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BACKGROUND Epothilones are a novel class of microtubule-stabilising agents, and sagopilone is a fully synthetic epothilone that has shown marked in vivo and in vitro preclinical activity. METHODS This phase I, open-label study investigated the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of weekly sagopilone. Twenty-three patients with(More)
The uptake of L-lactate was investigated in neuronal primary cultures derived from embryonic rat brain with a radioactive tracer method. After preincubation of the cells in glucose-free buffer for 30 min, uptake increased with time for at least 10 min. A saturable component of uptake was found with half-maximal uptake at 10 mM lactate. This saturable(More)
Cytosolic malic enzyme (EC was purified from bovine brain 5,600-fold to a specific activity of 47 U/mg. The enzyme is a homotetramer with a subunit molecular mass of 60 kDa and an isoelectric point of 6.2. Mouse monoclonal antibodies raised against this enzyme were purified and shown to be monospecific, as indicated by immunoblotting.(More)
Uptake and metabolism of mannose were studied in astroglia-rich primary cultures derived from neonatal rat brains. A saturable component of mannose uptake was found with half-maximal uptake at 6.7 +/- 1.0 mM mannose. In addition, a non-saturable component dominated the uptake at high concentrations of mannose. Glucose, cytochalasin B, or phloretin in the(More)
The enzyme argininosuccinate synthetase (ASS) is the rate limiting enzyme in the metabolic pathway leading from L-citrulline to L-arginine, the physiological substrate of all isoforms of nitric oxide synthases (NOS). ASS and inducible NOS (iNOS) expression in neurons and glia was investigated by immunohistochemistry in brains of Alzheimer disease (AD)(More)
Anion exchange chromatography on diethylaminoethyl cellulose was optimized to separate the cytosolic and mitochondrial isoforms of malic enzyme from rat brain. Extracts of adult rat brain and of astroglia-rich primary cultures derived from the brains of newborn rats were analyzed for their content of the two isozymes. In the case of brain tissue 45% of(More)
To elucidate the cellular location of mitochondrial malic enzyme in brain, immunocytochemical studies were performed. For this purpose, mitochondrial malic enzyme was purified to apparent homogeneity from bovine brain and used for the immunization of rabbits. Subjecting the antiserum to affinity purification on immobilized antigen as an absorbent yielded a(More)
Uptake of radiolabeled myo-inositol was studied in astroglia-rich primary cultures derived from neonatal mouse brains. The uptake was saturable in the presence of Na+ with a Km of 25 microM and a Vmax of 60 pmol.min-1.(mg protein)-1, suggesting a high-affinity transport system for myo-inositol in astroglial cells. In addition, a Na(+)-independent,(More)
Advanced glycation endproducts (AGEs) accumulate on long-lived protein deposits including beta-amyloid plaques in Alzheimer's disease (AD). AGE-modified amyloid deposits contain oxidized and nitrated proteins as markers of a chronic neuroinflammatory condition and are surrounded by activated microglial and astroglial cells. We show in this study that AGEs(More)
Uptake of L-[(14)C]citrulline was studied in cell culture models of the main neural cell populations, in astroglia-rich primary cultures derived from neonatal rat brain, in rat glioma cells C6-BU-1, in cells of the murine microglial clone N11 and in the glioma x neuroblastoma hybrid cell line 108CC15 with neuronal properties. For comparison, cells of the(More)