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PubMed1987

Localization in the gastrointestinal tract of immunoreactive prosomatostatin.

Antisera against 5 different regions of the entire prosomatostatin molecule were used for immunohistochemical mapping of prosomatostatin-containing structures in the pig gastrointestinal tract, and for radioimmunological and chromatographical analysis of the products of prosomatostatin in extracts of ileal mucosa. The latter showed that the antisera were capable of identifying components containing N-terminal as well as C-terminal parts of prosomatostatin. Endocrine cells were identified with all antisera in most parts of the gastrointestinal tract, and varicose nerve fibres were observed in all parts of the small intestine but not in the stomach and the colon. The colon contained very few immunoreactive structures. Immunoreactive nerve cell bodies were found in the submucous plexus of the small intestine. All immunoreactive endocrine cells in the stomach and the duodenum and all immunoreactive nerves were stained by all 5 antisera whereas the small intestinal endocrine cells did not stain for the most N-terminal region of prosomatostatin. The results suggest that all gastrointestinal somatostatin is derived from the same precursor molecule, which, however, in the small intestinal endocrine cells is processed differently from that of the other tissues.

Animals↗
PubMed1982

Gastrointestinal tract bleeding of unknown origin.

Gastrointestinal (GI) tract bleeding of unknown origin is a vexing clinical problem. In this review, we discuss those causes of GI tract hemorrhage most likely to escape detection by conventional diagnostic modalities and explain how newer techniques of flexible fiberoptic endoscopy, radionuclide scanning, and angiography may be used to establish a diagnosis. We reviewed the literature on the role of exploratory surgery in the diagnosis of occult GI tract bleeding and conclude that its diagnostic yield is small and its value limited. Finally, we present a diagnostic approach to the patient with GI tract bleeding of unknown origin.

Aneurysm↗
PubMed1994

Effect of iron deficiency on DMH-induced gastrointestinal tract tumors and occurrence of hepatocyte abnormalities in Fischer rats.

The relationship between iron deficiency and carcinogenesis was studied using the carcinogen dimethylhydrazine to induce gastrointestinal tumors in Fischer 344 control and iron-deficient rats. Dimethylhydrazine (30 mg/body wt) was administered by gastric intubation 10 times over nine weeks. After 32 weeks, rats were sacrificed, and tumor incidence was assessed. The overall incidence of gastrointestinal tract tumors (colonic and duodenal) was higher in the iron-deficient (66%) than in the control group (46%). Whereas the incidence of colonic tumors was identical in control and iron-deficient groups, the duodenal tumor incidence was significantly elevated in iron deficiency. Five of 15 rats, i.e., 33.3%, in the iron-deficient group developed duodenal tumors; in the control group, only 1 of 15 rats developed a tumor (i.e., 6.6%). Also, iron-deficient rats had multiple tumors. Histological examination of the colon and duodenum revealed that the tumors were adenocarcinomatous in nature. Another notable feature in the iron-deficient group was the presence of atypical cells in the livers of carcinogen-treated iron-deficient rats. This study thus suggests that there is a greater incidence of tumors in iron deficiency and that the proximal part of the intestines seems to be the preferred site. The presence of atypical cells in the liver suggests that in iron deficiency, besides gastrointestinal tract tumors, the liver may also be a favored site for abnormalities.

1,2-Dimethylhydrazine↗
PubMed1989

Ingestion of corrosive acids. Spectrum of injury to upper gastrointestinal tract and natural history.

We have prospectively evaluated 41 patients who ingested acid for location, extent, severity, and outcome of the injury to the upper gastrointestinal tract. The injury was assessed within 36 h of acid intake by endoscopy or surgery, or at autopsy. Symptoms and signs were unreliable in predicting the extent and severity of injury. The degree of burns was classified as follows: grade 0 in 2 patients, grade 1 in 3, grade 2 in 16, and grade 3 in 20. Esophageal injury was seen in 87.8% of the patients, gastric injury in 85.4%, and duodenal injury in 34.1%. All patients with grade 0, 1, and 2a injury recovered without sequelae. Acute complications occurred in 39.1% of the cases, and death in 12.2%. It is significant that all such patients had grade 3 burns. Five of the 8 patients with grade 2b injury and all survivors of grade 3 injury developed esophageal or gastric cicatrization, or both, which subsequently needed endoscopic or surgical treatment. We find that endoscopy is not only the tool of choice for diagnosis in such cases but also aids in deciding upon treatment and prognosis. We conclude that acid injury of the upper gastrointestinal tract is a very serious condition that affects the esophagus and stomach equally and results in high morbidity and mortality.

