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Early alterations of rat intestinal diamine oxidase activity by azoxymethane, an intestinal carcinogen.

Some mutagenic hydrazino compounds are also diamine oxidase inhibitors. Therefore, this interrelationship was studied for the intestinal carcinogen azoxymethane. In vitro, azoxymethane was a very weak inhibitor of rat intestinal diamine oxidase activity. In vivo, after subcutaneous injection of a single dose of azoxymethane, diamine oxidase activity was increased in the duodenum but was mainly inhibited in the colon. Intestinal diamine oxidase activity may then be influenced by regulatory processes induced by azoxymethane rather than by a direct effect.

Amine Oxidase (Copper-Containing)↗

Comparative assessment of D-xylose absorption between small intestine and large intestine.

The present study aimed to evaluate the absorption of D-xylose, a passively absorbed five-carbon monosaccharide, from the large intestine compared with the small intestine, in order to explore the absorption potential of the large intestine. D-Xylose absorption was evaluated in the intestinal loop and everted sacs in rats and comparisons were made between small intestine (mid-gut) and large intestine (colon). The absorption of D-xylose was smaller, by an order of magnitude or more, after administration into the loop of large intestine than after administration into that of small intestine, based on appearance in plasma and disappearance from the intestinal loop. D-Xylose absorption was practically insignificant (nominal 4.9%) in 60 min in the large intestine, whereas it was moderate (57.0%) in the small intestine. Consistently, the uptake of D-xylose in everted sacs was about 20 times larger in the small intestine than in the large intestine. Thus the passive membrane permeability of D-xylose was demonstrated to be negligible in the large intestine, even though the small intestine was fairly permeable. This result helps rationalize kinetic modelling strategies assuming the small intestine as the sole absorption site for gastrointestinal absorption in-vivo. It also suggests that hydrophilic drugs with molecular size similar to or larger than D-xylose may not be good candidates for colonic drug delivery by controlled release.

Animals↗

Detection and enumeration of colonic mucosal cells in amniotic fluid using a colon epithelial-specific monoclonal antibody.

Since its introduction, prenatal diagnosis of chromosomal and metabolic disorder by midtrimester amniocentesis has relied upon the use of a mixture of fetal cells obtained from amniotic fluid. Little knowledge has been gained in the sorting of these cells for diagnosis of tissue-specific disorders. In an attempt to determine the contribution of fetal colonic mucosal cells to the overall amniocyte population, we used the colonic epithelial-specific monoclonal antibody (MC-Ab) 7E12H12, IgM isotype. Specimens of the small intestine, colon, buccal mucosa, kidney, urinary bladder, and umbilical cord were obtained from electively aborted normal fetuses of 12-28 weeks' gestation. All of these specimens were examined with 7E12H12 by the immunoperoxidase technique. The MC-Ab reacted with the colonic epithelial cells but not with any of the other tissues. In addition, 40 amniotic fluid samples obtained from women between 16 and 18 weeks of gestation, who underwent amniocentesis because of advanced maternal age, were tested using a fluorescent activated cell sorter. Among the amniotic fluid specimens examined, 18.4 +/- 10.3 per cent cells reacted with 7E12H12. Double immunofluorescence studies revealed that all Mc-Ab-stained cells contained secretory component, confirming that they were epithelial in origin. All fetuses whose amniotic fluid was analysed had normal karyotypes and amniotic fluid alpha-fetoprotein levels that were also normal. This study demonstrates that cell-specific Mc-Ab can be used to detect colon cells in the amniotic fluid and that colon cells contribute significant numbers in the mixture of amniotic fluid cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid↗

[A case of Wegener's granulomatosis associated with refractory bowel granulomatous ulcers].

