Human Gut (human + gut)

Distribution by Scientific Domains

Selected Abstracts

The proportion of CD40+ mucosal macrophages is increased in inflammatory bowel disease whereas CD40 ligand (CD154)+ T cells are relatively decreased, suggesting differential modulation of these costimulatory molecules in human gut lamina propria

Dr. Hege S. Carlsen MD
Abstract Background: Signal transduction through binding of CD40 on antigen-presenting cells and CD40 ligand (CD154) on T cells appears to be crucial for mutual cellular activation. Antibodies aimed at blocking the CD40,CD154 costimulatory pathway dampen the severity of experimental colitis. To elucidate the microanatomical basis for signaling through this costimulatory pathway in human inflammatory bowel disease, we studied in situ the cellular distribution of these 2 molecules on lamina propria macrophages and T cells, respectively. Methods: Colonic specimens from 8 patients with ulcerative colitis and 8 with Crohn's disease, 8 small bowel specimens of Crohn's disease, and histologically normal control samples (6 from colon and 6 from small bowel) were included. Multicolor immunofluorescence in situ staining was performed to determine the percentage of subepithelial macrophages expressing CD40 and that of lamina propria T cells expressing CD154 while avoiding cells in lymphoid aggregates. Results: The proportion of subepithelial CD40highCD68+ macrophages was significantly increased in normal colon compared with normal small bowel and showed further elevation in both colon and small bowel afflicted with inflammatory bowel disease. In addition, on a per-CD68+ -cell basis, CD40 expression was significantly increased in severely inflamed compared with moderately inflamed colonic specimens. Conversely, the proportion of CD154+ T cells was similar in colon and small bowel, and interestingly, it was significantly reduced in colonic inflammatory bowel disease. Conclusions: Our findings suggested that modulation of CD40 expression by subepithelial macrophages and CD154 by lamina propria T cells is inversely modulated in the human gut. [source]

Prevalence of vaccine-derived polioviruses in stools of immunodeficient children in South Africa

D.N. Pavlov
Abstract Aims:, The aim of the study was to determine the prevalence of vaccine-derived polioviruses (VDPVs) in stool specimens of immunodeficient patients such as HIV-positive children (including those with an AIDS indicator condition, according to the Centres for Disease Control and Prevention classification) by applying various molecular techniques. Methods and Results:, A total of 164 stool samples from HIV-positive children and 23 stool samples from healthy immunocompetent children (the control group) were analysed during 2003 and 2004. By applying a reverse transcription polymerase chain reaction (RT-PCR) in combination with a nested PCR, a total of 54 enteroviruses were detected in the stool specimens of the immunodeficient children. The use of restriction enzymes and a Sabin specific RT-triplex PCR confirmed the presence of 13 polioviruses (PVs), such as seven Sabin PV type 1, four Sabin PV type 3 and two Sabin PV type 2 isolates. The 5,untranslated region and the VP1 capsid-encoding protein of the 13 PVs and the three PVs from the stools of the immunocompetent children were partially sequenced and their genetic relatedness was deduced from the constructed phylogenetic trees. The majority of the PVs isolated from the stools of the immunodeficient children (10 of 13 isolates) were classified as ,oral poliovirus vaccine (OPV)-like viruses', as these isolates had close sequence relationships (>99% in VP1 nucleotide sequences) to the original Sabin PV vaccine strains. Three PVs showed ,99% VP1 sequence identity to the Sabin PV vaccine strains and were classified as ,suspected' immunodeficient VDPVs (iVDPVs). All of the OPV-like isolates and the ,suspected' iVDPVs carried mutations at specific positions in their partially sequenced regions, which have been associated with reversion of the attenuated Sabin PV vaccine strains to increased neurovirulence. Conclusions:, Thus, this study adds further evidence to the observation that immunodeficient individuals may excrete OPV strains with potential neurovirulent phenotypes. Significance and Impact of the Study:, Prolonged excretion of PVs by immunodeficient individuals is of major concern, because continued replication of PVs in the human gut could result in the reversion of these viruses to greater neurovirulence. When exposed to OPV, immunodeficient patients may become chronically infected, spreading potentially neurovirulent VDPVs for many months or years to close contacts and children who are no longer being vaccinated after termination of OPV vaccination in the near future. [source]

