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PubMed2001

Colonic diversion for intractable constipation in children: colonic manometry helps guide clinical decisions.

BACKGROUND: Colonic manometry helps discriminate functional and behavioral causes for childhood constipation from colonic neuromuscular disease. METHODS: Of 375 colonic manometries performed for clinical indications, 12 could not be interpreted because of chronic colonic dilation. Based on colonic manometries that showed either no contractions or an absence of the gastrocolonic response or an absence of high-amplitude propagating contractions, the authors recommended diverting colostomies or ileostomies in 12 chronically constipated children (mean age, 4 years; range, 2-14 years, 5 boys). Before study, medical treatment was ineffective in all children. These children had persistently dilated colons with pathologic diagnoses of intestinal neuronal dysplasia (n = 4), hypoganglionosis (n = 2), hollow visceral myopathy (n = 1), and normal (n = 5). RESULTS: Six to 30 months after diversion, the authors restudied all the children. Eleven of 12 diverted colons were no longer dilated. In two patients, abnormal motility involving the entire colon was unchanged from the initial study, small bowel motility was abnormal, and we recommended no further surgery. In two cases, the colon remained abnormal but small bowel motility was normal, and we recommended subtotal colectomy and ileoproctostomy. In four cases, the left colon remained abnormal, but the right colon was normal, and we recommended reanastomosis after left hemicolectomy. In four cases, motility in the diverted colons was normal, including a gastrocolonic response and high-amplitude propagating contractions, and the authors recommended reanastomosis. Defecation problems resolved in 10 of 12 when followed up 5 to 30 months after treatment. CONCLUSION: These data suggest that in some cases of intractable childhood constipation associated with colonic distention, temporary diversion improved colonic motility. Colonic manometry may be used to predict which patients will benefit from resection or reanastomosis.

Adolescent↗
PubMed1995

Laser-induced fluorescence microscopy of normal colon and dysplasia in colonic adenomas: implications for spectroscopic diagnosis.

OBJECTIVES: To determine what structures fluoresce and to what extent in normal colon and colonic adenomas to fully exploit laser-induced fluorescence spectroscopy as a tool for the diagnosis of dysplasia at endoscopy. METHODS: Unstained frozen sections of normal colon and colonic adenomas were studied by fluorescence microscopy under 351-364-nm argon ion laser excitation. Tissue fluorescence was observed and compared to morphology in serial sections stained with hematoxylin and eosin (H&E), Movat pentachrome, mucicarmine, and oil red O. RESULTS: In normal colon, fluorescence correlated morphologically with connective tissue fibers (principally collagen) in all layers of the bowel wall and with cytoplasmic granules within eosinophils present between the crypts in the lamina propria of the mucosa. Fluorescence of absorptive cells in normal crypts was very faint, and Goblet cells did not fluoresce. However, marked fluorescence was observed in the cytoplasms of dysplastic epithelial cells in the crypts of colonic adenomas. Fewer fluorescent connective tissue fibers were present in the lamina propria of colonic adenomas resulting in decreased fluorescence intensity as compared to that of normal colon. Fluorescent eosinophil granules were present in larger numbers in adenomas as compared with normal colon. CONCLUSION: Laser-induced fluorescence in normal colon and colonic adenomas correlates with morphology. Previous reported differences in laser-induced fluorescence emission spectra of normal colon and colonic adenomas obtained in vitro and in vivo may be due to differences in the cytoplasmic fluorescence between the dysplastic epithelium in colonic adenomas and normal colonic epithelium. Laser-induced fluorescence spectroscopy may be useful in studying other forms of epithelial dysplasia such as that which occurs in ulcerative colitis.

Adenoma↗
PubMed1994

Early stages of 1,2-dimethylhydrazine-induced colon carcinogenesis suppress immune-regulated ion transport of mouse distal colon.

