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T Grisar

Publications and source records attributed to T Grisar.

At least 55 records · Page 3Linked to original sources
PubMed1989

Phenytoin dephosphorylates the alpha(-) catalytic subunit of (Na+, K+)-ATPase. A study in mouse, cat and human brain.

Phenytoin, a potent antiepileptic drug, has been thought to stimulate Na+, K+ transport across cell membranes, but its influence on (Na+, K+)-ATPase activity remains highly controversial. We have investigated the effects of the drug on the phosphorylation level of (Na+, K+)-ATPase partially purified from mouse, cat and human brain. (Na+, K+)-ATPase catalytic subunits [alpha(+) and alpha(-)] were resolved by sodium dodecylsulfate polyacrylamide gel electrophoresis. Previous experiments had shown that phenytoin dephosphorylates the (Na+, K+)-ATPase catalytic subunit by +/- 50% in C57/BL mice. In the present study, we showed that phenytoin (10(-4) M) decreases the phosphorylation level of (Na+, K+)-ATPase catalytic subunit by the same value in cat and human cortex. Moreover, that effect is predominant on the alpha(-) subunit, thought to be the predominant enzymatic form in non-neuronal or glial cells. The results are thus favoring the hypothesis that phenytoin stimulates the brain (Na+, K+)-ATPase. They further suggest that phenytoin mainly activates the glial enzymatic form, providing central nervous system with an enhanced ability to regulate extracellular K+.

Animals↗
PubMed1989

Sphingolipid activator protein deficiency in a 16-week-old atypical Gaucher disease patient and his fetal sibling: biochemical signs of combined sphingolipidoses.

We describe a patient who presented shortly after birth with hyperkinetic behaviour, myoclonia, respiratory insufficiency and hepatosplenomegaly. Gaucher-like storage cells were found in bone marrow. A liver biopsy showed massive lysosomal storage morphologically different to that in known lipid storage disorders. Biochemically, the patient had partial deficiencies of beta-galactocerebrosidase, beta-glucocerebrosidase and ceramidase in skin fibroblast extracts, but the sphingomyelinase activity was normal. Glucosyl ceramide and ceramide were elevated in liver tissue. Loading of cultured fibroblasts with radioactive sphingolipid precursors indicated a profound defect in ceramide catabolism. Immunological studies in fibroblasts showed a total absence of cross-reacting material to sphingolipid activator protein 2 (SAP-2). The patient died at 16 weeks of age. The fetus from his mother's next pregnancy was similarly affected. The possibility that the disorder results from a primary defect at the level of SAP-2 is discussed. We have named this unique disorder SAP deficiency.

Consanguinity↗
PubMed1986

Astroglial contribution in human temporal lobe epilepsy: K+ activation of Na+,K+-ATPase in bulk isolated glial cells and synaptosomes.

Potassium activation of Na+,K+-ATPase within glial cells and synaptosomes, bulk isolated from temporal neocortices of 15 patients with hippocampal-amygdalar epilepsy were compared to two patients with extratemporal complex partial epilepsies and 8 post-mortem temporal neocortices from patients with no known neurological ailments. Temporal neocortices were obtained from 17 patients who had undergone 'en bloc' anterior temporal lobectomy. In 15 patients with hippocampal amygdalar epilepsy, enzymatic activities of glial fractions were lower than those shown in 2 control lobectomy specimens and post-mortem brains. Glial enzymes had no or poor activation when K+ concentrations increased from 3 to 18 mM. Two patients served as control lobectomy specimens since they had normal neuropathological studies, and electroclinical correlations indicated an extratemporal lobe origin for complex partial seizures. In these two control specimens, glial Na+,K+-ATPase activities were similar to normal animals or post-mortem specimens. Na+,K+-ATPase activities were also slightly decreased in the synaptosomal fractions of patients with hippocampal-amygdalar epilepsy. K+ response of enzyme activities, however, corresponded to what had been described in controls, i.e. hyperbolic curves saturated at 3-6 mM K+. These results indicate that a defect in glial Na+,K+-ATPase exists in temporal neocortices of patients with hippocampal-amygdalar epilepsy.

