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J J Marr

Publications and source records attributed to J J Marr.

107 records · Page 6Linked to original sources
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Chemotherapy for Chagas' disease: a perspective of current therapy and considerations for future research.

Our current knowledge of the biology of Trypanosoma cruzi and its relation to the development of chemotherapy for Chagas' disease are reviewed. This includes recent developments in the understanding of kinetoplast DNA and glycosomes; the action of oxygen radicals; intermediary metabolism of purines, pyrimidines, and folic acid; and the formation of microtubules. At this time, these organelles and metabolic pathways appear to be the most promising for potential exploitation for chemotherapeutic purposes. Compounds of current experimental interest also are discussed. These are agents that have shown promise in the laboratory and for which data exist regarding probable mechanisms of action. The activities of these agents correlated, in so far as is possible, with those structures or metabolic pathways in the trypanonsome that are affected by their actions. The compounds are of two general groups: nitro compounds and purine analogues.

Animals↗
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Purine nucleoside and nucleobase cell membrane transport in Giardia lamblia.

Giardia lamblia is dependent on the salvage of preformed purines and pyrimidines. This study investigated purine nucleoside and nucleobase transport utilizing rapid uptake determinations. Nucleoside substrate/velocity curves exhibited the hyperbolic kinetics of a saturable carrier-mediated system. Deoxynucleosides exhibited a much lower affinity for the transporter. Inhibition studies confirmed the relative carrier affinities of these ribonucleosides and deoxyribonucleosides. The nucleobase adenine did not exhibit saturation kinetics at a comparable substrate range, and did not inhibit nucleoside transport. Dipyridamole markedly inhibited nucleoside but not nucleobase transport, confirming the separate entry pathways. When cells were depleted of ATP, the velocity of nucleoside and nucleobase transport was unchanged, indicating that it is a non-energy-dependent process. Three nucleoside analogs, formycin A, adenine arabinoside and 7-deazaadenosine, were studied. Transport kinetics ranged widely among this group and could not completely account for their cytotoxic effect. When the apparent Km and Vmax of the nucleosides were compared, an approximately linear relationship (r2 = 0.95) was noted. This suggests that a high affinity of the nucleoside permease for the substrate retards disassociation of the substrate-carrier complex, slowing net influx.

Adenosine↗