32 research outputs found
Haploinsufficiency for BRCA1 is associated with normal levels of DNA nucleotide excision repair in breast tissue and blood lymphocytes
BACKGROUND: Screening mammography has had a positive impact on breast cancer mortality but cannot detect all breast tumors. In a small study, we confirmed that low power magnetic resonance imaging (MRI) could identify mammographically undetectable tumors by applying it to a high risk population. Tumors detected by this new technology could have unique etiologies and/or presentations, and may represent an increasing proportion of clinical practice as new screening methods are validated and applied A very important aspect of this etiology is genomic instability, which is associated with the loss of activity of the breast cancer-predisposing genes BRCA1 and BRCA2. In sporadic breast cancer, however, there is evidence for the involvement of a different pathway of DNA repair, nucleotide excision repair (NER), which remediates lesions that cause a distortion of the DNA helix, including DNA cross-links.
CASE PRESENTATION: We describe a breast cancer patient with a mammographically undetectable stage I tumor identified in our MRI screening study. She was originally considered to be at high risk due to the familial occurrence of breast and other types of cancer, and after diagnosis was confirmed as a carrier of a Q1200X mutation in the BRCA1 gene. In vitro analysis of her normal breast tissue showed no differences in growth rate or differentiation potential from disease-free controls. Analysis of cultured blood lymphocyte and breast epithelial cell samples with the unscheduled DNA synthesis assay (UDS) revealed no deficiency in nucleotide excision repair (NER).
CONCLUSION: As new breast cancer screening methods become available and cost effective, patients such as this one will constitute an increasing proportion of the incident population, so it is important to determine whether they differ from current patients in any clinically important ways. Despite her status as a BRCA1 mutation carrier, and her mammographically dense breast tissue, we did not find increased cell proliferation or deficient differentiation potential in her breast epithelial cells, which might have contributed to her cancer susceptibility. Although NER deficiency has been demonstrated repeatedly in blood samples from sporadic breast cancer patients, analysis of blood cultured lymphocytes and breast epithelial cells for this patient proves definitively that heterozygosity for inactivation of BRCA1 does not intrinsically confer this type of genetic instability. These data suggest that the mechanism of genomic instability driving the carcinogenic process may be fundamentally different in hereditary and sporadic breast cancer, resulting in different genotoxic susceptibilities, oncogene mutations, and a different molecular pathogenesis
Elemental Analysis of Iraqi cement by Neutron Activation ‫الخالصة‬ ‫د‬ ‫د‬ ‫دلط‬ ‫دل‬ ‫التقد‬ ‫دطرتدة‬ ‫داد‬ ‫دت‬ ‫د‬ ‫دت‬ ‫لقد‬ ‫د‬ ‫د‬ ‫لد‬ ‫داي‬ ‫د‬ ‫لق‬ ‫للقي‬ ‫دن‬ ‫د‬ ‫دلن‬ ‫ا‬ ‫د‬ ‫الطنشد‬ 37 ‫دي‬ ‫د‬ ‫لد‬ ‫دل‬ ‫دعنا‬ ‫دتاد‬ ‫دي‬ ‫د‬ ‫دلد‬ ‫عنصد‬
Abstract Neutron Activation Analysis was used to measure concentrations of up to 37 elements in cement. Most major and minor elements are measurable except Si, Al and Mg. The method proved to be excellent in quarries investigation but not for daily quality control of cement product
Unusual form of superficial spreading microinvasive squamous cell carcinoma of uterine cervix involving the endometrium of uterus
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Racial Disparities in Access and Use of Diabetes Technology Among Adult Patients with Type 1 Diabetes in a U.S. Academic Medical Center
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Objective: Recent studies highlight racial disparities in insulin pump (PUMP) and continuous glucose monitor (CGM) use in children and adolescents with type 1 diabetes (T1D). This study explored racial disparities in diabetes technology among adult patients with T1D.
Research Design and Methods: Retrospective clinic-based cohort study of adult patients with T1D seen consecutively from April 2013 to January 2020. Race was categorized into non-Black (reference group) and Black. The primary outcomes were baseline and prevalent technology use, rates of diabetes technology discussions (CGMdiscn, PUMPdiscn), and prescribing (CGMrx, PUMPrx). Multivariable logistic regression analysis evaluated the association of technology discussions and prescribing with race, adjusting for social determinants of health and diabetes outcomes.Â
Results: Â Among 1,528 adults with T1D, baseline technology use was significantly lower for Black compared to non-Black patients (7.9% vs. 30.3% for CGM; 18.7% vs. 49.6% for pump), as was prevalent use (43.6% vs. 72.1% for CGM; 30.7% vs. 64.2% for pump). Black patients had adjusted odds ratios (aORs) of 0.51 (95% CI, 0.29, 0.90) and 0.61 (95% CI, 0.41, 0.93) for CGMdiscn and CGMrx, respectively. Black patients had aORs of 0.74 (95% CI, 0.44, 1.25) and 0.40 (95% CI, 0.22, 0.70), for PUMPdiscn and PUMPrx, respectively. Neighborhood context, insurance, marital and employment status, and number of clinic visits were also associated with the outcomes.
Conclusions and Relevance: Significant racial disparities were observed in discussions, prescribing, and use of diabetes technology. Further research is needed to identify the causes behind these disparities and develop and evaluate strategies to reduce them.</p