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Evaluation of ileal function using 23-selena-25-homotaurocholate, a-gamma-labeled conjugated bile acid. Initial clinical assessment.

23-Selena-25-homotaurocholate is a synthetic bile acid labeled with a gamma-ray-emitting radioisotope 75Se. It is readily measured using external detectors and is thus suitable for whole-body counting. Whole-body retention was measured at 0, 4, and 7 days after oral administration to normal controls and to patients with disease of the small intestine, colon, or ileocecal region. Whole-body retention of less than 25% of the administered radioactivity within 4 days is definitely abnormal, but there was overlap between normal and abnormal groups at this time. At 7 days, whole-body retention less than 12% is abnormal and greater than 19% is normal. Between these limits, values may represent minimal ileal dysfunction not demonstrable by older techniques. Excretion of 23-selena-25-homotaurocholate follows a biexponential curve. The faster component has a half-life similar to that of natural bile acid. It is uncertain whether the slower component represents a hitherto unrecognized slowly turning over pool of bile acid or is a metabolic product of 23-selena-25-homotaurocholate not yet identified in vitro. There is a significant relationship between the whole-body retention of 23-selena-25-homotaurocholate and total fecal and primary bile acids. 23-selena-25-homotaurocholate is simple and acceptable for investigating ileal function.

Adolescent↗

Observations on the Texas Star-SR avirulent A-B+ mutant candidate cholera vaccine.

Comprehensive controlled vaccine trials have revealed that neither conventional cholera vaccines nor cholera toxoid administered parenterally are effective in inducing durable immunity against cholera. The only truly effective means of immunization against cholera as yet demonstrated conclusively only in volunteers, are (a) recovery from the disease itself and (b) that observed following oral administration of living attenuated mutants. In both instances, the host is presented with a consortium of vibrio products at the important local level. Studies in our laboratory have resulted in the isolation from cholera vibrios of a soluble haemagglutinin (HA), which has inherent protease activity, and which appears to participate in adherence of the vibrios to the intestinal epithelium. Current observations indicate that this HA/lectin/protease (a) is produced in both a cell-associated and a soluble form in vivo and (b) that it hydrolyzes fibronectin, secretory immunoglobulin A (sIgA), and mucin, three host proteins which may be significant in specific and non-specific resistance. The Texas Star-SR mutant has been shown to have a mild side effect in volunteers in that, independent of the dose administered about 20% of the recipients manifest one or a few non-inconveniencing loose movements. It is possible that the mere act of intestinal colonization may alter fluid transport in the gut and that this could be a model for other diarrheal disease.

Cholera↗

Tissue reaction to Histoacryl Blue adhesive and histological investigation of its disappearance in various organs.

The effect of the adhesive Histoacryl Blue on the abdominal organs (liver, stomach, intestines, colon, kidneys, bladder, aorta inferior vena cava and skin wounds) of 15 dogs was investigated histologically. The adhesive was applied in thin or thick layers in various ways: applied on intact or injured surfaces, or introduced into the parenchymal organs. The animals were killed 1, 2, 4, 8 weeks and 3 and 6 months after application of the adhesive and the organs containing Histoacryl Blue were processed histologically. The success of adhesion depended, irrespective of the organ, upon the technique of application and on the quantity of the adhesive used.

Animals↗

[Histological survey on the behaviour of antidiarrheal drugs under in vitro conditions (author's transl)].

The effect of four antidiarrheal drugs (China clay, bentonite, pectin, Kaoprompt H) on the epithelia of murine small intestine and colon was studied under in vitro conditions with histological techniques. In this experiment, the drugs coarsely coated the guts' surface without outlining details or protruding into clefts. The resistance of the layers to rinsing is slightly different. None of the substances was able to protrude between the microvilli. Best intrusion was shown by pectin. The transfer of the experimental results to in vivo conditions is discussed.

Animals↗

Studies on the use of 9R strain of Salmonella gallinarum as a vaccine in chickens.

