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Receptors for vasoactive intestinal peptide and secretin on small intestinal epithelial cells.

Binding of 125I-labeled vasoactive intestinal peptide (VIP) to dispersed enterocytes prepared from guinea pig small intestine was saturable, temperature dependent, and reversible, and reflected interaction of the labeled peptide with a single class of binding sites. Each enterocyte possessed approximately 60,000 binding sites and binding of the tracer to these sites could be inhibited by VIP [concentration for half-maximal effect (Kd), 12 nM] and by secretin (Kd greater than 1 micro M), but not by glucagon, gastrin, cholecystokinin, calcitonin, bombesin, litorin, physalaemin, substance P, eledoisin, serotonin, carbamylcholine, or histamine. With VIP and secretin, there was a close correlation between the relative potency for inhibition of binding of 125I-VIP and that for increasing cellular cAMP. For a given peptide, however, a 10-fold higher concentration was required for half-maximal inhibition of binding than for half-maximal stimulation of cellular cAMP. In addition to inhibiting binding of 125I-VIP and increasing cellular cAMP in enterocytes, secretin caused an increase in short-circuit current across guinea pig small intestine in vitro. Prostaglandin E1 increased cellular cAMP, but did not alter binding of 125I-VIP and the increase in cAMP caused by prostaglandin E1 plus VIP or secretin was equal to the sum of the increase caused by each agent alone.

Animals↗

Study of species specificity in growth hormone-releasing factor (GRF) interaction with vasoactive intestinal peptide (VIP) receptors using GRF and intestinal VIP receptors from rat and human: evidence that Ac-Tyr1hGRF is a competitive VIP antagonist in the rat.

In order to determine species specificity in growth hormone-releasing factor (GRF) interaction with vasoactive intestinal polypeptide (VIP) receptors, we have tested rat (r) GRF (with a His1 such as in VIP), human (h) GRF and position 1 substituted analogs of hGRF (Ala1, Ac-Tyr1, His1, Phe1, and Trp1 in the place of Tyr1) for their ability to inhibit 125I-VIP binding and to stimulate adenylate cyclase activity in human and rat intestinal epithelial membranes. We show that rGRF has a much higher affinity than hGRF for both human and rat VIP receptors. In humans, the Ki values for inhibiting 125I-VIP binding are 0.5 (VIP), 26 (rGRF), and 830 nM (hGRF). In rats the values are 0.6 (VIP), 46 (rGRF), and 1100 nM (hGRF). This is due in part to the presence of His1 in rGRF since the analog His1 hGRF has a higher affinity than hGRF in man and rat, i.e., Ki = 320 nM and 460 nM, respectively. Studies of adenylate cyclase stimulation reveal that rGRF and His1 hGRF are full VIP agonists in man and rat, whereas hGRF and its other analogs behave as partial agonists in both species. One of the hGRF analogs tested (Ac-Tyr1hGRF) is of great interest since it inhibits 125I-VIP binding to rat intestinal membranes with a Ki = 430 nM but has a negligible intrinsic activity in stimulating adenylate cyclase activity (about 6% of the efficacy of VIP). This analog does inhibit the VIP-stimulated adenylate cyclase activity in a dose-dependent manner, complete inhibition of the VIP (0.01-1 nM) effect being obtained with 30 microM analog. The Schild plot of the inhibitory effect further indicates competitive antagonism. In contrast, Ac-Tyr1hGRF is a partial VIP agonist in humans (about 20% of the efficacy of VIP). These results evidence the important role of His1 for peptide interaction with VIP receptors and provide the first example of a competitive VIP antagonist.

Adenylyl Cyclases↗

Electron microscopic studies on the small intestine of rats after mechanical intestinal obstruction.

The morphologic changes of the small intestine after the mechanical obstruction were studied by light and electron microscopy. After the ligation of the upper small intestine, segments of jejunum, both proximal and distal to the site of obstruction, were removed at intervals varying from 45 min to 24 h. The essential changes were found in the epithelial cells of the tips of villi, and few morphologic differences were recognized between samples proximal and distal to the site of obstruction. The most remarkable changes in the mucosa were the pseudopodlike extension of the cytoplasm, vacuolar alteration of the villus epithelial cells, desquamation of these degenerated cells, and the dilatation of the epithelial intercellular spaces. A few epithelial cells showed hypertrophy of the smooth endoplasmic reticulum. In the submucosa, vascular stasis and edema were observed throughout the course. The mechanism of fluid loss into the intestinal lumen was discussed briefly.

