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Biomedical subjects

J Bernstein

Publications and source records attributed to J Bernstein.

At least 199 records · Page 11Linked to original sources
PubMed1985

Excessive glutamate as an inhibitor of excitatory transmission in rat hippocampal slice.

Exposure of rat hippocampal slices to perfusate containing 1-2 mM glutamate (GLU) induces reversible and relatively selective blockade of excitatory transmission. Intracellular recordings from 20 region CA1 hippocampal cells demonstrated only transient and mild effects on resting membrane properties and action potentials. In contrast, in 2 mM GLU excitatory postsynaptic potentials declined to 28% of control (P less than 0.001); inhibitory postsynaptic potentials remained robust at 88% of control. This suggests that excess exposure to GLU may result in a selective 'down-regulation' of excitatory synaptic transmission, while preserving inhibitory pathways. These observations may have practical implications for development of new anticonvulsant drugs.

Animals↗
PubMed1985

Conformational polymorphism VI: the crystal and molecular structures of form II, form III, and form V of 4-amino-N-2-pyridinylbenzenesulfonamide (sulfapyridine).

The crystal structures of three crystalline forms of 4-amino-N-pyridinylbenzenesulfonamide (sulfapyridine) have been determined by X-ray single crystal structure analysis. Form II crystallizes in space group P2(1)/c with four molecules in the unit cell: a = 0.6722(1) nm, b = 2.0593(5) nm, c = 0.8505(1) nm, beta = 101.14(1) degrees; Form III crystallizes in space group C2/c with eight molecules in the unit cell: a = 1.2830(2) nm, b = 1.1714(3) nm, c = 1.5400(3) nm, beta = 94.12(1) degrees; Form V crystallizes in the orthorhombic space group Pbca with 16 molecules in the unit cell: a = 2.4722(10) nm, b = 1.5710(15) nm, c = 1.2147(7) nm. The three structures were solved by direct methods and refined anisotropically to R factors of 0.045, 0.052, and 0.063, respectively. Bond lengths and bond angles agree well among the molecules in these structures; however, the system exhibits conformational polymorphism since the molecular conformation, as measured by torsion angles, differs significantly among the three forms. Sulfapyridine exhibits the imide configuration in all three structures rather than the amide form present in other sulfonamide compounds. Using the structural data, the powder patterns of the three forms have been computer generated to provide standard diffraction patterns for comparison with the variety of polymorphic forms reported in the literature.

Chemical Phenomena↗
PubMed1985

The role of p-aminophenol in acetaminophen-induced nephrotoxicity: effect of bis(p-nitrophenyl) phosphate on acetaminophen and p-aminophenol nephrotoxicity and metabolism in Fischer 344 rats.

Acetaminophen (APAP) produces proximal tubular necrosis in Fischer 344 (F344) rats. Recently, p-aminophenol (PAP), a known potent nephrotoxicant, was identified as a metabolite of APAP in F344 rats. The purpose of this study was to determine if PAP formation is a requisite step in APAP-induced nephrotoxicity. Therefore, the effect of bis(p-nitrophenyl) phosphate (BNPP), an acylamidase inhibitor, on APAP and PAP nephrotoxicity and metabolism was determined. BNPP (1 to 8 mM) reduced APAP deacetylation and covalent binding in F344 renal cortical homogenates in a concentration-dependent manner. Pretreatment of animals with BNPP prior to APAP or PAP administration resulted in marked reduction of APAP (900 mg/kg) nephrotoxicity but not PAP nephrotoxicity. This result was not due to altered disposition of either APAP or acetylated metabolites in plasma or renal cortical and hepatic tissue. Rather, BNPP pretreatment reduced the fraction of APAP excreted as PAP by 64 and 75% after APAP doses of 750 and 900 mg/kg. BNPP did not alter the excretion of APAP or any of its non-deacetylated metabolites nor did BNPP alter excretion of PAP or its metabolites after PAP doses of 150 and 300 mg/kg. Therefore, the BNPP-induced reduction in APAP-induced nephrotoxicity appears to be due to inhibition of APAP deacetylation. It is concluded that PAP formation, in vivo, accounts, at least in part, for APAP-induced renal tubular necrosis.

Acetaminophen↗
PubMed1985

Use of lectins in the study of histogenesis of renal cysts.

