Vitamin A abuse in cancer prophylaxis.
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Biomedical subjects
Publications and source records attributed to L Goldstein.
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The effects of mercurials and arsenicals on tyrosine absorption by the winter flounder Pseudopleuronectes americanus were studied using isolated intestinal strips mounted in Ussing chambers. The mercurials mercuric chloride (HgCl2), p-chloromercuriphenyl sulfonic acid (PCMBS), and phenylmercuric acetate (PMA) and the arsenicals oxophenylarsine and arsenamide were chosen for their different chemical properties. The transmural absorptive fluxes (mucosa to serosa, M----S) were inhibited by mucosal additions of 0.1 mM HgCl2 (64% inhibition), 1.0 mM PCMBS (41% inhibition), and 0.25 mM oxophenylarsine (48% inhibition). Tyrosine tissue accumulation was inhibited 68% by 0.1 mM HgCl2, 42% by 1.0 mM PCMBS, and 62% by 0.25 mM oxophenylarsine. Serosal addition of 1.0 mM PCMBS inhibited M----S flux by 45%. Transepithelial potential (TEP) was measured to monitor changes in ionic gradients across the epithelial membrane. Mucosal addition of 0.1 mM HgCl2, and of 0.25 and 0.05 mM oxophenylarsine significantly changed the TEP. Serosal additions of 0.1 mM HgCl2, 1.0 mM PCMBS, and 0.25 mM oxophenylarsine also altered the TEP significantly. These results indicate that Na+-dependent tyrosine uptake is inhibited by arsenicals and mercurials, but it is unclear whether the Na+-tyrosine cotransport system or the transmembrane ionic gradients were affected by these heavy metals.
Sera from persons seroreactive to both human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2), by whole-virus (VEIA) enzyme immunoassays (EIAs) for each virus, were selected from a seroprevalence study of 944 persons in Abidjan, Cote d'Ivoire, West Africa, in 1987. These sera were subsequently tested for HIV-1 and HIV-2 antibody specificity by type-specific peptide EIAs (PEIA) and western blot (WB) analysis for both viruses. Peripheral blood monocytes (PBMCs) from representative individuals were cultured in the presence of phytohemagglutinin-stimulated normal donor PBMCs. These cultures were periodically monitored for HIV-1 and HIV-2 proviral sequences by using the selective DNA amplification technique polymerase chain reaction (PCR). As an outgrowth of this study, we report the case of a person dually reactive by various serological techniques in whom proviral sequences from HIV-1 and HIV-2 were detected by PCR. This is the first confirmed case of a mixed HIV-1 and HIV-2 infection in a single individual.
The volume regulatory response of erythrocytes (RBCs) of the little skate Raja erinacea subjected to 30% dilution of their medium is mimicked by the application of phorbol ester or calcium ionophore, implicating protein kinase C and phosphoinositide metabolism in that response. To investigate the signaling link between dilution of the medium and cell response, we measured levels of inositol phosphates (associated with intracellular calcium release) and of diacylglycerol (the physiological activator of protein kinase C) in control and hyposmotically treated RBCs. Labeled inositol monophosphate (IP1) was significantly higher in osmotically shocked than in control cells. Inositol bis- and trisphosphate levels (IP2 and IP3) were low and did not alter with dilution treatment. Separation of the isomers in the IP1 fraction indicated that the dilution effect was likely to result from the breakdown of phosphatidylinositol directly, without the involvement of the IP3 and related messenger molecules. Hyposmotic treatment also elevated the diacylglycerol content of the skate RBCs, providing evidence for the activation of protein kinase C as part of the volume regulatory response. The results are interpreted as indicating that the response to hypotonic media in skate erythrocytes is mediated primarily by protein kinase C and any involvement of calcium is associated with that pathway rather than with the production and metabolism of IP3.
Two approaches to seeking stable patterns in the gestural organization of speech are examined: local organization (individual gestures coordinated with other individual gestures) and global organization (gestures forming larger conglomerates). Articulatory evidence from American English words with a variety of initial consonants and clusters shows that syllable-initial consonants form a global organization (indexed by a metric we term the C-center) that is coordinated with the syllable's vowel gesture. For syllable-final consonants, however, the evidence suggests that a local organization is employed: The first postvocalic consonant gesture is coordinated with the vowel gesture. Implications of these different styles of organization for the perceptual and phonological structure of speech are discussed.
Streptozotocin-induced diabetes increased sorbitol levels in the rat renal medulla. The activities of renal medullary aldose reductase and sorbitol dehydrogenase, responsible for the formation and metabolism of sorbitol, favor sorbitol formation and did not change in diabetes. The elevated sorbitol concentration appears to be due to an increase in medullary glucose concentration.
