The influence of ouabain and alpha angelica lactone on calcium metabolism of dog cardiac microsomes

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The influence of ouabain and alpha angelica lactone on 45calcium accumulation in cardiac microsomes was studied. Calcium binding (accumulation in the absence of excess oxalate or phosphate) was augmented by both ouabain and alpha angelica lactone in the presence of adenosine triphosphate (ATP) but unaffected in its absence. Calcium turnover (defined as the change in 45Ca++ bound to the microsomes after the specific activity is changed) was studied to determine if the augmented bound pool was freely exchangeable at equilibrium. Ouabain and alpha angelica lactone augmented calcium turnover in both the presence and absence of ATP. Calcium-stimulated ATPase was increased by both agents.

Authors

Mark L. Entman, Joseph W. Cook Jr., Rubin Bressler

Congenital dysfibrinogenemia: fibrinogen detroit

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A 17 yr old female with a congenital bleeding disorder was found to suffer from dysfibrinogenemia. Whole blood and plasma coagulation times were delayed and thrombelastograms were grossly abnormal. Clottability of plasma fibrinogen by addition of thrombin was not demonstrated during the 30 min test period. Fibrinogen was revealed by turbidometric and immunologic techniques. Other coagulation factors were present in normal amounts and prothrombin activation was normal. Patient's plasma inhibited thrombin clotting times of normal plasma and purified normal fibrinogen. Fibrinolysis was not detected.

Authors

Eberhard F. Mammen, Ananda S. Prasad, Marion I. Barnhart, Chi C. Au

A physiologic differentiation between delayed and immediate hypersensitivity

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Studies have been made of movement of various macromolecules into and out of the pleural space of guinea pigs during the course of a delayed hypersensitivity reaction to purified protein derivative (PPD), and a passively transferred immediate hypersensitivity reaction to ovalbumin. While the immediate hypersensitivity reaction transiently alters vascular permeability as shown by increased movement of macromolecules into the chest, the delayed hypersensitivity reaction is marked by a decreased capacity to resorb macromolecules from the pleural space. The data suggest that the two hypersensitivity reactions may be distinguished by these physiologic differences. Additional data from studies of a chemically induced pleural effusion in these animals suggest that some type of outflow obstruction is necessary for the development of effusion, but that the outflow defect caused by the irritating chemical is based on a different mechanism than that seen during the delayed hypersensitivity reaction.

Authors

Michael A. Apicella, James C. Allen

Mechanism of estrogenic action in acromegaly

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In four acromegalic patients, estrogen therapy did not significantly alter the mean values of basal radioimmunoassayable plasma growth hormone. In two patients, estrogen therapy did not qualitatively alter the lack of reduction of plasma growth hormone levels after oral administration of glucose, nor did it reduce in these patients the response of plasma growth hormone to insulin-induced hypoglycemia. In one of the patients, insulin sensitivity with respect to glucose and the hypoglycemia-induced growth hormone rise seemed greater during estrogen therapy. Despite the absence of demonstrable reductions inplasma growth hormone level under varying experimental circumstances, the administration of estrogen resulted in reduction of urinary calcium and hydroxyproline excretion, in reduction of radiocalcium bone accretion rates and exchangeable pools, in reduction of serum phosphorus, and in more negative nitrogen balances. The experimental data therefore suggest that estrogen may be a peripheral antagonist of the effects of excessive growth hormone secretion in acromegaly.

Authors

Ernest Schwartz, Elsa Echemendia, Martin Schiffer, Vincent A. Panariello

Effect of changes in renal perfusion pressure on the suppression of proximal tubular sodium reabsorption due to saline loading

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Rapid intravenous infusion of saline is known to suppress reabsorption of sodium and water in the proximal tubule. It has previously been shown that this suppression is accompanied by two changes which in combination might account for the over-all decrease in reabsorption: a reduction in the intrinsic reabsorptive capacity of the tubular epithelium (C/πr2) and a reduction in the ratio between tubular volume and GFR (πr2d/Vo). The present micropuncture experiments were carried out in order to study the possible role of altered peritubular physical forces (hydrostatic and colloid oncotic pressure) in mediating these two changes. Proximal tubular reabsorptive capacity, transit time, fractional reabsorption of sodium and water, πr2d/Vo, and intratubular hydrostatic pressure were measured in saline-loaded rats during acute changes in renal perfusion pressure induced by intermittent constriction of the abdominal aorta.

