PubMed · 9820292
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
D E Goodkin. 1998-11-07. Interferon beta therapy for multiple sclerosis.. https://doi.org/10.1016/s0140-6736(98)00057-9
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
FK506-induced polyneuropathies are rarely encountered. We report a case of axonal sensorimotor polyneuropathy in a lung transplant recipient that occurred during a FK506 overdosage. Onset was acute in the form of severe areflexic tetraparesis and resolution was observed after reduction of dosage. Because of increasing use of FK506 in solid organ transplantation, caution should be paid with FK506 dosage monitoring in cases of peripheral nervous system symptoms.
Results from our previous studies have demonstrated regulatory effects of estradiol on human gonadotropin-releasing hormone (GnRH) gene expression in human placental cells. The present study was designed to determine the molecular mechanisms whereby estrogens regulate the human GnRH gene expression in the placenta. The effects of estradiol on human GnRH upstream promoter activity in JEG-3 cells depends on the amounts of estrogen receptor (ER) alpha expression vector co-transfected, with the maximal effect obtained at the amount of 1.0 microg of ER expression vector cotransfected. Estriol, an isoform of estradiol, also possesses a regulatory effect on the upstream promoter activity, while estrone, another isoform, does not. Serial deletion studies revealed two estrogen responsive elements in the GnRH upstream promoter region. One element (-987 to -968 bp, E4 element) confers a negative estradiol response, while another one (-827 to -730 bp) is responsible for a positive estradiol effect. Replacement of these two elements with unrelated DNA sequences could abolish the responsiveness to estradiol treatment. Furthermore, footprinting and gel shift assays demonstrated that nuclear protein from estradiol-treated JEG-3 cells, but not from control cells, could bind to a 41 bp DNA fragment (-824 to -784 bp) within the estrogen positive responsive element. Results of gel-shift assay demonstrated that other protein(s) might also be involved in interacting the E4 element to mediate the negative effect of estradiol on the hGnRH upstream promoter activity in JEG-3 cells.
Zidovudine (ZDV) is a thymidine analogue activated to its triphosphate (ZDVTP) by the host's intracellular enzymes. The initial phosphorylation step is conversion to ZDV monophosphate (ZDVMP). The poor affinity of ZDVMP for thymidylate kinase results in intracellular accumulation of ZDVMP. Clinical use of ZDV is associated with cytotoxicity, thought to be mediated through mitochondrial damage. It has been suggested that ZDV cytotoxicity correlates with intracellular ZDVMP. Here we have further studied the role of ZDVMP in cytotoxicity and some of the mechanisms involved. Intracellular metabolism of ZDV in five lymphocyte/monocyte cell lines, U937, BSM, MOLT 4, JJAHN, and RAJI (4 x 10(6) cells), was investigated following 24 h incubation with [(3)H]ZDV (1.2 microCi; 0.1 microM) and cytotoxicity was determined by the MTT assay. Cytotoxicity was closely related to intracellular concentrations of the major metabolite (ZDVMP) but not with the active metabolite ZDVTP. ZDVMP was the only metabolite detected following incubation of viable mitochondria isolated from U937 cells with ZDV (1.2 microCi; 0.1 microM; 24 h) with mitochondrial levels of 0.27 +/- 0.11 pmol/microg protein (mean +/- SD; n = 3). No MTT toxicity was seen in isolated mitochondria. Following phytohemagglutinin (PHA) stimulation of peripheral blood mononuclear cells there was an increase in ZDV cytotoxicity compared to unstimulated cells. The results suggest that the mitochondrial isozyme of thymidine kinase (TK2) plays only a minor part in ZDVMP formation. Following PHA stimulation, activation of the cytosolic thymidine kinase isozyme (TK1) is associated with increased toxicity of ZDV. We conclude that ZDVMP responsible for mitochondrial toxicity is formed in the cytosol.