Adult↗
PubMed1986

Phenytoin dephosphorylates the catalytic subunit of the (Na+,K+)-ATPase in C57/BL mice.

The effects of phenytoin, a potent antiepileptic drug, on the active transport of cations within membranes remain controversial. To assess the direct effects of phenytoin on the Na+,K+ pump, we studied the drug's influence on the phosphorylation of partially purified (Na+,K+)-ATPase from mouse brain. (Na+,K+)-ATPase subunits were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Phenytoin, in vitro, decreased net phosphorylation of the (Na+,K+)-ATPase catalytic subunit in a dose-dependent manner (approximately 50% at 10(-4) M). When the conversion of E1-P to E2-P, e.g., the two major phosphorylated conformational states of (Na+,K+)-ATPase, was blocked by oligomycin or N-ethylmaleimide, phenytoin had no effect. The results suggest that phenytoin acts on the phosphatasic component of the reaction cycle, decreasing the phosphorylation level of the enzyme.

Adenosine Diphosphate↗
PubMed1986

Regional cerebral blood flow and metabolic rates in human focal epilepsy and status epilepticus.

Positron emission tomography with the oxygen-15 steady state or bolus inhalation technique was used to provide quantitative values of regional cerebral blood flow (CBF), oxygen extraction ratio (OER) and oxygen consumption (CMRO2) in 25 patients with partial complex seizures during the interictal state and in 5 patients during status epilepticus. Glucose utilization (CMRglu) was also studied in one case of status epilepticus with the 18F-fluorodeoxyglucose technique (18FDG). Interictal scans showed zone(s) of hypoperfusion and hypometabolism without significant variation of the OER in approximately 80% of patients. In 62%, there was a strong correlation between the overall EEG localization and the area(s) of hypoperfusion and hypometabolism. In all cases, ictal scans revealed a focal or multifocal increase in CBF and CMRO2. The localization of the most affected regions correlated well with the spatial distribution of the electroencephalograph (EEG) abnormalities. Comparison of the different values of CBF, CMRO2, and OER showed that the increase in perfusion always exceeded that of oxygen consumption and hence was accompanied by a significant decrease of OER; the latter was always the most prominent in the region of the epilepticus focus determined by serial EEG recordings. These results showed that the supply of oxygen by blood flow is large enough to meet metabolic demand. When comparing these values with CMRglu, it appeared that the relative changes in CMRglu and CBF were very similar, indicating that the increase in blood flow correlated with the enhancement in glucose utilization. The observed imbalance between blood flow, glucose utilization, and oxygen consumption could suggest that an impairment of oxygen utilization by the mitochondria could occur in the epileptic focus during prolonged status epilepticus.

Cerebrovascular Circulation↗
PubMed1984

Glial and neuronal Na+-K+ pump in epilepsy.

Because high extracellular K+ concentrations (18-20 mM) increased glial Na+- and K+ -dependent adenosine triphosphatase [(Na+ + K+)-ATPase] activities, while this increase was not observed in neuronal preparations, it is hypothesized that K+ released in the extracellular space during neuronal firing is actively taken up by glial cells. In acute and chronic epileptogenic lesions of cats, glial (Na+ + K+)-ATPase dramatically decreased when compared to both control animals and the perifocal area, while its activation by extracellular K+ in concentrations between 3 and 18 mM was absent 3, 6, and up to 45 days after production of freezing lesions. Similar results were observed in 13 specimens of anterolateral temporal neocortex obtained during temporal lobectomies in patients with intractable temporal lobe epilepsy, compared with postmortem human specimen or control brain tissues. Hence, a glial (Na+ + K+)-ATPase abnormality exists in epileptogenic tissue. Further experimental data are presented supporting the notion that this glial abnormality may favor the transition from interictal episodes to ictal phenomena.

Animals↗
PubMed1981

Histopathological correlation of the Kiel with the original Rappaport classification of malignant non-hodgkin lymphomas.

