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A radiologic study of chronic radiation-induced injuries of the small intestine and colon.

On the basis of 144 radiation-induced intestinal and colorectal lesions seen in 109 patients, the authors review the radiologic aspects associated with such affections. Two points are emphasized: (1) the chronic and still active nature of radiation-induced injury which can explain the appearance of lesions more than 10 years after irradiation, and (2) the locoregional nature of the affection which warrants systematic exploration of the urinary tract by intravenous pyelography in addition to radiologic and endoscopic investigation of the digestive tract. The authors also advise an echography and/or CT scan to detect any neoplastic recurrence.

Barium Sulfate↗

Technical note: pig model for studying nutrient assimilation by the intestine and colon.

We have developed a system for chronically catheterizing 10- to 25-d-old pigs that permits stable isotope tracer studies of intestinal or colonic assimilation of nutrients. This model also can be used to ensure constant enteral feeding or to assess the rate of entry into the terminal ileum of carbohydrates, fats, and amino acids. A plastic cannula with a luminal flange can be surgically placed in the stomach for tracer studies of sugar digestion or for controlled infusion of any formula diet. A similar cannula can be placed in the cecum for infusion of tracer and(or) substrates for studies of fermentation. The cannula has been machined so that a washer and nut can be threaded onto it, allowing the entire apparatus to be fixed to the abdominal wall. The distal end protruding above the skin was tapered to fit standard i.v. extension tubing. A carotid arterial catheter was used to sample substrates for isotopic enrichment measurements.

Amino Acids↗

Transport functions of riboflavin carriers in the rat small intestine and colon: site difference and effects of tricyclic-type drugs.

The present study was aimed at kinetically characterizing the newly found carrier-mediated riboflavin transport system in the rat colon, comparing it with that in the small intestine, and also probing the potential roles of these transport systems in intestinal drug absorption. Riboflavin transport, evaluated by measuring the initial uptake into everted intestinal tissue sacs, was saturable with a Michaelis constant (Km) of 0.13 microM and a maximum transport rate (Jmax) of 0.74 pmol/min/100 mg wet tissue weight (wtw) in the colon. Both the Km and the Jmax were smaller than those (0.57 microM and 4.26 pmol/min/100 mg wtw, respectively) in the small intestine, suggesting that the transport system in the colon has a higher affinity to substrates and a smaller transport capacity than its counterpart in the small intestine. The carrier-mediated riboflavin transport in the colon, similarly to that in the small intestine, was Na+-dependent and inhibited by lumiflavin, a riboflavin analogue with an isoalloxazine ring, but not by D-ribose, which forms the side-chain attached to the isoalloxazine ring in riboflavin. To further clarify the substrate specificities of the transport systems, we examined the effects of several drugs with a tricyclic structure similar to isoalloxazine ring on riboflavin transport. Chlorpromazine, a phenothiazine derivative, was found to inhibit riboflavin transport in both the small intestine and the colon. Methylene blue also was found to be a potent inhibitor in both sites. These results suggest that some tricyclic-type drugs could interfere with intestinal riboflavin absorption by specific carrier-mediated transport systems. These transport systems may play roles in the absorption of tricyclic-type drugs.

Animals↗

HlyA knock out yields a safer Escherichia coli A0 34/86 variant with unaffected colonization capacity in piglets.

Escherichia coli A0 34/86 (O83:K24:H31) has been successfully used for prophylactic and therapeutic intestinal colonization of premature and newborn infants, with the aim of preventing nosocomial infections. Although E. coli A0 34/86 was described as a nonpathogenic commensal, partial sequencing revealed that its genome harbours gene clusters highly homologous to virulence determinants of different types of E. coli, including closely linked genes of the alpha-haemolysin operon (hlyCABD) and for the cytotoxic necrotizing factor (cnf1). A haemolysin-deficient mutant (Delta hlyA) of E. coli A0 34/86 was generated and its colonization capacity was determined. The results show that a single dose of the A0 34/86 wild-type or Delta hlyA strains resulted in efficient intestinal colonization of newborn conventional piglets, and that this was still considerable after several weeks. No difference was observed between the wild-type and the mutant strains, showing that haemolysin expression does not contribute to intestinal colonization capacity of E. coli A0 34/86. Safety experiments revealed that survival of colostrum-deprived gnotobiotic newborn piglets was substantially higher upon colonization by the nonhaemolytic strain than following inoculation by its wild-type ancestor. We suggest that the E. coli A0 34/86 Delta hlyA mutant may represent a safer prophylactic and/or immunomodulatory tool with unaffected colonization capacity.

