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Biomedical subjects

B I Hirschowitz

Publications and source records attributed to B I Hirschowitz.

At least 163 records · Page 9Linked to original sources
PubMed1977

Radioimmunoassay of serum bile acid levels in biopsy-proved cirrhosis.

Serum bile acid levels were determined by a radioimmunoassay for conjugates of cholic acid in 18 patients with biopsy-proved cirrhosis and compared to results of conventional liver function tests. Serum bile acid levels were abnormal in all 18 patients whereas results of the other tests were abnormal in only 50% to 72% of patients. In this group of patients with a well established diagnosis of cirrhosis, serum bile acid levels were a more sensitive indicator of liver dysfunction than standard liver function tests.

Bile Acids and Salts↗
PubMed1977

Evidence for a histamine H2 receptor that inhibits pepsin secretion in the dog.

H+ and pepsin output were studied in four gastric fistula dogs with histamine and in five dogs with 4-methylhistamine (4(Me)H), an H2 histamine receptor agonist with little H1 effect. Each amine was given in 45-min incremental step doses to constitute full dose-response curves. Pepsin output was biphasic with both drugs. Peak pepsin output occurred at low doses (less than or equal to 5 microgram/kg-h) and progressive inhibition of output was seen at higher doses, but H+ output was stimulated at all doses. The H2 receptor antagonist, cimetidine, competitively inhibited H+ stimulation. The pepsin response to histamine or 4(Me)H was converted to a positive logsigmoid response when cimetidine was given at the same time. In the presence of cimetidine (1 mg/kg-h), the outputs of H+ and pepsin were positively correlated in the full histamine dose range. These data show that histamine effects on pepsin secretin are a mixture of stimulation and inhibition and that the receptor responsible for pepsin stimulation is of a high affinity, low Km, H2 type, whereas inhibition at high doses of histamine is probably mediated by a low affinity, high Km receptor, also H2 type.

Animals↗
PubMed1977

An 125I radioimmunoassay for primary conjugated bile salts.

Cholylglycylhistamine, a derivative of cholic acid, has been synthesized and characterized. This derivative has been iodinated using Na125I and chloramine-T and purified free from unlabeled cholylglycylhistamine. Application of this iodinated bile salt derivative to radioimmunoassay of bile salts in human serum is reported. Antibody titers have uniformly increased over titers used in tritium-based assays; some antibodies are usable in dilutions of 1:80,000. The radioimmunoassay described here was found to measure predominantly the primary conjugated bile salts. Sensitivity has been maintained, with the least detectable amount being 0.5 pmoles per assay tube. Normal values in human serum are 3.47 +/- 2.16 (SD) nmoles per ml.

Animals↗
PubMed1977

Evaluation of two commercial kits for serum gastrin assay, and comparison with a conventional radioimmunoassay procedure.

We compared two gastrin radioimmunoassay kits ("Immutope" kit, Squibb & Co.; "Gastrin R.I.A." kit, Schwarz/Mann) to the conventional gastrin radioimmunoassay of Yalow and Berson [Gastroenterology 58, 1 (1970)] as run by us and by a second reference laboratory. Although both kits were found to effectively discriminate above-normal and normal values for serum gastrin, they significantly underestimated very high values (greater than 1500 ng/liter). The Schwarz/Mann kit clearly had a superior quality label (lower nonspecific binding and higher specific activity) and a shorter incubation time. However, the 90-min incubation period cited for their kit caused overestimation of gastrin values in the lower range (5-300 ng/liter), which could be corrected by prolonging the incubation to 24 h. The Squibb antibody had fairly good cross reactivity to all gastrin species tested; the Schwarz/Mann antibody had poor affinity for natural human gastrin G34-II. Good correspondence was found for sera run by both reference laboratories (y = 0.96x + 10, r = 0.997), and values obtained with the Schwarz/Mann kit correlated best (+ 0.815) with those from the conventional radioimmunoassay procedure.

Antibody Specificity↗
PubMed1976

Gastric acid secretion.

Advances in the understanding of physiologic control of gastric secretion raise the hope that an effective nonsurgical therapy for peptic ulcer disease will be developed soon. This paper reviews these advances with special emphasis upon those aspects of hormonal control, cyclic nucleotide function, and histamine activity which may have therapeutic applications.

Gastric Juice↗
PubMed1976

Inhibition of basal and stimulated gastric H+ and pepsin secretion in duodenal ulcer patients by metiamide, an H-2 histamine antagonist.

Metiamide was given orally in one dose of 200 mg in 23 sutdies in patients with duodenal ulcer, 4 in the basal state, 11 during histamine infusion, and 8 before insulin hypoglycemia stimulation. In the latter 8 patients insulin was given at another time without metiamide. In 17 studies acid secretion was suppressed by metiamide--up to 75% in the basal state, 53% after histamine, and 80% after insulin. Pepsin secretion was reduced to the same extent as H+ in the histamine studies but not in the basal (57%) or insulin (44%) studies, so that in the latter pepsin/acid ratios were 3-fold greater than in controls. Blood levels of metiamide were measured in 17 studies. In 10 out of 11 who showed inhibition of 40% or more, peak blood levels of metiamide were 0.45 mug/ml to 1.25 mug/ml. In 5 of 6 who did not show inhibition, blood levels were 0.05-0.4 mug/ml; in the sixth it was 0.8 mug/ml. Therefore a critical blood level for suppression of basal or stimulated secretion appears to be approximately 0.45 mug/ml.

Adolescent↗
PubMed1976

Changed cholinergic receptor characteristics after vagotomy in gastric fistula dogs.