We describe a 58-year-old woman who developed Wegener's granulomatosis (WG) complicated by a perforation of the transverse colon caused by necrotizing granulomatous vasculitis. In addition, her colon lesion continued in spite of high dose corticosteroid and cyclophosphamide therapy. She was admitted to our hospital because of her severe tonsillitis in Dec., 1994. She was diagnosed as having WG because she had oral ulcer, antibiotics-resistant lung infiltration, renal dysfunction and positive C-ANCA. Just after we started high dose steroid therapy, the transverse colon was perforated because of vasculitis, and she underwent emergency operation. Many vasculitic lesions were found in the small intestine, colon, and mesenterium. The disease was improved by corticosteroid and cyclophosphamide therapy except for a sustained ulcer with necrotizing vasculitis in the sigmoid colon region even 1 year after the operation. Although WG rarely complicates digestive tract lesions as initial manifestations, they reach 12% of the causes of death of WG in Japan. Therefore, we should take care of digestive tract lesions when we follow-up patients with WG.

Antibodies, Antineutrophil Cytoplasmic↗

Naturally occurring Tyzzer's disease and intestinal spirochetosis in guinea pigs.

Bacillus piliformis infection (Tyzzer's disease) occurred in two young guinea pigs, causing unthriftiness and diarrhea which resulted in death. There was necrosis and inflammation of the ileum, cecum, and colon. Intestinal epithelial cells contained organisms resembling Bacillus piliformis. Spirochetes were found in the cecum and colon, mainly in crypts. Acute diarrhea occurred in another guinea pig which became cachetic and was killed. Histologically, large numbers of spirochetes were present in the wall of both the cecum and colon, and they were associated with severe necrosis and inflammation. Bacillus pilformis was not found in this animal.

Animals↗

Diarrhea and intestinal invasiveness of Aeromonas strains in the removable intestinal tie rabbit model.

Twelve Aeromonas strains were tested for virulence by using the removable intestinal tie adult rabbit diarrhea model. Mortality was 50% or greater for 7 of 12 strains; 23 of 37 rabbits that died developed diarrhea before death, and 11 of 27 surviving rabbits developed diarrhea. Aeromonas bacteremia was detected in 36 of 37 (97%) animals that died, but only in 2 of 27 (7%) survivors. Death, diarrhea, and bacteremia were all strongly strain dependent. Gastrointestinal lesions varied from moderate focal enteritis to severe multifocal necrosis and hemorrhage of the ileal mucosa, often accompanied by hepatic and splenic lesions. Intestinal colonization assays performed after infection indicated that the ileum was the most heavily colonized portion of the gut and the probable site of invasion. The application of the removable intestinal tie adult rabbit diarrhea model for intestinal challenge with Aeromonas strains has shown that some isolates are capable of invading the mucosa of rabbits, causing diarrhea and bacteremia. These data suggest that such strains may be important in causing human invasive diarrhea.

Aeromonas↗

Effect of carbohydrates on Salmonella typhimurium colonization in broiler chickens.

The effect of carbohydrates in the drinking water of broiler chickens on Salmonella typhimurium colonization was evaluated. Results indicate that mannose and lactose (2.5%) significantly (P less than 0.05) reduced intestinal colonization of S. typhimurium by at least one-half, as compared with dextrose, maltose, and sucrose. Lactose and mannose also significantly reduced (P less than 0.01) the mean log10 number of S. typhimurium in the cecal contents. Although mannose was the most effective sugar at blocking colonization, lactose may be more practical because it is effective and costs much less than mannose. Provision of carbohydrates in the drinking water had no significant effect on weight gain.

Animals↗

Intestinal paracoccidioidomycosis simulating colon cancer.

We report a case of intestinal involvement of Paracoccidioidomycosis, in a patient considered to have colonic cancer. The diagnosis of this mycosis should be considered when an abdominal mass associated with intra-lesional calcifications on X-ray is observed. CT scans increase the findings.

Colonic Diseases↗

Cytokeratin 19 expression in human gastrointestinal mucosa during human prenatal development and in gastrointestinal tumours: relation to cell proliferation.

