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Phytohaemagglutinin-induced lymphocyte transformation in patients before and after resection of large intestinal cancer.

Lymphocyte responses to stimulation with phytohaemagglutinin (PHA) have been compared in 20 patients with large intestinal cancer, 10 patients whose large intestinal cancers have been removed, and in 30 age- and sex-matched control individuals. Responses were markedly reduced in the tumour-bearing patients and were unaffected by substituting normal for autologous plasma during incubation. Responses, however, were normal after tumour resection suggesting that the defect in lymphocyte responsiveness is a reversible one and related to the presence of tumour tissue.

Anus Neoplasms↗

A new method: double Thiry-Vella fistulas in rats to compare the effects of small and large intestinal stimulation on behaviour.

A new method for comparing the effects of small and large intestinal mechanical stimulation was developed. Isolated intestinal loops were created by the Thiry-Vella method from the lower duodenal--upper jejunal, and from the upper colonic portion of the gut, respectively. This preparation allows parallel evaluation of stimulation effects and affects from both the small and the large intestine of the same animal. A balloon could be inserted into the isolated loops before each experimental session and removed afterward. Behavioral thresholds to changes in the volume of the gut were recorded and compared in the two loops. No essential differences between the two portions of the intestinal tract were detected by this method.

Animals↗

Improvement of large intestinal absorption of insulin by chemical modification with palmitic acid in rats.

The intestinal absorption of 125I-labelled palmitoyl insulin was examined following administration into in-situ closed large intestinal loops of rats. When mono- and dipalmitoyl insulins (Palins-1 and Palins-2, respectively) were administered in polyoxyethylene hydrogenated castor oil (HCO 60) micellar system into intestinal loops, a marked increase in plasma radioactivity and a corresponding disappearance of residual radioactivity in the intestinal lumen were observed in the following rank order: Palins-2 greater than Palins-1 greater than native insulin. In addition, the derivatives were more stable than native insulin in the mucosal tissue homogenates of the large intestine. These results suggest that chemical modification of insulin with palmitic acid may not only increase the lipophilicity of insulin but also reduce its degradation, resulting in the increased transfer of insulin across the large intestinal mucous membrane. The linoleic acid-HCO 60 mixed micelles system did not have a significant effect on the large intestinal absorption of radioactivity associated with the lipophilic insulin analogues.

Animals↗

Regional response leading to tumorigenesis after sulindac in small and large intestine of mice with Apc mutations.

Sulindac and other NSAIDs have been widely studied as potential chemopreventive agents for colon cancer. Short-term studies have shown adenomatous polyps to regress in patients with familial adenomatous polyposis (FAP). In this study the effect of sulindac on cancer as an endpoint was evaluated in ApcMin mice, a preclinical model of FAP with an Apc mutation in codon 850 that leads to gastrointestinal adenomas and carcinomas. Three groups of mice were studied all of which were fed AIN-76A diet: one group was fed AIN-76A diet alone, a second group received sulindac 200 p.p.m. premixed in the diet and a third group received sulindac 180 p.p.m. added in drinking water. ApcMin mice were killed 9 weeks after feeding was initiated. Mice receiving sulindac developed fewer tumors in the intestine overall; the major decrease in tumor development after sulindac was seen in the small intestine regardless of route of administration. In the large intestine, however, sulindac significantly increased the incidence, multiplicity and volume of tumors in the colon of ApcMin mice, a regional response to sulindac differing from previous reports. Quantitative measurements of apoptosis, Bax and Bcl-xL protein expression in the ApcMin mice revealed the ratio of Bax/Bcl-xL expression and apoptosis increased in the small intestine but decreased in the cecum, consistent with the regional tumorigenesis observed after sulindac. These findings thus suggest involvement of Bax and apoptosis in tumors developing after sulindac treatment in this mouse model.

Animals↗

Expression of IL-10 receptors on epithelial cells from the murine small and large intestine.

