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BACKGROUND: Chronic hepatitis B (HBV) and hepatitis C (HCV) patients have elevated plasma levels of soluble CD14 (sCD14). We examined whether human hepatocytes produce sCD14 in vivo, and whether HBV or HCV infections influence this chimeric production. METHODS: uPA-SCID mice were transplanted with primary human hepatocytes and some animals were subsequently infected with HBV or HCV. Plasma from these mice was analyzed for the presence of human sCD14. The liver was examined via immunohistochemistry. RESULTS: A soluble form of human CD14 could be detected in the plasma from successfully transplanted mice, while it was completely absent in non-transplanted control animals. The isoform of this human sCD14 corresponded with the most abundant isoform found in human plasma. CD14 levels in circulation were not significantly different between non-infected, HBV infected and HCV infected animals. CONCLUSIONS: Our data indicate that human hepatocytes produce sCD14 in vivo, and that liver cells might be the major source of sCD14 in normal human plasma. In addition we demonstrate that HBV and HCV infections have no direct influence on the production of sCD14 by human hepatocytes in this chimeric model.  相似文献   
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Our objectives were to summarize literature on the association of amyotrophic lateral sclerosis (ALS) with pesticides as a group and to evaluate associations of ALS with specific pesticides. We conducted a meta-analysis of published studies of ALS and pesticides as a group and investigated the association of ALS with specific pesticides, using data from the Agricultural Health Study (AHS), a cohort including 84,739 private pesticide applicators and spouses. AHS participants provided information on pesticide use at enrollment in 1993-1997. In mortality data collected through February 2010, ALS was recorded on death certificates of 41 individuals whom we compared to the remaining cohort (controls), using unconditional logistic regression adjusted for age and gender to calculate odds ratios (ORs) and 95% confidence intervals. In the meta-analysis, ALS was associated with use of pesticides as a group (1.9, 1.1-3.1). In the AHS, ALS was not associated with pesticides as a group, but was associated with use of organochlorine insecticides (OCs) (1.6, 0.8-3.5), pyrethroids (1.4, 0.6-3.4), herbicides (1.6, 0.7-3.7), and fumigants (1.8, 0.8-3.9). ORs were elevated forever use of the specific OCs aldrin (2.1, 0.8-5.1), dieldrin (2.6, 0.9-7.3), DDT (2.1, 0.9-5.0), and toxaphene (2.0, 0.8-4.9). None of these associations was statistically significant. Similar results were observed in an analysis restricted to men. In conclusion, the meta-analysis suggests that ALS risk is associated with use of pesticides as a group, and our analysis of AHS data points to OC use in particular. The latter results are novel but based on a small number of cases and require replication in other populations.  相似文献   
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At present chronic liver disease(CLD),the third commonest cause of premature death in the United Kingdom is detected late,when interventions are ineffective,resulting in considerable morbidity and mortality.Injury to the liver,the largest solid organ in the body,leads to a cascade of inflammatory events.Chronic inflammation leads to the activation of hepatic stellate cells that undergo transdifferentiation to become myofibroblasts,the main extra-cellular matrix producing cells in the liver;over time increased extra-cellular matrix production results in the formation of liver fibrosis.Although fibrogenesis may be viewed as having evolved as a“wound healing”process that preserves tissue integrity,sustained chronic fibrosis can become pathogenic culminating in CLD,cirrhosis and its associated complications.As the reference standard for detecting liver fibrosis,liver biopsy,is invasive and has an associated morbidity,the diagnostic assessment of CLD by non-invasive testing is attractive.Accordingly,in this review the mechanisms by which liver inflammation and fibrosis develop in chronic liver diseases are explored to identify appropriate and meaningful diagnostic targets for clinical practice.Due to differing disease prevalence and treatment efficacy,disease specific diagnostic targets are required to optimally manage individual CLDs such as non-alcoholic fatty liver disease and chronic hepatitis C infection.To facilitate this,a review of the pathogenesis of both conditions is also conducted.Finally,the evidence for hepatic fibrosis regression and the mechanisms by which this occurs are discussed,including the current use of antifibrotic therapy.  相似文献   
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Oncotype DX recurrence score (ODX) can predict risk of invasive breast cancer recurrence and benefit of chemotherapy. Literature is limited on the relationship of ODX and race in women with hormone receptor positive and node negative/positive disease. Our study examines the relationship between race and clinical characteristics within a population of highly screened women with newly diagnosed breast cancer. The institutional Breast Cancer Database was queried for patients with newly diagnosed breast cancer between January2010 and March2015. We analyzed clinical and tumor characteristics including ODX. Statistical analyses included Pearson's Chi‐Square and Fisher's Exact Tests. There were 2,092 women in our study cohort. The majority had college‐level education (84%), regular screening (78%), and clinical breast exams (88%). The majority had invasive ductal carcinoma (IDC) (62%), early stage (0, I, II) tumors (93%), ER+ (84%), PR+ (71%), Her2 negative (86%), and node negative disease (83%). There was a significantly higher proportion of later stage disease among African‐Americans (p = 0.001) and Asians (p = 0.006) and more triple negative breast cancers among African‐Americans (p < 0.0001). A majority of patients had a low ODX (56%). While ODX was not different among the race categories (p = 0.97), there were significant racial differences in Ki‐67 (p < 0.0001). In a population of highly screened women, differences were found between races regarding tumor histology. No statistical difference between race and ODX was noted, but there were racial differences in Ki67. Therefore we recommend that further research be focused on refining management algorithms by ethnicity.  相似文献   
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