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Biomedical subjects

S Gould

Publications and source records attributed to S Gould.

At least 73 records · Page 4Linked to original sources

Firefly luciferase is targeted to peroxisomes in mammalian cells.

Although several enzymes known to reside in peroxisomes have been studied extensively, no cis-acting amino acid sequences involved in the transport of these proteins to peroxisomes have been described. As a first step towards the determination of a putative peroxisomal targeting sequence, we have expressed the cDNA encoding the firefly luciferase [Photinus-luciferin:oxygen 4-oxidoreductase (decarboxylating, ATP-hydrolyzing), EC 1.13.12.7] in monkey kidney cells and found that the product of the gene is transported to peroxisomes. Luciferase is derived from the firefly (Photinus pyralis) and is synthesized and stored in the cells of the firefly's lantern organ, where it is also found in peroxisomes. The fact that this protein is similarly targeted in cells from such different organisms suggests that the process of protein transport to peroxisomes has been highly conserved through evolution.

Animals↗

Pharmacokinetics of ketanserin and its metabolite ketanserin-ol in man after intravenous, intramuscular and oral administration.

The pharmacokinetics of ketanserin (R 41 468), a novel serotonin S2-receptor blocking agent widely investigated for its effect on acute and chronic hypertension, has been studied in 10 healthy male subjects. They received single 10 mg doses i.v. and i.m., and 20, 40 and 60 mg solutions of ketanserin by mouth, in a five-way cross-over design. The model-independent kinetics of i.v. ketanserin were characterized by a terminal half-life of 14.3 +/- 4.4 h, a moderate plasma clearance (CL = 565 +/- 57 ml/min) and a large tissue distribution (Vss = 268 +/- 71 l, Vz = 703 +/- 204 l; mean +/- SD). Following i.m. administration, peak levels of nearly 200 ng/ml were attained within 10 minutes and the absolute bioavailability was 112 +/- 23%. After oral dosing, peak levels of ketanserin were reached within 1 h. The peak level and AUC increased in proportion to the dose. The absolute bioavailability was 46.8, 50.4 and 55.5% for 20, 40 and 60 mg doses and they conformed to the predicted bioavailability based on i.v. clearance data. The terminal half-life of 17 h and the urinary excretion of parent drug (about 0.7% of the dose) were similar after oral and parenteral dosing. The kinetics of ketanserin-ol, the major metabolite of ketanserin formed by ketone reduction, was also studied. Because of its negligible pharmacological activity, the contribution of ketanserin-ol to the overall therapeutic effect of ketanserin is small, in spite of its 1.6-times (parenteral) to 3.2-times (oral) higher plasma level than that of ketanserin.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

The relationship of dopamine receptor blockade to clinical response in schizophrenic patients treated with pimozide or haloperidol.

Pimozide and haloperidol were found to be equally effective in the treatment of acute schizophrenia in a double-blind clinical trial involving 22 patients. Drug plasma levels measured by radioimmunoassay (RIA) did not correlate with clinical response following either drug. Nor was there any correlation between clinical response and the dopamine receptor blocking activity of either drug as measured by radio receptor assay (RRA). Following pimozide plasma prolactin (PRL) levels correlated with clinical change, although the time courses of response of PRL and clinical response were dissimilar. There was no correlation between PRL and clinical response to haloperidol. RRA and RIA values correlated highly following pimozide but not haloperidol. Our findings lead us to conclude that the RRA technique reflects the plasma level of a drug rather than its central dopamine blocking activity. We also consider that the clinical response to antipsychotic drugs in schizophrenia may be less directly linked to dopamine receptor blockade than has previously been supposed.

Acute Disease↗

On stillbirth.

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Clergy↗

Pulmonary extraction of biogenic amines during septic shock.

The effect of live Escherichia coli on the pulmonary extraction of the biogenic amines 14C 5-hydroxytryptamine, (5-HT) and 3H-epinephrine was investigated. The labeled isotopes were injected into a central venous catheter and collected from an aortic catheter. One hundred per cent of the labeled epinephrine was recovered in the control and septic state. Only 32.8 +/- 3.6% SEM of the 5-hydroxytryptamine was recovered before sepsis and 42.5 +/- 4.9% SEM after sepsis. During sepsis, mean arterial pressure fell to 58 mm Hg from 121 mm Hg. Pulmonary shunt increased from .7 +/- .05 SEM to .33 +/- .09 SEM.