The 9R strain of Salmonella gallinarum produced hepatitis and splenic lesions without mortality in meat-type and brown-egg-producing strains of chicks, but not in Leghorns. It was not recovered from Leghorns for as long following vaccination as from the other strains of chicks. The infectivity of the 9R strain was determined by the genetic susceptibility and age of the host. Subcutaneous vaccination of 9R produced partial immunity to S. gallinarum in Leghorns as well as in meat-type and brown-egg-producing strains of chickens. Addition of an oil adjuvant appeared to interfere with protection and gave even less protection than did a vaccine prepared from an inactivated oil-adjuvanted smooth strain. Use of the 9R vaccine did not protect against intestinal colonization by S. typhimurium or S. infantis. Potential egg transmission of 9R following vaccination and of a pathogenic strain following challenge of vaccinated birds was indicated by ovarian infection with each strain and by isolation of the pathogenic strain from one egg. All chickens vaccinated subcutaneously with the 9R strain developed antibodies detectable by the microantiglobulin test, but only a few birds developed antibody levels detected by the whole-blood, microagglutination, and tube tests. The inactivated vaccine prepared from a smooth S. gallinarum strain produced the highest and most uniform antibody response. Antibody levels were not related to protection, which is probably dependent on cellular immunity.

Administration, Oral↗

[Regional blood filling in hypoxic hypoxia].

Unanesthetized rats put in the hermetic chamber breathed with a gas mixture containing 10.5% of oxygen in nitrogen during 30 and 60 min (moderate hypoxia), and 3.5% of oxygen in nitrogen for 30 min (severe hypoxia). The circulating blood volume increased in moderate hypoxia but was rather reduced in severe hypoxia. Mobilization of blood from the liver occurred in moderate hypoxia after 30 min, becoming less obvious after 60 min or in severe hypoxia. Redistribution of blood in the myocardium, skeletal muscles of the head and neck occurred in moderate hypoxia. Severe hypoxia led to depression of the regional circulating blod redistribution and the signs of pathological accumulation of the blood in the liver, small intestine, colon and testicles.

Acid-Base Equilibrium↗

Molecular cloning and expression of multiple isoforms of human prostaglandin E receptor EP3 subtype generated by alternative messenger RNA splicing: multiple second messenger systems and tissue-specific distributions.

Five distinct cDNA clones encoding four different isoforms of human prostaglandin (PG) E receptor EP3 subtype were isolated from a human kidney cDNA library. Two cDNA clones differed only in their 3'-untranslated regions. The four isoforms, tentatively named EP3-I, EP3-II, EP3-III, and EP3-IV, which were generated by alternative mRNA splicing, had identical amino acid sequences except for their different carboxyl-terminal tails. Transfection experiments revealed that all the four isoforms show high binding affinities to PGE2, PGE1, and M&B28767, an EP3-specific agonist, whereas their downstream signaling pathways are divergent. M&B28767 increased cAMP concentrations in cells expressing EP3-II and EP3-IV, whereas it inhibited forskolin-induced cAMP accumulations in cells expressing all EP3 isoforms. M&B28767 also stimulated phosphoinositide turnover in cells expressing EP3-I and EP3-II. Northern blot analysis revealed that the EP3 gene is expressed in a wide variety of human tissues. The human EP3 mRNA was present most abundantly in the kidney, pancreas, and uterus. A substantial expression was also detected in the heart, liver, skeletal muscle, small intestine, colon, prostate, ovary, and testis. Furthermore, reverse transcription-polymerase chain reaction analysis demonstrated tissue-specific expressions of the five different EP3 mRNA species. The present study suggests the presence of the multiple systems of PGE2/EP3 isoforms and leads to the better understanding of its physiological and pathophysiological implications in humans.

Alternative Splicing↗

Molecular cloning of human 5-hydroxytryptamine3 receptor: heterogeneity in distribution and function among species.

