Alterations in the plasma membrane properties of the myocardium of spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were used to investigate the adaptive biochemical changes in the myocardium in response to chronic afterload. Ouabain-inhibited Na+,K+-adenosine triphosphatase (ATPase) activity was decreased by 40% in myocardium of SHR compared with that from WKY, which may lead to increased intracellular Ca2+ through Na+-Ca2+ exchange. Similarly, alpha 1-adrenergic receptor density, estimated by [3H]prazosin binding, was decreased by 42% in myocardial membranes of SHR, while the affinity for the agonist and the antagonist was not altered.

Phosphorylation of cytoskeletal proteins tightly associated with the vascular smooth muscle membranes.

A study was performed to determine whether the proteins phosphorylated by cAMP dependent and calmodulin dependent protein kinase in vascular smooth muscle membrane fractions represent integral membrane proteins or are tightly associated cytoskeletal proteins. In the unextracted microsomal fraction cAMP dependent protein kinase phosphorylated proteins of 240K, 105K, and 48K daltons. Similarly, calmodulin dependent protein kinase phosphorylated 65K, 60K, 48K, and 20K dalton bands.

Phase I trial of recombinant interferon gamma in cancer patients.

Interferon gamma (IFN-gamma) is a lymphokine with potent in vitro effects on cell growth and immune function. We have investigated the effects of rIFN-gamma (sp act approximately 2 X 10(7) U/mg, purity greater than 99%) in 16 evaluable patients with advanced malignancy in a phase 1 trial. Patients were treated with six-hour intravenous (IV) infusions daily, five days a week for 2 weeks.

Increased Ca2+ sensitivity of alpha 1-adrenoceptor-stimulated contraction in SHR caudal artery.

Potassium and alpha-receptor-stimulated contractile responses of caudal artery rings of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were measured under conditions in which norepinephrine (NE) uptake and K+-induced NE release by nerve terminals were eliminated. The maximum isometric tension developed by SHR arterial rings was significantly more compared with WKY arterial rings when arteries were stimulated with NE but not when stimulated with K+. The Ca2+ sensitivity of NE-stimulated arterial rings was about twofold higher compared with WKY arterial rings.

Isolation and characterization of plasma membranes from bovine carotid arteries.

A plasma membrane fraction from bovine carotid arteries has been isolated by extraction of a crude microsomal fraction with a low-ionic-strength buffer containing ATP and Ca2+. This step was followed by sucrose-density-gradient centrifugation in the presence of 0.6 M KCl.

Age dependent changes in myosin ATPase activity in the myocardium of spontaneously hypertensive rats.

Male spontaneously hypertensive rats (SHR) and age matched Wistar Kyoto normotensive (WKY) rats of 5 weeks, 16 weeks, and 52 weeks of age were used to determine whether duration of hypertension has any effect on contractile protein ATPase and myosin isoenzyme distribution. Myofibrils, actomyosin, and myosin were isolated from the left ventricles of WKY rats and SHR and assayed for myosin ATPase activity and myosin isoenzyme distribution. Myofibrillar ATPase activity was assayed at various free [Ca++] ranging from 10(-7) to 10(-5) mol X litre-1.

Effect of swimming training on cardiac function and myosin ATPase activity in SHR.

Male spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive rats (WKY) were subjected to swimming training 6 times/wk, commencing at 4 wk of age, to determine whether this type of endurance exercise might alter contractile proteins and cardiac function in young adult SHR. The total duration of exercise was 190 h. Myofibrillar adenosinetriphosphatase (ATPase) activity was assayed at various free [Ca2+] ranging from 10(-7) to 10(-5) M.

Ferritin in neuroblastoma. Impact of tumor load and blood transfusions.

Serial serum ferritin (SF) levels were measured in 36 patients with neuroblastoma seen at Memorial Sloan-Kettering Cancer Center (MSKCC) between January 1981 and December 1982. The significance of the associations among SF, stage and extent of disease, number of blood transfusions, liver function, serum iron (Fe), total iron-binding capacity (TIBC), and transferrin saturation was investigated. Although a dominant statistical correlation was found between SF and number of blood transfusions, the results suggest that amount of disease contributes to increasing SF levels.

A study of the distribution pattern of fat in male gymnasts.

Girth and skinfold measurements were taken on male gymnasts of international standing. The results were compared with other groups, the data for which were taken from the literature. The ratio of central to appendicular girth was studied to find the differences in the fat proportions on extremities and trunk region.

Correlation between maternal and fetal immunoglobulin E levels.

Immunoglobulin E (IgE) concentrations were measured in 157 paired samples of maternal-fetal sera. A correlation was found between maternal and fetal IgE levels, in contrast to earlier reports dealing with smaller series. The correlation is probably not due to placental transfer of maternal IgE but rather to genetic factors.