Genetic events, such as gene deletion, mutation, and amplification, are involved in the development and progression of colonic neoplasia. The importance of interactions between immune cells and neoplastic cells in influencing the pathogenesis of colon cancer is suggested by the clinical efficacy of levamisole, an immunostimulant, in the treatment of colon cancer and by the association of local lymphocytic infiltration with improved prognosis. Thus, the immune cell-neoplastic cell interaction can be viewed as being analogous to various host-parasite relationships that involve the immune system attempting to contain the intruding parasite on the one hand and the parasite attempting to escape detection and rejection on the other. This study is an attempt to gain a better understanding of such interactions by examining possible effects of a developing tumor on the immune system. Colon cancer was experimentally induced in mice to examine potential effects of carcinogenesis in the colon on local mucosal immune function in situ, using the expression of type I hypersensitivity as an index of immune function. Antigen-induced changes in net ion transport, a quantifiable correlate of type I hypersensitivity, were measured in the colon of mice following the administration of the procarcinogen 1,2-dimethylhydrazine (DMH). Segments of colon and small intestine from mice immunized by infection with Trichinella spiralis secrete ions, manifested as a rise in transmural short-circuit current, when challenged with T. spiralis antigen in Ussing chambers. Antigen-induced rise in transmural short-circuit current is mast cell dependent and occurs only in immunized mice. To determine the effects of early stages of colon carcinogenesis on this mucosal immune response, mice were immunized with T. spiralis prior to and after 6 weekly injections of DMH. Responsiveness to antigenic challenge was suppressed in the distal colon 4-6 weeks after the final injection of DMH. Although responsiveness to antigen was suppressed, the colonic epithelium remained sensitive to direct stimulation by exogenous secretagogues. Decreased antigen responsiveness observed in the distal colon was not due to generalized immune suppression by DMH, because the proximal colon and the jejunum retained their responsiveness to antigen, and immune rejection of a secondary T. spiralis infection from the small intestine was not altered. Visible tumors eventually developed 30 weeks after the final injection of DMH only in the distal portions of the colon. These results suggest that early stages of DMH-induced carcinogenesis are associated with the suppression of mucosal immune function, as measured by immune-regulated ion secretion, in the distal colon but not in the proximal colon or jejunum.(ABSTRACT TRUNCATED AT 400 WORDS)

1,2-Dimethylhydrazine↗
PubMed1994

Helicobacter pylori colonization in children with gastritis and peptic ulcer. I. The colonization rate and effects of colonization on mucin content and mucosal inflammation in the antrum.

The incidence of Helicobacter pylori infection and effects of H. pylori colonization on mucin content and mucosal inflammation of the antral mucosa were studied quantitatively in 55 Japanese children with suspected gastritis and peptic ulcers (aged 6-16 years, mean 12.3 years). H. pylori was detected, using Warthin-Starry stain, in nine of the 22 cases (41%) with antral histological gastritis, but in none of the 33 histologically normal cases. Five out of seven duodenal ulcer cases showed histological gastritis, and all five cases were H. pylori positive. Severity of gastritis, evaluated by means of gastritis score, was significantly higher in H. pylori positive gastritis cases than in H. pylori negative gastritis cases (5.4 +/- 1.0 vs 3.1 +/- 0.3, P < 0.001). A PAS-AB index, a proportion of the periodic acid Schiff-alcian blue (PAS-AB) positive mucin area to the total epithelial area, was significantly lower in H. pylori positive cases than in H. pylori negative cases, irrespective of the existence of histological gastritis (23.5 +/- 7.6% vs 40.4 +/- 5.5%, 43.5 +/- 4.2%, P < 0.001). The decreased mucin content of gastric mucosa is likely to lead to weakening of an important defensive factor of gastric mucosa. These findings suggest that H. pylori plays an important role in gastritis and peptic ulcers in children, especially in cases with duodenal ulcer.

Adolescent↗
PubMed1997

Induction of DNA damage by risk factors of colon cancer in human colon cells derived from biopsies.

In order to increase the understanding of the factors responsible for causing human colon cancer, a technique was developed to detect genotoxic effects of chemicals in human colon cells. Risk factors suspected to be associated with the aetiology of human colon cancer were subsequently investigated: the method is based on the measurement of DNA damage in primary cells freshly isolated from human colon biopsies with the single cell microgel ectrophoresis technique ('Comet Assay'). 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3-methyl-3H-imidazo[4,5f]quinoline (IQ), N-methyl-N-nitro-N-nitrosoguanidine (MNNG), dinitrosocaffeidine (DNC) lithocholic acid (LCA), hydrogen peroxide (H2O2) and benzo[a]pyrene (B[a]P) were investigated for their genotoxic and cytotoxic effects following 30 min incubation with colon cells of human, and for comparative purposes also of the rat colon. The nitrosamides (MNNG, DNC) were very genotoxic in human colon cells. MNNG was more genotoxic in human than in rat colon cells. In contrast, the rat colon carcinogens PhIP and IQ were not genotoxic in human colon cells. PhIP did induce DNA damage in rat colon cells, which correlates to its capacity of inducing tumors in this animal tissue. LCA was toxic (rat > human) and concomitantly caused DNA damage in higher concentrations. The widespread contaminant B[a]P was not genotoxic in colon cells of either species using this system. H2O2 was found to be a potent genotoxic agent to both rat and human colon cells (human > rat). In summary, those compounds chosen as representatives of endogenously formed risk factors (MNNG, H2O2, LCA) have a higher toxic and/or genotoxic potency in human colon tissue than in rat colon. They are also more effective in this system than the contaminants tested so far (B[a]P, PhIP, IQ). The newly developed technique is rapid and yields relevant results. It is a novel and useful approach to assess different chemical compounds for genotoxic activities in tumour target tissues of the human.

