The Effect of Copper on Red Cell Enzyme Activities

• Text
• PDF

Abstract

Previous studies have shown a marked effect of very high levels of copper on red cell glucose-6-phosphate dehydrogenase and glutathione. When the effect of more nearly physiological levels of copper were studied, red cell hexokinase, phosphofructokinase, phosphoglyceric kinase, pyruvate kinase, and 6-phosphogluconate dehydrogenase were found to be inhibited. Inhibition was observed both when copper was added directly to hemolysates or when hemolysates were prepared from red cells from whole blood which had been incubated with copper and washed. The inhibition of red cell enzymes by copper was completely reversed by the addition of EDTA.

Authors

M. Boulard, K.-G. Blume, E. Beutler

Evaluation of Venous Bypass Grafts from Aorta to Coronary Artery by Inert Gas Desaturation and Direct Flowmeter Techniques

• Text
• PDF

Abstract

Blood flow through aorta-to-coronary artery bypass grafts has been measured selectively in 16 patients at or within 6 wk after operation. Inert gas desaturation curves were obtained from coronary venous blood samples after a 7-15 min infusion of dissolved H2 directly into the graft. Samples were analyzed chromatographically and curves resolved to 1-3% of initial H2 concentrations. Average flow per unit volume (F/V) was 67±21 (sd) ml/min per 100 g. Semilogarithmic plots showed F/V to be distributed heterogeneously in every case. In nine studies at operation, H2 measurements of average F/V were combined with electromagnetic measurements of total flow to estimate revascularized tissue mass. Electromagnetic flows ranged from 25 to 170 ml/min and averaged 69 ml/min. Tissue mass ranged from 46 to 155 g and averaged 88 g. We conclude that bypass grafts provide nutritive flow to significant amounts of myocardium at and shortly after operation. However, nutritive flow is not distributed evenly throughout the revascularized segment. The majority of the segment has a F/V within the accepted range of normal but there remain areas in which F/V is reduced significantly. The combination of inert gas and electromagnetic techniques allows a revascularized area to be characterized in terms of total flow, F/V, and tissue mass.

Authors

David G. Greene, Francis J. Klocke, George L. Schimert, Ivan L. Bunnell, Stephen M. Wittenberg, Thomas Lajos

Epinephrine: selective inhibition of the acute insulin response to glucose

• Text
• PDF

Abstract

An epinephrine infusion of 6 μg/min decreased the rapid insulin response to a 5 g glucose pulse by 96% (P < 0.001) compared with the preinfusion control. In contrast when an identical epinephrine infusion was superimposed on a prolonged glucose infusion, elevated steady-state insulin levels did not decrease, but increased from 26.9 ±6 (mean ±SD, μU/ml) to 56.8 ±15 μU/ml (P < 0.05) in parallel with the epinephrine-induced hyperglycemia. Thus epinephrine inhibition of insulin secretion was observed during acute but not chronic glucose stimulation. To evaluate further the insulin responses during a prolonged glucose infusion, a 5 g glucose pulse was given before and 60 min later during a concomitant epinephrine infusion. Although the acute insulin response to the first glucose pulse was observed during the elevated steady-state glucose and insulin levels associated with the glucose infusion, epinephrine again inhibited the acute insulin response to the subsequent 5 g glucose pulse by 91% (P < 0.01). Thus epinephrine appears to inhibit selectively the rapid insulin response to glucose but not to influence insulin output stimulated by prolonged hyperglycemia. These observations provide further evidence for a model of insulin secretion which includes a small storage pool available for immediate release to a glucose challenge and a more slowly responding pool regulating insulin secretion in the basal and steady state.

Authors

Roger L. Lerner, Daniel Porte Jr.

Isolation and translation of hemoglobin messenger RNA from thalassemia, sickle cell anemia, and normal human reticulocytes

• Text
• PDF

Abstract

Human hemoglobin messenger RNA was isolated by sucrose gradient centrifugation from reticulocytes of patients having various hemolytic anemias. Using a messenger RNA-dependent cell-free system derived entirely from rabbit reticulocytes, the human hemoglobin messenger RNA has been translated and the products analyzed by carboxymethylcellulose column chromatography. Normal messenger RNA directs synthesis of normal human α- and β-globin chains in nearly equal amounts. Sickle cell anemia messenger RNA directs the synthesis of normal α- and sickle β-chains, β-thalassemia messenger RNA directs the synthesis of normal α- and β-chains, but the amount of β-globin synthesized is markedly reduced. Thus the inability of the thalassemia reticulocyte to produce β-globin is clearly attributable to the β-globin messenger RNA.

