The guanido carbon of hepatic arginine is the common precursor of urea and of the arginine of plasma proteins synthesized in the liver. It is possible to measure the momentary synthetic rates of plasma proteins by “pulse labeling” this arginine pool with bicarbonate-14C. In the current study, this method has been adapted in order to use urinary urea data and was applied to control subjects and patients with gastrointestinal protein loss. The assumptions required for this determination are discussed.
R. Dean Wochner, Sherman M. Weissman, Thomas A. Waldmann, Delores Houston, Nathaniel I. Berlin
Urinary inorganic phosphate excretion was studied before and during the administration of sodium bicarbonate and acetazolamide in dogs that were not given infusions of phosphate. The excretion fraction of filtered phosphate increased after sodium bicarbonate or acetazolamide was given. This phosphaturia was attributed to decreased tubular reabsorption of phosphate consequent to alkalinization of either tubular urine or cells.
Milford Fulop, Paul Brazeau
Total body and area counts of intravenously injected 54Mn were measured periodically in 29 in-patients. A heterogeneous group of 19 control patients showed fair reproducibility in the immediate distribution, and considerable individual variance in the subsequent loss of the isotope. Eight studies of the effects of feeding excesses of manganous sulfate to five patients showed acceleration of the rate of loss of the radioisotope from the whole body and the liver. These findings seem compatible with the presence of control mechanisms in man, operating to vary the metal's excretion, while tending to preserve constancy of its concentration in tissues.
George C. Cotzias, Paul S. Papavasiliou, Edwin R. Hughes, Lily Tang, Donald C. Borg
Sodium taurolithocholate and sodium taurocholenate were infused intravenously into rats and hamsters. Each bile acid salt was given alone or in combination with varying amounts of a primary bile salt, either sodium taurocholate or sodium taurochenodeoxycholate. Bile flow, total bile acid salt excretion, and the excretion of sodium taurolithocholate were quantitatively determined. In addition, mannitol excretion in bile was determined at various flow rates.
Norman B. Javitt, Sidney Emerman
A lipid mixture (monoolein, oleic acid-1-14C, and palmitic acid-9,10-3H) was infused intraduodenally at a steady rate for 8 hr in fasted, unanesthetized rats. The same dose of lipid was given together with pure conjugated bile salts either as an emulsion, 2.5 mM bile salts, or as a micellar solution, 10 mM bile salts. The emulsion contained very little or no micellar lipid. Thoracic duct lymph was collected and in some experiments bile and pancreatic juice were drained to the exterior. After 4-5 hr infusion the same steady lymphatic output of radioactive fatty acids was obtained with emulsion as with micellar solution. It was concluded that absorption of fatty acid could proceed efficiently in the virtual absence of micellar solubilization. In rats with biliary plus pancreatic fistulae, labeled triglyceride was absorbed poorly relative to free fatty acids in the same emulsified particles. This suggested that fatty acids were transferred to the absorptive cells in monomolecular solution and not as emulsion particles.
W. J. Simmonds, T. G. Redgrave, R. L. S. Willix
The leukocyte-phagocytic function test which was found to be abnormal in boys with fatal granulomatous disease of childhood has been found to be abnormal to an intermediate extent in their mothers. Nine of nine mothers were shown to be abnormal, whereas none of eight fathers and none of five healthy brothers exhibited a defect. 10 of 16 female siblings were abnormal to the same degree as their mothers, as were all three maternal grandmothers available for study. Assuming that this intermediate functional defect represents the heterozygous state, the nine family pedigrees are entirely compatible with the concept that the trait is transmitted on the X-chromosome.
D. B. Windhorst, A. R. Page, B. Holmes, P. G. Quie, R. A. Good
A sensitive, specific, and relatively simple immunoassay permitting measurement of pharmacological levels of digitoxin in human serum has been developed. The assay involves binding of 125I-labeled tyrosine-digitoxigenin (specific activity > 400 mc/mg) by rabbit antibody to digitoxin. Antibody-bound radioactivity is precipitated by addition of a second antibody (goat anti-rabbit gamma globulin), and precipitate radioactivity is measured. Unlabeled digitoxin can be determined by the extent to which it competes with 125I-labeled digitoxigenin and thus reduces precipitation of radioactivity. Before the assay, unlabeled digitoxin is extracted from serum with chloroform, and the chloroform solution is evaporated to dryness. Quantitation is accomplished by reference to a standard curve in which known amounts of digitoxin are added to normal serum. As little as 1 mμg of digitoxin per ml of serum produces significant reduction in precipitate radioactivity.