Adult↗
PubMed1997

The distal colon provides reserve storage capacity during colonic fluid overload.

BACKGROUND: In addition to its absorptive function the capacity of the colon to retain fluid might be relevant in compensating for increased fluid loads and prevention of diarrhoea. The distal colon is considered to be mainly a conduit without extensive storage function. AIMS: To evaluate colonic volume capacity in a model of pure osmotic diarrhoea. METHODS: A non-absorbable, iso-osmotic solution (OS) containing polyethylene glycol (500 ml) was infused into the caecum of nine healthy volunteers; the control group (n = 5) received an equal amount of an easily absorbable electrolyte solution (ES). Fluids were radiolabelled with technetium-99m and gamma camera images were obtained for 48 hours. Counts in the proximal and distal colon were measured and regional and overall colonic transit and stool output were quantified. RESULTS: After OS, in contrast to ES, faecal output was increased significantly (p < 0.05), but colonic transit after OS was not different from transit after ES (p > 0.05). This indicates storage of OS in the colon: after OS infusion, counts in the proximal colon decreased linearly while the distal colon stored approximately 30% of radioactivity for the whole 48 hour study period. After OS, stool output correlated with distal (p < 0.01), but not with proximal (p > 0.05), colonic transit. In contrast, after ES, stool output was determined by proximal colonic transit (p < 0.05) but not by transit through the distal colon (p > 0.05). CONCLUSION: The distal colon retains non-absorbable fluid volumes extensively. In our model transit through the distal colon--but not the proximal colon--determined the time at which diarrhoea occurred.

Adult↗
PubMed2002

The motor efficacy of the artificial colonic pacemaker in colonic inertia patients.

We have recently demonstrated that the colon possesses at least 4 pacemakers which presumably generate electric waves and that colonic pacing evokes electric activity in colonic inertia. We tested the hypothesis that electric waves produced by artificial colonic pacing in colonic inertia patients may initiate colonic motilitiy and effect evacuation. 17 patients with constipation due to total colonic inertia were divided into 2 groups: 10 (age 45.6 ( 6.3 years, 7 women) in the study group and 7 (age 43.7 ( 5.8 years, 5 women) as controls. 7 healthy volunteers were included in the study. Colonic pacing was tested at 2 sites of pacemakers: mid-transverse colon and colosigmoid junction. A stimulating electrode was hooked to the colonic mucosa at the pacemaker site and 2-3 recording electrodes distally to it. Healthy volunteers showed resting electric waves in the form of pacesetter and action potentials which increased significantly on colonic pacing. Inertia patients exhibited no basal electric activity. Colonic pacing in the study group evoked electric waves and caused expulsion of small volume balloon. Balloon distension at pacemaker site produced mass movement of balloon, while away from pacemaker site step-wise movement. In conclusion, colonic pacing evoked electric waves in colonic inertia patients and effected balloon expulsion. We postulate that the pacemaker generates electric waves which spread along pacemaker branches that are composed of interstitial cells of Cajal and nerve fibers of the enteric nervous plexus and effect colonic mass contraction. Ex-pacemaker stimulation presumably leads to local activation of interstitial cells of Cajal and segmental step-wise contraction.

Action Potentials↗
PubMed1985

Nystatin prophylaxis of fungal colonization and infection in granulocytopenic patients: correlation of colonization and clinical outcome.

