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Biomedical subjects

R Fox

Publications and source records attributed to R Fox.

At least 55 records · Page 3Linked to original sources
PubMed1994

Thermodynamic characterization of an equilibrium folding intermediate of staphylococcal nuclease.

High-sensitivity differential scanning calorimetry and CD spectroscopy have been used to probe the structural stability and measure the folding/unfolding thermodynamics of a Pro117-->Gly variant of staphylococcal nuclease. It is shown that at neutral pH the thermal denaturation of this protein is well accounted for by a 2-state mechanism and that the thermally denatured state is a fully hydrated unfolded polypeptide. At pH 3.5, thermal denaturation results in a compact denatured state in which most, if not all, of the helical structure is missing and the beta subdomain apparently remains largely intact. At pH 3.0, no thermal transition is observed and the molecule exists in the compact denatured state within the 0-100 degrees C temperature interval. At high salt concentration and pH 3.5, the thermal unfolding transition exhibits 2 cooperative peaks in the heat capacity function, the first one corresponding to the transition from the native to the intermediate state and the second one to the transition from the intermediate to the unfolded state. As is the case with other proteins, the enthalpy of the intermediate is higher than that of the unfolded state at low temperatures, indicating that, under those conditions, its stabilization must be of an entropic origin. The folding intermediate has been modeled by structural thermodynamic calculations. Structure-based thermodynamic calculations also predict that the most probable intermediate is one in which the beta subdomain is essentially intact and the rest of the molecule unfolded, in agreement with the experimental data. The structural features of the equilibrium intermediate are similar to those of a kinetic intermediate previously characterized by hydrogen exchange and NMR spectroscopy.

Calorimetry, Differential Scanning↗
PubMed1994

Outcome of inadvertent administration of a gonadotrophin-releasing hormone agonist (buserelin) in early pregnancy.

All women undergoing pituitary down-regulation before planned in-vitro fertilization (IVF) treatment in two IVF units were studied to assess the risks of and to pregnancies occurring inadvertently when gonadotropin-releasing hormone agonists (GnRHa) were used to achieve pituitary desensitization during the luteal phase prior to planned IVF treatment. In 2670 cycles, 25 women conceived (0.9% of cycles). Of these, three resulted in pre-clinical abortions (12%) but there were no clinical abortions, and 22 have ended with live births at term of apparently normal infants. Collation of these and other published data suggest that pregnancy outcome is not adversely affected by GnRHa administration in the luteal phase of the conception cycle.

Abortion, Spontaneous↗
PubMed1994

Multiple follicular development associated with herbal medicine.

After three endocrinologically normal cycles while undergoing unstimulated in-vitro fertilization treatment, a woman took a herbal medicine (Vitex agnus castus) at the beginning of a fourth unstimulated IVF treatment cycle. In this fourth cycle, her serum gonadotrophin and ovarian hormone measurements were disordered. One embryo resulted from the three eggs collected but a pregnancy did not ensue. She had symptoms suggestive of mild ovarian hyperstimulation syndrome in the luteal phase. Two subsequent cycles were endocrinologically normal. We do not advocate the use of this herbal medicine to promote normal ovarian function.

Adult↗
PubMed1994

Seroconversion in patients attending sexually transmitted disease clinics.

OBJECTIVES: To characterize recent HIV seroconverters in a sexually transmitted disease (STD) clinic population, and examine changing transmission patterns. METHODS: We conducted a case-control study nested within a retrospectively defined cohort of individuals attending Baltimore STD clinics between January 1988 and July 1990. Seroconverters, who tested HIV-positive after having a negative test, were compared to both HIV-negative controls, who were also tested twice, and a second, prevalent HIV-positive control group. Controls were matched 2:1 by sex, clinic, and month of HIV test. RESULTS: Forty-nine out of 6175 (0.79%) patients tested at least twice had documented HIV-1 seroconversion. On multivariate analysis, seroconversion was significantly associated with self-reported injecting drug use [odds ratio (OR), 7.3; 95% confidence interval (CI), 2.3-23)], with being a man who has had sex with other men (OR, 3.5%; 95% CI, 1.2-10), or with having sex with a known HIV-infected person (OR, 11; 95% CI, 1.3-96). Thirty-five per cent of seroconverters did not report a risk for HIV infection, and a higher proportion of recent seroconverters also reported no risk. Compared to the prevalent positive control group, more seroconverters reported no risk and a lower proportion reported recognized risks. A diagnosis of gonorrhea was also significantly associated with seroconversion (OR, 2.5; 95% CI, 1.1-5.7). CONCLUSIONS: These data suggest increasing heterosexual transmission of HIV in this inner-city STD clinic population. Incident STD, in particular gonorrhea, may increase a patient's risk for HIV infection, suggesting that patients with STD should be targeted aggressively for HIV prevention activities.

Adult↗
PubMed1994

Zidovudine phosphorylation in HIV-infected patients and seronegative volunteers.

