Mutation of a specific, but as yet unidentified, gene BRCA1 on chromosome 17q results in increased susceptibility to breast and ovarian cancer. It is important to know the effects of this gene in ...terms of the age-specific risks of these cancers and the potential interaction of this gene with other known risk factors.
We performed detailed studies on a large multigenerational family, in which there is known 17q-linked breast and ovarian cancer, in order to characterize the effects of the BRCA1 mutation on development of breast and ovarian cancer.
Data from the Utah Population Database were used to identify a family (identified as K2082) with a cluster of premenopausal breast cancer and ovarian cancer at any age. Blood samples from 195 members of the family were obtained and these individuals were genotyped for a series of four chromosome 17q polymorphic markers. Information on reproductive history, cancer incidence and treatment, and lifestyle factors was collected on 72 women in the family by questionnaire or through contact with living relatives.
Odds in favor of linkage of breast and ovarian cancer in this family to the BRCA1 region of chromosome 17q are greater than 10(8) to 1. The estimated risks for breast or ovarian cancer because of the BRCA1 mutation in this family are 40% by age 50 years and 90% by age 70. No differences between affected and unaffected older BRCA1 gene carriers were observed for a number of known epidemiologic risk factors for these cancers. The gender of the parent from whom the mutant BRCA1 allele was inherited was significantly associated with phenotypic expression (P = .04). A recombinant which places BRCA1 distal to the marker Mfd191 was observed.
Women with the BRCA1 mutation are at increased risk of developing breast and ovarian cancer. In our study population, the mutation appears to confer a lower risk of cancer at younger ages than found in previous studies. Continued interaction with family K2082 will be useful in longitudinal follow-up studies and in studies of the psychosocial implications of providing DNA diagnosis of BRCA1.
Probes derived from cDNAs encoding isozymes of rat protein kinase C (PKC) were used to screen the genome of the budding yeast S. cerevisiae. A single gene (PKC1) was isolated that encodes a putative ...protein kinase closely related to the alpha, beta, and gamma subspecies of mammalian PKC. Deletion of PKC1 resulted in recessive lethality. Cells depleted of the PKC1 gene product displayed a uniform phenotype, a characteristic of cell division cycle (cdc) mutants, and arrested cell division at a point subsequent to DNA replication, but prior to mitosis. Unlike most cdc mutants, which continue to grow in the absence of cell division, PKC1-depleted cells arrested growth with small buds. PKC1 may regulate a previously unrecognized checkpoint in the cell cycle.
The production of Ξ(1321)- and Ξ¯(1321)+ hyperons in inelastic p+p interactions is studied in a fixed target experiment at a beam momentum of 158 Ge/c. Double differential distributions in rapidity y ...and transverse momentum pT are obtained from a sample of 33M inelastic events. They allow to extrapolate the spectra to full phase space and to determine the mean multiplicity of both Ξ- and Ξ¯+. The rapidity and transverse momentum spectra are compared to transport model predictions. The Ξ- mean multiplicity in inelastic p+p interactions at 158 Ge/c is used to quantify the strangeness enhancement in A+A collisions at the same centre-of-mass energy per nucleon pair.
Measurements of the Formula omitted, Formula omitted, and proton double differential yields emitted from the surface of the 90- Formula omitted-long carbon target (T2K replica) were performed for the ...incoming Formula omitted Formula omitted protons with the NA61/SHINE spectrometer at the CERN SPS using data collected during 2010 run. The double differential Formula omitted yields were measured with increased precision compared to the previously published NA61/SHINE results, while the Formula omitted and proton yields were obtained for the first time. A strategy for dealing with the dependence of the results on the incoming proton beam profile is proposed. The purpose of these measurements is to reduce significantly the (anti)neutrino flux uncertainty in the T2K long-baseline neutrino experiment by constraining the production of (anti)neutrino ancestors coming from the T2K target.
Abstract Background Proteolytically released extracellular matrix (ECM) fragments, matricryptins, are biologically active and play important roles in wound healing. Following myocardial infarction ...(MI), collagen I, a major component of cardiac ECM, is cleaved by matrix metalloproteinases (MMPs). Objectives This study identified novel collagen-derived matricryptins generated post-MI that mediate remodeling of the left ventricle (LV). Methods Recombinant collagen Ia1 was used in MMPs cleavage assays, the products were analyzed by mass spectrometry for identification of cleavage sites. C57BL6/J mice were given MI and animals were treated either with vehicle control or p1158/59 matricryptin. Seven days post-MI, LV function and parameters of LV remodeling were measured. Levels of p1158/59 were also measured in plasma of MI patients and healthy controls. Results In situ, MMP-2 and -9 generate a collagen Iα1 C-1158/59 fragment, and MMP-9 can further degrade it. The C-1158/59 fragment was identified post-MI, both in human plasma and mouse LV, at levels that inversely correlated to MMP-9 levels. We synthesized a peptide beginning at the cleavage site (p1158/59, amino acids 1159 to 1173) to investigate its biological functions. In vitro, p1158/59 stimulated fibroblast wound healing and robustly promoted angiogenesis. In vivo, early post-MI treatment with p1158/59 reduced LV dilation at day 7 post-MI by preserving LV structure (p < 0.05 vs. control). The p1158/59 stimulated both in vitro and in vivo wound healing by enhancing basement membrane proteins, granulation tissue components, and angiogenic factors. Conclusions Collagen Iα1 matricryptin p1158/59 facilitates LV remodeling post-MI by regulating scar formation through targeted ECM generation and stimulation of angiogenesis.