The 5-hydroxytryptamine3 receptor 5-HT3R has been implicated in gut and cardiac motility and in behavioral disorders. Characteristics of 5-HT3Rs appear to be heterogeneous among species, but human 5-HT3R cDNA has not been identified. We isolated a cDNA encoding 5-HT3R from human hippocampus. The mouse 5-HT3R gene has been reported to generate two alternative splicing isoforms that differ by six amino acids. All of our isolated human clones corresponded to the shorter isoform. Amino acid identities with mouse neuroblastoma N1E-115 and rat brain 5-HT3Rs were 84% for each. Southern blot analysis of human genomic DNA suggested that our cloned transcript encoded a human counterpart for the rodent 5-HT3Rs. This gene was assigned to chromosome 11 using polymerase chain reaction analysis of a human/rodent somatic cell hybrid panel. With the use of Northern blot analysis, 5-HT3R transcripts were identified in human small intestine, colon, and brain regions including hippocampus, amygdala, and striatum. In human heart, 5-HT3R expression was not detectable even with reverse transcriptase-polymerase chain reaction analysis, although it was detectable in mouse heart. Transfection of COS-1 with human 5-HT3R cDNA induced specific binding of the 5-HT3R-selective radioligand [3H]YM060. Human 5-HT3R showed typical characteristics of the 5-HT3R, but its affinity for the 5-HT3R agonist m-chlorophenylbiguanide was much lower than that of rat 5-HT3R. When injected with human 5-HT3R cRNA, the oocytes responded to 5-HT3R agonists with a rapidly developing inward current. The potency of the agonists to induce inward current paralleled that to compete with the radioligand binding, and 2-methyl-5-hydroxytryptamine, a partial agonist for mouse 5-HT3R, was a full agonist for human 5-HT3R. Our data revealed that the 5-HT3R molecule has interspecies differences in both tissue distribution and functional profile.

Amino Acid Sequence↗

[Crohn's disease of the esophagus. Apropos of a case].

The authors report a case of Crohn's disease of the esophagus, stomach, small intestine, colon and rectum in a 34-year-old patient. The esophagus was affected three months after diagnosis of the ileo-rectal lesion. They discuss clinical and therapeutic aspects of the condition. They stress the value of upper endoscopy with multiple biopsies in providing the diagnosis. Treatment is essentially medical, surgery being restricted to fistulas after failure of medical treatment and parenteral nutrition, and to severe stenoses after failure of endoscopic dilatation.

Adult↗

Primary structure and functional expression of a novel gastrointestinal isoform of the rat Na/H exchanger.

A cDNA encoding a new isoform of the rat Na/H exchanger (NHE) family has been identified by cross-hybridization with an NHE-1 cDNA probe. The 3.9-kilobase stomach cDNA encodes a protein of 813 amino acids with an M(r) of 91,296. The amino acid sequence of the protein, termed NHE-2, is 42% identical to NHE-1, 36% identical to NHE-3, and 57% identical to NHE-4. Na/H exchanger-deficient Chinese hamster ovary cells that were transfected with an expression construct containing the complete coding sequence of this cDNA exhibit amiloride-sensitive, H+-dependent 22Na+ influx, demonstrating that the protein it encodes is a functional Na/H exchanger. Northern hybridization analyses show that the corresponding mRNA is expressed predominantly in small intestine, colon, and stomach, with much lower levels present in skeletal muscle, kidney, brain, testis, uterus, heart, and lung. This suggests that NHE-2 plays an important role in gastrointestinal physiology and functions in many other organ systems as well.

Amino Acid Sequence↗

[Enterotoxigenic Escherichia coli K99+, serotype 08:K25, produce cytotoxic necrotizing factor CNF1 and alpha-hemolysin].

A total of 54 K99+ and/or F41+ Escherichia coli strains isolated of calves and piglets with diarrhoea in different countries were investigated for production of heat-labile (LT) and heat-stable (STa) enterotoxins, verotoxins (VT1 and VT2), cytotoxic necrotizing factors (CNF1 and CNF2), alpha-haemolysin (Hly) and enterohaemolysin (EntHly). Fifty-one (94%) strains were STa+, two (4%) were STa+CNF1+Hly+ and one (2%) was not toxigenic. The two STa+CNF1+Hly+ E. coli strains expressed the K99 intestinal colonization factor and belonged to serotype O8:K25. The majority of STa-producing E. coli were K99+ and F41+ and belonged to serotypes O9:K(A)35, O101:K(A)28 and O101:K(A)30. All enterotoxigenic strains assayed in this study were negative for expression of the Att25, Vir and B23 adhesins recently detected in E. coli that cause infections in calves.

Adhesins, Escherichia coli↗

Immunohistochemical analysis of Mcl-1 protein in human tissues. Differential regulation of Mcl-1 and Bcl-2 protein production suggests a unique role for Mcl-1 in control of programmed cell death in vivo.

