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Biomedical subjects

H J Hirsch

Publications and source records attributed to H J Hirsch.

36 records · Page 2Linked to original sources
PubMed1983

The role of thyrotrophin releasing hormone in the diagnosis of isolated gonadotrophin deficiency.

We studied the response of PRL and TSH to thyrotrophin-releasing hormone (TRH) in 15 boys with delayed adolescence and 6 male subjects with isolated gonadotrophin deficiency (IGD). TRH tests were repeated in the IGD subjects during and 1 month following hCG treatment. Male IGD subjects showed a significantly decreased basal and TRH induced PRL response compared to male controls and subjects with delayed adolescence. Human chorionic gonadotrophin (HCG) treatment of male IGD subjects restored basal and stimulated PRL levels to the range of normal controls. This was, presumably, an estrogenic effect since non aromatizable androgens did not increase the PRL response; moreover, the antioestrogen, clomiphene, decreased the PRL response when given with HCG. The TSH response to TRH in delayed adolescents was increased as compared to adult male controls and IGD subjects and was similar to adult female controls. HCG treatment of IGD subjects had no effect on basal nor peak TSH levels, although ethinyl oestradiol did increase the TSH response in two IGD subjects. These studies show that the PRL and TSH responses to TRH may differentiate delayed adolescence from IGD. The increased TSH response to TRH in delayed adolescence as compared to adult males, is a manifestation of an enhanced oestrogen effect in these patients. The abnormal PRL dynamics in IGD is a consequence of estrogen deficiency.

Adolescent↗
PubMed1981

The primary structure of fulvocin C from Myxococcus fulvus.

The primary structure of fulvocin C, a bacteriocin produced by Myxococcus fulvus strain Mx f16, has been determined. This new bactericidal protein is composed of 45 amino acid residues and has a molecular weight of 4672. It contains no lipids or carbohydrates, indicating that only the protein molecule is responsible for its biological activity.

Amino Acid Sequence↗
PubMed1980

Isolation and characterization of immunoreactive somatostatin from fish pancreatic islets.

Using a radioimmunoassay with labeled synthetic tetradecapeptide somatostatin, a large amount of immunoreactive somatostatin was found in the principal pancreatic islet of the channel catfish (Ictalurus punctata). The purpose of these experiments was to isolate and characterize the somatostatin-like material. Extracts of islets were chromatographed on a Bio-Gel P-30 column, and over 90% of the immunoreactive somatostatin migrated with proteins at least twice the size of synthetic tetradecapeptide somatostatin. This fraction was further purified by ion-exchange chromatography on carboxymethyl-cellulose and DEAE-cellulose columns. Two peptides were obtained with identical immunoreactivity, which was approximately 25% that of the synthetic somatostatin. Each peptide was judged to be >95% pure by thin-layer electrophoresis, polyacrylamide gel electrophoresis at pH 8.9, and highpressure liquid chromatography. Further criteria of purity included amino-terminal analysis of fraction IV yielding only aspartic acid. A total of 1.3 mg of fraction II, and 3.8 mg of fraction IV somatostatin-like peptides were obtained from 10 g of fresh frozen islets. Characterization of the two peptides revealed both peptides slightly more acidic than synthetic tetradecapeptide somatostatin. Fraction II had an isoelectric point of 8.0-8.3, and fraction IV 8.3-9.0. Molecular weight estimation by sodium dodecyl sulfate-urea polyacrylamide gel electrophoresis revealed similar mobility of both peptides, between pancreatic polypeptide (mol wt 4,500) and glucagon (mol wt 3,500). The mobility was not altered by reduction, and was approximately twice the size of synthetic tetradecapeptide somatostatin (mol wt 1,800). This confirmed that the peptides were single polypeptide chains and not aggregates, or somatostatin bound to larger proteins. Molecular weight determination by gel filtration chromatography on Bio-Gel P-6 in 8 M urea gave an estimated mol wt of 3,700. Amino acid analysis of the two immunoreactive somatostatins indicated that they were very similar in composition. Both pancreatic somatostatins (1 muM) had full biological activity relative to synthetic somatostatin measured as inhibition of growth hormone release from rat anterior pituitary cells.

Amino Acids↗
PubMed1980

Effects of E coli endotoxin on pancreatic hormones and blood flow.

Studies were performed on anesthetized dogs to determine the relationship between endotoxin-induced alterations in pancreatic blood flow (PBF) and hormones that originate partially or completely from the pancreas. PBF was estimated in six dogs by radioactive microspheres (praeendoxin, 25 and 240 minutes postendotoxin). Insulin, glucagon, pancreatic polypeptide (PP), and somatostatin-like immunoreactivity (SLI) were assayed in arterial and portal venous blood. Cardiac output and mean arterial blood pressure (MABP) decreased 25 minutes after endotoxin administration (50% and 40%, respectively) and returned toward normal levels by four hours. However, there was 74% decrease in PBF at 25 minutes and a further drop four hours after endotoxin. Hormonal responses were characterized by a short-lived increase in arterial insulin, corresponding to a transient increase in blood glucose. Insulin release increased shortly after endotoxin. Arterial glucagon and PP increased two to five hours after endotoxin. There was a suggestion that the increase in PP was of nonpancreatic origin. Little change in plasma SLI was noted following endotoxin. Thus, it appears that endotoxin altered the release of different pancreatic hormones with a variable time courses.

Animals↗
PubMed1979

Aldose reductase inhibition: studies with alrestatin.