Nystatin, one million units every four hours, was prospectively studied as a prophylactic antifungal agent in 164 neutropenic patients who were not initially colonized by fungi: 104 received nystatin and 60 served as controls. Fungal colonization occurred in 68/104 (65%) nystatin recipients and in 43/60 (71%) controls. However, nystatin significantly reduced multiple body site colonization and persistent oropharyngeal colonization. Despite these alterations in colonization profile, 16/104 (15%) nystatin recipients developed disseminated fungal infections, as compared to 5/60 (8%) control patients (0.5 greater than p greater than 0.1, N.S). Differences in the clinical course of colonized and non-colonized patients were observed. Eighteen of 111 (16%) colonized patients had afebrile clinical courses as compared to 16/53 (30%) non-colonized patients (p less than 0.05). Twenty-nine of 93 (31%) febrile episodes in colonized patients failed to respond to empiric antibiotic therapy as compared to 3/37 (8%) episodes in non-colonized patients (p less than 0.01). Disseminated fungal infections were diagnosed in 19/111 (17%) of colonized patients, as compared to 1/53 (2%) non-colonized patients (p less than 0.02). We conclude that colonized patients are more likely to develop febrile clinical courses, to fail to respond to empiric antibiotic therapy, and to develop disseminated fungal infection. Nystatin altered colonization patterns but did not prevent disseminated fungal infection.

Adolescent↗
PubMed1995

Differences in colonic tone and phasic response to a meal in the transverse and sigmoid human colon.

It is not yet clear whether the regional differences in the physical properties of the colon influence its motor responses. Tonic and phasic colonic motility and compliance of the transverse and sigmoid colon were therefore assessed using a combined barostat-manometry assembly in 22 healthy subjects. Measured colonic compliance was corrected by subtraction of the compliance of the closed barostat system. The mean (SEM) preprandial colonic volumes in the transverse and sigmoid colon were similar (150 (12) and 128 (13) ml, p = NS), corresponding to calculated mean (SEM) colonic diameters of 4.3 cm and 4.0 cm respectively. The mean increase in colonic tone postprandially was significantly greater in the transverse (24.1% (3.5)) than in the sigmoid colon (13.1% (3.0), p < 0.01). The mean increase in phasic contractility was significantly greater, however, in the sigmoid than in the transverse colon (1270 (210) and 425 (60) mm Hg/90 min respectively, p < 0.01). Compliance was greater in the transverse than sigmoid colon (7.6 (0.44) and 4.1 (0.15) ml/mm Hg, p < 0.001). The fasting volume of the colon was significantly correlated with the magnitude of the tonic response to the meal in the transverse and sigmoid colon (p < 0.001 for both). In conclusion, there are quantitatively different but qualitatively similar phasic and tonic responses to the meal in the two colonic regions. Differences in the viscoelastic and luminal dimensions may partly account for these differences in tonic responses.

Adult↗
PubMed1996

Modulating effect of amount and types of dietary fat on colonic mucosal phospholipase A2, phosphatidylinositol-specific phospholipase C activities, and cyclooxygenase metabolite formation during different stages of colon tumor promotion in male F344 rats.

Epidemiological and laboratory animal model studies suggest that the effect of dietary fat in colon carcinogenesis depends not only on the amount but on its fatty acid composition. Animal model studies demonstrated that high dietary corn oil or safflower oil rich in omega-6 fatty acids increased the colon tumor promotion, whereas diets containing fish oil high in omega-3 fatty acids had no such enhancing effect. One of the mechanisms by which high dietary fat enhances colon carcinogenesis may be through the modulation of colonic mucosal phospholipase A2 (PLA2) and phosphatidylinositol-specific phospholipase C (PI-PLC), which are dominant pathways for arachidonic acid release and formation of eicosanoids. PI-PLC is also responsible for diacylglycerol formation and protein kinase C-dependent signal transduction and cell proliferation. In the present study, we investigated the modulating effect of high fat diets rich in omega-3 and omega-6 fatty acids on colonic mucosal PLA2, PI-PLC activities, and eicosanoid (prostaglandins and thromboxane B2) formation from arachidonic acid via cyclooxygenase (COX) during different stages of azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. At 5 weeks of age, groups of animals were fed the low-fat diet containing 5% corn oil. Beginning at 7 weeks of age, all animals except those intended for vehicle treatment received AOM s.c. once weekly for 2 weeks at a dose rate of 15 mg/kg body weight. Vehicle-treated groups received an equal volume of normal saline. One day after the second AOM or vehicle treatment, groups of animals were transferred to experimental diets containing 23.5% corn oil and 20.5% fish oil + 3% corn oil, whereas one group continued on the low-fat diet containing 5% corn oil. Groups of animals were then sacrificed at weeks 1, 12, and 36 after the second AOM-or saline-treatment. Colonic mucosa harvested at weeks 1, 12, and 36 and colonic tumors obtained at week 36 were analyzed for PLA2, PI-PLC, and eicosanoid formation from arachidonic acid by the action of COX. The results demonstrate that colon carcinogen treatment increases the activities of colonic mucosal PLA2 and PI-PLC and the formation of prostaglandins and thromboxane A2 from arachidonic acid through COX throughout the study period compared to saline-treated animals fed similar diets. The activities of PLA2, PI-PLC, and COX were significantly higher in colon tumors compared to colonic mucosa. These results also demonstrate that a high-fat diet containing corn oil increases colonic mucosal and tumor PLA2 and PI-PLC and the formation of prostaglandins and thromboxane B2 by the action of COX as compared to low dietary corn oil or a diet high in fish oil. The results of our study offer one of the mechanisms by which the amount and types of dietary fat modulate colon carcinogenesis.