Using the Kiel and the Rappaport classifications, a comparative histopathological analysis of 486 cases with non-Hodgkin lymphomas from a prospective study of the Kiel Lymphoma Study Group, still in progress, was performed. The greater part of Rappaport's classical lymphoma entities was found to be inhomogeneous and to include tumors of considerable prognostic heterogeneity, as shown by differences in actuarial survival. Some of the Kiel lymphoma entities have been identified in several lymphoma types of the Rappaport classification, indicating that "translation" of one scheme into the other is difficult or impossible. In addition, centrocytic lymphoma of the Kiel classification may not be homogeneous. On the whole, the Kiel classification appears to be superior to the original Rappaport classification in categorizing the various prognostically diverse types of non-Hodgkin lymphomas.

Germany, West↗
PubMed1981

Lymphoplasmacytic/lymphoplasmacytoid lymphoma: a clinical entity distinct from chronic lymphocytic leukaemia?

Clinical data of 116 patients with chronic lymphocytic leukaemia (CLL) and of 114 patients with lymphoplasmacytic/lymphoplasmacytoid lymphoma (synonym: LP immunocytoma, IC) as diagnosed according to the Kiel classification were compared. This interim evaluation of a prospective multicenter study of the Kiel Lymphoma Study Group characterizes IC the less favorable lymphoma entity as evidenced by a more rapid lymph node enlargement, by a higher incidence of constitutional symptoms and of marked anaemia, and by a higher percentage of patients requiring early treatment. In addition, in IC autoimmune haemolytic anaemia was detected in 11.2% of investigated patients as compared to none of the patients with CLL, and monoclonal gammopathy was disclosed in 34.2% of investigated patients as compared to only three patients with CLL who could be, however, unrecognized cases of IC. Actuarial survival data after a follow-up period of 40 months are in favor of an overall better prognosis of patients with CLL than of patients with IC.

Adult↗
PubMed1981

Effect of changing potassium ion concentrations on rat cerebral slices in vitro: a study during development.

Adult rat cerebral cortex slices when incubated in media in increasing K+ concentrations, from 3 to 20 mM ("physiological" conditions), exhibited an increase of Ki+ and a decrease of Nai+ and Cli-. This phenomenon appeared at 30 days postnatally, which is fairly late during development. Over 20 mM-K+ ("pathological" conditions) an intense water uptake was observed together with an increase of Nai+ and Cli-. This was observed in both adult and young animals. The results are discussed in relation to the well known properties of glial (Na+,K+)-ATPase and carbonic anhydrase.

Animals↗
PubMed1979

Effect of K+ ions on kinetic properties of the (Na+, K+)-ATPase (EC 3.6.1.3) of bulk isolated glial cells, perikarya and synaptosomes from rabbit brain cortex.

Progress curves of the enzymatic reactions show that ATPases of bulk isolated glial cells, perikarya and synaptosomes exhibit hysteretic change. Initial velocities of enzyme activities were therefore obtained according to the equation valid for the hysteretic model. The (Na+, K+)-ATPase activities of the same brain fractions were measured before or after NaI treatment. Only glial and synaptosomal enzyme could be adequately extracted by using this procedure. Attempts to purify the (Na+, K+)-ATPase from brain perikarya by NaI extraction were unsuccessful. In order to determine the effect of the K+ ions on enzymic physiological efficiency (phys. eff.; i.e., the ratio Vmax/Kmapp) the variation of (Na+, K+)-ATPase activities from each brain fraction was measured as a function of Mg.ATP2- concentration in the presence of 5 and 20 mM K+ ions. High K+ ion concentrations (20 mM) increased the physiological efficiency of glial enzyme and decreased the same kinetic parameter in neuronal (perikaryal as well as synaptosomal) enzyme preparations. Results are discussed in relation to a possible distribution of distinct enzyme in different brain cell populations as well as a possible role of glial cells in an active regulation of K+ ion extracellular fluid in the CNS.

Adenosine Triphosphatases↗