Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0268596 (EMA)
 2,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Benztropine and its analogs are tropane ring-containing dopamine uptake inhibitors that produce behavioral effects markedly different from cocaine and other dopamine transporter blockers. We investigated the benztropine binding site on dopamine transporters by covalently attaching a benztropine-based photoaffinity ligand, [125I]N-[n-butyl-4-(4"'-azido-3"'-iodophenyl)]-4', 4"-difluoro-3alpha-(diphenylmethoxy)tropane ([125I]GA II 34), to the protein, followed by proteolytic and immunological peptide mapping. The maps were compared with those obtained for dopamine transporters photoaffinity labeled with a GBR 12935 analog, [125I]1-[2-(diphenylmethoxy)ethyl]-4-[2-(4-azido-3-iodophenyl)ethy l]p iperazine ([125I]DEEP), and a cocaine analog, [125I]3beta-(p-chlorophenyl)tropane-2beta-carboxylic acid, 4'-azido-3'-iodophenylethyl ester ([125I]RTI 82), which have been shown previously to interact with different regions of the primary sequence of the protein. [125I]GA II 34 became incorporated in a membrane-bound, 14 kDa fragment predicted to contain transmembrane domains 1 and 2. This is the same region of the protein that binds [125I]DEEP, whereas the binding site for [125I]RTI 82 occurs closer to the C terminal in a domain containing transmembrane helices 4-7. Thus, although benztropine and cocaine both contain tropane rings, their binding sites are distinct, suggesting that dopamine transport inhibition may occur by different mechanisms. These results support previously derived structure-activity relationships suggesting that benztropine and cocaine analogs bind to different domains on the dopamine transporter. These differing molecular interactions may lead to the distinctive behavioral profiles of these compounds in animal models of drug abuse and indicate promise for the development of benztropine-based molecules for cocaine substitution therapies.
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PMID:Differential binding of tropane-based photoaffinity ligands on the dopamine transporter. 988 May 83

We report an unusual case of systemic anaplastic large cell lymphoma (ALCL), ALK positive with leukemic involvement in a 57-year-old woman. The patient presented with a fulminant respiratory infection unresponsive to treatment requiring intensive care and ventilatory support. The CT scan demonstrated mediastinal and bilateral lymphadenopathy. On peripheral smear a few atypical lymphocytes were visualized. Based on the increasing number of atypical lymphocytes in the daily peripheral bloodsmears, the diagnosis ALCL was suggested. Definitive diagnosis was made on a bone marrow biopsy, with lymphocytes being immunoreactive for CD30, EMA, and ALK. Leukemic peripheral blood involvement in ALCL is an uncommon clinicopathologic entity with unfavorable prognosis. The case we present is perhaps unusual in that a complete respons was achieved, highlighting the importance of prompt diagnosis and judicious management.
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PMID:The masquerading presentation of a systemic anaplastic large cell lymphoma, ALK positive: a case report and review of the literature. 2844 13