Animals↗
PubMed1990

Colon wound management and prograde colonic lavage in large bowel trauma.

Between 1983 and 1987 prograde colonic lavage was prospectively evaluated in 389 patients with colon trauma. Predefined high risk patients had exteriorization of the primarily sutured colon. Intraperitoneal primary closure was otherwise used. Patients received prograde colonic lavage by random allocation. The healing exteriorized colon was interiorized 5-10 days after the initial surgery. The median age was 29 years and only 28 patients were women. Injuries were due to stab (316), gunshot (54), shotgun (10) or blunt trauma (9). Exteriorization of the primarily sutured colon was carried out in 217 patients of whom 101 had prograde colonic lavage. Twenty (9 per cent) died. Of the survivors, 150 (76 per cent) had their colon successfully interiorized and this rate was unaffected by prograde colonic lavage. Intraperitoneal primary closure was performed in 172 patients of whom 91 had prograde colonic lavage. Seven (4 per cent) died. Mortality was directly related to the number of associated injuries. Prograde colonic lavage, irrespective of the type of colonic wound management used, did not reduce the mortality rate, which was 7.2 per cent for those who had such lavage and 6.6 per cent for the rest. Prograde colonic lavage cannot therefore be recommended in colon trauma.

Adolescent↗
PubMed2002

On the mechanism of colonic motility: the electric activation theory of colonic contraction.

PURPOSE: A previous study has demonstrated that the longitudinal muscle possesses electric activity, while the circular does not (A. Shafik and A. A. Shafik, 2000, Front. Biosci. 5, b5). In the current study, we investigated the mechanism of action of the two colonic muscle coats in the motility of the gut. METHODS: Fourteen patients (43.8 years, 10 men) with left colon or rectal cancer were scheduled to have transverse colostomy as a part of their operation. The electric activity of the ascending colon was recorded by three electrodes applied to each of the circular and the longitudinal (taenia coli) muscle coats. Simultaneously, the colonic pressure was recorded before and after colonic distension. The test was repeated after longitudinal muscle anesthetization. RESULTS: Electric waves in the form of pacesetter (PPs) and action (APs) potentials were recorded from the longitudinal but not the circular muscle fibers. APs were associated with an intracolonic pressure rise. Colonic distension produced significant increase in the PPs and APs recorded from the longitudinal muscle with appearance of similar electric activity from the circular muscle. Electric activity and colonic pressure increased upon increase in the colonic distension until the balloon in the proximal part of the ascending colon moved to the transverse colon in one mass contraction. Ten minutes after longitudinal muscle anesthetization, no electric activity was recorded from the longitudinal and circular muscles upon colonic distension. CONCLUSIONS: The electric waves appear to be transmitted from the longitudinal to the circular muscle upon colonic distension. The giant migrating contractions of the colon that move the food bolus from the cecum to the transverse colon are suggested to be a function of the longitudinal muscle electric activation with gut lumen modulation by the circular fibers.

Action Potentials↗
PubMed1998

Long-term functional evaluation of straight coloanal anastomosis and colonic J-pouch: is the functional superiority of colonic J-pouch sustained?