Animals↗

[Experimental studies of the changes in the wall of the large intestine and in the parenchymatous organs in stasis of the large intestine].

The authors carried out experimental studies on 23 dogs to examine changes, which occurred in the wall of the anastomosed ileum and the large intestine as well as in some organs after performing traversed anastomoses. The results were evaluated on the basis of clinico-experimental observations, on the changes in laboratory indices (complete blood picture, proteinogram, ionogram, blood urea and cholesterol), in microflora and in bioelectrical, activity. They examined ionic absorption in the large intestine excluded from the passage. An analysis was made on the pathologo-histological finding in the colon, anastomised ileum, liver and spleen, kidneys, heart, pancreas. The authors come to conclusions, useful to the physicians performing large intestine surgery.

Animals↗

Technetium (99mTc)-labelled white cell scanning, 51Cr-EDTA and 14C-mannitol-labelled intestinal permeability studies: non-invasive methods of diagnosing acute intestinal graft-versus-host disease.

We describe a case of a 38-year-old female who presented with diarrhoea and abdominal pain 27 days after a second 'top-up' allogeneic marrow infusion for acute myeloid leukaemia (AML) in first remission. A clinical diagnosis of gut graft-versus-host disease (GVHD) was made. Technetium (99mTc)-labelled white cell scanning and intestinal permeability studies using 51Cr-EDTA and 14C-mannitol were undertaken to confirm the diagnosis. The 99mTc white cell scan showed extensive uptake in the small bowel and the urinary excretion of 51Cr-EDTA was increased, the results being consistent with intestinal inflammation and gut GVHD. 99mTc white cell scanning and intestinal permeability studies may assist in the diagnosis of gut GVHD and in assessing its extent and response to treatment.

Acute Disease↗

[Bioenergetic disorders of the intestinal wall in acute intestinal obstruction and the means for their correction].

Results of an investigation of bioenergetics of the mucous and intestinal layers of the adducting, strangulated and abducting parts of the small intestine at different terms after the creation and liquidation of acute occlusive and strangulated intestinal experimental ileus in 173 dogs are presented. The use of the method of correcting therapy described in the article for complex treatment of 326 patients with acute ileus has shown their advantage over traditional methods.

Acute Disease↗

Massive intestinal hemorrhage associated with intestinal amyloidosis. An investigation of underlying pathologic processes.

UNLABELLED: Two cases of systemic amyloidosis with massive intestinal hemorrhage necessitating bowel resection prompted an investigation of the possible pathologic processes leading to such hemorrhage, since no conclusive information about this has been published. METHODS: The two surgical specimens and, for comparison, one biopsy specimen and autopsy specimens from six cases of amyloidosis were investigated by various histologic techniques. RESULTS: Massive amyloid deposition in the muscularis mucosae was noted in both surgical specimens. The source of hemorrhage was identified as being located at the border between the muscularis mucosae and the overlying rectal or colonic mucosa. In the autopsy specimens, there was patchy or linear amyloid deposition in the muscularis mucosae, but no hemorrhage. CONCLUSIONS: Various factors could be involved in causing massive intestinal hemorrhage in systemic amyloidosis. Functional disturbances may be involved due to amyloid deposition in relation to blood vessels, lymphatics, nerves, and nerve plexuses, and, as it appeared to be the case in the two surgical specimens investigated, massive deposition in the muscularis mucosae. The reduced motility and increased rigidity of the musculature probably result in shearing forces being set up in the presence of mechanical strain (eg in coprostasis or colonoscopy) that lead to tears in the region of the muscularis mucosae and to massive hemorrhage. Intestinal hemorrhage in amyloidosis may also be related to disturbances of coagulation, which have been reported in occasional cases, and ulceration, probably resulting in some cases of ischemic colitis.

Aged↗

CDX2 co-localizes with liver-intestine cadherin in intestinal metaplasia and adenocarcinoma of the stomach.

CDX2 and liver-intestine (LI)-cadherin are intestine-specific markers and both are physiologically expressed in the small intestine and colon. Recent studies have demonstrated that CDX2 regulates LI-cadherin gene (CDH17) expression in colorectal cancer. The present study investigated the relationship of CDX2 and LI-cadherin expression in gastric cancer. One hundred and nine pairs of tumour and non-cancerous gastric mucosa were collected from gastrectomy specimens. Protein expression levels of CDX2 and LI-cadherin were determined by immunohistochemical staining. Semi-quantitative RT-PCR showed that the mRNAs of both CDX2 and CDH17 were highly expressed in tumour compared with non-cancerous mucosa. Overexpression of CDX2 was significantly associated with CDH17 in gastric adenocarcinoma. Furthermore, the expression of CDX2 and LI-cadherin proteins was strongly coupled in intestinal metaplasia. In conclusion, overexpression of CDH17 is significantly associated with CDX2.