Authors

Norman Bank, Karl M. Koch, Hagop S. Aynedjian, Marc Aras

Defective DNA synthesis in human megaloblastic bone marrow: effects of homocysteine and methionine

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In B12 deficiency, inadequate DNA synthesis seems due in large measure to a block of tetrahydrofolic acid (THFA) regeneration from 5-methyl THFA (via homocysteine transmethylation).

Authors

Samuel Waxman, Jack Metz, Victor Herbert

An inhibitory effect of furosemide on sodium reabsorption by the proximal tubule of the rat nephron

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The evidence from previous micropuncture studies for an inhibitory effect of furosemide on proximal sodium reabsorption in the rat has been conflicting. Intrinsic reabsorptive capacity, estimated in free flow and shrinking drop experiments, has been reported to be depressed, whereas fractional reabsorption usually remains unchanged.

Authors

Barry M. Brenner, Robert I. Keimowitz, Fred S. Wright, Robert W. Berliner

Regional pulmonary blood flow in sitting and supine man during and after acute hypoxia

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Regional pulmonary blood flow was measured by external counting of intravenously injected 133Xe during 20 min of breathing 14.2% oxygen and during 20 min of recovery from hypoxia. 16 normal human volunteers were studied, nine sitting and seven supine. During hypoxia there was a slight but significant increase in relative perfusion of the upper portions of the lungs in both the sitting and supine subjects. During recovery from hypoxia, blood flow distribution differed significantly from the control. The erect subjects showed increased relative perfusion of the lung bases and the supine subjects showed increased relative perfusion of the upper zones.

Authors

Arthur Dawson

Hemoglobin function in stored blood

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Serial oxygen dissociation curves were performed on blood units preserved in acid-citrate-dextrose (ACD), ACD-adenine, and ACD-adenine-inosine. Dividing blood from a single donor into two or more bags allowed direct comparison between preservatives. During the 1st wk of storage in ACD, a progressive increase in oxygen affinity was observed. Thereafter, little further change was noted. Oxygen affinity increased even more rapidly during initial storage in ACD-adenine. However, with the inclusion of inosine as a preservative, oxygen affinity remained unaltered during the first 2 wk. Increases in oxygen affinity correlated well with falling levels of red cell 2,3-diphosphoglycerate (2,3-DPG) during storage. No significant changes in glutathione, reduced form (GSH), or A3 (AI) hemoglobin levels were noted during the first 3 wk of storage. No significant accumulation of ferrihemoglobin was detected. When blood stored 20 days in ACD or ACD-adenine was incubated with inosine for 60 min at 37°C, 2,3-DPG and adenosine triphosphate (ATP) were resynthesized, and oxygen affinity was decreased. The distribution of 2,3-DPG in fresh and stored red cells appeared to influence experimental values for Hill's n, a measure of heme-heme interaction.

Authors

H. Franklin Bunn, Mary H. May, Walter F. Kocholaty, Charles E. Shields

Characteristics and lipid requirements of coagulant proteins extracted from lung and brain: the specificity of the protein component of tissue factor

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Soluble proteins were prepared from bovine lung and brain which, when combined with phospholipids, had the biological characteristics of tissue factor. The proteins were solubilized from delipidated (heptane; butanol-extracted) acetone powders with deoxycholate, and precipitated by (NH4)2SO4 (30-60% saturation). These soluble proteins, which contained less than 1% phospholipid, were essentially inert in an assay for tissue factor. When they were recombined with phospholipids, however, activity increased by a factor of 500-1000. Phosphatidylethanolamine was the most active specific phospholipid, followed by phosphatidylcholine. Phosphatidylserine was inert. Mixed phospholipids were from two to four times more active than phosphatidylethanolamine. Maximum activity was obtained at phospholipid to protein ratios of 1.5:1 (wt/wt), and when relipidation was performed in deoxycholate followed by dialysis against 0.05 M imidazole-0.375 M NaCl, pH 7.2.

Authors

Yale Nemerson

The glycosaminoglycans of human plasma

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A method is proposed for the measurement of glycosaminoglycans (GAG) on 5-10 ml of plasma. It is based on the adsorption of GAG on small ECTEOLA columns followed by measurement of the hexuronic acid in the NaCl eluates. Routine use of the method has indicated the presence of a GAG fraction that adsorbs readily on ECTEOLA (“free” GAG) and of another that adsorbs on it only after treatment with papain (“bound” GAG). “Free” and “bound” GAG have been measured in normal adults, normal children, and children affected by mucopolysaccharidosis type I; the results obtained are in good agreement with those previously reported in the literature.

