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Biomedical subjects

M W Watson

Publications and source records attributed to M W Watson.

30 records · Page 2Linked to original sources
PubMed1989

Chlamydia trachomatis 60 kDa cysteine rich outer membrane protein: sequence homology between trachoma and LGV biovars.

An 820 bp AccI-PstI fragment of the 60 kDa cysteine rich outer membrane protein (CrP) gene from C. trachomatis serovar L1 was used as a probe to locate the 60 kDa CrP gene of a recent serovar B trachoma isolate (Jali 20/OT). The probe hybridized to a single 1.8 kb SpeI fragment in Southern blot analyses of different restriction endonuclease digests of C. trachomatis serovar B DNA. This fragment was ligated into Lambda Zap II arms and Bluescript SK(-) recombinants, released by infection with the helper phage R408, were used as template for DNA sequence determination. Sequence analysis demonstrated a very high level of homology between the Jali 20/OT 60 kDa CrP and the previously published serovar L1 60 kDa CrP with only 8 out of 507 amino acid substitutions between the two proteins.

Amino Acid Sequence↗
PubMed1988

Treatment of tardive dyskinesia: preliminary report on use of tetrabenazine.

Tetrabenazine has been used for treatment of tardive dyskinesia sporadically over the past twenty years. Dose has usually been decided empirically without assaying blood levels. This report describes 23 cases treated successfully with tetrabenazine. Our method of measuring levels of tetrabenazine and its metabolites in biological samples is described briefly.

Adult↗
PubMed1986

Direct injection high-performance liquid chromatography of tetrabenazine and its metabolite in plasma of humans and rats.

A convenient, selective, and sensitive reversed-phase HPLC assay was developed to measure concentrations of the dopamine-depleting agent, tetrabenazine (1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy-2H-benzo(a)quinoli zin-2-one) and its dihydro metabolite in the plasma of patients with tardive dyskinesia receiving therapeutic doses of the drug and in the plasma of rats. The method involves plasma protein precipitation, oxidation of the compounds with mercuric acetate at 110 degrees C for 1 h, addition of internal standard, and injection into the instrument. Fluorescence detection was utilized at excitation and emission wavelengths of 265 and 418 nm, respectively. The peaks from the drug, its metabolite, and at least three other substances were best resolved at 60 degrees C using a mobile phase of water:acetonitrile:acetic acid:triethylamine (65:33:2:0.15) at a flow rate of 0.6 mL/min; the 4.6 mm X 10 cm column contained 5 micron of octadecylsilane packing. To assess the applicability of the assay, the drug was administered intravenously to rats, and plasma concentrations were determined before (by UV-HPLC) and after (by fluorescence-HPLC) the oxidative procedure. In addition, the MS spectra of tetrabenazine and the dihydro metabolite, isolated from biological samples, were identical to those of authentic samples. Excellent linearity was observed between the peak area ratios and concentrations over the ranges 0.5-200 and 2-1000 ng/mL of the drug and the metabolite, respectively. Minimum quantifiable concentrations of the drug and its metabolite were 0.5 and 2.0 ng/mL, respectively. The sensitivity was found to be adequate for pharmacokinetic studies of tetrabenazine in humans and rats.

Animals↗
PubMed1984

Agents and recipient objects in the development of early symbolic play.

The development of 2 components of early symbolic play--children's symbolic transformations of agents of action and recipient objects of action--was assessed in 48 children from 14 to 25 months of age. A 5-step sequence was predicted based on a combined weighting of agent substitutions and recipient object substitutions in each step. Children observed an adult model who pretended to talk into a telephone using each agent and object substitution in all combinations and then were allowed to demonstrate their own imitative pretending for each step. Based on the children's profiles of steps passed and failed, the sequence was found to form a Guttman scale and be age related. 2 types of possible underlying sequences were discussed.

Child Development↗
PubMedDate not supplied

The relationship of self-esteem to the health-related behaviors of the patients of a primary care clinic.

To clarify the relationship of self-esteem and health-related behaviors of primary care clinic patients, 500 family practice residency patients were invited to complete self-esteem and health-risk appraisal instruments. Of the final subject pool (N = 469), 154 responded to the single-mailing solicitation, thereby yielding a 32.8% response rate. Correlational analysis found self-esteem to be associated with predicted longevity, life satisfaction, social ties, overall health, personal loss, seatbelt use, age, physical activity, smoking, exposure to violence, and substance use. Multiple regression analysis of male subjects' data found self-esteem most closely related to the frequency of exposure to danger, self-perceptions of health, and tobacco use. Similar analysis of the women's data most closely associated self-esteem to perceived social support, self-perception of health, diastolic blood pressure, and seatbelt use. The data clearly link individuals' self-esteem to predicted longevity. Those with greater self-regard were predicted to live longer, while those with poorer self-esteem achieved shorter predicted longevity. Contributing factors may have included greater emphasis on self-care.

Adult↗
PubMedDate not supplied

Pharmacokinetics of tetrabenazine and its major metabolite in man and rat. Bioavailability and dose dependency studies.

The pharmacokinetics of tetrabenazine (TBZ), a catecholamine and serotonin depletor, and its major metabolite, dihydrotetrabenazine (HTBZ), were studied in four patients affected by tardive dyskinesia, who were under treatment with different doses of TBZ (12.5-37.5 mg, t.i.d.), and in the rat. In the patients, the steady-state area under the plasma concentration-time curves (AUCs) of the metabolite were 82.6-199-fold higher than those of TBZ. The drug showed a small and erratic bioavailability (F = 0.06 +/- 0.026, mean +/- SD). It appears to be extensively metabolized, as no unchanged TBZ could be detected in the urine of the patients. Single oral doses of 0.5-10 mg/kg and single iv dose of 1 mg/kg of TBZ were each administered to four to six rats. The clearance of the drug following iv administration to the rat (mean +/- SD, 58.9 +/- 6.01 ml X min-1 X kg-1) was very close to the rat hepatic blood flow indicating a perfusion-limited clearance. An F value of 0.17 was obtained following iv and po doses of 1 mg/kg TBZ in the rat. The oral absorption of TBZ seems to be rapid and almost complete. Plots of the AUCs of TBZ and HTBZ vs. five different po doses (0.5-10 mg/kg) were linear with correlation coefficients of 0.998 and 0.986 for TBZ and HTBZ, respectively, suggesting linear kinetics in the examined dosage range. In both the patients and rats, the plasma profile of TBZ followed characteristics of a multiexponential pharmacokinetic model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