Modulation of whole body protein metabolism, during and after exercise, by variation of dietary protein

The aim of this study was to investigate dietary protein-induced changes in whole body leucine turnover and oxidation and in skeletal muscle branched chain 2-oxo acid dehydrogenase (BCOADH) activity, at rest and during exercise. Postabsorptive subjects received a primed constant infusion of L-[1-13C,15N]leucine for 6 h, after previous consumption of a high- (HP; 1.8 g . kg-1 . day-1, n = 8) or a low-protein diet (LP; 0.7 g . kg-1 . day-1, n = 8) for 7 days. The subjects were studied at rest for 2 h, during 2-h exercise at 60% maximum oxygen consumption, then again for 2 h at rest. Exercise induced a doubling of both leucine oxidation from 20 micromol . kg-1 . h-1 and BCOADH percent activation from 7% in all subjects. Leucine oxidation was greater before (+46%) and during (+40%, P < 0.05) the first hour of exercise in subjects consuming the HP rather than the LP diet, but there was no additional change in muscle BCOADH activity. The results suggest that leucine oxidation was increased by previous ingestion of an HP diet, attributable to an increase in leucine availability rather than to a stimulation of the skeletal muscle BCOADH activity.     

Association of glutathione S-transferase GSTM1 and GSTT1 null genotypes with clinical outcome in epithelial ovarian cancer

Epithelial ovarian cancer is generally associated with a poor outcome, although the mechanisms that determine survival and progression-free interval (PFI) are unclear. Data from ovarian tumors showing associations between (a) null genotypes at the glutathione S-transferase GSTM1 and GSTT1 loci and expression of p53 protein and (b) outcome and expression of p53 suggest that polymorphism at these loci is a factor determining outcome. Accordingly, we have studied the association between the GSTM1 null and GSTT1 null genotypes and survival and PFI in 148 women with epithelial ovarian cancer. Although we did not find an association between individual genotypes and outcome, women with both GSTM1 null and GSTT1 null genotypes demonstrated poorer survival (P = 0.001) and reduced PFI (P = 0.003). Thus, no cases with both these genotypes survived past 42 months postdiagnosis. In contrast, 43% of the women without this combination survived beyond this time. Because response to chemotherapy is a major factor determining outcome in ovarian cancer, we also examined the data for associations between the glutathione S-transferase genotypes and response to such treatment. Thus, in 78 patients treated with chemotherapy, the combination of GSTM1 null and GSTT1 null was associated with unresponsiveness to primary chemotherapy (P = 0.004); none of the eight patients with both these genotypes responded, compared with 38 of 70 (54%) of patients with other genotype combinations. The effect of the combination of genotypes on survival and PFI was lost in a multivariate model that included response to chemotherapy as a confounding factor. This suggests that the combination of GSTM1 null/GSTT1 null is associated with outcome because of its influence on response to chemotherapy. These preliminary findings may provide a basis for the selection of patients for treatment with chemotherapeutic agents.     

Effect of intraocular lens design on neodymium:YAG laser capsulotomy rates

The activity of alkaline phosphatase (AP) was studied in adults of highly active (HA) and low active (LA) Drosophila melanogaster strains and their F1 hybrids, both under normal conditions and after a heat shock (38 degrees C). Under normal conditions, the HA strain expressed a higher AP activity compared to that in the wild-type strain Canton-S and dominated in respect to this character. The AP activity showed a sexual dimorphism, as it was higher in females of both strains. Heat shock (38 degrees C) induced no alterations in the AP activity of D. melanogaster.     

Effect of dietary restriction on benzo[a]pyrene (BaP) metabolic activation and pulmonary BaP-DNA adduct formation in mouse

Hepatic microsomal xenobiotic metabolizing enzyme activities of laboratory animals can be modulated by Dietary restriction (DR). The modulation of xenobiotic metabolizing enzyme activities can affect the metabolic activation of chemical carcinogens. Acute DR (60% of the food consumption of ad libitum (AL)-fed mice for 7 weeks) reduced the body weights of the male B6C3F1 mice, and increased mouse pulmonary cytochrome P4501A1-dependent BaP metabolizing enzyme activity. The effects of DR on the formation of the specific BaP-DNA adduct, 10-(N2-deoxyguanosinyl)-7,8,9-trihydroxy-7,8,9,10-tetrahydro-BaP (BaP-N2-dG) in mouse lung can be detected by using 32P-postlabeling technique. In both AL- and DR-mice total BaP-DNA adduct formation in lung reached a peak at 48 hours after treatment with [3H]BaP and the in vivo formation of BaP-N2-dG was greater in DR mouse lung than in that of AL-animals by 22%. DR increased in vitro BaP-N2-dG formation by 39% when calf-thymus DNA was incubated with BaP using liver microsomes obtained from DR- or AL-mice as the enzyme source. The formation of the specific BaP-N2-dG adducts, measured by 32P-postlabeling, was only 20% of the total [3H]BaP-DNA adducts as determined by liquid scintillation counting. The increase of BaP-DNA adduct formation in mouse lung was correlated to the enhancement of the mouse pulmonary BaP metabolizing enzyme activity. Our results indicated that the effect of DR on the metabolic activation of BaP in mouse lung was dependent upon the mouse lung cytochrome P4501A1-dependent BaP metabolizing enzymes activities which was significantly increased by DR.     

