠVLDLR is mainly detected in well-differentiated intestinal carcinoma tissues and gastric adenocarcinoma cells compared with the adjacent normal tissues. CONCLUSION: The results suggested that the variations of the VLDLR subtype expression might be correlated with the progress and differentiation of gastroenteric carcinoma.

  4. Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Varga, Nora [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Vereb, Zoltan; Rajnavoelgyi, Eva [Department of Immunology, Medical and Health Science Centre, University of Debrecen, Debrecen (Hungary); Nemet, Katalin; Uher, Ferenc; Sarkadi, Balazs [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Apati, Agota, E-mail: apati@kkk.org.hu [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary)

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer MSC like cells were derived from hESC by a simple and reproducible method. Black-Right-Pointing-Pointer Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. Black-Right-Pointing-Pointer MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

  5. The Gastrointestinal Aspects of Halitosis

    Directory of Open Access Journals (Sweden)

    Sivan Kinberg

    2010-01-01

    Full Text Available BACKGROUND: Halitosis is a common human condition for which the exact pathophysiological mechanism is unclear. It has been attributed mainly to oral pathologies. Halitosis resulting from gastrointestinal disorders is considered to be extremely rare. However, halitosis has often been reported among the symptoms related to Helicobacter pylori infection and gastroesophageal reflux disease.

  6. Peptide Hormones in the Gastrointestinal Tract

    DEFF Research Database (Denmark)

    Rehfeld, Jens F.

    2015-01-01

    Gastrointestinal hormones are peptides released from endocrine cells and neurons in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gastrointestinal tract, which makes the gut the largest hormone-producing organ in the body. Modern biology makes it feasi...

  7. Obscure Gastrointestinal Bleeding from an Ampullary Tumour in a Patient with a Remote History of Renal Cell Carcinoma: A Diagnostic Conundrum

    Directory of Open Access Journals (Sweden)

    Rhonda M Janzen

    1998-01-01

    Full Text Available Metastasis of renal cell carcinoma to the ampulla of Vater is a rare occurrence. The outlined case, which presented as an upper gastrointestinal bleed, is only the eighth such reported case in the English-language literature. This case is the longest reported time interval between surgical nephrectomy to presentation with ampullary metastasis at 17.5 years. The ampullary source of bleeding in this case was initially obscure and missed by conventional gastroscopy. Diagnosis was made with a side-viewing endoscope, emphasizing the usefulness of this instrument in the investigation of active bleeding from a small bowel source.

  8. Stem cells in the human breast

    DEFF Research Database (Denmark)

    Petersen, Ole William; Polyak, Kornelia

    2010-01-01

    The origins of the epithelial cells participating in the development, tissue homeostasis, and cancer of the human breast are poorly understood. However, emerging evidence suggests a role for adult tissue-specific stem cells in these processes. In a hierarchical manner, these generate the two main...

  9. Human hair genealogies and stem cell latency

    Directory of Open Access Journals (Sweden)

    Tavaré Simon

    2006-02-01

    Full Text Available Abstract Background Stem cells divide to reproduce themselves and produce differentiated progeny. A fundamental problem in human biology has been the inability to measure how often stem cells divide. Although it is impossible to observe every division directly, one method for counting divisions is to count replication errors; the greater the number of divisions, the greater the numbers of errors. Stem cells with more divisions should produce progeny with more replication errors. Methods To test this approach, epigenetic errors (methylation in CpG-rich molecular clocks were measured from human hairs. Hairs exhibit growth and replacement cycles and "new" hairs physically reappear even on "old" heads. Errors may accumulate in long-lived stem cells, or in their differentiated progeny that are eventually shed. Results Average hair errors increased until two years of age, and then were constant despite decades of replacement, consistent with new hairs arising from infrequently dividing bulge stem cells. Errors were significantly more frequent in longer hairs, consistent with long-lived but eventually shed mitotic follicle cells. Conclusion Constant average hair methylation regardless of age contrasts with the age-related methylation observed in human intestine, suggesting that error accumulation and therefore stem cell latency differs among tissues. Epigenetic molecular clocks imply similar mitotic ages for hairs on young and old human heads, consistent with a restart with each new hair, and with genealogies surreptitiously written within somatic cell genomes.

  10. Human neutrophils facilitate tumor cell transendothelial migration.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    Tumor cell extravasation plays a key role in tumor metastasis. However, the precise mechanisms by which tumor cells migrate through normal vascular endothelium remain unclear. In this study, using an in vitro transendothelial migration model, we show that human polymorphonuclear neutrophils (PMN) assist the human breast tumor cell line MDA-MB-231 to cross the endothelial barrier. We found that tumor-conditioned medium (TCM) downregulated PMN cytocidal function, delayed PMN apoptosis, and concomitantly upregulated PMN adhesion molecule expression. These PMN treated with TCM attached to tumor cells and facilitated tumor cell migration through different endothelial monolayers. In contrast, MDA-MB-231 cells alone did not transmigrate. FACScan analysis revealed that these tumor cells expressed high levels of intercellular adhesion molecule-1 (ICAM-1) but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and of ICAM-1 on MDA-MB-231 cells significantly attenuated TCM-treated, PMN-mediated tumor cell migration. These tumor cells still possessed the ability to proliferate after PMN-assisted transmigration. These results indicate that TCM-treated PMN may serve as a carrier to assist tumor cell transendothelial migration and suggest that tumor cells can exploit PMN and alter their function to facilitate their extravasation.

  11. In-situ visualization and evaluation of neoplastic lesions of the human gastrointestinal tract using endoscopic optical coherence tomography

    Science.gov (United States)

    Rollins, Andrew M.; Westphal, Volker; Das, Ananya; Pfau, Patrick; Chak, Amitabh; Wong, Richard C. K.; Sivak, Michael J., Jr.; Izatt, Joseph A.

    2001-06-01

    Optical coherence tomography (OCT) is a novel biomedical imaging technique that uses low-coherence optical interferometry to obtain micron-scale resolution cross- sectional images of tissue microstructure noninvasively. OCT fills a valuable niche in imaging of tissue structure, providing subsurface imaging with high spatial resolution (on the order of 10 micrometers) and penetration depths of 1 - 2 mm with no contact or matching medium needed between the probe and the tissue. An OCT system for gastrointestinal (GI) endoscopy has been developed using a small-diameter rotary-scanning probe compatible with standard GI endoscopes and capable of imaging in real-time. To date more than 100 volunteers have been imaged during routine upper and lower endoscopic procedures. Results of imaging in normal organs have demonstrated visualization of morphological layers (epithelium, lamina propria, muscularis mucosa, submucosa, muscularis propria) and microscopic structures (glands, villi, crypts, vessels) in all endoscopically accessible GI organs. It has been observed in more than 30 patients that the EOCT appearance of Barrett's mucosa is clearly differentiable from normal gastric or esophageal mucosa. Furthermore, the EOCT appearance of dysplasia and neoplastic lesions, including adenocarcenoma in Barrett's and villous tumor in colon have been observed and are under investigation. Preliminary data indicate the potential of EOCT for routine clinical diagnostics in GI tissues, including early cancer detection and staging and detection of tumor margins.

  12. Encapsulation of probiotic Bifidobacterium longum BIOMA 5920 with alginate-human-like collagen and evaluation of survival in simulated gastrointestinal conditions.

    Science.gov (United States)

    Su, Ran; Zhu, Xiao-Li; Fan, Dai-Di; Mi, Yu; Yang, Chan-Yuan; Jia, Xin

    2011-12-01

    Alginate (ALg)-human-like collagen (HLC) microspheres were prepared by the technology of electrostatic droplet generation in order to develop a biocompatible vehicle for probiotic bacteria. Microparticles were spherical with mean particle size of 400μm. The encapsulation efficiency (EE) of ALg-HLC microspheres could reach 92-99.2%. Water-soluble and fibrous human-like collagen is combined with sodium alginate through intermolecular hydrogen bonding and electrostatic force which were investigated by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC), thus the matrix of ALg-HLC was very stable. Bifidobacterium longum BIOMA 5920, as a kind of probiotic bacteria, was encapsulated with alginate-human-like collagen to survive and function in simulated gastrointestinal juice. Microparticles were very easy to degradation in simulated intestinal juices. After incubation in simulated gastric (pH 2.0, 2h), the encapsulated B. longum BIOMA 5920 numbers were 4.81 ± 0.38 log cfu/g. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. NOTCH1 and NOTCH2 regulate epithelial cell proliferation in mouse and human gastric corpus.

    Science.gov (United States)

    Demitrack, Elise S; Gifford, Gail B; Keeley, Theresa M; Horita, Nobukatsu; Todisco, Andrea; Turgeon, D Kim; Siebel, Christian W; Samuelson, Linda C

    2017-02-01

    The Notch signaling pathway is known to regulate stem cells and epithelial cell homeostasis in gastrointestinal tissues; however, Notch function in the corpus region of the stomach is poorly understood. In this study we examined the consequences of Notch inhibition and activation on cellular proliferation and differentiation and defined the specific Notch receptors functioning in the mouse and human corpus. Notch pathway activity was observed in the mouse corpus epithelium, and gene expression analysis revealed NOTCH1 and NOTCH2 to be the predominant Notch receptors in both mouse and human. Global Notch inhibition for 5 days reduced progenitor cell proliferation in the mouse corpus, as well as in organoids derived from mouse and human corpus tissue. Proliferation effects were mediated through both NOTCH1 and NOTCH2 receptors, as demonstrated by targeting each receptor alone or in combination with Notch receptor inhibitory antibodies. Analysis of differentiation by marker expression showed no change to the major cell lineages; however, there was a modest increase in the number of transitional cells coexpressing markers of mucous neck and chief cells. In contrast to reduced proliferation after pathway inhibition, Notch activation in the adult stomach resulted in increased proliferation coupled with reduced differentiation. These findings suggest that NOTCH1 and NOTCH2 signaling promotes progenitor cell proliferation in the mouse and human gastric corpus, which is consistent with previously defined roles for Notch in promoting stem and progenitor cell proliferation in the intestine and antral stomach. Here we demonstrate that the Notch signaling pathway is essential for proliferation of stem cells in the mouse and human gastric corpus. We identify NOTCH1 and NOTCH2 as the predominant Notch receptors expressed in both mouse and human corpus and show that both receptors are required for corpus stem cell proliferation. We show that chronic Notch activation in corpus stem

  14. INTERACTIONS BETWEEN THE HUMAN GASTRIC CARCINOMA CELL AND THE HUMAN VASCULAR ENDOTHELIAL CELL

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To definite the interactions between the human gastric carcinoma cell and the human vascular endothelial cell during the establishment and maintenance of the tumor vascular system and the tumor hematogenous metastasis.Methods We prepared the conditioned mediums of each cell so as to study the effect of the conditioned medium on itself or others by MTT colorimetry. The comprehensive effect of interactions between two cells was determined by stratified transfilter co-culture or direct contact co-culture.Results The conditioned medium of human gastric carcinoma cell can stimulate the proliferation of the human vascular endothelial cell, but the CM of HVEC can inhibit the growth of HGCC. Both kinds of cells can inhibit the growth of itself. The ultimate comprehensive effect of the interactions between two kinds of cells was increase of total cell numbers.Conclusion There exist the complicated interactions between the human gastric carcinoma cell and the human vascular endothelial cell during the tumor angiogenesis and the tumor hematogenous metastasis. The ultimate comprehensive effect of the interactions is increase of total cells numbers and tumor volume.

  15. Tissue resident memory T cells in the human conjunctiva and immune signatures in human dry eye disease

    National Research Council Canada - National Science Library

    Tanima Bose; Ryan Lee; Aihua Hou; Louis Tong; K George Chandy

    2017-01-01

    Non-recirculating resident memory (TRM ) and recirculating T cells mount vigorous immune responses to both self and foreign antigens in barrier tissues like the skin, lung and gastrointestinal tract...

  16. The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system.

    Science.gov (United States)

    Pelaseyed, Thaher; Bergström, Joakim H; Gustafsson, Jenny K; Ermund, Anna; Birchenough, George M H; Schütte, André; van der Post, Sjoerd; Svensson, Frida; Rodríguez-Piñeiro, Ana M; Nyström, Elisabeth E L; Wising, Catharina; Johansson, Malin E V; Hansson, Gunnar C

    2014-07-01

    The gastrointestinal tract is covered by mucus that has different properties in the stomach, small intestine, and colon. The large highly glycosylated gel-forming mucins MUC2 and MUC5AC are the major components of the mucus in the intestine and stomach, respectively. In the small intestine, mucus limits the number of bacteria that can reach the epithelium and the Peyer's patches. In the large intestine, the inner mucus layer separates the commensal bacteria from the host epithelium. The outer colonic mucus layer is the natural habitat for the commensal bacteria. The intestinal goblet cells secrete not only the MUC2 mucin but also a number of typical mucus components: CLCA1, FCGBP, AGR2, ZG16, and TFF3. The goblet cells have recently been shown to have a novel gate-keeping role for the presentation of oral antigens to the immune system. Goblet cells deliver small intestinal luminal material to the lamina propria dendritic cells of the tolerogenic CD103(+) type. In addition to the gel-forming mucins, the transmembrane mucins MUC3, MUC12, and MUC17 form the enterocyte glycocalyx that can reach about a micrometer out from the brush border. The MUC17 mucin can shuttle from a surface to an intracellular vesicle localization, suggesting that enterocytes might control and report epithelial microbial challenge. There is communication not only from the epithelial cells to the immune system but also in the opposite direction. One example of this is IL10 that can affect and improve the properties of the inner colonic mucus layer. The mucus and epithelial cells of the gastrointestinal tract are the primary gate keepers and controllers of bacterial interactions with the host immune system, but our understanding of this relationship is still in its infancy.

  17. STI571 (Glivec) suppresses the expression of vascular endothelial growth factor in the gastrointestinal stromal tumor cell line, GIST-T1

    Institute of Scientific and Technical Information of China (English)

    Toufeng Jin; Hajime Nakatani; Takahiro Taguchi; Takumi Nakano; Takehiro Okabayashi; Takeki Sugimoto; Michiya Kobayashi; Keijiro Araki

    2006-01-01

    AIM: To estimate whether STI571 inhibits the expression of vascular endothelial growth factor (VEGF) in the gastrointestinal stromal tumor (GIST) cells.METHODS: We used GIST cell line, GIST-T1. It has a heterogenic 57-bp deletion in exon 11 to produce a mutated c-KIT, which results in constitutive activation of c-KIT. Cells were treated with/without STI571 or stem cell factor (SCF). Transcription and expression of VEGF were determined by RT-PCR and flow cytometry or Western blotting, respectively. Activated c-KIT was estimated by immunoprecipitation analysis. Cell viability was determined by MTT assay.RESULTS: Activation of c-KIT was inhibited by STI571 treatment. VEGF was suppressed at both the transcriptional and translational levels in a temporal and dose-dependent manner by STI571. SCF upregulated the expression of VEGF and it was inhibited by STI571.STI571 also reduced the cell viability of the GIST-T1cells, as determined by MTT assay.CONCLUSION: Activation of c-KIT in the GIST-T1regulated the expression of VEGF and it was inhibited by STI571. STI571 has antitumor effects on the GIST cells with respect to not only the inhibition of cell growth. but also the suppression of VEGF expression.

  18. Fibronectin production by human mammary cells

    Energy Technology Data Exchange (ETDEWEB)

    Stampfer, M.R. (Univ. of California, Berkeley); Vlodavsky, I.; Smith, H.S.; Ford, R.; Becker, F.F.; Riggs, J.

    1981-01-01

    Human mammary cells were examined for the presence of the high-molecular-weight surface glycoprotein fibronectin. Early passage mammary epithelial cell and fibroblast cultures from both carcinomas and normal tissues were tested for the presence of cell-associated fibronectin by immunofluorescence microscopy and for the synthesis and secretion of fibronectin by specific immunoprecipitation of metabolically labeled protein. In vivo frozen sections of primary carcinomas and normal tissues were tested for the localization of fibronectin by immunofluorescence microscopy. In contrast to the extensive fibrillar networks of fibronectin found in the fibroblast cultures, the epithelial cell cultures from both tissue sources displayed a pattern of cell-associated fibronectin characterizd by powdery, punctate staining. However, the cultured epithelial cells, as well as the fibroblasts, secreted large quantities of fibronectin into the medium. Putative myoepithelial cells also displayed extensive fibrillar networks of fibronectin. The difference in cell-associated fibronectin distribution between the epithelial cells and the fibroblasts and putative myoepithelial cells provided a simple means of quantitating stromal and myoepithelial cell contamination of the mammary epithelial cells in culture. In vivo, normal tissues showed fibronectin primarily localized in the basement membrane surrounding the epithelial cells and in the stroma. Most primary carcinomas displayed powdery, punctate staining on the epithelial cells in addition to the fibronectin present in the surrounding stroma.

  19. Lineage-specific expression of bestrophin-2 and bestrophin-4 in human intestinal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Go Ito

    Full Text Available Intestinal epithelial cells (IECs regulate the absorption and secretion of anions, such as HCO3(- or Cl(-. Bestrophin genes represent a newly identified group of calcium-activated Cl(- channels (CaCCs. Studies have suggested that, among the four human bestrophin-family genes, bestrophin-2 (BEST2 and bestrophin-4 (BEST4 might be expressed within the intestinal tissue. Consistently, a study showed that BEST2 is expressed by human colonic goblet cells. However, their precise expression pattern along the gastrointestinal tract, or the lineage specificity of the cells expressing these genes, remains largely unknown. Here, we show that BEST2 and BEST4 are expressed in vivo, each in a distinct, lineage-specific manner, in human IECs. While BEST2 was expressed exclusively in colonic goblet cells, BEST4 was expressed in the absorptive cells of both the small intestine and the colon. In addition, we found that BEST2 expression is significantly down-regulated in the active lesions of ulcerative colitis, where goblet cells were depleted, suggesting that BEST2 expression is restricted to goblet cells under both normal and pathologic conditions. Consistently, the induction of goblet cell differentiation by a Notch inhibitor, LY411575, significantly up-regulated the expression of not BEST4 but BEST2 in MUC2-positive HT-29 cells. Conversely, the induction of absorptive cell differentiation up-regulated the expression of BEST4 in villin-positive Caco-2 cells. In addition, we found that the up- or down-regulation of Notch activity leads to the preferential expression of either BEST4 or BEST2, respectively, in LS174T cells. These results collectively confirmed that BEST2 and BEST4 could be added to the lineage-specific genes of humans IECs due to their abilities to clearly identify goblet cells of colonic origin and a distinct subset of absorptive cells, respectively.

  20. Laser printing of skin cells and human stem cells.

    Science.gov (United States)

    Koch, Lothar; Kuhn, Stefanie; Sorg, Heiko; Gruene, Martin; Schlie, Sabrina; Gaebel, Ralf; Polchow, Bianca; Reimers, Kerstin; Stoelting, Stephanie; Ma, Nan; Vogt, Peter M; Steinhoff, Gustav; Chichkov, Boris

    2010-10-01

    Laser printing based on laser-induced forward transfer (LIFT) is a new biofabrication technique for the arrangement of biological materials or living cells in well-defined patterns. In the current study, skin cell lines (fibroblasts/keratinocytes) and human mesenchymal stem cells (hMSC) were chosen for laser printing experiments due to their high potential in regeneration of human skin and new application possibilities of stem cell therapy. To evaluate the influence of LIFT on the cells, their survival rate, their proliferation and apoptotic activity, and the DNA damages and modifications of their cell surface markers were assessed and statistically evaluated over several days. The cells survived the transfer procedure with a rate of 98%  +/- 1% standard error of the mean (skin cells) and 90%  +/- 10% (hMSC), respectively. All used cell types maintain their ability to proliferate after LIFT. Further, skin cells and hMSC did not show an increase of apoptosis or DNA fragmentation. In addition, the hMSC keep their phenotype as proven by fluorescence activated cell sorting (FACS) analysis. This study demonstrates LIFT as a suitable technique for unharmed computer-controlled positioning of different cell types and a promising tool for future applications in the ex vivo generation of tissue replacements.

  1. Gastrointestinal events with clopidogrel

    DEFF Research Database (Denmark)

    Grove, Erik Lerkevang; Würtz, Morten; Schwarz, Peter

    2013-01-01

    Clopidogrel prevents cardiovascular events, but has been linked with adverse gastrointestinal (GI) complications, particularly bleeding events.......Clopidogrel prevents cardiovascular events, but has been linked with adverse gastrointestinal (GI) complications, particularly bleeding events....

  2. Human spleen and red blood cells

    Science.gov (United States)

    Pivkin, Igor; Peng, Zhangli; Karniadakis, George; Buffet, Pierre; Dao, Ming

    2016-11-01

    Spleen plays multiple roles in the human body. Among them is removal of old and altered red blood cells (RBCs), which is done by filtering cells through the endothelial slits, small micron-sized openings. There is currently no experimental technique available that allows us to observe RBC passage through the slits. It was previously noticed that people without a spleen have less deformable red blood cells, indicating that the spleen may play a role in defining the size and shape of red blood cells. We used detailed RBC model implemented within the Dissipative Particle Dynamics (DPD) simulation framework to study the filter function of the spleen. Our results demonstrate that spleen indeed plays major role in defining the size and shape of the healthy human red blood cells.

  3. Deriving human ENS lineages for cell therapy and drug discovery in Hirschsprung disease.

    Science.gov (United States)

    Fattahi, Faranak; Steinbeck, Julius A; Kriks, Sonja; Tchieu, Jason; Zimmer, Bastian; Kishinevsky, Sarah; Zeltner, Nadja; Mica, Yvonne; El-Nachef, Wael; Zhao, Huiyong; de Stanchina, Elisa; Gershon, Michael D; Grikscheit, Tracy C; Chen, Shuibing; Studer, Lorenz

    2016-03-03

    The enteric nervous system (ENS) is the largest component of the autonomic nervous system, with neuron numbers surpassing those present in the spinal cord. The ENS has been called the 'second brain' given its autonomy, remarkable neurotransmitter diversity and complex cytoarchitecture. Defects in ENS development are responsible for many human disorders including Hirschsprung disease (HSCR). HSCR is caused by the developmental failure of ENS progenitors to migrate into the gastrointestinal tract, particularly the distal colon. Human ENS development remains poorly understood owing to the lack of an easily accessible model system. Here we demonstrate the efficient derivation and isolation of ENS progenitors from human pluripotent stem (PS) cells, and their further differentiation into functional enteric neurons. ENS precursors derived in vitro are capable of targeted migration in the developing chick embryo and extensive colonization of the adult mouse colon. The in vivo engraftment and migration of human PS-cell-derived ENS precursors rescue disease-related mortality in HSCR mice (Ednrb(s-l/s-l)), although the mechanism of action remains unclear. Finally, EDNRB-null mutant ENS precursors enable modelling of HSCR-related migration defects, and the identification of pepstatin A as a candidate therapeutic target. Our study establishes the first, to our knowledge, human PS-cell-based platform for the study of human ENS development, and presents cell- and drug-based strategies for the treatment of HSCR.

  4. Rotating cell culture systems for human cell culture: human trophoblast cells as a model.

    Science.gov (United States)

    Zwezdaryk, Kevin J; Warner, Jessica A; Machado, Heather L; Morris, Cindy A; Höner zu Bentrup, Kerstin

    2012-01-18

    The field of human trophoblast research aids in understanding the complex environment established during placentation. Due to the nature of these studies, human in vivo experimentation is impossible. A combination of primary cultures, explant cultures and trophoblast cell lines support our understanding of invasion of the uterine wall and remodeling of uterine spiral arteries by extravillous trophoblast cells (EVTs), which is required for successful establishment of pregnancy. Despite the wealth of knowledge gleaned from such models, it is accepted that in vitro cell culture models using EVT-like cell lines display altered cellular properties when compared to their in vivo counterparts. Cells cultured in the rotating cell culture system (RCCS) display morphological, phenotypic, and functional properties of EVT-like cell lines that more closely mimic differentiating in utero EVTs, with increased expression of genes mediating invasion (e.g. matrix metalloproteinases (MMPs)) and trophoblast differentiation. The Saint Georges Hospital Placental cell Line-4 (SGHPL-4) (kindly donated by Dr. Guy Whitley and Dr. Judith Cartwright) is an EVT-like cell line that was used for testing in the RCCS. The design of the RCCS culture vessel is based on the principle that organs and tissues function in a three-dimensional (3-D) environment. Due to the dynamic culture conditions in the vessel, including conditions of physiologically relevant shear, cells grown in three dimensions form aggregates based on natural cellular affinities and differentiate into organotypic tissue-like assemblies. The maintenance of a fluid orbit provides a low-shear, low-turbulence environment similar to conditions found in vivo. Sedimentation of the cultured cells is countered by adjusting the rotation speed of the RCCS to ensure a constant free-fall of cells. Gas exchange occurs through a permeable hydrophobic membrane located on the back of the bioreactor. Like their parental tissue in vivo, RCCS

  5. Autophagy in human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Thien Tra

    Full Text Available Autophagy (macroautophagy is a degradative process that involves the sequestration of cytosolic material including organelles into double membrane vesicles termed autophagosomes for delivery to the lysosome. Autophagy is essential for preimplantation development of mouse embryos and cavitation of embryoid bodies. The precise roles of autophagy during early human embryonic development, remain however largely uncharacterized. Since human embryonic stem cells constitute a unique model system to study early human embryogenesis we investigated the occurrence of autophagy in human embryonic stem cells. We have, using lentiviral transduction, established multiple human embryonic stem cell lines that stably express GFP-LC3, a fluorescent marker for the autophagosome. Each cell line displays both a normal karyotype and pluripotency as indicated by the presence of cell types representative of the three germlayers in derived teratomas. GFP expression and labelling of autophagosomes is retained after differentiation. Baseline levels of autophagy detected in cultured undifferentiated hESC were increased or decreased in the presence of rapamycin and wortmannin, respectively. Interestingly, autophagy was upregulated in hESCs induced to undergo differentiation by treatment with type I TGF-beta receptor inhibitor SB431542 or removal of MEF secreted maintenance factors. In conclusion we have established hESCs capable of reporting macroautophagy and identify a novel link between autophagy and early differentiation events in hESC.

