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61.
A multi-exonic BRCA1 deletion identified in multiple families through single nucleotide polymorphism haplotype pair analysis and gene amplification with widely dispersed primer sets 下载免费PDF全文
Ward BD Hendrickson BC Judkins T Deffenbaugh AM Leclair B Ward BE Scholl T 《The Journal of molecular diagnostics : JMD》2005,7(1):139-142
The identification of intragenic rearrangements is important for a comprehensive understanding of mutations that occur in some clinically important genes. Single nucleotide polymorphism haplotypes obtained from clinical sequence data have been used to identify patients at high risk for rearrangement mutations. Application of this method identified a novel 26-kb deletion of BRCA1 exons 14 through 20 in patients from multiple families with hereditary breast and ovarian cancer. Clinical sequence data from 5911 anonymous patients were screened for genotypes that were inconsistent with known pairs of canonical haplotypes in BRCA1 that could be explained by hemizygous deletions involving exon 16. Long-range polymerase chain reaction demonstrated that two of six samples identified by this search contained a deletion in the expected region encompassing exons 14 through 20. The breakpoint was fully characterized by DNA sequencing and demonstrated that the deletion resulted from Alu-mediated recombination. This mutation was also identified twice in a set of 982 anonymous specimens that had negative clinical test results, but uninformative haplotypes. Three additional occurrences of this mutation were found by testing 10 other patients with the indicative genotype. An assay for this mutation was added to a comprehensive clinical breast/ovarian cancer test and eight more instances were found in 20,649 probands. This multiexon deletion has therefore been detected in 15 different North American families with hereditary breast/ovarian cancer. In conclusion, this primarily computational approach is highly effective and identifies specimens using existing data that are enriched for deletion mutations. 相似文献
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63.
Prevention Science - Although financial incentives are a well-accepted strategy for raising parent participation rates in prevention studies, they are rarely employed in practice due to concerns... 相似文献
64.
Britta M. Thompson Dale W. Bratzler Mark J. Fisher Amie Torres EPIC Faculty Rhonda A. Sparks 《Journal of interprofessional care》2016,30(6):754-761
Interprofessional education (IPE) involving an interactive and longitudinal clinic experience at an inner-city charitable clinic from September to May 2013/2014 was evaluated. Pre-, mid-, and post-intervention data were collected from students in 13 different professions including medicine (medical and physician assistant), dentistry (dental and dental hygiene), nursing (undergraduate and clinical nurse specialist), public health, pharmacy, physical therapy, occupational therapy, nutritional sciences, speech and language pathology, and social work. To evaluate their interprofessional attitudes, students completed the TeamSTEPPS Teamwork Attitudes Questionnaire (T-TAQ) and Readiness for Interprofessional Learning Scale (RIPLS). They also completed a unique measure, healthcare professionals circles diagrams (HPCDs), that indicated student conceptualisation of a healthcare team caring for a complex patient, along with perception of their team’s progress towards meeting patient goals. Results from the T-TAQ and RIPLS scores indicated small but significant increases from pre- to post-intervention (p = 0.005 and 0.012, respectively). Analysis of the HPCDs revealed significant increases in students’ perceptions of the types of interprofessional team members, relationships, and communication between professions to provide medical care to patients (p < 0.01). Most HPCDs included pharmacists, nurses, and physicians as part of the care team at all time points. Students significantly increased their inclusion of dentistry, public health, social work, and physician assistants as members of the healthcare team from pre- to post-intervention. Implications of our data indicated the importance of IPE interventions that include not only classroom-based sessions, but actual patient care experiences within interprofessional teams. It also reinforced the importance of new and unique methods to assess IPE. 相似文献
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Students in nursing education programs have a right to privacy as they engage in their learning. At the same time, their faculty may be engaged in nursing education research in order to facilitate student learning. These two goals may conflict when faculty engage students as participants in nursing education research while at the same time facilitating their learning. Faculty as researchers with their students may encounter a conflict of interest in collecting data for their research while providing learning experiences for the same students. As a basic principle, students must be engaged as participants in an ethical manner that respects their rights for privacy. In this article, we explore the issues of faculty as researchers of their students and suggest strategies for addressing these issues. 相似文献
66.