OBJECTIVES AND DESIGN: Measurement of phosphorylated zidovudine (ZDV) inside infected cells is more likely to provide satisfactory dose response relationships than serum concentrations. This study provides information on ZDV phosphorylation in HIV-seronegative volunteers (n = 5) and in patients with HIV infection (n = 12). METHODS: Intracellular ZDV phosphate metabolites were measured in peripheral blood mononuclear cells isolated from whole blood by density cushion centrifugation. Cells were washed and extracted overnight with 60% methanol prior to analysis by high performance liquid chromatography. Fractions eluted from the column corresponding to ZDV, ZDV monophosphate (ZDV-MP), ZDV diphosphate (ZDV-DP) and ZDV triphosphate (ZDV-TP) were collected, hydrolysed by acid phosphatase and ZDV levels quantified by radioimmunoassay. RESULTS: The area under the plasma ZDV concentration-time curve (AUC0-6 h) was similar in seronegative volunteers and patients [mean +/- SD, 4.64 +/- 2.50 versus 5.56 +/- 2.67 mumoles/l h; 95% confidence interval (CI), -4.39-2.23; P = 0.646, Mann-Whitney U test]. However, ZDV phosphorylation was greater in patients, with the AUC0-6 h for total phosphate metabolites being 5.91 +/- 3.42 pmoles/10(6) cells h compared with seronegative volunteers (0.66 +/- 0.48 pmoles/10(6) cells h; 95% CI, -8.35 to -2.32; P = 0.0003). The concentration of ZDV-TP was similar in both groups, the increase in total phosphates in patients being due primarily to ZDV-MP. ZDV-MP AUC0-6 h and total ZDV phosphate AUC0-6 h were closely correlated (r2 = 0.94). The relationship between total ZDV phosphate AUC0-6 h and the CD4 count demonstrates that patients with a count < 100 x 10(6)/l have much higher ZDV phosphate levels, predominantly ZDV-MP. CONCLUSION: ZDV is phosphorylated to a greater extent in patients than in healthy volunteers. The increased ZDV-MP in patients with low CD4 counts may explain the well known occurrence of increased ZDV toxicity in patients with more advanced disease. The ability to measure ZDV phosphorylated metabolites (without the administration of radiolabelled nucleoside) represents a significant advance in our understanding of the clinical pharmacology of the drug.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Identification, localization, and distribution of the PilT protein in Neisseria gonorrhoeae.

A monoclonal antibody (MAb) directed against a highly conserved protein of Neisseria gonorrhoeae with a molecular size of 40 kDa was isolated and characterized. The protein antigen detected by this MAb was detected by enzyme-linked immunosorbent assay and immunoblotting in all strains of N. gonorrhoeae tested across a wide range of serovars. The 40-kDa protein was found to be expressed at relatively low levels and localized to both the cytosolic and cytoplasmic membrane fractions. Screening of a lambda gt11 expression library derived from gonococcal genomic DNA with the anti-40-kDa MAb and DNA sequence analysis suggested that the 40-kDa protein and the product of the gonococcal pilT gene were identical. Immunoblotting analysis of gonococcal mutants carrying defined mutations in the pilT gene confirmed that the 40-kDa protein was indeed PilT. The N-terminal sequence derived by microsequencing of the protein purified from gonococci led to the correction of the previously published pilT gene sequence. Sequencing of the pilT gene from three different strains revealed an extremely high degree of conservation at both the amino acid and DNA levels.

Adenosine Triphosphatases↗
PubMed1993

Ultrasound diagnosis of polycystic ovaries.

Ultrasound characterization of ovarian morphology has become an important aspect of gynecological endocrinology. The classic ultrasound features of polycystic ovaries are an increased number of small follicles together with abundant stroma. The exact criteria vary according to the ultrasound technique used. The method, however, has been validated both laparoscopically and histologically. Using laparoscopic inspection as a reference test, ultrasonography was calculated to have a sensitivity of 91% and a specificity of 100%. As a group, anovulatory women with PCO have the classic endocrine features of polycystic ovarian syndrome, but in a proportion of cases the finding of PCO at scan appears to be irrelevant to the presenting disorder. Ultrasound diagnosis of PCO is also limited by its inability to display either ovary in about 16% of women.

Female↗
PubMed1993

Early bactericidal and sterilizing activities of ciprofloxacin in pulmonary tuberculosis.

The early bactericidal and sterilizing activities of ciprofloxacin were evaluated in the treatment of adult patients with smear positive pulmonary tuberculosis. Two randomized prospective studies were performed in Northern Tanzania. In study 1, ten patients received either 750 mg ciprofloxacin or 300 ng isoniazid daily for 7 days. Counts of colony-forming units (cfu) of Mycobacterium tuberculosis in early morning sputum were performed. In study 2, twenty patients received either a standard regimen of rifampin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E) (regimen HRZE) or a trial regimen of ciprofloxacin (C), isoniazid (H), and rifampin (R) (regimen HRC). Sputum colony counts were performed for 8 wk. Patients were tested for antibodies to human immunodeficiency virus (HIV)-1. The results demonstrate that ciprofloxacin alone has useful early bactericidal activity, resulting in a mean daily fall of 0.20 log10cfu/ml/day during 7 days compared with 0.25 log10cfu/ml/day for isoniazid. When HRZE and HRC regimens were compared, the HRC regimen appeared to be inferior in its sterilizing ability, with a culture conversion rate of 67% at 2 months compared with 100% for HRZE. The difference in outcome was most marked in HIV-1 positive patients. The role of ciprofloxacin in combination regimens may be as a bactericidal rather than a sterilizing agent.

Adult↗
PubMed1993

Paederus (Nairobi fly) vesicular dermatitis in Tanzania.

Four cases of dermatitis following contact with insects of the genus Paederus are described. The insects are known in East Africa as Nairobi fly and cause an acute, painful toxic epidermolysis when crushed on skin. Local clinicians are familiar with the condition, but it should also be borne in mind as a cause of unusual skin lesions in visitors returning from East Africa.

Adult↗