  6. Intragastric formation and modulation of N-nitrosodimethylamine in a dynamic in vitro gastrointestinal model under human physiological conditions

    NARCIS (Netherlands)

    Krul, C.A.M.; Zeilmaker, M.J.; Schothorst, R.C.; Havenaar, R.

    2004-01-01

    Human exposure to carcinogenic N-alkylnitrosamines can occur exogenously via food consumption or endogenously by formation of these compounds through nitrosation of amine precursors. Information on the intragastric formation of NDMA from complex mixtures of precursors and inhibitors in humans is not

  7. What Are Gastrointestinal Stromal Tumors?

    Science.gov (United States)

    ... system, also known as the digestive system. The gastrointestinal system The gastrointestinal (GI) system (or digestive system) processes ... in “ How are gastrointestinal stromal tumors diagnosed? ” Other gastrointestinal tract cancers It is important to understand that GISTs ...

  8. Human embryonic stem cells for neuronal repair.

    Science.gov (United States)

    Ben-Hur, Tamir

    2006-02-01

    Human embryonic stem cells may serve as a potentially endeless source of transplantable cells to treat various neurologic disorders. Accumulating data have shown the therapeutic value of various neural precursor cell types in experimental models of neurologic diseases. Tailoring cell therapy for specific disorders requires the generation of cells that are committed to specific neural lineages. To this end, protocols were recently developed for the derivation of dopaminergic neurons, spinal motor neurons and oligodendrocytes from hESC. These protocols recapitulate normal development in culture conditions. However, a novel concept emerging from these studies is that the beneficial effect of transplanted stem cells is not only via cell replacement in damaged host tissue, but also by trophic and protective effects, as well as by an immunomodulatory effect that down-regulates detrimental brain inflammation.

  9. Novel agents inhibit human leukemic cells

    Institute of Scientific and Technical Information of China (English)

    Wei-ping YU; Juan LI

    2012-01-01

    Ouabain (OUA) and pyrithione zinc (PZ) have been proved as the potential drugs for treating acute myeloid leukemia (AML).Selected from a screening among 1040 Food and Drug Administration-approved pharmacological agents,both drugs showability to induce apoptosis of the culturing AML cells,exhibiting the poisoning effect on the cells.Studies also reveal the efficiency of the drugs in inhibiting the growth of human AML cells injected into the mice lacking of immunity and killing primary AML cells from the peripheral blood of AML patients[1].

  10. Robotics in gastrointestinal endoscopy

    Directory of Open Access Journals (Sweden)

    Khek-Yu Ho

    2012-01-01

    Full Text Available The application of robotics in gastrointestinal endoscopy is a much anticipated technological advancement that is attracting an enormous amount of interest from innovators and end-users alike. Emerging robotics-enhanced endoscopy platforms for performance of various endoscopic interventional procedures are already in development and some are expected to be in the pipeline for commercialization in another few years′ time. In particular, the Master And Slave Transluminal Endoscopic Robot (MASTER developed by a collaboration between the National University of Singapore and the Nanyang Technological University, Singapore is already in human trials for an endoluminal procedure, endoscopic submucosal dissection (ESD. The results on trials performed on five patients with early gastric neoplasia have demonstrated the feasibility and safety of using the system for such procedure, while also shortening the procedure time. This article will highlight the advantages of robotics innovations in gastrointestinal endoscopy, with the MASTER as an example, and explore some of the many possibilities for future applications of robotics-enhanced endoscopy.

  11. 3 CFR - Guidelines for Human Stem Cell Research

    Science.gov (United States)

    2010-01-01

    ... 3 The President 1 2010-01-01 2010-01-01 false Guidelines for Human Stem Cell Research Presidential Documents Other Presidential Documents Memorandum of July 30, 2009 Guidelines for Human Stem Cell Research..., scientifically worthy human stem cell research, including human embryonic stem cell research, to the extent...

  12. Myristoylation profiling in human cells and zebrafish

    Directory of Open Access Journals (Sweden)

    Malgorzata Broncel

    2015-09-01

    Full Text Available Human cells (HEK 293, HeLa, MCF-7 and zebrafish embryos were metabolically tagged with an alkynyl myristic acid probe, lysed with an SDS buffer and tagged proteomes ligated to multifunctional capture reagents via copper-catalyzed alkyne azide cycloaddition (CuAAC. This allowed for affinity enrichment and high-confidence identification, by delivering direct MS/MS evidence for the modification site, of 87 and 61 co-translationally myristoylated proteins in human cells and zebrafish, respectively. The data have been deposited to ProteomeXchange Consortium (Vizcaíno et al., 2014 Nat. Biotechnol., 32, 223–6 (PXD001863 and PXD001876 and are described in detail in Multifunctional reagents for quantitative proteome-wide analysis of protein modification in human cells and dynamic protein lipidation during vertebrate development׳ by Broncel et al., Angew. Chem. Int. Ed.

  13. Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

    Science.gov (United States)

    Fukusumi, Hayato; Shofuda, Tomoko; Bamba, Yohei; Yamamoto, Atsuyo; Kanematsu, Daisuke; Handa, Yukako; Okita, Keisuke; Nakamura, Masaya; Yamanaka, Shinya; Okano, Hideyuki; Kanemura, Yonehiro

    2016-01-01

    Human neural progenitor cells (hNPCs) have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC) clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB) formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi). Our results showed that expandable hNPCs could be generated from hiPSC clones with diverse somatic tissue origins. The established hNPCs exhibited a mid/hindbrain-type neural identity and uniform expression of neural progenitor genes. PMID:27212953

  14. Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins.

    Science.gov (United States)

    Fukusumi, Hayato; Shofuda, Tomoko; Bamba, Yohei; Yamamoto, Atsuyo; Kanematsu, Daisuke; Handa, Yukako; Okita, Keisuke; Nakamura, Masaya; Yamanaka, Shinya; Okano, Hideyuki; Kanemura, Yonehiro

    2016-01-01

    Human neural progenitor cells (hNPCs) have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC) clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB) formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi). Our results showed that expandable hNPCs could be generated from hiPSC clones with diverse somatic tissue origins. The established hNPCs exhibited a mid/hindbrain-type neural identity and uniform expression of neural progenitor genes.

  15. Efficient derivation and genetic modifications of human pluripotent stem cells on engineered human feeder cell lines.

    Science.gov (United States)

    Zou, Chunlin; Chou, Bin-Kuan; Dowey, Sarah N; Tsang, Kitman; Huang, Xiaosong; Liu, Cyndi F; Smith, Cory; Yen, Jonathan; Mali, Prashant; Zhang, Yu Alex; Cheng, Linzhao; Ye, Zhaohui

    2012-08-10

    Derivation of pluripotent stem cells (iPSCs) induced from somatic cell types and the subsequent genetic modifications of disease-specific or patient-specific iPSCs are crucial steps in their applications for disease modeling as well as future cell and gene therapies. Conventional procedures of these processes require co-culture with primary mouse embryonic fibroblasts (MEFs) to support self-renewal and clonal growth of human iPSCs as well as embryonic stem cells (ESCs). However, the variability of MEF quality affects the efficiencies of all these steps. Furthermore, animal sourced feeders may hinder the clinical applications of human stem cells. In order to overcome these hurdles, we established immortalized human feeder cell lines by stably expressing human telomerase reverse transcriptase, Wnt3a, and drug resistance genes in adult mesenchymal stem cells. Here, we show that these immortalized human feeders support efficient derivation of virus-free, integration-free human iPSCs and long-term expansion of human iPSCs and ESCs. Moreover, the drug-resistance feature of these feeders also supports nonviral gene transfer and expression at a high efficiency, mediated by piggyBac DNA transposition. Importantly, these human feeders exhibit superior ability over MEFs in supporting homologous recombination-mediated gene targeting in human iPSCs, allowing us to efficiently target a transgene into the AAVS1 safe harbor locus in recently derived integration-free iPSCs. Our results have great implications in disease modeling and translational applications of human iPSCs, as these engineered human cell lines provide a more efficient tool for genetic modifications and a safer alternative for supporting self-renewal of human iPSCs and ESCs.

  16. [Human pluripotent stem cell and neural differentiation].

    Science.gov (United States)

    Wataya, Takafumi; Muguruma, Keiko; Sasai, Yoshiki

    2008-10-01

    Recovery of lost brain function is an important issue in medical studies because neurons of the central nervous system (CNS) have poor potential for regeneration. Since few CNS diseases can be treated completely by medicines, regenerative therapy by using stem cells should be studied as a new type of therapeutic intervention. The efficacy of cell replacement therapy in Parkinson's disease has been well investigated. Several studies on fetal tissue transplantation have revealed that quantity and purity of transplanted cells are necessary for recovery of symptoms. SFEB (Serum-free floating culture of embryoid body-like aggregates) method is capable of inducing multi-potential CNS progenitors that can be steered to differentiate into region-specific tissues. On the basis of the existing knowledge of embryology, we have succeeded in the generating of various types of neurons such as telencephalic, cerebeller (Purkinje and granule cells), retinal (photoreceptor cells) and hypothalamic neurons. Application of this culture method to human ES (hES) cells is necessary for clinical purpose: however, poor survival of hES cells in SFEB culture might limit the possibility of using these cells for future medical applications. We found that a selective Rho-associated kinase (ROCK) inhibitor, Y-27632, markedly diminished the dissociation-induced apoptosis of hES cells and enabled the cells to form aggregates in SFEB culture. For both mouse and human ES cells, SFEB culture is a favorable method that can generate large amounts of region-specific neurons. However, stem cell-based therapy continues to face several obstacles. It is important that researchers in the basic sciences and clinical medicine should discuss these problems together to overcome both scientific and ethical issues related to stem cells.

  17. Applications of Recombinant DNA Technology in Gastrointestinal Medicine and Hepatology: Basic Paradigms of Molecular Cell Biology. Part A: Eukaryotic Gene Structure and DNA Replication

    Directory of Open Access Journals (Sweden)

    Gary E Wild

    2000-01-01

    Full Text Available Progress in the basic sciences of cell and molecular biology has provided an exciting dimension that has translated into clinically relevant information in every medical subspecialty. Importantly, the application of recombinant DNA technology has played a major role in unravelling the intricacies related to the molecular pathophysiology of disease. This series of review articles constitutes a framework for the integration of the database of new information into the core knowledge base of concepts related to the pathogenesis of gastrointestinal disorders and liver disease. The goal of this series of three articles is to review the basic principles of eukaryotic gene expression. The first article examines the role of DNA in directing the flow of genetic information in eukaryotic cells.

  18. Injected TFF1 and TFF3 bind to TFF2-immunoreactive cells in the gastrointestinal tract in rats

    DEFF Research Database (Denmark)

    Poulsen, S S; Thulesen, J; Hartmann, B

    2003-01-01

    intravenously to female Wistar rats. The tissue distribution was assessed by gamma counting of organ samples and by autoradiography of histological sections. The degradation of 125I-TFF3 was studied by means of trichloracetic acid (TCA) precipitation and the saturability of the binding by administration...... and that injected TFF2 ends up in the mucus layer. In the present study, tissue binding and metabolism of parenterally administered human TFF1 and TFF3 in rats were described and compared to the immunohistochemical localization of the TFF peptides. 125I-TFF1 monomer and 125I-TFF3 mono- and dimer were given...... of excess unlabelled peptide. The TFF peptides were localized in histologic sections from the GI tract by immunohistochemistry. Injected TFF3 dimer (12%) was taken up by the GI tract. At autoradiography, grains were localized to the same cells that were immunoreactive to TFF2. The binding could be displaced...

  19. T-cell response in human leishmaniasis

    DEFF Research Database (Denmark)

    Kharazmi, A; Kemp, K; Ismail, A

    1999-01-01

    In the present communication we provide evidence for the existence of a Th1/Th2 dichotomy in the T-cell response to Leishmania antigens in human leishmaniasis. Our data suggest that the pattern of IL-4 and IFN-gamma response is polarised in these patients. Lymphocytes from individuals recovered......+. Furthermore, IL-10 plays an important role in the development of post kala azar dermal leishmaniasis (PKDL) from VL. The balance between the parasitic-specific T-cell response plays an important regulatory role in determining the outcome of Leishmania infections in humans....

  20. Characterization of human pluripotent stem cells.

    Science.gov (United States)

    Gokhale, Paul J; Andrews, Peter W

    2013-12-18

    Human pluripotent stem cells (PSCs), whether embryonic stem cells or induced PSCs, offer enormous opportunities for regenerative medicine and other biomedical applications once we have developed the ability to harness their capacity for extensive differentiation. Central to this is our ability to identify and characterize such PSCs, but this is fraught with potential difficulties that arise from a tension between functional definitions of pluripotency and the more convenient use of 'markers', a problem exacerbated by ethical issues, our lack of knowledge of early human embryonic development, and differences from the mouse paradigm.

  1. CLOSTRIDIUM SPORE ATTACHMENT TO HUMAN CELLS

    Energy Technology Data Exchange (ETDEWEB)

    PANESSA-WARREN,B.; TORTORA,G.; WARREN,J.

    1997-08-10

    This paper uses high resolution scanning electron microscopy (SEM) with a LaB6 gun and the newest commercial field emission guns, to obtain high magnification images of intact clostridial spores throughout the activation/germination/outgrowth process. By high resolution SEM, the clostridial exosporial membrane can be seen to produce numerous delicate projections (following activation), that extend from the exosporial surface to a nutritive substrate (agar), or cell surface when anaerobically incubated in the presence of human cells (embryonic fibroblasts and colon carcinoma cells). Magnifications of 20,000 to 200,000Xs at accelerating voltages low enough to minimize or eliminate specimen damage (1--5 kV) have permitted the entire surface of C.sporogenes and C.difficile endospores to be examined during all stages of germination. The relationships between the spore and the agar or human cell surface were also clearly visible.

  2. Human pluripotent stem cells in contemporary medicine

    Directory of Open Access Journals (Sweden)

    S. A. Rodin

    2015-01-01

    Full Text Available Human pluripotent stem cells (hPSCs are capable of indefinite proliferation and can be differentiated into any cell type of the human body. Therefore, they are a promising source of cells for treatment of numerous degenerative diseases and injuries. Pluripotent stem cells are also associated with a number of ethical, safety and technological issues. In this review, we describe various types of hPSCs, safety issues that concern all or some types of hPSCs and methods of clinical-grade hPSC line development. Also, we discuss current and past clinical trials involving hPSCs, their outcomes and future perspectives of hPSC-based therapy. 

  3. Uvangoletin induces mitochondria-mediated apoptosis in HL-60 cells in vitro and in vivo without adverse reactions of myelosuppression, leucopenia and gastrointestinal tract disturbances.

    Science.gov (United States)

    Zheng, Zhuanzhen; Qiao, Zhenhua; Gong, Rong; Wang, Yalin; Zhang, Yiqun; Ma, Yanping; Zhang, Li; Lu, Yujin; Jiang, Bo; Li, Guoxia; Dong, Chunxia; Chen, Wenliang

    2016-02-01

    This study investigated the cytotoxic effect of uvangoletin on HL-60 cells, and the effects of uvangoletin on myelosuppression, leucopenia, gastrointestinal tract disturbances and the possible cytotoxic mechanisms by using CCK-8, flow cytometry, western blot, xenograft, cyclophosphamide-induced leucopenia, copper sulfate-induced emesis and ethanol-induced gastric mucosal lesions assays. The results of CCK-8, flow cytometry and western blot assays indicated that uvangoletin showed the cytotoxic effect on HL-60 cells and induced the apoptosis of HL-60 cells by downregulating the expression levels of anti-apoptotic proteins (Survivin, Bcl-xl and Bcl-2), upregulating the expression levels of pro-apoptotic proteins (Smac, Bax, Bad, c-caspase-3 and c-caspase-9), and promoting the release of cytochrome c from mitochondria to cytoplasm. Further, the results of xenograft assay suggested that uvangoletin inhibited the HL-60-induced tumor growth without adverse effect on body weight of nude mice in vivo by regulating the expression levels of above apoptotic proteins. The results indicated that the reductions of WBCs count and thighbone marrow granulocytes percentage in cyclophosphamide-induced leucopenia assay, the incubation period and number of emesis in copper sulfate-induced emesis assay and the gastric mucosal lesions in ethanol-induced gastric mucosal lesions assay were not exacerbated or reversed by uvangoletin. In conclusion, the research preliminarily indicated that uvangoletin induced apoptosis of HL-60 cells in vitro and in vivo without adverse reactions of myelosuppression, leucopenia and gastrointestinal tract disturbances, and the pro-apoptotic mechanisms may be related to mitochondria-mediated apoptotic pathway.

  4. Cell pattern in adult human corneal endothelium.

    Directory of Open Access Journals (Sweden)

    Carlos H Wörner

    Full Text Available A review of the current data on the cell density of normal adult human endothelial cells was carried out in order to establish some common parameters appearing in the different considered populations. From the analysis of cell growth patterns, it is inferred that the cell aging rate is similar for each of the different considered populations. Also, the morphology, the cell distribution and the tendency to hexagonallity are studied. The results are consistent with the hypothesis that this phenomenon is analogous with cell behavior in other structures such as dry foams and grains in polycrystalline materials. Therefore, its driving force may be controlled by the surface tension and the mobility of the boundaries.

  5. Merkel cell distribution in the human eyelid

    Directory of Open Access Journals (Sweden)

    C.A. May

    2013-10-01

    Full Text Available Although Merkel cell carcinoma of the eye lid is reported frequently in the literature, only limited information exists about the distribution of Merkel cells in this tissue. Therefore, serial sections of 18 human cadaver eye lids (donors ages ranging between 63 and 97 years were stained for cytokeratin 20 in various planes. The overall appearance of Merkel cells in these samples was low and mainly located in the outer root layer of the cilia hair follicles. Merkel cells were more frequent in the middle, and almost not detectable at the nasal and temporal edges. The localization is in accordance with that of Merkel cell carcinoma, but concerning the scarce appearance within this adulthood group, a specific physiological role of these cells in the eye lid is difficult to establish.

  6. Natural killer cells in human autoimmune disorders

    Science.gov (United States)

    2013-01-01

    Natural killer (NK) cells are innate lymphocytes that play a critical role in early host defense against viruses. Through their cytolytic capacity and generation of cytokines and chemokines, NK cells modulate the activity of other components of the innate and adaptive immune systems and have been implicated in the initiation or maintenance of autoimmune responses. This review focuses on recent research elucidating a potential immunoregulatory role for NK cells in T-cell and B-cell-mediated autoimmune disorders in humans, with a particular focus on multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematous. A better understanding of the contributions of NK cells to the development of autoimmunity may lead to novel therapeutic targets in these diseases. PMID:23856014

  7. Human Colon Cancer Cells Cultivated in Space

    Science.gov (United States)

    1995-01-01

    Within five days, bioreactor cultivated human colon cancer cells (shown) grown in Microgravity on the STS-70 mission in 1995, had grown 30 times the volume of the control specimens on Earth. The samples grown in space had a higher level of cellular organization and specialization. Because they more closely resemble tumors found in the body, microgravity grown cell cultures are ideal for research purposes.

  8. Quercetin Inhibits Cell Migration and Invasion in Human Osteosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Haifeng Lan

    2017-09-01

    Full Text Available Background/Aims: Osteosarcoma is a malignant tumor associated with high mortality; however, no effective therapies for the disease have been developed. Several studies have focused on elucidating the pathogenesis of osteosarcoma and have aimed to develop novel therapies for the disease. Quercetin is a vital dietary flavonoid that has been shown to have a variety of anticancer effects, as it induces cell cycle arrest, apoptosis, and differentiation and is involved in cell adhesion, metastasis and angiogenesis. Herein, we aimed to investigate the effects of quercetin on osteosarcoma migration and invasion in vitro and in vivo and to explore the molecular mechanisms underlying its effects on osteosarcoma migration and invasion. Methods: Cell viability, cell cycle activity and cell apoptosis were measured using CCK-8 assay and flow cytometry, and cell migration and invasion were evaluated by wound healing and transwell assays, respectively. The mRNA and protein expression levels of several proteins of interest were assessed by real-time quantitative PCR and western blotting, respectively. Moreover, a nude mouse model of human osteosarcoma lung metastasis was established to assess the anti-metastatic effects of quercetin in vivo. Results: We noted no significant differences in cell cycle activity and apoptosis between HOS and MG63 cells and control cells. Treatment with quercetin significantly attenuated cell migration and invasion in HOS and MG63 cells compared with treatment with control medium. Moreover HIF-1α, VEGF, MMP2, and MMP9 mRNA and protein expression levels were significantly downregulated in HOS cells treated with quercetin compared with HOS cells treated with controls. Additionally, treatment with quercetin attenuated metastatic lung tumor formation and growth in the nude mouse model of osteosarcoma compared with treatment with controls. Conclusion: Our findings regarding the inhibitory effects of quercetin on cell migration and

  9. Human Mammary Luminal Epithelial Cells Contain Progenitors to Myoepithelial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Pechoux, Christine; Gudjonsson, Thorarinn; Ronnov-Jessen, Lone; Bissell, Mina J; Petersen, Ole

    1999-02-01

    The origin of the epithelial and myoepithelial cells in the human breast has not been delineated. In this study we have addressed whether luminal epithelial cells and myoepithelial cells are vertically connected, i.e., whether one is the precursor for the other. We used a primary culture assay allowing preservation of basic phenotypic traits of luminal epithelial and myoepithelial cells in culture. The two cell types were then separated immunomagnetically using antibodies directed against lineage-specific cell surface antigens into at best 100% purity. The cellular identity was ascertained by cytochemistry, immunoblotting, and 2-D gel electrophoresis. Luminal epithelial cells were identified by strong expression of cytokeratins 18 and 19 while myoepithelial cells were recognized by expression of vimentin and {alpha}-smooth muscle actin. We used a previously devised culture medium (CDM4) that allows vigorous expansion of proliferative myoepithelial cells and also devised a medium (CDM6) that allowed sufficient expansion of differentiated luminal epithelial cells based on addition of hepatocyte growth factor/scatter factor. The two different culture media supported each lineage for at least five passages without signs of interconversion. We used parallel cultures where we switched culture media, thus testing the ability of each lineage to convert to the other. Whereas the myoepithelial lineage showed no signs of interconversion, a subset of luminal epithelial cells, gradually, but distinctly, converted to myoepithelial cells. We propose that in the mature human breast, it is the luminal epithelial cell compartment that gives rise to myoepithelial cells rather than the other way around.

  10. Genetic Manipulation of Human Embryonic Stem Cells.

    Science.gov (United States)

    Eiges, Rachel

    2016-01-01

    One of the great advantages of embryonic stem (ES) cells over other cell types is their accessibility to genetic manipulation. They can easily undergo genetic modifications while remaining pluripotent, and can be selectively propagated, allowing the clonal expansion of genetically altered cells in culture. Since the first isolation of ES cells in mice, many effective techniques have been developed for gene delivery and manipulation of ES cells. These include transfection, electroporation, and infection protocols, as well as different approaches for inserting, deleting, or changing the expression of genes. These methods proved to be extremely useful in mouse ES cells, for monitoring and directing differentiation, discovering unknown genes, and studying their function, and are now being extensively implemented in human ES cells (HESCs). This chapter describes the different approaches and methodologies that have been applied for the genetic manipulation of HESCs and their applications. Detailed protocols for generating clones of genetically modified HESCs by transfection, electroporation, and infection will be described, with special emphasis on the important technical details that are required for this purpose. All protocols are equally effective in human-induced pluripotent stem (iPS) cells.

  11. Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells

    Directory of Open Access Journals (Sweden)

    Yuen Kit M

    2009-10-01

    data suggests that viremia, secondary to, for example, gastro-intestinal infection, can potentially lead to infection of the lung. HPAI H5N1 virus was a more potent inducer of cytokines (e.g. IP-10, RANTES, IL-6 in comparison to H1N1 virus in alveolar epithelial cells, and these virus-induced chemokines were secreted onto both the apical and basolateral aspects of the polarized alveolar epithelium. Conclusion The predilection of viruses for different routes of entry and egress from the infected cell is important in understanding the pathogenesis of influenza H5N1 infection and may help unravel the pathogenesis of human H5N1 disease.

  12. Enriched retinal ganglion cells derived from human embryonic stem cells

    Science.gov (United States)

    Gill, Katherine P.; Hung, Sandy S. C.; Sharov, Alexei; Lo, Camden Y.; Needham, Karina; Lidgerwood, Grace E.; Jackson, Stacey; Crombie, Duncan E.; Nayagam, Bryony A.; Cook, Anthony L.; Hewitt, Alex W.; Pébay, Alice; Wong, Raymond C. B.