The appearance of chronic intestinal inflammation in IL-10 knockout mice suggests IL-10 may inhibit adverse responses to luminal antigen. Moreover, this inflammation is associated with an increase in class II MHC molecule expression on intestinal epithelial cells. Thus, the role of IL-10 regulation in epithelial cell function was investigated. Using RT-PCR, it was shown that intestinal epithelial cells express mRNA for both subunits of the IL-10 receptor-signaling complex. In addition, biotinylated IL-10 was shown to bind to both cultured and freshly isolated intestinal epithelial cells prepared from the small or large intestine. This binding appeared specific as it was blocked by neutralizing antibodies to IL-10 but not the isotype control. Moreover, an excess of native IL-10 also inhibited the binding of radiolabeled IL-10. To evaluate whether IL-10 mediated any functions through this receptor, epithelial cells were cultured with IL-10 alone or with IFN-gamma plus IL-10. IL-10 alone had no detectable effects on epithelial cell growth or their expression of class II MHC molecules but it did antagonize the effect of IFN-gamma on the viability of cultured cells. In addition, IL-10 blocked the IFN-gamma-induced expression of class II MHC molecules on cultured epithelial cells. These results suggest that IL-10 binds to a specific receptor on intestinal epithelial cells and may regulate the contribution of epithelial cells to the inflammatory and immune response in the digestive tract.

Animals↗

The effect of luminal pH on large intestinal absorption in ulcerative proctocolitis.

The sensitivity of large intestinal absorption to pH and the absorption of short-chain fatty acids were measured in ulcerative proctocolitis by a dialysis bag method. Lowering luminal pH from 7 to 5.5 significantly reduced absorption of salt and water in proctocolitis, but not in normal controls. Short-chain fatty acid absorption was not affected by inflammation or change in pH when patients with ulcerative proctocolitis were compared with controls.

Adult↗

Multifocal carcinoma of the large intestine.

Five cases of multifocal carcinoma of the large intestine are described, including one multifocal recurrence, the only one described in the literature. All of them were recognised radiologically before operation. The importance of a thorough examination of the whole colon in suspected cases is stressed, even when a single lesion has been demonstrated.

Adenocarcinoma↗

Effect of dietary copper sulfate, Aureo SP250, or clinoptilolite on ureolytic bacteria found in the pig large intestine.

The predominant ureolytic bacteria in the pig large intestine were determined while growing pigs were fed a basal diet or basal diet plus copper sulfate, Aureo SP250, or clinoptilolite. Fecal samples were collected from four pigs fed each diet at 3, 9, and 14 weeks and analyzed for total colony counts and percent ureolytic bacteria. Fecal urease activity, ammonia nitrogen, and identity of the ureolytic bacteria were determined at 14 weeks. Copper sulfate and Aureo SP250 reduced the number of ureolytic organisms, with a marked decrease occurring in the Streptococcus spp., which made up 74% of the ureolytic isolates from the pigs on the basal diet. Other ureolytic species detected at lower concentrations were Staphylococcus spp., Selenomonas ruminantium, Bacteroides multiacidus, and Eubacterium limosum. Copper sulfate also reduced fecal urease activity (P less than 0.10). Fecal ammonia concentrations were not different between pigs fed the various diets. These data suggest that the streptococci are the most numerous ureolytic species in the pig intestinal tract and are significantly reduced by copper sulfate and Aureo SP250; however, only copper sulfate reduced intestinal urease activity.

Aluminum Silicates↗

Production, metabolism, and excretion of hydrogen in the large intestine.

Hydrogen is produced during fermentation in the large intestine and may be excreted in breath and flatus or further metabolized by the flora. However, there is little information about total H2 excretion from different substrates or the extent to which it is metabolized in the colon. We have therefore measured total H2 and methane excretion in 10 healthy subjects using a whole body calorimeter. Breath gases were measured simultaneously with total excretion in response to lactulose, pectin, and banana starch. Metabolic activities of the predominant H2 consuming anaerobes (methanogenic, sulfate reducing, and acetogenic bacteria) were measured in fecal samples. Total H2 excretion on a starch and fiber-free diet was 35 +/- 6.1 mL/24 h +/- SEM. H2 from 7.5 g, 15 g, and 22.5 g lactulose was 88.1 +/- 22.4 mL, 227.0 +/- 60.7 mL, and 321.8 +/- 79.2 mL. Four of the subjects also excreted CH4, which was 51.3 +/- 5.5 mL, 97.3 +/- 18.4 mL, and 157.5 +/- 36.3 mL for the respective lactulose doses. H2 excretion was less in methanogenic subjects (7.9 mL/g lactulose) than in nonmethanogenic (17.3 mL/g), but total H2 excreted as, hydrogen + methane, was 34.9 mL/g. H2 from pectin (20 g) was 14.1% +/- 3.2% and from starch (22.2 g) 38.6% +/- 9.2% of an equivalent lactulose dose. Sixty-five percent of total H2 and CH4 was expired in breath at total excretion rates up to 200 mL/24 h. Over this the proportion decreased to 25% with an overall average of 58%. Only subjects with CH4 excretion in vivo showed methanogenesis in feces, whereas nonmethanogenic subjects showed high sulfate-reducing activity in feces (58.7 +/- 5.6 nmol 35SO4 reduced.h-1.g-1 wet wt vs. 7.9 +/- 2.0 nmol.h-1.g-1 in methanogens). Acetogenesis rates were very low in both groups. It was concluded that H2 excretion varies with different substrates. The proportion of H2 that is exhaled in breath is higher than currently accepted and varies with total excretion rate. Substantial amounts of H2 are consumed by methanogenic and sulfate-reducing bacteria.

