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11.
FJ Couch ML DeShano MA Blackwood K Calzone J Stopfer L Campeau A Ganguly T Rebbeck BL Weber 《Canadian Metallurgical Quarterly》1997,336(20):1409-1415
BACKGROUND: To define the incidence of BRCA1 mutations among patients seen in clinics that evaluate the risk of breast cancer, we analyzed DNA samples from women seen in this setting and constructed probability tables to provide estimates of the likelihood of finding a BRCA1 mutation in individual families. METHODS: Clinical information, family histories, and blood for DNA analysis were obtained from 263 women with breast cancer. Conformation-sensitive gel electrophoresis and DNA sequencing were used to identify BRCA1 mutations. RESULTS: BRCA1 mutations were identified in 16 percent of women with a family history of breast cancer. Only 7 percent of women from families with a history of breast cancer but not ovarian cancer had BRCA1 mutations. The rates were higher among women from families with a history of both breast and ovarian cancer. Among family members, an average age of less than 55 years at the diagnosis of breast cancer, the presence of ovarian cancer, the presence of breast and ovarian cancer in the same woman, and Ashkenazi Jewish ancestry were all associated with an increased risk of detecting a BRCA1 mutation. No association was found between the presence of bilateral breast cancer or the number of breast cancers in a family and the detection of a BRCA1 mutation, or between the position of the mutation in the BRCA1 gene and the presence of ovarian cancer in a family. CONCLUSIONS: Among women with breast cancer and a family history of the disease, the percentage with BRCA1 coding-region mutations is less than the 45 percent predicted by genetic-linkage analysis. These results suggest that even in a referral clinic specializing in screening women from high-risk families, the majority of tests for BRCA1 mutations will be negative and therefore uninformative. 相似文献
12.
A rapid, multiresidue solid-phase extraction (SPE) technique for determination of organochlorine pesticide and polychlorinated biphenyl (PCB) residues in nonfatty fish was modified for use with fatty fish. In the modified procedures, samples are extracted with acetonitrile, and the extract is cleaned up with both C18 and Florisil SPE columns. Residues are determined by gas chromatography with electron capture detection. The original method was modified for use with fatty fish by reducing the amount of tissue extracted and by using an improved Florisil SPE cleanup. Recovery data are presented for 24 fortified organochlorine pesticide residues (0.12 ppm) and 3 fortified PCB residues (0.80 ppm) from flounder, bluefish, and shad samples, which contained 0.8, 5.4, and 22.6% fat, respectively. For the 3 types of fish, recoveries of 23 of 24 fortified organochlorine pesticide residues ranged from 55 to 129%, and recoveries of 3 fortified PCB residues ranged from 55 to 104%. There were no significant differences in recovery based on fish species and/or fat content for the majority of residues studied. This SPE method and the official AOAC method yielded comparable results for fish containing incurred organochlorine residues. 相似文献
13.
EF Bernstein FJ Sullivan JB Mitchell GD Salomon E Glatstein 《Canadian Metallurgical Quarterly》1993,20(3):435-453
Radiation therapy exerts both acute and chronic effects on normal tissue included within treatment fields. The physics of radiation therapy and treatment techniques to minimize deleterious effects of radiation are presented. Management of radiation-damaged skin is discussed. Radiation effect on tissue, wound healing, and tumorigenesis also are reviewed. 相似文献
14.
Prostaglandin A2 (PGA2) potently inhibits cell proliferation and suppresses tumor growth in vivo, but little is known regarding the molecular mechanisms mediating these effects. Here we demonstrate that treatment of breast carcinoma MCF-7 cells with PGA2 leads to G1 arrest associated with a dramatic decrease in the levels of cyclin D1 and cyclin-dependent kinase 4 (cdk4) and accompanied by an increase in the expression of p21. We further show that these effects occur independent of cellular p53 status. The decline in cyclin D and cdk4 protein levels is correlated with loss in cdk4 kinase activity, cdk2 activity is also significantly inhibited in PGA2-treated cells, an effect closely associated with the upregulation of p21. Immunoprecipitation experiments verified that p21 was indeed complexed with cdk2 in PGA2-treated cells. Additional experiments with synchronized MCF-7 cultures stimulated with serum revealed that treatment with PGA2 prevents the progression of cells from G1 to S. Accordingly, the kinase activity associated with cdk4, cyclin E, and cdk2 immunocomplexes, which normally increases following serum addition, was unchanged in PGA2-treated cells. Furthermore, the retinoblastoma protein (Rb), a substrate of cdk4 and cdk2 whose phosphorylation is necessary for cell cycle progression, remains underphosphorylated in PGA2-treated serum-stimulated cells. These findings indicate that PGA2 exerts its growth-inhibitory effects through modulation of the expression and/or activity of several key G1 regulatory proteins. Our results highlight the chemotherapeutic potential of PGA2, particularly for suppressing growth of tumors lacking p53 function. 相似文献
15.