Cytokeratin (CK) immunohistochemistry revealed changes in the CK19 immunoreactivity in human gastrointestinal epithelium during embryonic and fetal development. These changes were particularly marked in the jejunum and ileum. CK19 immunoreactivity was strong up to the 11th week of pregnancy, but was absent between weeks 12 and 17, and reappeared weakly from week 18 to week 24. This temporal pattern correlated with that of cell proliferation investigated by immunohistochemical detection of proliferating cell nuclear antigen. Marked CK expression was associated with a low proliferative rate and vice versa. To test whether these results were relevant to the assessment of intestinal metaplasia and the risk of malignant transformation with poor cell differentiation, adenomas and adenocarcinomas of the colon, intestinal metaplasia of the stomach, and two types of gastric carcinoma were also examined by CK19 immunohistochemistry. Substantial CK19 immunoreactivity was found in well-differentiated cancers and low-grade dysplasias with low cell proliferation, whereas only weak CK19 immunoreactivity was found in poorly differentiated carcinomas and high-grade dysplasias with a high proliferation rate.

Adenocarcinoma↗

Improved longevity and functionality of a canine model providing portal vein and multi-site intestinal access.

BACKGROUND AND PURPOSE: The canine intestinal and venous access port (IVAP) model is valuable for investigating hepatic elimination and region-specific intestinal absorption of pharmaceuticals. Previously, long-term functionality of this preparation has been variable. METHODS: Catheters of different construction were placed in the proximal and distal portions of the small intestine, colon, and portal vein of subject animals and were attached to separate subcutaneous access ports. Intraoperative, postoperative, and long-term maintenance techniques were developed, modified, and analyzed. RESULTS: Intestinal catheter infections and access site failures were associated with breakdown at the intestinal insertion site. The ileal catheter was prone to obstruction with ingesta. A modified Witzel technique, specialized port-catheter systems, scheduled port-flushing methods, and venous port infection treatment protocols improved the model's longevity. CONCLUSIONS: The canine IVAP model is a powerful tool for investigation of regional differences in intestinal absorption and hepatic elimination of drugs. Other researchers can derive increased longevity with the IVAP model by using the technical modifications detailed here: strict sterile technique, closed-end slit-valve catheters, GPV ports, the Witzel tunnel technique, routine portal vein infection surveillance, 50% dextrose intestinal catheter infusion, rapid removal of infected intestinal catheters, and critical appraisal of their results. Longevity of the model continues to be improved.

Animals↗

Biochemical and immunohistochemical analysis of glycosaminoglycans in inflamed and non-inflamed intestinal mucosa of patients with Crohn's disease.

OBJECTIVES: Changes in extracellular matrix glycosaminoglycans (GAGs) of the intestinal mucosa have been associated with inflammatory bowel disease. The aim of the present study was to follow the changes in GAGs metabolism during the progression from non-inflamed to inflamed intestinal colon of patients with Crohn's disease (CD), using direct biochemical analysis and specific immunohistochemistry against chondroitin/dermatan sulfate and heparan sulfate. DESIGN AND METHODS: The content of GAGs from inflamed and non-inflamed colon of eight patients with active CD was estimated by uronic acid per dry weight of tissue and analyzed by agarose gel electrophoresis and ion-exchange chromatography. Intestinal sections were stained using antibodies against dermatan sulfate/chondroitin 4-sulfate (DS/CS), heparan sulfate (HS), and ICAM-1 (CD54), and analyzed by confocal microscopy. RESULTS: There was a reduction in the amount of GAGs in the non-inflamed colon of patients with CD. In the inflamed colon, HS, CS and DS showed increased concentrations compared with the non-inflamed colon. GAGs showed a diffuse distribution in the lamina propria and in the basement membrane of both inflamed and non-inflamed mucosa of patients with CD. CONCLUSION: We observed a marked reduction in GAGs with altered patterns of distribution in the non-inflamed colon of patients with CD. The increase in the synthesis of GAGs observed in the inflamed colon may be a compensatory mechanism for the restoration of the integrity of the intestinal mucosa.

Adult↗

Effect of serotonin treatment on intestinal transport in the rabbit.

