Complete ureteral ligation of 24-h duration significantly reduced stop-flow and estimated glomerular capillary pressures in nephrons accessible to micropuncture in obstructed kidneys. In kidneys without ureteral obstruction, a similar response occurred in single tubules blocked for 24 h without affecting nearby unblocked tubules. Thus, the response to tubular obstruction occurs on an individual nephron basis and results from constriction of individual afferent arterioles. The mechanism leading to the response is unknown, but a feedback mechanism operating through the juxtaglomerular apparatus of individual nephrons is an attractive possibility.
William J. Arendshorst, William F. Finn, Carl W. Gottschalk
A large pedigree containing a child with severe combined immunodeficiency disease (CID) associated with adenosine deaminase (ADA) deficiency was investigated to ascertain if heterozygotes could be detected by measuring red cell ADA activity. 9 of 17 individuals in three generations who were at risk for being heterozygous had decreased red cell ADA activity. This genetic information establishes one form of CID as an autosomal recessive disorder. The identified heterozygote population had a mean ADA value of 19.2 U/g hemoglobin (0.95 confidence interval; 14.0 to 24.4 U/g hemoglobin), which was approximately one-half the mean, 36.1 U/g hemoglobin, of a randomly selected control population (0.95 confidence interval; 22.5-58.1 U/g hemoglobin). Statistical comparisons of the heterozygotes to the normal population indicates that within a high-risk family heterozygotes may be identified with 90% confidence.
C. Ronald Scott, Shi-Han Chen, Eloise R. Giblett
Superoxide dismutase activity has been identified in both human neutrophils and rabbit alveolar macrophages by two distinct assay procedures. The enzyme is insensitive to both cyanide and azide and is present in the cytosol of the cell. The identification of this enzyme in phagocytic cells is compatible with the theory that superoxide anion might be involved in the bactericidal activity of the cell. It is proposed that the enzyme functions to protect the cell against superoxide generated during the phagocytic process.
Lawrence R. Dechatelet, Charles E. McCall, Linda C. McPhail, Richard B. Johnston Jr.
To gain further insight into the mechanism of action of cholera toxin, solubilized preparations of adenylate cyclase from control and toxin-treated rat livers were studied. Adenylate cyclase activity was measured in both particulate and solubilized form in rat liver under control conditions and after intravenous injection of cholera toxin. Cholera toxin caused a 3.3-fold activation of adenylate cyclase in the particulate preparation and a 5.8-fold increase in the solubilized preparation. Thus, the ability of cholera toxin to stimulate adenylate cyclase is present even when the enzyme membrane environment is disrupted. Furthermore, the solubilized enzyme, after treatment with cholera toxin, retained its ability to respond to catecholamines, but not to glucagon. In contrast, the control enzyme lost its responsiveness to catecholamines and glucagon after solubilization.
Barbara Beckman, Jorge Flores, Patricia A. Witkum, Geoffrey W. G. Sharp
Two normal collie dogs were given 1,200 R total body irradiation followed by successful marrow grafts from their grey collie littermates with cyclic hematopoiesis. During observation periods of 97 and 41 days after grafting, both previously normal recipients showed regular cyclic fluctuations of their granulocyte and reticulocyte counts similar to those observed in their donors. These findings suggest that canine cyclic neutropenia is due to a defect in the marrow stem cell.
Paul L. Weiden, Barbra Robinett, Theodore C. Graham, John Adamson, Rainer Storb
The uptake of acetate in the human forearm was studied in five fasting (14 h) subjects during 10-min periods of ergometer work at 7 and 10 kilopond-meters per minute (kpm/min). A constant arterial acetate concentration was established by administration of a small quantity of alcohol (25 g) to the subjects after a control work period. Blood flow was measured by an indicator dilution technique. Acetate uptake varied linearly with the product of arterial acetate concentration and blood flow. Acetate metabolism was calculated to account for about 6.5% of the energy metabolism, assuming complete combustion to carbon dioxide and water. Oxygen uptake and blood flow did not change in the presence of acetate and ethanol.
F. Lundquist, L. Sestoft, S. E. Damgaard, J. P. Clausen, J. Trap-Jensen
Bacterial lipopolysaccharides from dead bacteria have been blamed for the continuing high mortality from gram-negative infections despite antibiotic treatment. Because animal antiserum against these lipopolysaccharides has been shown to protect against several of the effects of endotoxin, we undertook the development of antiserum in human subjects. 21 men were immunized with a single injection of Salmonclla typhimurium or Escherichia coli 0:111 heat-killed cells and immune serum was collected at 2 wk. Preimmune serum was obtained as a control in all animal experiments. 1 ml antiserum given intravenously protected mice against a lethal intravenous dose of homologous endotoxin (P < 0.005 for both antisera). E. coli antiserum reduced the incidence of positive local Shwartzman reactions with E. coli endotoxin from 100 to 38%; S. typhimurium antiserum reduced the incidence from 92 to 35%. (P < 0.0005 for both antisera). There was no protection against heterologous endotoxin in either animal model. These experiments demonstrate for the first time that human antiserum confers exceedingly potent passive immunity to the effects of endotoxin.
Elizabeth J. Ziegler, Herndon Douglas, Abraham I. Braude
Human peripheral blood lymphocytes have membrane receptors for EAC43b (sheep erythrocytes sensitized with antibody and complement) and also for EAC43d, obtained by treating EAC43b with C3b inactivator. Human granulocytes bind only EAC43b, C3 fragments obtained by limited trypsin digestion of purified human C3 display both C3b and C3d sites, since they inhibit rosette formation of lymphocytes with EAC43b and EAC43d. These findings raise the possibility that C3b and C3d receptor sites may be selectively distributed among normal subpopulations of B lymphocytes as well as among leukemic leukocytes.
Aline Eden, Gary W. Miller, Victor Nussenzweig
The effect of high doses of 25-hydroxycholecalciferol on plasma calcium concentration was studied in rats receiving a low-calcium normal vitamin D diet. In bilaterally nephrectomized animals, as in sham-operated controls, 62.5 nmol of 25-hyroxycholecalciferol did not produce a rise of plasma calcium concentration. In contrast, the administration of 125 or 625 nmol, doses 1,000-5,000 times the minimal active dose in D-deficient rats, was followed in both groups of animals by a significant increase of plasma calcium concentration. Removal of either parathyroids alone or parathyroid and thyroid glands did not suppress this effect. These data suggest that when large doses are used in vivo, the renal conversion of 25-hydroxycholecalciferol to more polar metabolites is not an obligatory step for its calcium-mobilizing action. The present study does not elucidate, however, the exact mechanism(s) of this effect.
Henriette Pavlovitch, Michele Garabedian, Sonia Balsan
It has been postulated that 2,3-diphosphoglycerate (DPG)-mediated changes in oxyhemoglobin affinity play an important role in oxygen delivery; however, the effect of an acute increase in affinity without changing red cell mass has not been systematically evaluated. This study was designed to measure changes in oxygen transport and oxygen consumption produced by an acute increase in oxyhemoglobin affinity caused by an autologous exchange transfusion using DPG-depleted stored blood.
Thomas E. Riggs, A. William Shafer, Clarence A. Guenter
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