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Biomedical subjects

R A Fishman

Publications and source records attributed to R A Fishman.

At least 55 records · Page 3Linked to original sources
PubMed1982

Alterations of membrane integrity and cellular constituents by arachidonic acid in neuroblastoma and glioma cells.

Effects of arachidonic acid on cellular metabolism, cation content, lipid peroxidation, sodium pump activities and release of labeled arachidonic acid were studied in C-6 glioma cells and N18TG2 neuroblastoma cells. Arachidonic acid caused a significant increase in intracellular sodium levels concomitant with a decrease in intracellular potassium in both cell lines. Both (Na+ + K+)-ATPase and p-nitrophenyl phosphatase of glioma cells were inhibited by arachidonic acid whereas only the p-nitrophenyl phosphatase of neuroblastoma cell was inactivated. Low concentrations of arachidonic acid stimulated lactic acid release whereas high concentrations had an opposite effect. In addition, the lipid peroxide content of glioma cells was increased abruptly by 50 microM arachidonic acid whereas only a slight increase of malondialdehyde was observed in neuroblastoma cells. When the cultured cells of both cell lines were incubated with exogenous labeled arachidonic acid, 78-95% of the label was incorporated into membrane phospholipids. Only a very small fraction of prostaglandin E2 and prostaglandin F2 alpha was synthesized. Exogenous arachidonic acid and free radicals generated with xanthine-xanthine oxidase caused a significant release of endogenous labeled arachidonic acid from cellular membrane phospholipids. These data further support our hypothesis that the arachidonic acid and its oxygen radical metabolites induce pathological alterations in membrane permeability and cellular volume.

Animals↗
PubMed1982

Intracellular volume of osmotically regulated C-6 glioma cells.

The intracellular volume of neoplastic brain cells was investigated with regard to the effects of hypo-osmolality and hyperosmolality utilizing double isotopic labeling with 3-0-methyl-D-glucose or tritiated water to measure the total volume of the pellet and inulin or polyethyleneglycol to measure the extracellular volume of the pellet. The cellular pellets were rapidly separated from the incubation medium by centrifugation after addition of an oil mixture. After 60 minutes incubation in Hanks balanced salt medium, the intracellular volume was 7.50 +/- 0.64, 8.48 +/- 0.19, and 2.97 +/- 0.18 ml H2O per 10(6) packed cells for C-6 glioma cells, N18TG-2 neuroblastoma cells, and NG108-15 neuroblastoma X glioma hybrid cells, respectively. The extracellular trapped space of these cultured cells was about one third of the intracellular volume. The intracellular volume of C-6 glioma cells was increased in hypotonic environment, whereas it was decreased with hyperosmolality. Both intracellular sodium and potassium were increased with increased osmolality of the incubation media. These data indicate iso-osmotic regulation by tumor cells, i.e., there is a good correlation between the intracellular volume, intracellular cations and lactate levels of C-6 glioma cells under various osmotic conditions.

Animals↗
PubMed1982

Phospholipid degradation and cellular edema induced by free radicals in brain cortical slices.

Cellular edema and increased lactate production were induced in rat brain cortical slices by xanthine oxidase and xanthine, in the presence of ferric dialdehyde, was increased 174%. Among the various subcellular fractions of brain cortex, xanthine oxidase-stimulated lipid peroxidation was highest in myelin, mitochondria, and synaptosomes, followed by microsomes and nuclei. Antioxidants, catalase, chlorpromazine, and butylated hydroxytoluene inhibited lipid peroxidation in both homogenates and synaptosomes, indicating H2O2 and radicals were involved. Further, several free fatty acids, especially oleic acid (18:1), arachidonic acid (20:4), and docosahexaenoic acid (22:6) were released from the phospholipid pool concomitant with the degradation of membrane phospholipids in xanthine oxidase-treated synaptosomes. These data suggest that lipases are activated by free radicals and lipid peroxides in the pathogenesis of cellular swelling.

Animals↗
PubMed1981

Differential effects of hypertonic mannitol and glycerol on rat brain metabolism and amino acids.

