Publications by authors named "LASKER N"

Background: Previously reported causes of renal pelvocalyceal thickening (PCT) include infection, acute tubular necrosis and obstruction. This study was performed to evaluate the significance of PCT noted sonographically in patients with hyperechoic native kidneys.

Methods: We evaluated sonograms of 178 consecutive patients with hyperechoic native (excluding small and hydronephrotic) kidneys for the presence of PCT, and reviewed medical charts of patients with this finding.

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In this study, human platelets were used as a cellular model for exploring cytosolic free Ca (Cai) regulation in non-insulin-dependent diabetes mellitus (NIDDM). Cai levels were monitored in resting and thrombin-stimulated platelets from obese females with NIDDM; obese, nondiabetic women, and nonobese, nondiabetic women. All subjects were black.

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Earlier investigations showed a positive correlation between basal cytosolic free calcium in human platelets and blood pressure; however, recent studies have failed to show this relation. We undertook the present work to examine which platelet cytosolic calcium parameters (namely, cytosolic calcium in resting or stimulated states in calcium-containing and calcium-free media) present the least variability and best correlation with blood pressure. We studied 17 healthy white men on three different occasions separated by 1- and 4-week intervals.

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Objective: To study differences in cytosolic free calcium regulation between African Americans and Caucasians, using platelets as a model for studying cellular physiology.

Design: Platelet calcium regulation in apparently healthy African American and Caucasian males was examined.

Methods: Using fura-2, calcium influx and cytosolic calcium extrusion were monitored after treatment with thapsigargin, an inhibitor of the Ca-ATPase in the dense tubular membrane system.

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1. In this work we explored the effect of thapsigarin on the intracellular Ca2+, pH, Na+ and membrane potential in human platelets. These parameters were monitored using the fluorescent probes fura-2, 2',7'-bis-(2-carboxyethyl)-5,6-carboxyfluorescein, sodium-binding benzofuran isophthalate, and 3,3'-dipropylthiadicarbocyanine iodide.

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Although abnormalities in cellular ion transport have been shown in a variety of cells of essential hypertensives, the mechanistic link between these abnormalities and elevated blood pressure is poorly understood. Reduced sodium-potassium ATPase activity, with and without elevated levels of a circulating inhibitor of this transport system, has been reported by a number of studies. The recent characterization of the endogenous ouabain or its isomer will facilitate the testing of the hypothesis that salt-sensitive essential hypertension relates to higher levels of this factor.

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In this investigation we correlated platelet Na-H antiport parameters with blood pressure and serum lipids in a sample population of non-insulin-dependent diabetic obese, nondiabetic obese, and nondiabetic nonobese black women. Parameters of the Na-H antiport were examined in aspirin-treated platelets. These parameters were not altered in resting or in thrombin-stimulated platelets of diabetic patients.

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Previously, we demonstrated that removal of fetal bovine serum (FBS) from the medium of human skin fibroblasts resulted in an accelerated 86Rb+ washout, decreased cellular K+, and increased Na+ contents. In the present study we examined the mechanism underlying these changes. The efflux rate constant for 86Rb+, and the cellular contents of Na+ and K+ were measured.

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In this work, we explored the role of cyclic nucleotides in modulating parameters of the Na/H antiport in human platelets. Sodium nitroprusside and iloprost, as well as cyclic nucleotide analogues, were used to raise cellular levels of cAMP and cGMP. Cyclic nucleotides reversed the thrombin-evoked alkaline shift in cytosolic pH set point and the activity of the Na/H antiport, concurrently with attenuation of thrombin-induced rise in cytosolic free Ca.

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Objective: Sweat volume and ionic composition depend to a large extent upon the cytosolic free calcium level in secretory sweat cells and sodium and potassium transport in the reabsorptive sweat duct. Since essential hypertension and its treatment with antihypertensive drugs is likely to be associated with altered cellular ionic regulation, the objective of this research was to explore sweat formation and sweat parameters in hypertensive and normotensive subjects.

Design: Black and white hypertensive and normotensive subjects of both genders were studied.

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The role of Ca2+ was examined in regulating the binding of phorbol 12,13-dibutyrate (PdBu) to intact human platelets. Alterations in the cytosolic free Ca2+ concn. [( Ca2+]i), but not extracellular Ca2+, substantially influenced the binding parameters of the phorbol ester.

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Angiotensin converting enzyme (ACE) inhibitors, particularly enalapril and captopril, have been shown to decrease proteinuria in diabetic animals and human subjects. Since heparan sulfate proteoglycan confers a negative charge on the glomerular basement membrane, and either decreased synthesis or loss of this charge causes albuminuria in diabetic animals, we examined the possibility that enalapril prevents albuminuria through glomerular preservation of heparan sulfate in long-term diabetic rats. A total of 22 male Wistar rats were used in the study.

