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T Ha

Publications and source records attributed to T Ha.

59 records · Page 4Linked to original sources

Hemoglobin-catalyzed transformation of elliptinium acetate into electrophilic species. Evidences for oxidative activation of the drug in human red blood cells.

The anti-tumor drug N2-methyl-9-hydroxyellipticinium acetate (NMHE, Celiptium) after incubation with various N or S containing amino acids (alanine, histidine, aspartic acid, cysteine, glutathione) with hemoglobin and hydrogen peroxide or an organic peroxide (terbutylhydroperoxide) leads to the formation of the corresponding covalent binding adducts, via an oxidative activation. The formation of the covalent adduct glutathione-elliptinium was also demonstrated in human red blood cells. The importance of such process under in vivo conditions is discussed.

Alkaloids↗

Neurite extension on dibutyryl cyclic AMP-stimulated astrocytes.

Although both central and peripheral neurons successfully regenerate cut axons along peripheral nerve and other suitable substrates, axonal elongation through the mature central nervous system (CNS) is limited. It has been proposed that the presence of reactive astrocytes formed in response to CNS injury act as a barrier to axonal regeneration. In contrast, in vitro, astrocytes in a flat or unstimulated state have been shown to be a preferred substrate for neurite extension. We have investigated whether induced modifications of astrocytes alter the capacity of these cells to act as a substrate for axonal elongation. Treatment with dibutyryl cyclic AMP (dBcAMP) results in a marked morphological and biochemical change in astrocytes, considered by some to be a model of reactive astrocytosis. Retinal and dorsal root ganglia explants from embryonic mice were cultured on top of untreated glial monolayers and those treated with dBcAMP. The subsequent neuritic growth was measured at 48 h. No difference was found between the groups, indicating that astrocytes are an excellent substrate for axonal growth, even after they develop a stellate shape and high levels of glial fibrillary acidic protein.

Animals↗

Ribose as the preferential target for the oxidized form of elliptinium acetate in ribonucleos(t)ides. Biological activities of the resulting adducts.

The covalent binding of the oxidized form of elliptinium acetate, an antitumor drug, to various ribonucleos(t)ides is described. In the absence of a strong nucleophile on the bases, e.g., a sulfhydryl group, the main target of this quinone imine derivative is the sugar moiety. With unmodified regular bases, the first electrophilic addition always occurs on the 2'-oxygen of ribose (more slowly for pyrimidine than for purine); in a second step, cyclization of the reoxidized product leads to a spiro derivative: only one stereoisomer is detected with purine nucleoside; the other stereoisomer appears as a minor product (10-20%) with nucleotides and pyrimidine nucleosides. With modified bases, no change is observed except for bases exhibiting an additional strong nucleophilic center: oxidized elliptinium alkylates thioguanine and thioguanosine on the sulfur atom and in this last case not on the ribose moiety. All spiro derivatives are less cytotoxic than the parent compound even if the base is an antimetabolite (azauridine); however, thio-elliptinium adducts maintain high cytotoxicity.

Alkaloids↗

Characterisation of a new cell line (CJ18) from a patient with 'hairy' cell leukaemia.

A cell line (CJ18) has been established from the peripheral blood of a patient with hairy cell leukaemia (HCL) in a leukaemic phase. They grow slowly in large clumps with a doubling time of 3-4 d. 8% show positivity for surface immunoglobulin G and a small percentage (5%) are positive for intracytoplasmic immunoglobulin. They are B1,Ia1 positive and CALL, TdT and OKM1 negative. Although they are Epstein Barr Virus Nuclear Antigen (EBNA) positive they have several features not found in other EBNA positive B lymphoblastoid cell lines which suggest they may be derived from the patient's leukaemic hairy cells. They are strongly positive for tartrate resistant acid phosphatase, esterase positive, contain numerous lysosomes and are able to phagocytose sheep red blood cells after exposure to tetradecanoyl-12, 13-phorbol acetate (TPA). Following exposure to retinoic acid and TPA they adhere to plastic with numerous slender processes, a feature seen in HCL cells.

Antibodies, Monoclonal↗

Keeping genetics simple.

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Genetic Predisposition to Disease↗