    2016-01-01

    Optic neuropathies are characterised by a loss of retinal ganglion cells (RGCs) that lead to vision impairment. Development of cell therapy requires a better understanding of the signals that direct stem cells into RGCs. Human embryonic stem cells (hESCs) represent an unlimited cellular source for generation of human RGCs in vitro. In this study, we present a 45-day protocol that utilises magnetic activated cell sorting to generate enriched population of RGCs via stepwise retinal differentiation using hESCs. We performed an extensive characterization of these stem cell-derived RGCs by examining the gene and protein expressions of a panel of neural/RGC markers. Furthermore, whole transcriptome analysis demonstrated similarity of the hESC-derived RGCs to human adult RGCs. The enriched hESC-RGCs possess long axons, functional electrophysiological profiles and axonal transport of mitochondria, suggestive of maturity. In summary, this RGC differentiation protocol can generate an enriched population of functional RGCs from hESCs, allowing future studies on disease modeling of optic neuropathies and development of cell therapies. PMID:27506453

  13. Human ES cells: starting culture from frozen cells.

    Science.gov (United States)

    Trish, Erin; Dimos, John; Eggan, Kevin

    2006-11-09

    Here we demonstrate how our lab begins a HuES human embryonic stem cell line culture from a frozen stock. First, a one to two day old ten cm plate of approximately one (to two) million irradiated mouse embryonic fibroblast feeder cells is rinsed with HuES media to remove residual serum and cell debris, and then HuES media added and left to equilibrate in the cell culture incubator. A frozen vial of cells from long term liquid nitrogen storage or a -80 C freezer is sourced and quickly submerged in a 37 C water bath for quick thawing. Cells in freezing media are then removed from the vial and placed in a large volume of HuES media. The large volume of HuES media facilitates removal of excess serum and DMSO, which can cause HuES human embryonic stem cells to differentiate. Cells are gently spun out of suspension, and then re-suspended in a small volume of fresh HuES media that is then used to seed the MEF plate. It is considered important to seed the MEF plate by gently adding the HuES cells in a drop wise fashion to evenly disperse them throughout the plate. The newly established HuES culture plate is returned to the incubator for 48 hrs before media is replaced, then is fed every 24 hours thereafter.

  14. Sodium Valproate Induces Cell Senescence in Human Hepatocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Hong-Mei An

    2013-12-01

    Full Text Available Hepatocarcinogenesis is associated with epigenetic changes, including histone deacetylases (HDACs. Epigenetic modulation by HDAC inhibition is a potentially valuable approach for hepatocellular carcinoma treatment. In present study, we evaluated the anticancer effects of sodium valproate (SVP, a known HDAC inhibitor, in human hepatocarcinoma cells. The results showed SVP inhibited the proliferation of Bel-7402 cells in a dose-dependent manner. Low dose SVP treatment caused a large and flat morphology change, positive SA-β-gal staining, and G0/G1 phase cell cycle arrest in human hepatocarcinoma cells. Low dose SVP treatment also increased acetylation of histone H3 and H4 on p21 promoter, accompanied by up-regulation of p21 and down-regulation of RB phosphorylation. These observations suggested that a low dose of SVP could induce cell senescence in hepatocarcinoma cells, which might correlate with hyperacetylation of histone H3 and H4, up-regulation of p21, and inhibition of RB phosphorylation. Since the effective concentration inducing cell senescence in hepatocarcinoma cells is clinically available, whether a clinical dose of SVP could induce cell senescence in clinical hepatocarcinoma is worthy of further study.

  15. Human embryonic stem cell lines model experimental human cytomegalovirus latency.

    Science.gov (United States)

    Penkert, Rhiannon R; Kalejta, Robert F

    2013-05-28

    Herpesviruses are highly successful pathogens that persist for the lifetime of their hosts primarily because of their ability to establish and maintain latent infections from which the virus is capable of productively reactivating. Human cytomegalovirus (HCMV), a betaherpesvirus, establishes latency in CD34(+) hematopoietic progenitor cells during natural infections in the body. Experimental infection of CD34(+) cells ex vivo has demonstrated that expression of the viral gene products that drive productive infection is silenced by an intrinsic immune defense mediated by Daxx and histone deacetylases through heterochromatinization of the viral genome during the establishment of latency. Additional mechanistic details about the establishment, let alone maintenance and reactivation, of HCMV latency remain scarce. This is partly due to the technical challenges of CD34(+) cell culture, most notably, the difficulty in preventing spontaneous differentiation that drives reactivation and renders them permissive for productive infection. Here we demonstrate that HCMV can establish, maintain, and reactivate in vitro from experimental latency in cultures of human embryonic stem cells (ESCs), for which spurious differentiation can be prevented or controlled. Furthermore, we show that known molecular aspects of HCMV latency are faithfully recapitulated in these cells. In total, we present ESCs as a novel, tractable model for studies of HCMV latency.

  16. Conditional IL-4/IL-13-deficient mice reveal a critical role of innate immune cells for protective immunity against gastrointestinal helminths.

    Science.gov (United States)

    Oeser, K; Schwartz, C; Voehringer, D

    2015-05-01

    Approximately one-third of the world population is infected with gastrointestinal helminths. Studies in mouse models have demonstrated that the cytokines interleukin (IL)-4 and IL-13 are essential for worm expulsion, but the critical cellular source of these cytokines is poorly defined. Here, we compared the immune response to Nippostrongylus brasiliensis in wild-type, T cell-specific IL-4/IL-13-deficient and general IL-4/IL-13-deficient mice. We show that T cell-derived IL-4/IL-13 promoted T helper 2 (Th2) polarization in a paracrine manner, differentiation of alternatively activated macrophages, and tissue recruitment of innate effector cells. However, innate IL-4/IL-13 played the critical role for induction of goblet cell hyperplasia and secretion of effector molecules like Mucin5ac and RELMβ in the small intestine. Surprisingly, T cell-specific IL-4/IL-13-deficient and wild-type mice cleared the parasite with comparable efficiency, whereas IL-4/IL-13-deficient mice showed impaired expulsion. These findings demonstrate that IL-4/IL-13 produced by cells of the innate immune system is required and sufficient to initiate effective type 2 immune responses resulting in protective immunity against N. brasiliensis.

  17. Immunohistochemical study on the ontogenetic development of the regional distribution of peptide YY, pancreatic polypeptide, and glucagon-like peptide 1 endocrine cells in bovine gastrointestinal tract.

    Science.gov (United States)

    Pyarokhil, Asadullah Hamid; Ishihara, Miyuki; Sasaki, Motoki; Kitamura, Nobuo

    2012-04-10

    The regional distribution and relative frequency of peptide YY (PYY)-, pancreatic polypeptide (PP)-, and glucagon-like peptide 1 (GLP-1)-immunoreactive (IR) cells were determined immunohistochemically in the gastrointestinal tract at seven ontogenetic stages in pre- and postnatal cattle. Different frequencies of PYY-, PP-, and GLP-1-IR cells were found in the intestines at all stages; they were not found in the esophagus and stomach. The frequencies varied depending on the intestinal segment and the developmental stage. The frequencies of PYY- and PP-IR cells were lower in the small intestine and increased from ileum to rectum, whereas GLP-1-IR cells were more numerous in duodenum and jejunum, decreased in ileum and cecum, and increased again in colon and rectum. The frequencies also varied according to pre- and postnatal stages. All three cell types were most numerous in fetus, and decreased in calf and adult groups, indicating that the frequencies of these three types of endocrine cells decrease with postnatal development. The results suggest that these changes vary depending on feeding habits and adaptation of growth, secretion, and motility of intestine at different ontogenetic stages of cattle.

  18. Functional role of the Ca{sup 2+}-activated Cl{sup −} channel DOG1/TMEM16A in gastrointestinal stromal tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Berglund, Erik, E-mail: erik.berglund@ki.se [Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Department of Breast and Endocrine Surgery, Karolinska University Hospital, Stockholm (Sweden); Akcakaya, Pinar [Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Stockholm (Sweden); Berglund, David [Section for Transplantation Surgery, Department of Surgical Sciences, Uppsala University Hospital, Uppsala (Sweden); Karlsson, Fredrik [Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Department of Breast and Endocrine Surgery, Karolinska University Hospital, Stockholm (Sweden); Vukojević, Vladana [Department of Clinical Neuroscience, Karolinska Institutet, Stockholm (Sweden); Lee, Linkiat [Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Stockholm (Sweden); Bogdanović, Darko [Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Lui, Weng-Onn; Larsson, Catharina [Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Stockholm (Sweden); Zedenius, Jan [Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Department of Breast and Endocrine Surgery, Karolinska University Hospital, Stockholm (Sweden); Fröbom, Robin [Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Bränström, Robert [Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Department of Breast and Endocrine Surgery, Karolinska University Hospital, Stockholm (Sweden)

    2014-08-15

    DOG1, a Ca{sup 2+}-activated Cl{sup −} channel (CaCC), was identified in 2004 to be robustly expressed in gastrointestinal stromal tumors (GIST). It was rapidly included as a tumor marker in routine diagnostics, but the functional role remained unknown. CaCCs are important regulators of normal physiological functions, but also implicated in tumorigenesis, cancer progression, metastasis, cell migration, apoptosis, proliferation and viability in several malignancies. We therefore investigated whether DOG1 plays a role in the three latter in GIST by utilizing in vitro cell model systems. Confocal microscopy identified different subcellular localizations of DOG1 in imatinib-sensitive and imatinib-resistant cells. Electrophysiological studies confirmed that DOG1-specific pharmacological agents possess potent activating and inhibiting properties. Proliferation assays showed small effects up to 72 h, and flow cytometric analysis of adherent cells with 7-AAD/Annexin V detected no pharmacological effects on viable GIST cells. However, inhibition of DOG1 conveyed pro-apoptotic effects among early apoptotic imatinib-resistant cells. In conclusion, DOG1 generates Cl{sup −} currents in GIST that can be regulated pharmacologically, with small effects on cell viability and proliferation in vitro. Inhibition of DOG1 might act pro-apoptotic on some early apoptotic GIST cell populations. Further studies are warranted to fully illuminate the function of DOG1 and its potential as therapeutic target. - Highlights: • Subcellular DOG1 localization varies between GIST cells. • DOG1 in GIST is voltage- and Ca{sup 2+}-activated. • Known TMEM16A modulators, like A01 and Eact, modulate DOG1. • DOG1 has small effects on cell viability and proliferation in vitro. • DOG1 impact early apoptotic GIST cells to undergo late apoptosis.

  19. IL-17a and IL-22 Induce Expression of Antimicrobials in Gastrointestinal Epithelial Cells and May Contribute to Epithelial Cell Defense against Helicobacter pylori.

    Directory of Open Access Journals (Sweden)

    Beverly R E A Dixon

    Full Text Available Helicobacter pylori colonization of the human stomach can lead to adverse clinical outcomes including gastritis, peptic ulcers, or gastric cancer. Current data suggest that in addition to bacterial virulence factors, the magnitude and types of immune responses influence the outcome of colonization. Specifically, CD4+ T cell responses impact the pathology elicited in response to H. pylori. Because gastritis is believed to be the initiating host response to more detrimental pathological outcomes, there has been a significant interest in pro-inflammatory T cell cytokines, including the cytokines produced by T helper 17 cells. Th17 cells produce IL-17A, IL-17F, IL-21 and IL-22. While these cytokines have been linked to inflammation, IL-17A and IL-22 are also associated with anti-microbial responses and control of bacterial colonization. The goal of this research was to determine the role of IL-22 in activation of antimicrobial responses in models of H. pylori infection using human gastric epithelial cell lines and the mouse model of H. pylori infection. Our data indicate that IL-17A and IL-22 work synergistically to induce antimicrobials and chemokines such as IL-8, components of calprotectin (CP, lipocalin (LCN and some β-defensins in both human and primary mouse gastric epithelial cells (GEC and gastroids. Moreover, IL-22 and IL-17A-activated GECs were capable of inhibiting growth of H. pylori in vitro. While antimicrobials were activated by IL-17A and IL-22 in vitro, using a mouse model of H. pylori infection, the data herein indicate that IL-22 deficiency alone does not render mice more susceptible to infection, change their antimicrobial gene transcription, or significantly change their inflammatory response.

  20. [Immune system evolution. (From cells to humans)].

    Science.gov (United States)

    Belek, A S

    1992-01-01

    The great variety of cells and molecules observed in the mammalian immune system can be explained by stepwise acquisition of them during phylogeny. Self/nonself discrimination and cell-mediated immunity have been present since the early stages of evolution. Although some inducible antimicrobial molecules have been demonstrated in invertebrates, immunoglobulins appear in vertebrates. T and B cell diversity, development of the lymphoid organs, MHC molecules, complement and cytokines are the characteristics that appear through the evolution of vertebrates. Further knowledge that will be obtained from phylogenetic studies will improve our understanding of the immune system of human.

  1. Centre for human development, stem cells & regeneration.

    Science.gov (United States)

    Oreffo, Richard O C

    2014-01-01

    The Centre for Human Development, Stem Cells and Regeneration (CHDSCR) was founded in 2004 as a cross-disciplinary research and translational program within the Faculty of Medicine at the University of Southampton. The Centre undertakes fundamental research into early development and stem cells together with applied translational research for patient benefit. The Centre has vibrant and thriving multidisciplinary research programs that harness the translational strength of the Faculty together with an innovative Stem Cell PhD program, outstanding clinical infrastructure and enterprise to deliver on this vision.

  2. Biobanking human embryonic stem cell lines

    DEFF Research Database (Denmark)

    Holm, Søren

    2016-01-01

    Stem cell banks curating and distributing human embryonic stem cells have been established in a number of countries and by a number of private institutions. This paper identifies and critically discusses a number of arguments that are used to justify the importance of such banks in policy...... are curiously absent from the particular stem cell banking policy discourse. This to some extent artificially isolates this discourse from the broader discussions about the flows of reproductive materials and tissues in modern society, and such isolation may lead to the interests of important actors being...

  3. Probiotics for Gastrointestinal Conditions: A Summary of the Evidence.

    Science.gov (United States)

    Wilkins, Thad; Sequoia, Jacqueline

    2017-08-01

    Probiotics contain microorganisms, most of which are bacteria similar to the beneficial bacteria that occur naturally in the human gut. Probiotics have been widely studied in a variety of gastrointestinal diseases. The most-studied species include Lactobacillus, Bifidobacterium, and Saccharomyces. However, a lack of clear guidelines on when to use probiotics and the most effective probiotic for different gastrointestinal conditions may be confusing for family physicians and their patients. Probiotics have an important role in the maintenance of immunologic equilibrium in the gastrointestinal tract through the direct interaction with immune cells. Probiotic effectiveness can be species-, dose-, and disease-specific, and the duration of therapy depends on the clinical indication. There is high-quality evidence that probiotics are effective for acute infectious diarrhea, antibiotic-associated diarrhea, Clostridium difficile- associated diarrhea, hepatic encephalopathy, ulcerative colitis, irritable bowel syndrome, functional gastrointestinal disorders, and necrotizing enterocolitis. Conversely, there is evidence that probiotics are not effective for acute pancreatitis and Crohn disease. Probiotics are safe for infants, children, adults, and older patients, but caution is advised in immunologically vulnerable populations.

  4. Extensive hemangiomatosis diagnosed by scintigraphy with 99mTc-labeled red blood cells in a patient with lower gastrointestinal bleeding

    Energy Technology Data Exchange (ETDEWEB)

    Souza, D.S.F.; Ichiki, W.A.; Borges, A.C.; Coura Filho, G.B.; Vecchia, J.F.; Sapienza, M.T.; Ono, C.R.; Watanabe, T.; Costa, P.L.A.; Hironaka, F.; Cerri, G.G.; Buchpiguel, C.A. [Universidade de Sao Paulo (FM/USP), SP (Brazil). Inst. de Radiologia. Servico de Medicina Nuclear

    2008-07-01

    Full text: Introduction: The gastrointestinal bleeding may be caused by vascular tumors and other lesions like inflammatory disorders, intestinal obstruction or vascular malformation. The Klippel-Trenaunay syndrome and blue rubber bleb nevus syndrome are hemangiomatosis diseases that may involve the gastrointestinal tract and cause recurrent hemorrhage. The signs and symptoms usually appear at childhood. Case report: male patient, 31 years old, presenting three days of gastrointestinal bleeding and an hemorrhage shock (Hb=3,9). Previous reports of small volume bleeding since childhood and schistossomosis. Dilated veins, hemorrhoid and port wine stain lesions were detected at physical examination in perineal region, penis and scrotum. Inferior limbs were symmetric at inspection. The upper endoscopy showed esophageal varices with no signs of active bleeding. The scintigraphy with {sup 99m}Tc-labeled red blood cells showed active hemorrhage at recto-sigmoid topography during the first hour of study. Extensive and heterogeneous uptake was seen in gluteus, posterior right thigh and scrotum at the second and fifth hours of study. Then the hypothesis of vascular tumor was considered. The magnetic resonance (MR) of pelvis demonstrated extensive hemangiomatosis at the regions described by the scintigraphy. The clinical and imaging findings suggested the diagnosis of Klippel-Trenaunay syndrome. Discussion: The Klippel-Trenaunay syndrome is a rare disease characterized by congenital vascular and lymphatic malformations (port wine stain lesions, congenital varices) and bone growth and soft tissue disorder. Dilated veins may involve abdominal and pelvic structures, with rectal bleeding and haematuria occurring on average of 20%. The clinical investigation must approach the type, the extent and the severity of the malformation, since the morbidity and the mortality depends on the visceral involvement. The Doppler ultrasound, scanometry of lower extremities, MR, angiography and

  5. Gastrointestinal hormones and their targets

    DEFF Research Database (Denmark)

    Rehfeld, Jens F.

    2014-01-01

    Gastrointestinal hormones are peptides released from endocrine cells and neurons in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gastrointestinal tract, which makes the gut the largest hormone producing organ in the body. Modern biology makes......, paracrine, spermiocrine secretion etc.), so the same peptide may act as a blood-borne hormone, a neurotransmitter, a local growth factor, or a fertility factor. The molecular targets of each bioactive peptide are specific G-protein coupled receptors expressed in the cell membranes of different target cells...... it feasible to conceive the hormones under five headings: The structural homology groups a majority of the hormones into nine families, each of which is assumed to originate from one ancestral gene. The individual hormone gene often has multiple phenotypes due to alternative splicing, tandem organization...

  6. Lactic acid bacteria protect human intestinal epithelial cells from Staphylococcus aureus and Pseudomonas aeruginosa infections.

    Science.gov (United States)

    Affhan, S; Dachang, W; Xin, Y; Shang, D

    2015-12-16

    Staphylococcus aureus and Pseudomonas aeruginosa are opportunistic pathogens that cause nosocomial and food-borne infections. They promote intestinal diseases. Gastrointestinal colonization by S. aureus and P. aeruginosa has rarely been researched. These organisms spread to extra gastrointestinal niches, resulting in increasingly progressive infections. Lactic acid bacteria are Gram-positive bacteria that produce lactic acid as the major end-product of carbohydrate fermentation. These bacteria inhibit pathogen colonization and modulate the host immune response. This study aimed to investigate the effects of Lactobacillus acidophilus and Lactobacillus rhamnosus on enteric infections caused by the paradigmatic human pathogens S. aureus ATCC25923 and P. aeruginosa ATCC27853. The effect of whole cells and neutralized cell-free supernatant (CFS) of the lactobacilli on LoVo human carcinoma enterocyte (ATCC CCL-229) infection was analyzed by co-exposure, pre-exposure, and post-exposure studies. Simultaneous application of whole cells and CFS of the lactobacilli significantly eradicated enterocyte infection (P cells and CFS were added after or prior to the infection (P > 0.05). This result could be attributed to interference by extracellular polymeric substances and cell surface hydrophobicity, which resulted in the development of a pathogen that did not form colonies. Furthermore, results of the plate count and LIVE/ DEAD BacLight bacterial viability staining attributed this inhibition to a non-bacteriocin-like substance, which acted independently of organic acid and H2O2 production. Based on these results, the cell-free supernatant derived from lactobacilli was concluded to restrain the development of S. aureus and P. aeruginosa enteric infections.

  7. Advances in human B cell phenotypic profiling

    Directory of Open Access Journals (Sweden)

    Denise A Kaminski

    2012-10-01

    Full Text Available To advance our understanding and treatment of disease, research immunologists have been called-upon to place more centralized emphasis on impactful human studies. Such endeavors will inevitably require large-scale study execution and data management regulation (Big Biology, necessitating standardized and reliable metrics of immune status and function. A well-known example setting this large-scale effort in-motion is identifying correlations between eventual disease outcome and T lymphocyte phenotype in large HIV-patient cohorts using multiparameter flow cytometry. However, infection, immunodeficiency, and autoimmunity are also characterized by correlative and functional contributions of B lymphocytes, which to-date have received much less attention in the human Big Biology enterprise. Here, we review progress in human B cell phenotyping, analysis, and bioinformatics tools that constitute valuable resources for the B cell research community to effectively join in this effort.

  8. Human plasma cells express granzyme B.

    Science.gov (United States)

    Xu, Wei; Narayanan, Priya; Kang, Ning; Clayton, Sandra; Ohne, Yoichiro; Shi, Peiqing; Herve, Marie-Cecile; Balderas, Robert; Picard, Capucine; Casanova, Jean-Laurent; Gorvel, Jean-Pierre; Oh, Sangkon; Pascual, Virginia; Banchereau, Jacques

    2014-01-01

    While studying the plasma cell (PC) compartment in human tonsils, we identified that immunoglobulin kappa or lambda chain-expressing PCs are the main cells expressing granzyme B (GrzB). In vitro studies revealed that activated B cells differentiated into GrzB-expressing PCs when co-cultured with macrophages and follicular helper T cells. This effect could be reproduced on combined stimulation of IL-15 (produced by macrophages) and IL-21 (produced by T follicular helper cells) in a STAT3-dependent manner. Whereas IL-21 triggers the transcription of mRNA of GrzB, IL-15 synergizes the translation of GrzB proteins. The precise role of GrzB in PC biology remains to be understood and studies in mice will not help as their PCs do not express GrzB.

  9. Human CD56bright NK Cells

    DEFF Research Database (Denmark)

    Michel, Tatiana; Poli, Aurélie; Cuapio, Angelica

    2016-01-01

    Human NK cells can be subdivided into various subsets based on the relative expression of CD16 and CD56. In particular, CD56(bright)CD16(-/dim) NK cells are the focus of interest. They are considered efficient cytokine producers endowed with immunoregulatory properties, but they can also become...... cytotoxic upon appropriate activation. These cells were shown to play a role in different disease states, such as cancer, autoimmunity, neuroinflammation, and infection. Although their phenotype and functional properties are well known and have been extensively studied, their lineage relationship with other...... NK cell subsets is not fully defined, nor is their precise hematopoietic origin. In this article, we summarize recent studies about CD56(bright) NK cells in health and disease and briefly discuss the current controversies surrounding them....

  10. Human embryonic stem cells: preclinical perspectives

    Directory of Open Access Journals (Sweden)

    Sarda Kanchan

    2008-01-01

    Full Text Available Abstract Human embryonic stem cells (hESCs have been extensively discussed in public and scientific communities for their potential in treating diseases and injuries. However, not much has been achieved in turning them into safe therapeutic agents. The hurdles in transforming hESCs to therapies start right with the way these cells are derived and maintained in the laboratory, and goes up-to clinical complications related to need for patient specific cell lines, gender specific aspects, age of the cells, and several post transplantation uncertainties. The different types of cells derived through directed differentiation of hESC and used successfully in animal disease and injury models are described briefly. This review gives a brief outlook on the present and the future of hESC based therapies, and talks about the technological advances required for a safe transition from laboratory to clinic.

  11. Stress, Anxiety and Functional Gastrointestinal Disorders

    Directory of Open Access Journals (Sweden)

    Sermin Kesebir

    2012-04-01

    Full Text Available Stress has major role in functional gastrointestinal system disorders. The most typical example of this situation is Irritable bowel syndrome. Gastrointestinal system’s response to acute or short-term of stress is delay of gastric emptying and stimulation of colonic transition. While CRF2 receptors are mediate the upper section inhibition, CRF1 is responsible for the lower part colonic and anxiogenic response. Visceral hypersensitivity is managed by the emotional motor system, the amygdala plays a significant role and mucosal mast cells arise. But in people with symptoms of functional gastrointestinal, how is differ motility response in healthy individuals, this situation is due to lack of autonomous nervous system or an increased sensitivity of stress is not adequately understood. The brain-gastrointestinal axis frequency and severity of symptoms associated with negative emotions. American Gastroenterology Association is closely associated with the quality of life and is very difficult to treat the symptoms of gastrointestinal disorders, re-interpreted under the heading of 'Gastrointestinal Distress'. This review is defined as gastrointestinal distresses, physical, emotional, and behavioral components as a disorder in which, almost like an anxiety disorder are discussed. Physical component is pain, gas, and defecation problems, cognitive component is external foci control, catastrophization and anticipatory anxiety, the emotional component is somatic anxiety, hypervigilance, and avoidance of gastrointestinal stimuli as defined. [Archives Medical Review Journal 2012; 21(2.000: 122-133

  12. Survival and digestibility of orally-administered immunoglobulin preparations containing IgG through the gastrointestinal tract in humans.

    Science.gov (United States)

    Jasion, Victoria S; Burnett, Bruce P

    2015-03-07

    Oral immunoglobulin (Ig) preparations are prime examples of medicinal nutrition from natural sources. Plasma products containing Ig have been used for decades in animal feed for intestinal disorders to mitigate the damaging effects of early weaning. These preparations reduce overall mortality and increase feed utilization in various animal species leading to improved growth. Oral administration of Ig preparations from human serum as well as bovine colostrum and serum have been tested and proven to be safe as well as effective in human clinical trials for a variety of enteric microbial infections and other conditions which cause diarrhea. In infants, children, and adults, the amount of intact IgG recovered in stool ranges from trace amounts up to 25% of the original amount ingested. It is generally understood that IgG can only bind to antigens within the GI tract if the Fab structure is intact and has not been completely denatured through acidic pH or digestive proteolytic enzymes. This is a comprehensive review of human studies regarding the survivability of orally-administered Ig preparations, with a focus on IgG. This review also highlights various biochemical studies on IgG which potentially explain which structural elements are responsible for increased stability against digestion.