Accidents, Home↗
PubMed2001

Vascular amyloid of unknown origin and senile transthyretin amyloid in the lung and gastrointestinal tract of old age: histological and immunohistochemical studies.

The histological and immunohistochemical characteristics and the incidence of amyloid deposits in the tissues of the lung and gastrointestinal tract were investigated in 64 autopsied individuals who were 80 years and older (age range: 80-92 years; mean: 83.3 years). Immunohistochemical examination was performed with antibodies against amyloid A, transthyretin, immunoglobulin lambda and kappa light chain amyloid fibril proteins, beta2-microglobulin, beta protein, apolipoprotein AI, apolipoprotein AII, atrial natriuretic peptide, apolipoprotein E, and amyloid P component. Transthyretin amyloid fibril protein (ATTR) deposits were observed in five cases (7.8%). Gastrointestinal amyloid deposits of unknown origin were observed in the veins of the gastrointestinal tract in 26 cases (40.6%). This amyloid was regarded as portal amyloid with respect to distribution pattern. Pulmonary vascular amyloid deposits of unknown origin were observed in 12 cases (18.8%). These amyloid deposits were found mainly in medium-sized veins in the lungs and did not react with any antibodies against amyloid fibril proteins except apolipoprotein E and amyloid P component. Eleven of the 26 cases (42.3%) showing portal amyloid also showed pulmonary vascular amyloid of unknown origin. The pulmonary vascular amyloid deposits were similar to the portal amyloid deposits with respect to their morphological features and their relation to elastic fibers in the vessels. Further morphological investigation and biochemical analysis of the pulmonary vascular amyloid and portal amyloid will resolve questions of their origins and relation.

Aged↗
PubMed2001

Effects of CCK2 receptor blockade on growth parameters in gastrointestinal tract and pancreas in rats.

Gastrin has a growth-promoting effect on the oxyntic mucosa of the stomach but has been claimed also to affect other parts of the gastrointestinal tract and pancreas. This report describes the effects of the cholecystokinin, (CCK2) receptor antagonists YM022 and YF476 on various growth parameters in the gastrointestinal tract and pancreas of the rat. YM022 and YF476 were given subcutaneously in doses known to produce maximum and sustained CCK2 receptor blockade. The body weight was not affected. However, the oxyntic mucosal weight, thickness and protein and DNA contents were reduced by 15-20% already within 1-2 days and by about 30% after 4-8 weeks of CCK2 receptor blockade. Hence, the response of the oxyntic mucosa to CCK2 receptor blockade was in the form of hypotrophy (reduced protein content) and hypoplasia (reduced DNA content). There were no obvious effects of CCK2 receptor blockade on the intestine or pancreas (nor on liver, kidney or thyroid). The proton pump inhibitor omeprazole was used to induce hypergastrinaemia and was given with or without YM022. Omeprazole treatment for 4 weeks increased the oxyntic mucosal weight and thickness by 15-20%. YM022 prevented these effects. We conclude that while elevated circulating gastrin levels, acting on CCK2 receptors, exert a growth-promoting effect on the oxyntic mucosa (but not elsewhere), normal serum gastrin levels exert a mucosa-preserving effect.

Animals↗
PubMed2005

Determination of genes related to gastrointestinal tract origin cancer cells using a cDNA microarray.

PURPOSE: We evaluated the genome-wide gene expression profiles of various cancer cell lines to identify the gastrointestinal tract cancer cell-related genes. EXPERIMENTAL DESIGN: Gene expression profilings of 27 cancer cell lines and 9 tissues using 7.5K human cDNA microarrays in indirect design with Yonsei reference RNA composed of 11 cancer cell line RNAs were done. The significant genes were selected using significant analysis of microarray in various sets of data. The selected genes were validated using real-time PCR analysis. RESULTS: After intensity-dependent, within-print-tip normalization by loess method, we observed that expression patterns of cell lines and tissues were substantially different, divided in two discrete clusters. Next, we selected 115 genes that discriminate gastrointestinal cancer cell lines from others using significant analysis of microarray. Among the expression profiles of five gastric cancer cell lines, 66 genes were identified as differentially expressed genes related to metastatic phenotype. YCC-16, which was established from the peripheral blood of one advanced gastric cancer patient, produced a unique gene expression pattern resembling the profiles of lymphoid cell lines. Quantitative real-time reverse transcription-PCR results of selected genes, including PXN, KRT8, and ITGB5, were correlated to microarray data and successfully discriminate the gastrointestinal tract cancer cell lines from hematologic malignant cell lines. CONCLUSIONS: A gene expression database could serve as a useful source for the further investigation of cancer biology using the cell lines.