Adenocarcinoma↗

Gastro-intestinal bleeding caused by leiomyoma of the small intestine in a child with neurofibromatosis.

UNLABELLED: Gastro-intestinal bleeding is an uncommon presentation in children with neurofibromatosis. Gastro-intestinal involvement caused by jejunal leiomyoma has only been described in adults. To the best of our knowledge, this is the first paediatric case of jejunal leiomyoma associated with neurofibromatosis. We present a 10-year-old girl with a 9-month history of anaemia and low gastro-intestinal bleeding. Abdominal sonography and small bowel series showed a submucosal mass in the proximal jejunum. On surgery, a submucosal tumour was excised and histological examination suggested a diagnosis of "smooth muscle tumour of undetermined malignant potential". There were no recurrence of symptoms for 4 years after the operation. CONCLUSION: Jejunal leiomyoma should be considered in a child with neurofibromatosis presenting with gastro-intestinal bleeding.

Child↗

Influence of various antimicrobial agents on the intestinal flora in an intestinal MRSA-carrying rat model.

Using an intestinal methicillin-resistant Staphylococcus aureus (MRSA)-carrying rat model, we compared the influence of piperacillin (PIPC) on the intestinal flora to those of cefazolin (CEZ), cefmetazole (CMZ), and flomoxef (FMOX). The number of MRSA did not increase after PIPC and CEZ administrations compared with the nontreated group. However, it significantly increased in the cases of FMOX and CMZ administration (P < 0.01). In the FMOX- and CMZ-treated groups, the intestinal flora was severely disrupted and the recovery of the number of Escherichia coli and Bacteroides spp. cells was delayed. On the other hand, in the PIPC- and CEZ-treated groups, the rapid recovery of bacteria that composed the intestinal flora was observed. The C(max)/MIC(50) and C(trough)/MIC(50) ratios in E. coli and Bacteroides spp. in the case of FMOX and CMZ were relatively higher than those in the case of the PIPC- and CEZ-treated groups.

Animals↗

Disseminated intestinal hypoganglionosis treated by colectomy and tapering of the small intestine. A case report.

A girl suffering from chronic constipation and abdominal distension from her first year of life underwent internal anal sphincter myectomies at 5 and 7 years of age without resolution of her symptoms. At the age of 8, an ileostomy was performed because of excessive colonic dilation and hypomotility. Biopsies from the colon and distal ileum showed intestinal neuronal dysplasia TYPE B (INDB) with hypoganglionic areas. Colectomy and ileorectal anastomosis were done at the age of 10. Three years later, however, an ileostomy was re-established because of recurrent episodes of pseudo-obstruction. In the hope of improving intestinal motility, the dilated small intestine was tapered over its entire length of 3.6 meters. Histological findings still demonstrated oligoneuronal hypoganglionosis and INDB all along the resected strip of bowel wall. After 6 months, the stoma was closed. At the age of 15 years, tapering of the distal 80 cm of the ileum was repeated in combination with cholecystectomy for cholecystolithiasis. Intestinal transit time decreased from 55 hours before the first to 18 hours after the second tapering procedure. Now, 7 years after the last operation, the patient passes 3 - 4 soft stools daily, is physically active, on a normal diet and not on any regular medication.

Child↗

Effect of early enteral nutrition on intestinal permeability, intestinal protein loss, and outcome in dogs with severe parvoviral enteritis.

