The red cells of 63 members of 11 families were tested with 125I-labeled anti-Rh0(D). Families with a history of hemolytic disease of the newborn due to fetomaternal Rh incompatibility were selected for study. In such families it was possible to determine the antibody binding to the Rh0(D) heterozygous red cells of the children and to compare within each family this value with the antibody bound to the father's Rh0(D)-positive red cells and the mother's Rh0(D)-negative red cells. The fathers in all the families studied could be assigned to two classes on the basis of the quantity of antibody bound to their red cells. One group bound about the same quantity of antibody to their cells as did their children, indicating that they were heterozygous for the Rh0(D) antigen. The other bound about twice as much antibody to their cells as did their children, indicating that they were homozygous for the antigen. The Rh genotype of the father in all 11 families could be ascertained by using the children in each family as a reference point. The members of two families showed a poor correspondence between antibody binding and zygosity. In one family an Rh heterozygous child (R1r) took up 85% of the antibody bound to the father's homozygous cells (R1R1), and in the other family an Rh heterozygous child (R1r) took up 20% more antibody than did the cells of her father, which were of the same Rh phenotype (Rh1) and zygosity.
S. P. Masouredis, Mary Edith Dupuy, Margaret Elliot
The role of “leakage” of tubular fluid in anuria produced by mercury poisoning was studied in rats by micropuncture techniques. After an initial brisk diuresis, almost all animals were completely anuric 24 hours after HgCl2 injection. Lissamine green injected intravenously in the early stage of anuria appeared in the beginning of the proximal tubule, but the color became progressively lighter as the dye traversed the proximal convolutions. The dye was barely visible in the terminal segments of the proximal tubule; it did not appear at all in the distal tubules. These observations suggest that the proximal epithelium had become abnormally permeable to Lissamine green.
Norman Bank, Bertrand F. Mutz, Hagop S. Aynedjian
In normotensive subjects, acute reduction of mean arterial pressure to from 60 to 75 mm Hg by infusion of sodium nitroprusside caused significant increase in renin activity of renal venous plasma and also in the renal-systemic difference of renin activity. At the same time, the products of the renal-systemic difference of renin activity and renal plasma flow increased significantly, whereas renin substrate activity of plasma was unchanged, indicating that there was an increase in renin release during reduction in pressure. Renin activity of renal venous plasma, expressed in logarithms, showed a significant correlation with the degree of reduction in pressure; an increase in renin activity became significant when mean arterial pressure was reduced to below a level of 70 to 75 mm Hg.
Yoshihiro Kaneko, Takao Ikeda, Tadanao Takeda, Hideo Ueda
After intravenous and oral administration of radioactive aldosterone to normal subjects, 7.3 ± 0.4 (SE) and 5.4 ± 0.5 (SE)%, respectively, of the dose was recovered from a 48-hour collection of urine as aldosterone released by mild acid hydrolysis (from aldosterone 18-glucuronide), and 35 ± 5 (SE) and 39 ± 4 (SE)%, respectively, was recovered as tetrahydroaldosterone after incubation with β-glucuronidase.
C. Flood, G. Pincus, J. F. Tait, S. A. S. Tait, S. Willoughby
The content of aldosterone, corticosterone, and cortisol has been assayed in normal adrenal tissue obtained at autopsy and in adrenal adenomas from both normotensive and hypertensive patients obtained at autopsy and from patients with primary aldosteronism obtained at surgery. The content of aldosterone and corticosterone in the adenomas of patients with essential hypertension was similar to that of normal adrenal tissue and much less than that of adenomas from patients with primary aldosteronism.
Norman M. Kaplan
Double diffusion in agarose was employed for the characterization of a soluble nucleoprotein antigen that gave precipitin reactions with sera from patients with systemic lupus erythematosus. The soluble antigen that was isolated from calf thymus nuclei was demonstrated by enzyme degradation and ultracentrifugation studies, and by immunologic analysis, to be a complex of deoxyribonucleic acid and a moiety susceptible to proteolytic digestion. Antibody to soluble nucleoprotein did not react with the DNA portion of the complex released after proteolytic digestion or with purified calf thymus DNA. Immunologic reaction of identity was obtained between the soluble nucleoprotein antigen and synthesized DNA-histone complex, suggesting that the protein moiety of soluble nucleoprotein might in part be composed of histone. Antibody to soluble nucleoprotein was present in 51% of systemic lupus erythematosus sera examined and was more common than antibody to deoxyribonucleic acid.