The mcl-1 gene encodes an approximately 37-kd protein that has significant homology with Bcl-2, an inhibitor of programmed cell death that is expressed in many types of long-lived cells. In this study we determined the in vivo patterns of Mcl-1 protein production in normal human tissues by immunohistochemical means, using specific polyclonal antisera, and made comparisons with Bcl-2. Like Bcl-2, Mcl-1 immunostaining was observed in epithelial cells in a variety of tissues, including prostate, breast, endometrium, epidermis, stomach, intestine, colon, and respiratory tract. However, often the expression of mcl-1 and bcl-2 in complex epithelia occurred in gradients with opposing directions, such that Bcl-2 immunostaining tended to be higher in the less differentiated cells lining the basement membrane, whereas Mcl-1 immunostaining was more intense in the differentiated cells located in the upper layers of these epithelia. The in vivo patterns of mcl-1 and bcl-2 expression were also strikingly different in several other tissues as well. Within the secondary follicles of lymph nodes and tonsils, for example, germinal center lymphocytes were Mcl-1 positive but mostly lacked Bcl-2; whereas mantle zone lymphocytes expressed bcl-2 but not mcl-1. Intense Mcl-1 immunoreactivity was also detected in several types of neuroendocrine cells, including the adrenal cortical cells that are Bcl-2 negative, sympathetic neurons that also contain Bcl-2, a subpopulation of cells in the pancreatic islets, Leydig cells of the testis, and granulosa lutein cells of the ovarian corpus luteum but not in thyroid epithelium, which is strongly Bcl-2 positive. Little or no Mcl-1 was detected in neurons in the brain and spinal cord, in contrast to Bcl-2, which is present in several types of central nervous system neurons. Conversely, strong Mcl-1 immunostaining was found in cardiac and skeletal muscle, which contain comparatively less Bcl-2. Additional types of cells that are Bcl-2-negative but that expressed mcl-1 include chondrocytes and hepatocytes. These findings demonstrate that mcl-1 expression is widespread in vivo and imply that the Mcl-1 and Bcl-2 proteins fulfill different roles in the overall physiology of cell death regulation.

Apoptosis↗

[Dual arterial infusion chemotherapy, continuous hyperthermic peritoneal perfusion, and total parietal peritonectomy for peritoneal dissemination in gastric cancer--a case report].

A 36-year-old man developed massive ascites, of which cytology proved Class V, and upper gastrointestinal endoscopy disclosed Borrmann type 4 gastric cancer. We performed dual arterial infusion chemotherapy (DAIC) through the celiac axis and superior mesenteric artery, followed by the operation including continuous hyperthermic peritoneal perfusion, total gastrectomy, subtotal colectomy, massive intestinal resection, splenectomy, cholecystectomy, appendectomy, and total parietal peritonectomy (TPP). Ascites disappeared and the CA125 level was normalized by DAIC. This operation was well tolerated. Though the histopathological study revealed multiple peritoneal disseminations on the visceral peritoneum of stomach, small intestine, colon, and parietal peritoneum such as Douglas' pouch, there were denatured cancer cells in the visceral peritoneum to which blood supply under DAIC was distributed. These results suggested the effect of neoadjuvant DAIC and the significance of TPP.

Adult↗

[Diarrhea due to rare forms of colitis: microscopic (lymphocytic, collagenous) colitis and spirochetosis].

Lymphocytic and collagenous colitis, uncommon entities that are identifiable by histopathologic examination only, and intestinal spirochetosis may cause chronic diarrhea. Data on incidence, histopathology, and diseases associated with these infrequent forms of colitis are reviewed. Etiology and pathogenesis of lymphocytic and collagenous colitis are still unknown, but immuno-inflammatory factors may be involved in both forms as well as, in collagenous colitis, primary disorders of collagen metabolism or drug-induced toxic effects. The significance of intestinal colonization by spirochetes is disputed; however, recent results indicate that these microorganisms are capable of inducing disease.

Adult↗

GEP31, a new gastric epithelial protein, early expressed during ontogenesis.