George C. Oliver Jr., Brent M. Parker, Daniel L. Brasfield, Charles W. Parker
The concentrations of bile salt, lecithin, and cholesterol were determined on each of 66 samples of gall bladder bile from patients with cholesterol gallstones and 25 samples of normal gall bladder bile. When these three constituents were plotted simultaneously on triangular coordinates, a complete separation of the normal and “abnormal” bile was achieved. This separation was the result of an increase in the quantity of cholesterol relative to the amounts of bile salts and lecithin contained in the bile from patients with cholesterol gallstones.
William H. Admirand, Donald M. Small
Umbilical cord serum and adult serum antibodies reactive with heat-stable somatic antigens of Gram-negative bacteria (Neisseria gonorrhoeae, Escherichia coli, and Salmonella typhosa) were assayed by using an indirect fluorescent antibody test. Reactive IgG, IgM, and IgA antibodies were identified by using fluoresceinconjugated antisera specific for these immunoglobulin classes.
Irun R. Cohen, Leslie C. Norins
The regional distribution of pulmonary ventilation and perfusion and regional alveolar ventilation/perfusion ratios were measured with radioactive xenon (133xenon) in 10 patients with asthma in remission. Four subjects had normal ventilation distribution, four had hypoventilation in some regions and normal ventilation in others, and two patients had abnormal ventilation in almost all lung regions. The lung bases were involved most frequently and the middle zones least frequently. Correlation was good between the degree of over-all ventilatory impairment calculated from 133xenon values and measurement of the maximal midexpiratory flow rate the same day.
T. Heckscher, H. Bass, A. Oriol, B. Rose, N. R. Anthonisen, D. V. Bates
The effect of i.v. Pitressin (ADH) in a dose of 1 U/hr on permeability characteristics and on absorptive capacity of the normal human small intestine was investigated. The method of continuous intestinal perfusion was employed with polyethylene glycol 4000 as a nonabsorbable marker. Unidirectional flux rates of Na and H2O were calculated from the disappearance of 22Na and of 3HOH from isotonic saline solution within the intestinal lumen. Each study consisted of two successive perfusion periods: one while the subject was hydrated, the other during ADH infusion or while the subject was dehydrated. Water and sodium absorption from isotonic NaCl occurred in the hydrated state and was abolished by ADH as well as by dehydration in the jejunum. In some instances, net gain of water and sodium in the lumen occurred. In the ileum, ADH and dehydration caused a decrease in water and sodium absorption rate. By contrast, unidirectional flux into the intestinal lumen of water and sodium, as well as dextrose and D-xylose diffusion, remained unchanged by ADH. During perfusions with hypertonic urea solutions the rates of sodium and water entry into the intestine were greatly increased during i.v. ADH infusion, whereas urea loss from the study segment remained constant. ADH in the dosage used did not affect human intestinal motility. The results suggest that circulating ADH in physiologic concentrations affects the small intestine in one of two ways: increased secretion of water and salt into the lumen or direct interference with the active sodium transport mechanism.
Konrad H. Soergel, George E. Whalen, John A. Harris, Joseph E. Geenen
These studies demonstrate that the circulating human small lymphocyte synthesizes ribonucleic acid (RNA) of high molecular weight which is not primarily a ribosomal precursor and which is, in part, complementary to human deoxyribonucleic acid (DNA). The stimulation of these lymphocytes by PHA brings a cell population in which few ribosomes are synthesized to a functional condition in which a large amount of these particles are produced. This increase in the synthesis of ribosomal RNA is one of the earliest and most relevant effects of PHA on the RNA metabolism of small lymphocytes.