AIM: This study was designed to analyze the functional and clinical outcomes of straight coloanal anastomosis compared with colonic J-pouch performed after low anterior resection. MATERIALS AND METHODS: Between September 1989 and June 1996, all patients who underwent low anterior resection with anastomosis less than 4 cm from the dentate line were classified into two groups based on the restoration of intestinal continuity: "straight" coloanal anastomosis (n = 39) or colonic J-pouch (n = 44). Both groups were assessed according to the level of anastomosis, anastomotic complications (stricture, leak, pelvic abscess), age, and gender. For comparison of functional outcome, daily bowel movements, tenesmus, urgency, incontinence score (range, 0-20), and anorectal manometric findings were evaluated preoperatively and at six months, and one and two years after surgery. RESULTS: There were no significant differences between the groups relative to age: (coloanal anastomosis, 66.3 +/- 10.1 (range, 46-86), vs. colonic J-pouch, 64.9 +/- 13.2 (range, 39-88) years); gender (females): (coloanal anastomosis, 46.2 percent vs. colonic J-pouch; 38.6 percent); diagnosis: (rectal carcinoma: coloanal anastomosis, 84.6 percent, vs. colonic J-pouch, 77.3 percent); preoperative incontinence score (coloanal anastomosis, 1.5 +/- 4.6, vs. colonic J-pouch, 1.1 +/- 4); bowel movements: (coloanal anastomosis, 2.1 +/- 2.3, vs. colonic J-pouch, 2.1 +/- 1.9/day); level of anastomosis: (coloanal anastomosis, 1.8 +/- 1.3, vs. colonic J-pouch, 1.5 +/- 1.3 cm from the dentate line); history of perioperative radiation therapy: (coloanal anastomosis, 15.4 percent, vs. colonic J-pouch, 20.5 percent); or manometric findings. There was also no significant difference in postoperative mortality: (coloanal anastomosis, 5.1 percent, vs. colonic J-pouch, 2.3 percent); or anastomotic complications: (coloanal anastomosis, 7/39 (17.9 percent), vs. colonic J-pouch, 2/44 (4.5 percent) P = 0.08); strictures: (10.3 vs. 0 percent); leaks: (5.1 vs. 2.3 percent); bleeding: (2.6 vs. 0 percent); rectovaginal fistula: (0 vs. 2.3 percent). Also, in the colonic J-pouch group, two patients developed pouchitis, and one patient experienced difficult evacuation one year after surgery. There was a statistically significant better function judged by less frequent bowel movements (4 +/- 2 vs. 2.4 +/- 1.3/day; P < 0.005) and urgency (36.7 vs. 7.7 percent; P < 0.05), incontinence score (2.2 +/- 3.7 vs. 0.8 +/- 1.6; P < 0.05) up to one year after surgery. At two years, the coloanal anastomosis group did not show statistical improvement in functional results compared with one year postoperatively. Rectal compliance in manometric findings was significantly increased in the coloanal anastomosis group at one year after surgery (12.4 +/- 12.6 vs. 4.2 +/- 1.5 ml/mmHg; P < 0.05). However, these differences were less profound after two years. CONCLUSION: The functional superiority of the colonic J-pouch was greatest at one year after surgery. By two years, adaptation of the "straight" coloanal anastomosis yielded similar functional results. However, the almost fourfold reduction in anastomotic complications in the colonic J-pouch group reveals a second potential advantage of this technique.

Aged↗
PubMed2006

Abnormal expression of the peptide transporter PepT1 in the colon of massive bowel resection rat: a potential route for colonic mucosa damage by transport of fMLP.

The aim of this study was to investigate the effect of abnormal intestinal oligopeptide transporter (PepT1) on rat colon inflammation by transportion of N-formyl-methionyl-leucyl-phenylalanine (fMLP). We induced upregulation of PepT1 in the colon of rats by 80% small bowel resection and examined colonic PepT1 di-tripeptide transport activity. By Western blot analysis, PepT1 was clearly detected in the colon of bowel resection rats, while it was absent from the colon of bowel transection and reanastomosis rats. The experiment with cephalexin colon perfusion showed that the arterial cephalexin concentration in resection rats was five to nine times that in transection rats. Inhibition of PepT1 by Gly-Gly completely abolished cephalexin absorption from the colon of resection rats. We found that 10 microM fMLP perfusion in the colon of resection rats for 4 hr significantly increased myeloperoxidase (MPO) activity and caused colon wall damage. In contrast, 10 muM fMLP perfusion in the colon of transection rats did not induce any inflammation. A 5 mM Gly-Gly perfusion completely inhibited the MPO activity and colonic wall damage induced by 10 muM fMLP. We conclude that colonic PepT1 induced by bowel resection may provide a mechanism for oligopeptide transport and may serve as a potential cause of colonic mucosa damage by transport of the bacterial product fMLP in rat colon.