Authors

Alberto Calatroni, Patricia V. Donnelly, Nicola Di Ferrante

Albumin synthesis in cirrhotic subjects with ascites studied with carbonate-¹⁴C

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The synthesis of serum albumin was measured in 19 patients with cirrhosis of the liver and ascites. Carbonate-14C was used to label the guanido carbon of arginine in albumin.

Authors

Marcus A. Rothschild, Murray Oratz, David Zimmon, Sidney S. Schreiber, Irwin Weiner, Adrian Van Caneghem

Studies on the purification of antihemophilic factor (factor VIII): I. Precipitation Of Antihemophilic Factor By Concanavalin A

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Concanavalin A precipitates antihemophilic factor from normal plasma. Combining this precipitation with other techniques, we were able to separate fractions rich in antihemophilic activity from human plasma with rapidity. The molecular weight of antihemophilic factor was estimated to be greater than 2 million. Presumably, antihemophilic factor is a large glycoprotein.

Authors

Lawrence Kass, Oscar D. Ratnoff, Myron A. Leon

Production rates and metabolic clearance rates of human follicle—stimulating hormone in premenopausal and postmenopausal women

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The production rates (PR) and the metabolic clearance rates (MCR) of human follicle—stimulating hormone (HFSH) were determined in six pre- and five postmenopausal women. Human FSH (PER-780) labeled with 131I to specific activities of 50-150 μc/μg was used as a tracer. Both double antibody and trichloroacetic acid (TCA) precipitation techniques were used to determine HFSH-131I levels in infusate and plasma. In four of the subjects MCRs measured by both constant infusion and single injection techniques were the same. By constant infusion, plasma HFSH-131I levels reached equilibrium between 4-5 hr.

Authors

Yank D. Coble Jr., Peter O. Kohler, Charles M. Cargille, Griff T. Ross

Renal metabolic response to acid base changes: I. Enzymatic control of ammoniagenesis in the rat

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Experiments were done on rats to investigate the nature of the renal response to metabolic acidosis and the changes in enzyme activity associated with increased ammoniagenesis.

Authors

George A. O. Alleyne, George H. Scullard

The conversion of testosterone to 5α-Androstan-17β-ol-3-one (dihydrotestosterone) by Skin Slices Of man

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The conversion of testosterone-1,2-3H to dihydrotestosterone by slices of human skin obtained from various anatomical sites in 112 normal subjects and three individuals with the syndrome of testicular feminization has been measured under standardized conditions. Very low rates of dihydrotestosterone formation were observed in sites obtained from the mons or from miscellaneous areas of the trunk and limbs of the control subjects. The mean rates of conversion were very high, however, in slices of skin obtained from several perineal sites (labia majora, scrotum, prepuce, and clitoris). Furthermore, as measured here, the rate of dihydrotestosterone formation by prepuce rises during the 3 months after birth and then falls progressively thereafter, reaching a level in the adult that is almost as low as that observed in the slices of nonperineal skin from all ages. In the patients with testicular feminization dihydrotestosterone formation by slices of skin obtained from the mons was within the normal range, whereas the rates observed in labia majora were lower than the average values obtained in the normal subjects.

Authors

Jean D. Wilson, Joanne D. Walker

Studies on phenolic steroids in human subjects: VIII. Metabolism of estriol-16α-glucosiduronate

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6,7-3H-Estriol-16α-glucosiduronate-14C was administered to eight women (nine studies) by several routes: both injection and infusion (300 min) into the cubital vein, injection into the portal vein system, ingestion and instillation into the duodenum, jejunum, and ileum. Urine, collected from 0-2, 2-4, 4-8, 8-12, and 12-24 hr, was analyzed by countercurrent distribution for its content of radioactive 3- and 16-glucosiduronate (E3-3Gl,E3-16Gl) and sulfoglucosiduronate (E3-3S,16Gl) of estriol as well as for 3H/14C ratio of each conjugate. After peripheral injection 50-60% of the injected E3-16Gl was excreted unchanged along with about 5% as E3-3S,16Gl with an unchanged 3H/14C ratio, indicating direct sulfation of the injected E3-16Gl. During a 300 min infusion, urinary excretion closely resembled that following injection. But 2-4 hr after the end of the infusion excretion of E3-3S, 16Gl stopped, excretion of E3-3Gl (17%/24 hr) with an elevated 3H/14C ratio started, and excretion of E3-16Gl continued (70%/24 hr), but with a rapidly increasing 3H/14C ratio. This indicated sequestration in a sluggishly metabolizing compartment where two processes occurred: (a) extensive hydrolysis of E3-16Gl followed by reconjugation at either C3 or C16 with unlabeled uridine diphosphate glucuronic acid (UDPGA), thereby increasing the 3H/14C ratio; and (b) transconjugation from C16 to C3, thereby producing E3-3Gl with finite 3H/14C ratios. Instillation into various segments of the small intestine produced results qualitatively similar to those after intravenous infusion, whereas ingestion and intraportal injection resembled peripheral intravenous injection. Therefore, we have postulated the possibility of an enteric circulation (in addition to an enterohepatic circulation) in which the steroid or its conjugates are transported into the small intestine in the succus entericus, modified, and then reabsorbed and excreted in the urine-a process which requires several hours.

