Reproduction and fetal development in mice chronically exposed to nitrous oxide

The effects of exposure to nitrous oxide on reproductive indices, fetal development, and male fertility were examined in Swiss/ICR mice. In experiment I, female mice were exposed for 4 hours per day on days 6-15 of pregnancy, to 0.5% (5,000 ppm), 5.0% (50,000 ppm), or 50% (500,000 ppm) nitrous oxide. Control mice were untreated, exposed to compressed air, or treated with retinoic acid on day 8 of gestation. In experiment II, male mice were treated, as above, for 9 weeks and then mated nightly for 7 nights to untreated, virgin females. In experiment I, 1,761 fetuses from 154 dams were examined and found to be without evidence of adverse nitrous oxide treatment effects. In experiment II there were no differences among the groups in the ability of males to impregnate females or in litter size, fetal wastage, or fetal size. When we compare nitrous oxide with other inhalation anesthetics we have studied employing a similar protocol, we find the order of reproductive toxicity to be: halothane greater than enflurane greater than methoxyflurane greater than nitrous oxide. None of the agents were toxic, however, at the trace concentrations usually found in operating rooms.     

Impairment of diazepam metabolism by low-dose estrogen-containing oral-contraceptive steroids

The longterm use of low-dose estrogen containing oral contraceptives (OCs) and its impairment of diazepam clearance is reported. 8 healthy women, ranging in age from 52 to 72 years, participated in the study. All of the women had been taking low-dose estrogen containing OCs for more than 3 months. 1 of the subjects was a cigarette smoker. 8 healthy controls (all nonsmokers) who were not using OCs also participated. They ranged in age from 27-31 years. Diazepam (10 mg) was given by intravenous infusion over 15-30 seconds. Venous blood samples were drawn into heparinized tubes before the infusion, at the end of the infusion, at 5, 15, 30, and 45 minutes, at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours, and daily for 7 days after the infusion. Plasma concentrations of diazepam after intravenous infusion were analyzed by weighted iterative nonlinear least-squares regression techniques. The volume of distribution of diazepam was not significantly different between the groups, but the apparent elimination half-life of diazepam was significantly longer and the total metabolic clearance significantly less in the OC users than in the control group. The differences were not confounded by variations in protein binding. The mean diazepam free fraction was identical in the 2 groups. The clinical result of the decrease in diazepam clearance reported here would be increased steady-state plasma diazepam concentration after longterm use at a given daily dose, with the potential for increasing the clinical effects of diazepam in this population.     

Similar characteristics of the CDR3 of V(H)1-69/DP-10 rearrangements in normal human peripheral blood and chronic lymphocytic leukaemia B cells

The variable heavy chain (V(H)) gene segment V(H)1-69/DP-10 has been shown to be over-represented in B-cell chronic lymphocytic leukaemia (CLL). Because of certain similar characteristics of their complementarity determining region 3 (CDR3), including preferential utilization of J(H)6 elements and an extended length, it has been suggested that antigenic stimulation might be involved in leukaemogenesis. Utilizing single-cell PCR to amplify and sequence genomic DNA from individual normal human peripheral blood B cells, we have obtained 7/421 productively and 1/69 nonproductively rearranged V(H) genes that used V(H)1-69/DP-10. All productive rearrangements were unmutated, used J(H)6 and had an average CDR3 length similar to that previously found in V(H)1-69/DP-10-expressing CLL cells. These results suggest that CLL may arise from B cells commonly found in the peripheral B-cell repertoire and do not represent expansion of a unique subset of specific antigen-reactive B cells.     

Further studies on the influence of genotype and dietary protein on the performance of broilers