Animals↗

Defective arachidonate release and PGE2 production in Gi alpha2-deficient intestinal and colonic subepithelial myofibroblasts.

BACKGROUND: Mice lacking the pertussis toxin-sensitive G-protein subunit Gi alpha2 spontaneously develop colitis and colon cancer. In the gut, arachidonate-derived prostaglandin E2 (PGE2) modulates intestinal immune responses and epithelial restitution and is derived largely from subepithelial myofibroblasts. METHODS: We tested whether known decreases in arachidonate release in cells lacking Gi alpha2 would result in decreased PGE2 production and tissue PGE2 levels. PGE2 levels were significantly decreased in the colon of Gi alpha2-/- mice. RESULTS: Gi alpha2-/- myofibroblasts from the small intestine and colon both released asymptotically equal to 50% less arachidonate and 3- to 7-fold less PGE2 and 6-keto PGF1alpha in response to adenosine triphosphate, thrombin, tumor necrosis factor-alpha, or lipopolysaccharide, in a partially cyclooxygenase (COX)-2-dependent manner. Decreased arachidonate release did not appear to be caused by a defect in cPLA2 translocation in the absence of Gi alpha2. Basal myofibroblast COX-1 and COX-2 expression was downregulated in Gi alpha2-/- cells. No differences in proliferation rates were found between serum-starved or serum-activated wild-type (WT) and Gi alpha2-/- myofibroblasts. Finally, treatment of Gi alpha2-/- mice with the EP4-specific PGE2 receptor agonist ONO-AE1-329 significantly decreased the severity of established colitis. CONCLUSIONS: These findings confirm a requirement for Gi alpha2 in intestinal and colonic myofibroblast-derived prostanoid production and confirm the importance of mucosal PGE2 in the suppression of colitis.

Animals↗

Characterization of Salmonella california and S. typhimurium strains with reduced ability to colonize the intestinal tract of broiler chicks.

This study determined the ability of eight strains of Salmonella and their agarsubcultured variants to colonize the intestinal tract of broiler chicks. Nalidixic-acid (NAL)-resistant and streptomycin-resistant subcultured strains (S. california 1989/A and S. typhimurium 3366/A) that persisted in the ceca of chicks in lower numbers than their NAL-resistant parent strains (1989/O and 3366/O) were selected for additional study S. typhimurium strain 3366/A was present in the ceca of chicks in lower numbers than the parent strain 3366/O when given concomitantly with the parent strain or when the two strains were given separately to different chicks. S. california 1989/A strain was present in the ceca in lower numbers than the parent strain after concomitant oral or intracloacal inoculation. Strains 3366/O and 3366/A of S. typhimurium differed in growth rates in BHI broth and cecal mucus. The lipopolysaccharide (LPS) profile indicated that LPS components present in S. california 1989/O were missing from strain 1989/A. A mutant of 1989/O--2095/R--was also LPS- and colonization-deficient.

Animals↗

Differential expression of three matrix metalloproteinases, MMP-19, MMP-26, and MMP-28, in normal and inflamed intestine and colon cancer.

Several matrix metalloproteinases (MMPs) have been implicated in intestinal inflammation, mucosal wound healing, and cancer progression. The purpose of this study was to examine the cellular location and putative function of MMP-19, MMP-26 (matrilysin-2), and MMP-28 (epilysin), in normal, inflammatory, and malignant conditions of the intestine. Peroperative tissue specimens from patients with ulcerative colitis (UC) (n = 16) and archival tissue samples of ischemic colitis (n = 9), Crohn's disease (n = 7), UC (n = 8), colon cancer (n = 20), and healthy intestine (n = 5) were examined using immunohistochemical analyses with polyclonal antibodies. Unlike many classical MMPs, MMP-19, MMP-26, and MMP-28 were all expressed in normal intestine. In inflammatory bowel disease (IBD), MMP- 19 was expressed in nonmigrating enterocytes and shedding epithelium. MMP-26 was detected in migrating enterocytes, unlike MMP-28. In colon carcinomas, MMP-19 and MMP-28 expression was downregulated in tumor epithelium. Staining for MMP-26 revealed a meshwork-like pattern between cancer islets, which was absent from most dedifferentiated areas. Our results suggest that MMP-19 is involved in epithelial proliferation and MMP-26 in enterocyte migration, while MMP-28 expression is not associated with inflammatory and destructive changes seen in IBD. In contrast to many previously characterized MMPs, MMP-19 and MMP-28 are downregulated during malignant transformation of the colon and may play a prominent role in tissue homeostasis.