Combustion emissions cause pro-atherosclerotic responses in apolipoprotein E-deficient (ApoE/?) mice, but the causal components of these complex mixtures are unresolved. In studies previously reported, ApoE?/? mice were exposed by inhalation 6?h/day for 50 consecutive days to multiple dilutions of diesel or gasoline exhaust, wood smoke, or simulated "downwind" coal emissions. In this study, the analysis of the combined four-study database using the Multiple Additive Regression Trees (MART) data mining approach to determine putative causal exposure components regardless of combustion source is reported. Over 700 physical-chemical components were grouped into 45 predictor variables. Response variables measured in aorta included endothelin-1, vascular endothelin growth factor, three matrix metalloproteinases (3, 7, 9), metalloproteinase inhibitor 2, heme-oxygenase-1, and thiobarbituric acid reactive substances. Two or three predictors typically explained most of the variation in response among the experimental groups. Overall, sulfur dioxide, ammonia, nitrogen oxides, and carbon monoxide were most highly predictive of responses, although their rankings differed among the responses. Consistent with the earlier finding that filtration of particles had little effect on responses, particulate components ranked third to seventh in predictive importance for the eight response variables. MART proved useful for identifying putative causal components, although the small number of pollution mixtures (4) can provide only suggestive evidence of causality. The potential independent causal contributions of these gases to the vascular responses, as well as possible interactions among them and other components of complex pollutant mixtures, warrant further evaluation. 相似文献
67.
JD McDonald M Doyle-Eisele D Kracko A Lund JD Surratt SP Hersey JH Seinfeld AC Rohr EM Knipping 《Inhalation toxicology》2012,24(11):689-697
The biological response to inhalation of secondary organic aerosol (SOA) was determined in rodents exposed to SOA derived from the oxidation of toluene, a precursor emitted from anthropogenic sources. SOA atmospheres were produced to yield 300 μg·m(-3) of particulate matter (PM) plus accompanying gases. Whole-body exposures were conducted in mice to assess both pulmonary and cardiovascular effects. ApoE(-/-) mice were exposed for 7 days and measurements of TBARS and gene expression of heme-oxygenase-1 (HO-1), endothelin-1 (ET-1), and matrix metalloproteinase-9 (MMP-9) were made in aorta. Pulmonary inflammatory responses in both species were measured by bronchoalveolar lavage fluid (BALF) cell counts. No pulmonary inflammation was observed. A mild response was observed in mouse aorta for the upregulation of ET-1 and HO-1, with a trend for increased MMP-9 and TBARS, and. Overall, toluene-derived SOA revealed limited biological response compared with previous studies using this exposure protocol with other environmental pollutants. 相似文献
68.
Brachet D Mucci S Desolneux G Leboulanger G Amie F Pessaux P Arnaud JP 《European journal of gastroenterology & hepatology》2007,19(9):801-804
The occurrence of mucinous cystadenomas localized to the liver and pancreas simultaneously and treated with a single surgical procedure has been described for the first time in this report. A 47-year-old woman attended the outpatient clinic complaining of abdominal pain and the appearance of an abdominal mass. On clinical examination, hepatomegaly was found. An abdominal computed tomography scan showed a large cystic lesion of the left lobe of the liver, thus causing the hepatomegaly. Moreover, the computed tomography scan showed a cystic lesion of the pancreas. Both lesions had thick walls and septa. Magnetic resonance imaging of the liver and pancreas confirmed the presence of septa within the cysts. Surgery was performed owing to the suspected malignancy. It should be emphasized that the patient had preoperatively received prophylactic treatment for hydatosis. A hepatic pericystectomy and enucleation of the pancreatic lesion were performed during the surgery. Pathology showed a mucinous cystadenoma without sign of malignancy. At the 4-year follow-up, no recurrence was found. This case is of interest for several reasons: the unusual double presentation, the treatment, and the follow-up. This case report confirms the common origin of mucinous cystic tumours of liver and pancreas. 相似文献
69.