  13. Stem cell factor and c-Kit in human primordial germ cells and fetal ovaries

    DEFF Research Database (Denmark)

    Høyer, Poul Erik; Byskov, Anne Grete; Møllgård, Kjeld

    2005-01-01

    Prenatal ovary (human), Primordial germ cells, Folliculogenesis, c-Kit, Stem cell factor, immunohistochemistry......Prenatal ovary (human), Primordial germ cells, Folliculogenesis, c-Kit, Stem cell factor, immunohistochemistry...

  14. Probiotic yogurt consumption may improve gastrointestinal symptoms, productivity, and nutritional intake of people living with human immunodeficiency virus in Mwanza, Tanzania.

    Science.gov (United States)

    Irvine, Stephanie L; Hummelen, Ruben; Hekmat, Sharareh

    2011-12-01

    The gut-associated lymphoid tissue is a major site of human immunodeficiency virus (HIV) activity and significantly influences disease prognosis. Reducing immune activation due to gastroenteritis may thus help slow disease progression. Probiotic microorganisms have considerable immunomodulatory effects at the level of the gut-associated lymphoid tissue. A probiotic yogurt initiative was thus established in Mwanza, Tanzania, to improve gastrointestinal (GI) integrity and reduce the incidence and severity of opportunistic infections among people with HIV. The research objective was to retrospectively evaluate the effects of yogurt supplemented with Lactobacillus rhamnosus as an adjunct to the diet of people living with HIV on systemic and GI symptoms, daily routine activities, and nutritional intake. Eighty-five people with HIV consuming probiotic yogurt and 86 controls were interviewed. Demographics and HIV disease stage were comparable between groups. Probiotic yogurt consumers reported an ability to work a median of 2 hours more daily (P = .01), experienced a lower fever incidence (P = .01), and were more likely to achieve daily nutrient requirements for vitamin A, several B complex vitamins, and calcium (P = .02). Antiretroviral users experienced less drug-induced stomach pain (P = .02) and a lower overall impact of GI symptoms on routine activities (P = .03). The results of this study need be further substantiated because of limits imposed by the observational, retrospective study design; however, results suggest that yogurt supplemented with L rhamnosus may effectively alleviate GI symptoms and improve productivity, nutritional intake, and tolerance to antiretroviral treatment among people with HIV in Mwanza.

  15. Differences in the microrheology of human embryonic stem cells and human induced pluripotent stem cells.

    Science.gov (United States)

    Daniels, Brian R; Hale, Christopher M; Khatau, Shyam B; Kusuma, Sravanti; Dobrowsky, Terrence M; Gerecht, Sharon; Wirtz, Denis

    2010-12-01

    Embryonic and adult fibroblasts can be returned to pluripotency by the expression of reprogramming genes. Multiple lines of evidence suggest that these human induced pluripotent stem (hiPS) cells and human embryonic stem (hES) cells are behaviorally, karyotypically, and morphologically similar. Here we sought to determine whether the physical properties of hiPS cells, including their micromechanical properties, are different from those of hES cells. To this end, we use the method of particle tracking microrheology to compare the viscoelastic properties of the cytoplasm of hES cells, hiPS cells, and the terminally differentiated parental human fibroblasts from which our hiPS cells are derived. Our results indicate that although the cytoplasm of parental fibroblasts is both viscous and elastic, the cytoplasm of hiPS cells does not exhibit any measurable elasticity and is purely viscous over a wide range of timescales. The viscous phenotype of hiPS cells is recapitulated in parental cells with disassembled actin filament network. The cytoplasm of hES cells is predominantly viscous but contains subcellular regions that are also elastic. This study supports the hypothesis that intracellular elasticity correlates with the degree of cellular differentiation and reveals significant differences in the mechanical properties of hiPS cells and hES cells. Because mechanical stimuli have been shown to mediate the precise fate of differentiating stem cells, our results support the concept that stem cell "softness" is a key feature of force-mediated differentiation of stem cells and suggest there may be subtle functional differences between force-mediated differentiation of hiPS cells and hES cells.

  16. Phenotypical characterization, distribution and quantification of different mast cell subtypes in transmural biopsies from the gastrointestinal tract of cats with inflammatory bowel disease.

    Science.gov (United States)

    Kleinschmidt, Sven; Harder, Jasmine; Nolte, Ingo; Marsilio, Sina; Hewicker-Trautwein, Marion

    2010-10-15

    In this study subtypes, distribution and number of mast cells were investigated within mucosa and submucosa of the gastrointestinal tract of 24 cats with inflammatory bowel disease (IBD) in comparison to 11 control cats. Paraffin sections of formalin-fixed transmural gastrointestinal biopsies from stomach, duodenum, jejunum, ileum and colon were examined. Mast cells were phenotyped and quantified based on their chymase and tryptase content, by applying a combined enzyme-histochemical and immunohistochemical double-labeling technique and on their heparin content by a metachromatic staining method (kresylecht-violet, MC(KEV)). Mast cells containing both chymase and tryptase were not found in any of the samples examined. Furthermore, in the stomach neither chymase (MC(C)) nor tryptase (MC(T)) bearing mast cells were detected. In cats with lymphocytic-plasmacytic enteritis or enterocolitis elevated numbers of MC(T) or MC(C) were identified in comparison to controls mainly located in the inflamed segments. The highest quantity of MC(C) was found in cats with eosinophilic gastroenterocolitis or enterocolitis in comparison to other IBD forms, but only minor numbers of MC(T) were detected in these cases. In cats with fibrosing enteropathy (FE) a decrease of MC(C) and mast cells containing heparin was detected in affected segments, while increased numbers of MC(T) were detected in all locations. The elevation in the number of MC(T) was higher in unaffected areas than in fibrotic regions. Regarding all IBD cases higher counts of MC(C) were found especially in the inflamed locations, whereas in unaffected segments increased numbers of MC(T) were detected. The clear predominance of MC(C) and MC(T) within the mucosa and of MC(KEV) within the submucosa of all cats examined possibly represents differences of the cytokine milieu within the intestinal layers. In FE, mast cells are possibly pivotal for the containment of the inflammatory process because of their antiinflammatory

  17. [Metagenomics in studying gastrointestinal tract microorganism].

    Science.gov (United States)

    Xu, Bo; Yang, Yunjuan; Li, Junjun; Tang, Xianghua; Mu, Yuelin; Huang, Zunxi

    2013-12-01

    Animal gastrointestinal tract contains a complex community of microbes, whose composition ultimately reflects the co-evolution of microorganisms with their animal host. The gut microbial community of humans and animals has received significant attention from researchers because of its association with health and disease. The application of metagenomics technology enables researchers to study not only the microbial composition but also the function of microbes in the gastrointestinal tract. In this paper, combined with our own findings, we summarized advances in studying gastrointestinal tract microorganism with metagenomics and the bioinformatics technology.

  18. Generation of mature hematopoietic cells from human pluripotent stem cells.

    Science.gov (United States)

    Togarrati, Padma Priya; Suknuntha, Kran

    2012-06-01

    A number of malignant and non-malignant hematological disorders are associated with the abnormal production of mature blood cells or primitive hematopoietic precursors. Their capacity for continuous self-renewal without loss of pluripotency and the ability to differentiate into adult cell types from all three primitive germ layers make human embryonic stem cells and induced pluripotent stem cells (hiPSCs) attractive complementary cell sources for large-scale production of transfusable mature blood cell components in cell replacement therapies. The generation of patient-specific hematopoietic stem/precursor cells from iPSCs by the regulated manipulation of various factors involved in reprograming to ensure complete pluripotency, and developing innovative differentiation strategies for generating unlimited supply of clinically safe, transplantable, HLA-matched cells from hiPSCs to outnumber the inadequate source of hematopoietic stem cells obtained from cord blood, bone marrow and peripheral blood, would have a major impact on the field of regenerative and personalized medicine leading to translation of these results from bench to bedside.

  19. 99mTechnetium-labelled red blood cell scintigraphy as an alternative to angiography in the investigation of gastrointestinal bleeding: clinical experience in a district general hospital.

    Science.gov (United States)

    Bearn, P.; Persad, R.; Wilson, N.; Flanagan, J.; Williams, T.

    1992-01-01

    99mTechnetium-labelled red blood cell scintigraphy (99mTc RBC scintigraphy) was used as the second-line investigation to localise bleeding in 23 patients (11 male, 12 female; mean age 67 years) presenting with active bleeding per rectum. Scintigraphy was available on a 24 h basis. A total of 18 patients had positive scans (78%). Surgery was performed urgently in 11 patients and the site of bleeding, as predicted by scintigraphy, was confirmed in 9 (82%). 99mTc RBC scintigraphy was less useful in patients who were not bleeding actively or who were being investigated for chronic anaemia. This study suggests that 99mTc RBC scintigraphy can play a useful role in the preoperative localisation of unexplained gastrointestinal bleeding in hospitals with nuclear medicine facilities, but confirms it has little place in the management of patients unless they are bleeding actively. PMID:1319696

  20. Synchronous Occurrence of Diffuse Large B-cell Lymphoma of the Duodenum and Gastrointestinal Stromal Tumor of the Ileum in a Patient with Immune Thrombocytopenic Purpura

    Science.gov (United States)

    Takahashi, Tohru; Maruyama, Yumiko; Saitoh, Mayuko; Itoh, Hideto; Yoshimoto, Mitsuru; Tsujisaki, Masayuki; Nakayama, Masato

    2016-01-01

    A 64 year-old woman with steroid-dependent immune thrombocytopenia developed anemia. Esophagogastroduodenoscopy revealed the presence of a tumor, which was diagnosed to be diffuse large B-cell lymphoma, in the second portion of the duodenum. 18F-fluorodeoxy glucose positron emission tomography showed an increased uptake mass in the pelvic cavity as well as in the duodenum. Though the duodenal tumor disappeared after 4 cycles of chemotherapy, the pelvic mass did not shrink in size. As a result, laparoscopic resection of the pelvic tumor was performed and the tumor was histologically diagnosed to be a gastrointestinal stromal tumor. Subsequently, the patient was treated with 2 more cycles of the chemotherapy. Eventually, thrombocytopenia completely resolved. PMID:27746431

  1. Human colostral cells. I. Separation and characterization.

    Science.gov (United States)

    Crago, S S; Prince, S J; Pretlow, T G; McGhee, J R; Mestecky, J

    1979-12-01

    Analyses of the cells present in human colostrum obtained from fifty-four healthy donors during the first four days of lactation revealed that there were 3.3 x 10(6) (range 1.1 x 10(5)--1.2 x 10(7)) cells per ml of colostrum. Based on histochemical examinations, it was found that this population consisted of 30--47% macrophages, 40--60% polymorphonuclear leucocytes, 5.2--8.9% lymphocytes, and 1.3--2.8% colostral corpuscles; epithelial cells were rarely encountered. The identity of various cell types was confirmed by Wright's stain and by a series of histochemical techniques which disclosed the presence of non-specific esterase, peroxidase, and lipids. For further characterization, the different types of cells were separated by various methods, such as Ficoll-Hypaque density centrifugation, isokinetic centrifugation on a linear Ficoll gradient, adherence to glass or plastic, and phagocytosis of carbonyl iron. Immunohistochemical staining with FITC- and/or TRITC-labelled reagents to IgA, IgM, IgG, K- and lambda-chains, secretory component, lactoferrin, and alpha-lactalbumin were applied to unseparated as well as separated colostral cells. Polymorphonuclear leucocytes (staining for peroxidase) as well as macrophages and colostral corpuscles (staining for non-specific esterase) exhibited numerous intracellular vesicles that contained lipids as well as various combinations of milk proteins. Lymphoid cells did not stain with any of these reagents and plasma cells were not detected among the colostral cells. Individual phagocytic cells contained immunoglobulins of the IgA and IgM classes, both K and lambda light chains, secretory component, lactoferrin, and alpha-lactalbumin. The coincidental appearance of these proteins in single, phagocytic cells but not in lymphoid cells indicate that the cells acquired these proteins by ingestion from the environment. Markers commonly used for the identification of B lymphocytes (surface immunoglobulins) and T lymphocytes (receptors

  2. 21 CFR 864.2280 - Cultured animal and human cells.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cultured animal and human cells. 864.2280 Section... (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Cell And Tissue Culture Products § 864.2280 Cultured animal and human cells. (a) Identification. Cultured animal and human cells are in vitro...

  3. DNA repair responses in human skin cells

    Energy Technology Data Exchange (ETDEWEB)

    Hanawalt, P.C.; Liu, S.C.; Parsons, C.S.

    1981-07-01

    Sunlight and some environmental chemical agents produce lesions in the DNA of human skin cells that if unrepaired may interfere with normal functioning of these cells. The most serious outcome of such interactions may be malignancy. It is therefore important to develop an understanding of mechanisms by which the lesions may be repaired or tolerated without deleterious consequences. Our models for the molecular processing of damaged DNA have been derived largely from the study of bacterial systems. Some similarities but significant differences are revealed when human cell responses are tested against these models. It is also of importance to learn DNA repair responses of epidermal keratinocytes for comparison with the more extensive studies that have been carried out with dermal fibroblasts. Our experimental results thus far indicate similarities for the excision-repair of ultraviolet-induced pyrimidine dimers in human keratinocytes and fibroblasts. Both the monoadducts and the interstrand crosslinks produced in DNA by photoactivated 8-methoxypsoralen (PUVA) can be repaired in normal human fibroblasts but not in those from xeroderma pigmentosum patients. The monoadducts, like pyrimidine dimers, are probably the more mutagenic/carcinogenic lesions while the crosslinks are less easily repaired and probably result in more effective blocking of DNA function. It is suggested that a split-dose protocol that maximizes the production of crosslinks while minimizing the yield of monoadducts may be more effective and potentially less carcinogenic than the single ultraviolet exposure regimen in PUVA therapy for psoriasis.

  4. The use of double-balloon enteroscopy in retrieving mucosal biopsies from the entire human gastrointestinal tract

    DEFF Research Database (Denmark)

    Rhee, Nicolai Alexander; Vilmann, Peter; Hassan, Hazem

    2014-01-01

    OBJECTIVE: The aim of this explorative study was to evaluate double-balloon enteroscopy (DBE) as a new tool for collecting mucosal biopsies from well-defined parts of the entire small and large bowel in patients with type 2 diabetes and in matched healthy subjects. MATERIAL AND METHODS: Twelve su...... possibility to access hitherto unexplored human anatomy and physiology....... subjects with type 2 diabetes and 12 body mass index and age-matched healthy subjects underwent anterograde and retrograde DBE under nurse-administered propofol sedation on two separate days. We attempted to collect two mucosal biopsies from every 30 cm from pylorus to rectum. RESULTS: A mean of 21 biopsy...

  5. Clinical Validation and Implementation of a Targeted Next-Generation Sequencing Assay to Detect Somatic Variants in Non-Small Cell Lung, Melanoma, and Gastrointestinal Malignancies

    Science.gov (United States)

    Fisher, Kevin E.; Zhang, Linsheng; Wang, Jason; Smith, Geoffrey H.; Newman, Scott; Schneider, Thomas M.; Pillai, Rathi N.; Kudchadkar, Ragini R.; Owonikoko, Taofeek K.; Ramalingam, Suresh S.; Lawson, David H.; Delman, Keith A.; El-Rayes, Bassel F.; Wilson, Malania M.; Sullivan, H. Clifford; Morrison, Annie S.; Balci, Serdar; Adsay, N. Volkan; Gal, Anthony A.; Sica, Gabriel L.; Saxe, Debra F.; Mann, Karen P.; Hill, Charles E.; Khuri, Fadlo R.; Rossi, Michael R.

    2017-01-01

    We tested and clinically validated a targeted next-generation sequencing (NGS) mutation panel using 80 formalin-fixed, paraffin-embedded (FFPE) tumor samples. Forty non-small cell lung carcinoma (NSCLC), 30 melanoma, and 30 gastrointestinal (12 colonic, 10 gastric, and 8 pancreatic adenocarcinoma) FFPE samples were selected from laboratory archives. After appropriate specimen and nucleic acid quality control, 80 NGS libraries were prepared using the Illumina TruSight tumor (TST) kit and sequenced on the Illumina MiSeq. Sequence alignment, variant calling, and sequencing quality control were performed using vendor software and laboratory-developed analysis workflows. TST generated ≥500× coverage for 98.4% of the 13,952 targeted bases. Reproducible and accurate variant calling was achieved at ≥5% variant allele frequency with 8 to 12 multiplexed samples per MiSeq flow cell. TST detected 112 variants overall, and confirmed all known single-nucleotide variants (n = 27), deletions (n = 5), insertions (n = 3), and multinucleotide variants (n = 3). TST detected at least one variant in 85.0% (68/80), and two or more variants in 36.2% (29/80), of samples. TP53 was the most frequently mutated gene in NSCLC (13 variants; 13/32 samples), gastrointestinal malignancies (15 variants; 13/25 samples), and overall (30 variants; 28/80 samples). BRAF mutations were most common in melanoma (nine variants; 9/23 samples). Clinically relevant NGS data can be obtained from routine clinical FFPE solid tumor specimens using TST, benchtop instruments, and vendor-supplied bioinformatics pipelines. PMID:26801070

  6. Evaluation of antioxidant activity and antiproliferative effect of fruit juices enriched with Pycnogenol® in colon carcinoma cells. The effect of in vitro gastrointestinal digestion.

    Science.gov (United States)

    Frontela-Saseta, Carmen; López-Nicolás, Rubén; González-Bermúdez, Carlos A; Peso-Echarri, Patricia; Ros-Berruezo, Gaspar; Martínez-Graciá, Carmen; Canali, Raffaella; Virgili, Fabio

    2011-12-01

    The aim of this study was to examine the effect of in vitro gastrointestinal digestion on the antioxidant and antiproliferative effect of fruit juices enriched with Pycnogenol® (0.5 g/L) on a colon carcinoma cell line (Caco-2). The total phenolic concentration (TPC), antioxidant activity and inhibition cell growth were studied in fresh and digested pineapple juice and red fruits juice (both enriched with pine bark extract and not). After in vitro digestion the level of detectable phenolic compounds (expressed as gallic acid equivalent) was higher in both pineapple and red fruits juices enriched with Pycnogenol® than in non-enriched commercial juices (155.6 mg/100 mL vs 94.6 mg/100 mL and 478.5 mg/100 mL vs 406.9 mg/100 mL, respectively). Increased antioxidant activity (measured by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and oxygen radical absorbance capacity assay (ORAC) methods) was observed in digested enriched juices with respect to the same samples before digestion. Pycnogenol® enrichment led to a high antiproliferative effect between 24 and 72 h of incubation with undigested pineapple juice compared with the non-enriched juice. It can be concluded that enrichment of fruit juices with Pycnogenol® provides a source of phenolic compounds with high stability to in vitro gastrointestinal conditions; however, the antioxidant properties of fruit juices were affected to a different extent.

  7. Human T Cell Memory: A Dynamic View

    Directory of Open Access Journals (Sweden)

    Derek C. Macallan

    2017-02-01

    Full Text Available Long-term T cell-mediated protection depends upon the formation of a pool of memory cells to protect against future pathogen challenge. In this review we argue that looking at T cell memory from a dynamic viewpoint can help in understanding how memory populations are maintained following pathogen exposure or vaccination. For example, a dynamic view resolves the apparent paradox between the relatively short lifespans of individual memory cells and very long-lived immunological memory by focussing on the persistence of clonal populations, rather than individual cells. Clonal survival is achieved by balancing proliferation, death and differentiation rates within and between identifiable phenotypic pools; such pools correspond broadly to sequential stages in the linear differentiation pathway. Each pool has its own characteristic kinetics, but only when considered as a population; single cells exhibit considerable heterogeneity. In humans, we tend to concentrate on circulating cells, but memory T cells in non-lymphoid tissues and bone marrow are increasingly recognised as critical for immune defence; their kinetics, however, remain largely unexplored. Considering vaccination from this viewpoint shifts the focus from the size of the primary response to the survival of the clone and enables identification of critical system pinch-points and opportunities to improve vaccine efficacy.

  8. Biological impact of human embryonic stem cells.

    Science.gov (United States)

    Martín, Miguel; Menéndez, Pablo

    2012-01-01

    Research on human embryonic stem cells (hESCs) and induced pluripotent (iPS) stem cells is currently a field of great potential in biomedicine. These cells represent a highly valuable tool for developmental biology studies, disease models, and drug screening and toxicity. The ultimate goal of hESCs and iPS cell research is the treatment of diseases or disorders for which there is currently no treatment or existing therapies are only partially effective. Despite the disproportionate short-term hopes generated, which are putting too much pressure on scientists, the international scientific community is making rapid progress in understanding hESCs and iPS cells. Nonetheless, great efforts have to be made to provide an answer to still quite basic questions concerning their biology. Moreover, translation to clinical applications in cell replacement therapy requires prior solution to ethical barriers. The recent development of iPS cells has provided a strong alternative to overcome ethical issues concerning hESCs. However, an in-depth characterization of their genetic and epigenetic features, as well as their differentiation potential still remains to be undertaken. This chapter will describe, precisely, what the critical issues are, where scientific and ethical barriers stand, and how we are to overcome them. Only then, we shall finally discover whether hESCs and iPS cells will allow building reproducible disease models, and whether they really are a safe tool, with great potential for regenerative medicine.

  9. Nonvariceal upper gastrointestinal bleeding

    Energy Technology Data Exchange (ETDEWEB)

    Burke, Stephen J.; Weldon, Derik; Sun, Shiliang [University of Iowa, Department of Radiology, Iowa, IA (United States); Golzarian, Jafar [University of Iowa, Department of Radiology, Iowa, IA (United States); University of Iowa, Department of Radiology, Carver College of Medicine, Iowa, IA (United States)

    2007-07-15

    Nonvariceal upper gastrointestinal bleeding (NUGB) remains a major medical problem even after advances in medical therapy with gastric acid suppression and cyclooxygenase (COX-2) inhibitors. Although the incidence of upper gastrointestinal bleeding presenting to the emergency room has slightly decreased, similar decreases in overall mortality and rebleeding rate have not been experienced over the last few decades. Many causes of upper gastrointestinal bleeding have been identified and will be reviewed. Endoscopic, radiographic and angiographic modalities continue to form the basis of the diagnosis of upper gastrointestinal bleeding with new research in the field of CT angiography to diagnose gastrointestinal bleeding. Endoscopic and angiographic treatment modalities will be highlighted, emphasizing a multi-modality treatment plan for upper gastrointestinal bleeding. (orig.)

  10. Gastrointestinal Morbidity in Obesity

    Science.gov (United States)

    Acosta, Andres; Camilleri, Michael

    2014-01-01

    Obesity is a complex disease that results from increased energy intake and decreased energy expenditure. The gastrointestinal system plays a key role in the pathogenesis of obesity and facilitates caloric imbalance. Changes in gastrointestinal hormones and the inhibition of mechanisms that curtail caloric intake result in weight gain. It is not clear if the gastrointestinal role in obesity is a cause or an effect of this disease. Obesity is often associated with type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). Obesity is also associated with gastrointestinal disorders, which are more frequent and present earlier than T2DM and CVD. Diseases such as gastro-esophageal reflux disease, cholelithiasis or non-alcoholic steatohepatitis are directly related to body weight and abdominal adiposity. Our objective is to assess the role of each gastrointestinal organ in obesity and the gastrointestinal morbidity resulting in those organs from effects of obesity. PMID:24602085

  11. Human gastrointestinal tract resistance of Lactobacillus strains isolated from infant faecesResistência ao trato gastrointestinal humano de linhagens de Lactobacillus isoladas de fezes de crianças

    Directory of Open Access Journals (Sweden)

    Sandra Garcia

    2011-08-01

    Full Text Available The probiotic bacteria survival during the gastrointestinal transit is primordial, and implies in the ability of microorganisms to survive at the stomach acidity and bile, so they can exert their beneficial effects on the host. The aim of this study was to evaluate, “in vitro”, Lactobacillus strains originated from one year old children fecal material in the selection of probiotic microorganisms. Two commercial strains, L. casei (Lc 01TM and L. acidophilus (La-05 TM were used as controls. The first screening resulted in 75 colonies and they were isolated from six samples faeces. Isolates were Gram positive, mostly rod shaped (cocobacilli, long and thin rods and rarely cocci. They were submitted to catalase test and evaluated for the presence of spores, resulting in 30 pre-selected strains. Among those strains, eight strains: L4, L5, L12, L19, L20, L22, L23, L24 were the most resistant to Oxgall (bile salts concentration (0.3 w/v. These eight strains were also resistant to acid conditions (pH 3.0 and all strains were able to grow in the presence of 0.3 w/v of phenol. The results of treatments were compared to the Neuman Keuls Student test at 5% of probability, with regression analyses made at different times for tolerance to intestinal conditions. The results demonstrated that all these strains were able to survive under gastrointestinal stress condition, indicating potential use as probiotics. The high survival rate of probiotic strains, in conditions that simulate the gastrointestinal transit, is strain dependent and thus, a proper selection of strains in the development of dairy probiotic products is vital.