The opioid system in the gastrointestinal tract

C. Sternini
Abstract ľ-, ,- and ,-opioid receptors (ORs) mediate the effects of endogenous opioids and opiate drugs. Here we report (1) the distribution of ľOR in the guinea-pig and human gastrointestinal tract in relation to endogenous ligands, to functionally distinct structures in the gut and to ,OR and ,OR; and (2) the ligand-induced ľOR endocytosis in enteric neurones using in vitro and in vivo models. In the guinea pig, ľOR immunoreactivity is confined mainly to the myenteric plexus. ľOR myenteric neurones are most numerous in the small intestine, followed by the stomach and the proximal colon. ľOR immunoreactive fibres are dense in the muscle layer and the deep muscular plexus, where they are in close association with interstitial cells of Cajal. This distribution closely matches the pattern of enkephalin. ľOR enteric neurones comprise functionally distinct populations of neurones of the ascending and descending pathways of the peristaltic reflex. In human gut, ľOR immunoreactivity is localized to myenteric and submucosal neurones and to immune cells of the lamina propria. ,OR immunoreactivity is located in both plexuses where it is predominantly in varicose fibres in the plexuses, muscle and mucosa, whereas ,OR immunoreactivity appears to be confined to the myenteric plexus and to bundles of fibres in the muscle. ľOR undergoes endocytosis in a concentration-dependent manner, in vitro and in vivo. Pronounced ľOR endocytosis is observed in neurones from animals that underwent abdominal surgery that has been shown to induce delay in gastrointestinal transit. We can conclude that all three ORs are localized to the enteric nervous system with differences among species, and that ľOR endocytosis can be utilized as a means to visualize enteric neurones activated by opioids and sites of opioid release. [source]

Cross-talk of human gut with bifidobacteria

Ilja Trebichavsky
The gut constitutes a prominent part of the immune system. Its commensal microflora plays an important role in defense and in tolerance to diet allergens. Disturbances in immune regulations may lead to food allergy. Among commensal bacteria, bifidobacteria are able to induce mechanisms of immune tolerance. Comprehension of their mutual cross-talk with the host is necessary for understanding their role in the diet and in food supplements. [source]

Evaluation of the NK2 Homeobox 1 Gene (NKX2-1) as a Hirschsprung's Disease Locus THIS ARTICLE HAS BEEN RETRACTED

M.-M. Garcia-Barceló
Summary Hirschsprung's disease (HSCR, colonic aganglionosis) is an oligogenic entity that usually requires mutations in RET and other interacting loci. Decreased levels of RET expression may lead to the manifestation of HSCR. We previously showed that RET transcription was decreased due to alteration of the NKX2,1 binding site by two HSCR-associated RET promoter single nucleotide polymorphisms (SNPs). This prompted us to investigate whether DNA alterations in NKX2-1 could play a role in HSCR by affecting the RET -regulatory properties of the NKX2,1 protein. Our initial study on 86 Chinese HSCR patients revealed a Gly322Ser amino acid substitution in the NKX2,1 protein. In this study, we have examined 102 additional Chinese and 70 Caucasian patients and 194 Chinese and 60 Caucasian unselected, unrelated, subjects as controls. The relevance of the DNA changes detected in NKX2-1 by direct sequencing were evaluated using bioinformatics, reporter and binding-assays, mouse neurosphere culture, immunohistochemistry and immunofluorescence techniques. Met3Leu and Pro48Pro were identified in 2 Caucasian and 1 Chinese patients respectively. In vitro analysis showed that Met3Leu reduced the activity of the RET promoter by 100% in the presence of the wild-type or HSCR-associated RET promoter SNP alleles. The apparent binding affinity of the NKX2,1 mutated protein was not decreased. The Met3Leu mutation may affect the interaction of NKX2,1 with its protein partners. The absence of NKX2-1 expression in mouse but not in human gut suggests that the role of NKX2,1 in gut development differs between the two species. NKX2-1 mutations could contribute to HSCR by affecting RET expression through defective interactions with other transcription factors. [source]