Animals↗
PubMed2000

Colon signet ring cell adenocarcinoma: immunohistochemical characterization and comparison with gastric and typical colon adenocarcinomas.

Colon signet ring cell adenocarcinomas are uncommon, high-grade neoplasms. Given their rarity, the question of primary colon or metastatic gastric adenocarcinoma frequently arises when signet ring cell carcinoma is seen in a colonoscopic biopsy or in biopsies procured from other regions of the body. A second related question regarding colon and gastric signet ring cell carcinomas is their immunophenotypic similarities with the glandular form of adenocarcinoma in each site. We studied the immunohistochemical phenotype of 14 colonic signet ring cell adenocarcinomas and compared them with immunophenotype of 27 gastric signet ring cell adenocarcinomas. We also compared the immunophenotype of the 27 gastric signet ring cell with the immunophenotype of 19 gastric gland-forming adenocarcinomas, and the immunophenotype of the 14 colonic signet ring cell adenocarcinomas to the immunophenotype of 20 colonic gland-forming adenocarcinomas to identify staining differences in the neoplastic cells of the two architectures. Antibodies studied were cytokeratins 7, 17, 19, and 20, CA 19-9, CA-125. estrogen receptor, and gross cystic disease fluid protein 15. Sixty-four percent of colon signet ring cell adenocarcinomas had either no staining or focal staining with cytokeratin 7 compared with diffuse staining in 63% of gastric signet ring cell adenocarcinomas (P = 0.016). Seventy-two percent of colon signet ring cell adenocarcinomas had diffuse staining with cytokeratin 20 compared with no or focal staining in 50% of gastric signet ring cell adenocarcinomas (P = 0.019). Fifty-seven percent of the colon signet ring cell adenocarcinomas had a cytokeratin 7 (-)/cytokeratin 20 (+) staining pattern compared with 11% of gastric signet ring cell adenocarcinomas (P = 0.004). Forty-four percent of gastric signet ring cell adenocarcinomas had a cytokeratin 7 (+)/cytokeratin 20 (-) pattern, compared with none of the colon signet ring cell adenocarcinomas (P = 0.004). The staining distribution of the antibody battery was similar in colon signet ring cell and colon glandular adenocarcinoma and gastric signet ring cell and gastric glandular adenocarcinomas. When signet ring cell adenocarcinoma is encountered in a colon biopsy, a colon primary is supported if the neoplastic cells have a cytokeratin 7 (-)/cytokeratin 20 (+) staining pattern, and a gastric primary is supported if they have a cytokeratin 7 (+)/cytokeratin 20 (-) staining pattern. The signet ring morphology at each site had an identical immunophenotype as the cells forming their glandular counterpart.

Adenocarcinoma↗
PubMed1985

Isolation and characterization of a colonic autoantigen specifically recognized by colon tissue-bound immunoglobulin G from idiopathic ulcerative colitis.

Patients with idiopathic ulcerative colitis (UC) have a colonbound antibody (CCA-IgG) that reacts with colon tissue extracts. We have partially characterized a colonic protein that is specifically recognized by CCA-IgG. CCA-IgG was eluted from operative colon specimens from 10 patients with UC. A colon tissue-bound IgG was similarly eluted from six patients with Crohn's colitis, two with ischemic colitis, and one with diverticulitis. Purified serum IgG from patients with Crohn's disease, from normal subjects and a patient with myeloma were also used as additional controls. For detection of antigen(s), tissue extracts were prepared from 26 specimens of colon (UC, 12; Crohn's disease, 6; normal, 4; other controls, 4), 8 specimens of human normal stomach, duodenum, ileum, and liver (2 each). Tissue extracts were also prepared from rats and mice, including germ-free rat colons and rat's fetal colons. Immunorecognition of CCA-IgG to the tissue extracts was examined by affinity-column chromatography and by transblot analysis. Tissue-extracted proteins were electrophoresed in SDS-polyacrylamide gel, transferred to nitrocellulose sheet, and probed with iodinated CCA-IgG, colonic IgG from other inflammatory bowel disease patients, UC serum IgG, and control serum IgG. Although many proteins were present in colon tissue extracts, 9 of 10 CCA-IgG consistently recognized a protein of 40 kD. None of the nine IgG preparations from colon specimens of patients with Crohn's colitis and other colonic inflammatory diseases reacted with the 40-kD protein. Five of six symptomatic UC serum IgG and none of eight control serum IgG reacted with the 40-kD protein. The 40-kD protein was present in all colon specimens and it appeared to be organ specific. It was absent in mouse and rat tissues, including colon. The 40-kD protein is not actin and nor a part of the Ig molecule. These results suggest that the 40-kD protein is a colonic "autoantigen" that may initiate a specific IgG antibody response in UC.