A set of monoclonal antibodies directed against various gastric markers was produced in order to study the developmental expression of the gastric mucosa. A previously described monoclonal antibody, mab 146.14, labeled the proton pump (H+, K+) ATPase specifically located in gastric parietal cells. Mabs 15.1 and 121.17 revealed the mucus of mucous neck cells and mucous surface cells, respectively. By addition, mab 81.1 was directed against a cell surface membrane protein antigen composed of a major 31 kDa component (called GEP31). Our study mainly focused on the characterization of GEP31. This protein was typically located in the gastrointestinal epithelial tract (stomach, small intestine, colon). Moreover, interesting features were observed during the study of the early ontogenesis of the gastric mucosa. The 31 kDa protein was detected at the onset of gland formation (day 18), and a gradual increase in expression of the protein could be observed between day 18 and day 19. Furthermore, a comparative study of the expression of different terminal differentiation markers of gastric epithelial cells ((H+, K+) ATPase, mucins) during the early period of ontogenesis revealed that GEP31 could be detected well before the appearance of these markers. To our knowledge, GEP31 thus appears as the earliest expressed specific cell surface epithelial gastric antigen described to date. Furthermore, the partial N-terminal amino acid sequence of GEP31 was determined and revealed that it is not a known protein.

Amino Acid Sequence↗

Dieulafoy-like lesion of the rectum presenting with exsanguinating hemorrhage: successful endoscopic sclerotherapy.

The classic Dieulafoy lesion is a minute gastric mucosal defect that bleeds massively from an exposed artery. Similar lesions have been identified in the small intestine, colon, and rectum. In this report, we describe a patient who presented with an exsanguinating hemorrhage from a small rectal ulcer with a visible vessel. Control of the bleeding was achieved with endoscopic sclerotherapy using absolute alcohol and 1.5% sodium tetradocyl sulfate, with eventual complete healing of the site.

Adult↗

Agonist effect of erythromycin and its analogues on motilin receptors. A new family of prokinetics? Clinical interest.

It has been known since long that erythromycin may cause unpleasant gastro-intestinal side-effects such as nausea and vomiting. Recent studies however show that at low doses erythromycin may have a beneficial effect. Erythromycin induces the migrating motor complex in the fasted state and after a meal it accelerates gastric emptying. Although largely preliminary, its effects on esophageal, small intestinal, colonic and biliary tract motility have now been studied in several pathological conditions. Erythromycin is certainly a powerful gastrokinetic. Its antibiotic properties are a disadvantage, but more powerful derivatives devoid of antibacterial properties may soon become available. They form a new family of prokinetics.

Erythromycin↗

Beta-adrenergic-dependent and -independent actions of naloxone on perfusion during endotoxin shock.

Naloxone, an opioid antagonist, has been shown to improve cardiovascular status during endotoxin shock, including splanchnic perfusion. Enhancement of adrenergic action has been implicated as a physiological path by which naloxone effects changes in cardiac function during endotoxin shock, but the mechanism for changes in various splanchnic vascular beds has not been examined. In this study, we examined the role of beta-adrenergic actions in cardiovascular performance and the splanchnic perfusion changes caused by naloxone during endotoxin shock. Rats were instrumented with catheters in the tail artery, left cardiac ventricle, and jugular vein. Twenty-four hours later, rats received saline or endotoxin (2 mg/kg) challenge intravenously over 30 min, followed at 40 min by i.v. naloxone (or saline) treatment (4 mg/kg + 2 mg/kg.hr) in the presence or absence of propranolol (1 mg/kg + 1 mg/kg.hr). Radiolabelled microspheres were used to determine cardiac outputs and blood flows at 0, 30, 60, and 120 min after beginning endotoxin infusion. Blood pressure was not affected by endotoxin challenge, but cardiac output and most organ blood flows fell over time. beta-Adrenergic blockade did not alter this response. Naloxone improved cardiac output and blood flow to the stomach, small intestine, colon, and spleen but not to other splanchnic organs. Naloxone also increased renal and coronary blood flows. The improvements in cardiac output with naloxone were ablated in the presence of propranolol, as were the increases in gastric, colonic, splenic, coronary, and renal blood flows. However, the beneficial effect of naloxone on small bowel blood flow was not diminished by blockage of beta receptors. These results suggest that the effects of opioid antagonism are mediated, in part, by enhancing endogenous beta-adrenergic actions in vivo. Improvements in the splanchnic circulation are selectively altered by naloxone during endotoxin shock, some independent of beta-adrenergic actions. Understanding this phenomenon can lead to the appropriate use of opioid antagonism, should it prove clinically useful in the treatment of septic shock.

Animals↗