Intraperitoneal injections in rats of two different dosages of hypertonic solutions containing mannitol or glycerol caused complex and differential changes in brain amino acids. When plasma osmolalities were elevated to toxic levels of 397--432 mOsm/kg H2O, brain sodium was increased, whereas plasma sodium was decreased. Brain potassium was not affected. Brain water decreased significantly, concomitant with elevation of plasma osmolality. Both brain lactic acid and [125I]albumin space rose significantly. Brain amino acids (mostly aliphatic and basic amino acids) as well as Gaba and glycine (putative inhibitory neurotransmitters) increased after both mannitol and glycerol. Ammonia was stimulated by mannitol but was unaffected by glycerol. Plasma amino acids, which generally increased after mannitol, were decreased by glycerol. When the plasma osmolalities were elevated only to moderate levels (about 350 mOsm/kg H2O), only glycerol induced a significant increase in brain taurine, aspartic acid, alanine, leucine and lysine. Thus, with moderate hyperosmolality, glycerol has striking effects on brain amino acid metabolism that are not observed with mannitol.

Amino Acids↗
PubMed1980

Proteinuria during long-term captopril therapy.

Proteinuria developed in six of 81 hypertensive patients given captopril for at least four months (protein excretion, greater than 200 mg/24 hr). Two had previously elevated protein excretion. In all patients the increased protein excretion occurred by the fourth month of treatment. It subsided in four after two to nine months, despite continued therapy. In two of the four, proteinuria cleared completely within seven months after onset, while in the other two it subsided to the range of 600 mg/24 hr. However, in the remaining two patients proteinuria persisted during captopril therapy and was associated with hypoalbuminemia and hypercholesterolemia. Renal biopsy specimens showed mild membranous nephropathy in two patients, one of whom had a remittance of proteinuria during continued captopril treatment.

Adult↗
PubMed1980

Arachidonic acid-induced swelling in incubated rat brain cortical slices. Effect of bovine serum albumin.

The influence of bovine serum albumin (BSA) on the rat brain cortical swelling induced by sodium arachidonate and polyunsaturated fatty acids has been studied. Coincubation of arachidonate with BSA at a molar ratio of 5 (arachidonate/BSA) or less greater inhibited the arachidonate-induced swelling. As the molar ratio of arachidonate/BSA increased, the degree of swelling increased. The swelling was not reversed by BSA, although the BSA released 46% of the previously incorporated [3H]arachidonic acid from the cortical slices. The entry of [3H]arachidonate into the slice was completely abolished by 0.1 mM BSA or partially inhibited by exogenous arachidonate. It is concluded that the induction of brain swelling by arachidonate requires the intracellular transport of exogenous arachidonate.

Animals↗
PubMed1980

Transient formation of superoxide radicals in polyunsaturated fatty acid-induced brain swelling.

The involvement of superoxide free radicals and lipid peroxidation in brain swelling induced by free fatty acids has been studied in brain slices and homogenates. The polyunsaturated fatty acids linoleic acid (18:2), linolenic acid (18:3), arachidonic acid (20:4), and docosahexaenoic acid (22:6) caused brain swelling concomitant with increases in superoxide and membrane lipid peroxidation. Palmitic acid (16:0) and oleic acid (18:1) had no such effect. Furthermore, superoxide formation was stimulated by NADPH and scavenged by the addition of exogenous superoxide dismutase in cortical slice homogenates. These in vitro data support the hypothesis that both superoxide radicals and lipid peroxidation are involved in the mechanism of polyunsaturated fatty acid-induced brain edema.

Animals↗
PubMed1980

Metabolic basis of brain edema.

A large number of metabolic factors have been incriminated in the pathogenesis of the various forms of brain edema. Ultimately we must learn more about the factors responsible for the integrity of the membranes of the capillary endothelium, neurons, and glia. What determines normal membrane fluidity, and how is it modified in disease? What is the mechanism of action of glucocorticosteroids in the treatment of vasogenic edema? The role of free radicals, polyunsaturated fatty acids, and excitatory neurotransmitters on cellular membranes and the distribution of sodium and water in the various compartments of the brain require further study.

Animals↗
PubMed1978

Brain edema: induction in cortical slices by polyunsaturated fatty acids.

The presence of polyunsaturated and saturated fatty acids in leukocytic membranes prompted study of their possible role in the induction of brain edema. Polyunsaturated fatty acids including sodium arachidonate, sodium linoleate, sodium linolenate, and docasahexaenoic acids induced edma in slices of rat brain cortex. This cellular edema was specific, since neither saturated fatty acids nor a fatty acid containing a single double bond had such effect.

Animals↗