Biomarkers↗

Expression of sucrase-isomaltase and dipeptidylpeptidase IV in human small intestine and colon.

One monoclonal antibody (8A9) against the human sucrase-isomaltase complex and one (4H3) against the human dipeptidylpeptidase IV were produced in the rat and used to immunolabel thin frozen sections of human small intestine and colon. Both enzymes were found to be expressed in the poorly differentiated crypt cells of the small intestine as well as in the mature villous cells, and very low levels were found to be expressed in the colon. Homogeneous immunolabeling of the whole colonic epithelium with the monoclonal antibody 4H3 was often observed, whereas labeling with the monoclonal antibody 8A9, if any, was either restricted to a few crypts and plateaus. The two antibodies were used to perform specific immunoprecipitation of the corresponding antigen, the N-terminal sequence of which was determined after sodium dodecyl sulfate-polyacrylamide gel electrophoresis purification and electroblotting, and were compared with those of other species. In secretor blood group A humans, both the sucrase-isomaltase and the dipeptidylpeptidase IV have type 3 blood group A determinants.

Amino Acid Sequence↗

Induction of specific immunoglobulin A in the small intestine, colon-rectum, and vagina measured by a new method for collection of secretions from local mucosal surfaces.

In order study patterns of local antibody responses following mucosal immunization of mice via different routes, a method for collection of secretions directly from mucosal surfaces was developed. Mice were immunized on days 0, 10, 17, and 24 by administration of cholera toxin into the oral cavity, stomach, colon-rectum, or vagina. At sacrifice on day 32, absorbent wicks were placed in the oral cavity and, via an applicator tube, into the vagina and distal colon-rectum and along the entire small intestine after flushing of luminal contents. Protein was quantitatively extracted from wicks, and specific anti-cholera toxin immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay. Concentrations of specific IgA in secretions at various mucosal sites were dramatically influenced by the route of immunization. Oral immunization effectively induced IgA in saliva, and the intragastric route was optimal for induction of IgA in the small intestine. High levels of specific IgA appeared on the colonic-rectal mucosal surface only after rectal delivery of antigen. Oral, gastric, and rectal immunizations also produced distant responses in the vagina. Following vaginal immunization, however, neither local nor distant IgA responses were detected. These results suggest that vaccines intended for protection of colonic-rectal and vaginal mucosal surfaces might best be administered by the rectal route.

Animals↗

Primary early-stage intestinal and colonic non-Hodgkin's lymphoma: clinical features, management, and outcome of 37 patients.

AIM: To analyze the clinical features, management, and outcome of treatment of patients with primary intestinal and colonic non-Hodgkin's lymphoma (PICL). METHODS: A retrospective study was performed in 37 patients with early-stage PICL who were treated in our hospital from 1958 to 1998. Their clinical features, management, and outcome were assessed. Prognostic factors for survival were analyzed by univariate analysis using the Kaplan-Meier product-limit method and log-rank test. RESULTS: Twenty-five patients presented with Ann Arbor stage I PICL and 12 with Ann Arbor stage II PICL. Thirty-five patients underwent surgery (including 31 with complete resection), 22 received postoperative chemotherapy or radiotherapy or both. Two patients with rectal tumors underwent biopsy and chemotherapy with or without radiotherapy. The 5- and 10-year overall survival (OS) rates were 51.9% and 44.5%. The corresponding disease-free survival (DFS) rates were 42.4% and 37.7%. In univariate analysis, multiple-modality treatment was associated with a better DFS rate compared to single treatment (P = 0.001). While age, tumor size, tumor site, stage, histology, or extent of surgery were not associated with OS and DFS, use of adjuvant chemotherapy significantly improved DFS (P = 0.031) for the 31 patients who underwent complete resection. Additional radiotherapy combined with chemo-therapy led to a longer survival than chemotherapy alone in six patients with gross residual disease after surgery or biopsy. CONCLUSION: Combined surgery and chemotherapy is recommended for treatment of patients with PICL. Additional radiotherapy is needed to improve the outcome of patients who have gross residual disease after surgery.