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Renal brush border membrane vesicles (bbmv) from the aglomerular toadfish (Opsanus tau), isolated by differential precipitation, were tested for their ability to actively translocate (i) taurine, known to be secreted by the kidney of several marine teleosts, and (ii) L-alanine, L-glutamic acid, and D-glucose, solutes that are normally reabsorbed in the filtering nephron. Vesicular taurine uptake displayed a Na+ dependence. Transport was greatest under conditions of an inward-directed Na+ gradient, but a significant stimulation by Na+ over K+ could also be observed in the absence of a salt gradient. At high extravesicular K+, the addition of valinomycin reduced taurine uptake. Na+-dependent 3H-taurine flux was almost completely inhibited by non-labeled taurine (tracer replacement) or beta-alanine, but was unaffected by L-alanine. Replacement of medium chloride by SCN- or NO3- in the presence of Na+ resulted in significantly lower uptake rates under both anion gradient and anion equilibrium conditions, whereas Br- could almost fully substitute for the stimulatory Cl- action. These results indicate the presence of an electrogenic Na+-cotransport mechanism with specificity for beta-amino acids in the toadfish renal brush border. Whether the system under physiological conditions mediates reabsorption or secretion of taurine remains to be determined. Toadfish bbmv also translocated L-alanine and L-glutamic acid in a Na+-dependent manner. Possible roles for these most likely reabsorptive transport systems in a non-filtering kidney are discussed. D-glucose uptake, however, appeared to occur via Na+-independent pathways, since it was not affected by phlorizin in the presence of Na+, or by Na+ replacement.
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In a multicenter cooperative study, an enzyme immunoassay (EIA) using purified antigen of lymphadenopathy-associated virus was compared with radioimmune precipitation (RIP) for detection of antibody to human immunodeficiency virus (HIV) in 634 patients with acquired immunodeficiency syndrome or related conditions, 687 apparently healthy persons at risk for HIV infection, 93 controls with cancer or autoimmune diseases, and 10,038 blood or plasma donors. Excluding the donors, the EIA was reactive in 875 (61.9%) of 1,414 subjects; compared with RIP, the sensitivity and specificity of EIA both were 99.8%. There was one false-positive EIA among 148 intravenous drug abusers and two false-negative EIAs among 472 apparently healthy homosexual men; no other discordant results between EIA and RIP occurred in these subjects. The EIA was repeatably reactive in 20 donors (0.2%), among whom 13 (65%) were positive by RIP; none of 529 randomly selected EIA-negative donors was RIP positive. In addition to its utility as a screening test in low-risk populations, the EIA for antibody to lymphadenopathy-associated virus is useful as a diagnostic test in persons with clinical evidence of or at risk for HIV infection.
Wounding with lambda-carrageenan results in a marked decrease in the intracellular-free glutamine content of rat skeletal muscle. The potential mechanisms for this finding, including alterations in glutamine release, glutamine utilization, and glutamine synthesis, were investigated in rats under pentobarbital anesthesia. Wounding did not increase glutamine release from muscle during incubation or isolated hindlimb perfusion. Wounded muscle utilized more glutamine than nonwounded muscle, as measured both by the production of [14C]O2 and of -glutamate from labeled glutamine. Maximal glutamine synthetase activity was increased by wounding. The increase in glutamine synthetase activity in wounded muscle was prevented by adrenalectomy and restored by replacement doses of corticosterone in wounded adrenalectomized animals. The decrease in muscle free glutamine induced by wounding is therefore not mediated by an increase in the release of this amino acid, nor by a reduction in the tissue capacity for glutamine synthesis, but by an increase in glutamine utilization at the site of injury. This difference is apparently determined by the utilization of glutamine by the cellular components of the inflammatory infiltrate, which were shown to be capable of active glutaminolysis.
Tyrosine absorption across the brush border of the intestinal epithelium of the winter flounder Pseudopleuronectes americanus was studied in Ussing chambers modified to determine early rates of uptake. At 0.1 mM tyrosine, the 4-min rate of uptake (influx) of tyrosine across the brush border averaged 37.5 nmol X cm-2 X h-1. Omission of Na decreased influx by 60%, indicating that tyrosine influx occurs, at least in part, by a Na-coupled process. Ouabain inhibited influx by 80%. Inhibition of brush border Na+-K+-2Cl- cotransport by bumetanide, 8-bromo-cyclic GMP, or Cl replacement stimulated tyrosine influx 2.5- to 4-fold. However, atriopeptin III, which also inhibits Na+-K+-2Cl- cotransport, did not stimulate tyrosine influx. Cyclic AMP, which does not appear to inhibit ion cotransport, did not stimulate tyrosine influx. Both cyclic GMP and bumetanide also stimulated the net mucosa-to-serosa tyrosine flux (43 and 29%, respectively) and increased the cellular concentration of tyrosine by 50%. Thus tyrosine's influx is increased to a greater extent than is its transmural flux or its cellular concentration, suggesting that the main change occurs at the brush border and represents large increases in both influx and efflux of tyrosine across this membrane.
