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141.
Livasy CA Perou CM Karaca G Cowan DW Maia D Jackson S Tse CK Nyante S Millikan RC 《Human pathology》2007,38(2):197-204
Microarray profiling of invasive breast carcinomas has identified subtypes including luminal A, luminal B, HER2-overexpressing, and basal-like. The poor-prognosis, basal-like tumors have been immunohistochemically characterized as estrogen receptor (ER)-negative, HER2/neu-negative, and cytokeratin 5/6-positive and/or epidermal growth factor receptor (EGFR)-positive. The aim of this study was to determine the prevalence of basal-like ductal carcinoma in situ in a population-based series of cases using immunohistochemical surrogates. A total of 245 pure ductal carcinoma in situ cases from a population-based, case-control study were evaluated for histologic characteristics and immunostained for ER, HER2/neu, EGFR, cytokeratin 5/6, p53, and Ki-67. The subtypes were defined as: luminal A (ER+, HER2-), luminal B (ER+, HER2+), HER2 positive (ER-, HER2+), and basal-like (ER-, HER2-, EGFR+, and/or cytokeratin 5/6+). The prevalence of breast cancer subtypes was basal-like (n = 19 [8%]); luminal A, n = 149 (61%); luminal B, n = 23 (9%); and HER2+/ER-, n = 38 (16%). Sixteen tumors (6%) were unclassified (negative for all 4 defining markers). The basal-like subtype was associated with unfavorable prognostic variables including high-grade nuclei (P < .0001), p53 overexpression (P < .0001), and elevated Ki-67 index (P < .0001). These studies demonstrate the presence of a basal-like in situ carcinoma, a potential precursor lesion to invasive basal-like carcinoma. 相似文献
142.
Estradiol activates mast cells via a non-genomic estrogen receptor-alpha and calcium influx 总被引:3,自引:0,他引:3
Zaitsu M Narita S Lambert KC Grady JJ Estes DM Curran EM Brooks EG Watson CS Goldblum RM Midoro-Horiuti T 《Molecular immunology》2007,44(8):1977-1985
BACKGROUND: Allergic airway diseases are more common in females than in males during early adulthood. A relationship between female hormones and asthma prevalence and severity has been suggested, but the cellular and molecular mechanisms are not understood. OBJECTIVE: To elucidate the mechanism(s) by which estrogens enhance the synthesis and release of mediators of acute hypersensitivity. METHODS: Two mast cell/basophil cell lines (RBL-2H3 and HMC-1) and primary cultures of bone marrow derived mast cells, all of which naturally express estrogen receptor-alpha, were examined. Cells were incubated with physiological concentrations of 17-beta-estradiol with and without IgE and allergens. Intracellular Ca(2+) concentrations and the release of beta-hexosaminidase and leukotriene C(4) were quantified. RESULTS: Estradiol alone induced partial release of the preformed, granular protein beta-hexosaminidase from RBL-2H3, BMMC and HMC-1, but not from BMMC derived from estrogen receptor-alpha knock-out mice. The newly synthesized LTC(4) was also released from RBL-2H3. Estradiol also enhanced IgE-induced degranulation and potentiated LTC(4) production. Intracellular Ca(2+) concentration increased prior to and in parallel with mediator release. Estrogen receptor antagonists or Ca(2+) chelation inhibited these estrogenic effects. CONCLUSION: Binding of physiological concentrations of estradiol to a membrane estrogen receptor-alpha initiates a rapid onset and progressive influx of extracellular Ca(2+), which supports the synthesis and release of allergic mediators. Estradiol also enhances IgE-dependent mast cell activation, resulting in a shift of the allergen dose response. 相似文献
143.
Foulkes WD 《The New England journal of medicine》2007,357(25):2539-2541
144.
SimPEL: Simulation‐based power estimation for sequencing studies of low‐prevalence conditions 下载免费PDF全文
Chen Cao Paul Gordon Maja Tarailo‐Graovac Chad Bousman Pei Wang Quan Long 《Genetic epidemiology》2018,42(5):480-487
Power estimations are important for optimizing genotype‐phenotype association study designs. However, existing frameworks are designed for common disorders, and thus ill‐suited for the inherent challenges of studies for low‐prevalence conditions such as rare diseases and infrequent adverse drug reactions. These challenges include small sample sizes and the need to leverage genetic annotation resources in association analyses for the purpose of ranking potential causal genes. We present SimPEL, a simulation‐based program providing power estimations for the design of low‐prevalence condition studies. SimPEL integrates the usage of gene annotation resources for association analyses. Customizable parameters, including the penetrance of the putative causal allele and the employed pathogenic scoring system, allow SimPEL to realistically model a large range of study designs. To demonstrate the effects of various parameters on power, we estimated the power of several simulated designs using SimPEL and captured power trends in agreement with observations from current literature on low‐frequency condition studies. SimPEL, as a tool, provides researchers studying low‐frequency conditions with an intuitive and highly flexible avenue for statistical power estimation. The platform‐independent “batteries included” executable and default input files are available at https://github.com/precisionomics/SimPEL . 相似文献
145.
A pragmatic neurological screen for patients with suspected cord compressive myelopathy 总被引:2,自引:0,他引:2
Physical therapists commonly use screening tests to identify upper motoneuron lesions such as cord compressive myelopathy (CCM), the presence of which necessitates appropriate medical referral. Signs and symptoms of CCM include sensory and ataxic changes of the lower extremities, poorly coordinated gait, weakness, tetraspasticity, clumsiness, spasticity, hyperreflexia, and primitive reflexes. Clinical tests and measures such as Hoffmann sign, clonus, Lhermitte sign, the grip and release test, the finger escape sign, the Babinski test, and the inverted supinator sign have historically been used as screens for CCM. For effectiveness as a screen, a clinical test or measure should demonstrate high sensitivity. Diagnostic accuracy studies have shown that clinical tests and measures for CCM often display low sensitivity, indicating that a negative finding may falsely suggest the absence of a condition or disease that actually is present. To counter the low levels of sensitivity, screening should include a combination of a thorough patient history, recognition of and appropriate referral for cauda equina symptoms, and clusters of any pertinent contributory tests and measures. 相似文献
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This column discusses the factors affecting hemostasis and the common coagulation studies used to assess patients with bleeding disorders. 相似文献
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