Umberto L. Torelli, Patrick H. Henry, Sherman M. Weissman
Mature human erythrocytes were incubated with 14C-labeled palmitic acid bound to crystalline human albumin. Energy-dependent incorporation of the labeled palmitic acid into cell membrane phospholipids occurred, and various stages in this incorporation were defined.
Stephen B. Shohet, David G. Nathan, Manfred L. Karnovsky
The effect of anti-γ-globulin factors on 7S γ-globulin opsonins from patients with subacute bacterial endocarditis has been examined with a quantitative in vitro phagocytosis system. Human anti-γ-globulin factors from patients with subacute bacterial endocarditis and rheumatoid arthritis inhibited the opsonic action of 7S γ-globulin specifically bound to bacteria. A similar antiopsonic effect was obtained with rabbit antiserum to human γG globulin. The antiopsonic effect of anti-γ-globulin factors did not correlate with their ability to potentiate agglutination of bacteria by 7S antibody. Competition was demonstrated between the antiopsonic effect of anti-γ-globulin factors and the phagocytosis-promoting action of heat-labile serum factors containing hemolytically active complement.
Ronald P. Messner, Throstur Laxdal, Paul G. Quie, Ralph C. Williams Jr.
A reproducible method, adapted from renal micropuncture techniques, was developed for sampling 10-40 mμl of a clear fluid from epiphyseal cartilage of normal or rachitic rats in vivo, either from the hypertrophic cell zone (Cf1) or surface resting cell cartilage (Lf1).
David S. Howell, Julio C. Pita, Juan F. Marquez, Juan E. Madruga
The effect of luminal sodium on intestinal glucose absorption at a variety of glucose concentrations was studied with a segmental perfusion technique in normal subjects.
Ward A. Olsen, Franz J. Ingelfinger
Left ventricular function was assessed in six patients with essentially normal cardiopulmonary function, in five patients with primary myocardial disease, and in 16 patients with chronic obstructive pulmonary disease by determining the response of the ventricle to an increased resistance to ejection. Studies were performed at the time of cardiac catheterization and increased resistance to left ventricular ejection was produced by the intravenous infusion of methoxamine.
John F. Williams Jr., Richard H. Childress, Daniel L. Boyd, Lawrence M. Higgs, Roy H. Behnke
The effect of prostaglandin E1 (PGE1) on the water permeability response to vasopressin, theophylline, and cyclic adenosine 3′,5′-monophosphate (C-AMP) of isolated, perfused collecting tubules of the rabbit was investigated in vitro. Prostaglandin is a naturally occurring substance present in a number of tissues, including kidney. It has been implicated in the action of a variety of hormones, many of which are known to exert their physiological effects through the intermediacy of the C-AMP system. In the collecting tubule, PGE1 (10-7 M) elicited a minimal increase in net water absorption along an osmotic gradient. However, when administered in association with a concentration of vasopressin (2.5 μU ml-1) selected to induce a submaximal increment in water absorption, the effect of the latter was reduced by approximately 50%. Theophylline (5 × 10-3 M) also increased net water absorption, an effect not previously demonstrated in renal tissue. This effect was potentiated by the simulataneous addition of PGE1. In contrast, PGE1 did not influence the increase in net water absorption induced by C-AMP (10-2 M). Since C-AMP is responsible for the permeability effects of vasopressin in renal tissue, the present results are consistent with the view that PGE1 interferes with the action of the octapeptide by competing with it at a site which influences the generation of C-AMP. In addition it is proposed that prostaglandin may be an important modulator of the action of vasopressin. The tubule is exquisitely sensitive to the hormone, responding to as little as 0.25 μU ml-1. It is conceivable that in the intact animal prostaglandin may serve to dampen the effects of small amounts of residual hormone and thereby prevent overshoots in permeability which might otherwise occur.