Cell Line, Tumor↗
PubMed2005

The role of phosphoinositide-3-kinase in mast cell homing to the gastrointestinal tract.

Phosphoinositide-3-kinases (PI3Ks) are a family of lipid kinases essential in a variety of physiological reactions. A series of gene-targeted mice lacking different PI3Ks and related molecules has enabled us to understand their in vivo roles, particularly those of class IA members. Studies on knockout mice lacking class IA PI3Ks and knock-in mice expressing mutant forms of enzymes have revealed the importance of this class of PI3Ks in mast cell development in the gastrointestinal tract. Here we studied the role of the p85a regulatory subunit, the most abundantly expressed regulatory subunit of class IA PI3Ks, using p85a knockout mice. Development of mast cells in the gastrointestinal tract but not in the skin was severely impaired in mice lacking the p85a regulatory subunit. Stem cell factor (SCF)-mediated signalling functions including proliferative response and chemotactic activities were both impaired in p85a knockout mast cells, likely due to the mast cell deficiency. Mastocytosis upon Strongyloides veneZuelensis infection was also impaired in p85alpha knockout mice. Reconstitution with Th2-conditioned but not untreated bone marrow-derived mast cells (BMMCs) restored anti-bacterial immunity, indicating the importance of Th2 response in addition to the recruitment of mast cells in the control of nematode infection.

Animals↗
PubMed1990

Composite (adenocarcinoid) tumors of the gastrointestinal tract.

Tumors of the gut with composite features of both adenocarcinoma and carcinoid have been recognized mainly in the appendix. There also have been isolated reports of similar tumors arising from other parts of the gastrointestinal tract. It is generally concluded that these tumors have better prognosis than adenocarcinomas of the gastrointestinal tract. We reported six patients with composite tumors arising from the stomach in one, small intestine in two, cecum in two, and rectum in one patient. Clinical presentations in each was suggestive of malignancy with extension to either serosa and/or lymph nodes. Metastasis to liver was present in two patients. Histologically, the tumor showed glands with surface microvilli resembling adenocarcinoma and also organoid pattern with neurosecretory granules in cells resembling carcinoid. Two patients died three and nine months after surgery. The clinical presentation, findings at operation, and the postsurgical course of these six patients reveal that these tumors behave more like an adenocarcinoma than carcinoid and do not appear to have a better prognosis than ordinary adenocarcinoma.

Adenocarcinoma↗
PubMed2006

Podocalyxin-like protein 1 expression is useful to differentiate pancreatic ductal adenocarcinomas from adenocarcinomas of the biliary and gastrointestinal tracts.

Metastases of adenocarcinomas from the pancreas, liver, and gastrointestinal tract are difficult to distinguish from each other because of their similar morphological and immunohistochemical features. So far, no specific marker for pancreatic ductal adenocarcinomas has been described. Podocalyxin-like protein 1 (PODXL-1) is expressed on vascular endothelium, hematopoietic precursor cells, and renal podocytes. We found that 44% (71/160) of pancreatic ductal adenocarcinomas expressed PODXL-1 in a membranous pattern. There was no expression in intrahepatic cholangiocarcinomas (0/18, P < .001), rarely in adenocarcinomas of the extrahepatic bile ducts (1/13, P = .009), and none in duodenal adenocarcinomas (0/5, P = .070). PODXL-1 expression was seen in only 9% of hepatocellular carcinomas (5/56, P < .001), 9% (4/47, P < .001) of gastric carcinomas, 10% of esophageal adenocarcinomas (2/20, P = .003), and 6% of colonic adenocarcinomas (1/17, P = .001). When used as a differential diagnostic marker, ampullary carcinoma needs to be excluded, as 30% (6/20, P = .24) of ampullary carcinomas stain positive, especially those of the signet-ring type (3/3). Adenocarcinomas of the lung and prostate, and liver metastases of colorectal carcinomas lacked PODXL-1 expression. It is concluded that immunoreactivity for PODXL-1 favors a pancreatic origin if ampullary carcinoma is excluded.