The hormone serotonin (5-hydroxytryptamine) has been implicated as the cause of the diarrhea seen in many patients with the carcinoid syndrome. To determine whether serotonin is an intestinal secretagogue, the effect of serotonin on intestinal water and electrolyte transport was evaluated in the rabbit. Two weeks of daily subcutaneous injection of serotonin suspended in oil resulted in a blood serotonin level elevated to twice that of controls. Intestinal transport was studied in vivo by a perfusion technique. Serotonin treatment resulted in ileal secretion and decreased mid-jejunal absorption of water and electrolytes but did not effect water absorption in the proximal jejunum or colon. Intestinal absorption of D-glucose and the amino acid L-tryptophan and glucose-dependent water and electrolyte absorption were normal in serotonin-treated animals. Serotonin-induced ileal secretion was reversed by methysergide, a peripheral antagonist of serotonin action. No alterations in intestinal histology or permeability occurred in serotonin-treated animals. Serotonin-induced intestinal secretion was not associated with alterations in the activities of intestinal mucosal adenylate cyclase, cyclic nucleotide phosphodiesterase, or Na-K-ATPase.

Animals↗

Survival of Escherichia coli host-vector systems in the mammalian intestine.

Survival in the mouse and human intestine of Escherichia coli host-vector systems used and proposed for recombinant DNA technology was assessed. There was no detectable survival of severely disabled E. coli K12 strain X1776 in mice or in human subjects 24 hours after ingestion. The same strain bearing the plasmid pBR322, however, was recovered from human subjects for 4 days in amounts of six organisms for every million ingested. Nondisabled E. coli K12 strain X1666, with or without pBR322, survived in 10(4)-fold greater numbers and for 2 days longer, with better recovery of the plasmid-containing derivative. Although the plasmid-bearing strains were recovered for longer periods, no intestinal colonization was noted. Despite the presence of pBR322 for a maximum of 6 days in the human intestine, there was no evidence that it was transferred from either bacterial host to endogenous aerobic fecal bacteria.

Animals↗

Morphology of myenteric plexuses in the human large intestine: comparison between large intestines with and without colonic diverticula.

BACKGROUND: Large intestines with diverticula exhibit functionally abnormal peristaltic activity and elevated luminal pressure that may indicate functional changes in the myenteric plexus; however, no studies have investigated the characteristics of either normal or diverticula myenteric plexuses. METHODS: Tissue specimens obtained from 93 colorectal cancer patients without diverticula, 14 patients with perforated diverticulitis, and 12 colorectal cancer patients with asymptomatic diverticula were included in this study. Myenteric plexuses and ganglion cells were counted per centimeter, and the area and maximum diameter of the nuclei of ganglion cells were measured using an image analyzer. RESULTS: The number of myenteric plexuses and ganglion cells per centimeter was significantly higher in the descending colon, sigmoid colon, and rectum than in the cecum, ascending colon, and transverse colon. The area of the nuclei of ganglion cells was significantly larger in the descending colon and sigmoid colon than in the cecum and ascending colon. Compared with large intestines without diverticula, the number of myenteric plexuses was significantly higher in large intestines with diverticula, whereas the number of ganglion cells decreased in both right-sided and left-sided large intestines with perforated diverticulitis or asymptomatic diverticula. The area of the nuclei of ganglion cells was significantly smaller in large intestines with diverticula. CONCLUSION: The morphology of myenteric plexuses and the ganglion cells differs significantly among segments of the human large intestine. Large intestines with diverticula had significantly more plexuses but significantly fewer ganglion cells than large intestines without diverticula. The area of the nuclei of ganglion cells was also significantly smaller in large intestines with diverticula. Further studies are required to clarify how these changes are related to intestinal function and how they are involved in the etiology of diverticulosis.

Adult↗

Characterization and tissue specificity of a monoclonal antibody against human uridine 5'-diphosphate-glucuronosyltransferase.

A monoclonal antibody against human liver uridine 5'-diphosphate-glucuronosyltransferase (UDPGTase) was developed. Enzyme inhibition studies with this monoclonal antibody showed inhibition of human liver UDPGTase activity with bilirubin, 4-methylumbelliferone, and 4-nitrophenol as substrates. Testosterone, estrone, and phenolphthalein UDPGTase activity was not inhibited. The monoclonal antibody probably recognizes the uridine 5'-diphosphate-glucuronic acid binding site at 4-nitrophenol UDPGTase. Proteins with a molecular mass of 54,000 daltons were immunopurified from solubilized human liver using the monoclonal antibody as ligand coupled to Sepharose 4B beads. The distribution of UDPGTase isoforms in various human tissues was studied by immunofluorescence. The enzyme could be detected in liver, kidney, stomach, small intestine, colon, and skin. In liver, only hepatocytes contain UDPGTase. In kidney, the enzyme was localized exclusively in proximal tubuli and in stomach in epithelial mucous cells. In small intestinal epithelium, maximal fluorescence was seen at the villous tip. In colon, all lining epithelial cells were stained. In colon polyps, staining for UDPGTase was clearly decreased, and in colon carcinoma it was undetectable. In skin, the stratum corneum was intensely stained, whereas the stratum basale showed no fluorescence.