Assessment of uterine arterial notching as a screening test for adverse pregnancy outcome

Recombinant papillomavirus-like particles have recently been shown to be highly effective for the prevention of papillomavirus infections and associated tumors, and a virus-like particle-based vaccine against the most prevalent HPV causing genital infection in humans will be developed in the near future. Another use of these virus-like particles may lie in gene therapy and DNA immunization. We report here that human papillomavirus-like particles composed of the major capsid protein (L1) of HPV-16 are able to package unrelated plasmid DNA in vitro and then to deliver this foreign DNA to eukaryotic cells with the subsequent expression of the encoded gene. The results indicate higher gene transfer than with DNA alone or with liposome. Virus-like particles are a very promising vehicle for delivering genetic material into target cells. Moreover, the preparation of the gene transfer vehicle is relatively easy.     

Estrogen replacement therapy and worsening of radiographic knee osteoarthritis: the Framingham Study

OBJECTIVE: To examine whether estrogen replacement therapy (ERT) prevents worsening of radiographic knee osteoarthritis (OA) in elderly women. METHODS: A total of 551 women ages 63-91 years (mean age 71) in the Framingham Study were followed up from biennial examination 18 (1983-1985) to examination 22 (1992-1993). Data on postmenopausal ERT were obtained every 2 years. Subjects were classified into 3 groups according to their estrogen use at biennial examination 18: never users (n = 349), past users (n = 162), and current users (n = 40). Women received anteroposterior weight-bearing knee radiographs at examinations 18 and 22. Using the Kellgren and Lawrence criteria, global radiographic knee OA was assessed, (grade range 0-4) and individual radiographic features, such as osteophytes and joint space narrowing, were scored from 0 to 3. Worsening was defined as either development of radiographic OA that was not present at baseline (incident OA) or progression of baseline radiographic OA by > or =1 Kellgren and Lawrence grade (progressive OA). Potential confounding factors included age, body mass index, weight change, smoking, knee injury, physical activity level, and bone mineral density at the femoral neck. RESULTS: During 8 years of followup, 17.4% of knee radiographic scores worsened by 1 grade and 5.8% by 2 or 3 grades among never users of ERT. Among current estrogen users, only 11.7% of knee radiographic scores worsened by 1 grade and none worsened by more than 1 grade. After adjusting for age and other potential confounding factors, the relative risk of incident radiographic knee OA in comparison with never users of estrogen was 0.8 (95% confidence interval [95% CI] 0.5-1.4) in past users and 0.4 (95% CI 0.1-3.0) in current users. Current use of estrogen also showed a trend toward decreased risk of progressive knee OA compared with never use (odds ratio [OR] 0.5, 95% CI 0.1-2.9). When both incident and progressive radiographic knee OA cases were combined, current ERT use had a 60% decreased risk compared with never use (OR 0.4, 95% CI 0.1-1.5). CONCLUSION: This is the first prospective cohort study to examine the effects of ERT on radiographic knee OA. The results indicate that current use of ERT had a moderate, but not statistically significant, protective effect against worsening of radiographic knee OA among elderly white women. These findings corroborate those of cross-sectional studies and point further to a potential benefit of female hormones in OA.     

Holographic interferometry measurement of the thermal refractive index coefficient and the thermal expansion coefficient of Nd:YAG and Nd:YALO

Accurate values for the thermal expansion coefficient α and the thermal coefficient of refractive indexdn/dTare important in the design of a solid-state laser. This paper presents values of α anddn/dTthat were measured for Nd:YAG and Nd:YALO by a single-exposure holographic interferometry technique. The value of α for Nd:YAG agrees closely with that reported before, yet significantly different values ofdn/dTfor Nd:YAG and α for Nd: YALO were obtained. A discussion of the measurement techniques is given.     

Estimating frequency-response function using periodic signals and the f.f.t.

A technique for estimating a frequency-response function using a periodic pseudorandom binary sequence which is compatible with the fast-Fourier-transform algorithm is presented. A method of synchronising the p.r.b.s. and the sampling for the f.f.t. using a single clock source and two binary counters is described. A simple check on the synchronisations and the identification of an 8th-order lowpass Butterworth filter is provided.