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91.
Agnieszka Pluta Tadeusz Robak Barbara Cebula Agata Majchrzak Piotr Pluta Kamil Brzozowski Konrad Stpka Anna Szmigielska-Kapon Olga Grzybowska-Izydorczyk Magdalena Czemerska Piotr Smolewski Agnieszka Wierzbowska 《Archives of Medical Science》2021,17(3):700
IntroductionThe misbalance between a family of inhibitor of apoptosis proteins (IAP), regulated by the nuclear factor kappa B (NF-κB) and their natural antagonist second mitochondrial-derived activator of caspases/direct IAP binding protein with low pI (Smac/DIABLO) are important to biology of acute myeloid leukemia (AML).Material and methodsThe aim of the study was to assess NF-κB and Smac/DIABLO proteins expression in blasts of 109 newly diagnosed AML patients using the multicolor flow cytometry and evaluate their influence on AML patients outcome.ResultsExpression of NF-κB and of Smac/DIABLO proteins were found in 95% and 98% of the patients, respectively. A negative correlation between Smac/DIABLO and NF-κB was observed. Age < 60 years old as well as higher Smac/DIABLO expression were associated with a higher probability of complete response achievement in the multivariate analysis. Longer overall survival (OS) in the univariate and multivariate analyses was influenced by age < 60 years old, a favorable or intermediate-risk karyotype and high Smac/DIABLO expression. Additionally, in the survival analysis of the subgroups, the patients aged < 60 years old, with high Smac/DIABLO expression, lower NF-κB expression and < 50% of bone marrow blasts who were treated with standard treatment had better OS.ConclusionsLower NF-κB and higher Smac/DIABLO expression may influence AML patients outcome. 相似文献
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Konrad Oexle Barbara Schormair Janina S Ried Darina Czamara Katharina Heim Birgit Frauscher Birgit H?gl Claudia Trenkwalder G Martin Fiedler Joachim Thiery Peter Lichtner Holger Prokisch Michael Specht Bertram Müller-Myhsok Angela D?ring Christian Gieger Annette Peters H-Erich Wichmann Thomas Meitinger Juliane Winkelmann 《European journal of human genetics : EJHG》2013,21(4):410-414
Restless legs syndrome (RLS) is a common multifactorial disease. Some genetic risk factors have been identified. RLS susceptibility also has been related to iron. We therefore asked whether known iron-related genes are candidates for association with RLS and, vice versa, whether known RLS-associated loci influence iron parameters in serum. RLS/control samples (n=954/1814 in the discovery step, 735/736 in replication 1, and 736/735 in replication 2) were tested for association with SNPs located within 4 Mb intervals surrounding each gene from a list of 111 iron-related genes using a discovery threshold of P=5 × 10−4. Two population cohorts (KORA F3 and F4 with together n=3447) were tested for association of six known RLS loci with iron, ferritin, transferrin, transferrin-saturation, and soluble transferrin receptor. Results were negative. None of the candidate SNPs at the iron-related gene loci was confirmed significantly. An intronic SNP, rs2576036, of KATNAL2 at 18q21.1 was significant in the first (P=0.00085) but not in the second replication step (joint nominal P-value=0.044). Especially, rs1800652 (C282Y) in the HFE gene did not associate with RLS. Moreover, SNPs at the known RLS loci did not significantly affect serum iron parameters in the KORA cohorts. In conclusion, the correlation between RLS and iron parameters in serum may be weaker than assumed. Moreover, in a general power analysis, we show that genetic effects are diluted if they are transmitted via an intermediate trait to an end-phenotype. Sample size formulas are provided for small effect sizes. 相似文献
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Increased pulmonary prostacyclin synthesis in rats with chronic hypoxic pulmonary hypertension 总被引:3,自引:0,他引:3
Blumberg FC Lorenz C Wolf K Sandner P Riegger GA Pfeifer M 《Cardiovascular research》2002,55(1):171-177