An experiment was conducted to quantify genetic differences in response to dietary protein level of male vs female broilers. Broilers (1 d old) from a "high-yield" strain cross (Ross x Ross 208) and a "fast-growing" strain cross (Peterson x Arbor Acres) were placed on fresh pine shavings in floor pens. From Day 0 to 18, all birds were fed a 23% CP starter diet. During Days 18 to 53 male birds were fed either a 16, 18, 20, 22, 24, or 26% CP diet (3,200 kcal ME/kg) and female birds were fed the 16, 20, or 24% CP diet. Significant differences (P < 0.05) were noted in the performance of the different strains. Ross x Ross 208 male birds had a higher body weight (3.37 vs 3.16 kg), higher feed intake (7.08 vs 6.78 kg), higher breast yield (31.76 vs 29.25%), higher carcass yield (73.90 vs 71.85%), and a lower adjusted feed conversion ratio (FCR; 2.10 vs 2.16 g:g) than Peterson x Arbor Acres males at 53 d of age. As compared to Peterson x Arbor Acres females, Ross x Ross 208 female broilers also had a higher body weight (2.68 vs 2.55 kg), higher breast meat yield (33.61 vs 30.80%), higher carcass yield (75.31 vs 73.91%), and lower adjusted FCR (1.97 vs 2.04 g:g). Qualitative differences in the response of these strains were confirmed and better qualitative data is presented that can be used to predict the important output parameters from the import inputs in broiler production.     

Dynamics of clot growth induced by thrombin diffusing into nonstirred citrate human plasma

We have tested whether action potential-evoked Ca2+ influx is required to initiate clathrin-mediated synaptic vesicle endocytosis in the lamprey reticulospinal synapse. Exo- and endocytosis were temporally separated by a procedure involving tonic action potential stimulation and subsequent removal of extracellular Ca2+ (Ca2+e). A low concentration of Ca2+ ([Ca2+]e of 11 microM) was found to be required for the induction of early stages of endocytosis. However, the entire endocytic process, from the formation of clathrin-coated membrane invaginations to the generation of synaptic vesicles, proceeded in the absence of action potential-mediated Ca2+ entry. Our results indicate that the membrane of synaptic vesicles newly incorporated in the plasma membrane is a sufficient trigger of clathrin-mediated synaptic vesicle endocytosis.     

Gustin from human parotid saliva is carbonic anhydrase VI

It has been found that yeast mutants deficient in cytosolic superoxide dismutase CuZnSOD are hypersensitive to ferrous iron. In contrast mutants that are deficient in catalases and cytochrome c peroxidase do not differ from the standard strain in this respect. These findings suggest that iron toxicity may depend on the redox status of the cell. They also shed light on the role of superoxide dismutases in preventing the toxic effects of oxygen.     

Consideration of conformational transitions and racemization during process development of recombinant glucagon-like peptide-1

This article summarizes the results of a combined analysis from two identical multicenter clinical trials that investigated the efficacy and safety of sertraline versus placebo for treating panic disorder. Patients with panic disorder who were treated with sertraline had a statistically significant reduction in the mean number of panic attacks per week (the primary efficacy measure) as compared with placebo (4.8 vs. 2.5, p < .001). Sertraline-treated patients also showed greater improvement that was statistically significant on several ratings of panic disorder symptomatology and functioning. The design characteristics, clinical rating measures, and outcome measures in these trials included most of the features deemed essential by Shear and Maser (1994) in their summary of the NIMH Consensus Conference for the development of standardized assessments for panic disorder. This suggests that the NIMH Consensus Conference played a key role in developing successful multicenter pharmacological treatment studies, such as this one that ultimately demonstrated that sertraline was an effective treatment for panic disorder.     

Oestrogen-regulated genes in breast cancer: association of pLIV1 with response to endocrine therapy

Northern hybridization analyses of the oestrogen-inducible mRNAs pLIV1 and pS2 were compared with oestrogen receptor (ER) immunocytochemistry assessments in 40 untreated primary or early recurrent breast tumours. Significant associations were observed between pLIV1/ER (P < 0.03), pS2/ER (P < 0.001) and pLIV1/pS2 (P < 0.04) status. After disease recurrence, patients were treated with assessable courses of endocrine therapies. Positive pLIV1, pS2 and ER statuses in primary disease were consequently found to be predictive of endocrine responsiveness in the secondary lesions (P < 0.03, P < 0.02, P < 0.005 respectively). However, despite these associations, a number of pLIV1- and/or pS2-positive tumours failed to respond to therapy.     

Body-size corrections for in vivo neutron activation analysis

Differences in body size and shape can cause large variances in the results of in vivo neutron activation analysis. Preliminary body-size correction data were obtained for the delayed-gamma neutron activation facility (DGNA) at Brookhaven National Laboratory (BNL), based on phantom standards of different sizes, used in combination with computer simulations on the effect of different body sizes.