Reduced cAMP levels and glycogen phosphorylase activation in isoproterenol perfused SHR myocardium.

The effect of isoproterenol perfusion on cAMP levels and phosphorylase activity was investigated in the spontaneously hypertensive rat (SHR) and Kyoto Wistar normotensive control rat (WKY) heart. The basal force of contraction in physiological salt solution perfused hearts was comparable between SHR and WKY. However, the force of contraction in response to 10 nM isoproterenol perfusion was decreased approximately 20-30% in SHR heart as compared to WKY heart.

Administration of gallium nitrate by continuous infusion: lack of chronic nephrotoxicity confirmed by studies of enzymuria and beta 2-microglobulinuria.

Enzymuria and beta 2-microglobulinuria are sensitive markers of injury to renal tubular cells. We evaluated these markers in 41 patients with advanced malignant lymphoma who received gallium nitrate administered as a continuous infusion during a recent phase I-II study. In contrast to our findings with cisplatin, we observed no significant increase in enzyme excretion or beta 2-microglobulinuria in these patients even after long-term treatment.

Properties of adenylate cyclase in the cardiovascular tissues of renal hypertensive rats.

Adenylate cyclase activity in the myocardium and aorta of Grollman one-kidney renal hypertensive rats (RHR) and sham-operated control rats was compared. The experimental rats revealed significantly higher blood pressure and cardiac hypertrophy 6-8 weeks postoperation as compared to controls. Basal, guanine nucleotide-, fluoride-, and isoproterenol-stimulated adenylate cyclase activities were consistently decreased in the myocardium of RHR as compared to control rats.

Isolation of two myosin light-chain kinases from bovine carotid artery and their regulation by phosphorylation mediated by cyclic AMP-dependent protein kinase.

Myosin light-chain kinase was purifed from bovine carotid artery. Approx. 90% of myosin kinase was extracted in the supernatant fraction with buffer containing EDTA during myofibril preparation.

Altered distribution and properties of cAMP-dependent protein kinase isozymes in spontaneously hypertensive rat aorta.

cAMP-dependent protein kinase activity was reduced in the cytosol fraction of spontaneously hypertensive rat (SHR) aorta compared to that of the Kyoto Wistar control rat (WKY). Two major peaks, isozymes I and II, of soluble cyclic AMP-dependent protein kinase activity could be separated by DEAE-cellulose chromatography. The distributions of isozymes I and II were 40 and 60%, respectively, in WKY compared to 26 and 74% in SHR.

Temperature dependence of [3H]dihydroalprenolol binding in rat myocardium.

The beta-adrenergic antagonist, [3H]dihydroalprenolol, was used to label binding sites in crude rat myocardial plasma membranes. The specificity of binding was dependent on the temperature of the assay. Specific binding at 22 and 37 degree C and at concentrations of radioligand less than 5 nM was consistent with binding to the myocardial beta-receptor.

Characteristics of hormone-stimulated adenylate cyclase in vascular smooth muscle: altered activity in spontaneously hypertensive rat.

The stimulation of adenylate cyclase activity by guanine nucleotides, isoproterenol and fluoride has been investigated in KCl washed rat aortic membranes. We observed that the presence of guanine nucleotides in the assay was obligatory for the isoproterenol stimulation of adenylate cyclase activity. Guanine nucleotides could stimulate adenylate cyclase in the absence of catecholamines; however, the extent of stimulation was significantly lower (p less than 0.

Ultrastructural characteristics of endothelial permeability in chronic hypertension.

This study examined characteristics of paracellular and pinocytotic permeability pathways across the middle cerebral artery endothelium of 12- to 16- month-old spontaneously hypertensive rats (SHR). Interendothelial junctions in SHR, like those of age-matched Wistar-Kyoto controls, were impermeable to lanthanum and horseradish peroxidase (HRP) tracers. Freeze-fracture preparations revealed that interendothelial junctions of chronically hypertensive rats are characterized by a twofold increase over controls in the number of tight junctional strands and the mean apical-basal depth.

Ontogenetic development of isoproterenol subsensitivity of myocardial adenylate cyclase and beta-adrenergic receptors in spontaneously hypertensive rats.

[3H]Dihydroalprenolol binding and adenylate cyclase activity in the myocardial membranes of Kyoto Wistar normotensive rats and spontaneously hypertensive rats were compared at various stages of postnatal development ranging from 2 to 36 weeks. Basal as well as agonist-stimulated myocardial adenylate cyclase activity was consistently decreased in spontaneously hypertensive rats as compared to normotensive rats as early as 2 weeks of age with significant differences (P < 0.05) observed after 6 weeks of age.