Studies with the aldose reductase inhibitor alrestatin in animal models have suggested that the sorbitol pathway may be of etiologic significance in the pathogenesis of peripheral neuropathy in diabetes. In normal subjects and in highly selected diabetic patients with severe peripheral neuropathy, alrestatin given either intravenously (50 mg/kg body weight) or orally (1 gm q.i.d.) produced no acute toxicity. The serum half-life of alrestatin was approximately 1 hr, and 99% was recovered in the urine within 24 hr. Two diabetic patients receiving alrestatin intravenously reported subjective improvements in clinical symptoms 2 days following the start of infusions. These improvements lasted approximately 3 wk after infusions were discontinued. However, there were no significant objective changes in peripheral nerve condition velocities, or on neurologic examination. In a 30-day oral trial with alrestatin in 4 diabetics, there were no subjective improvements in clinical symptoms nor were there objective improvements on neurologic examination or in peripheral nerve conduction velocities. In this study, peak serum levels of alrestatin were approximately 3 times lower than those obtained on intravenous administration, and it is possible that a high peak serum level is critical to the attainment of adequate tissue drug concentrations. Furthermore, the patients were suffering from severe clinical peripheral neuropathy, which could represent a stage of permanent irreversible nerve damage. Studies with alrestatin in newly diagnosed diabetics with peripheral nerve conduction velocity deficits but without clinical neuropathy might provide a better test of the sorbitol pathway hypothesis.

Absorption↗
PubMed1978

Purification and effects of fulvocin C, a bacteriocin from Myxococcus fulvus Mx f16.

Fulvocin C is a bacteriocin from Myxococcus fulvus Mx f16. It has a molecular weight of 4672 and is one of the smallest bacteriocins known. Four disulfide bonds give the molecule a tight structure, so that its native form was not attacked by chymotrypsin or pronase. Fulvocin C was stable in various organic solvents and could tolerate 80 degrees C in aqueous solution without loss of activity. The killing effect of fulvocin C was observed only at concentrations higher than 0.25 mumol/1. Macromolecular synthesis (DNA, RNA, protein) was affected very gradually. Viability in growing cultures decreased slowly from 100 to 25% during one generation (8 h). Cell division was affected early. After one generation v-shaped cell pairs had accumulated in the culture. Electron microscopic pictures revealed extended membrane systems connected with the inner membrane. The most striking effect was that often the outer membranes of neighbouring cells seemed to have fused laterally. With further incubation many cells lost their rod shape and empty bags became predominant.

Bacterial Proteins↗
PubMed1977

Bacteriocins from Myxococcus fulvus (Myxobacterales).

Bacteriocin-like activities were found in several Myxococcus fulvus strains. One strain, Mx f16, exerted strong inhibitory effects on several myxobacterial strains. Synthesis of its bacteriocinic activity could not be induced by mitomycin. Electrophoresis and molecular sieve chromatography revealed at least three different bacteriocinic substances of low molecular weight.

Bacteriocins↗
PubMed1977

Hypoglycemia of infancy and nesidioblastosis. Studies with somatostatin.

We treated a two-month-old infant with servere intractable hypoglycemia and nesidioblastosis with continuous glucose infusions (0.75 g per kilogram per hour) via a central venous catheter. Preprandial glucose levels on this regimen were 37+/-2 mg per deciliter (+/-S.E.M.). Basal serum insulin levels were within normal fasting levels for this age group but inappropriately elevated for the blood glucose levels. The beta cells were exquisitely sensitive to infusions of synthetic cyclic somatostatin, with a dose-dependent rise in blood glucose and concomitant suppression of serum insulin levels. There was only minimal suppression of plasma glucagon levels. Single subcutaneous injections of 50 microng of protamine zinc somatostatin raised preprandial blood glucose levels to 83+/-3 mg per deciliter for four to five days although preprandial hormone levels were unchanged. These findings indicate that hypoglycemia of infancy is a hyperinsulin state with abnormal basal regulation of insulin secretion.

Adenoma, Islet Cell↗
PubMed1977

Ultrastructural localization of pancreatic polypeptide in human pancreas.

Human pancreatic polypeptide (HPP) was localized in surgically obtained human pancreas by immunocytochemical electron microscopy. HPP was localized to the secretory granules of cells distinct from the alpha, beta, or delta cells of endocrine islets. The PP cells in 10 patients surveyed were most frequently located in the periphery of the islets. Immunolocalization distinguishes a fifth endocrine cell type in human islets which distinct ultrastructurally by its smaller granule diameter and lack of PP immunoreactivity.

Humans↗
PubMedDate not supplied

Nesidioblastosis associated with insulin-mediated hypoglycemia in an adult.

Nesidioblastosis, the process of differentiation of pancreatic islets from ductular epithelium, is a well-described cause of insulin-mediated hypoglycemia in neonates and infants, but not in adults. A 58-yr-old woman with characteristic clinical features of fasting hypoglycemia had inappropriately elevated plasma immunoreactive insulin levels during symptomatic episodes of fasting hypoglycemia. Angiography, palpation at laparotomy, and resection of the distal three-quarters of the pancreas provided no evidence of a tumor. Pathologic examination of the resected pancreas revealed the findings of nesidioblastosis, i.e., budding of islets from the wall of ductules, and also increased number and size of islets and abnormal shape and location of islets. An entire spectrum of islet cell abnormalities including nesidioblastosis can cause insulin-mediated hypoglycemia in adults, as it does in neonates and infants.

Adenoma, Islet Cell↗