Cellular mechanisms for developmental toxicity of chlorpyrifos: targeting the adenylyl cyclase signaling cascade 总被引:8,自引:0,他引:8
X Song FJ Seidler JL Saleh J Zhang S Padilla TA Slotkin 《Canadian Metallurgical Quarterly》1997,145(1):158-174
Developmental neurotoxicity caused by chlorpyrifos exposure is generally thought to target cholinesterase but chlorpyrifos may also act on cellular intermediates, such as adenylyl cyclase, that serve global functions in the coordination of cell development. In the current study, neonatal rats were exposed to apparently subtoxic doses of chlorpyrifos (no weight loss, no mortality) either on Postnatal Days 1-4 or on Postnatal Days 11-14, and the effects on components of the adenylyl cyclase cascade were evaluated in brain regions that are enriched (forebrain) or sparse (cerebellum) in cholinergic innervation, as well as in a nonneural tissue (heart). In all three, chlorpyrifos evoked deficits in multiple components of the adenylyl cyclase cascade: expression and activity of adenylyl cyclase itself, functioning of G-proteins that link neurotransmitter and hormone receptors to cyclase activity, and expression of neurotransmitter receptors that act through this cascade. Disruption of signaling function was not restricted to transduction of cholinergic signals but rather extended to adrenergic signals as well. In most cases, the adverse effects were not evident during the immediate period of chlorpyrifos administration, but appeared after a delay of several days. These results suggest that chlorpyrifos can affect cell development by altering the activity and reactivity of the adenylyl cyclase signaling cascade, a major control point for trophic regulation of cell differentiation. The effects are not restricted to cholinergic targets, nor even to the central nervous system. Hence, disruption of cell development by chlorpyrifos is likely to be more widespread than previously thought. 相似文献
16.
17.
Carballo V.M.B. Chefdeville M. Fransen M. van der Graaf H. Melai J. Salm C. Schmitz J. Timmermans J. 《Electron Device Letters, IEEE》2008,29(6):585-587
An unpackaged microchip is used as the sensing element in a miniaturized gaseous proportional chamber. This letter reports on the fabrication and performance of a complete radiation imaging detector based on this principle. Our fabrication schemes are based on wafer-scale and chip-scale postprocessing. Compared to hybrid-assembled gaseous detectors, our microsystem shows superior alignment precision and energy resolution, and offers the capability to unambiguously reconstruct 3D radiation tracks on the spot. 相似文献
18.
19.
Researchers have carried out a variety of investigations to determine the properties of available dentin bonding systems. The test methods and variables used in 50 published investigations of bond strength were analyzed. Among the studies analyzed, shear tests predominated, being used in 80% of the studies; dentin from human molar teeth was used most often (in 88% of investigations); and the most prevalent time of testing was 24 hours postcuring. However, a number of potential variables were not recorded in a high proportion of articles, among these the film thickness, the type of dentin tested, and the surface condition (moist or dry). The mode of failure was recorded in only 42% of the investigations assessed. It was found that there is little standardization of test methods in studies of dentin bond strength and that a number of variables are often either not recorded or reported. 相似文献
20.
We describe twin girls with bilateral cerebrovascular disease. In one child, a diagnosis of moyamoya disease was made after presentation in infancy with an acute hemiparesis; her asymptomatic sibling was found to have significant bilateral cerebrovascular disease after neuropsychological evaluation and assessment with transcranial Doppler ultrasound. Both subjects showed a discrepancy between verbal and performance IQ and deficits on a test of frontal-lobe function suggesting that these domains should be targeted in cognitive assessment. Family members of subjects with moyamoya are at risk of cerebrovascular disease. Clinical symptoms do not reliably predict disease and those at risk should be offered screening with non-invasive vascular imaging. 相似文献