OBJECTIVE: The regulation of pulmonary prostacyclin synthesis is not completely understood. We tested the hypothesis that prostacyclin production is predominantly stimulated by hemodynamic factors, such as increased shear-stress, and is thus increased in rats with chronic hypoxic pulmonary hypertension. METHODS: To this end, we determined pulmonary prostacyclin synthase (PGIS) gene expression, circulating levels of the stable prostacyclin metabolite 6-keto prostaglandin F(1alpha) (6-keto-PGF(1alpha)), pulmonary endothelin (ET)-1 gene expression, and ET-1 plasma levels in rats exposed to 4 weeks of hypoxia (10% O(2)) in the presence or absence of either the nitric oxide (NO) donor molsidomine (MD, 15 mg/kg/day) or the ET-A receptor antagonist LU135252 (LU, 50 mg/kg/day). RESULTS: Right ventricular systolic pressure (RVSP), the cross-sectional medial vascular wall area of pulmonary arteries, and ET-1 production increased significantly during hypoxia. PGIS mRNA levels increased 1.7-fold, and 6-keto-PGF(1alpha) plasma levels rose from 8.2+/-0.8 to 12.2+/-2.2 ng/ml during hypoxia (each P<0.05 vs. normoxic controls). MD and LU reduced RVSP and pulmonary vascular remodeling similarly (each P<0.05 vs. hypoxia), but only MD inhibited pulmonary ET-1 formation (P<0.05 vs. hypoxia). Nevertheless, both drugs attenuated the increase in PGIS gene expression and plasma 6-keto-PGF(1alpha) levels (each P<0.05 vs. hypoxia). CONCLUSION: Our data suggest that prostacyclin production in hypertensive rat lungs is predominantly increased by hemodynamic factors while hypoxia, NO and ET-1 per are less important stimuli, and that this increase may serve as a compensatory mechanism to partially negate the hypoxia-induced elevation in pulmonary vascular tone. 相似文献
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What effect does increasing inpatient time have on outpatient-oriented internist satisfaction?
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Saint S Zemencuk JK Hayward RA Golin CE Konrad TR Linzer M;SGIM Career Satisfaction Group 《Journal of general internal medicine》2003,18(9):725-729
OBJECTIVE: Because career satisfaction among general internists is relatively low, we sought to understand the impact on satisfaction of general internists managing patients both in and outside of the hospital. Using data from a national survey, we asked, “Among outpatient-oriented general internists (i.e., internists who spend less than 50% of their clinical time caring for inpatients), what effect does time spent in the hospital have on physician satisfaction, stress, and burnout?” DESIGN/PARTICIPANTS: The Physician Worklife Study, in which 5,704 physicians in primary and specialty nonsurgical care selected from the American Medical Association’s Masterfile were surveyed (adjusted response rate=52%), was used. Our analyses focused on clinically active outpatient-oriented general internists (N=339). MEASUREMENTS AND MAIN RESULTS: We constructed multivariate linear models to test for statistically significant associations between the amount of time spent seeing inpatients and physician satisfaction as measured by several satisfaction scales. Even after controlling for total hours worked and other possible confounding variables, we found that increased time working in the hospital was significantly associated with decreases in satisfaction with administration, specialty, autonomy, and personal time, and significantly associated with an increase in life stress. There was also a significant association between increased time spent in the hospital and burnout. CONCLUSIONS: Our findings imply that there may be a tension between the practice of inpatient and outpatient medicine by general internists, and suggest that fewer hospital duties may increase career satisfaction for outpatient-oriented internists. Although additional studies are warranted in order to better understand why these relationships exist, our data suggest that the hospitalist model of inpatient care might be one approach to alleviate stress and improve satisfaction for many general internists. 相似文献
100.
Anja K. Büscher Bodo B. Beck Anette Melk Julia Hoefele Birgitta Kranz Daniel Bamborschke Sabrina Baig B?rbel Lange-Sperandio Theresa Jungraithmayr Lutz T. Weber Markus J. Kemper Burkhard T?nshoff Peter F. Hoyer Martin Konrad Stefanie Weber 《Clinical journal of the American Society of Nephrology》2016,11(2):245-253