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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Culture of neuroblastoma cells in a medium of low-thiamine concentration (6 nM) and in the presence of the transport inhibitor amprolium leads to the appearance of overt signs of necrosis; i.e., the chromatin condenses in dark patches, the oxygen consumption decreases, mitochondria are uncoupled, and their cristae are disorganized. Glutamate formed from glutamine is no longer oxidized and accumulates, suggesting that the thiamine diphosphate-dependent α-ketoglutarate dehydrogenase activity is impaired. When thiamine (10 µM) is added to the cells, the O2 consumption increases, respiratory control is restored, and normal cell and mitochondrial morphology is recovered within 1 h. Succinate, which is oxidized via the thiamine diphosphate-independent succinate dehydrogenase, is also able to restore a normal O2 consumption (with respiratory control) in digitonin-permeabilized thiamine-deficient cells. Our results therefore suggest that the slowing of the citric acid cycle is the main cause of the biochemical lesion induced by thiamine deficiency as observed in Wernicke's encephalopathy.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 66 (1996), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Total thiamine (the sum of thiamine and its phosphate esters) concentrations are two- to fourfold lower in human brain than in the brain of other mammals. There were no differences in the total thiamine content between biopsied and autopsied human brain, except that in the latter, thiamine triphosphate was undetectable. The main thiamine phosphate-metabolizing enzymes could be detected in autopsied brain, and the kinetic parameters were comparable to those reported in other species. Thiamine diphosphate levels were lowest in hippocampus (15 ± 4 pmol/mg of protein) and highest in mammillary bodies (24 ± 4 pmol/mg of protein). Maximal levels of thiamine and its phosphate ester were found to be present at birth. In parietal cortex and globus pallidus, mean levels of total thiamine in the oldest age group (77–103 years) were, respectively, 21 and 26% lower than those in the middle age group (40–55 years). Unlike cerebral cortex, the globus pallidus showed a sharp drop in thiamine diphosphate levels during infancy, with concentrations in the oldest group being only ∼50% of the levels present during the first 4 months of life. These data, consistent with previous observations conducted in blood, suggest a tendency toward decreased thiamine status in older people.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: When neuroblastoma cells were transferred to a medium of low (6 nM) thiamine concentration, a 16-fold decrease in total intracellular thiamine content occurred within 8 days. Respiration and ATP levels were only slightly affected, but addition of a thiamine transport inhibitor (amprolium) decreased ATP content and increased lactate production. Oxygen consumption became low and insensitive to oligomycin and uncouplers. At least 25% of mitochondria were swollen and electron translucent. Cell mortality increased to 75% within 5 days. [3H]PK 11195, a specific ligand of peripheral benzodiazepine receptors (located in the outer mitochondrial membrane) binds to the cells with high affinity (KD = 1.4 ± 0.2 nM). Thiamine deficiency leads to an increase in both Bmax and KD. Changes in binding parameters for peripheral benzodiazepine receptors may be related to structural or permeability changes in mitochondrial outer membranes. In addition to the high-affinity (nanomolar range) binding site for peripheral benzodiazepine ligands, there is a low-affinity (micromolar range) saturable binding for PK 11195. At micromolar concentrations, peripheral benzodiazepines inhibit thiamine uptake by the cells. Altogether, our results suggest that impairment of oxidative metabolism, followed by mitochondrial swelling and disorganization of cristae, is the main cause of cell mortality in severely thiamine-deficient neuroblastoma cells.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Analysis of purified Na+, K+-ATPase from cat and human cortex by sodium dodecyl sulfate-polyacrylamide gel electrophoresis reveals two large catalytic subunits called α(-) (lower molecular weight) and α(+) (higher molecular weight). Differences in K+ dephosphorylation of these two molecular forms have been investigated by measuring the phosphorylation level of each protein after their separation on sodium dodecyl sulfate gels. In the presence of Na+, Mg2+, and ATP, both subunits are phosphorylated. Increasing concentrations (from 0 to 3 mM) of K+ induce progressive dephosphorylation of both α-subunits, although the phosphoprotein content of α(-) is decreased significantly less than that of α(+). Ka values of α(-) for K+ are 40% and 50% greater in cat and human cortex, respectively, than values of α(+), α(-) and α(+) are thought to be localized in specific cell types of the brain: α(-) is the exclusive form of nonneuronal cells (astrocytes), whereas α(+) is the only form of axolemma. Our results support the hypothesis that glial and neuronal Na+, K+-ATPases are different molecular entities differing at least by their K+ sensitivity. Results are discussed in relation to the role of glial cells in the regulation of extracellular K+ in brain.