Jared J. Grantham, Jack Orloff
The physicochemical nature of γA was investigated in normal male and female urine concentrated approximately 1000 times. Sucrose density gradient ultracentrifugation and Sephadex G-200 chromatography revealed that urinary γA has sedimentation properties intermediate between 19S and 7S molecules. Isolation of urinary γA by DE 52 chromatography free of other immunoglobulins with subsequent antigenic analysis showed that the urinary γA-molecule is antigenically indistinguishable from the γA-molecules found in other external secretions and has a corrected sedimentation coefficient of 11.8S. In addition, like other secretory γA-molecules and unlike serum polymeric γA, urinary γA resisted mild reductive measures with 0.1M β-mercaptoethanol. Free or unattached secretory “piece” was found in all normal urines tested and in agammaglobulinemic urine. Secretory “piece” antigenic determinants were also found in ureteric urine. The average daily excretion of urinary γA was 1.1 mg. The maximum excretion of urinary 7S γG per 24 hr was approximately 3 mg.
John Bienenstock, Thomas B. Tomasi Jr.
A method for studying inhibitors of the contact stages of blood coagulation is described. A number of positively charged substances were shown to inhibit the contact stages. The inhibitory substances include spermine, cytochrome c, ribonuclease, and lysozyme. The inhibitory effect of these substances was neutralized by the addition of an activated plasma thromboplastin antecedent, factor XI, (PTA) fraction. Other positively charged substances including protamine, hexadimethrine, polylysine, polyornithine, methylene blue, and ortho-toluidine blue also inhibited the contact stages of coagulation, but the inhibitory effect on coagulation was not neutralized by the activated PTA fraction. Negatively charged substances such as heparin and insulin did not inhibit the contact stages of coagulation.
H. L. Nossel, H. Rubin, M. Drillings, R. Hsieh
Metabolic alkalosis was induced in dogs by administering ethacrynic acid and sustained by feeding a chloride-deficient diet. At the height of the alkalosis extracellular fluid was expanded “isometrically,” i.e., with an infusion that duplicated plasma sodium, chloride, and bicarbonate concentrations. Correction of metabolic alkalosis promptly followed such expansion and was attributed to the selective retention by the kidneys of chloride from the administered solution. Since plasma chloride concentration was not increased as an immediate consequence of the infusion, it is concluded that the change in renal tubular function that led to the selective retention of chloride must have been mediated by factors independent of filtrate chloride concentration.
Jordan J. Cohen
Adenine inhibited the de novo synthesis of purines in both normal and gouty man as shown by inhibition of the incorporation of glycine-15N into urinary uric acid without altering the incorporation of glycine-15N into urinary creatinine. The diminished purine synthesis did not result in a diminution in the 24 hr excretion of uric acid. This observation was explainable in part by the prompt conversion of adenine to uric acid. In addition to this direct conversion, adenine-8-13C provided a slow and prolonged contribution to urinary uric acid.
J. Edwin Seegmiller, James R. Klinenberg, John Miller, R. W. E. Watts
Human serum albumin and human γG globulin were labeled with 131I, and the labeled proteins were then mixed with different amounts of the respective unlabeled protein. These mixtures were injected intravenously into pregnant mice near term, and the amounts of protein-bound radioactivity present in the fetuses and in maternal serum 24 hr later were determined.
David Gitlin, Christian Koch
The site and characteristics of gastrointestinal electrolyte loss were investigated in eight dogs with experimental cholera induced by orogastric administration of 6-hr broth cultures of Vibrio cholerae, strain Ogawa 395. In these animals, all electrolyte losses originated in the small bowel, predominantly from the jejunum and ileum. The bicarbonate concentration of the small bowel fluid showed a progressive increase from duodenum, where it was less than that of plasma, to the terminal ileum, where it was significantly greater than that of simultaneously obtained plasma.
Charles C. J. Carpenter, R. Bradley Sack, John C. Feeley, Richard W. Steenberg
Coarctation of the mid-thoracic aorata was surgically produced in mongrel dogs which were sacrificed from 4-12 wk after the operation. As compared to the findings in control animals, the sodium, chloride, and water content of the hypetensive portion of the coarcted thoracic aorta was significantly elevated, whereas the electrolyte and water content of the relatively normotensive portion of the coarcted aorta was normal. The sodium, potassium, and water content of the pulmonary artery, skeletal muscle, and cardiac muscle of the coarcted dog was not altered. These observations suggest that an elevated arterial pressure may influence the electrolyte and water composition of the arteries.
William Hollander, Dieter M. Kramsch, Melvin Farmelant, Irving M. Madoff