  12. Rare gastrointestinal lymphomas: the endoscopicinvestigation

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Gastrointestinal lymphomas represent up to 10% ofgastrointestinal malignancies and about one third of non-Hodgkin lymphomas. The most prominent histologies aremucosa-associated lymphoid tissue lymphoma and diffuselarge B-cell lymphoma. However, the gastrointestinaltract can be the site of rarer lymphoma subtypes as aprimary or secondary localization. Due to their rarity andthe multifaceted histology, an endoscopic classificationhas not been validated yet. This review aims to analyzethe endoscopic presentation of rare gastrointestinallymphomas from disease diagnosis to follow-up,according to the involved site and lymphoma subtype.Existing, new and emerging endoscopic technologieshave been examined. In particular, we investigated thediagnostic, prognostic and follow-up endoscopic featuresof T-cell and natural killer lymphomas, lymphomatouspolyposis and mantle cell lymphoma, follicular lymphoma,plasma cell related disease, gastrointestinal lymphomasin immunodeficiency and Hodgkin's lymphoma ofthe gastrointestinal tract. Contrarily to more frequentgastrointestinal lymphomas, data about rare lymphomasare mostly extracted from case series and casereports. Due to the data paucity, a synergism betweengastroenterologists and hematologists is required in order to better manage the disease. Indeed, clinicaland prognostic features are different from nodal andextranodal or the bone marrow (in case of plasma celldisease) counterpart. Therefore, the approach shouldbe based on the knowledge of the peculiar behavior andnatural history of disease.

  13. Human fetal liver stromal cells expressing erythropoietin promote hematopoietic development from human embryonic stem cells.

    Science.gov (United States)

    Yang, Chao; Ji, Lei; Yue, Wen; Shi, Shuang-Shuang; Wang, Ruo-Yong; Li, Yan-Hua; Xie, Xiao-Yan; Xi, Jia-Fei; He, Li-Juan; Nan, Xue; Pei, Xue-Tao

    2012-02-01

    Blood cells transfusion and hematopoietic stem cells (HSCs) transplantation are important methods for cell therapy. They are widely used in the treatment of incurable hematological disorder, infectious diseases, genetic diseases, and immunologic deficiency. However, their availability is limited by quantity, capacity of proliferation and the risk of blood transfusion complications. Recently, human embryonic stem cells (hESCs) have been shown to be an alternative resource for the generation of hematopoietic cells. In the current study, we describe a novel method for the efficient production of hematopoietic cells from hESCs. The stable human fetal liver stromal cell lines (hFLSCs) expressing erythropoietin (EPO) were established using the lentiviral system. We observed that the supernatant from the EPO transfected hFLSCs could induce the hESCs differentiation into hematopoietic cells, especially erythroid cells. They not only expressed fetal and embryonic globins but also expressed the adult-globin chain on further maturation. In addition, these hESCs-derived erythroid cells possess oxygen-transporting capacity, which indicated hESCs could generate terminally mature progenies. This should be useful for ultimately developing an animal-free culture system to generate large numbers of erythroid cells from hESCs and provide an experimental model to study early human erythropoiesis.

  14. Risk factors for gastrointestinal parasite infections of dogs living around protected areas of the Atlantic Forest: implications for human and wildlife health

    Directory of Open Access Journals (Sweden)

    N. H. A. Curi

    Full Text Available Abstract Despite the ubiquity of domestic dogs, their role as zoonotic reservoirs and the large number of studies concerning parasites in urban dogs, rural areas in Brazil, especially those at the wildlife-domestic animal-human interface, have received little attention from scientists and public health managers. This paper reports a cross-sectional epidemiological survey of gastrointestinal parasites of rural dogs living in farms around Atlantic Forest fragments. Through standard parasitological methods (flotation and sedimentation, 13 parasite taxa (11 helminths and two protozoans were found in feces samples from dogs. The most prevalent were the nematode Ancylostoma (47% followed by Toxocara (18% and Trichuris (8%. Other less prevalent (<2% parasites found were Capillaria, Ascaridia, Spirocerca, Taeniidae, Acantocephala, Ascaris, Dipylidium caninum, Toxascaris, and the protozoans Cystoisospora and Eimeria. Mixed infections were found in 36% of samples, mostly by Ancylostoma and Toxocara. Previous deworming had no association with infections, meaning that this preventive measure is being incorrectly performed by owners. Regarding risk factors, dogs younger than one year were more likely to be infected with Toxocara, and purebred dogs with Trichuris. The number of cats in the households was positively associated with Trichuris infection, while male dogs and low body scores were associated with mixed infections. The lack of associations with dog free-ranging behavior and access to forest or villages indicates that infections are mostly acquired around the households. The results highlight the risk of zoonotic and wildlife parasite infections from dogs and the need for monitoring and controlling parasites of domestic animals in human-wildlife interface areas.

  15. Cell phoney: human cloning after Quintavalle.

    Science.gov (United States)

    Morgan, Derek; Ford, Mary

    2004-12-01

    Reproductive cloning has thrown up new scientific possibilities, ethical conundrums, and legal challenges. An initial question, considered by the English courts in 2003, was whether the technique presently available, that of cell nucleus replacement, falls outside the provisions of the Human Fertilisation and Embryology Act 1990. If it does, the creation and use, including use in research protocols, of human embryos would be unregulated, disclosing a need to consider remedial legislation. The resolution by the courts of this legal question dramatically engages them in a resolution of fundamental ethical dilemmas, and discloses the possibilities and limitation of negotiating science policy through the processes of litigation.

  16. Elevation of serum interleukins 8, 4, and 1β levels in patients with gastrointestinal low-grade B-cell lymphoma.

    Science.gov (United States)

    Miyata-Takata, Tomoko; Takata, Katsuyoshi; Toji, Tomohiro; Goto, Naoe; Kasahara, Senji; Takahashi, Takeshi; Tari, Akira; Noujima-Harada, Mai; Miyata, Takafumi; Sato, Yasuharu; Yoshino, Tadashi

    2015-12-17

    Proinflammatory cytokines that are produced by helper T cells (Th) regulate immune reactions, facilitate class switching of B cells, and prolong the lifespan of B and T cells. Eradication therapy using antibiotics is sometimes effective against gastrointestinal (GI) malignant lymphoma, suggesting that the tumor development or progression is affected by the inflammatory microenvironment. In the present study, serum samples from 148 patients with various subtypes of malignant lymphoma were tested for 11 proinflammatory Th1/Th2 cytokines. In the comparison by subtype or GI lesions, serum interleukin (IL)-8 (P = 6.7E-05), IL-4 (P = 7.5E-05), and IL-1β (P = 0.0043) levels showed significant differences among subtypes, being particularly elevated in follicular lymphomas (FL) and mucosa-associated lymphoid tissue (MALT) lymphomas. Serum IL-8 levels were elevated in GI-FL and MALT lymphomas, and serum IL-4 and IL-1 β levels were elevated in MALT lymphomas. These findings show that GI low-grade B-cell lymphoma could develop against the background of an inflammatory microenvironment. Thus, these cytokines may be useful as diagnostic markers and could provide new insights into tumor development.

  17. Influenza and SARS-coronavirus activating proteases TMPRSS2 and HAT are expressed at multiple sites in human respiratory and gastrointestinal tracts.

    Directory of Open Access Journals (Sweden)

    Stephanie Bertram

    Full Text Available The type II transmembrane serine proteases TMPRSS2 and HAT activate influenza viruses and the SARS-coronavirus (TMPRSS2 in cell culture and may play an important role in viral spread and pathogenesis in the infected host. However, it is at present largely unclear to what extent these proteases are expressed in viral target cells in human tissues. Here, we show that both HAT and TMPRSS2 are coexpressed with 2,6-linked sialic acids, the major receptor determinant of human influenza viruses, throughout the human respiratory tract. Similarly, coexpression of ACE2, the SARS-coronavirus receptor, and TMPRSS2 was frequently found in the upper and lower aerodigestive tract, with the exception of the vocal folds, epiglottis and trachea. Finally, activation of influenza virus was conserved between human, avian and porcine TMPRSS2, suggesting that this protease might activate influenza virus in reservoir-, intermediate- and human hosts. In sum, our results show that TMPRSS2 and HAT are expressed by important influenza and SARS-coronavirus target cells and could thus support viral spread in the human host.

  18. Ubiquitin proteasome system research in gastrointestinal cancer.

    Science.gov (United States)

    Zhong, Jia-Ling; Huang, Chang-Zhi

    2016-02-15

    The ubiquitin proteasome system (UPS) is important for the degradation of proteins in eukaryotic cells. It is involved in nearly every cellular process and plays an important role in maintaining body homeostasis. An increasing body of evidence has linked alterations in the UPS to gastrointestinal malignancies, including esophageal, gastric and colorectal cancers. Here, we summarize the current literature detailing the involvement of the UPS in gastrointestinal cancer, highlighting its role in tumor occurrence and development, providing information for therapeutic targets research and anti-gastrointestinal tumor drug design.

  19. Interaction between Campylobacter and intestinal epithelial cells leads to a different proinflammatory response in human and porcine host.

    Science.gov (United States)

    Aguilar, Carmen; Jiménez-Marín, Ángeles; Martins, Rodrigo Prado; Garrido, Juan J

    2014-11-15

    Campylobacter jejuni and Campylobacter coli are recognized as the leading causes of human diarrheal disease throughout the development world. Unlike human beings, gastrointestinal tract of pigs are frequently colonized by Campylobacter to a high level in a commensal manner. The aim of this study was to identify the differences underlying the divergent outcome following Campylobacter challenge in porcine versus human host. In order to address this, a comparative in vitro infection model was combined with microscopy, gentamicin protection assay, ELISA and quantitative PCR techniques. Invasion assays revealed that Campylobacter invaded human cells up to 10-fold more than porcine cells (pCampylobacter in human epithelial cell at early times of infection, whereas a very reduced cytokine gene expression was detected in porcine epithelial cells. These data indicate that Campylobacter fails to invade porcine cells compared to human cells, and this leads to a lack of proinflammatory response induction, probably due to its pathogenic or commensal behavior in human and porcine host, respectively. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Lymphoid Cell-Glioma Cell Interaction Enhances Cell Coat Production by Human Gliomas: Novel Suppressor Mechanism

    Science.gov (United States)

    Dick, Steven J.; Macchi, Beatrice; Papazoglou, Savvas; Oldfield, Edward H.; Kornblith, Paul L.; Smith, Barry H.; Gately, Maurice K.

    1983-05-01

    Certain human glioma lines produce mucopolysaccharide coats that impair the generation of cytolytic lymphocytes in response to these lines in vitro. Coat production is substantially enhanced by the interaction of glioma cells with a macromolecular factor released by human peripheral blood mononuclear cells in culture. This interaction thus constitutes an unusual mechanism by which inflammatory cells may nonspecifically suppress the cellular immune response to at least one class of solid tumors in humans.

  1. Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells.

    Directory of Open Access Journals (Sweden)

    Leonardo D'Aiuto

    Full Text Available Human cytomegalovirus (HCMV infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs, neural progenitor cells (NPCs and neurons suggests that (i iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii Neural stem cells have impaired differentiation when infected by HCMV; (iii NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv most iPS-derived neurons are not permissive to HCMV infection; and (v infected neurons have impaired calcium influx in response to glutamate.

  2. Human somatic cell nuclear transfer and cloning.

    Science.gov (United States)

    2012-10-01

    This document presents arguments that conclude that it is unethical to use somatic cell nuclear transfer (SCNT) for infertility treatment due to concerns about safety; the unknown impact of SCNT on children, families, and society; and the availability of other ethically acceptable means of assisted reproduction. This document replaces the ASRM Ethics Committee report titled, "Human somatic cell nuclear transfer (cloning)," last published in Fertil Steril 2000;74:873-6. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  3. Identification and Phylogeny of the First T Cell Epitope Identified from a Human Gut Bacteroides Species.

    Directory of Open Access Journals (Sweden)

    Maria Elisa Perez-Muñoz

    Full Text Available Host T cell reactivity toward gut bacterial epitopes has been recognized as part of disease pathogenesis. However, the specificity of T cells that recognize this vast number of epitopes has not yet been well described. After colonizing a C57BL/6J germ-free mouse with the human gut symbiotic bacteria Bacteroides thetaiotaomicron, we isolated a T cell that recognized these bacteria in vitro. Using this T cell, we mapped the first known non-carbohydrate T cell epitope within the phylum Bacteroidetes. The T cell also reacted to two other additional Bacteroides species. We identified the peptide that stimulated the T cell by using a genetic approach. Genomic data from the epitope-positive and epitope-negative bacteria explain the cross-reactivity of the T cell to multiple species. This epitope degeneracy should shape our understanding of the T cell repertoire stimulated by the complex microbiome residing in the gastrointestinal tract in both healthy and disease states.

  4. Dopamine receptor repertoire of human granulosa cells

    Directory of Open Access Journals (Sweden)

    Kunz Lars

    2007-10-01

    Full Text Available Abstract Background High levels of dopamine (DA were described in human ovary and recently evidence for DA receptors in granulosa and luteal cells has been provided, as well. However, neither the full repertoire of ovarian receptors for DA, nor their specific role, is established. Human granulosa cells (GCs derived from women undergoing in vitro fertilization (IVF are an adequate model for endocrine cells of the follicle and the corpus luteum and were therefore employed in an attempt to decipher their DA receptor repertoire and functionality. Methods Cells were obtained from patients undergoing IVF and examined using cDNA-array, RT-PCR, Western blotting and immunocytochemistry. In addition, calcium measurements (with FLUO-4 were employed. Expression of two DA receptors was also examined by in-situ hybridization in rat ovary. Effects of DA on cell viability and cell volume were studied by using an ATP assay and an electronic cell counter system. Results We found members of the two DA receptor families (D1- and D2 -like associated with different signaling pathways in human GCs, namely D1 (as expected and D5 (both are Gs coupled and linked to cAMP increase and D2, D4 (Gi/Gq coupled and linked to IP3/DAG. D3 was not found. The presence of the trophic hormone hCG (10 IU/ml in the culture medium for several days did not alter mRNA (semiquantitative RT-PCR or protein levels (immunocytochemistry/Western blotting of D1,2,4,5 DA receptors. Expression of prototype receptors for the two families, D1 and D2, was furthermore shown in rat granulosa and luteal cells by in situ hybridization. Among the DA receptors found in human GCs, D2 expression was marked both at mRNA and protein levels and it was therefore further studied. Results of additional RT-PCR and Western blots showed two splice variants (D2L, D2S. Irrespective of these variants, D2 proved to be functional, as DA raised intracellular calcium levels. This calcium mobilizing effect of DA was observed

  5. New insights into gastrointestinal anthrax infection.

    Science.gov (United States)

    Owen, Jennifer L; Yang, Tao; Mohamadzadeh, Mansour

    2015-03-01

    Bacterial infections are the primary cause of gastrointestinal (GI) disorders in both developing and developed countries, and are particularly dangerous for infants and children. Bacillus anthracis is the 'archetype zoonotic' pathogen; no other infectious disease affects such a broad range of species, including humans. Importantly, there are more case reports of GI anthrax infection in children than inhalational disease. Early diagnosis is difficult and widespread systemic disease develops rapidly. This review highlights new findings concerning the roles of the gut epithelia, commensal microbiota, and innate lymphoid cells (ILCs) in initiation of disease and systemic dissemination in animal models of GI anthrax, the understanding of which is crucial to designing alternative therapies that target the establishment of infection.

  6. TALEN-Induced Translocations in Human Cells.

    Science.gov (United States)

    Piganeau, Marion; Renouf, Benjamin; Ghezraoui, Hind; Brunet, Erika

    2016-01-01

    Induction of chromosomal translocations in human cells is of a great interest to study tumorigenesis and genome instability. Here, we explain in detail a method to induce translocations using the transcription activator-like effector nucleases (TALENs). We describe how to detect translocation formation by PCR, calculate translocation frequency by 96-well PCR screen, and analyze breakpoint junctions. When inducing cancer translocations, it is also possible to detect the fusion gene by FISH analysis or western blot.

  7. Acute stress modulates the histamine content of mast cells in the gastrointestinal tract through interleukin-1 and corticotropin-releasing factor release in rats.

    Science.gov (United States)

    Eutamene, Helene; Theodorou, Vassilia; Fioramonti, Jean; Bueno, Lionel

    2003-12-15

    Stress results in activation of the hypothalamic pituitary adrenal axis and affects illnesses such as neuroinflammatory syndrome. In vivo acute stress (restraint stress) induces gastrointestinal function disturbances through colonic mast cell activation. This study investigated the effect of acute stress in histamine content of colonic mast cells, and the central role of interleukin-1 (IL-1) and corticotropin-releasing factor (CRF) in this effect. After a restraint stress session colonic segments were isolated and submitted to three protocols: (i) determination of histamine levels by radioimmunoassay (RIA) after incubation with 48/80 compound, (ii) evaluation by histology of mucosal mast cell (MMC) number and (iii) determination of histamine immunoreactivity of MMC. These procedures were conducted (1) in sham or stressed rats, (2) in stressed rats previously treated with intracerebroventricular (I.C.V.) IL-1ra or alpha-helical CRF9-41, (3) in naive rats pretreated with I.C.V. rhIL-1beta or CRF and (4) in rats treated with central IL-1beta and CRF plus alpha-helical CRF and IL-1ra, respectively (cross-antagonism reaction). Acute stress increases histamine content in colonic mast cells, without degranulation. I.C.V. pretreatment with IL-1ra or alpha-helical CRF9-41 blocked stress-induced mast cell histamine content increase. Both I.C.V. rhIL-1beta and CRF injections reproduced the stress-linked changes. I.C.V. treatment with CRF antagonist blocked I.C.V. rhIL-1beta-induced mast cell histamine content increase, whereas central IL-1ra did not affect stress events induced by I.C.V. CRF administration. These results suggest that in rats acute stress increases colonic mast cell histamine content. This effect is mediated by the release in cascade in the brain first of IL-1 and secondly of CRF.

  8. PKCθ activation in pancreatic acinar cells by gastrointestinal hormones/neurotransmitters and growth factors is needed for stimulation of numerous important cellular signaling cascades

    Science.gov (United States)

    Sancho, Veronica; Berna, Marc J.; Thill, Michelle; Jensen, R. T.

    2011-01-01

    The novel PKCθ isoform is highly expressed in T-cells, brain and skeletal muscle and originally thought to have a restricted distribution. It has been extensively studied in T-cells and shown to be important for apoptosis, T-cell activation and proliferation. Recent studies showed its presence in other tissues and importance in insulin signaling, lung surfactant secretion, intestinal barrier permeability, platelet and mast-cell functions. However, little information is available for PKCθ activation by gastrointestinal(GI) hormones/neurotransmitters and growth factors. In the present study we used rat pancreatic acinar cells to explore their ability to activate PKCθ and the possible interactions with important cellular mediators of their actions. Particular attention was paid to cholecystokinin(CCK), a physiological regulator of pancreatic function and important in pathological processes affecting acinar function, like pancreatitis. PKCθ-protein/mRNA were present in the pancreatic acini, and T538-PKCθ phosphorylation/activation was stimulated only by hormones/neurotransmitters activating phospholipase C. PKCθ was activated in time- and dose-related manner by CCK, mediated 30% by high-affinity CCKA-receptor activation. CCK stimulated PKCθ translocation from cytosol to membrane. PKCθ inhibition (by pseudostrate-inhibitor or dominant negative) inhibited CCK- and TPA-stimulation of PKD, Src, RafC, PYK2, p125FAK and IKKα/β, but not basal/stimulated enzyme secretion. Also CCK- and TPA-induced PKCθ activation produced an increment in PKCθ’s direct association with AKT, RafA, RafC and Lyn. These results show for the first time PKCθ presence in pancreatic acinar cells, its activation by some GI hormones/neurotransmitters and involvement in important cell signaling pathways mediating physiological responses (enzyme secretion, proliferation, apoptosis, cytokine expression, and pathological responses like pancreatitis and cancer growth). PMID:21810446

  9. The core regulatory network in human cells.

    Science.gov (United States)

    Kim, Man-Sun; Kim, Dongsan; Kang, Nam Sook; Kim, Jeong-Rae

    2017-03-04

    In order to discover the common characteristics of various cell types in the human body, many researches have been conducted to find the set of genes commonly expressed in various cell types and tissues. However, the functional characteristics of a cell is determined by the complex regulatory relationships among the genes rather than by expressed genes themselves. Therefore, it is more important to identify and analyze a core regulatory network where all regulatory relationship between genes are active across all cell types to uncover the common features of various cell types. Here, based on hundreds of tissue-specific gene regulatory networks constructed by recent genome-wide experimental data, we constructed the core regulatory network. Interestingly, we found that the core regulatory network is organized by simple cascade and has few complex regulations such as feedback or feed-forward loops. Moreover, we discovered that the regulatory links from genes in the core regulatory network to genes in the peripheral regulatory network are much more abundant than the reverse direction links. These results suggest that the core regulatory network locates at the top of regulatory network and plays a role as a 'hub' in terms of information flow, and the information that is common to all cells can be modified to achieve the tissue-specific characteristics through various types of feedback and feed-forward loops in the peripheral regulatory networks. We also found that the genes in the core regulatory network are evolutionary conserved, essential and non-disease, non-druggable genes compared to the peripheral genes. Overall, our study provides an insight into how all human cells share a common function and generate tissue-specific functional traits by transmitting and processing information through regulatory network.

  10. Secreted human adipose leptin decreases mitochondrial respiration in HCT116 colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Einav Yehuda-Shnaidman

    Full Text Available Obesity is a key risk factor for the development of colon cancer; however, the endocrine/paracrine/metabolic networks mediating this connection are poorly understood. Here we hypothesize that obesity results in secreted products from adipose tissue that induce malignancy-related metabolic alterations in colon cancer cells. Human HCT116 colon cancer cells, were exposed to conditioned media from cultured human adipose tissue fragments of obese vs. non-obese subjects. Oxygen consumption rate (OCR, mostly mitochondrial respiration and extracellular acidification rate (ECAR, mostly lactate production via glycolysis were examined vis-à-vis cell viability and expression of related genes and proteins. Our results show that conditioned media from obese (vs. non-obese subjects decreased basal (40%, p<0.05 and maximal (50%, p<0.05 OCR and gene expression of mitochondrial proteins and Bax without affecting cell viability or expression of glycolytic enzymes. Similar changes could be recapitulated by incubating cells with leptin, whereas, leptin-receptor specific antagonist inhibited the reduced OCR induced by conditioned media from obese subjects. We conclude that secreted products from the adipose tissue of obese subjects inhibit mitochondrial respiration and function in HCT116 colon cancer cells, an effect that is at least partly mediated by leptin. These results highlight a putative novel mechanism for obesity-associated risk of gastrointestinal malignancies, and suggest potential new therapeutic avenues.

  11. Myricitrin Inhibits Acrylamide-Mediated Cytotoxicity in Human Caco-2 Cells by Preventing Oxidative Stress

    Science.gov (United States)

    Chen, Wei; Feng, Lina; Shen, Yang; Su, Hongming; Li, Ya; Zhuang, Jingjing; Zhang, Lingxia; Zheng, Xiaodong

    2013-01-01

    Oxidative stress was thought to be associated with acrylamide cytotoxicity, but the link between oxidative stress and acrylamide cytotoxicity in the gastrointestinal tract, the primary organ in contact with dietary acrylamide, is still unclear. This study was conducted to evaluate the antioxidant activity of natural dietary compound myricitrin and its protective role against acrylamide cytotoxicity. We found that myricitrin can effectively scavenge multiple free radicals (including DPPH free radical, hydroxyl radical, and ABTS free radical) in a concentration-dependent manner. Our results further indicated that the presence of myricitrin (2.5–10 μg/mL) was found to significantly inhibit acrylamide-induced cytotoxicity in human gastrointestinal Caco-2 cells. Moreover, acrylamide-induced cytotoxicity is closely related to oxidative stress in Caco-2 cells. Interestingly, myricitrin was able to suppress acrylamide toxicity by inhibiting ROS generation. Taken together, these results demonstrate that myricitrin had a profound antioxidant effect and can protect against acrylamide-mediated cytotoxicity. PMID:24224177

  12. Cell Culture Assay for Human Noroviruses [response

    Energy Technology Data Exchange (ETDEWEB)

    Straub, Tim M.; Honer Zu Bentrup, Kerstin; Orosz Coghlan, Patricia; Dohnalkova, Alice; Mayer, Brooke K.; Bartholomew, Rachel A.; Valdez, Catherine O.; Bruckner-Lea, Cindy J.; Gerba, Charles P.; Abbaszadegan, Morteza A.; Nickerson, Cheryl A.