Summary Background Diastolic dysfunction might represent an important pathophysiological intermediate between hypertension and heart failure. Our aim was to determine whether inhibitors of the ...renin-angiotensin-aldosterone system, which can reduce ventricular hypertrophy and myocardial fibrosis, can improve diastolic function to a greater extent than can other antihypertensive agents. Methods Patients with hypertension and evidence of diastolic dysfunction were randomly assigned to receive either the angiotensin receptor blocker valsartan (titrated to 320 mg once daily) or matched placebo. Patients in both groups also received concomitant antihypertensive agents that did not inhibit the renin-angiotensin system to reach targets of under 135 mm Hg systolic blood pressure and under 80 mm Hg diastolic blood pressure. The primary endpoint was change in diastolic relaxation velocity between baseline and 38 weeks as determined by tissue doppler imaging. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00170924. Findings 186 patients were randomly assigned to receive valsartan; 198 were randomly assigned to receive placebo. 43 patients were lost to follow-up or discontinued the assigned intervention. Over 38 weeks, there was a 12·8 (SD 17·2)/7·1 (9·9) mm Hg reduction in blood pressure in the valsartan group and a 9·7 (17·0)/5·5 (10·2) mm Hg reduction in the placebo group. The difference in blood pressure reduction between the two groups was not significant. Diastolic relaxation velocity increased by 0·60 (SD 1·4) cm/s from baseline in the valsartan group (p<0·0001) and 0·44 (1·4) cm/s from baseline in the placebo group (p<0·0001) by week 38. However, there was no significant difference in the change in diastolic relaxation velocity between the groups (p=0·29). Interpretation Lowering blood pressure improves diastolic function irrespective of the type of antihypertensive agent used.
An abstract of a study by Forte el al investigating animal performance differences of pre-conditioned beef calves fed with annual ryegrass (Lolium multiflorum) baleage, bermudagrass (Cynodon ...dactylon) hay, or corn (Zea mays) silage-based diets is presented. The 45-d background trial began on 9 September 2015 after animals were sorted and acclimated to the diets. 108 weaned calves and steers were placed into nine pens. Sex was distributed evenly across treatments. Results show forage options achieved a similar level of gain when supplemented for preconditioning beef calves. However, an economic analysis is needed to determine feasibility and potential break-even costs for using these options in beef operations.
Numerical sediment quality targets (SQTs) for the protection of sediment-dwelling organisms have been established for the St. Louis River Area of Concern (AOC), 1 of 42 current AOCs in the Great ...Lakes basin. The two types of SQTs were established primarily from consensus-based sediment quality guidelines. Level I SQTs are intended to identify contaminant concentrations below which harmful effects on sediment-dwelling organisms are unlikely to be observed. Level II SQTs are intended to identify contaminant concentrations above which harmful effects on sediment-dwelling organisms are likely to be observed. The predictive ability of the numerical SQTs was evaluated using the matching sediment chemistry and toxicity data set for the St. Louis River AOC. This evaluation involved determination of the incidence of toxicity to amphipods ( Hyalella azteca) and midges (Chironomus tentans) within five ranges of Level II SQT quotients (i.e., mean probable effect concentration quotients PEC-Qs). The incidence of toxicity was determined based on the results of 10-day toxicity tests with amphipods (endpoints: survival and growth) and 10-day toxicity tests with midges (endpoints: survival and growth). For both toxicity tests, the incidence of toxicity increased as the mean PEC-Q ranges increased. The incidence of toxicity observed in these tests was also compared to that for other geographic areas in the Great Lakes region and in North America for 10- to 14-day amphipod (H. azteca) and 10- to 14-day midge (C. tentans or C. riparius) toxicity tests. In general, the predictive ability of the mean PEC-Qs was similar across geographic areas. The results of these predictive ability evaluations indicate that collectively the mean PEC-Qs provide a reliable basis for classifying sediments as toxic or not toxic in the St. Louis River AOC, in the larger geographic areas of the Great Lakes, and elsewhere in North America.
Measuring the scintillation light in noble gases is an important detection technique in particle physics. Numerous rare event searches like neutrino beam experiments, neutrino-less double beta-decay, ...and dark matter searches use argon-based detectors. In liquid argon, the light yield can be enhanced by the addition of a small quantity of xenon, where \(\sim 10 - 1000\) ppm are added. The general enhancement mechanism and its pathway via an energy transfer between argon and xenon excimers is well known, however the importance of absorption of argon excimer emission by atomic xenon has not been fully appreciated. This absorption significantly reduces the light yield in commercially available argon which contains trace amounts (\(\rm \sim 0.1\) ppm) of xenon. The addition of a small xenon dopant of \(\sim 10\) ppm recovers this lost light resulting in an increased light yield over un-doped argon of about a factor of two. In this paper we introduce a model for the light production in xenon doped argon, including absorption and re-emission, and compare it to the measured time dependence of light emission in xenon-doped argon.
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