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Biomedical subjects

S Dowell

Publications and source records attributed to S Dowell.

At least 19 recordsLinked to original sources
PubMed2003

Complex chimeras to map ligand binding sites of GPCRs.

Family 1a GPCRs are thought to bind small molecule ligands in a pocket comprising sequences from non-contiguous transmembrane helices. In this study, receptor-ligand binding determinants were defined by building a series of complex chimeras where multiple sequences were exchanged between related G-protein coupled receptors. Regions of P2Y(1), P2Y(2) and BLT(1) predicted to interact with nucleotide and leukotriene ligands were identified and receptors were engineered within their transmembrane helices to transpose the ligand binding site of one receptor on to another receptor. Ligand-induced activation of chimeras was compared with wild-type receptor activation in a yeast reporter gene assay. Binding of ligand to a P2Y(2)/BLT(1) chimera confirmed that the ligand binding determinants of BLT(1) are located in the upper regions of the helices and extracellular loops of this receptor and that they had been successfully transferred to a receptor that normally binds unrelated ligands.

Amino Acid Sequence↗
PubMed2001

Comparison of two commercial microimmunofluorescence kits and an enzyme immunoassay kit for detection of serum immunoglobulin G antibodies to Chlamydia pneumoniae.

We compared the MRL and the Labsystems Chlamydia pneumoniae microimmunofluorescence (MIF) immunoglobulin G (IgG) kits and the Labsystems enzyme immunoassay (EIA) kit in a blinded study of 83 serum samples in which we evaluated titers, cross-reactivity to other species, and reproducibility. There was no statistically significant difference between the MRL and the Labsystems MIF kits in the endpoint titers of IgG antibody to C. pneumoniae. The correlation between the results obtained with these two MIF kits was excellent (r = 0.95; P = 0.001). The cross-reactivity of the C. pneumoniae-positive sera with C. trachomatis- and C. psittaci-positive sera was assessed for each MIF kit. For C. pneumoniae-positive sera with titers of > or =32, the Labsystems MIF kit exhibited more cross-reactivity to C. psittaci than the MRL kit did. The values obtained with the Labsystems EIA kit represented single dilutions of serum specimens expressed as enzymeimmuno units on a continuous scale. The results obtained with the Labsystems EIA kit correlated moderately well with those obtained with each MIF kit when they were compared for their abilities to detect IgG antibodies to C. pneumoniae (for the MRL MIF kit, r = 0.79 [P = 0.001]; for the Labsystems MIF kit, r = 0.78 [P = 0.001]). The results obtained with the commercial MRL and Labsystems MIF kits and the Labsystems EIA kit tested were reproducible; and the kits were standardized, had quality control reagents, and are suitable for detection of C. pneumoniae antibodies in serum and for use in interlaboratory studies. Validation of the use of these kits for clinical diagnosis still needs further evaluation.

Antigens, Bacterial↗
PubMed1998

Mutagenesis of human Mel1a melatonin receptor expressed in yeast reveals domains important for receptor function.

A yeast functional colorimetric assay was employed to test the effects of site-directed point mutations on the function of the human Mel1a melatonin receptor. Seven mutants were created in transmembrane domains III, V, and VII of the receptor to test the rhodopsin-based model of melatonin recognition. Two mutants in transmembrane domains III and VI were created to investigate the mechanisms of G protein activation in the melatonin receptor. Mutations in transmembrane domain V either potentiated agonist efficiencies (H195A) or totally abolished all responses to tested compounds (V192T+H195A). Mutation N124A in the conserved NRY motif in the end of transmembrane domain III seriously impaired receptor activation. Several mutants were found to have decreased ability to activate functional responses, reflecting the importance of these residues for receptor function. These data also suggest that activation of the receptor involves interaction of the 5-methoxy group of melatonin with the conserved histidine H195 in transmembrane domain V.

Binding Sites↗
PubMed1998

Vitamin D and its major metabolites: serum levels after graded oral dosing in healthy men.

