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Biomedical subjects

S Loo

Publications and source records attributed to S Loo.

33 records · Page 2Linked to original sources

Coordinate inactivation of class III genes during the Gastrula-Neurula Transition in Xenopus.

We have identified a period during early Xenopus development when several different genes transcribed by RNA polymerase III (class III genes) are coordinately inactivated. During the late gastrula stage a major reduction in the number of active transcription complexes gives rise to a pattern of class III gene activity typical of adult somatic cells. This event is referred to as the Gastrula-Neurula Transition and involves the inactivation of genes encoding oocyte-type tRNAs and 5S RNA, along with several heterogeneous RNAs expressed during the blastula and gastrula stages of embryogenesis.

Animals↗

Evaluation of human exposure to the heptachlor epoxide contamination of milk in Hawaii.

The commercial milk supply on Oahu was contaminated by heptachlor epoxide for as long as 15 months during 1981-82 at levels possibly as high as 1.2 ug/g, fat basis. Following the contamination, several investigators attempted to evaluate potential adverse health outcomes, especially among infants and young children. However, results of the initial investigations are inconclusive due to lack of reliable measures of heptachlor exposure, use of non-random sampling techniques, and lack of definitive health outcomes attributable to heptachlor epoxide. The design of a current study to assess the body concentrations of heptachlor epoxide and related pesticides in Hawaii is presented. The study is designed (1) to relate these concentrations to prior exposure via the milk contamination, and (2) to assess the reliability of breast milk and serum pesticide concentrations as objective biological markers of body burden. No attempt is made to relate these data to health outcomes; instead, the findings may provide the foundation for future health studies or surveillance of environmental exposure to pesticides in Hawaii.

Animals↗

Dipstick chemical urinalysis: an accurate cost-effective screening test.

In a double-blind prospective study of 200 sequential urine specimens the sediment count of leukocytes in the centrifuged urine (white blood cells per high power field) was compared to a chamber count of leukocytes in uncentrifuged urine (white blood cells per microliter.). There was good correlation (coefficient of correlation 0.783, sensitivity 91.9 per cent, specificity 97.6 per cent and efficiency 96.6 per cent) between the more precise chamber count and the more commonly performed sediment count if the methodology of the sediment count was standardized. In a double-blind prospective study the results of the sediment count for leukocytes and erythrocytes were compared to the leukocyte esterase and hemoglobin dipstick results of urine specimens from 1,346 adults who underwent multiphasic screening. The dipsticks were found to be sensitive to physiologic limits for leukocytes and erythrocytes, with only 0.9 per cent false negative results for each. Formed elements in the urine not detectable by dipstick, such as casts and crystals, were present in 3 per cent of the specimens. Among patients who had significant pyuria, hematuria or formed elements not detectable by dipstick chemical urinalysis, no significant pathological condition was detected upon retrospective review. Because the chemical dipstick is not quantitative and because the sensitivity of the dipsticks resulted in many false positive findings compared to the sediment count (red and white blood cells 16.4 and 13.2 per cent, respectively) a protocol is offered in which results of screening urine specimens that are positive on dipstick culture would be confirmed by a properly performed microscopic urinalysis. This protocol as applied to an adult screening population would be an accurate, cost-effective method of urine testing.

Adolescent↗

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↗

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↗

Somatostatin and pancreatic polypeptide secretion: effects of glucagon, insulin, and arginine.

The isolated perfused canine pancreas with duodenal exclusion was used to examine islet hormone output in response to arginine and exogenous glucagon and insulin. Exogenous glucagon (100 ng/ml) stimulated insulin and somatostatin secretion, which occurred in a biphasic pattern. The insulin response to glucagon was markedly enhanced by increased perfusate glucose, unlike the somatostatin response, which was little affected. The insulin and somatostatin responses were seen between 15 and 45 s after the glucagon stimulus. Pancreatic polypeptide secretion was uninfluenced by exogenous glucagon. Biphasic release of glucagon, somatostatin, and pancreatic polypeptide was evoked by 10 mM arginine, the responses first being apparent within less than 30 s. Exogenous insulin (50 mU/ml) infused for 10 min had no statistically significant effect on glucagon, somatostatin, or pancreatic polypeptide secretion. This study suggests that these four islet hormones may all be involved in the dynamic mechanisms of nutrient metabolism. In addition, potential intra-islet paracrine effects are identified.

Animals↗

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↗

The rate of reaction between cytochrome C peroxidase and hydrogen peroxide is not diffusion limited.

The apparent biomolecular rate constant for the cytochrome C peroxidase (EC 1.11.1.5)-hydrogen peroxide reaction has been measured as a function of temperature between 5 and 25 degree C at pH 4,5.5, and 7 and as a function of viscosity over a fifteen-fold range. From the independence of the rate constant on the viscosity, it is concluded that the reaction is not diffusion limited.

Cytochrome-c Peroxidase↗

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↗

A kinetic study of the reaction between cytochrome c peroxidase and hydrogen peroxide. Dependence on pH and ionic strength.

The rate of the reaction between cytochrome c peroxidase and hydrogen peroxide was investigated using the stopped-flow technique. The apparent bimolecular rate constant was determined between pH 3.3 and pH 11 as a function of ionic strength. The pH dependence of the apparent bimolecular rate constant can be explained by assuming that two ionizable groups on the enzyme strongly influence the rate of the reaction. At 0.1 M ionic strength, a group with a pKa of 5.5 must be unprotonated and a group with a pKa of 9.8 must be protonated for the enzyme to react rapidly with hydrogen peroxide. The apparent acid dissociation constants depend upon the ionic strength. The true bimolecular rate constant has a value of (4.5 +/- 0.3) X 10(7) M-1 sec-1 and is independent of ionic strength.

Binding Sites↗

Pancreatic polypeptide causes diarrhea and weight loss in obese mice but not in lean littermates.

Pancreatic polypeptide was infused into obese-hyperglycemic (ob/ob) mice and lean littermates to determine its effect on weight gain. Obese mice continuously infused with 30, 60, or 100 micrograms/day for 7 days developed both diarrhea and weight loss in a dose dependent fashion. Lean littermates infused with 100 micrograms/day developed neither diarrhea nor weight loss. Light microscopic study of ileum and colon revealed no abnormalities. These studies indicate that the effects of pancreatic polypeptide are in part genetically determined since the obese and non-obese mice differ at only one gene locus.

Animals↗