Animals↗

Comparative effects of strain, species, and sex on the acyltransferase- and sulfotransferase-catalyzed activations of N-hydroxy-N-2-fluorenylacetamide.

The arylhydroxamic acid acyltransferase, an enzyme that promotes the introduction of arylamine groups into nucleic acids, is greater in the stomach, small intestine, colon, and lung of the Sprague-Dawley rat than in comparable tissues of Fischer animals. The enzyme is distributed relatively evenly from the glandular stomach to the distal portion of the colon. No consistent differences in acyltransferase activities of the liver, kidney, brain, or spleen of these two strains were noted. Acyltransferase activity was readily demonstrable in the livers of guinea pigs, hamsters, rabbits, and monkeys; in the kidneys of guinea pigs and hamsters; in the stomachs of guinea pigs and hamsters; in the small intestines of guinea pigs, hamsters, rabbits, and monkeys; in the colons of guinea pigs and hamsters; and in lungs of hamsters. Mouse, dog, and goat tissues were essentia-ly devoid of acyltransferase activity. The transformation of N-hydroxy-N-2-fluorenylacetamide into a reactive species by conjugation with sulfate was carried out with 105,000 times g supernatants of liver from Sprague-Dawley and Fischer rats and their Flhydrids. The abilities of liver extracts from the hybrids to carry out this activation were intermediate between those from animals of the same sex of the two parental strains.

Acetyltransferases↗

Mucinous adenocarcinoma of the colon metastatic to the intestinal mucosa.

Autometastasis of colon cancer to the intestinal mucosa is a condition that has not been previously described. The 70-year-old man presented in this case report was seen for routine surveillance colonoscopy 14 months after low anterior resection, without anastomosis, of a Dukes' stage C mucinous adenocarcinoma of the rectosigmoid. The patient had received adjuvant chemotherapy according to Southwest Oncology Group protocol 8899. The routine colonoscopy revealed many new polypoid lesions in the remaining left and transverse colon, and the patient underwent completion total abdominal colectomy. Examination of the specimen revealed more than 100 polyps; the histologic examination identified these polyps as metastatic signet ring mucinous adenocarcinoma.

Adenocarcinoma, Mucinous↗

Typhlocolitis associated with spirochaetes in goose flocks.

The role of Brachyspira bacteria in the aetiology of increased mortality observed in two breeder goose flocks (Flock A consisting of 1,500 and Flock B comprising 4,500 laying geese) at the end of the first egg-laying season, in the period of moulting, was studied. In Flock A 415 geese (28%) died during an 8-week period while in Flock B 834 geese (18%) died during a 12-week period. On gross pathological examination, the geese were found to have haemorrhagic-to-necrotic inflammation of the large intestine (colon and rectum) and fibrinonecrotic typhlitis accompanied by severe degeneration. Often, fibrosis of the kidneys, and in five of the geese secondary visceral urate deposition ("visceral gout") was also observed. Histopathological examination consistently demonstrated spirochaetes in the mucous membrane of the affected large intestine. This was confirmed by the results of immunohistochemical and electron microscopic examination. In addition, Trichomonas stages were also detected from the large intestine of 11 geese. On the basis of their cultural and biochemical properties, and PCR sequencing analysis, eight out of the nine spirochaete strains isolated from the geese by culture on special media under anaerobic conditions were identified as Brachyspira alvinipulli. This is the first report on the isolation of B. alvinipulli from laying geese affected with fibrinonecrotic typhlocolitis.

Animals↗