Adolescent↗

Small-intestinal and colonic changes after biliopancreatic bypass for morbid obesity.

Morphologic and functional adaptations of the functioning intestine were evaluated in 41 patients before and after biliopancreatic bypass for morbid obesity. This surgical procedure diverts pancreatobiliary secretions via the duodenum and the jejunum into the colon, the remaining small intestine being anastomosed to the stomach after antrectomy. In the proximal ileum there was an 80% increase of the height of villi; the specific activities of maltase, sucrase, and aminopeptidase in brush border membranes remained unaffected, and that of lactase tended to decrease. In the distal ileum villi heights increased only by 58%, and disaccharidase activities (except for maltase) were slightly enhanced. In the colon the mucosa displayed, in some patients, focal appearance of true villi, and brush border enzyme activities increased concomitantly. We conclude that biliopancreatic bypass induces an adaptation of all intestinal segments of the functioning intestine; this adaptation tends to compensate for the shortening of the gut continuity.

Adult↗

[The possibility of colonizing the intestines of white mice with Lactobacillus acidophilus during bacterial therapy].

The study revealed the possibility, on principle, for L. acidophilus strain VKM V-2020 D to colonize the intestine of white mice with the preservation of the viability of lactobacilli subjected to the action of antibiotics. The culture of this strain, isolated from the animals, showed the stability of its biological properties: resistance to polymyxin M, kanamycin, cyprofloxacin, nalidixic acid (including acquired resistance to rifampicin), as well as pronounced antagonism with respect to Vibrio cholerae. Good prospects for the use of L. acidophilus strain VKM V-2020 D for further studies regarding its use for prophylaxis and therapy were noted.

Animals↗

Bacterial infections of the small intestine and colon.

Bacterial infections of the small and large intestine are widespread and continue to be topics of active research. Surveys document the importance of diarrheal disease in many settings. Major breakthroughs in the understanding of pathogenic mechanisms (especially the interactions of bacteria and intestinal cells) continue, particularly with respect to shigella, salmonella, Yersinia species, and enteropathogenic Escherichia coli. Pathogenic mechanisms of other bacteria, such as campylobacter and entero-aggregative E. coli, are not well defined. Vaccines for cholera and typhoid fever are available, and new vaccines are in various stages of development ranging from synthesis of novel constructs to large-scale field trials. Several candidate vaccines are being exploited as carriers of antigens from other pathogens. Extraintestinal complications from salmonella, shigella, campylobacter, Yersinia species, and Shiga toxin-expressing E. coli are receiving much attention. Genomic sequencing of several of these pathogens is underway. The impact of this work is hard to predict, but expectations are high.

Journal Article↗

[Differential diagnostic and prognostic criteria of precancerous processes and cancer of the large intestine].

Colon epithelial tumours from 682 patients have been analyzed. The incidence of the background processes in the mucous membrane adjacent to the tumour is established as a function of tumour progression. Transition of the mucus formation to the sialomucin synthesis in the transitional mucous membrane was observed in 1/3 of the cases. Of prognostic value for the 5-year survival were such indices as a stage of the disease according to Guttman and Dukes, tumour macroscopy, the state of regional lymph nodes and the degree of carcinoma differentiation. The data on the content of the immunocompetent cells, tissue basophils and their degranulation, eosinophils, lymphocyte plasmatization, depending on the stage of the disease are also presented.

Adenocarcinoma↗

Abnormal intestinal permeability pattern in colonic Crohn's disease. Absorption of low molecular weight polyethylene glycols after oral or colonic load.

Intestinal permeability to different-sized polyethylene glycols in Crohn's disease of the colon was compared with that in ileal Crohn's disease and in controls without inflammatory bowel affection. The permeability was assessed both after ingestion of the marker (oral load) and after deposition in the colon during colonoscopy (colonic load). After oral load the absorption was least in the patients with colonic Crohn's disease, intermediate in ileal disease, and greatest in the controls. After colonic load, however, the values were highest in colonic Crohn's disease. The study indicated that in Crohn's disease of the colon there is abnormal permeability in apparently uninvolved proximal small intestine as well as in the colon. Since oral load tests preferentially reflect the absorptive properties of the proximal small bowel, regional tests of absorption are important when the aim is to assess the permeability of the distal small intestine or the colon.