A randomized, controlled clinical trial investigated the effect of early enteral nutrition (EN) on intestinal permeability, intestinal protein loss, and outcome in parvoviral enteritis. Dogs were randomized into 2 groups: 15 dogs received no food until vomiting had ceased for 12 hours (mean 50 hours after admission; NPO group), and 15 dogs received early EN by nasoesophageal tube from 12 hours after admission (EEN group). All other treatments were identical. Intestinal permeability was assessed by 6-hour urinary lactulose (L) and rhamnose (R) recoveries (%L, %R) and L/R recovery ratios. Intestinal protein loss was quantified by fecal alpha1-proteinase inhibitor concentrations (alpha1-PI). Median time to normalization of demeanor, appetite, vomiting, and diarrhea was 1 day shorter for the EEN group for each variable. Body weight increased insignificantly from admission in the NPO group (day 3: 2.5 +/- 2.8%; day 6: 4.3 +/- 2.3%; mean +/- SE), whereas the EEN group exhibited significant weight gain (day 3: 8.1 +/- 2.7%; day 6: 9.7 +/- 2.1%). Mean urinary %L was increased, %R reduced, and L/R recovery ratios increased compared to reference values throughout the study for both groups. Percent lactulose recovery decreased in the EEN group (admission: 22.6 +/- 8.0%; day 6: 17.9 +/- 2.3%) and increased in the NPO group (admission: 11.0 +/- 2.6%; day 6: 22.5 +/- 4.6%, P = .035). Fecal alpha1-PI was above reference values in both groups and declined progressively. No significant differences occurred for %R, L/R ratios, or alpha1-PI between groups. Thirteen NPO dogs and all EEN dogs survived (P = .48). The EEN group showed earlier clinical improvement and significant weight gain. The significantly decreased %L in the EEN versus NPO group might reflect improved gut barrier function, which could limit bacterial or endotoxin translocation.

Animals↗

Hepatic intestinal uptake and release of catecholamines in alcoholic cirrhosis. Evidence of enhanced hepatic intestinal sympathetic nervous activity.

Hepatic intestinal and whole body plasma clearance and appearance of noradrenaline (NA) was quantified in patients with alcoholic cirrhosis (n = 12) and in controls (n = 6). As NA may be released as well as removed in the same vascular bed, infusion of tritium labelled NA (3H-NA) was carried out during hepatic vein catheterisation in order to determine both flux rates. In alcoholic cirrhosis plasma concentrations of endogenous NA and adrenaline (A) were significantly above control values (NA: median 2.4 v 1.7 nmol/l, p less than 0.02; A: 0.38 v 0.19 nmol/l, p less than 0.01). Whole body clearance of 3H-NA equal in the two groups (1.6 v 1.7 l/min, ns), while as the overall appearance rate of NA was significantly higher in alcoholic cirrhosis (4.2 v 2.6 nmol/min, p less than 0.02) indicating an enhanced sympathoadrenal activity in this group. The hepatic intestinal clearances of A, NA, and 3H-NA were not significantly different in patients and controls, but the estimated hepatic intestinal spillover rate of NA was 0.24 nmol/min in patients as compared with 0.0 nmol/min in controls (p less than 0.02). As a result of portosystemic shunting in cirrhosis the present estimation of NA spillover represents a minimum value. Our results indicate that the augmented circulating catecholamines in cirrhosis do not result from diminished removal but are contributed to from increased sympathetic nervous activity in the hepatic intestinal area (enhanced mesenteric sympathetic nervous activity).

Adult↗

Fetal intestinal fibroblasts respond to insulin-like growth factor (IGF)-II better than adult intestinal fibroblasts.

BACKGROUND: We compared IGF responses of fetal and adult intestinal fibroblasts to identify a developmental difference in the IGF-axis. Intestinal fibroblasts were isolated from maternal and fetal jejunum. Media was conditioned at confluence and one week afterwards. The proliferative response at confluence to 5 nM IGF-I or -II was compared. RESULTS: There were no significant differences in IGFBP expression at confluence. Post-confluence, fetal fibroblasts had no significant changes in IGFBP-2 and IGFBP-3 expression. Post-confluent maternal fibroblasts had increased IGFBP-3 levels that were significant compared to the fetal fibroblasts. IGF-I increased in post-confluent fetal fibroblasts, while in maternal fibroblasts it decreased (p < 0.001). IGF-II secretion decreased significantly in post-confluent maternal fibroblasts (p < 0.05). Maternal fibroblasts proliferated more with IGF-I than IGF-II (p < 0.001). Fetal fibroblasts responded to IGF-II slightly better than IGF-I and significantly greater than maternal cells (p < 0.001). CONCLUSION: Fetal intestinal fibroblasts respond to IGF-II with greater proliferation and do not have the increased IGFBPs seen post-confluence in adult intestinal fibroblasts.

Age Factors↗

[Persistent intestinal motility disorder after transient intestinal nematode infection in rats].