Animals↗

Cardiac output response to extreme hemodilution with hemoglobin solutions of various P50 values.

Cardiovascular responses have been studied in baboons, after total exchange transfusion with hemoglobin solutions having various P50 values. At the end of the exchange transfusion, the hematocrit was 1.5%, the mean hemoglobin concentration was 4.4 g/dl, and the P50 varied between 12 and 26 mm Hg. Cardiac output did not change during the study, although heart rate increased, and stroke volume and MAP decreased. Hemoglobin concentration, per se, does not appear to be the critical stimulus for an increase in cardiac output with hemoglobin solution. In addition, the position of the hemoglobin-oxygen dissociation curve does not appear to influence these hemodynamic responses. The physiological response to anemia in the presence of hemoglobin solution appears different from that observed in the absence of plasma O2 carriers.

Anemia↗

Role of androgenic hyperactivity in anovulation.

In the course of an investigation of 60 patients with clomiphene-resistant anovulation, 35 cases of androgenic hyperacitvity were detected. Fractionation of urinary 17-ketosteroids (17-KS) by a rapid method of chromatography proved to be both practical and reliable for the detection and classification of androgenic disorders of adrenal, ovarian, or mixed origin. In contrast to the total 17-KS values, the fractionated 17-KS values were elevated in all but one of these cases. Following dexamethasone suppression, individual 17-KS showed significant decreases in both adrenal and mixed adrenal-ovarian cases, in contrast to ovarian cases in which no significant change was detected. Human chorionic gonadotropin (HCG) stimulation combined with dexamethasone suppression did not cause any significant change in individual 17-KS values in the adrenal group, whereas both the mixed adrenal-ovarian and ovarian cases showed significant increases. Of 34 treated patients, 22 conceived, 21 had normal deliveries, and 1 aborted. Twelve became ovulatory. Eleven patients were treated with dexamethasone, nineteen with combined dexamethasone and clomiphene, two with dexamethasone and HCG, and two with HCG only.

17-Hydroxycorticosteroids↗

Organizational career stage as a moderator of the satisfaction-performance relationship.

The relationship between performance and dimensions of job satisfaction is studied among 132 employees of a public agency located in a large southwestern city. The results of this study indicate that the relationship between performance and a particular dimension of job satisfaction may be a function of an individual's career stage within the organization.

Career Mobility↗

Mood changes in puerperium, and plasma tryptophan and cortisol concentrations.

Eighteen women aged 18-31 years were studied daily during the second to fifth postpartum days to assess mood changes and plasma tryptophan and cortisol concentrations. Psychiatric rating scales, clinical interviews, and published biochemical methods were used. Over the period plasma free tryptophan concentrations tended to rise and plasma cortisol concentrations to decline. There was a positive correlation between plasma free tryptophan concentrations and mood state.

Adolescent↗

Experimental studies with Staphylococcus aureus in M-K media.

This study reviewed the potential for survival of a pathogenic bacteria when inoculated into McCarey-Kaufman modified tissue culture media 199. A clinically isolated specimen of Staphylococcus aureus was selected and rabbit eyes inoculated with 0.1 ml. of the organism in a suspension of 1 to 3 x 10(-5). Upon enucleation 12 hours later no clinical signs of infection were noted. Limbal-conjunctival cultures were obtained on all eyes before and after application of the antibiotic. Corneas were stored in M-K media with standard penicillin-streptomycin added and cultured up to 48 hours. Our studies showed some recovery of the infecting organism from the media with topical antibiotic application but none following complete immersion of eyes in antibiotic. Direct cultures from corneal buttons taken 48 to 72 hours after antibiotic application by either method showed 1 to 3 colonies per plate in 25 per cent of eyes. In this study improperly applied antibiotic allowed some survival of S. aureus in the media.

Animals↗