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Biomedical subjects

S Segal

Publications and source records attributed to S Segal.

At least 541 records · Page 30Linked to original sources

Spontaneous Fanconi syndrome in the dog.

Three dogs with spontaneous renal tubular defects similar to idiopathic Fanconi syndrome are characterized. Renal clearance studies revealed a fractional reabsorption of glucose ranging from 31% to 82%. Abnormal glucose thulium values were present in all dogs. A generalized aminoaciduria occurred in two dogs while one had aminoaciduria characteristic of canine cystinuria. Fractional reabsorption of phosphate ranged from 47% to 79%. In vitro uptake of alpha-methyl-D-glucoside was significantly depressed (p less than 0.001). In vitro uptake of amino isobutyric acid was similar to controls. Renal biopsy revealed nonspecific interstitial change in two dogs and normal histology in the other. These animals represent a useful new model for the study of renal tubular transport defects.

Amino Acids↗

The transport and metabolism of L-proline-14C in the rat in vivo.

The physiologic disposition, metabolic fate, and renal clearance of intravenously injected 14C-L-proline was determined in the rat. The disappearance of radioactivity from plasma occurred with a biphasic curve, the initial high levels reaching a nadir about 30 min after injection with subsequent increasing amounts of radioactivity. Examination of the 14C components in plasma revealed that 14C-proline disappeared rapidly during the first 30 min. At this time, the labeling of circulating plasma proteins ensued and continued to increase during the following 45 min of observations. Plasma glucose became labeled 10 min after injection and, thereafter, increased its 14C content. The extensive labeling of plasma proteins and glucose accounted for the increasing 14C found in plasma 30 min after injection. The course of radioactive labeling of brain, kidney, diaphragm, and liver was assessed. The greatest number of cpm/mg of tissue was found in the kidney. Determination of the distribution ratio, the ratio of cpm/ml intracellular nonprotein 14C to that in plasma in kidney revealed a peak of 3.9 within 15 min, a value comparable to that found in vitro. Twelve percent of the administered radioactivity was excreted as 14CO2 within 180 min. The oxidation was inhibited by known transport and metabolic inhibitors, the greatest effect observed with hydroxyproline, followed in order by thioproline, 3,4-dihydroproline, and glycine. The fractional urinary excretion of proline, Cproline/Cinulin, was determined and found to be 1% or less. This was increased by inhibitors, the greatest effect due to hydroxyproline followed in order by dehydroproline and glycine, a result similar to the observed extent of inhibition of proline oxidation to 14C O2. The physiologic disposition of proline was not altered by ligation of the renal vasculature.

Amino Acids↗

Galactose and glucose metabolism in the isolated perfused suckling and adult rat liver.

The development of the technique for the perfusion of the immature liver has enabled us to characterize metabolic differences in carbohydrate metabolism in the suckling versus adult rat livers. Livers of fasted suckling and adult rats were perfused with 4 mM galactose or 4 mM glucose. Galactose uptake was the same for both age groups during the first 35 min. The adult liver maintained the initial rate of uptake after this period while the immature liver began to take up galactose more rapidly. By the end of the experimental period, on a weight basis, uptake by the young liver was three times that of the adult. Analysis of the livers at the end of the 90 min perfusion showed hepatic galactose concentrations to be one-half of circulating media levels. Glucose output was observed in each group during perfusion with either galactose or glucose. In the immature liver, galactose perfusion stimulated more glucose output than did the glucose perfusion. In the adult, however, both sugars resulted in the same levels of glucose output. Galactose perfusion resulted in glucose levels in young liver being higher than the media; while in the adult, the level was lower than the media. Galactose perfused livers of the suckling and adult contained significantly more uridine-5'-diphosphogalactose than the glucose perfused livers of each age.

Aging↗

Glycine therapy in isovaleric acidemia.

The therapeutic efficacy of oral glycine was tested in a 3-year-old girl with isovaleric acidemia. An oral leucine load (25 mg/kg) caused a rise of the blood levels of isovaleric, lactic, and pyruvic acids as well as an increase of urinary excretion of the ketone bodies. These changes did not occur when oral glycine (250 mg/kg) was given with the leucine. Glycine supplementation favored the formation of isovalerylglycine, a nontoxic conjugate of isovaleric acid which is excreted rapidly. Excretion of isovalerylglycine rose threefold when leucine and glycine were administered simultaneously. Chronic glycine therapy was tolerated well and may have prevented one episode of ketoacidosis.

Acidosis↗

Tuftsin (an Ig-associated tetrapeptide) triggers the immunogenic function of macrophages: implications for activation of programmed cells.

The immunoglobulin heavy-chain-associated tetrapeptide, tuftsin (Thr-Lys-Pro-Arg), known for its phagocytosis-stimulating activity, was found to augment the antigen-specific, macrophage-dependent education of T lymphocytes. The investigation of stereospecific characteristics of the tetrapeptide, by use of structural analogs with different modifications, revealed strict structural requirements for eliciting the immunogenic activity of macrophages. It was found that the most important moiety for its activity is the dipeptide Pro-Arg. This finding is of interest in view of the appearance of this particular dipeptide in other bioregulatory peptides, including many of the peptide hormones. The significance of the appearance of a common structure in such molecules, which may act through specific receptors on different target cells, is discussed.

Amino Acid Sequence↗

Myoinositol and phosphatidylinositol metabolism in synaptosomes from galactose-fed rats.

