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L Swick

Publications and source records attributed to L Swick.

6 recordsLinked to original sources

Characterization of GTP cyclohydrolase I gene expression in the human neuroblastoma SKN-BE(2)M17: enhanced transcription in response to cAMP is conferred by the proximal promoter.

GTP cyclohydrolase I (GTPCH) gene expression was investigated in the human monoamine-containing neuroblastoma cell line SK-N-BE(2)M17. Northern blot analysis revealed a single GTPCH mRNA transcript that was confirmed by RNase protection assay to encode for Type 1 GTPCH; no alternatively spliced forms of GTPCH mRNA were detected with this assay. Incubation with 8Br-cAMP, but not nerve growth factor or leukemia inhibitory factor, produced a rapid increase in GTPCH mRNA and protein levels; protein levels remained elevated during the entire treatment period while mRNA content declined rapidly between 10 and 24 h. Treatment with 8Br-cAMP did not significantly modify the stability of GTPCH mRNA but did increase GTPCH transcription as determined by transient transfection assays of a luciferase reporter construct containing 1171 bp of human GTPCH 5'-flanking sequence. Cis-acting elements required for maximal basal and cAMP-dependent transcription were localized by deletion analysis to the 146 bp proximal promoter. DNase I footprint analysis of the proximal promoter using SK-N-BE(2)M17 nuclear extracts identified two protein binding domains: one an upstream Sp1-like site and the other a combined CRE-Sp1-CCAAT-box element. EMSA and supershift assays demonstrated that the combined CRE-Sp1-CCAAT-box element recruits ATF-2 and NF-Y but not Sp1-4 or Egr-1-3. NF-Y binding was confirmed using pure recombinant human NF-Y protein. Transcription of the human GTPCH gene in human SK-N-BE(2)M17 cells is thus enhanced by cAMP acting through regulatory elements located in the proximal promoter and may involve the transcription factors NF-Y and ATF-2.

8-Bromo Cyclic Adenosine Monophosphate↗

Reduced plasma concentrations of antituberculosis drugs in patients with HIV infection.

BACKGROUND: Reports suggest that antituberculosis drugs are malabsorbed in patients with advanced HIV disease. OBJECTIVE: To evaluate the pharmacokinetics of antituberculosis agents in HIV-seropositive patients at different stages of disease. DESIGN: Parallel study. SETTING: Two hospital outpatient clinics. PARTICIPANTS: 12 healthy volunteers, 12 patients with asymptomatic HIV disease, 12 patients with symptomatic HIV disease, and 12 patients with symptomatic HIV disease and diarrhea. MEASUREMENTS: Drug plasma concentrations were measured over 24 hours on day 4 of concurrent therapy. INTERVENTION: Oral isoniazid (300 mg/d), rifampin (600 mg/d), pyrazinamide (1000 mg/d), and ethambutol (1000 mg/d). RESULTS: Reduced total drug exposure to rifampin and pyrazinamide was associated with D-xylose malabsorption in persons with HIV infection or AIDS. Peak drug exposure to isoniazid was lower in patients with diarrhea. CONCLUSIONS: Reduced total drug exposure may be related to malabsorption in persons with HIV infection or AIDS.

Adult↗

Team-based organization: the fruits of employee empowerment.

Tennalum, a division of Kaiser Aluminum, received the 1995 Shingo Prize for Excellence in Manufacturing. The plant also received the 1995 Tennessee Quality Achievement Award, the criteria for which are based on the Malcolm Baldridge National Quality Award. In 1994, Tennalum received the Clemson University's 21st Century Organizational Excellence Award, 33 Metal Producing Magazine's T.O.P. Award, and the Tennessee Quality Interest Award, and it was a finalist in Industry Week magazine's Top 10 Plants in America. Tennalum also earned ISO-9002 certification during that year. This article explains how Tennalum's people work together as self-directed work teams in an atmosphere of empowerment, involvement, and continuous improvement that translates into outstanding performance results.

Employment↗

Effect of rifabutin on the pharmacokinetics of zidovudine in patients infected with human immunodeficiency virus.

We investigated the effects of rifabutin (300 mg daily administered for 7 or 14 days) on the pharmacokinetics of zidovudine in nine patients who were infected with human immunodeficiency virus (HIV). Serial blood and urine samples were collected over a 6-hour period on each day that the pharmacokinetics of zidovudine were studied. Pharmacokinetic parameters were determined for zidovudine and its glucuronide metabolite and compared with use of analysis of variance (ANOVA) appropriate for a repeated-measures design. Except for a statistically significant decrease (28%) in the terminal half-life of zidovudine from 1.5 to 1.1 hours (P = .005) after coadministration of both agents for 14 days, concurrent administration of rifabutin for 7 or 14 days had no statistically significant effects on zidovudine plasma and urine pharmacokinetic parameters (the difference among treatment means was < 25%). Treatment with rifabutin is unlikely to influence the effectiveness of treating HIV-infected patients with zidovudine because of any pharmacokinetic interaction between these drugs.

Adult↗

Human suppressor lymphocytes. II. Changes in concanavalin A inducible suppressor cells with age.

Suppressor cells were induced in peripheral blood mononuclear cells from young and old individuals by two day culture with Concanavalin A (Con A). Suppressor activity was quantitated using an alloantigen driven cytotoxicity assay. The proliferative responses of lymphocytes from young and old individuals to Con A and alloantigens were also determined. Results demonstrated that the numbers of Con A inducible suppressor cells were markedly decreased but equivalent proliferative responses to Con A were reduced compared to young individuals but equivalent proliferative responses to alloantigens were noted. Even though not statistically significant, alloantigen-induced cytotoxic responses were slightly increased in older persons. The increased alloantigen-induced cytotoxic responses of individuals noted in the present study may be related to the decreased numbers of suppressor cells in this group.

Adult↗