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Biomedical subjects

A Grossmann

Publications and source records attributed to A Grossmann.

62 records · Page 4Linked to original sources
PubMed1976

The effect of dimethylaminoadamantane on neuronal membranes.

The effect of dimethylaminoadamantane (DMAA), an amantadine derivative with an anti-Parkinson property, on rat sensory nerve fibres was studied with the sucrose gap method. DMAA 10(-4) M in normal Locke solution reduced the spike amplitude without changing the resting potential, increased the membrane resistance and depressed repetitive spike activity elicited by depolarizing currents. From experiments performed with changed concentrations of sodium, potassium, calcium and chloride ions in the suspension medium it appears that the permeability of sodium, potassium and chloride ions is reduced by DMAA. The possible implication of the membrane effects of the drug in its action on dopaminergic transmission in the brain is discussed.

Amantadine↗
PubMedDate not supplied

Intracellular calcium response is reduced in CD4+ lymphocytes in Alzheimer's disease and in older persons with Down's syndrome.

Abnormalities in intracellular free calcium ([Ca2+]i) regulation are likely to play a role in brain aging and have been described in cells from patients with Alzheimer's disease (AD). [Ca2+]i acts as a second messenger in transmembrane signaling and regulates diverse functions in many cell types. Therefore, abnormalities in [Ca2+]i response may have far-ranging effects. Using flow cytometric assay for [Ca2+]i, we examined whether mitogen-induced increases in [Ca2+]i are abnormal in CD4+ T-lymphocytes from patients with familial AD (FAD), other AD, and Down's syndrome (DS) compared to age-matched controls. We observed that the peak [Ca2+]i responses were significantly decreased in CD4+ cells from 6 FAD patients (59% of control), 34 other AD patients (69% of age-matched control), and 6 older persons with DS (> 25 years old, 47% of control), after stimulation with 10 micrograms/ml anti-CD3 monoclonal antibody (mAb). The number of CD3 receptors on T lymphocytes of the AD patients was not decreased. In contrast, lymphocytes from subjects with FAD, other AD and older DS patients had no decrease in response to phytohemagglutinin (30 micrograms/ml). CD3 and related classes of membrane receptors are present on many cells of the central nervous system. Therefore, receptor signaling defects via this receptor in T lymphocytes of AD patients may be relevant to the central nervous system pathology seen in AD and DS.

Adult↗
PubMedDate not supplied

Inhibition of histone deacetylases: a new strategy to target epigenetic modifications for anticancer treatment.

The role of epigenetic modifications due to deregulated acetylation of nucleosomes with respect to its role in progression and etiology of human cancer is discussed. Among the mediators of these phenomena are the histone deacetylases, a class of enzymes consisting of at least two subfamilies with a total of at least 7 members in mammals. Depending on the cell-type, inhibition of HDACs in cancer cells can lead to transcriptional activation and silencing of about 2% of human genes, cell-cycle arrest and induction of apoptosis and differentiation in vitro and in vivo. This paper discusses several inhibitors of HDACs primarily derived from natural sources, their physiological consequences in different in vitro and in vivo cancer-related systems, their stage of preclinical and clinical development as well as their potential as antineoplastic agents. It is of paramount importance to elucidate the molecular mechanisms resulting in cell-cycle arrest, apoptosis or differentiation after inhibition of HDACs and to investigate the physiological function of the different HDAC isoenzymes and their deregulation in human cancers in order to devise optimized therapeutic intervention in cancer patients.

Acetylation↗
PubMedDate not supplied

Active-specific immunotherapy of pancreatic carcinoma: usefulness of human pancreatic carcinomas in preparing autologous tumor vaccines.

Using a mouse model we investigate whether pancreatic carcinoma cells can serve as a basic material for the preparation of tumour vaccines. Human pancreatic carcinomas grown in nude mice were dissociated and stimulated with interferon-gamma and tocopherol acetate. Due to the very homogenous tumour material the yield of vital tumour cells even from small specimens was high enough to produce at least three vaccine doses each. Flow cytometric analyses of stimulated cells showed a significant increase in MHC I presenting cells compared to nonstimulated cells. These preliminary data suggest that beneath the successful application of tumor vaccines to renal carcinoma, melanoma, colon carcinoma and different gynaecological carcinomas pancreatic carcinoma could be a further candidate for this kind of therapy.

Animals↗