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: We compared the thiamine and thiamine phosphate contents in the frontal, temporal, parietal, and occipital cortex of six patients with frontal lobe degeneration of the non-Alzheimer's type (FNAD) or frontotemporal dementia with five age-, postmortem delay-, and agonal status-matched control subjects. Our results reveal a 40–50% decrease in thiamine diphosphate (TDP) in the cortex of FNAD patients, whereas thiamine monophosphate was increased 49–119%. TDP synthesizing and hydrolyzing enzymes were unaffected. The activity of citrate synthase, a mitochondrial marker enzyme, was decreased in the frontal cortex of patients with FNAD, but no correlation with TDP content was found. These results suggest that decreased contents of TDP, which is essentially mitochondrial, is a specific feature of FNAD. As TDP is an essential cofactor for oxidative metabolism and neurotransmitter synthesis, and because low thiamine status (compared with other species) is a constant feature in humans, a nearly 50% decrease in cortical TDP content may contribute significantly to the clinical symptoms observed in FNAD. This study also provides a basis for a trial of thiamine, to improve the cognitive status of the patients.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    FEBS Letters 89 (1978), S. 173-176 
    ISSN: 0014-5793
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0584
    Keywords: Non-Hodgkin lymphoma ; Kiel classification ; Low-grade malignancy ; High-grade malignancy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary On the basis of the retrospective analysis of 405 patients, suggesting the clinical relevance of the Kiel classification of non-Hodgkin lymphomas (NHL), a prospective multicenter study was started on October 1st, 1975, by the Kiel Lymphoma Study Group in order to further clarify the clinical and prognostic features of the different lymphoma entities defined by this histopathologic scheme. Diagnostic protocol provides initial staging evaluation according to a modification of the Ann Arbor classification. Therapeutic approach is based on the hypothesis that, like Hodgkin's disease, NHL originate, at least in part, as localized lymphatic or extralymphatic tumors. Thus, extended field irradiation is performed in stages I and II (except for lymphoblastic lymphoma in children and young adults) whereas in the more advanced stages III and IV (except for stage III of centroblastic-centrocytic lymphoma) chemotherapy with additional radiotherapy is applied. Until June 1979, 815 patients entered the study (69.7% with NHL of low-grade malignancy). For the interim evaluation underlying the present and the other papers of this series data of 511 patients were available. Survival of patients with NHL of low-grade malignancy significantly exceeds that of patients with NHL of high-grade malignancy. NHL with good prognosis such as chronic lymphocytic leukaemia and centroblastic-centrocytic lymphoma can be differentiated from NHL with a poor course such as lymphoblastic and immunoblastic lymphomas. In addition, the existence of a third group with an intermediate prognosis comprising centrocytic and centroblastic lymphomas and, possibly, also LP immunocytoma is suggested. However, different initial slope of survival curves shows that this latter group of NHL is not homogeneous with regard to prognosis.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0584
    Keywords: Non-Hodgkin lymphoma ; Chronic lymphocytic leukaemia ; Immunocytoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0584
    Keywords: Non-Hodgkin lymphoma ; Kiel classification ; Rappaport classification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1076
    Keywords: Sphingolipid activator protein deficiency ; Farber disease ; Gaucher disease ; Krabbe disease ; Prenatal diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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 β-galactocerebrosidase, β-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.
    Type of Medium: Electronic Resource
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