Eng M. Tan
The infusion of thyrocalcitonin (TCT) into thyroparathyroidectomized rats, given either no exogenous parathyroid hormone or a constant infusion of this hormone, leads to a transient phosphaturia and a decreased excretion of urinary magnesium, calcium, and hydroxyproline without a change in glomerular filtration rate. The changes in phosphate excretion may be due to a direct effect of the hormone upon renal tubular function or they may be a consequence of the fall in plasma calcium brought about by the action of TCT upon bone. In support of this latter alternative is the fact that the infusion of sodium ethylenebis-oxyethylenenitrilotetraäcetic acid (EGTA, a specific chelator of calcium) also leads to phosphaturia presumably as a consequence of hypocalcemia. However, EGTA infusion leads to enhanced urinary hydroxyproline excretion and sustained phosphaturia. These latter observations are interpreted to mean that alterations in the local ionic environment of osteolytic cells lead to changes in their activity and constitute a local regulatory system whose activity is modulated by the hormones, thyrocalcitonin and parathyroid hormone.
Howard Rasmussen, Constantine Anast, Claude Arnaud
Complement coating and hemolysis were observed when erythrocytes from patients with paroxysmal nocturnal hemoglobinuria (PNH) were incubated in isotonic sucrose solution in the presence of small amounts of serum. Normal cells were likewise coated with complement components but did not hemolyze. Both normal and PNH erythrocytes reduced the hemolytic complement activity of the serum used in this reaction.
David E. Jenkins Jr., Robert C. Hartmann, Albert L. Kerns
A mathematical analysis of the plasma disappearance curves of simultaneously injected thyroxine-131I and albumin-125I allows the development of simple formulas for estimating the pool size and transfer kinetics of rapidly exchangeable intracellular thyroxine in man. Evidence is presented that the early distribution kinetics of albumin-125I can be used to represent the expansion of the thyroxine-131I-plasma protein complex into the extracellular compartment. Calculations indicate that approximately 37% of total body extrathyroidal thyroxine is within such exchangeable tissue stores. The average cellular clearance of thyroxine is 42.7 ml per minute, a value far in excess of the metabolic clearance of this hormone. Results of external measurements over the hepatic area and studies involving hepatic biopsies indicate that the liver is an important but probably not the exclusive component of the intracellular compartment. The partition of thyroxine between cellular and extracellular compartments is determined by the balance of tissue and plasma protein binding factors. The fractional transfer constants are inversely related to the strength of binding of each compartment and directly proportional to the permeability characteristic of the hypothetical membrane separating compartments. Appropriate numerical values for these factors are assigned. An increased fractional entrance of thyroxine-131I into the cellular compartment was noted in a patient with congenital decrease in the maximal binding capacity of thyroxine-binding globulin and in three patients after the infusion of 5,5-diphenylhydantoin. Decreased intracellular space and impaired permeability characteristics were observed in five patients with hepatic disease. Studies of the rate of entrance of thyroxine-131I and albumin-125I into the pleural effusion of a patient with congestive heart failure suggested that transcapillary passage of thyroxine independent of its binding protein is not a predominant factor in the total distribution kinetics of thyroxine-131I. The thesis is advanced that the distribution of thyroxine, both within the extracellular compartment and between the extracellular and intracellular compartments, is accomplished largely by the carrier protein and the direct transfer of thyroxine from one binding site to another. The concept of free thyroxine is reassessed in terms of this formulation.
Jack H. Oppenheimer, Gerald Bernstein, Julian Hasen
The isolated perfused rat liver can serve as a bioassay system for glucagon, capable of detecting 10 mμg of this agent. Seven 15-ml plasma specimens obtained from different healthy volunteers after an overnight fast were assayed in this system; glucagon could not be detected in any of them, indicating concentrations significantly below 0.67 mμg per ml in all subjects. The effects of administering small doses of glucagon to patients were consistent with these results; imposition of increments to plasma glucagon concentration below 1 mμg per ml induced distinct and sustained increases in blood glucose.