Adolescent↗

Morphology of lymphatics in the canine large intestine.

The finer distribution of lymphatics in the large intestine of adult dogs was morphologically examined by puncture injection of colored dyes, intra-arterial injection of silver nitrate mixed with India ink, and electron microscopy. In the lamina propria there was a double-layer of lymphatic channels - a shallow network (near the mucosal surface) and a deep compartment (just above the muscularis mucosae). Sparse lymph capillaries also extended vertically paralleling intestinal glands. Some lymphatics penetrated into the submucosa where they demonstrated prominent valves and formed collecting lymphatic trunks alongside blood vessels.

Animals↗

[Ultrastructural changes in the nerve endings in the large intestine mucosa in Sonne dysentery].

Biopsies of the large intestine of patients with dysentery due to Shigella sonnei were examined. Electron microscopy examinations showed changes in nerve endings in the stroma of the mucous membrane to correlate with the intensity of general histopathological lesions in it. Changes in the nervous apparatus may be of reversible, structural-functional nature in mild cases of the disease or become irreversible in the structures providing transformation and transmission of the nervous signal in synaptic parts of neurites.

Biopsy↗

[A method of preparing the large intestine for surgery by using the peroral administration of a polyethylene oxide solution].

A new method for preparing the large intestine for operation is suggested, it is based on oral administration of a solution of polyethylene oxides with chloramphenicol. The preparation possesses a marked hydrophilic activity, which causes inhibition of absorption processes in the lumen of the intestinal tube. This leads to accumulation of the intestinal contents and their quicker passage. Polyethylene oxides also ensure accumulation of antibiotics in the tissues of the intestinal wall. The suggested method was used to prepare the intestine for operation in 93 patients. Comparative evaluation proved its advantages according to the main clinico-laboratory criteria: the method is technically simple, reduces the period of preparation of the intestine, has no negative effect on the homeostasis values, ensures adequate preparation of the large intestine with decrease of the level of its microbial contamination. With the use of the method the number of postoperative purulent complications in interventions on the large intestine reduced.

Administration, Oral↗

Abnormalities in subset distribution, activation, and differentiation of T cells isolated from large intestine biopsies in HIV infection. The Berlin Diarrhoea/Wasting Syndrome Study Group.

Intestinal T cells have a unique state of activation and differentiation which might specifically affect or be affected by HIV infection. Lymphocyte subsets in the peripheral blood are well characterized, but our knowledge about intestinal lymphocytes in HIV infection is incomplete. We therefore analysed lymphocytes isolated from large intestine biopsies of AIDS patients and controls by three-colour cytofluorometry. In the large intestine of HIV-infected patients CD4 T cells were reduced and CD8 T cells were increased compared with controls. Most of the CD8 T cells in the colorectal mucosa of AIDS patients were of the cytotoxic phenotype. Activated and resting CD4 T cells were similarly reduced, the expression of CD25 and HLA-DR of CD8 T cells was unaltered and increased, respectively. In intestinal CD4 T cells the expression of CD29 was decreased, but the expression of CD45RO and HML-1 was normal. CD8 T cells had a decreased expression of all these differentiation markers. Our findings demonstrate substantial alterations in subset distribution, activation, and differentiation of large intestine T cells, which may contribute to the secondary infections and malignancies commonly observed in the gut of AIDS patients.

Acquired Immunodeficiency Syndrome↗

Dual effect of orally administered sennosides on large intestine transit and fluid absorption in the rat.

Quantity and consistency of the faecal output, large intestine transit time, and colonic net fluid absorption were investigated in rats after oral administration of sennosides A + B (12.5-200 mg kg-1). The release of normal faecal pellets was accelerated 3-4 h after drug administration; excretion of soft faeces was evident within 4-5 h and reached its maximum 5-7 h after administration. Large intestine transit time was dose- and time-dependently influenced by sennoside treatment. A highly significant reduction in transit time from more than 6 h in controls to 90 min for a 2 h pretreatment and a nearly maximal reduction to 30 min for a 4 h pretreatment was induced by a dose of 50 mg kg-1. Inhibition of net fluid absorption in the colon was maximal with the same dose, but clearly more pronounced after a 6 h pretreatment period than after a 4 h period. Since the increase in fluid volume due to net fluid secretion is delayed compared with the acceleration of large intestine transit, the early motility effect seems to be largely independent of the changes in absorption mechanisms. Therefore, the laxative effect of the sennosides consists of changes in colon motility as well as in colonic fluid absorption, but motility may be an earlier and more sensitive parameter than net absorption.