Adenocarcinoma↗
PubMed1998

Coexistence of proguanylin (1-15) and somatostatin in the gastrointestinal tract.

In order to identify proguanylin-secreting cells, we have raised an antiserum against the synthetic fragment of human proguanylin (1-15) and have examined the proguanylin-positive cells in the human and rat gastrointestinal tract by immunohistochemical methods. Numerous proguanylin (1-15)-immunoreactive cells were found in the gastrointestinal tract. They were either pyramidal or spindle shaped in the stomach. Spindle-shaped cells, frequently possessing long slender processes, were located at the base of the pyloric epithelium and did not extend to the lumen. In the duodenum and jejunum, these cells were mostly pyramidal in shape and often had a slender process towards the lumen. The immunostaining was completely blocked by the human proguanylin (1-15) fragment. Paneth and goblet cells were negative against this antiserum. The number of serotonin-positive cells was much larger than that of proguanylin-positive cells in all the segments tested. The number of proguanylin-positive cells decreased from the jejunum to the ileum and very few cells were observed in the colon. In contrast to serotonin-positive cells, most somatostatin-positive cells were also positive for proguanylin. Thus, proguanylin (1-15) or its related protein appears to coexist with somatostatin in intestinal endocrine D cells which may be a source of circulating proguanylin. Proguanylin, like somatostatin, may also regulate intestinal function as a local regulator.

Animals↗
PubMed1997

Morphological relations between haem oxygenases, NO-synthase and VIP in the canine and feline gastrointestinal tracts.

Carbon monoxide (CO), produced by haem oxygenase (HO), has been suggested as a messenger molecule in the central and peripheral nervous systems. In the present study, we have investigated the occurrence of the two isoforms of HO, HO-2 and HO-1 in the canine and feline gastrointestinal tracts, including the small and large intestine and the gastrointestinal sphincters. An abundance of nerve cell bodies that contained immunoreactivity for HO-2 was found in the submucosal and myenteric plexuses. HO-2 immunoreactivity was frequently co-localized with nitric oxide synthase (NOS) or vasoactive intestinal peptide (VIP) immunoreactivities and was also observed in some nerve fibres, certain non-neuronal cells dispersed among smooth muscle bundles, and in vascular endothelium. The antiserum against HO-1 revealed immunoreactivity in nerve cell bodies in the enteric plexuses, in nerve fibres and in non neuronal cells in the smooth muscle layers. Some of the nerve structures were also NOS- or VIP-immunoreactive. These results demonstrate the presence of HO isoenzymes in nerves and other structures of the canine and feline gastrointestinal tracts and support the view that CO may have a role as a messenger molecule in the enteric nervous system.

Animals↗
PubMedDate not supplied

Evaluation of fixed- versus variable-modulation treatment modes for charged-particle irradiation of the gastrointestinal tract.

The clinical usefulness of variable-modulation dose delivery of neon ion and proton beams over fixed-modulation beams is evaluated for several patients with tumors in the gastrointestinal tract by comparing dose distributions, dose volume histograms, and predictions of normal tissue complication probabilities calculated with the two methods. Both techniques provide excellent coverage of the target volume with neon ion and proton beams. The advantage of variable modulation is that less dose is delivered proximal to the target volume. For tumors in the gastrointestinal tract, this implies that less dose is given to the liver, gut, kidneys, and lungs. For the ten patients considered in this study, variable-modulation reduced the total integral dose by an average of 17% for neon ion beams and by 18% for protons as compared to fixed-modulation. If the tumor volume is excluded, the reduction in the integral dose to normal tissues ranged from 15% to 32% for neon ions and from 18% to 34% for proton beams. These gains are larger than those anticipated on the basis of an analytic study by Goitein and Chen [Med. Phys. 10, 831-840 (1983)], which predicted integral dose reductions of the order of 10% for protons and 14% for neon ions. They are also larger than those reported in a similar study by Urie and Goitein [Med. Phys. 16, 593-601 (1989)] for proton irradiation of skull-base tumors. This is probably because the tumors in the GI tract considered in this study were more irregularly shaped than Goitein and Chen's analytic model assumes. The results of this study also suggest that due to increased sparing of normal tissues, the number of different portal directions required to achieve a satisfactory treatment plan will be reduced for variable-modulation beam delivery systems. This implies that variable-modulation treatment plans will be easier to execute than current fixed-modulation plans.

Adenocarcinoma↗
PubMed1996

Management of the gastrointestinal tract and nutrition in patients with cloacal exstrophy.