Authors

Arthur W. Nienhuis, W. French Anderson

Hydrogen peroxide utilization in myeloperoxidase-deficient leukocytes: a possible microbicidal control mechanism

• Text
• PDF

Abstract

Phagocytosis-induced formate and glucose C-1 oxidation by the polymorphonuclear leukocytes of a patient with hereditary myeloperoxidase deficiency was considerably greater than normal. The addition of catalase to the leukocyte suspension was required for optimum formate oxidation. Azide and cyanide increased glucose C-1 oxidation by normal leukocytes but had little or no effect on myeloperoxidase-deficient leukocytes suggesting that these agents normally stimulate glucose C-1 oxidation, in part, by inhibition of myeloperoxidase. It is suggested that the inhibition or absence of myeloperoxidase results in an increased utilization of H2O2 in nonmyeloperoxidase-mediated H2O2-dependent reactions such as formate oxidation and hexose monophosphate pathway activation. The possibility of a microbicidal control mechanism in which a decrease in the microbicidal activity of myeloperoxidase is offset, in part, by an increase in the nonenzymatic microbicidal activity of H2O2 is considered.

Authors

Seymour J. Klebanoff, Stephanie H. Pincus

Effective glomerular filtration pressure and single nephron filtration rate during hydropenia, elevated ureteral pressure, and acute volume expansion with isotonic saline

• Text
• PDF

Abstract

Free-flow and stop-flow intratubular pressures were measured in rats with an improved Gertz technique using Landis micropipets or a Kulite microtransducer. In hydropenia, average single nephron glomerular filtration rate was 29.3 nl/min, glomerular hydrostatic pressure (stop-flow pressure + plasma colloid osmotic pressure) was 70 cm H2O and mean glomerular effective filtration pressure was 12.7-14.3 cm H2O, approaching zero at the efferent end of the glomerulus. Thus, the glomerulus is extremely permeable, having a filtration coefficient four to five times greater than previously estimated. Mean effective filtration pressure and single nephron glomerular filtartion rate fell with elevated ureteral pressure and rose with volume expansion, more or less proportionately. Changes in effective filtration pressure were due primarily to increased intratubular pressure in ureteral obstruction and to reduced plasma colloid osmotic pressure in volume expansion; glomerular hydrostatic pressure remained constant in both conditions and thus played no role in regulation of filtration rate.

Authors

Vittorio E. Andreucci, Jaime Herrera-Acosta, Floyd C. Rector Jr., Donald W. Seldin

Progeria: a cell culture study on aging

• Text
• PDF

Abstract

Progeria is an autosomal recessive disorder showing precocious senility. The cultured skin fibroblast from both the homozygous affected individual and the heterozygous parents can be distinguished from normals by decreased cell growth in culture. Mitotic activity, DNA synthesis, and cloning efficiency are markedly reduced.

Authors

B. Shannon Danes

Stimulation of granulocytopoiesis by a diffusible factor in vivo

• Text
• PDF

Abstract

A millipore diffusion chamber system was used to cultivate mouse marrow in the abdomens of irradiated and unirradiated host mice for 24 hr. When the irradiated hosts were 72, 96, or 120 hr postirradiation, the number of blasts and promyelocytes in the implanted chambers after cultivation was greater than those in the same marrow cultivated in unirradiated hosts. These data indicate that in vivo, there is stimulation of granulocytopoiesis by a diffusible factor or factors.

Authors

G. Rothstein, E. H. Hügl, C. R. Bishop, J. W. Athens, H. E. Ashenbrucker

Ventricular arrhythmias induced in monkeys by the inhalation of aerosol propellants

• Text
• PDF

Abstract

After inhaling fluoroalkane gases, which are used as aerosol propellants, some people have died suddently and unexpectedly. Seeking an explanation, we had 14 monkeys inhale these gases. All developed ventricular premature beats, bigeminy, or tachycardia, which began at an average of 39 (SE ±4.2) sec. Fluoroalkanes were present in blood, but arterial hypoxemia or hypercapnia was absent, and arterial pressure was reduced only slightly. In contrast, without fluoroalkanes, 3 min of asphyxia or anoxia caused arrhythmias in only one monkey whose arterial oxygen tension had fallen to 16 mm Hg. The ventricular arrhythmias caused in well oxygenated monkeys by fluoroalkane gases may either be mediated through beta adrenergic receptors, since propranolol abolished these arrhythmias, or result from a nonadrenergic, direct, toxic effect of these gases on the heart. These results suggest that some deaths after propellant inhalation may be caused by ventricular tachycardia or fibrillation.

Authors

George J. Taylor IV, Willard S. Harris, Morton D. Bogdonoff

Dose-Response relationship of luteinizing hormone to luteinizing hormone—releasing hormone in man

• Text
• PDF

Abstract

In previous clinical studies with highly purified porcine luteinizing hormone-releasing hormone (LH-RH), administration of the somewhat arbitrarily chosen doses of 700-1500 μg resulted in increased serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The present study determined the minimum effective dose as well as the relationship of the response of serum LH and FSH to the dose of LH-RH administered. Three normal men received i.v. injections of 1.1-810 μg of LH-RH. A dose of 10 μg of LH-RH caused a statistically significant elevation in serum LH. 30 μg of LH-RH significantly increased serum FSH levels. A highly significant linear trend was observed in the log dose-response curve. The results indicate that both LH and FSH release occurs in man with doses of LH-RH much lower than previously used and that a linear log dose-response relationship can be obtained.

Authors

Abba J. Kastin, Andrew V. Schally, Carlos Gual, A. Rees Midgley Jr., M. Clinton Miller III, Angela Cabeza