Administration, Oral↗

A large pool of available folate exists in the large intestine of human infants and piglets.

Many microorganisms in the large intestine are capable of synthesizing folate. Preliminary evidence suggests that this folate may be absorbed. The purpose of the 2 experiments reported herein was to estimate the pool of folate in the feces of human infants and piglets and to ascertain, if absorbed, whether the quantity and form of folate are sufficient to potentially affect the folate status of the host organism. The folate content of milk fed to and of fecal solids collected from exclusively human milk-fed (n = 12) and formula-fed (n = 10) term infants (1-6 mo old) was determined microbiologically before (short-chain folates) and after folate conjugase (total folate) treatment. The folate content of formula fed and of feces collected from 10-d-old piglets (n = 10) was also determined microbiologically. The proportion of 5-methyltetrahydrofolate (5-methylTHF) in feces of human infants and piglets that was monoglutamylated was determined by HPLC analysis. The folate content of fecal solids collected from infants was 93.2 +/- 92.8 nmol/d (mean +/- SD), representing on average 50% (8.0-170.1%) of their mean estimated dietary folate intake. Fecal folate was largely present as short-chain folate (66 +/- 21.3%) with the predominant form being 5-methylTHF, 52.5 +/- 30.1% of which was monoglutamylated. In piglets, the folate content of feces was 301.3 +/- 145.7 nmol/d, representing 36% of their dietary folate intake. Piglet fecal folate was largely present as short-chain folate (68.1 +/- 12.6%) with the predominant species being 5-methylTHF, 29.3 +/- 33.2% of which was monoglutamylated. Collectively, these data suggest that the quantity and form of folate (monoglutamylated) in the large intestine of human infants and piglets are sufficiently large to potentially affect folate status.

Animals↗

Glycosphingolipids of human large intestine: detailed structural characterization with special reference to blood group compounds and bacterial receptor structures.

Non-acid glycosphingolipid expression was studied in the large intestines from four individuals with the A1Le(a-b+), BLe(a-b+), and OLe(a-b+) blood group phenotypes. In the A1Le(a-b+) case, specimens were taken from the ascending and sigmoid parts of the large intestine in order to compare the expression of glycolipids in the proximal and distal regions of the intestine. In one blood group OLe(a-b+) individual, epithelial cells were isolated from the residual stroma to compare the glycolipid compositions in these two tissue compartments. GlcCer, GalCer, LacCer, Gb3Cer, and Gb4Cer were the major compounds in all three individuals, as shown by mass spectrometry, proton NMR spectroscopy, and degradation studies. The Lea-5 glycolipid was the major complex blood group glycolipid in all individuals, except in the proximal ascending part of the large intestine of the A1Le(a-b+) case, in which the Leb-6 glycolipid was predominant. There were trace amounts of blood group ABH glycolipids, in agreement with the ABO blood group phenotypes of the donors, Lewis antigens with more than six sugar residues in the carbohydrate chain, and blood group X and Y glycolipid antigens. The epithelial cells were dominated by monoglycosylceramides and the Lea-5 glycolipid, while only trace amounts of di-, tri-, and tetraglycosylceramide structures were present. No reactivity was seen in the epithelial cell fraction with Gal alpha 1-4Gal specific Escherichia coli, anti-Pk, or anti-P antibodies, indicating the absence of the glycolipid-borne Gal alpha 1-4Gal sequence in human large intestinal epithelial cells.

Attachment Sites, Microbiological↗

THE ABSORPTION OF WATER, SODIUM, AND POTASSIUM IN THE LARGE INTESTINE WITH PARTICULAR REFERENCE TO THE EFFECTS OF VILLOUS PAPILLOMAS.

The absorption of water, sodium, and potassium from isolated segments of the large intestine has been studied in 11 patients. In eight control segments adjacent to a carcinoma of the colon, absorption of water and sodium and secretion of potassium occurred. In five segments of intestine containing a villous papilloma, water, sodium, and potassium were secreted. The difference is mainly due to an increase in exsorption of sodium and water, insorption being relatively unaffected.

Absorption↗