By the use of small doses of atropine (0.2-10 mug/kg-h) the kinetics of atropine antagonism to the gastric stimuli Urecholine and pentagastrin could be defined in intact dogs and in dogs after fundic vagotomy. Though pentagastrin was a much less effective stimulus after vagotomy, atropine had very similar effects on the pentagastrin response before and after vagotomy. Stimulation of both acid and pepsin by Urecholine remained unchanged by vagotomy but was uncompetitively inhibited by atropine in the intact dog, suggesting irreversible binding of atropine to gastric cholinergic receptors. After vagotomy, however, atropine inhibited Urecholine competitively, suggesting that atropine was now bound reversibly to cholinergic receptors. These changes are analogous to those occurring in muscle after denervation and suggest the growth of new cholinergic receptors with changed characteristics after denervation of the stomach.

Animals↗
PubMed1976

Inhibition of gastric secretion in the dog by 16,16-dimethyl prostaglandin E2.

The synthetic prostaglandin 16,16-dimethyl E2 (PGE2) given by intravenous infusion at 0.4 mug/kg-h inhibited gastric secretion of H+, K+, Cl-, and pepsin in four fistula dogs stimulated by histamine (H), pentagastrin (P), urecholine (U), and 2-deoxy-D-glucose (2-DG). When given for 90 min during steady infusions of near-maximal doses of H, P, and U, PG-E2 caused 75% inhibition of H+ maximally at 90 min and over 85% inhibition of pepsin secretion maximally at 45 min. Recovery of secretion took 1-2 h after infusion of PGE2 was stopped. Injection of KCl, 1 meq/kg, during inhibition of histamine by PGE2 gave only a 15-min transient reversal in inhibition. When PGE2 was given as background to 45-min step-dose responses, 0.1 mug/kg competitively inhibited histamine stimulation and 0.4 mug/kg-h gave 100% inhibition. Against pentagastrin, 0.1 mug PGE2/kg-h had no effect and 0.4 mug caused uncompetitive inhibition; against urecholine, 0.4 mug PGE2/kg-h caused competitive inhibition of H+ secretion. Pepsin was more markedly inhibited in each case. There were no side effects at either dose of PGE2, which is a potent inhibitor of gastric secretion with all forms of stimuli.

Animals↗
PubMed1976

Fulminant hepatitis and lymphocyte sensitization due to propylthiouracil.

Fulminant hepatic failure developed in a 24-year-old black woman who had been treated with propylthiouracil and propranolol for hyperthyroidism. Clinical and biochemical recovery followed discontinuation of drug therapy. Liver biopsy disclosed submassive hepatic necrosis. During the acute phase of the disease, lymphocyte transformation studies revealed sensitization of the patient's lymphocytes to propylthiouracil but not to propranolol. Sensitization remained demonstrable 2 months after cessation of the former drug. Lymphocytes obtained from a hyperthyroid patient treated with propylthiouracil without complications failed to show evidence of sensitization. These observations indicate that submassive hepatic necrosis may result from treatment with propylthiouracil and are consistent with the notion that sensitization mechanisms may be responsible for the hepatic injury induced by this drug.

Adult↗
PubMed1976

Double lumen esophagus due to reflux esophagitis with fibrous septom formation.

The unique endoscopic finding of a double lumen esophagus due to the development of a fibrous septum within an area of peptic reflux esophagitis is presented. The pathogenesis of this septum was felt to represent adherence to granulation tissue from opposing esophageal walls. This abnormality was easily managed by esophageal bouginage.

Esophageal Diseases↗
PubMed1976

Purification and characterization of a liver-specific antigen.

A liver-specific antigen (F-antigen) previously demonstrated in saline extracts of BALB/c mouse liver by double immunodiffusion was isolated and characterized. The antigen was found widely distributed among mammals but absent from avian and frog liver extracts. In immunoelectrophoresis it had an electrophoretic mobility similar to that of serum beta2-globulins, was relatively thermolabile, and was precipitated at 30 to 70% saturated ammonium sulfate concentrations. Evidence was presented that this antigen is a protein or a moiety closely associated with protein. Gel-filtration on Sephadex G-200 revealed liver-specific antigenicity in the second peak. Ion-exchange chromatography on DEAE-Sephadex A-50 revealed four peaks of which only the third one exhibited liver-specific antigenicity. This active peak contained 11 polypeptides on SDS polyacrylamide gel electrophoresis. After electrophoresis on acrylamide gel in the absence of SDS, antigenic activity was detected on one fast-moving band. Extraction of the protein band followed by SDS gel electrophoresis showed one major component of m.w. 75,000 and two major bands of m.w. 72,000 and 93,000, respectively.

Animals↗
PubMed1975

Correlation of lower esophageal sphincter pressure and serum gastrin level in man.

Resting lower esophageal sphincter pressures and fasting serum gastrin levels were measured in 35 consecutive patients. 28 of these patients were subdivided into Group I, which consisted of 9 patients with symptomatic gastroesophageal reflux and hiatus hernia, and Group II was further subdivided into Group IIA, 5 patients with hiatus hernias, and Group IIB, 14 patients without hiatus hernia. Mean LES pressures for Groups I, IIA, and IIB were 9.7, 36.8, and 25.6 cm H2O, and serum gastrin levels were 129, 74, and 116 pg/ml, respectively. Examination of these data as a whole or as subgroups failed to demonstrate a correlation between these two variables. The remaining 7 patients had abnormal sphincters (3 patients which scleroderma and 2 with achalasia) or abnormal serum gastrin levels (1 patient with pernicious anemia and 1 patient with antrectomy and Billroth II anastomosis). For these patients as well, no correlation between LES pressure and serum gastrin level was found. These results cast doubt on the hypothesis that endogenous gastrin is a major factor in the maintenance of resting LES pressure.

Adult↗