An acid transporting enzyme in human gastric mucosa.

Isolation of a microsomal fraction from human gastric mucosa followed by density gradient centrifugation yielded a vesicular membrane preparation free of mitochondrial markers, containing a K+-activated, ouabain-insensitive ATPase with an activity of 20.7 mumol P1 released/mg protein per h. Sodium dodecyl sulfate gel electrophoresis showed that the human gastric membrane vesicles contained a major polypeptide of 110,000 daltons, which accounted for approximately or equal to 30% of the total protein stained and was phosphorylated by [gamma-32P]ATP and dephosphorylated in the presence of K+. Electron microscopy revealed the presence of vesicles with an average size of 0.13 micrometer in diameter. Addition of 0.65 microM ATP to this vesicular preparation resulted in the uptake of 17 nmol H+/mg protein which was dependent on the presence of K+. The gradient was dissipated by a combination of valinomycin and protonophore after consumption of the ATP. Incubation of fixed human fundic sections or human gastric biopsy with monospecific hog gastric membrane antibody followed by fluorescein-conjugated goat anti-rabbit gamma-globulin, showed fluorescent staining in the middle portion of the gastric glands. These data indicate that human stomach contains a H+ transport ATPase with characteristics similar to those established for lower species.

Immunologic studies on a pancreatic oncofetal protein.

Immunization of rabbits with a human fetal pancreas extract produced precipitating antibody against an antigen present only in fetal pancreas and extracts of human pancreatic carcinoma. Pancreatic oncofetal protein (POP) migrated on immunoelectrophoresis in the alpha1-alpha2 region, thus making possible its detection by counterimmunoelectrophoresis. POP was found in the 12,000 X g supernatant of fetal pancreas and could be precipitated with (NH4)2SO4 at concentrations between 30 and 45%. The antigen was partially purified by consecutive centrifugation at 12,000 X g, 40% (NH4)2SO4 precipitation, and ion-exchange chromatography. Treatment of the POP with trypsin completely abolished its antigenic activity; this suggested that the antigen was a protein or a moiety closely associated with protein.

Value of gallium-67 citrate scanning in Crohn's disease: concise communication.

A frequent problem in Crohn's disease is the distinction between exacerbated inflammation of the bowel, which can be treated medically, and intra-abdominal abscess, a common complication that requires surgical management. We present evidence that the gallium scan is of value in making this distinction. From a series of 11 studies, negative gallium scans correctly excluded abscess in over half. All patients were symptomatic at the time of the scan. Most patients with active Crohn's disease do not have abnormal gallium uptake and in these patients the gallium scan is useful to exclude the possibility of abscess.

Multiple synchronous primaries of the gastrointestinal tract: a molecular case report.

Six synchronous gastrointestinal primaries were identified in a 70 year old male with no known cancer predisposition syndrome or recognized risk factors except alcohol abuse. These specimens appeared to be independent and unrelated by gross and histopathological examination. In order to further evaluate the six tumors, we analyzed selected DNA sequences for alterations in the K-ras oncogene and p53 tumor suppressor gene. In addition, three loci were analyzed to determine microsatellite instability. Using the polymerase chain reaction, single stranded conformational polymorphism, and DNA sequencing, we demonstrated that each primary manifests genetic characteristics typical of the tissue of origin. In addition, one primary, a moderately differentiated colon adenocarcinoma, exhibited mutations not detected in the other specimens. This study suggests that these synchronous primaries arose independently and progressed along different carcinogenic pathways.

Protective effects of zinc in indomethacin-induced gastric mucosal injury: evidence for a dual mechanism involving lipid peroxidation and nitric oxide.

BACKGROUND: Indomethacin causes gastric mucosal injury, although the pathogenesis is not fully understood. Zinc, is known to have gastroprotective effects in both humans and experimental animals. AIM: To determine (i) the protective effects of zinc in indomethacin-induced gastric mucosal injury in rats, and (ii) whether these cytoprotective effects are mediated by changes in gastric lipid peroxidation and/or nitric oxide synthase activity. METHODS: Gastric lesions were induced in rats by the intragastric administration of indomethacin. Morphological changes, lipid peroxidation (malondialdehyde levels) and nitric oxide synthase activity were determined in animals pre-treated with zinc sulphate and in controls. RESULTS: Indomethacin significantly increased malondialdehyde levels and decreased NOS activity. These effects were attenuated by pre-treatment with zinc (P < 0.005 and 0.0001, respectively). The protective effects of zinc were readily abolished in animals pre-treated with N-nitro-L-arginine methyl ester (L-NAME). Morphologically, indomethacin induced large areas of mucosal ulcerations, which were completely prevented by zinc pre-treatment. CONCLUSIONS: Zinc provides protection against indomethacin-induced gastric mucosal injury. These protective effects result from the inhibition of lipid peroxidation and the preservation of mucosal nitric oxide synthase.