The effects of experimental galactose toxicity on inositol and phosphatidylinositol (PtdIns) metabolism in synaptosomes from 0- to 30-day-old rats were investigated. Galactose toxicity was induced by feeding mothers a 40% galactose diet from the 12th day of pregnancy until 19 days postpartum when the offspring were weaned onto the maternal diet. There was no decrease in myoinositol concentrations and only a small decrease in PtdIns in synaptosomes from galactose-fed rats relative to glucose-fed controls. Synaptosomes from rats on the two diets converted equivalent amounts of [U-14C]glucose to inositol and PtdIns. Acetylcholine stimulated [2-3H]inositol incorporation into PtdIns while producing a net decrease in PtdIns concentration in synaptosomes from 22- to 30-day-old rats. However, the phospholipid response to acetylcholine in synaptosomes from galactose-fed rats was impaired. Thus, the acetylcholine-stimulated labeling of PtdIns was 40--50% lower in these synaptosomes while the effect on PtdIns concentration was reduced by a maximum of 55%. The data suggest that galactose-fed rats may have either a deficiency in the number of acetylcholine receptors or a defect in some step between receptor-neurotransmitter interaction and PtdIns breakdown.

Acetylcholine↗

RNA associated with murine intracisternal type A particles codes for the main particle protein.

Intracisternal type A particles were isolated from MOPC-104E myeloma grown subcutaneously and from N 4 neuroblastoma cells in culture. Polyadenylated RNA was prepared from the particles and tested in a cell-free translation system derived from rabbit reticulocytes. RNA from the two sources directed the synthesis of multiple polypeptides with similar distributions of electrophoretic mobilities in sodium dodecyl sulfate-containing polyacrylamide gels, including one conponent of the same size as the major A-particle structural protein (73,000 daltons). Analysis of the RNAs by electrophoresis in methyl mercury-containing agarose gels revealed a 35S component common to A-particles from both cell types. This was a major component of the N4 preparations, whereas a 28S species predominated in the case of MOPC-104E. These two RNAs (35S from N4 cells and 28S from MOPC-104E), when isolated on isokinetic sucrose gradients, each directed the synthesis of a 73,000-molecular-weight polypeptide that comigrated on gels with authentic A-particle structural protein. Idnetity of the cell-free product was confirmed by two-dimensional analysis of the [35S]methionine-labeled tryptic peptides. The N4 RNA preparations also contained a major32S component which did not code effectively for the A-particle structural protein.

Cell-Free System↗

Induction of spermatogenesis in hypogonadotrophic hypogonadism.

A young male who presented with isolated bihormonal gonadotrophin deficiency is described, Basal levels of LH and FSH were low and there was no response to clomiphene citrate or LHRH. The remaining anterior pituitary function was intact. The administration of a combination of human menopausal gonadotrophin and human chorionic gonadotrophin caused testicular maturation with spermatogenesis and full androgenization. The patient was able to father a child.

Adult↗

Developmental aspects of maleic acid-induced inhibition of sugar and amino acid transport in the rat renal tubule.

The transport of alpha-aminoisobutyric acid and alpha-methyl-d-glucoside by isolated tubules from Sprague-Dawley rats at different stages of development follows a separate age-dependent pattern for each substrate. The effects of 6 M maleic acid on transport processes differ for amino acids and sugars and become manifest at distinct points during development. Maximum inhibition by maleic acid occurs at a time subsequent to maturity of these transport systems. In an effort to explain these transport phenomena, the uptake and metabolism of 14C-labeled maleic acid by the newborn or adult renal tubule was studied, showing significant binding by the tubule membrane, penetration of the cell by diffusion, and no conversion to 14CO2. Maleic acid has no demonstrable effect on the membrane-associated enzymes which are thought to play a role in the transport of small molecules.

Age Factors↗

The ontogeny of sugar transport in kidney.

Concentrative uptake of alpha-methyl-d-glucoside (AMG) by isolated renal tubule fragments from the newborn Sprague-Dawley rat has been demonstrated and the validity of this phenomenon confirmed by an in vivo demonstration of AMG uptake by the newborn kidney cortex. A kinetic analysis of the entry phenomenon in the newborn tubule reveals the presence of two distinct membrame transport systems for AMG, only one of which is present in the adult tubule. All transport of sugar in both newborn and adult tubules was phlorizin-sensitive, but was only partially ingibited in Na+-free buffer. Glucose was shown to inhibit uptake competitively on the shared, high capacity system. Uptake on the high affinity system in the newborn represents 15-20% of the total at physiologic sugar concentrations. It is concluded that active sugar transport is a characteristic of the newborn rat kidney and that the isolated tubule preparation is a more accurate reflection of this phenomenon than is the renal cortical slice.

Age Factors↗

Prolactin in seminal plasma of infertile men.

Twenty-one fertile and 103 infertile patients with oligospermia, azoospermia, impaired sperm motility and hypogonadism were evaluated for prolactin concentrations in serum, seminal plasma and split seminal plasma of two fractions. Prolactin concentration in the seminal plasma was two to three times higher than serum prolactin levels in fertile and infertile men. Prolactin concentration of the fraction 2 of the split ejaculate was higher than that of the fraction 1 and of the serum. Excessive high levels of serum prolactin and/or seminal plasma were found only among infertile patients with oligo- and azoospermia, impaired motility and hypogonadotropic hypogonadism. Prolactin is selectively accumulated in fraction 2 of the split ejaculate and affects the constituents of the seminal vesicular fluid, and excessive high prolactin concentrations of either seminal plasma or serum may be associated with male infertility.

Humans↗