Joseph E. Sokal, Ediz Z. Ezdinli
The effect of colchicine on the uptake of oxygen by human leukocytes during phagocytosis of live streptococci or of killed staphylococci was compared with the effect of colchicine on phagocytosis per se, measured in a sensitive bacterial system.
Stephen E. Malawista, Phyllis T. Bodel
A kinetic study of the conversion of blood cholesterol into hydrocortisone was carried out in two patients through prolonged infusions of cholesterol-4-14C. The following points appear to be established by our observations:
Abraham J. Borkowski, Sam Levin, Claude Delcroix, Antoinette Mahler, Vera Verhas
A technique is described for studying the respiratory function of the placenta using carbon monoxide, a gas whose exchange across the placenta between the maternal and fetal circulations is limited by diffusion rather than blood flow.
Lawrence D. Longo, Gordon G. Power, Robert E. Forster II
In studies by continuous flow electrophoresis the coumarin anticoagulant drug warfarin sodium was found to be bound solely to the albumin fraction of the plasma proteins. The interaction was studied in detail by equilibrium dialysis of solutions of crystalline human plasma albumin and warfarin sodium. Analysis of the data showed that albumin possesses a single strong binding site for warfarin with an association constant of 154,000 at 3° C and secondary classes of several sites with a much lower affinity. The free energy of binding for the first anion determined at 3° and 37° C was -6.54 and -7.01 kcal per mole, respectively. The standard enthalpy change for the interaction was -3.48 kcal per mole, and the entropy change was +11.2 U.
Robert A. O'Reilly
Interference with cerebral energy metabolism due to excess ammonia has been postulated as a cause of hepatic encephalopathy. Furthermore, consideration of the neurologic basis of such features of hepatic encephalopathy as asterixis, decerebrate rigidity, hyperpnea, and coma suggests a malfunction of structures in the base of the brain and their cortical connections.
Steven Schenker, David W. McCandless, Edward Brophy, Michael S. Lewis
Cerebral blood flow and metabolism were measured by the iodoantipyrine-4-131I method in nine patients and by the nitrous oxide method in three patients with the Wernicke-Korsakoff syndrome.
Sadatomo Shimojyo, Peritz Scheinberg, Oscar Reinmuth
Phagocytic function of the reticuloendothelial system as measured by the clearance of 125I-labeled aggregated human serum albumin (AA) was studied in patients with Hodgkin's disease. Each more advanced stage of the disease was associated with more rapid clearance of the AA. Production of remission by radiation therapy or by chemotherapy was associated in some patients with slowing of the clearance rate, whereas relapse seemed to be associated with acceleration. Thus, impaired phagocytosis cannot be implicated in the several defects in immunity known to be present in Hodgkin's disease. Furthermore, determination of the clearance rate of AA in patients with Hodgkin's disease may have clinical usefulness as another indicator of extent or activity of disease.
John N. Sheagren, Jerome B. Block, Sheldon M. Wolff
Pressure-volume characteristics and surface tension measurements of the lamb of 120 to 130 days gestational age were typical of the mature lung in the upper lobes and the immature lung in the lower lobes. By term both upper and lower lobes had findings characteristic of the mature animal.
George W. Brumley, Victor Chernick, W. Alan Hodson, Colin Normand, Axel Fenner, Mary Ellen Avery
The absorption of cholesterol has been studied in man by perfusing the upper jejunum with a micellar solution of bile salt, 1-monoglyceride, and cholesterol-14C, with a triple lumen tube with collection sites 50 cm apart. The absorption of micellar components between the collection sites was calculated from their concentration changes relative to those of the watersoluble marker, polyethylene glycol. Control experiments were performed with cholesterol-free perfusions of saline or bile salt-monoglyceride solutions. Steady state conditions were obtained.
Wilfred J. Simmonds, Alan F. Hofmann, Emanuel Theodor
The average plasma testosterone concentration of women with either hirsutism or polycystic ovaries and hirsutism was higher (p < 0.01) than that of normal women although the ranges overlapped. Testosterone blood production rates averaged 830 ± 120 SE and 1,180 ± 310 SE μg per day in the two groups of hirsute women and 230 ± 33 SE μg per day in normal women. The ranges did not overlap.
C. Wayne Bardin, Mortimer B. Lipsett