    2007-07-01

    We appreciate the comments provided by Leung et al., in response to our recently published article “In Vitro Cell Culture Infectivity Assay for Human Noroviruses” by Straub et al. (1). The specific aim of our project was to develop an in vitro cell culture infectivity assay for human noroviruses (hNoV) to enhance risk assessments when they are detected in water supplies. Reverse transcription (RT) qualitative or quantitative PCR are the primary assays for waterborne NoV monitoring. However, these assays cannot distinguish between infectious vs. non-infectious virions. When hNoV is detected in water supplies, information provided by our infectivity assay will significantly improve risk assessment models and protect human health, regardless of whether we are propagating NoV. Indeed, in vitro cell culture infectivity assays for the waterborne pathogen Cryptosporidium parvum that supplement approved fluorescent microscopy assays, do not result in amplification of the environmentally resistant hard-walled oocysts (2). However, identification of life cycle stages in cell culture provides evidence of infectious oocysts in a water supply. Nonetheless, Leung et al.’s assertion regarding the suitability of our method for the in vitro propagation of high titers of NoV is valid for the medical research community. In this case, well-characterized challenge pools of virus would be useful for developing and testing diagnostics, therapeutics, and vaccines. As further validation of our published findings, we have now optimized RT quantitative PCR to assess the level of viral production in cell culture, where we are indeed finding significant increases in viral titer. The magnitude and time course of these increases is dependent on both virus strain and multiplicity of infection. We are currently preparing a manuscript that will discuss these findings in greater detail, and the implications this may have for creating viral challenge pools

  13. Preliminary study on human fibroblasts as feeder layer for human embryonic stem cells culture in vitro

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    To avoid the direct contact with mouse cells and possible heterogeneous pathogen in future application, we need to replace mouse embryonic fibroblastswith human fibroblasts as the feeder layer to maintain human embryonic stem cells growth in the undifferentiated state. We successfully use human fibroblasts derived from aborted fetus and adult prepuce as feeder layer to maintain human embryonic stem cells growth. During the passage and growth on this feeder layer, the human embryonic stem cells can keep their undifferentiated state.

  14. Transcriptome analysis of the human T lymphocyte cell line Jurkat and human peripheral blood mononuclear cells exposed to deoxynivalenol (DON): New mechanistic insights

    Energy Technology Data Exchange (ETDEWEB)

    Katika, Madhumohan R. [RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Wageningen (Netherlands); Department of Health Risk Analysis and Toxicology, Maastricht University (Netherlands); Netherlands Toxicogenomics Centre (Netherlands); Hendriksen, Peter J.M. [RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Wageningen (Netherlands); Netherlands Toxicogenomics Centre (Netherlands); Shao, Jia [RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Wageningen (Netherlands); Department of Health Risk Analysis and Toxicology, Maastricht University (Netherlands); Netherlands Toxicogenomics Centre (Netherlands); Loveren, Henk van [Department of Health Risk Analysis and Toxicology, Maastricht University (Netherlands); National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Netherlands Toxicogenomics Centre (Netherlands); Peijnenburg, Ad, E-mail: ad.peijnenburg@wur.nl [RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Wageningen (Netherlands); Netherlands Toxicogenomics Centre (Netherlands)

    2012-10-01

    Deoxynivalenol (DON) or vomitoxin is a commonly encountered type-B trichothecene mycotoxin, produced by Fusarium species predominantly found in cereals and grains. DON is known to exert toxic effects on the gastrointestinal, reproductive and neuroendocrine systems, and particularly on the immune system. Depending on dose and exposure time, it can either stimulate or suppress immune function. The main objective of this study was to obtain a deeper insight into DON-induced effects on lymphoid cells. For this, we exposed the human T-lymphocyte cell line Jurkat and human peripheral blood mononuclear cells (PBMCs) to various concentrations of DON for various times and examined gene expression changes by DNA microarray analysis. Jurkat cells were exposed to 0.25 and 0.5 μM DON for 3, 6 and 24 h. Biological interpretation of the microarray data indicated that DON affects various processes in these cells: It upregulates genes involved in ribosome structure and function, RNA/protein synthesis and processing, endoplasmic reticulum (ER) stress, calcium-mediated signaling, mitochondrial function, oxidative stress, the NFAT and NF-κB/TNF-α pathways, T cell activation and apoptosis. The effects of DON on the expression of genes involved in ER stress, NFAT activation and apoptosis were confirmed by qRT-PCR. Other biochemical experiments confirmed that DON activates calcium-dependent proteins such as calcineurin and M-calpain that are known to be involved in T cell activation and apoptosis. Induction of T cell activation was also confirmed by demonstrating that DON activates NFATC1 and induces its translocation from the cytoplasm to the nucleus. For the gene expression profiling of PBMCs, cells were exposed to 2 and 4 μM DON for 6 and 24 h. Comparison of the Jurkat microarray data with those obtained with PBMCs showed that most of the processes affected by DON in the Jurkat cell line were also affected in the PBMCs. -- Highlights: ► The human T cell line Jurkat and human

  15. Primitive cardiac cells from human embryonic stem cells.

    Science.gov (United States)

    Hudson, James; Titmarsh, Drew; Hidalgo, Alejandro; Wolvetang, Ernst; Cooper-White, Justin

    2012-06-10

    Pluripotent stem cell-derived cardiomyocytes are currently being investigated for in vitro human heart models and as potential therapeutics for heart failure. In this study, we have developed a differentiation protocol that minimizes the need for specific human embryonic stem cell (hESC) line optimization. We first reduced the heterogeneity that exists within the starting population of bulk cultured hESCs by using cells adapted to single-cell passaging in a 2-dimensional (2D) culture format. Compared with bulk cultures, single-cell cultures comprised larger fractions of TG30(hi)/OCT4(hi) cells, corresponding to an increased expression of pluripotency markers OCT4 and NANOG, and reduced expression of early lineage-specific markers. A 2D temporal differentiation protocol was then developed, aimed at reducing the inherent heterogeneity and variability of embryoid body-based protocols, with induction of primitive streak cells using bone morphogenetic protein 4 and activin A, followed by cardiogenesis via inhibition of Wnt signaling using the small molecules IWP-4 or IWR-1. IWP-4 treatment resulted in a large percentage of cells expressing low amounts of cardiac myosin heavy chain and expression of early cardiac progenitor markers ISL1 and NKX2-5, thus indicating the production of large numbers of immature cardiomyocytes (~65,000/cm(2) or ~1.5 per input hESC). This protocol was shown to be effective in HES3, H9, and, to a lesser, extent, MEL1 hESC lines. In addition, we observed that IWR-1 induced predominantly atrial myosin light chain (MLC2a) expression, whereas IWP-4 induced expression of both atrial (MLC2a) and ventricular (MLC2v) forms. The intrinsic flexibility and scalability of this 2D protocol mean that the output population of primitive cardiomyocytes will be particularly accessible and useful for the investigation of molecular mechanisms driving terminal cardiomyocyte differentiation, and potentially for the future treatment of heart failure.

  16. Mast cell expression of the serotonin1A receptor in guinea pig and human intestine.

    Science.gov (United States)

    Wang, Guo-Du; Wang, Xi-Yu; Zou, Fei; Qu, Meihua; Liu, Sumei; Fei, Guijun; Xia, Yun; Needleman, Bradley J; Mikami, Dean J; Wood, Jackie D

    2013-05-15

    Serotonin [5-hydroxytryptamine (5-HT)] is released from enterochromaffin cells in the mucosa of the small intestine. We tested a hypothesis that elevation of 5-HT in the environment of enteric mast cells might degranulate the mast cells and release mediators that become paracrine signals to the enteric nervous system, spinal afferents, and secretory glands. Western blotting, immunofluorescence, ELISA, and pharmacological analysis were used to study expression of 5-HT receptors by mast cells in the small intestine and action of 5-HT to degranulate the mast cells and release histamine in guinea pig small intestine and segments of human jejunum discarded during Roux-en-Y gastric bypass surgeries. Mast cells in human and guinea pig preparations expressed the 5-HT1A receptor. ELISA detected spontaneous release of histamine in guinea pig and human preparations. The selective 5-HT1A receptor agonist 8-hydroxy-PIPAT evoked release of histamine. A selective 5-HT1A receptor antagonist, WAY-100135, suppressed stimulation of histamine release by 5-HT or 8-hydroxy-PIPAT. Mast cell-stabilizing drugs, doxantrazole and cromolyn sodium, suppressed the release of histamine evoked by 5-HT or 8-hydroxy-PIPAT in guinea pig and human preparations. Our results support the hypothesis that serotonergic degranulation of enteric mast cells and release of preformed mediators, including histamine, are mediated by the 5-HT1A serotonergic receptor. Association of 5-HT with the pathophysiology of functional gastrointestinal disorders (e.g., irritable bowel syndrome) underlies a question of whether selective 5-HT1A receptor antagonists might have therapeutic application in disorders of this nature.

  17. 树突细胞肿瘤疫苗用于治疗胃肠管恶性肿瘤的研究进展%Research progress of dendritic cells based cancer vaccines against gastrointestinal cancers

    Institute of Scientific and Technical Information of China (English)

    胡健卫; 牛伟新

    2008-01-01

    胃肠管恶性肿瘤是人类最常见的恶性肿瘤.在目前以手术切除为主的综合治疗中,传统放、化疗由于其治疗模式的非特异性特点,常难以达到理想的结果.树突状细胞(dendritic cell,DC)肿瘤疫苗作为近年来兴起的一个免疫治疗新方法,被越来越多地应用到临床试验中,在用于治疗胃肠管恶性肿瘤中也取得了一些效果.虽然目前疫苗的设计尚无公认的标准,且其免疫学效果和临床预后也未能取得正相关的联系,但对DC免疫机制的深入了解和相应新方法的研究有可能在治疗恶性肿瘤方面发挥更大的作用.%Gastrointestinal cancers are the most common types of malignant tumors in Human Beings.The main treatment remains surgery resection,in addition to which,adjunctive therapies are far not satisfactory for the target of which are not specific.Dendritic cells cancer vaccine is one of the most promising immunotherapy ways developed in the decades and some results have showed that the vaccines may help in the treatment of gastrointestinal cancers.Till now,there is no recognized standard in the design of the vaccine and no positive correlations between the immunologic effect and clinical prognosis are showed,but we believe that with the further research in the immunological mechanism and the use of new designed methods,dendritic cells cancer vaccines will play a greater role in the treatment of malignant tumors.

  18. Appearance of Human Plasma Cells Following Differentiation of Human B Cells in NOD/SCID Mouse Spleen

    OpenAIRE

    2003-01-01

    Relatively little is known for the differentiation and maturation process of human B cells to plasma cells. This is particularly important in reconstitution work involving transfer of autoantibodies. To address this issue, we transplanted human peripheral blood mononuclear cells (PBMC) directly into the spleen of irradiated NOD/SCID mice depleted of natural killer cell activity. Within 6 weeks, naïve B cells differentiated into memory B cells and, importantly, the numbers of human CD138+ plas...

  19. Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

    Directory of Open Access Journals (Sweden)

    Hayato Fukusumi

    2016-01-01

    Full Text Available Human neural progenitor cells (hNPCs have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi. Our results showed that expandable hNPCs could be generated from hiPSC clones with diverse somatic tissue origins. The established hNPCs exhibited a mid/hindbrain-type neural identity and uniform expression of neural progenitor genes.

  20. Effect of the gastrointestinal environment on pH homeostasis of Lactobacillus plantarum and Lactobacillus brevis cells as measured by real-time fluorescence ratio-imaging microscopy.

    Science.gov (United States)

    Ramos, Cíntia Lacerda; Thorsen, Line; Ryssel, Mia; Nielsen, Dennis S; Siegumfeldt, Henrik; Schwan, Rosane Freitas; Jespersen, Lene

    2014-04-01

    In the present work, an in vitro model of the gastrointestinal tract (GIT) was developed to obtain real-time observations of the pH homeostasis of single cells of probiotic Lactobacillus spp. strains as a measure of their physiological state. Changes in the intracellular pH (pHi) were determined using fluorescence ratio imaging microscopy (FRIM) for potential probiotic strains of Lactobacillus plantarum UFLA CH3 and Lactobacillus brevis UFLA FFC199. Heterogeneous populations were observed, with pHi values ranging from 6.5 to 7.5, 3.5 to 5.6 and 6.5 to 8.0 or higher during passage of saliva (pH 6.4), gastric (pH 3.5) and intestinal juices (pH 6.4), respectively. When nutrients were added to gastric juice, the isolate L. brevis significantly decreased its pH(i) closer to the extracellular pH (pH(ex)) than in gastric juice without nutrients. This was not the case for L. plantarum. This study is the first to produce an in vitro GIT model enabling real-time monitoring of pH homeostasis of single cells in response to the wide range of pH(ex) of the GIT. Furthermore, it was possible to observe the heterogeneous response of single cells. The technique can be used to determine the survival and physiological conditions of potential probiotics and other microorganisms during passage through the GIT.

  1. Human microglial cells synthesize albumin in brain.

    Directory of Open Access Journals (Sweden)

    Sung-Min Ahn

    Full Text Available Albumin, an abundant plasma protein with multifunctional properties, is mainly synthesized in the liver. Albumin has been implicated in Alzheimer's disease (AD since it can bind to and transport amyloid beta (Abeta, the causative agent of AD; albumin is also a potent inhibitor of Abeta polymerization. Despite evidence of non-hepatic transcription of albumin in many tissues including kidney and pancreas, non-hepatic synthesis of albumin at the protein level has been rarely confirmed. In a pilot phase study of Human Brain Proteome Project, we found evidence that microglial cells in brain may synthesize albumin. Here we report, for the first time, the de novo synthesis of albumin in human microglial cells in brain. Furthermore, we demonstrate that the synthesis and secretion of albumin from microglial cells is enhanced upon microglial activation by Abeta(1-42- or lipopolysaccharide (LPS-treatment. These data indicate that microglial cells may play a beneficial role in AD by secreting albumin that not only inhibits Abeta polymerization but also increases its clearance.

  2. Neocortical glial cell numbers in human brains

    DEFF Research Database (Denmark)

    Pelvig, D.P.; Pakkenberg, H.; Stark, A.K.

    2008-01-01

    and neurons and counting were done in each of the four lobes. The study showed that the different subpopulations of glial cells behave differently as a function of age; the number of oligodendrocytes showed a significant 27% decrease over adult life and a strong correlation to the total number of neurons...... while the total astrocyte number is constant through life; finally males have a 28% higher number of neocortical glial cells and a 19% higher neocortical neuron number than females. The overall total number of neocortical neurons and glial cells was 49.3 billion in females and 65.2 billion in males......, a difference of 24% with a high biological variance. These numbers can serve as reference values in quantitative studies of the human neocortex. (C) 2007 Elsevier Inc. All rights reserved Udgivelsesdato: 2008/11...

  3. Characterizing motility dynamics in human RPE cells

    Science.gov (United States)

    Liu, Zhuolin; Kurokawa, Kazuhiro; Zhang, Furu; Miller, Donald T.

    2017-02-01

    Retinal pigment epithelium (RPE) cells are vital to health of the outer retina, however, are often compromised in ageing and ocular diseases that lead to blindness. Early manifestation of RPE disruption occurs at the cellular level, but while in vivo biomarkers at this scale hold considerable promise, RPE cells have proven extremely challenging to image in the living human eye. Recently we addressed this problem by using organelle motility as a novel contrast agent to enhance the RPE cell in conjunction with 3D resolution of adaptive optics-optical coherence tomography (AO-OCT) to section the RPE layer. In this study, we expand on the central novelty of our method - organelle motility - by characterizing the dynamics of the motility in individual RPE cells, important because of its direct link to RPE physiology. To do this, AO-OCT videos of the same retinal patch were acquired at approximately 1 min intervals or less, time stamped, and registered in 3D with sub-cellular accuracy. Motility was quantified by an exponential decay time constant, the time for motility to decorrelate the speckle field across an RPE cell. In two normal subjects, we found the decay time constant to be just 3 seconds, thus indicating rapid motility in normal RPE cells.

  4. Human cell culture in a space bioreactor

    Science.gov (United States)

    Morrison, Dennis R.

    1988-01-01

    Microgravity offers new ways of handling fluids, gases, and growing mammalian cells in efficient suspension cultures. In 1976 bioreactor engineers designed a system using a cylindrical reactor vessel in which the cells and medium are slowly mixed. The reaction chamber is interchangeable and can be used for several types of cell cultures. NASA has methodically developed unique suspension type cell and recovery apparatus culture systems for bioprocess technology experiments and production of biological products in microgravity. The first Space Bioreactor was designed for microprocessor control, no gaseous headspace, circulation and resupply of culture medium, and slow mixing in very low shear regimes. Various ground based bioreactors are being used to test reactor vessel design, on-line sensors, effects of shear, nutrient supply, and waste removal from continuous culture of human cells attached to microcarriers. The small Bioreactor is being constructed for flight experiments in the Shuttle Middeck to verify systems operation under microgravity conditions and to measure the efficiencies of mass transport, gas transfer, oxygen consumption and control of low shear stress on cells.

  5. Frequent detection of human adenovirus from the lower gastrointestinal tract in men who have sex with men.

    Directory of Open Access Journals (Sweden)

    Marcel E Curlin

    Full Text Available BACKGROUND: The association between baseline seropositivity to human adenovirus (HAdV type 5 and increased HIV acquisition in the Step HIV Vaccine Study has raised questions concerning frequency of acquired and/or persistent Adenovirus infections among adults at high risk of HIV-1 infection. METHODOLOGY: To evaluate the frequency and pattern of HAdV shedding from the lower GI tract, we retrospectively tested rectal swabs for HAdVs in a cohort of 20 HSV-2 positive HIV-positive Peruvian men who have sex with men (MSM undergoing rectal swabbing three times/week for 18 consecutive weeks, in a prospective study of HSV-2 suppression in HIV infection. Viral DNA was extracted and amplified using a sensitive multiplex PCR assay that detects all currently recognized HAdV types. Molecular typing of viruses was performed on selected samples by hexon gene sequencing. Baseline neutralizing antibody titers to HAdVs -5, -26, -35 and -48 were also assessed. PRINCIPAL FINDINGS: 15/20 individuals had HAdV detected during follow up. The median frequency of HAdV detection was 30% of samples (range 2.0% to 64.7%. HAdV shedding typically occurred on consecutive days in clustered episodes lasting a median of 4 days (range 1 to 9 days separated by periods without shedding, suggesting frequent new infections or reactivation of latent infections over time. 8 of the 15 shedders had more than one type detected in follow-up. 20 HAdV types from species B, C, and D were identified, including HAdV-5, -26 and -48, HAdV types under development as potential vaccine candidates. 14/20 subjects were seropositive for HAdV-5; 15/20 for HAdV-26; 3/20 for HAdV-35; and 2/20 for HAdV-48. HAdV shedding did not correlate with CD4 count, plasma HIV-1 viral load, or titers to HAdV-5 or HAdV-35. The sole individual with HAdV-5 shedding was HAdV-5 seropositive. CONCLUSIONS: HAdV shedding was highly prevalent and diverse, including types presently under consideration as HIV vaccine vectors

  6. Estrogen and its role in gastrointestinal health and disease.

    LENUS (Irish Health Repository)

    Hogan, Aisling M

    2012-02-01

    INTRODUCTION: While the concept of a role of estrogen in gastrointestinal (in particular, colonic) malignancy has generated excitement in recent years, no review has examined the role of this potent and omnipresent steroid hormone in physiological states or its contribution to the development of benign pathological processes. Understanding these effects (and mechanisms therein) may provide a platform for a deeper understanding of more complex disease processes. METHODS: A literature search was conducted using the PubMed database and the search terms were "estrogen," "estrogen AND gastrointestinal tract," "estrogen AND colon," "estrogen AND esophagus," "estrogen AND small intestine," "estrogen AND stomach," "estrogen AND gallbladder," and "estrogen AND motility." Bibliographies of extracted studies were further cross-referenced. In all, 136 full-text articles were selected for review. A logical organ-based approach was taken to enable extraction of data of clinical relevance and meaningful interpretation thereof. Insight is provided into the hypotheses, theories, controversies, and contradictions generated over the last five decades by extensive investigation of estrogen in human, animal, and cell models using techniques as diverse as autoradiographic studies of baboons to human population analysis. CONCLUSIONS: Effects from esophagus through to the colon and rectum are summarized in this first concise collection of data pertaining to estrogenic actions in gastrointestinal health and disease. Mechanisms of these actions are discussed where possible. Undoubtedly, this hormone exerts many actions yet to be elucidated, and its potential therapeutic applications remain, as yet, largely unexplored.

  7. Appearance of Human Plasma Cells Following Differentiation of Human B Cells in NOD/SCID Mouse Spleen

    Directory of Open Access Journals (Sweden)

    Kentaro Kikuchi

    2003-01-01

    Full Text Available Relatively little is known for the differentiation and maturation process of human B cells to plasma cells. This is particularly important in reconstitution work involving transfer of autoantibodies. To address this issue, we transplanted human peripheral blood mononuclear cells (PBMC directly into the spleen of irradiated NOD/SCID mice depleted of natural killer cell activity. Within 6 weeks, naïve B cells differentiated into memory B cells and, importantly, the numbers of human CD138+ plasma cells in spleen increased by 100 fold after transplantation. Plasma cell numbers correlated with the detection of human IgM and IgG in serum, indicating that human B cells had differentiated into mature plasma cells in the murine spleen. In addition to CD19+ plasma cells, a distinct CD19- plasma cell population was detected, suggesting that downregulation of CD19 associated with maturation of plasma cells occurred. When purified human B cells were transplanted, those findings were not observed. Our results indicate that differentiation and maturation of human B cells and plasma cells can be investigated by transplantation of human PBMC into the spleen of NOD/SCID mice. The model will be useful for studying the differentiation of human B cells and generation of plasma cells.

  8. Upper gastrointestinal physiology and diseases.

    Science.gov (United States)

    Waldum, Helge L; Kleveland, Per M; Fossmark, Reidar

    2015-06-01

    Nordic research on physiology and pathophysiology of the upper gastrointestinal tract has flourished during the last 50 years. Swedish surgeons and physiologists were in the frontline of research on the regulation of gastric acid secretion. This research finally led to the development of omeprazole, the first proton pump inhibitor. When Swedish physiologists developed methods allowing the assessment of acid secretion in isolated oxyntic glands and isolated parietal cells, the understanding of mechanisms by which gastric acid secretion is regulated took a great step forward. Similarly, in Trondheim, Norway, the acid producing isolated rat stomach model combined with a sensitive and specific method for determination of histamine made it possible to evaluate this regulation qualitatively as well as quantitatively. In Lund, Sweden, the identification of the enterochromaffin-like cell as the cell taking part in the regulation of acid secretion by producing and releasing histamine was of fundamental importance both physiologically and clinically. Jorpes and Mutt established a center at Karolinska Institutet in Stockholm for the purification of gastrointestinal hormones in the 1960s, and Danes followed up this work by excelling in the field of determination and assessment of biological role of gastrointestinal hormones. A Finnish group was for a long period in the forefront of research on gastritis, and the authors' own studies on the classification of gastric cancer and the role of gastrin in the development of gastric neoplasia are of importance. It can, accordingly, be concluded that Nordic researchers have been central in the research on area of the upper gastrointestinal physiology and diseases.

  9. Human somatic cell nuclear transfer is alive and well.

    Science.gov (United States)

    Cibelli, Jose B

    2014-06-05

    In this issue, Chung et al. (2014) generate human embryonic stem cells by fusing an adult somatic cell to a previously enucleated human oocyte, in agreement with recent reports by the Mitalipov and Egli groups. We can now safely say that human somatic cell nuclear transfer is alive and well.

  10. The association between human papillomavirus and oropharyngeal squamous cell Carcinoma

    DEFF Research Database (Denmark)

    Walvik, Lena; Svensson, Amanda Björk; Friborg, Jeppe

    2016-01-01

    There is emerging evidence of the association between human papillomavirus and a subset of head and neck cancers. However, the role of human papillomavirus as a causal factor is still debated. This review addresses the association between human papillomavirus and oropharyngeal squamous cell...... of well-defined premalignant lesions. However, a causal relationship between human papillomavirus infection and oropharyngeal squamous cell carcinoma seems evident....

  11. Cell cycle regulation in human embryonic stem cells: links to adaptation to cell culture.

    Science.gov (United States)

    Barta, Tomas; Dolezalova, Dasa; Holubcova, Zuzana; Hampl, Ales

    2013-03-01

    Cell cycle represents not only a tightly orchestrated mechanism of cell replication and cell division but it also plays an important role in regulation of cell fate decision. Particularly in the context of pluripotent stem cells or multipotent progenitor cells, regulation of cell fate decision is of paramount importance. It has been shown that human embryonic stem cells (hESCs) show unique cell cycle characteristics, such as short doubling time due to abbreviated G1 phase; these properties change with the onset of differentiation. This review summarizes the current understanding of cell cycle regulation in hESCs. We discuss cell cycle properties as well as regulatory machinery governing cell cycle progression of undifferentiated hESCs. Additionally, we provide evidence that long-term culture of hESCs is accompanied by changes in cell cycle properties as well as configuration of several cell cycle regulatory molecules.

  12. Glycomics of human embryonic stem cells and human induced pluripotent stem cells.

    Science.gov (United States)

    Furukawa, Jun-Ichi; Okada, Kazue; Shinohara, Yasuro

    2016-10-01

    Most cells are coated by a dense glycocalyx composed of glycoconjugates such as glycosphingolipids, glycoproteins, and proteoglycans. The overall glycomic profile is believed to be crucial for the diverse roles of glycans, which are mediated by specific interactions that regulate cell-cell adhesion, the immune response, microbial pathogenesis, and other cellular events. Many cell surface markers were discovered and identified as glycoconjugates such as stage-specific embryonic antigen, Tra-1-60/81 and various other cell surface molecules (e.g., cluster of differentiation). Recent progress in the development of analytical methodologies and strategies has begun to clarify the cellular glycomics of various cells including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). The glycomic profiles of these cells are highly cell type-specific and reflect cellular alterations, such as development, differentiation and cancerous change. In this mini review, we briefly summarize the glycosylation spectra specific to hESCs and hiPSCs, which cover glycans of all major glycoconjugates (i.e., glycosphingolipids, N- and O-glycans of glycoproteins, and glycosaminoglycans) and free oligosaccharides.