We determined the quantitative relationships between graded oral dosing with vitamin D3, 25(OH)D3, and 1,25(OH)2D3 for short treatment periods and changes in circulating levels of these substances. The subjects were 116 healthy men (mean age, 28 +/- 4 years, with usual milk consumption of < or = 0.47 l/day and mean serum 25(OH)D of 67 +/- 25 nmol/l). They were distributed among nine open-label treatment groups: vitamin D3 (25, 250 or 1250 micrograms/day for 8 weeks), 25(OH)D3 (10, 20 or 50 micrograms/day for 4 weeks) and 1,25(OH)2D3 (0.5, 1.0 or 1.0 microgram/day for 2 weeks). All treatment occurred between January 3 and April 3. We measured fasting serum, calcium, parathyroid hormone, vitamin D3, 25(OH)D and 1,25(OH)2D immediately before and after treatment. In the three groups treated with vitamin D3, mean values for circulating vitamin D3 increased by 13, 137 and 883 nmol/l and serum 25(OH)D increased by 29, 146 and 643 nmol/l for the three dosage groups, respectively. Treatment with 25(OH)D3 increased circulating 25(OH)D by 40, 76 and 206 nmol/l, respectively. Neither compound changed serum 1,25(OH)2D levels. However, treatment with 1,25(OH)2D3 increased circulating 1,25(OH)2D by 10, 46 and 60 pmol/l, respectively. Slopes calculated from these data allow the following estimates of mean treatment effects for typical dosage units in healthy 70-kg adults: an 8-week course of vitamin D3 at 10 micrograms/day (400 IU/day) would raise serum vitamin D by 9 nmol/l and serum 25(OH)D by 11 nmol/l; a 4-week course of 25(OH)D3 at 20 micrograms/day would raise serum 25(OH)D by 94 nmol/l; and a 2-week course of 1,25(OH)2D3 at 0.5 microgram/day would raise serum 1,25(OH)2D by 17 pmol/l.

Adult↗
PubMed1996

Ground zero: Ebola.

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Centers for Disease Control and Prevention, U.S.↗
PubMed1993

AHIMA (American Health Information Management Association) executives expand their role in electronic record issues. Interview by Carolyn Dunbar.

Four of the top leaders in the American Health Information Management Association met with Computers in Healthcare, detailing their coalition-building efforts to make the computer-based patient record a reality. They reinforce their belief in the eventual reality of the CPR and its security, and call for sanctions and penalties for those who misappropriate or misuse patient records.

Confidentiality↗
PubMed1992

Treatment of intestinal microsporidiosis with albendazole in patients with AIDS.

OBJECTIVE: To determine the clinical and parasitological response to treatment of intestinal microsporidiosis with albendazole. DESIGN: Open prospective study. SETTING: Hospital-based HIV/genito-urinary medicine unit. PATIENTS, PARTICIPANTS: Six consecutive AIDS patients with small intestinal microsporidiosis as the only identified cause of diarrhoea after intensive gastrointestinal investigations. RESULTS: Diarrhoea resolved completely in all patients within 1 week of starting treatment, and body weight stabilized or increased. Four patients who relapsed at 19-31 days after the cessation of treatment responded to a second course of albendazole. Degenerative changes occurred in the parasites after treatment, which had not been seen either in pre-treatment biopsies or, in four patients, following therapy with other drugs. CONCLUSIONS: Albenazole is a useful palliative treatment for microsporidial diarrhoea.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Leadership logic.

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Leadership↗
PubMed1990

Perioperative and long-term prognostic value of intravenous dipyridamole thallium scintigraphy in patients with peripheral vascular disease.

The prognostic value of long-term risk stratification of patients with peripheral vascular disease who undergo intravenous dipyridamole thallium scintigraphy has not been well studied. We screened 131 patients with peripheral vascular disease who underwent intravenous dipyridamole thallium testing to determine cardiac event rates over an average follow-up of 18 +/- 10 months. Of the 131 patients, 111 subsequently had peripheral vascular surgery. The patients with abnormal thallium scans after dipyridamole had a significantly higher risk of death or myocardial infarction, both in the perioperative phase (7% versus 0%; p less than 0.001) and at late follow-up (17% versus 6%; p less than 0.01). The risk of a cardiac event was two-fold greater when a reversible as compared to a fixed thallium defect was present. Multivariate analysis selected the number of thallium segments with perfusion defects, prior history of angina pectoris, and chest pain during dipyridamole testing as perioperative predictors of a cardiac event. A reversible thallium defect was the only predictor of death or nonfatal myocardial infarction during late follow-up. Thus intravenous dipyridamole thallium scintigraphy is a useful noninvasive test for risk stratification of patients before peripheral vascular surgery and provides prognostic information as to the risk of a cardiac event in the 2-year period after the test. A reversible thallium defect is associated with a significant increased risk and would indicate that coronary angiography should be considered and preoperative coronary revascularization.

Aged↗
PubMed1990

Crossbow injuries.

The crossbow is an uncommon source of fatal injury. In Los Angeles County, two crossbow homicides have occurred in the past 20 years. Following the second case, a crossbow was test-fired into a fresh pork thigh, resulting in distinctive wounds. Experimental studies also showed that the vanes of the bolt (arrow) may be a source of trace material found in the wound.

Adult↗