A critical evaluation of a procedure for measurement of serum bile acids by radioimmunioassay.

A radioimmunoassay for the quantitative determination of cholic acid conjugates has been developed. Antisera were raised in rabbits injected with cholylglycine coupled by amide linkage to bovine serum albumin. The antibodies reported in this communication were not found to be mono-specific in the strictest sense. This assay is relatively simple, rapid, sensitive, reliable, and most importantly, specific for bile acids; the specificity of each antibody, however, must be thoroughly characterized at the dilution in routine use. The range of normal values for cholic acid conjugates in serum was found to be 0.1--1.6 micronmol/l (mean: 0.62, +/- S.D.: 0.4).

Circulating immune complexes in carcinoma of the pancreas.

Circulating immune complexes were detected by the Clq binding assay in 45% of patients with pancreatic carcinoma. 75% of patients with primary biliary cirrhosis and 60% of patients with sclerosing cholangitis. The immune complexes present in most sera from these three groups were not reactive in the Raji cell radioimmune assay or monoclonal rheumatoid factor radioimmunoassay for soluble immune complexes. Thus, it was not possible to differentiate among these diseases on the basis of circulating immune complexes.

Surgical treatment of the celiac axis compression syndrome.

Six patients with symptomatic celiac axis compression syndrome are reported on. Four were treated surgically with arterial reconstruction. None of these four patients was benefited more than temporarily by the corrective surgery. One patient had an abdominal exploration and highly selective vagotomy unrelated to the celiac axis and is symptom-free ten months after surgery. One patient had no surgery and remains symptomatic. Angiographic evaluation in all patients demonstrated that despite high grade stenosis of the celiac axis, there was no radiographically discernible reduction in constrast flow to the celiac axis because of well developed collaterals from the superior mesenteric artery. These results indicate that compression of the celiac axis may be merely an incidental angiographic finding, so this syndrome needs cautious evaluation.

Ethanol enhances desialylation of transferrin by liver endothelial cells in the rat.

Desialylated transferrin is emerging as a reliable index of alcoholism, and liver endothelial cells are known to partially desialylate transferrin. The effect of a single intraperitoneal injection of ethanol on the desialylation of transferrin in the rat was studied. In pulse-chase experiments, fully sialylated diferric transferrin labeled with 125I (protein moiety) or 3H (sialyl residues) was incubated with isolated, fractionated liver endothelial cells from rats that were given ethanol. The supernatants then were subjected to column chromatography using RCA120-agarose to separate and quantify the desialylated fraction of transferrin. Saline-treated animals served as controls. Incubation of the endothelial cells derived from the liver of ethanol-treated rats resulted in a 263% increase in desialylation level of transferrin. Our data indicate that administering ethanol in rats enhances the desialylation of transferrin by rat liver endothelial cells.

The effect of ethanol on the uptake, binding, and desialylation of transferrin by rat liver endothelium: implications in the pathogenesis of alcohol-associated hepatic siderosis.

Chronic alcoholism has been reported to be associated with a reduced carbohydrate content of transferrin (TF), particularly, its reduced sialylation state. Low sialylation state of TF now serves as an objective marker of chronic alcohol abuse. To investigate the pathophysiological significance of this finding in relation to hepatic siderosis, also commonly associated with chronic alcoholism, the authors have investigated the effect of ethanol on the uptake, binding, and desialylation of transferrin by isolated rat liver endothelium in vitro. In pulse-chase experiments, transferrin labeled with either 125I (protein-labeled) or 3H (sialic acid-labeled) was incubated with isolated, fractionated liver endothelium with and without ethanol, and the supernates were subjected to column chromatography using RCA120- agarose. Incubation of the endothelium with increasing concentrations of ethanol resulted in a progressive increase in the desialylation rate of transferrin which was maximal when 160 mM concentration of ethanol was used. These data indicate that ethanol significantly promotes the desialylation of transferrin by rat liver endothelium. The implications of these findings in the pathogenesis of hepatic siderosis of the alcoholic are discussed.

Laboratory markers of ethanol intake and abuse: a critical appraisal.

Laboratory markers for ethanol intake and abuse and chronic alcoholism currently in use have been critically reviewed. The merits and pitfalls of each test have been evaluated. The clinical use of the new test of carbohydrate-deficient transferrin has been particularly emphasized. Carbohydrate-deficient transferrin currently provides the highest specificity and sensitivity of all commonly used markers of alcoholism.

Case reports: pseudomelanosis duodeni: association with systemic hypertension.

Two male patients with mild gastrointestinal bleeding had peculiar dark pigmentation of their duodenum on upper endoscopy. These pigmented lesions were still present 3 months after the original endoscopy and after resolution of all other mucosal lesions. Both patients had other medical problems, including hypertension. They have been on multiple antihypertensive medications for many years. Biopsies of these duodenal lesions showed the pigment to be present inside the macrophages found in the lamina propria and in between the epithelial cells. Electron microscopy revealed a lysosomal localization of this pigment. This melanin-like pigment proved to contain varying amounts of iron, sulfur, and calcium. This pigmentation is closely associated with systemic hypertension, even in the pediatric population.