  13. Isolation and characterization of human spermatogonial stem cells

    Directory of Open Access Journals (Sweden)

    Liu Shixue

    2011-10-01

    Full Text Available Abstract Background To isolate and characterization of human spermatogonial stem cells from stem spermatogonium. Methods The disassociation of spermatogonial stem cells (SSCs were performed using enzymatic digestion of type I collagenase and trypsin. The SSCs were isolated by using Percoll density gradient centrifugation, followed by differential surface-attachment method. Octamer-4(OCT4-positive SSC cells were further identified using immunofluorescence staining and flow cytometry technques. The purity of the human SSCs was also determined, and a co-culture system for SSCs and Sertoli cells was established. Results The cell viability was 91.07% for the suspension of human spermatogonial stem cells dissociated using a two-step enzymatic digestion process. The cells isolated from Percoll density gradient coupled with differential surface-attachement purification were OCT4 positive, indicating the cells were human spermatogonial stem cells. The purity of isolated human spermatogonial stem cells was 86.7% as assessed by flow cytometry. The isolated SSCs were shown to form stable human spermatogonial stem cell colonies on the feeder layer of the Sertoli cells. Conclusions The two-step enzyme digestion (by type I collagenase and trypsin process is an economical, simple and reproducible technique for isolating human spermatogonial stem cells. With little contamination and less cell damage, this method facilitates isolated human spermatogonial stem cells to form a stable cell colony on the supporting cell layer.

  14. Cell entry by human pathogenic arenaviruses.

    Science.gov (United States)

    Rojek, Jillian M; Kunz, Stefan

    2008-04-01

    The arenaviruses Lassa virus (LASV) in Africa and Machupo (MACV), Guanarito (GTOV) and Junin viruses (JUNV) in South America cause severe haemorrhagic fevers in humans with fatality rates of 15-35%. The present review focuses on the first steps of infection with human pathogenic arenaviruses, the interaction with their cellular receptor molecules and subsequent entry into the host cell. While similarities exist in genomic organization, structure and clinical disease caused by pathogenic Old World and New World arenaviruses these pathogens use different primary receptors. The Old World arenaviruses employ alpha-dystroglycan, a cellular receptor for proteins of the extracellular matrix, and the human pathogenic New World arenaviruses use the cellular cargo receptor transferrin receptor 1. While the New World arenavirus JUNV enters cells via clathrin-dependent endocytosis, evidence occurred for clathrin-independent entry of the prototypic Old World arenavirus lymphocytic choriomeningitis virus. Upon internalization, arenaviruses are delivered to the endosome, where pH-dependent membrane fusion is mediated by the envelope glycoprotein (GP). While arenavirus GPs share characteristics with class I fusion GPs of other enveloped viruses, unusual mechanistic features of GP-mediated membrane fusion have recently been discovered for arenaviruses with important implications for viral entry.

  15. Markers of T Cell Senescence in Humans

    Directory of Open Access Journals (Sweden)

    Weili Xu

    2017-08-01

    Full Text Available Many countries are facing the aging of their population, and many more will face a similar obstacle in the near future, which could be a burden to many healthcare systems. Increased susceptibility to infections, cardiovascular and neurodegenerative disease, cancer as well as reduced efficacy of vaccination are important matters for researchers in the field of aging. As older adults show higher prevalence for a variety of diseases, this also implies higher risk of complications, including nosocomial infections, slower recovery and sequels that may reduce the autonomy and overall quality of life of older adults. The age-related effects on the immune system termed as “immunosenescence” can be exemplified by the reported hypo-responsiveness to influenza vaccination of the elderly. T cells, which belong to the adaptive arm of the immune system, have been extensively studied and the knowledge gathered enables a better understanding of how the immune system may be affected after acute/chronic infections and how this matters in the long run. In this review, we will focus on T cells and discuss the surface and molecular markers that are associated with T cell senescence. We will also look at the implications that senescent T cells could have on human health and diseases. Finally, we will discuss the benefits of having these markers for investigators and the future work that is needed to advance the field of T cell senescence markers.

  16. Human embryonic stem cells and microenvironment

    Directory of Open Access Journals (Sweden)

    Banu İskender

    2014-09-01

    Full Text Available Human embryonic stem cells (hESCs possess a great potential in the field of regenerative medicine by their virtue of pluripotent potential with indefinite proliferation capabilities. They can self renew themselves and differentiate into three embryonic germ layers. Although they are conventionally grown on mitotically inactivated mouse feeder cells, there are in vitro culture systems utilizing feeder cells of human origin in order to prevent cross-species contamination. Recently established in vitro culture systems suggested that direct interaction with feeder cells is not necessary but rather attachment to a substrate is required to ensure long-term, efficient hESC culture in vitro. This substrate is usually composed of a mixture of extracellular matrix components representing in vivo natural niche. In hESC biology, the mechanism of interaction of hESCs with extracellular matrix molecules remained insufficiently explored area of research due to their transient nature of interaction with the in vivo niche. However, an in vitro culture system established using extracellular matrix molecules may provide a safer alternative to culture systems with feeder cells while paving the way to Good Manufacturing Practice-GMP production of hESCs for therapeutic purposes. Therefore, it is essential to study the interaction of extracellular matrix molecules with hESCs in order to standardize in vitro culture systems for large-scale production of hESCs in a less labor-intensive way. This would not only provide valuable information regarding the mechanisms that control pluripotency but also serve to dissect the molecular signaling pathways of directed differentiation for prospective therapeutic applications in the future. J Clin Exp Invest 2014; 5 (3: 486-495

  17. Arecoline is cytotoxic for human endothelial cells.

    Science.gov (United States)

    Ullah, Mafaz; Cox, Stephen; Kelly, Elizabeth; Boadle, Ross; Zoellner, Hans

    2014-11-01

    Oral submucous fibrosis is a pre-malignant fibrotic condition caused by areca nut use and involves reduced mucosal vascularity. Arecoline is the principal areca nut alkaloid and is cytotoxic for epithelium and fibroblasts. Endothelial cell cycle arrest is reported on exposure to arecoline, as is cytotoxicity for endothelial-lung carcinoma hybrid cells. We here describe cytotoxicity for primary human endothelial cultures from seven separate donors. Human umbilical vein endothelial cells were exposed to increasing concentrations of arecoline and examined by: phase-contrast microscopy, haemocytometer counts, transmission electron microscopy, lactate dehydrogenase release and the methyl-thiazol-tetrazolium assay. Vacuolation and detachment of endothelium were observed at and above arecoline concentrations of 333 μg/ml or more. Ultrastructural features of cellular stress were seen after 24-h treatment with 111 μg/ml arecoline and included reduced ribosomal studding of endoplasmic reticulum, increased autophagolysosomal structures, increased vacuolation and reduced mitochondrial cristae with slight swelling. Similar changes were seen at 4 h with arecoline at 333 μg/ml or above, but with more severe mitochondrial changes including increased electron density of mitochondrial matrix and greater cristal swelling, while by 24 h, these cells were frankly necrotic. Haemocytometer counts were paralleled by both lactate dehydrogenase release and the methyl-thiazol-tetrazolium assays. Arecoline is cytotoxic via necrosis for endothelium, while biochemical assays indicate no appreciable cellular leakage before death and detachment, as well as no clear effect on mitochondrial function in viable cells. Arecoline toxicity may thus contribute to reduced vascularity in oral submucous fibrosis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Histiocytic disorders of the gastrointestinal tract

    DEFF Research Database (Denmark)

    Detlefsen, Sönke; Fagerberg, Christina R; Ousager, Lilian Bomme;

    2013-01-01

    , xanthogranulomatous inflammation, juvenile xanthogranuloma, Whipple's disease and malacoplakia are discussed as well. We also briefly go into primary histiocytic disorders of neoplastic origin, systemic diseases with secondary gastrointestinal tract involvement like the lysosomal storage disorders, and pigmented......The morphologic diagnosis of histiocytic lesions of the gastrointestinal tract can be challenging, and several disorders have to be considered in their differential diagnosis. We present one of the most widespread examples of xanthomatosis of the gastrointestinal tract published so far and give...... a short review on histiocytic disorders of the gastrointestinal tract in general. The primary histiocytic disorders of uncertain origin, Rosai-Dorfman disease, Langerhans cell histiocytosis, and Erdheim-Chester disease, are addressed. Reactive and infectious conditions such as xanthomatosis...

  19. Identification of a candidate stem cell in human gallbladder

    Directory of Open Access Journals (Sweden)

    Rohan Manohar

    2015-05-01

    In conclusion, we have isolated a distinct clonogenic population of epithelial cells from primary human fetal gallbladder with stem cell characteristics and found it to be unique compared to IHBD cells.

  20. Cell cycle regulation by glucosamine in human pulmonary epithelial cells.

    Science.gov (United States)

    Chuang, Kun-Han; Lu, Chih-Shen; Kou, Yu Ru; Wu, Yuh-Lin

    2013-04-01

    Airway epithelial cells play an important role against intruding pathogens. Glucosamine, a commonly used supplemental compound, has recently begun to be regarded as a potential anti-inflammatory molecule. This study aimed to uncover how glucosamine impacts on cellular proliferation in human alveolar epithelial cells (A549) and bronchial epithelial cells (HBECs). With trypan blue-exclusion assay, we observed that glucosamine (10, 20, 50 mM) caused a decrease in cell number at 24 and 48 h; with a flow cytometric analysis, we also noted an enhanced cell accumulation within the G(0)/G(1) phase at 24 h and induction of late apoptosis at 24 and 48 h by glucosamine (10, 20, 50 mM) in A549 cells and HBECs. Examination of phosphorylation in retinoblastoma (Rb) protein, we found an inhibitory effect by glucosamine at 20 and 50 mM. Glucosamine at 50 mM was demonstrated to elevate both the mRNA and protein expression of p53 and heme oxygenase-1 (HO-1), but also caused a reduction in p21 protein expression. In addition, glucosamine attenuated p21 protein stability via the proteasomal proteolytic pathway, as well as inducing p21 nuclear accumulation. Altogether, our results suggest that a high dose of glucosamine may inhibit cell proliferation through apoptosis and disturb cell cycle progression with a halt at G(0)/G(1) phase, and that this occurs, at least in part, by a reduction in Rb phosphorylation together with modulation of p21, p53 and HO-1 expression, and nuclear p21 accumulation.

  1. Effect of anti-IgE therapy on food allergen specific T cell responses in eosinophil associated gastrointestinal disorders

    Directory of Open Access Journals (Sweden)

    Prussin Calman

    2011-04-01

    Full Text Available Abstract Background Anti-IgE therapy inhibits mast cell and basophil activation, blocks IgE binding to both FcεRI and CD23 and down regulates FcεRI expression by antigen (Ag presenting cells (APCs. In addition to its classical role in immediate hypersensitivity, IgE has been shown in vitro to facilitate Ag presentation of allergens, whereby APC bound IgE preferentially takes up allergens for subsequent processing and presentation. The purpose of this study was to determine whether anti-IgE therapy, by blocking facilitated Ag presentation in vivo, attenuates allergen specific Th2 cell responses. Methods To test this hypothesis, food allergen specific T cell responses were examined during a 16-week clinical trial of omalizumab in nine subjects with eosinophilic gastroenteritis and food sensitization. Allergen specific T cell responses were measured using carboxyfluorescein succinimidyl ester dye dilution coupled with intracellular cytokine staining and polychromatic flow cytometry. Four independent indices of allergen specific T cell response (proliferation, Ag dose response, precursor frequency, and the ratio of Th2:Th1 cytokine expression were determined. Results Eight of the 9 subjects had measurable food allergen specific responses, with a median proliferation index of 112-fold. Allergen specific T cell proliferation was limited to CD4 T cells, whereas CD8 T cell did not proliferate. Food allergen specific responses were Th2 skewed relative to tetanus specific responses in the same subjects. In contradistinction to the original hypothesis, anti-IgE treatment did not diminish any of the four measured indices of allergen specific T cell response. Conclusions In sum, using multiple indices of T cell function, this study failed to demonstrate that anti-IgE therapy broadly or potently inhibits allergen specific T cell responses. As such, these data do not support a major role for IgE facilitated Ag presentation augmenting allergen specific T cell

  2. A case of feline gastrointestinal eosinophilic sclerosing fibroplasia.

    Science.gov (United States)

    Suzuki, Manabu; Onchi, Miyako; Ozaki, Masakazu

    2013-03-01

    Feline gastrointestinal eosinophilic sclerosing fibroplasia was diagnosed in an 8-month-old Scottish fold that had a primary gastrointestinal mass involving the stomach, duodenum and mesenteric lymph nodes. Histopathologically, the most characteristic feature of this mass was granulation tissue with eosinophil infiltration and hyperplasia of sclerosing collagen fiber. Immunohistochemically, large spindle-shaped cells were positive for smooth muscle actin and vimentin. This case emphasizes the importance of feline gastrointestinal eosinophilic sclerosing fibroplasia as a differential diagnosis of gastrointestinal neoplastic lesions such as osteosarcoma and mast cell tumor in cats.

  3. Human embryonic stem cells and patent protection

    Directory of Open Access Journals (Sweden)

    Radovanović Sanja M.

    2015-01-01

    Full Text Available Given the importance of biotechnological research in modern diagnostics and therapeutics, on the one hand, and stimulative function of a patent, on the other hand, this work deals with the question of the possibility of pa-tent protection of human embryonic stem cells. Taking into account that this is a biotechnological invention, the key question that this paper highlights is the interpretation of the provisions of their patentability. Namely, thanks to the advanced methods of isolation, purification and preparation for implementation, modern patent systems do not exclude a priori living organisms from patent protection. Therefore, the analysis of representative administrative decisions or court rulings sought to define the criteria that would be applied in order to give patent protection to a certain biotechnological invention (stem cells while others do not.

  4. Generation of human induced pluripotent stem cells from dermal fibroblasts

    OpenAIRE

    2008-01-01

    The generation of patient-specific pluripotent stem cells has the potential to accelerate the implementation of stem cells for clinical treatment of degenerative diseases. Technologies including somatic cell nuclear transfer and cell fusion might generate such cells but are hindered by issues that might prevent them from being used clinically. Here, we describe methods to use dermal fibroblasts easily obtained from an individual human to generate human induced pluripotent stem (iPS) cells by ...

  5. Restriction of human adenovirus replication in Chinese hamster cell lines and their hybrids with human cells.

    Science.gov (United States)

    Radna, R L; Foellmer, B; Feldman, L A; Francke, U; Ozer, H L

    1987-11-01

    We have found that the replication of human adenovirus (Ad2) is restricted in multiple Chinese hamster cell lines including CHO and V79. The major site of restriction involves differential accumulation of late viral proteins as demonstrated by immunofluorescence assay and polyacrylamide gel electrophoresis with and without prior immunoprecipitation. Synthesis of fiber and penton base are markedly reduced, whereas others, such as the 100K polypeptide, are synthesized efficiently. This pattern of restriction is similar to that previously reported for Ad2 infection of several monkey cell lines; however, the restriction is more marked in the Chinese hamster cell lines. The restriction is most likely due to a deficient cellular function since stable cell hybrids between V79 or CHO and human cells are permissive for virus replication. By analysis of a series of hybrids with reduced numbers of human chromosomes, fiber synthesis was correlated with the presence of the short arm of human chromosome 3. More hybrids showed restoration of fiber synthesis than production of progeny virus, suggesting that more than one unlinked function is required for the latter.

  6. Phenotypic changes of human cells in human-rat liver during partial hepatectomy-induced regeneration

    Institute of Scientific and Technical Information of China (English)

    Yan Sun; Dong Xiao; Hong-An Li; Jin-Fang Jiang; Qing Li; Ruo-Shuang Zhang; Xi-Gu Chen

    2009-01-01

    AIM: To examine the human hepatic parenchymal and stromal components in rat liver and the phenotypic changes of human cells in liver of human-rat chimera (HRC) generated by in utero transplantation of human cells during partial hepatectomy (PHx)-induced liver regeneration. METHODS: Human hepatic parenchymal and stromal components and phenotypic changes of human cells during liver regeneration were examined by flow cytometry, in situ hybridization and immunohistochemistry. RESULTS: ISH analysis demonstrated human Alupositive cells in hepatic parenchyma and stroma of recipient liver. Functional human hepatocytes generated in this model potentially constituted human hepatic functional units with the presence of donor-derived human endothelial and biliary duct cells in host liver. Alpha fetoprotein (AFP)+, CD34+ and CD45+ cells were observed in the chimeric liver on day 10 after PHxinduced liver regeneration and then disappeared in PHx group, but not in non-PHx group, suggesting that dynamic phenotypic changes of human cells expressing AFP, CD34 and CD45 cells may occur during the chimeric liver regeneration. Additionally, immunostaining for human proliferating cell nuclear antigen (PCNA) showed that the number of PCNA-positive cells in the chimeric liver of PHx group was markedly increased, as compared to that of control group, indicating that donor-derived human cells are actively proliferated during PHx-induced regeneration of HRC liver.

  7. HIF induces human embryonic stem cell markers in cancer cells.

    Science.gov (United States)

    Mathieu, Julie; Zhang, Zhan; Zhou, Wenyu; Wang, Amy J; Heddleston, John M; Pinna, Claudia M A; Hubaud, Alexis; Stadler, Bradford; Choi, Michael; Bar, Merav; Tewari, Muneesh; Liu, Alvin; Vessella, Robert; Rostomily, Robert; Born, Donald; Horwitz, Marshall; Ware, Carol; Blau, C Anthony; Cleary, Michele A; Rich, Jeremy N; Ruohola-Baker, Hannele

    2011-07-01

    Low oxygen levels have been shown to promote self-renewal in many stem cells. In tumors, hypoxia is associated with aggressive disease course and poor clinical outcomes. Furthermore, many aggressive tumors have been shown to display gene expression signatures characteristic of human embryonic stem cells (hESC). We now tested whether hypoxia might be responsible for the hESC signature observed in aggressive tumors. We show that hypoxia, through hypoxia-inducible factor (HIF), can induce an hESC-like transcriptional program, including the induced pluripotent stem cell (iPSC) inducers, OCT4, NANOG, SOX2, KLF4, cMYC, and microRNA-302 in 11 cancer cell lines (from prostate, brain, kidney, cervix, lung, colon, liver, and breast tumors). Furthermore, nondegradable forms of HIFα, combined with the traditional iPSC inducers, are highly efficient in generating A549 iPSC-like colonies that have high tumorigenic capacity. To test potential correlation between iPSC inducers and HIF expression in primary tumors, we analyzed primary prostate tumors and found a significant correlation between NANOG-, OCT4-, and HIF1α-positive regions. Furthermore, NANOG and OCT4 expressions positively correlated with increased prostate tumor Gleason score. In primary glioma-derived CD133 negative cells, hypoxia was able to induce neurospheres and hESC markers. Together, these findings suggest that HIF targets may act as key inducers of a dynamic state of stemness in pathologic conditions.

  8. Effect of anti-IgE therapy on food allergen specific T cell responses in eosinophil associated gastrointestinal disorders

    National Research Council Canada - National Science Library

    Foster, Barbara; Foroughi, Shabnam; Yin, Yuzhi; Prussin, Calman

    2011-01-01

    .... To test this hypothesis, food allergen specific T cell responses were examined during a 16-week clinical trial of omalizumab in nine subjects with eosinophilic gastroenteritis and food sensitization...

  9. Derivation of human embryonic stem cells in defined conditions.

    Science.gov (United States)

    Ludwig, Tenneille E; Levenstein, Mark E; Jones, Jeffrey M; Berggren, W Travis; Mitchen, Erika R; Frane, Jennifer L; Crandall, Leann J; Daigh, Christine A; Conard, Kevin R; Piekarczyk, Marian S; Llanas, Rachel A; Thomson, James A

    2006-02-01

    We have previously reported that high concentrations of basic fibroblast growth factor (bFGF) support feeder-independent growth of human embryonic stem (ES) cells, but those conditions included poorly defined serum and matrix components. Here we report feeder-independent human ES cell culture that includes protein components solely derived from recombinant sources or purified from human material. We describe the derivation of two new human ES cell lines in these defined culture conditions.

  10. Indolent T-cell lymphoproliferative disease of the gastrointestinal tract after treatment with adalimumab in resistant Crohn's colitis.

    Science.gov (United States)

    Edison, Natalia; Belhanes-Peled, Hila; Eitan, Yuval; Guthmann, Yifat; Yeremenko, Yelena; Raffeld, Mark; Elmalah, Irit; Trougouboff, Philippe

    2016-11-01

    We report a case of intestinal indolent T-cell lymphoproliferative disease (TCLPD) occurring after the initiation of tumor necrosis factor-α (TNF-α) inhibitor therapy for resistant Crohn's disease. A prominent T-cell infiltrate positive for CD8, TIA-1, and T-cell receptor-βF1 was associated with the foci of active inflammation. T-cell receptor gene clonality studies (BIOMED-2) demonstrated monoclonality. After the TNF-α inhibitor treatment was withdrawn, the T-cell infiltrates regressed, but 2 years later, the same monoclonal T-cell infiltrate reappeared at the only site of active inflammation. To the best of our knowledge, this report is the first to show a link between active inflammation and the TCLPD. In addition, it suggests a possible influence of the TNF-α inhibitor treatment on the evolution of the TCLPD. A high degree of suspicion is required in the presence of any unusual lymphoid infiltrate in inflammatory bowel disease to avoid overlooking an indolent TCLPD or misdiagnose an aggressive lymphoma. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Introduction: characterization and functions of human T regulatory cells.

    Science.gov (United States)

    Romagnani, Sergio

    2005-06-01

    The field of human T regulatory (Treg) cells is a rapidly progressing, but still confused field of immunology. The effects of dendritic cell (DC) manipulation in Treg generation and the main features of human "natural" Treg cells, as well as of different populations of adaptive Treg subsets, are still partially unclear. However, it is clear that Treg cells play an important role in human diseases, such as autoimmune disorders, allergy, HIV infection, tumors and graft-versus-host disease.

  12. Secreted human adipose leptin decreases mitochondrial respiration in HCT116 colon cancer cells.

    Science.gov (United States)

    Yehuda-Shnaidman, Einav; Nimri, Lili; Tarnovscki, Tanya; Kirshtein, Boris; Rudich, Assaf; Schwartz, Betty

    2013-01-01

    Obesity is a key risk factor for the development of colon cancer; however, the endocrine/paracrine/metabolic networks mediating this connection are poorly understood. Here we hypothesize that obesity results in secreted products from adipose tissue that induce malignancy-related metabolic alterations in colon cancer cells. Human HCT116 colon cancer cells, were exposed to conditioned media from cultured human adipose tissue fragments of obese vs. non-obese subjects. Oxygen consumption rate (OCR, mostly mitochondrial respiration) and extracellular acidification rate (ECAR, mostly lactate production via glycolysis) were examined vis-à-vis cell viability and expression of related genes and proteins. Our results show that conditioned media from obese (vs. non-obese) subjects decreased basal (40%, pobese subjects. We conclude that secreted products from the adipose tissue of obese subjects inhibit mitochondrial respiration and function in HCT116 colon cancer cells, an effect that is at least partly mediated by leptin. These results highlight a putative novel mechanism for obesity-associated risk of gastrointestinal malignancies, and suggest potential new therapeutic avenues.

  13. Primary pediatric gastrointestinal lymphoma

    Directory of Open Access Journals (Sweden)

    Ranjana Bandyopadhyay

    2011-01-01

    Full Text Available Background: Primary non-Hodgkin′s lymphoma (NHL of the gastrointestinal (GI tract is the most common extranodal lymphoma in pediatric age group. Yet, the overall incidence is very low. The rarity of the disease as well as variable clinical presentation prevents early detection when the possibility of cure exists. Materials and Methods: We studied six cases of primary GI NHL in pediatric age group with reference to their clinical presentation, anatomic distribution and histopathologic characteristics. Results: All were males except one. Intestinal obstruction was the presenting feature in 50%. Half the cases showed ileocaecal involvement, while large bowel was involved in 16%. Histology showed four cases of diffuse large B-cell lymphoma (DLBCL, one case of Burkitt lymphoma, and one Burkitt-like lymphoma. Immunohistochemistry for Tdt, CD20, CD3, CD30, bcl2, bcl6 confirmed the morphological diagnosis. Conclusion: Pediatric GI lymphoma commonly involves the ileocaecal region and presents with intestinal obstruction. A higher prevalence of DLBCL is found compared to other series. A high proliferative index is useful in differentiating Burkitt-like lymphoma from DLBCL.

  14. Gastrointestinal microbiology enters the metagenomics era.

    Science.gov (United States)

    Frank, Daniel N; Pace, Norman R

    2008-01-01

    Advances in DNA sequence-based technologies now permit genetic analysis of complex microbial populations without the need for prior cultivation. This review summarizes the molecular methods of culture-independent microbiology ('metagenomics') and their recent application to studies of the human gastrointestinal tract in both health and disease. Culture-independent metagenomic surveys reveal unprecedented microbial biodiversity in the human intestine. Upwards of 40,000 bacterial species are estimated to comprise the collective gastrointestinal microbiome, most of which have not been characterized by culture. Diverse conditions such as antibiotic-associated diarrhea, Crohn's disease, ulcerative colitis, obesity, and pouchitis have been correlated with large-scale imbalances in gastrointestinal microbiota, or 'dysbiosis'. These findings demonstrate the importance of commensal microorganisms in maintaining gastrointestinal health. Through technological and conceptual innovations in metagenomics, the complex microbial habitat of the human gastrointestinal tract is now amenable to detailed ecological analysis. Large-scale shifts in gut commensal populations, rather than occurrence of particular microorganisms, are associated with several gastroenterological conditions; redress of these imbalances may ameliorate the conditions.