Hong Xie Amie L. Holmes Jamie L. Young Qin Qin Kellie Joyce Cheng Peng Sandra S. Wise Antony S. Jeevarajan Dianne Hammond 《Toxicology and applied pharmacology》2009,234(3):293-1629
Hexavalent chromium Cr(VI) is a respiratory toxicant and carcinogen, with solubility playing an important role in its carcinogenic potential. Zinc chromate, a water insoluble or ‘particulate’ Cr(VI) compound, has been shown to be carcinogenic in epidemiology studies and to induce tumors in experimental animals, but its genotoxicity is poorly understood. Our study shows that zinc chromate induced concentration-dependent increases in cytotoxicity, chromosome damage and DNA double strand breaks in human lung cells. In response to zinc chromate-induced breaks, MRE11 expression was increased and ATM and ATR were phosphorylated, indicating that the DNA double strand break repair system was initiated in the cells. In addition, our data show that zinc chromate-induced double strand breaks were only observed in the G2/M phase population, with no significant amount of double strand breaks observed in G1 and S phase cells. These data will aid in understanding the mechanisms of zinc chromate toxicity and carcinogenesis. 相似文献
70.
Concentrations of zidovudine- and lamivudine-triphosphate according to cell type in HIV-seronegative adults 总被引:1,自引:0,他引:1
Anderson PL Zheng JH King T Bushman LR Predhomme J Meditz A Gerber J Fletcher CV 《AIDS (London, England)》2007,21(14):1849-1854
INTRODUCTION: Concentrations of zidovudine (ZDV)- and lamivudine (3TC)-triphosphates (TP) have been quantified in unfractionated peripheral blood mononuclear cells (PBMC) from HIV+ patients. The objective of this study was to determine whether concentrations of ZDV-TP and 3TC-TP in PBMC reflect the concentrations within CD4 T cells in HIV-seronegative adults. METHODS: Volunteers had taken 300 mg of ZDV plus 150 mg of 3TC twice daily for > or = 7 days. Blood (60 mL) was collected 2 or 5 h post observed dose. PBMC were processed into three cell fractions using CD4 magnetic immunobeads: CD4-purified cells; unfractionated PBMC; and CD4-depleted PBMC. TP were determined in each cell fraction with liquid chromatography-mass spectrometry and compared across cell types by non-parametric analyses. RESULTS: Six males and two females participated. The median (range) percentage of CD4 T cells (CD4%) in each fraction were: CD4-purified, 99%; unfractionated, 63% (range, 53-70); and CD4-depleted, 14% (range, 4-29). Corresponding median (range) ZDV-TP concentrations were 8.0 (5.3-10.3), 26.5 (12.9-42.2), and 34.2 (16.4-52.2) fmol/1 x 10 cells (Friedman P = 0.0008). The 3TC-TP values were 4.6 (2.3-6.7), 4.8 (3.5-8.8), and 6.8 (4.0-13.1) pmol//1 x 10 cells (Friedman P = 0.01). In mixed model analyses: ZDV-TP (fmol/1 x 10 cells) = 42-0.32 (CD4%); P < 0.001 and 3TC-TP (pmol/1 x 10 cells) = 7.3-0.03(CD4%); P = 0.003. CONCLUSIONS: In HIV-seronegative volunteers, 3TC-TP concentrations in PBMC reflected the concentrations within CD4 T cells, but ZDV-TP concentrations were more than 70% lower in CD4 T cells than in PBMC. Thus, TP concentrations differ according to cell type in vivo with corresponding efficacy and toxicity implications for cells with low or high triphosphates. 相似文献