Spontaneous bacterial peritonitis in cirrhosis: clinical and laboratory features, survival and prognostic indicators.

This is a retrospective study of 35 patients with spontaneous bacterial peritonitis and liver cirrhosis identified between 1981 and 1989. The mean age of all patients was 44 years, with a range of 16 to 68. Criteria for spontaneous bacterial peritonitis included either a positive ascites culture with a polymorphonuclear cell concentration greater than 250 cells per mm3 (18 cases) or a negative ascitic fluid culture with a polymorphonuclear cell count greater than 500 cells per mm3 and no evident intra-abdominal source of infection (17 cases). Twenty-one patients were male and 14 female. The most frequent presenting symptoms were abdominal pain and fever, noted in 20 (57%) and 19 (54%) patients, respectively, while 5 patients (14%) were completely asymptomatic. The overall mortality in this series was 54% (19 of 35 patients). The presence of encephalopathy or renal insufficiency was associated with a high mortality rate (73% and 87%, respectively). Encephalopathy was present in 67% of the non-survivors, but in only 25% of the survivors (p < 0.0025); likewise, renal failure was observed in 68% of the non-survivors, but in only 12.5% of those who survived (p < 0.001). The use of newer-generation cephalosporins and penicillins led to a diminished mortality (42%) as compared with that (64%) observed in patients treated with conventional antibiotic regimens.

Eosinophilic gastro-enteritis associated with protein-losing enteropathy and protein C deficiency.

Reported below is a case of eosinophilic gastro-enteritis involving the colon, stomach and duodenum in a patient who was also found to have marked hypoalbuminaemia and protein C deficiency due to severe protein-losing enteropathy. The most recent literature is reviewed and the challenging differential diagnosis of the disease is discussed.

When to suspect ischemic colitis. Why is this condition so often missed or misdiagnosed?

Ischemic colitis is one of the most often seen disorders of the large intestine in the elderly. Common predisposing factors are atherosclerosis, shock, and congestive heart failure, but often, elderly patients have no obvious predisposing or precipitating factors. The typical clinical presentation is acute sudden abdominal pain and distention with bloody diarrhea. Common early radiographic signs are bowel-wall thickening with thumbprinting, and later, ulceration and strictures may be found. Endoscopy is valuable in revealing the sharp demarcation between viable and necrotic colonic mucosa that is a strong indicator of ischemia. Within 48 hours, most patients show favorable response to conservative measures consisting of intravenous hydration, bowel rest, antibiotic therapy, and correction of precipitating processes. Vasoconstricting drugs and corticosteroids are contraindicated. When surgical intervention is indicated, it usually consists of resection of the ischemic segment and exteriorization of the remaining ends of the bowel.

Alcoholic hepatitis. Recent advances in pathogenesis and therapy.

Although the pathogenesis of alcoholic hepatitis is not fully understood, significant progress has been achieved in recent years. The role of the immune system in initiating and perpetuating the injury is being defined. Abstinence from alcohol is probably the most effective treatment. Nutritional support has not had a consistently beneficial effect on survival rates. There is renewed interest in the use of corticosteroids in patients with severe disease. Orthotopic liver transplantation is appropriate for some patients with end-stage liver disease.

Serum alpha 1-antitrypsin levels in alcoholic hepatitis.

Serum alpha 1-antitrypsin concentrations have been measured in 68 patients with liver disease. High mean values (359 +/- 18.0) were found in patients with alcoholic hepatitis whereas patients with acute viral hepatitis and chronic active hepatitis did not show any significant differences from the controls. In a group of patients with both alcoholic hepatitis and acute pancreatitis the mean value (218 +/- 5.8) was significantly lower than in the control group. The mechanism for the reduction of serum alpha 1-antitrypsin levels in this group remains to be clarified but low serum alpha 1-antitrypsin may be due to increased proteolytic enzyme concentrations in acute pancreatitis.

Prostaglandin E1 cytoprotection against CCl4-induced necrosis in isolated rat liver cells.

The role of the prostaglandin E1 (PGE1) analog misoprostol in hepatocellular injury induced by carbon tetrachloride (CCl4) was investigated in isolated rat hepatocytes. Exogenously added PGE1 at nanomolar concentrations attenuated significantly liver cell injury and death induced by CCl4. This cytoprotection, however, was accomplished only when a "crude" liver cell preparation was used. When the small nonparenchymal liver cell fraction (Kupffer and endothelial cells) was eliminated, the beneficial effects of PGE1 could no longer be observed. The results indicate that nonparenchymal liver cells play an important role in the cytoprotection provided by PGE1 at the initial stage of cellular damage in our isolated rat liver cell system.