Administration, Oral↗

beta-Hexosaminidase isoenzymes in tissues, cultured cells, and media from human fetal intestine and colonic adenocarcinoma.

Isoelectric focusing of tissue homogenates revealed a predominance of beta-hexosaminidase B in colonic adenocarcinoma, whereas beta-hexosaminidase A was greater in paired normal-appearing colonic mucosa from the same patients as well as in a specimen of human fetal colonic mucosa. Because of the recognized cellular heterogeneity of these tissues, our studies were extended to an examination of these isoenzymes in 20 cultured epithelial cell lines derived from human fetal intestine and colonic carcinoma as well as the secreted enzymes in their culture media. While the B:A isoenzyme ratio was higher in human cancer cells as compared to fetal cells, some of the cancer cell lines had a greater proportion of the A isoenzyme. Examination of the isoenzyme profiles in the media of these cells revealed a greater B:A ratio whether of fetal or cancer cell origin. These studies parallel the apparent biological differences of neoplastic colonic epithelium occurring in vivo and are reminiscent of reported oncodevelopmental changes in enzymatic properties present in some malignant tissues. The differential stabilities of these two isoenzymes derived from the culture media of both types of cell lines in vitro may limit their value as markers of human colonic neoplasia.

Adenocarcinoma↗

Comparative assessment of small intestinal and colonic permeability in HIV-infected homosexual men.

OBJECTIVES: To investigate both small and large intestinal permeability in HIV-positive subjects, and correlate variation in intestinal mucosal abnormality with immunological and nutritional markers of HIV disease. METHODS: Small and large intestinal permeability studies were performed in 14 HIV-seropositive patients and eight healthy men. Eight out of the 14 patients had diarrhoea and all subjects were negative for enteropathogens. Small intestinal permeability was determined using the lactulose-mannitol test and large intestinal permeability using the colonic absorption of 51Cr-EDTA. In addition, CD4 cell count, beta 2-microglobulin, C-reactive protein estimation and anthropometry were carried out in all subjects. RESULTS: HIV-seropositive subjects had higher lactulose-mannitol ratios (LMR; 0.084 +/- 0.007 versus 0.013 +/- 0.0008) and lower 51Cr activity (1.986 +/- 0.066 versus 3.115 +/- 0.560) than controls (P < 0.0004 and P < 0.05, respectively). Colonic uptake of 51Cr-EDTA was no different between subjects with and those without diarrhoea (2.04 +/- 0.124 versus 1.92 +/- 0.143, P > 0.05). A negative correlation was found between LMR and 51Cr-EDTA, but only for patients with diarrhoea (r = -0.81; P = 0.015). CONCLUSION: Regional variation affecting intestinal absorptive function occurs in patients with HIV-related diarrhoea and is characterized by increased LMR and reduced colonic uptake of 51Cr-EDTA. The pathogenesis and clinical significance of such changes are unknown.

AIDS-Related Opportunistic Infections↗

Distribution of vasoactive intestinal polypeptide and substance P receptors in human colon and small intestine.

Vasoactive intestinal polypeptide (VIP) and substance P are found in neurons in the lamina propria and submucosa and muscularis propria of human small intestine and colon. VIP receptors coupled to adenylate cyclase are present on epithelial, smooth muscle, and mononuclear cells. This study analyzes the distribution of [125I]VIP binding and [125I]substance P in human colon and small intestine using autoradiographic techniques. [125I]VIP binding was present in high density in the mucosal layer of colon and small intestine. [125I]VIP binding was not significantly greater than nonspecific binding in smooth muscle layers or the lymphoid follicles. In contrast, [125I]substance P binding was present in high density over the colonic muscle but was not present over the mucosal layer. In human colon cancer, [125I]VIP grain density over the malignant tissue was only slightly higher than background. These autoradiographic studies of [125I]VIP binding indicate that the highest density of VIP receptors was found in the small intestine and superficial colonic mucosa, whereas the density of substance P receptors was highest over the smooth muscle layers. These findings suggest a mismatch between immunochemical content of the peptide and autoradiographic density of the receptor.

Autoradiography↗