Authors

N. Inoue, A. A. Sandberg, J. B. Graham, W. R. Slaunwhite Jr.

Studies on phenolic steroids in human subjects: IX. Role of the intestine in the conjugation of estriol

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In order to compare the enteric circulation of estriol-16α-glucosiduronate (see preceding paper) with that of estriol (E3), labeled estriol was administered to six women by several routes: both injection and infusion (300 min) into the cubital vein, injection into the portal vein system, ingestion and instillation into the jejunum and ileum. Urine, collected from 0-2, 2-4, 4-8, 8-12, and 12-24 hr, was analyzed by countercurrent distribution for its content of radioactive 3- and 16-glucosiduronate (E3-3Gl,E3-16Gl) and sulfoglucosiduronate (E3-3S,16Gl) of estriol. After peripheral injection of E3, E3-16Gl was excreted rapidly and E3-3S,16Gl at a slower and more constant rate. E3-3Gl was barely detectable after infusion. After injection of E3 into the portal vein, the excretion of E3-3S,16Gl was greater and quicker than after peripheral injection. Even in a subject with a complete bile fistula, the urinary excretion of E3-3S,16Gl was essentially unchanged. Ingestion also produced the same result. Only after instillation into the ileum was a large and rapid excretion of E3-3Gl obtained, whereas the excretion of E3-3S,16Gl, and E3-16Gl were depressed. These results together with those of the preceding paper suggest that E3 does not readily appear in the small intestine except via a hepatoenteric circulation that produces very little E3-3Gl. When present in the distal segment of the small intestine, however, absorption, conjugation, and elimination proceed readily.

Authors

N. Inoue, A. A. Sandberg, J. B. Graham, W. R. Slaunwhite Jr.

Ventricular function in noncardiacs with alcoholic fatty liver: role of ethanol in the production of cardiomyopathy

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Since many patients with cardiomyopathy have a history of chronic ethanolism often associated with malnutrition, we have evaluated left ventricular (LV) function in alcoholics with fatty liver, who had no clinical evidence of cardiac or nutritional disease.

Authors

Timothy J. Regan, Gilbert E. Levinson, Henry A. Oldewurtel, Martin J. Frank, Allen B. Weisse, Christos B. Moschos

Esophageal responses to distension and electrical stimulation

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The opossum esophagus contains only smooth muscle in the distal two-thirds; it can be used to study autonomic control of esophageal smooth muscle. Three different preparations of opossum esophagus were used; the esophagus in vivo, the isolated whole esophagus, and isolated strips of the three layers of esophageal smooth muscle. Responses were examined to localized distension and to electrical stimulation. Distension of the esophagus in vivo produced three separate responses: inflation of a distending balloon caused a brief contraction rostral to the point of distension, the on response; maintenance of distension produced shortening of the esophagus, sustained for the duration of the distension, the duration response; and deflation of the balloon caused a single brief caudal circumferential contraction, apparently propagated caudad, the off response. In the isolated whole esophagus distension produced the same three responses. Electrical stimulation in this preparation produced apparently identical responses. Electrical stimulation of isolated strips of the three muscle layers showed that the muscularis mucosae and the longitudinal layer of the muscularis propria always respond with a duration response only. The circular layer of the muscularis propria responds with on and off responses only. These observations suggest that both types of stimuli excite the same afferent nerve fibers in local reflex pathways. Peristalsis can be maintained by these reflexes in the smooth muscle part of the esophagus independent of central nervous connections.

Authors

James Christensen, Gordon F. Lund

Plasma lipids and urinary excretion of catecholamines in man during experimentally induced emotional stress, and their modification by nicotinic acid

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Effect of sodium phenobarbital on bilirubin metabolism in an infant with congenital, nonhemolytic, unconjugated hyperbilirubinemia, and kernicterus

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