Immunoreactive insulin, like inulin, quickly equilibrates with interstitial fluid, as evidenced by recovery in thoracic duct lymph in man. Insulin-like activity not accounted for by immunoreactive insulin behaves as a large protein and is confined to the vascular compartment.
Eugenio A. Rasio, Constantine L. Hampers, J. Stuart Soeldner, George F. Cahill Jr.
The renal handling of insulin was studied by insulin immunoassay in arterial blood, renal venous blood, and urine of fasting patients with normal renal function and in peripheral venous blood and urine of normal subjects and patients with renal disease before and after an oral glucose load. A renal arteriovenous insulin concentration difference of approximately 29% was found and suggests that in normal subjects renal insulin clearance is significantly in excess of glomerular filtration rate. The insulin excreted in the urine of normal individuals at no time exceeded 1.5% of the load filtered at the glomerulus. This contrasts with the finding of a urinary insulin clearance approaching glomerular filtration rate in patients with severely impaired renal tubular function.
M. J. Chamberlain, L. Stimmler
We used three methods to examine the relationship among intracellular pH, transmembrane potential, and extracellular pH. Single-barreled electrodes permitted the determination of resting potential and intracellular pH with a minimum of cellular injury. Double-barreled electrodes, which incorporated a reference as well as a pH-sensitive electrode in a single tip, facilitated the direct measurement of intracellular pH without the interposition of the transmembrane potential. Triple-barreled electrodes permitted measurement of intracellular pH during the controlled hyperpolarization or depolarization of the cell membrane.
Norman W. Carter, Floyd C. Rector Jr., David S. Campion, Donald W. Seldin
The forces governing the movement of water across the pulmonary capillaries were studied in 39 intact, spontaneously breathing dogs. A situation favoring the net movement of water out of the pulmonary capillaries was created by means of partial pulmonary venous obstruction (left atrial balloon catheter) followed by rapid saline hemodilution. A predetermined difference between pulmonary capillary and plasma colloid osmotic pressures was maintained for periods of 1 to 2 hours. Left atrial (PLA) and plasma colloid osmotic pressures (πpl) were measured directly. The water content of the lungs was measured serially by an indicator-dilution technique, and at autopsy by drying the lungs. The rate of accumulation of lung water was measured in four groups of animals: in three of the groups, the capillary hydrostatic and colloid osmotic pressures were varied; in the fourth group, the right lymphatic duct was obstructed in addition.
O. Robert Levine, Robert B. Mellins, Robert M. Senior, Alfred P. Fishman
The plasma concentration of a pituitary hormone is determined by the rate of secretion, degradation, and the volume of distribution of that hormone. Using a radioimmunoassay for human thyrotropin (TSH) and human TSH-131I, we have estimated the rates of degradation and distribution of TSH in man and calculated the rate of secretion. Either 0.5 or 5 μg of TSH-131I with specific activities of 1 to 50 μc per μg was administered intravenously to 12 euthyroid subjects. Serial determinations were made of TSH-131I, and the half-time of disappearance (t½) was thus estimated. The average t½ in euthyroid subjects was 53.9 minutes with a volume of distribution averaging 5.8% of body weight. The mean endogenous plasma TSH concentration was 1.8 mμg per ml (2.7 μU per ml in terms of the human TSH reference standard A). The mean total TSH pool, excluding the pituitary, was 5.8 μg (8.7 mU). From these data the mean secretion rate of TSH in euthyroid man was calculated to be 110.1 μg per day (165.2 mU).
W. D. Odell, R. D. Utiger, J. F. Wilber, P. G. Condliffe
The secretion rates [34 ± 6 (SE) μg per day, 9 subjects] and metabolic clearance rates (MCR) [1,288 ± 120 (SE) L of plasma per day, 9 subjects] of aldosterone in elderly subjects are significantly lower than those of young subjects [77 ± 7 (SE) μg per day and 1,631 ± 106 (SE) L per day, respectively]. There is a correlation of the MCR and secretion rate values (p = 0.02), but the calculated plasma concentrations (secretion rate/MCR) are also significantly low in the elderly subjects [2.6 ± 0.3 (SE) compared with concentrations in the plasma from young subjects of 4.7 ± 0.6 (SE) μg per 100 ml plasma].