Cloacal exstrophy is a rare condition in which there is a complex set of congenital anomalies that affect multiple-organ systems, including the gastrointestinal tract. Twenty-six patients with cloacal exstrophy have been treated at the authors' institution during the last 20 years. Gastrointestinal features usually included omphalocele, exstrophy of an everted cecal plate, a short blind-ending distal colon, imperforate anus, and, occasionally, a shortened small bowel. Additional gastrointestinal anomalies included four cases of colonic duplication, one duodenal web, and one malrotation. The average time until the initiation of enteral feeding after initial surgery was 15.6 days, and the time until discontinuation of total parenteral nutrition (TPN) was 36 days. One patient with short bowel syndrome died of TPN-associated liver failure. Five other patients exhibited short bowel physiology, but ultimately each was weaned from supplemental intravenous hyperalimentation. Four patients have undergone posterior sagittal anorectoplasty, and one has had perineal anoplasty. Of these patients, two are continent and one is free of soilage on a bowel management program. In the authors' experience with management of the gastrointestinal tract and nutrition in patients born with cloacal exstrophy, many patients initially exhibited short bowel physiology, although most eventually adapted. However, very few patients have been able to achieve bowel control.

Abnormalities, Multiple↗
PubMed1996

Distribution of alpha-vascular smooth muscle actin in the smooth muscle cells of the gastrointestinal tract of the chicken.

Immunoreactivity specific for alpha-vascular smooth muscle actin (ASMA) was examined in the enteric smooth muscle cells along the entire length of the gastrointestinal tract of the chicken. Specificity for gamma-smooth muscle actin (GSMA) and desmin was also examined. All smooth muscle layers, i.e. the muscularis mucosae, and the circular and longitudinal muscle layers, showed immunoreactivity specific for GSMA and desmin throughout the gastrointestinal tract whereas immunoreactivity for ASMA differed between regions and muscle layers. In the oesophagus and crop, immunoreactivity for ASMA was observed in the muscularis mucosae and the inner and outer muscle layers, together with staining for GSMA and desmin. In the proventriculus, immunoreactivity for ASMA was observed in all smooth muscle cells in the inner layer of the muscularis mucosae and the longitudinal muscle layer. In the outer layer of the muscularis mucosae, immunoreactivity for ASMA on smooth muscle cells was observed on the luminal side and decreased in the serosal direction. In the intermediate muscles, immunoreactivity for ASMA was observed in the luminal portion, the intensity of staining decreasing gradually in the serosal direction. In contrast to the intermediate muscles, the latter muscles were negative for ASMA. In the pyloric region, the outer part was weakly immunopositive, while the inner part was intensely positive. In the small and large intestines, the muscularis mucosae and the longitudinal muscle layer were positive for ASMA. The outer part of the circular muscle layer was immunonegative for ASMA whereas the inner part was positive. The complex structure and contractile functions of each organ and muscle layers may be related to the difference patterns of expression of ASMA molecules in the smooth muscle cells.

Actins↗
PubMed2002

Adenocarcinomas of the gastrointestinal tract with prominent rhabdoid features.

Rhabdoid tumor, first described in kidneys of infants and children, is an aggressive tumor that has been reported in several extrarenal locations. Gastrointestinal tumors with rhabdoid features are extremely rare. The effect of the rhabdoid phenotype on the aggressiveness of gastrointestinal tumors remains unclear. We present four cases of rhabdoid tumors of the gastrointestinal tract involving the esophagus, stomach, and small intestine and discuss the clinicopathologic, immunohistochemical, and ultrastructural features. In the four cases reported herein, the patients' ages ranged from 52 to 73 years, and tumor size ranged from 3.8 to 13 cm in greatest dimension. The noncohesive rhabdoid cells exhibited an eccentric nucleus with a paranuclear inclusion, which was shown by electron microscopic examination to be composed of intermediate filaments. On immunohistochemical staining, the tumor cells were positive for vimentin and cytokeratin. Three patients developed distant metastasis shortly after diagnosis and died of disease within 2 to 10 months after initial presentation. A retrospective review of outcomes of the current cases and previously published literature showed that 12 (75%) of the 16 patients died within 6 months of presentation. Recognition of the rhabdoid phenotype in gastrointestinal tract neoplasms is important because this feature is associated with poor prognosis and unresponsiveness to conventional therapy.

Adenocarcinoma↗