Human liver CYP2B6-catalyzed hydroxylation of RP 73401

RP 73401 is a potent inhibitor of cyclic nucleotide phosphodiesterase type IV. RP 73401 is metabolized by human liver microsomes almost exclusively by transhydroxylation of the cyclopentyl group to RPR 113406. Liquid chromatography/mass spectrometry/mass spectrometry analysis of plasma from patients given RP 73401 also revealed a molecular ion and fragmentation consistent with RPR 113406. Thus, the objective was to determine the oxidative enzyme(s) responsible for RP 73401 hydroxylation. Kinetic constants of RP 113406 formation ranged from 8 to 26 MM and 0.83 to 5.99 nmol/min/mg protein for K(m) and V(max), respectively (n = 3). Enzyme activity varied 23-fold among 15 human liver microsome samples and correlated with CYP2A6-catalyzed coumarin hydroxylase (r2 = 0.85, P < .01) and CYP2B6-catalyzed 7-ethoxytrifluoromethylcoumarin O-deethylase (r2 = 0.82, P < .01) activities. Chemical inhibition studies showed a 63% decrease in RP 73401 hydroxylation by 500 microM orphenadrine. Coumarin (10 microM), however, did not inhibit RP 73401 hydroxylation. Also, anti-CYP2B1 IgG produced 85% inhibition of RP 73401 hydroxylation, but only a negligible decline in coumarin hydroxylase activity. Of the 10 expressed P450 forms studied, only CYP2B6 catalyzed RP 73401 hydroxylation. Finally, expressed CYP2B6 showed a high affinity (K(m) = 22.5 microM) for RP 73401 hydroxylation, similar to the human liver microsome studies.     

Phylogenetic relationships of Australian strongyloid nematodes inferred from ribosomal DNA sequence data

The sequence of the second internal transcribed spacer of the ribosomal DNA was determined for the following strongyloid nematodes: Cylicocyclus insignis, Chabertia ovina, Oesophagostomum venulosum, Cloacina communis, Cloacina hydriformis, Labiostrongylus labiostrongylus, Parazoniolaimus collaris, Macropostrongylus macropostrongylus, Macropostrongylus yorkei, Rugopharynx australis, Rugopharynx rosemariae, Macropostrongyloides baylisi, Oesophagostomoides longispicularis and Paramacropostrongylus toraliformis, and compared with published sequences for species of Strongylus and for Hypodontus macropi. The resultant phylogenetic trees supported current hypotheses based on morphological evidence for the separation of the families Strongylidae and Chabertiidae, but did not support the separation of the endemic Australian genera as a distinctive clade within the Chabertiidae. The implications of this finding for the phylogenetic origins of the Australian strongyloids are discussed.     

Comparison of RDC, DSM-III, DSM-III-R diagnostic criteria for generalized anxiety disorder

The aim of the present study is to conduct an observation of a time series of job-event/life event and depressive symptoms, prospectively. Ten male computer software engineers were observed every two weeks for five months and every following week for two months. In total, one hundred and eighty-one observations were made. A semi-structured interview was conducted to survey the week-unit job-events on each sampling day. The depressive symptoms were measured using Zung's Self-reporting Depressive Scale (SDS). It was found that the events had a significant effect on the SDS raw score. It also showed that the effective time period of the events on depression is within two weeks. With a week-based analysis in a prospective approach, the present study showed the immediate effects of job events or life events on depressive symptoms.     

The influence of knowledge and attitudes about breast cancer on mammography use among Latinas and Anglo women

We conducted a telephone survey of randomly selected Latinas (n = 208) and Anglo women (n = 222) to determine predictors of mammography use. The cooperation rate was 78.5%. Relatively high proportions of Latinas (61%) and Anglo women (79%) reported mammography use within the past 2 years. A logistic regression analysis revealed that knowledge and attitudes did not independently predict use. On the other hand, having health insurance, being married, and being Latino were consistent independent predictors. We conclude that mammography use among Latinas and Anglo women is increasing. However, further gains in use must address difficult barriers such as lack of health insurance.     