Two peroxidase-labeled lectins, from Tetragonolobus lotus and from peanut (Arachis hypogaea), were used in the study of five cases of polycystic kidney of different types. The two lectins bind with high selectivity of proximal tubules and collecting ducts, respectively. It was found that in infantile polycystic kidneys the cyst walls consistently stained with peanut lectin but not with Tetragonolobus lectin, confirming their origin from collecting ducts only. In adult polycystic kidneys there was mixture of two types of cysts: one positive for peanut, the other positive for Tetragonolobus. The two lectins were, however, mutually exclusive. Moreover, some cysts did not stain for either lectin. The findings suggest that in this type of disease a cyst can originate from any portion of the nephron. The data are also consistent with reports in the literature which used microdissection techniques or chemical analysis of the cyst content. The use of lectins will probably be useful in investigating other types of cystic kidneys, such as dysplastic kidneys and experimental models. The technique is relatively easy to use, but must be applied under strictly controlled conditions, especially when using surgical or postmortem material.

Adult↗
PubMed1985

The Na+/Ca2+ exchange system of the liver cell.

The efflux of 45Ca (Caeff) from rat liver slices incubated in a Krebs Ringer bicarbonate buffer showed two components with first order rate constants (kCa) of 0.0625 min-1 and 0.0101 min-1 respectively. The slow component corresponds to Caeff from the intracellular medium. Ouabain decreased kCa from the slow component (ksCa) by about 30%. External Na+ or Ca2+ did not affect ksCa. However, the inhibitory effect of ouabain was not observed in the absence of either Na+ or Ca2+ from the incubation medium. Concomitant to a decrease in ksCa, ouabain increased 45Ca uptake (Caup) by about 30%. Sodium ionophores also increased Caup, an effect which was not observed in the absence of external Na+. 22Na efflux was inhibited 50% by ouabain. In the presence of ouabain, external Ca2+ was able to significantly increase ksNa from 0.0475 min-1 to 0.0506 min-1. External Na+ dit not affect ksCa from preloaded slices containing high calcium and low sodium when incubated in a Ca2+-free medium. These results would indicate that a Na+/Ca2+ exchange system in operative in the plasma membrane of the hepatocyte. It is estimated that about 60% of the calcium entering the hepatocyte moves in through this exchanger. The evidence obtained also suggests that the Na+/Ca2+ exchanger operates unidirectionally, extruding internal Na+ in exchange for external Ca2+.

Animals↗
PubMed1985

Dipeptides of glutamate and aspartate may be endogenous neuroexcitants in the rat hippocampal slice.

The dipeptide N-acetylaspartylglutamate (NAAG), and possibly the related dipeptide aspartylglutamate (AG), have been found in high concentrations in rat brain, and have been shown to bind avidly and selectively to a subset of glutamate (GLUT) receptors. Certain observations regarding GLUT and aspartate might be explained if the endogenous transmitter were a compound composed of both amino acids. We therefore examined the electrophysiological actions of NAAG and AG in the rat in vitro rat hippocampal slice model. NAAG or AG and GLUT were applied locally to cells by a dual-barrel pressure technique. Intracellular recordings from 34 CA1 pyramidal neurons showed depolarizations and conductance increases resembling evoked excitatory postsynaptic potential in 15 of 20 cells exposed to NAAG, and 14 of 14 exposed to AG. Many GLUT-responsive sites did not respond to AG, and most did not respond to NAAG. Responses to NAAG were usually too small to induce cell firing; they were best detected, therefore, by intracellular recording. With extracellular unit recordings, GLUT was equally excitatory in stratum radiatum and pyramidale of CA1 (N = 19; p greater than 0.10, one-way analysis of variance). In contrast, AG was considerably more potent (N = 21; p less than 0.01) in stratum radiatum. NAAG was not noted to excite cells when applied to stratum pyramidale. The region of maximal responsiveness to AG in CA1 coincided with the area of the dendritic tree receiving Schaffer collateral-commissural afferents. This spatial profile, together with other neuropharmacological evidence, support the candidacy of glutamate-containing peptides as endogenous excitatory compounds in certain pathways of hippocampus.

Animals↗
PubMed1984

A family study of renal dysplasia.

A family study was undertaken to investigate genetic involvement in renal dysplasia, which is defined as abnormal metanephric differentiation. Probands were ascertained through the retrospective examination of necropsy records and the reevaluation of available material, which included microscopic examinations of the kidneys, gross descriptions of organs, and gross photographs. We obtained family histories and performed physical examinations and renal ultrasonography on parents and sibs of the 21 probands. In only one family a sibling with renal dysplasia was discovered; both the proband and the previous stillborn sib had renal dysplasia in association with posterior urethral values. Renal dysplasia could have resulted from urinary tract obstruction secondary to the urethral valves, with inheritance of the valves as the primary abnormality. However, we cannot exclude primary inheritance of the renal abnormality, perhaps with multifactorial determination with a threshold. The empiric recurrence risk of 2.1%, calculated from this family study, was statistically not significantly different from zero. We can assume, therefore, that the multicystic and aplastic types of renal dysplasia, which predominated in this study, are sporadic or rarely familial, but certain other types of renal dysplasia, identified in the literature as familial, probably carry a higher recurrence risk.