Autoantigens↗
PubMed1999

A novel colon pouch and its comparison with a straight coloanal and colon J-pouch--anal anastomosis: preliminary results in pigs.

BACKGROUND: Early functional results after complete rectal resection and straight coloanal anastomosis are often characterized by frequent bowel movements, urgency, and varying degrees of stool incontinence. The formation of a colon reservoir improves early and long-term function. We evaluated the feasibility of a novel, modified design of a colon pouch--anal anastomosis in pigs and compared the results with those of pigs with straight coloanal anastomosis and colon J-pouch. METHODS: Complete rectal resection followed by either a straight coloanal anastomosis, a colon J-pouch, or a novel design of a colon pouch was performed in equal numbers in 15 pigs. By transversely closing a longitudinal colotomy, the new, technically simpler pouch is formed. Functional results were assessed during a period of 6 weeks. RESULTS: All 15 procedures were successful. The novel colon pouch required less surgical time than the colon J-pouch, and the formation of the pouches did not reduce tissue perfusion as assessed by laser Doppler flowmetry. The mean volume of the novel colon pouch was significantly smaller than the volume of the colon J-pouch. All the pigs with the novel colon pouch had normal stool frequency and consistency during a period of 6 weeks. In the group with straight coloanal anastomosis, two pigs had increased frequency of defecation, one pig showed signs of urgency and perianal dermatitis, and three had substantially reduced stool consistency. Of the four pigs with colon J-pouch, three had signs of impaired pouch evacuation and two had reduced stool frequency. CONCLUSIONS: The novel colon pouch is feasible in pigs and technically simpler than the colon J-pouch. These preliminary results indicate that the smaller capacity of this pouch seems sufficient for normal defecation. Its short-term functional results were better than those after reconstruction with a colon J-pouch or a straight coloanal anastomosis.

Anal Canal↗
PubMed1995

Colonic protein fermentation and promotion of colon carcinogenesis by thermolyzed casein.

Thermolyzed casein is known to promote the growth of aberrant crypt foci (ACF) and colon cancer when it is fed to rats that have been initiated with azoxymethane. We speculated that the promotion was a consequence of increased colonic protein fermentation (i.e., that the thermolysis of the casein decreases its digestibility, increases the amount of protein reaching the colon, and increases colonic protein fermentation and that the potentially toxic products of this fermentation promote colon carcinogenesis). We found that the thermolysis of casein reduces its digestibility and increases colonic protein fermentation, as assessed by fecal ammonium and urinary phenol, cresol, and indol-3-ol. Thermolysis of two other proteins, soy and egg white protein, also increases colonic protein fermentation with increased fecal ammonia and urinary phenols, and thermolysis of all three proteins increases the levels of ammonia and butyric, valeric, and i-valeric acids in the cecal contents. We found, however, that the increased protein fermentation observed with thermolysis is not associated with promotion of colon carcinogenesis. With casein, the kinetics of protein fermentation with increasing thermolysis time are clearly different from the kinetics of promotion of ACF growth. The formation of the fermentation products was highest when the protein was thermolyzed for one hour, whereas promotion was highest for protein that had been thermolyzed for two or more hours. With soy and egg white, thermolysis increased colonic protein fermentation but did not promote colon carcinogenesis. Thus, although thermolysis of dietary casein increases colonic protein fermentation, products of this fermentation do not appear to be responsible for the promotion of colon carcinogenesis. Indeed, the results suggest that protein fermentation products do not play an important role in colon cancer promotion.

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