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排序方式: 共有7136条查询结果,搜索用时 15 毫秒
61.
Rajakulendran T Sahmi M Kurinov I Tyers M Therrien M Sicheri F 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(8):2836-2841
RAF kinase functions in the mitogen-activated protein kinase (MAPK) pathway to transmit growth signals to the downstream kinases MEK and ERK. Activation of RAF catalytic activity is facilitated by a regulatory complex comprising the proteins CNK (Connector enhancer of KSR), HYP (Hyphen), and KSR (Kinase Suppressor of Ras). The sterile alpha-motif (SAM) domain found in both CNK and HYP plays an essential role in complex formation. Here, we have determined the x-ray crystal structure of the SAM domain of CNK in complex with the SAM domain of HYP. The structure reveals a single-junction SAM domain dimer of 1:1 stoichiometry in which the binding mode is a variation of polymeric SAM domain interactions. Through in vitro and in vivo mutational analyses, we show that the specific mode of dimerization revealed by the crystal structure is essential for RAF signaling and facilitates the recruitment of KSR to form the CNK/HYP/KSR regulatory complex. We present two docking-site models to account for how SAM domain dimerization might influence the formation of a higher-order CNK/HYP/KSR complex. 相似文献
62.
Miller K Myers TJ Robertson K Shah N Delgado RM Gregoric ID 《Congestive heart failure (Greenwich, Conn.)》2004,10(5):226-229
Research suggests that ventricular assist devices improve quality of life for congestive heart failure patients awaiting heart transplantation. Axial flow ventricular assist devices like the Jarvik 2000 (Jarvik Heart, Inc., New York, NY) represent the newest type of ventricular assist device technology, but their effects on quality of life are not well understood. Therefore, the authors administered the Minnesota Living with Heart Failure Questionnaire to patients who had the Jarvik 2000 implanted as a bridge to heart transplantation. Patients completed the Minnesota Living with Heart Failure Questionnaire immediately before device implantation, 1 month after implantation, immediately before heart transplantation, and 1 month after transplantation. One month after implantation of the device, the nine patients who completed the study showed significant improvements in physical (p<0.008), emotional (p<0.02), and overall (p<0.008) quality of life. These improvements were maintained until the device was explanted. The authors conclude that implantation of the Jarvik 2000 ventricular assist device can substantially improve quality of life for patients awaiting heart transplantation. 相似文献
63.
64.
Kulminski AM Arbeev KG Kulminskaya IV Ukraintseva SV Land K Akushevich I Yashin AI 《Journal of the American Geriatrics Society》2008,56(1):105-110
OBJECTIVES: To investigate the relationship between body mass index (BMI) and 9-year mortality in older (≥65) Americans with and without disability.
DESIGN: Cohort study.
SETTING: The unique disability-focused National Long Term Care Survey (NLTCS) data that assessed the health and well-being of older individuals in 1994 were analyzed.
PARTICIPANTS: Four thousand seven hundred ninety-one individuals in the 1994 survey.
MEASUREMENTS: BMI (kg/m2 ) was calculated from self- or proxy reports of height and weight. The analysis was adjusted for 1-year change in BMI and demographic and health-related factors, as well as reports by proxies, and death occurring during the first 2 years after the interview.
RESULTS: The relative risk of death as a function of BMI formed a nonsymmetric U-shaped pattern, with larger risks associated with lower BMI (<22.0) and minimal risks for BMI of 25.0 to 34.9. (BMI 22.0–24.9 was the reference.) Adjustments for demographic and health-related factors had little effect on this pattern. Nondisabled individuals exhibited a similar U-shaped pattern but with lower risks associated with lower BMI. For disabled individuals, the mortality–risk pattern was higher for lower BMI (<22.0) and flat for higher BMI, thus exhibiting an inverse J shape. BMI patterns were age sensitive, with disability status affecting sensitivity.
CONCLUSION: Overweight or mild (grade 1) obesity was not a risk factor for 9-year mortality in older Americans participating in the 1994 NLTCS. A flatter BMI pattern of the relative risk of death for disabled than for nondisabled individuals suggests that optimal body weight can be sensitive to age and health and well-being. 相似文献
DESIGN: Cohort study.
SETTING: The unique disability-focused National Long Term Care Survey (NLTCS) data that assessed the health and well-being of older individuals in 1994 were analyzed.
PARTICIPANTS: Four thousand seven hundred ninety-one individuals in the 1994 survey.
MEASUREMENTS: BMI (kg/m
RESULTS: The relative risk of death as a function of BMI formed a nonsymmetric U-shaped pattern, with larger risks associated with lower BMI (<22.0) and minimal risks for BMI of 25.0 to 34.9. (BMI 22.0–24.9 was the reference.) Adjustments for demographic and health-related factors had little effect on this pattern. Nondisabled individuals exhibited a similar U-shaped pattern but with lower risks associated with lower BMI. For disabled individuals, the mortality–risk pattern was higher for lower BMI (<22.0) and flat for higher BMI, thus exhibiting an inverse J shape. BMI patterns were age sensitive, with disability status affecting sensitivity.
CONCLUSION: Overweight or mild (grade 1) obesity was not a risk factor for 9-year mortality in older Americans participating in the 1994 NLTCS. A flatter BMI pattern of the relative risk of death for disabled than for nondisabled individuals suggests that optimal body weight can be sensitive to age and health and well-being. 相似文献
65.
