Search PubMed⌕ Search

Biomedical subjects

M Cogoli-Greuter

Publications and source records attributed to M Cogoli-Greuter.

25 records · Page 2Linked to original sources
PubMed1992

Activation of microcarrier-attached lymphocytes in microgravity.

A technology has been developed to achieve optimal attachment of adhesion-independent lymphocytes to microcarrier beads. The activation of T-lymphocytes by concanavalin A was tested under microgravity conditions in an experiment carried out in space during the first Spacelab Life Science Mission. Activation, measured as the synthesis of deoxyribonucleic acid (DNA) and the production of interferon-gamma, more than doubled in attached lymphocytes in microgravity. The depression of the activation discovered in previous space experiments is due to an impairment not of the lymphocyte but of the macrophage function. The system described here may be useful for radiobiological investigations on the effect of high-energy particles and for testing the efficiency of the immune system in humans during the long-duration space flight planned in the future. The biotechnological significance of the increased lymphokine production in space remains to be assessed.

Biotechnology↗
PubMed1992

Metabolism of 5-fluoro-dopa and 6-fluoro-dopa enantiomers in aggregating cell cultures of fetal rat brain.

The cerebral metabolism of enantiomers of 5-fluoro-DOPA (5F-DOPA) and 6-fluoro-DOPA (6F-DOPA) was characterized in organotypic cell cultures of fetal rat brain. This system permits the investigation of metabolic processes in brain tissue exclusively, without the effects of peripheral metabolism and transport. Metabolic profiles for each substrate were determined in comparison with those of L-DOPA and D-DOPA. The uptake of DOPA and fluoro-DOPA in aggregating brain cell cultures is strongly preferential for L-enantiomers. Decarboxylation by aromatic L-amino acid decarboxylase is an active step: the major products are dopamine (DA) or 6F-DA and their corresponding products of oxidative deamination, i.e. dihydroxyphenylacetic acid (DOPAC) or 6F-DOPAC, respectively. Decarboxylation products of D-enantiomers occur in lower amounts, and 5F-D-DOPA is not decarboxylated. However, 5F-DOPA is O-methylated to a great extent, and levels of 3-O-methyl-5F-DOPA are higher after incubation with 5F-D-DOPA than with 5F-L-DOPA. These data may serve as a support for more detailed modeling of [18F]F-DOPA metabolism than can be applied to the evaluation of the cerebral biochemistry of the DA system with positron emission tomography in vivo.

Animals↗
PubMed1992

Comparative metabolism of fluorinated 3,4-dihydroxyphenylalanine isomers in aggregating brain cell cultures.

Fluorinated analogues of 3,4-dihydroxyphenylalanine (DOPA) were tested for intracellular metabolic conversion in aggregating cell cultures prepared from fetal rat brain. 5-Fluoro-D/L-DOPA was methylated almost exclusively to 3-O-methyl-5-fluoro-D/L-DOPA. Metabolism of 6-fluoro-D/L-DOPA resulted in 6-fluorodopamine, 6-fluoro-3,4-dihydroxyphenylacetic acid, and 3-O-methyl-6-fluoro-D/L-DOPA, but with a qualitatively and quantitatively different metabolite pattern compared with that of L-DOPA and D/L-DOPA, respectively. Homovanillic acid and fluorohomovanillic acid have not been found intracellularly in the cultures. On the basis of these data, the model development of the cerebral metabolism of tracers used in positron emission tomography can be improved.

Animals↗
PubMed1981

Formation of hydroxypyruvaldehyde phosphate in human erythrocytes.

Human erythrocytes when incubated with [U-14C]glucose formed radioactively labeled hydroxypyruvaldehyde-P (CHOCOCH2OPO3(2-)). Using a "diagonal" chromatographic procedure on an anion exchange column for isolation and quantitative detection, up to 0.3 mumol of hydroxypyruvaldehyde-P/liter of packed cells was found. If glycolysis was blocked by inhibition of glyceraldehyde-3-P dehydrogenase with N-ethylmaleimide and iodoacetate, 0.7 mumol of hydroxypyruvaldehyde-P/liter of packed erythrocytes was detected. Hydroxypyruvaldehyde-P, found for the first time in eukaryotic cells, might be one of the long sought natural substrates of the glyoxalases.

Aldehydes↗
PubMed1979

Irreversible inactivation of pyruvate decarboxylase in the presence of substrate and an oxidant. An example of paracatalytic enzyme inactivation.

Pyruvate decarboxylase from yeast is progressively inactivated in the presence of pyruvate and an extrinsic oxidant such as 2,6-dichloroindophenol or hexacyanoferrate(III). The inactivation is linked to the oxidation of the hydroxyethylthiamine diphosphate intermediate to acetate. Removal of low-molecular compounds by gel filtration does not reactivate the enzyme. The rate of inactivation obeys saturation kinetics with respect to substrate concentration and is independent of enzyme concentration. In analogy to the paracatalytic inactivation of other enzymes forming oxidizable carbanion intermediates [Christen, P. (1977) Methods Enzymol.46, 48--54], the oxidation of enzyme-bound hydroxyethylthiamine diphosphate is thought to generate a transiently reactive intermediate which, without being released from the enzyme, covalently modifies a group at or near the active site. Reconstitution experiments indicate that the protein rather than the coenzyme moiety is modified.

2,6-Dichloroindophenol↗
PubMed1976

Specific irreversible inhibition of enzymes concomitant to the oxidation of carbanionic enzyme-substrate intermediates by hexacyanoferrate (III).

Four different enzymes, class I fructose-1,6-biphosphate aldolase from rabbit muscle, class II fructose-1,6-bisphosphate aldolase from yeast, transaldolase, and transketolase, are inactivated progressively in the presence of their specific substrates and hexacyanoferrate(III). The inactivation is strictly linked to the oxidation of the carbanionic enzyme-substrate intermediates of these enzymes reported previously [Healy, M. J. and Christen, P. (1973) Biochemistry, 12, 35]. However, the loss of activity is not due to the products of this oxidation, i.e. to hexacyanoferrate(II), or to the oxidation product of the substrate such as hydroxypyruvaldehyde phosphate in the case of aldolase [Healy, M. J. and Christen, P. (1972) J. Am. Chem. Soc. 94, 7911]. The inactivation is not reversed on removal of low-molecular-weight compounds by gel filtration or extensive dialysis indicating a covalent modification of the enzyme. The rate of inactivation obeys saturation kinetics with respect to substrate concentration. Hence, the modifying agent is a transiently reactive intermediate formed during the oxidation of the carbanionic enzyme-substrate intermediate by hexacyanoferrate(III).

Animals↗