Prognostic significance of prior preterm twin delivery on subsequent singleton pregnancy

OBJECTIVE: Our purpose was to determine whether preterm birth of twins is associated with an increased risk of preterm birth in a subsequent singleton pregnancy. STUDY DESIGN: The Medical University of South Carolina perinatal database was accessed to identify a cohort of patients who were delivered of twins followed by a singleton gestation (1981 to 1993). Maternal transports were excluded to minimize referral bias. Preterm birth was defined as < 37 weeks' gestation. Relative risks with 95% confidence intervals were calculated. RESULTS: One hundred forty-four patients were identified who were delivered of twins followed by a singleton gestation. Preterm delivery occurred in 86 (59.7%) of the twins and 21 (14.6%) of the subsequent singletons. Preterm birth of twins was associated with a significantly increased risk of preterm delivery in a subsequent singleton pregnancy (relative risk 2.87, 95% confidence interval 1.02 to 8.09). In the subset of women who were delivered of twins at < 30 weeks' gestation, 42% of the subsequent singletons were delivered preterm (relative risk 6.11, 95% confidence interval 2.07 to 18.02). The relative risk of preterm birth of a singleton after delivery of twins between 30 and 34 weeks' gestation was 3.63 (95% confidence interval 1.02 to 12.92). However, if the preceding twins delivered between 34 and 37 weeks' gestation, the relative risk of preterm birth of the subsequent singleton was not significantly increased (relative risk 1.42, 95% confidence interval 0.40 to 5.01). CONCLUSIONS: Preterm birth of twins before 34 weeks' gestation is associated with a significant risk for preterm delivery in a subsequent singleton pregnancy. The magnitude of risk increases with decreasing gestational age of the preceding twin delivery.     

Interpersonal Hostility Assessment Technique: description and validation against the criterion of coronary artery disease

High levels of hostility are associated with adverse health outcomes. The Interpersonal Hostility Assessment Technique (IHAT; Barefoot, 1992) measures hostility from verbal behavior during a standardized interview. Four types of behaviors are scored as hostility: evading the question, irritation, and indirect and direct challenges to the interviewer. The sum of the frequencies of these acts is a Hostile Behavior Index (HBI), which is divided into two components: verbal, scored with speech content in mind, and paraverbal, based on vocal stylistics. This study examined characteristics of IHAT assessments in 129 male coronary patients. Satisfactory interrater reliabilities were obtained. The HBI correlated highly (.58) with coronary artery disease severity after controlling for traditional risk factors. This relation was not affected by question topic or by differential weighting of the four hostile behaviors. Both HBI components were significantly correlated with disease. Results are discussed in terms of their implications for hostility assessment.     

SPECT imaging of dopamine transporters in human brain with iodine-123-fluoroalkyl analogs of beta-CIT

Iodine-123-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane (beta-CIT) is a useful SPECT tracer for imaging the dopamine transporter. Its slow kinetics, however, necessitate imaging on the day after the injection. Two N-omega-fluoroalkyl analogs of beta-CIT, the fluoropropyl and fluoroethyl compounds (beta-CIT-FP and beta-CIT-FE, respectively), characterized by faster kinetics in baboons, were tested in humans as potential tracers for the dopamine transporter. Four healthy volunteers were injected with [123I]-beta-CIT-FP and another four were injected with [123I]beta-CIT-FE. SPECT data were acquired for 1149 +/- 590 min and 240 +/- 30 min, respectively. Both tracers demonstrated high brain uptake (6.37% +/- 0.37% and 7.8% +/- 1.5% of the injected dose, respectively). Activity concentrated with time in the striatal area, reaching a peak within 30 min, with little or no washout for [123I]beta-CIT-FP and a faster washout for [123I]beta-CIT-FE (14.7% +/- 6.9%). Occipital and midbrain activity showed similar patterns, displaying a peak within 15 min and rapid washout, followed by stable levels at approximately 100 min for both tracers. The ratio of peak specific striatal-to-peak specific midbrain activity was 9.1 +/- 1.8 for [123I]beta-CIT-FP and 7.7 +/- 0.7 for [123I]beta-CIT-FE, showing high in vivo selectivity for the dopamine transporter. These preliminary results suggest that both compounds could be used as SPECT (labeled with 123I) or PET (labeled with 18F) radiotracers to image the dopamine transporters in the living human brain.     

Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy

Uptake of foreign material and its subsequent lysosomal degradation is an important function of macrophages. The mechanisms involved in the binding, uptake and delivery of such material to lysosomal organelles, are, however, poorly understood. Here we describe a method using organelle electrophoresis to study the uptake and trafficking of heat-killed yeast particles within murine macrophages. Such yeast particles, which were fluorescently labeled, could be readily detected in intact cells as well as in subcellular fractions. Organelle electrophoresis of a homogenate from macrophages that had internalized yeast particles resulted in the separation of yeast-containing organelles from most other subcellular membranes. In addition, this method was used to follow the kinetics of yeast particle transport within macrophages could be followed readily. Organelle electrophoresis may be a valuable tool for the analysis of phagocytosis.