Renal arteriovenous (A-V) concentration differences of the major potential respiratory substrates were measured in whole blood of control, NH4Cl-acidotic and diabetic ketoacidotic (DKA) rats. Net renal substrate extractions were calculated from A-V differences and renal blood flows. In fed control rats lactate accounted for 78% of the total substrate extracted. Small amounts (10-12%) of citrate and the ketone bodies 3-hydroxybutyrate and acetoacetate were also extracted. There was no significant extraction of either free fatty acids, glucose, glutamine, or pyruvate. In NH4Cl-acidotic rats lactate extraction was lower (40%) than in controls, but glutamine extraction increased (28%). The amount of extra glutamine extracted approximated the fall in lactate extraction. In DKA rats, ketone bodies accounted for the major portion of the extracted substrates (56%) but a significant part of the net extraction was due to urinary excretion of these compounds. Glutamine extraction represented 23% of the total. Lactate extraction was low (14%) in DKA rats, probably as a result of the low arterial lactate concentration. In vitro studies done on renal cortical slices suggest that each of the three major substrates extracted by the kidneys of normal, NH4Cl, and DKA rats could serve as major respiratory fuels.
Glutamine, the principal source of urinary ammonia, can be fully oxidized or converted to glucose by the kidney. To be oxidized, the carbon skeleton of glutamine must enter the TCA cycle as acetyl CoA formed by pyruvate dehydrogenase (PDH). The purpose of this study was to measure kidney PDH activity (active and total) following acute acid-base changes in vivo. PDHa activity was elevated after acute metabolic alkalosis and acidosis and unchanged by respiratory acidosis. Kidney ADP/ATP, CoA/acetyl CoA and calculated mitochondrial NAD+/NADH ratios were also determined and revealed an increase in kidney ADP/ATP with alkalosis but no changes during metabolic and respiratory acidosis.
A study was performed to evaluate and compare the sensitivity of magnetic resonance imaging (MRI) and radionuclide blood-pool scanning in the detection of hepatic hemangiomas. All patients had known hemangiomas which were first detected on either ultrasound or computed tomography. Sixteen patients with a total of 23 lesions were investigated. Eleven patients had both MRI and blood-pool scans performed. In the group studied by both modalities, 18 lesions were detected ranging in size from 1 to 11 cm. All lesions were detected by both techniques. However, two of the 18 lesions had an atypical appearance on MRI. Our experience to date indicates that the anatomic location and specific diagnosis of hemangiomas can be made with a high degree of certainty when both MRI and blood-pool scanning techniques are utilized.
To examine the possibility that pathological gambling is related to the deficits in impulse control associated with attention deficit disorder, 14 pathological gamblers and 16 controls were administered questionnaires concerning their childhood behaviors. These self-reports indicated a strong correlation between pathological gambling and childhood behaviors related to attention deficit disorder.
The Saccharomyces cerevisiae secretory process was studied by evaluating secretion efficiency, processing efficiency, and the efficiency of protein folding for hybrid proteins containing the yeast prepro-alpha-factor leader region. Secretion of three proteins, beta-endorphin, calcitonin, and a consensus alpha-interferon (IFN-Con1), were compared in terms of secretion efficiency into the culture medium, beta-Endorphin and calcitonin, both small proteins, were found to be efficiently secreted from logarithmically grown cells. In contrast, the larger IFN-Con1 accumulated in the periplasmic space and cell wall. The glycosylated, unprocessed prepro-alpha-factor/IFN-Con1 fusion protein was also found to be secreted into the culture medium. The presence of (Glu-Ala) dipeptides in the alpha-factor spacer peptide increased the efficiency of cleavage at Lys-Arg in the prepro-alpha-factor/IFN-Con1 protein fusion. Purified secreted IFN-Con1 was structurally characterized to determine the effect of passage through the yeast secretory pathway on the fidelity and efficiency of protein folding. The disulfide structure of the secreted protein was found to be identical with that reported for the native human alpha-interferons.