Abnormalities, Multiple↗
PubMed1984

Identification of the phoM gene product and its regulation in Escherichia coli K-12.

Plasmids containing the chromosome region of Escherichia coli encoding phoM, whose product is a positive regulator of alkaline phosphatase expression, were isolated from the Clarke and Carbon plasmid bank. A 9.9-kilobase EcoRI fragment of plasmid pLC17-39 (subcloned into pBR322) was able to complement both phoM and thrB mutations. Restriction endonuclease analysis and in vitro mutagenesis of the hybird plasmids enabled the localization of the phoM gene locus to 3 kilobases of the cloned chromosomal fragment. The phoM gene product was identified, with maxicell techniques, as a protein with an approximate molecular weight of 55,000. A phoM-lacZ protein fusion was constructed by using a plasmid carrying the phoM gene and a derivative of phage lambda, lambda plac Mu2. Restriction endonuclease analysis of the plasmid carrying the fusion indicated that phoM is transcribed in a clockwise direction on the circular E. coli chromosome. Analysis of strains bearing the fusion on a multiple-copy plasmid or integrated at the lambda attachment site of the chromosome indicated that the synthesis of the phoM gene product was unaffected by phosphate limitation of growth. The expression of the phoM gene was studied in strains with mutations in genes encoding effectors of the pho regulon. A threefold increase in phoM expression was seen in a phoU strain in comparison with the wild-type strain.

Alkaline Phosphatase↗
PubMed1984

Anxiety and performance in two ego threatening situations.

The relationship between trait and state anxiety and performance was studied in two ego threatening situations among 312 subjects. Candidates with high scores in trait and state anxiety measured just prior to a selection interview for medical school were predicted to receive poorer interview ratings than those candidates with low scores. High trait anxiety, but not state anxiety, measured prior to selection interviews was predicted to be negatively related to academic performance measured up to 1 year later. Neither trait nor state anxiety was found to be significantly related to interview performance ratings. Trait anxiety, but not state anxiety, was found to be significantly related to academic performance: low trait anxious subjects performed better than medium and high trait anxious subjects. This relationship was found to be sustained when controlled for academic aptitude.

Achievement↗
PubMed1984

Localization of collagen types IV and V, laminin, and heparan sulfate proteoglycan to the basal lamina of kidney epithelial cells in transfilter metanephric culture.

Mouse metanephric mesenchyme and embryonic spinal cord were cultured on opposite sides of a filter membrane. This resulted in formation of prenephronic vesicles after 36 hours in culture, S-shaped bodies after 2-3 days, and glomeruli and tubules after 4-7 days. The glomeruli consisted of an arborizing tuft of podocytes lying on a basement membrane without vascularization or a mesangial ingrowth. We have used antibodies to study the molecular composition of the nephron basement membrane at each stage of development. By immunofluorescence light microscopy, collagen Types IV and V, laminin, and heparin sulfate proteoglycan were expressed within the pericellular/intercellular matrix at the onset of morphologic differentiation. The molecules were organized into a linear basement membrane associated with epithelial cells during the prenephronic vesicle, S-shaped body, and glomerulus and tubule stages of development.

Animals↗
PubMed1984

Further characterization of the pulmonary ethanol metabolizing system (PET).

A postmitochondrial preparation of rat lung homogenate was able to metabolize ethanol (205.8 mumoles/g X hr) only in the presence of uridine diphosphate glucuroniate, with a Km for ethanol of about 14 mM. Lung slices from the same animals incubated in a Krebs ringer bicarbonate buffer showed a biphasic time-curve for ethanol metabolism. The amount of metabolized ethanol first increased and then decreased. The metabolic product of this system (PET-I) was sensitive to the action of betaglucuronidase. Lung slices from some animals, however, showed a monophasic time-curve for ethanol metabolism. The metabolic product of this system (PET-II) was insensitive to the action of beta-glucuronidase but sensitive to that of sulfatase. These results confirm our previous suggestion that the lung of the rat is able to metabolize ethanol by a conjugation process catalyzed by a glucuronyl-transferase. In addition, the evidence obtained in this work also suggests that in some animals PET is represented by a sulfotransferase.

Animals↗
PubMed1984

[Are retinoids of value in bladder tumors? Pharmacological study and literature review].

Retinoids are vitamin A derivatives with a modified final radical, lateral chain or initial cycle. Their action on malignant cells is not fully known, but probably consists of the control of cell growth and differentiation. Experiments suggest that retinoids are non-toxic, and that they are far more effective against severe lesions than against dysplasia. Their effect is dose-related and dependent on the type of carcinogen.

Animals↗