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To explore the role of the Na-H antiport in essential hypertension, we studied the kinetics of cytosolic pH and external sodium activation of this transport system in platelets from 65 normotensive and essential hypertensive subjects on and off antihypertensive medications. Subjects included both blacks and whites, as well as men and women. The fluorescent dye 2'7-bis(carboxyethyl)-5,6-carboxyfluorescein was used to monitor the cytosolic pH in these cells.

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To explore the etiology of altered Ca metabolism in essential hypertension, we studied parameters, i.e., maximal initial reaction velocity (Vmax) and Michaelis constant (Km), of Ca activation kinetics of Ca2(+)-ATPase in membrane fractions (isolated by a sucrose gradient) from platelets of blacks and whites, 27 of whom were essential hypertensives, 17 of whom were normotensives with a family history of essential hypertension, and 10 of whom were normotensives without a family history of the disease.

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Clinical decision-making conference will be a new quarterly feature. Suggestions or contributions should be addressed to the authors. The authors discuss a 67-year-old male with coronary heart disease and renal failure.

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Differences in cellular Na+ and K+ regulation may relate to the pathogenesis of essential hypertension and the predisposition of blacks to this disease. To explore these tenets, we examined several aspects of cellular Na+ homeostasis in serially passed, cultured skin fibroblasts from 30 subjects (15 hypertensive blacks and whites and normotensive subjects matched for sex, age, and race.) Fibroblasts from blacks demonstrated higher cellular Na+ turnover rates than did those from whites.

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Because biotin treatment may lower blood glucose in insulin-dependent diabetes, we chose to study such an effect in non-insulin dependent diabetes. Twenty-six diabetic KK mice, moderately hyperglycemic and insulin resistant, were treated for 10 weeks: 9 animals with 2 mg of biotin/Kg, 8 with 4 mg of biotin/Kg, and 9 with saline (controls). Blood glucose levels, oral glucose tolerance, insulin response to oral glucose, and blood glucose decrease in response to insulin were quantitated.

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Folate, thiamin, nicotinate, biotin, riboflavin, pantothenate, vitamins A, B6, B12, C, E, and beta-carotene were determined in: (a) eight patients before and after one plasma exchange; (b) in one patient after five consecutive treatments; (c) in three patients before and 2-8 weeks after plasmapheresis. Vitamin B12, beta-carotene, vitamin B6, and vitamins A, C, E were depressed after acute or chronic plasmapheresis. Concentrations of folate, thiamin, nicotinate, biotin, riboflavin, and pantothenate were essentially unchanged after one plasma exchange.

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To examine the relationship between body mass index, blood pressure, and the Na+,K+-adenosine triphosphatase (ATPase) system, we measured the erythrocyte ghost Na+,K+-ATPase and the erythrocyte Na+ concentration in 120 blacks and 127 whites (136 males and 111 females). Blacks showed a 13.9% higher erythrocyte Na+ (7.

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In a previous study, we demonstrated that the red blood cell Na+ concentration and Na+,K+-ATPase activity are sex-dependent and race-dependent: a higher intracellular Na+ concentration in blacks and men was associated with a lower Na+,K+-ATPase activity. To examine whether the low Na+,K+-ATPase activity is due to a decreased number of enzyme units, altered structure of the enzyme, or the presence of an endogenous digoxinlike substance, ouabain binding studies were performed on the same subject group. The measurements included displacement of [3H]ouabain from its specific binding sites by unlabeled ouabain or potassium.

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Thyroid hormone is known to modulate cell membrane sodium/potassium adenosine triphosphatase (Na/K-ATPase). To determine whether the activity of this enzyme differed in patients with nonthyroidal illness with low levels of circulating thyroid hormones and patients with documented clinical hypothyroidism, we measured Na/K-ATPase activity in red blood cells from patients with hypo- and hyperthyroidism, patients with nonthyroid disease with and without reduced circulating levels of thyroid hormone, and normal subjects. We also assessed whether the activity of this enzyme reflects decreased thyroid hormone action at the cellular level in patients with nonthyroidal illness.

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Several reports indicate that erythrocytes (RBCs) from blacks and men have higher sodium concentrations than those from whites and women. One possible mechanism to explain this finding is a difference in the activity of Na+-K+-ATPase. To explore this possibility, we have studied the Na+ and K+ kinetics of RBC Na+-K+-ATPase and RBC Na+ and K+ concentrations in 37 normotensive blacks and whites, both males and females.

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Platelet-associated IgG (PAIgG) levels, a useful adjunct for the evaluation of patients with immunologic mediated thrombocytopenia, were obtained in 36 patients with end stage renal disease undergoing maintenance hemodialysis. Twenty-five of the 36 had elevated PAIgG. Nine of the 36 were thrombocytopenic and only 3 of the 9 had elevated PAIgG.

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