  15. Human pancreatic cell autotransplantation following total pancreatectomy.

    Science.gov (United States)

    Traverso, L W; Abou-Zamzam, A M; Longmire, W P

    1981-01-01

    During total pancreaticoduodenectomy for chronic pancreatitis, four patients received an intraportal pancreatic mixed-cell autograft prepared by collagenase digestion. The technique of this autotransplantation procedure was successfully developed using a normal canine pancreas, but has proved difficult to apply in the human chronic pancreatitis model. Our four patients became insulin-dependent, with proof of intrahepatic insulin production in only one patient. Three factors have contributed to the lack of graft success: 1) the preoperative endocrine status, 2) systemic hypotension and portal hypertension secondary to graft infusion, and 3) difficulty applying the successful technique in a normal dog pancreas to an extensively scarred human pancreas. The preoperative insulin response during a glucose tolerance test was blunted or delayed in the three patients tested. An immediate decrease in blood pressure and rise in portal pressure occurred in every patient and prevented infusion of the entire graft (30-50%) in three patients. Unfortunately, the patient with the most compromised insulin status was the only patient able to receive the entire graft. Our experience would indicate that further refinements in technique are necessary to prevent the vascular reaction and allow infusion of the entire graft. Furthermore, normal islet cell function is necessary before a successful graft can be expected. PMID:6781424

  16. Sourcing human embryos for embryonic stem cell lines: Problems & perspectives

    OpenAIRE

    Mehta, Rajvi H.

    2014-01-01

    The ability to successfully derive human embryonic stem cells (hESC) lines from human embryos following in vitro fertilization (IVF) opened up a plethora of potential applications of this technique. These cell lines could have been successfully used to increase our understanding of human developmental biology, transplantation medicine and the emerging science of regenerative medicine. The main source for human embryos has been ′discarded′ or ′spare′ fresh or frozen human embryos following IVF...

  17. Immunology of the gastrointestinal tract and liver

    Energy Technology Data Exchange (ETDEWEB)

    Heyworth, M.F.; Jones, A.L.

    1988-01-01

    This book contains 11 chapters. Some of the chapter titles are: T cells and Other Non-B Lymphocytes; Mucosal Mast Cells and IgE; Genetic Aspects of Gastrointestinal Immunology; Immunological Functions of the Liver; Lymphocyte Migration and Mucosal Immunity; and Immunoglobulin Circulation and Secretion.

  18. Assessment of okadaic acid effects on cytotoxicity, DNA damage and DNA repair in human cells.

    Science.gov (United States)

    Valdiglesias, Vanessa; Méndez, Josefina; Pásaro, Eduardo; Cemeli, Eduardo; Anderson, Diana; Laffon, Blanca

    2010-07-07

    Okadaic acid (OA) is a phycotoxin produced by several types of dinoflagellates causing diarrheic shellfish poisoning (DSP) in humans. Symptoms induced by DSP toxins are mainly gastrointestinal, but the intoxication does not appear to be fatal. Despite this, this toxin presents a potential threat to human health even at concentrations too low to induce acute toxicity, since previous animal studies have shown that OA has very potent tumour promoting activity. However, its concrete action mechanism has not been described yet and the results reported with regard to OA cytotoxicity and genotoxicity are often contradictory. In the present study, the genotoxic and cytotoxic effects of OA on three different types of human cells (peripheral blood leukocytes, HepG2 hepatoma cells, and SHSY5Y neuroblastoma cells) were evaluated. Cells were treated with a range of OA concentrations in the presence and absence of S9 fraction, and MTT test and Comet assay were performed in order to evaluate cytotoxicity and genotoxicity, respectively. The possible effects of OA on DNA repair were also studied by means of the DNA repair competence assay, using bleomycin as DNA damage inductor. Treatment with OA in absence of S9 fraction induced not statistically significant decrease in cell viability and significant increase in DNA damage in all cell types at the highest concentrations investigated. However, only SHSY5Y cells showed OA induced genotoxic and cytotoxic effects in presence of S9 fraction. Furthermore, we found that OA can induce modulations in DNA repair processes when exposure was performed prior to BLM treatment, in co-exposure, or during the subsequent DNA repair process. Copyright 2010 Elsevier B.V. All rights reserved.

  19. Efficient Induction and Isolation of Human Primordial Germ Cell-Like Cells from Competent Human Pluripotent Stem Cells.

    Science.gov (United States)

    Irie, Naoko; Surani, M Azim

    2017-01-01

    We recently reported a robust and defined culture system for the specification of human primordial germ cell-like cells (hPGCLCs) from human pluripotent stem cells (hPSCs), both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro (Irie et al. Cell 160: 253-268, 2015). Similar attempts previously produced hPGCLCs from hPSCs at a very low efficiency, and the resulting cells were not fully characterized. A key step, which facilitated efficient hPGCLC specification from hPSCs, was the induction of a "competent" state for PGC fate via the medium containing a cocktail of four inhibitors. The competency of hPSCs can be maintained indefinitely and interchangeably with the conventional/low-competent hPSCs. Specification of hPGCLC occurs following sequential expression of key germ cell fate regulators, notably SOX17 and BLIMP1, as well as initiation of epigenetic resetting over 5 days. The hPGCLCs can be isolated using specific cell surface markers without the need for generating germ cell-specific reporter hPSC lines. This powerful method for the induction and isolation of hPGCLCs can be applied to both hESCs and iPSCs, which can be used for advances in human germ line biology.

  20. Effects of bile acids on human airway epithelial cells: implications for aerodigestive diseases

    Directory of Open Access Journals (Sweden)

    Adil Aldhahrani

    2017-03-01

    Full Text Available Gastro-oesophageal reflux and aspiration have been associated with chronic and end-stage lung disease and with allograft injury following lung transplantation. This raises the possibility that bile acids may cause lung injury by damaging airway epithelium. The aim of this study was to investigate the effect of bile acid challenge using the immortalised human bronchial epithelial cell line (BEAS-2B. The immortalised human bronchial epithelial cell line (BEAS-2B was cultured. A 48-h challenge evaluated the effect of individual primary and secondary bile acids. Post-challenge concentrations of interleukin (IL-8, IL-6 and granulocyte−macrophage colony-stimulating factor were measured using commercial ELISA kits. The viability of the BEAS-2B cells was measured using CellTiter-Blue and MTT assays. Lithocholic acid, deoxycholic acid, chenodeoxycholic acid and cholic acid were successfully used to stimulate cultured BEAS-2B cells at different concentrations. A concentration of lithocholic acid above 10 μmol·L−1 causes cell death, whereas deoxycholic acid, chenodeoxycholic acid and cholic acid above 30 μmol·L−1 was required for cell death. Challenge with bile acids at physiological levels also led to a significant increase in the release of IL-8 and IL6 from BEAS-2B. Aspiration of bile acids could potentially cause cell damage, cell death and inflammation in vivo. This is relevant to an integrated gastrointestinal and lung physiological paradigm of chronic lung disease, where reflux and aspiration are described in both chronic lung diseases and allograft injury.

  1. Sodium butyrate induces DRP1-mediated mitochondrial fusion and apoptosis in human colorectal cancer cells.

    Science.gov (United States)

    Tailor, Dhanir; Hahm, Eun-Ryeong; Kale, Raosaheb K; Singh, Shivendra V; Singh, Rana P

    2014-05-01

    Sodium butyrate (NaBt) is the byproduct of anaerobic microbial fermentation inside the gastro-intestinal tract that could reach up to 20mM, and has been shown to inhibit the growth of various cancers. Herein, we evaluated its effect on mitochondrial fusion and associated induction of apoptosis in colorectal cancer cells (CRC). NaBt treatment at physiological (1-5mM) concentrations for 12 and 24h decreased the cell viability and induced G2-M phase cell cycle arrest in HCT116 (12h) and SW480 human CRC cells. This cell cycle arrest was associated with mitochondria-mediated apoptosis accompanied by a decrease in survivin and Bcl-2 expression, and generation of reactive oxygen species (ROS). Furthermore, NaBt treatment resulted in a significant decrease in the mitochondrial mass which is an indicator of mitochondrial fusion. Level of dynamin-related protein 1 (DRP1), a key regulator of mitochondrial fission and fusion where its up-regulation correlates with fission, was found to be decreased in CRC cells. Further, at early treatment time, DRP1 down-regulation was noticed in mitochondria which later became drastically reduced in both mitochondria as well as cytosol. DRP1 is activated by cyclin B1-CDK1 complex by its ser616 phosphorylation in which both cyclin B1-CDK1 complex and phospho-DRP1 (ser616) were strongly reduced by NaBt treatment. DRP1 was observed to be regulated by apoptosis as pan-caspase inhibitor showing rescue from NaBt-induced apoptosis also caused the reversal of DRP1 to the normal level as in control proliferating cells. Together, these findings suggest that NaBt can modulate mitochondrial fission and fusion by regulating the level of DRP1 and induce cell cycle arrest and apoptosis in human CRC cells.

  2. The similarity between human embryonic stem cell-derived epithelial cells and ameloblast-lineage cells

    Institute of Scientific and Technical Information of China (English)

    Li-Wei Zheng; Logan Linthicum; Pamela K DenBesten; Yan Zhang

    2013-01-01

    This study aimed to compare epithelial cells derived from human embryonic stem cells (hESCs) to human ameloblast-lineage cells (ALCs), as a way to determine their potential use as a cell source for ameloblast regeneration. Induced by various concentrations of bone morphogenetic protein 4 (BMP4), retinoic acid (RA) and lithium chloride (LiCI) for 7 days, hESCs adopted cobble-stone epithelial phenotype (hESC-derived epithelial cells (ES-ECs)) and expressed cytokeratin 14. Compared with ALCs and oral epithelial cells (OE), ES-ECs expressed amelogenesis-associated genes similar to ALCs. ES-ECs were compared with human fetal skin epithelium, human fetal oral buccal mucosal epithelial cells and human ALCs for their expression pattern of cytokeratins as well. ALCs had relatively high expression levels of cytokeratin 76, which ,vas also found to be upregulated in ES-ECs. Based on the present study, with the similarity of gene expression with ALCs, ES-ECs are a promising potential cell source for regeneration, which are not available in erupted human teeth for regeneration of enamel.

  3. Radiosensitivity of Human Melanoma Cell Lines

    Energy Technology Data Exchange (ETDEWEB)

    Bergoc, R. M.; Medina, V.; Cricco, G.; Mohamed, N.; Martin, G.; Nunez, M.; Croci, M.; Crescenti, E. J.; Rivera, E. S.

    2004-07-01

    Cutaneous melanoma is a skin cancer resulting from the malign transformation of skin-pigment cells, the melanocytes. The radiotherapy, alone or in combination with other treatment, is an important therapy for this disease. the objective of this paper was to determine in vitro the radiosensitivity of two human melanoma cell lines with different metastatic capability: WM35 and MI/15, and to study the effect of drugs on radiobiological parameters. The Survival Curves were adjusted to the mathematical Linear-quadratic model using GrapsPad Prism software. Cells were seeded in RPMI medium (3000-3500 cells/flask), in triplicate and irradiated 24 h later. The irradiation was performed using an IBL 437C H Type equipment (189 TBq, 7.7 Gy/min) calibrated with a TLD 700 dosimeter. The range of Doses covered from 0 to 10 Gy and the colonies formed were counted at day 7th post-irradiation. Results obtained were: for WM35, {alpha}=0.37{+-}0.07 Gy''-1 and {beta}=0.06{+-}0.02 Gy''-2, for M1/15m {alpha}=0.47{+-}0.03 Gy''-1 and {beta}=0.06{+-}0.01 Gy''-2. The {alpha}/{beta} values WM35: {alpha}/{beta} values WM35: {alpha}/{beta}=6.07 Gy and M1/15: {alpha}/{beta}{sub 7}.33 Gy were similar, independently of their metastatic capabillity and indicate that both lines exhibit high radioresistance. Microscopic observation of irradiated cells showed multinuclear cells with few morphologic changes non-compatible with apoptosis. By means of specific fluorescent dyes and flow cytometry analysis we determined the intracellular levels of the radicals superoxide and hydrogen peroxide and their modulation in response to ionizing radiation. The results showed a marked decreased in H{sub 2}O{sub 2} intracellular levels with a simultaneous increase in superoxide that will be part of a mechanism responsible for induction of cell radioresistance. This response triggered by irradiated cells could not be abrogated by different treatments like histamine or the

  4. Inhibitory Effects of Probiotic Lactobacillus on the Growth of Human Colonic Carcinoma Cell Line HT-29

    Directory of Open Access Journals (Sweden)

    Zhung-Yuan Chen

    2017-01-01

    Full Text Available This study was conducted to investigate the inhibitory effect of Lactobacillus cells and supernatants on the growth of the human colon cancer cell line HT-29. Our study results indicated that the PM153 strain exhibits the best adhesion ability and the highest survival in the gastrointestinal tract simulation experiment. Furthermore, after an 8-h co-culture of PM153 and HT-29 cells, the PM153 strain can induce the secretion of nitric oxide from the HT-29 cells. In addition, after the co-culture of the BCRC17010 strain (109 cfu/mL and HT-29 cells, the Bax/Bcl-2 ratio in the HT-29 cells was 1.19, which showed a significant difference from the other control and LAB groups (p < 0.05, which therefore led to the inference that the BCRC17010 strain exerts a pro-apoptotic effect on the HT-29 cells. Upon co-culture with HT-29 cells for 4, 8 and 12 h, the BCRC14625 strain (109 cfu/mL demonstrated a significant increase in lactate dehydrogenase (LDH activity (p < 0.05, causing harm to the HT-29 cell membrane; further, after an 8-h co-culture with the HT-29 cells, it induced the secretion of nitric oxide (NO from the HT-29 cells. Some lactic acid bacteria (LAB strains have ability to inhibit the growth of the colorectal cancer cell line HT-29 Bax/Bcl-2 pathway or NO production. In summary, we demonstrated that the BCRC17010 strain, good abilities of adhesion and increased LDH release, was the best probiotic potential for inhibition of HT-29 growth amongst the seven LAB strains tested in vitro.

  5. Generation of human induced pluripotent stem cells from dermal fibroblasts.

    Science.gov (United States)

    Lowry, W E; Richter, L; Yachechko, R; Pyle, A D; Tchieu, J; Sridharan, R; Clark, A T; Plath, K

    2008-02-26

    The generation of patient-specific pluripotent stem cells has the potential to accelerate the implementation of stem cells for clinical treatment of degenerative diseases. Technologies including somatic cell nuclear transfer and cell fusion might generate such cells but are hindered by issues that might prevent them from being used clinically. Here, we describe methods to use dermal fibroblasts easily obtained from an individual human to generate human induced pluripotent stem (iPS) cells by ectopic expression of the defined transcription factors KLF4, OCT4, SOX2, and C-MYC. The resultant cell lines are morphologically indistinguishable from human embryonic stem cells (HESC) generated from the inner cell mass of a human preimplantation embryo. Consistent with these observations, human iPS cells share a nearly identical gene-expression profile with two established HESC lines. Importantly, DNA fingerprinting indicates that the human iPS cells were derived from the donor material and are not a result of contamination. Karyotypic analyses demonstrate that reprogramming of human cells by defined factors does not induce, or require, chromosomal abnormalities. Finally, we provide evidence that human iPS cells can be induced to differentiate along lineages representative of the three embryonic germ layers indicating the pluripotency of these cells. Our findings are an important step toward manipulating somatic human cells to generate an unlimited supply of patient-specific pluripotent stem cells. In the future, the use of defined factors to change cell fate may be the key to routine nuclear reprogramming of human somatic cells.

  6. Lower gastrointestinal bleeding.

    Science.gov (United States)

    Feinman, Marcie; Haut, Elliott R

    2014-02-01

    This article examines causes of occult, moderate and severe lower gastrointestinal (GI) bleeding. The difference in the workup of stable vs unstable patients is stressed. Treatment options ranging from minimally invasive techniques to open surgery are explored.

  7. Citrulline as a Biomarker in the Non-human Primate Total- and Partial-body Irradiation Models: Correlation of Circulating Citrulline to Acute and Prolonged Gastrointestinal Injury.

    Science.gov (United States)

    Jones, Jace W; Bennett, Alexander; Carter, Claire L; Tudor, Gregory; Hankey, Kim G; Farese, Ann M; Booth, Catherine; MacVittie, Thomas J; Kane, Maureen A

    2015-11-01

    The use of plasma citrulline as a biomarker for acute and prolonged gastrointestinal injury via exposure to total- and partial-body irradiation (6 MV LINAC-derived photons; 0.80 Gy min) in nonhuman primate models was investigated. The irradiation exposure covered gastrointestinal injuries spanning lethal, mid-lethal, and sub-lethal doses. The acute gastrointestinal injury was assessed via measurement of plasma citrulline and small intestinal histopathology over the first 15 d following radiation exposure and included total-body irradiation at 13.0 Gy, 10.5 Gy, and 7.5 Gy and partial-body irradiation at 11.0 Gy with 5% bone marrow sparing. The dosing schemes of 7.5 Gy total-body irradiation and 11.0 Gy partial-body irradiation included time points out to day 60 and day 180, respectively, which allowed for correlation of plasma citrulline to prolonged gastrointestinal injury and survival. Plasma citrulline values were radiation-dependent for all radiation doses under consideration, with nadir values ranging from 63-80% lower than radiation-naïve NHP plasma. The nadir values were observed at day 5 to 7 post irradiation. Longitudinal plasma citrulline profiles demonstrated prolonged gastrointestinal injury resulting from acute high-dose irradiation had long lasting effects on enterocyte function. Moreover, plasma citrulline did not discriminate between total-body or partial-body irradiation over the first 15 d following irradiation and was not predictive of survival based on the radiation models considered herein.

  8. Evaluation of /sup 99m/Tc labeled red blood cell scintigraphy for the detection and localization of gastrointestinal bleeding sites

    Energy Technology Data Exchange (ETDEWEB)

    Markisz, J.A.; Front, D.; Royal, H.D.; Sacks, B.; Parker, J.A.; Kolodny, G.M.

    1982-08-01

    /sup 99m/Tc labeled red blood cell scintigraphy was performed upon 39 patients with clinical evidence for acute lower gastrointestinal bleeding from an unknown source. Seventeen of 39 patients (44%) had a scan became positive 6 or more h after injection, consistent with intermittent bleeding, in 8 of 17 patients (47%). In the 11 patients in whom the bleeding site was definitely identified by arteriography, surgery, or colonoscopy, scintigraphy correctly localized the bleeding site in 10 of 11 patients (91%). Four of 11 patients (36%) had an active bleeding site identified by arteriography. Ten of 17 patients (58%) with a positive scan required either gelfoam embolization (4 patients) or surgery (6 patients) to control the bleeding, whereas only 1 of 22 patients (5%) required surgery when the scan was negative. Six deaths occurred in the scan-positive patients compared with no deaths in the scan-negative patients. None of the 8 patients who had arteriography and no active bleeding site by scintigraphy had arteriographically demonstrable active bleeding. Scintigraphy provides a reliable noninvasive test to screen patients in whom arteriography is being considered to localize active bleeding sites. If the arteriogram is negative, the scintigraphic findings alone may guide the surgical or arteriographic intervention. In addition, scintigraphy identifies two patient populations which have considerably different morbidity and mortality.

  9. Effect of the gastrointestinal environment on pH homeostasis of Lactobacillus plantarum and Lactobacillus brevis cells as measured by real-time fluorescence ratio-imaging microscopy

    DEFF Research Database (Denmark)

    Ramos, Cíntia Lacerda; Thorsen, Line; Ryssel, Mia;

    2014-01-01

    using fluorescence ratio imaging microscopy (FRIM) for potential probiotic strains of Lactobacillus plantarum UFLA CH3 and Lactobacillus brevis UFLA FFC199. Heterogeneous populations were observed, with pHi values ranging from 6.5 to 7.5, 3.5 to 5.6 and 6.5 to 8.0 or higher during passage of saliva (p......In the present work, an in vitro model of the gastrointestinal tract (GIT) was developed to obtain real-time observations of the pH homeostasis of single cells of probiotic Lactobacillus spp. strains as a measure of their physiological state. Changes in the intracellular pH (pHi) were determined......H 6.4), gastric (pH 3.5) and intestinal juices (pH 6.4), respectively. When nutrients were added to gastric juice, the isolate L. brevis significantly decreased its pHi closer to the extracellular pH (pHex) than in gastric juice without nutrients. This was not the case for L. plantarum. This study...

  10. Stereological quantification of mast cells in human synovium

    DEFF Research Database (Denmark)

    Damsgaard, T E; Sørensen, Flemming Brandt; Herlin, T;

    1999-01-01

    Mast cells participate in both the acute allergic reaction as well as in chronic inflammatory diseases. Earlier studies have revealed divergent results regarding the quantification of mast cells in the human synovium. The aim of the present study was therefore to quantify these cells in the human...... synovium, using stereological techniques. Different methods of staining and quantification have previously been used for mast cell quantification in human synovium. Stereological techniques provide precise and unbiased information on the number of cell profiles in two-dimensional tissue sections of......, in this case, human synovium. In 10 patients suffering from osteoarthritis a median of 3.6 mast cells/mm2 synovial membrane was found. The total number of cells (synoviocytes, fibroblasts, lymphocytes, leukocytes) present was 395.9 cells/mm2 (median). The mast cells constituted 0.8% of all the cell profiles...

  11. Technical Challenges in the Derivation of Human Pluripotent Cells

    Directory of Open Access Journals (Sweden)

    Parinya Noisa

    2011-01-01

    Full Text Available It has long been discovered that human pluripotent cells could be isolated from the blastocyst state of embryos and called human embryonic stem cells (ESCs. These cells can be adapted and propagated indefinitely in culture in an undifferentiated manner as well as differentiated into cell representing the three major germ layers: endoderm, mesoderm, and ectoderm. However, the derivation of human pluripotent cells from donated embryos is limited and restricted by ethical concerns. Therefore, various approaches have been explored and proved their success. Human pluripotent cells can also be derived experimentally by the nuclear reprogramming of somatic cells. These techniques include somatic cell nuclear transfer (SCNT, cell fusion and overexpression of pluripotent genes. In this paper, we discuss the technical challenges of these approaches for nuclear reprogramming, involving their advantages and limitations. We will also highlight the possible applications of these techniques in the study of stem cell biology.

  12. Gastrointestinal motility and functional gastrointestinal diseases.

    Science.gov (United States)

    Kusano, Motoyasu; Hosaka, Hiroko; Kawada, Akiyo; Kuribayashi, Shiko; Shimoyama, Yasuyuki; Zai, Hiroaki; Kawamura, Osamu; Yamada, Masanobu

    2014-01-01

    Digestive tract motility patterns are closely related to the pathophysiology of functional gastrointestinal diseases (FGID), and these patterns differ markedly between the interdigestive period and the postprandial period. The characteristic motility pattern in the interdigestive period is so-called interdigestive migrating contraction (IMC). IMCs have a housekeeping role in the intestinal tract, and could also be related to FGID. IMCs arising from the stomach are called gastrointestinal IMCs (GI-IMC), while IMCs arising from the duodenum without associated gastric contractions are called intestinal IMCs (I-IMC). It is thought that I-IMCs are abnormal in FGID. Transport of food residue to the duodenum via gastric emptying is one of the most important postprandial functions of the stomach. In patients with functional dyspepsia (FD), abnormal gastric emptying is a possible mechanism of gastric dysfunction. Accordingly, delayed gastric emptying has attracted attention, with prokinetic agents and herbal medicines often being administered in Japan to accelerate gastric emptying in patients who have anorexia associated with dyspepsia. Recently, we found that addition of monosodium L-glutamate (MSG) to a high-calorie liquid diet rich in casein promoted gastric emptying in healthy men. Therefore, another potential method of improving delayed gastric emptying could be activation of chemosensors that stimulate the autonomic nervous system of the gastrointestinal tract, suggesting a role for MSG in the management of delayed gastric emptying in patients with FD.

  13. Human B cell activating factor (BCAF): production by a human T cell tumor line.

    Science.gov (United States)

    Fevrier, M; Diu, A; Mollier, P; Abadie, A; Olive, D; Mawas, C; Theze, J

    1989-01-01

    In a previous study, we demonstrated that supernatants from human T cell clones stimulated by a pair of anti-CD2 monoclonal antibodies cause resting human B cells to become activated and to proliferate in the absence of any other signals. The activity responsible for these effects was shown to be different from already characterized lymphokines and in particular from IL-2 and IL-4, and was named B Cell Activating Factor or BCAF. In this paper, we describe the production of BCAF by a human T cell tumor line T687 after phorbol myristate acetate (PMA) stimulation; this production can be potentiated by phytohemagglutinin (PHA). We further show that the stimulatory phase can be separated from the secretory phase thereby avoiding contamination of BCAF-containing supernatant by PMA and PHA. Supernatants produced under these conditions do not contain either IL-4 or IFN but contain traces of lymphotoxin and 2 to 10 ng/ml of IL-2. The T687 cell line will allow us to obtain a large volume of supernatant for biochemical study and purification of the molecule(s) responsible for BCAF activity.

  14. Trichloroethylene toxicity in a human hepatoma cell line

    Energy Technology Data Exchange (ETDEWEB)

    Thevenin, E.; McMillian, J. [Medical Univ. of Charleston South Carolina, SC (United States)

    1994-12-31

    The experiments conducted in this study were designed to determine the usefullness of hepatocyte cultures and a human hepatoma