C. Flood, C. Gherondache, G. Pincus, J. F. Tait, S. A. S. Tait, S. Willoughby
The turnover rate of plasma total esterified cholesterol was measured after the intravenous injection of tritiated mevalonic acid in 16 men with coronary heart disease. Four subjects were normocholesterolemic and 12 were hypercholesterolemic; among the latter, 3 suffered from familial hypercholesterolemia and 6 were overweight.
P. J. Nestel, E. A. Monger
Cystathionine is more readily cleared from the plasma than other amino acids. This is because the amino acid has a very low tubular maximum (Tm), in the order of 1 μmole per minute per 1.73 square meters body surface area (BSA). No essential differences in the reabsorption of cystathionine were observed in four normal subjects, two patients with homozygous cystathioninuria, one patient with heterozygous cystathioninuria, and one patient with cystinuria.
George W. Frimpter, Abby J. Greenberg
Vitamin D3-3H has been administered intravenously to seven normal subjects, three patients with biliary fistulas, and four patients with cirrhosis. Plasma D3-3H half-times normally ranged from 20 to 30 hours. in vivo evidence that a metabolic transformation of vitamin D occurs was obtained, and a polar biologically active vitamin D metabolite was isolated from plasma.
Louis V. Avioli, Sook Won Lee, Joseph E. McDonald, Judith Lund, Hector F. DeLuca
Ceruloplasmin was highly purified from one patient with Wilson's disease and partially purified from a second unrelated patient. The highly purified ceruloplasmin was indistinguishable from normal ceruloplasmin by electrophoresis, tryptic peptide map, oxidase activity, and copper, amino acid, and sugar composition. The partially purified ceruloplasmin was indistinguishable electrophoretically from normal ceruloplasmin. With penicillamine therapy, ceruloplasmin disappeared from the serum of the first patient; it reappeared after the drug was discontinued. The significance of this observation in regard to the basic defect in Wilson's disease is discussed.
Neil A. Holtzman, Michael A. Naughton, Frank L. Iber, Bonnie M. Gaumnitz
The plasma concentration, production rate, and conversion ratio of androstenedione and testosterone were studied in seven children with congenital adrenal hyperplasia (CAH) of the 21-hydroxylase type. Plasma androstenedione and testosterone measured by double isotope derivative assay and estimated blood production rates were manyfold increased in the untreated state, markedly suppressed with glucocorticoid, and increased after the administration of ACTH.
R. Horton, S. D. Frasier
Selected tissues from human embryos of 6 to 9 weeks' gestation, from rat fetuses of 15 days' gestation, and from rats 2 days of age were incubated with 14C-labeled amino acids. Immunoelectrophoresis of the culture fluid after incubation, using rabbit antisera against human and rat fetal serum proteins, followed by radioautography revealed that: 1) Radioactive α-fetoprotein was present in cultures of human liver, rat liver, and rat yolk sac, but not in cultures of human or rat brain, lung, heart, kidney, intestines, skeletal muscle, skin, or placenta; human yolk sac was not studied. 2) Radioactive transferrin was also present in rat yolk sac cultures, and the same protein was found in rat liver cultures as well. 3) Rat liver and rat placenta cultures both produced radioactive serum Rα2-globulin.
David Gitlin, Mary Boesman
When human erythrocytes were incubated in vitro with 14C-labeled free fatty acids bound to serum albumin, labeled fatty acids were incorporated into erythrocyte triglycerides and phospholipids. The first step in this reaction was the transfer of free fatty acids from the albumin to the cells. This transfer was rapid and reversible. The acids were distributed between albumin and cells according to the relative quantities of albumin and cells present. Each acid had a different distribution coefficient. At equilibrium, relatively larger fractions of the stearic and palmitic acids and smaller fractions of the oleic and linoleic were associated with the cells. All these fatty acids were then slowly incorporated into phospholipids and triglycerides. The rate of incorporation of each was a function of its concentration in the cells, but larger fractions of the oleic and linoleic were incorporated than of the stearic, palmitic, myristic, or lauric. The two processes of transfer and incorporation thus had almost opposite selectivities for the different fatty acids. As a result, the fatty acids incorporated into triglycerides and phospholipids resembled in composition the fatty acids on the albumin except for moderately less stearic acid.
Richard K. Donabedian, Arthur Karmen