OBJECTIVE: To investigate the intestinal motor function (distal colonic manometry and gastrointestinal transit time) after T. spiralis infection in rats. METHODS: Sprague-Dawley rats were infected by administering T. spiralis larvae. Rats were studied on 14, 42, and 56 days post-infection (PI). Age matched non-infected animals served as controls. All rats underwent colonic manometry and gastrointestinal transit time test. RESULTS: (1) The small intestinal inflammation became the most severe on day 14 PI, and returned to normal on day 56. (2) The distal colonic manometry showed significantly active motility in acute infected rats either at rest or upon balloon stimulating. (3) Rat colonic motility parameters were not different from those of the control rats either at rest or upon small volume (1mL) balloon stimulating on day 42 and day 56 PI. But when the balloon was inflated with 2 mL of air, the colonic activity increased significantly compared with that of the control. (4) Gastrointestinal transit time was slower in acute and PI rats than that in the control group. CONCLUSION: Intestinal motility function was abnormal persistently after transient intestinal nematode infection in rats either in distal colonic manometry or in gastrointestinal transit time.

Animals↗

[Expression of intestine-specific transcription factor CDX2 in different subtypes of intestinal metaplasia and gastric carcinoma].

BACKGROUND & OBJECTIVE: Intestinal metaplasia (IM) is thought as the precancerous lesion of gastric carcinoma, and CDX2 gene plays important roles in development and differentiation of intestinal epithelium, and maintenance of intestinal phenotype. Recent studies found that CDX2 were expressed aberrantly in IM of chronic atrophic gastritis (CAG) and some gastric carcinomas, which implied that CDX2 may play an important role in IM formation and gastric carcinogenesis. This study was to investigate the roles of CDX2 in the development and progression of IM and gastric carcinogenesis, and determine the correlation of IM to gastric carcinogenesis. METHODS: A tissue microarray containing 46 cases of CAG with IM, 40 cases of gastric carcinoma, and 32 cases of IM foci in paracancerous tissues was constructed. High iron diamine/alcian blue (HID/AB) and HE staining were used to classify IM and gastric carcinoma, and the expression of CDX2 protein and mRNA in different gastric lesions was assessed with immunohistochemistry and in situ hybridization, respectively. RESULTS: The proportion of type III IM was significantly higher in IM foci in paracancerous tissues than in CAG with IM (56.25% vs. 21.74%, P<0.01). The positive rates of CDX2 protein were 69.56% in IM foci in CAG, 53.13% in IM foci in paracancerous tissues, and 42.50% in gastric carcinomas, and the positive rates of CDX2 mRNA were 63.04%, 46.87%, and 35.00%, respectively. The positive rates were significantly lower in gastric cancer than in IM in CAG (P<0.01), but there was no significant difference between gastric cancer and IM foci in paracancerous tissues (P>0.05). The expression of CDX2 protein and mRNA was significantly higher in intestinal-type gastric cancer than in diffuse-type gastric cancer (54.55% vs. 27.78%, 45.45% vs. 22.22%, P<0.05). The expression of CDX2 protein was significantly lower in type III IM than in type I IM (46.42% vs. 79.31%, P<0.05). CONCLUSIONS: CDX2 may play important roles in the development and progression of IM and gastric carcinogenesis.

CDX2 Transcription Factor↗

[Constipation and chronic intestinal pseudoobstruction as a clinical expression of intestinal neuronal dysplasia (IND)].

BACKGROUND: Intestinal neuronal dysplasia (IND) belongs to the group of dysganglionosis. It may occur as part of a syndrome of early chronic constipation, neonatal intestinal occlusion, chronic intestinal pseudo obstruction. The aim of this study was to report the cases examined by the Istituto G. Gaslini in Genoa and to discuss the numerous aspects of this disease which are still unclear. METHODS: 787 children were included in the study and underwent biopsy between 1984 and 1997. Rectal biopsies were obtained by suction or in some cases during surgery and were treated using enzymohistochemical techniques, such as acetylcholinesterase, rapid acetylcholinesterase and alpha-naphthylesterase. RESULTS: 574 children were found to be suffering from innervative alterations: 348 (60.6%) presented isolated Hirschsprung's disease, IND was found in 83 (14.5%), in 8 of the latter in association with other dysganglionosis. IND was accompanied by other diseases in 40 cases (48.2%). Over the past three years (since October 1994) a total of 164 dysganglionosis have been diagnosed, including 55 cases of aganglia. During this period IND was the most frequently observed alteration and affected 61 children. CONCLUSIONS: Rectal biopsy is the essential diagnostic test for the diagnosis of intestinal dysganglionosis. Biopsies are performed in outpatient clinics without sedation, and do not represent an invasive procedure for the young patients. Radiological and manometric examinations cannot provide reliable data for the diagnosis of IND. In our experience, the incidence of IND over the past few years has increased and its diagnosis is essential for correct treatment which is not surgical in the majority of cases. The real incidence of IND and its pathogenesis still need to be clarified.

English Abstract↗