Bertini M Ziacchi M Biffi M Martignani C Saporito D Valzania C Diemberger I Cervi E Frisoni J Sangiorgi D Branzi A Boriani G 《The American journal of cardiology》2008,102(10):1373-1377
Present devices for cardiac resynchronization therapy offer the possibility of tailoring the hemodynamic effect of biventricular pacing by optimization of the interventricular delay (VV) beyond atrioventricular (AV)-interval optimization. It was not yet defined whether a QRS width-based strategy may be a helpful tool for echocardiography for device programming. The aim of the study was to investigate the relation between VV-interval optimization guided by echocardiography and guided by QRS interval width. One hundred six patients with a cardiac resynchronization therapy device for > or =3 months were enrolled. All patients underwent echocardiographic AV and VV delay optimization. The AV interval was optimized according to the E wave-A wave (EA) interval and left ventricular filling time. At the optimal AV delay, VV optimization was performed by measuring the aortic velocity time integral at 5 different settings: simultaneous right and left ventricle output, left ventricle pre-excitation (left ventricle + 40 and 80 ms, respectively), and right ventricle pre-excitation (right ventricle + 40 and 80 ms, respectively). A 12-lead electrocardiogram was recorded and QRS duration was measured in the lead with the greatest QRS width. The electrocardiographic (ECG)-optimized VV interval was defined according to the narrowest achievable QRS interval among 5 VV intervals. The echocardiographic-optimized VV interval was left ventricle + 40 ms in 28 patients, left ventricle + 80 ms in 15 patients, simultaneous in 46 patients, right ventricle + 40 ms in 14 patients, and right ventricle + 80 ms in 3 patients. Significant concordance (kappa = 0.69, p <0.001) was found between the echocardiographic- and ECG-optimized VV interval. In conclusion, significant concordance appeared to exist during biventricular pacing between VV programming based on the shortest QRS interval at 12-lead ECG pacing and echocardiographic-guided VV-interval optimization. A combined ECG- and echocardiographic approach could be a less time-consuming solution in performing this operation. 相似文献
66.
67.
Saidy Vásconez Noguera Evelyn Patrícia Sánchez Espinoza Marina Farrel Côrtes Izabel Cristina Vilela Oshiro Fernanda de Sousa Spadão Laura Maria Brasileiro Brandão Ana Natiele da Silva Barros Sibeli Costa Bianca Leal de Almeida Paula Gemignani Soriano Alessandra Grassi Salles Mirian Elizabete Marques Escorcio Cristina Madeira Barretti Fernanda Spadotto Baptista Glaura Souza Alvarenga Igor Marinho Leila Suemi Harima Letaif Ho Ye Li Silvia Figueiredo Costa 《American journal of infection control》2021,49(4):512-515
68.
Mayra Guerrero Amit Pursnani Akhil Narang Michael Salinger Dee Dee Wang Mackram Eleid Susheel K. Kodali Isaac George Lowell Satler Ron Waksman Christopher U. Meduri Vivek Rajagopal Ignacio Inglessis Igor Palacios Mark Reisman Marvin H. Eng Hyde M. Russell Ashish Pershad Charanjit Rihal 《JACC: Cardiovascular Interventions》2021,14(8):859-872
ObjectivesThe aim of this study was to assess 1-year clinical outcomes among high-risk patients with failed surgical mitral bioprostheses who underwent transseptal mitral valve-in-valve (MViV) with the SAPIEN 3 aortic transcatheter heart valve (THV) in the MITRAL (Mitral Implantation of Transcatheter Valves) trial.BackgroundThe MITRAL trial is the first prospective study evaluating transseptal MViV with the SAPIEN 3 aortic THV in high-risk patients with failed surgical mitral bioprostheses.MethodsHigh-risk patients with symptomatic moderate to severe or severe mitral regurgitation (MR) or severe mitral stenosis due to failed surgical mitral bioprostheses were prospectively enrolled. The primary safety endpoint was technical success. The primary THV performance endpoint was absence of MR grade ≥2+ or mean mitral valve gradient ≥10 mm Hg (30 days and 1 year). Secondary endpoints included procedural success and all-cause mortality (30 days and 1 year).ResultsThirty patients were enrolled between July 2016 and October 2017 (median age 77.5 years [interquartile range (IQR): 70.3 to 82.8 years], 63.3% women, median Society of Thoracic Surgeons score 9.4% [IQR: 5.8% to 12.0%], 80% in New York Heart Association functional class III or IV). The technical success rate was 100%. The primary performance endpoint in survivors was achieved in 96.6% (28 of 29) at 30 days and 82.8% (24 of 29) at 1 year. Thirty-day all-cause mortality was 3.3% and was unchanged at 1 year. The only death was due to airway obstruction after swallowing several pills simultaneously 29 days post-MViV. At 1-year follow-up, 89.3% of patients were in New York Heart Association functional class I or II, the median mean mitral valve gradient was 6.6 mm Hg (interquartile range: 5.5 to 8.9 mm Hg), and all patients had MR grade ≤1+.ConclusionsTransseptal MViV in high-risk patients was associated with 100% technical success, low procedural complication rates, and very low mortality at 1 year. The vast majority of patients experienced significant symptom alleviation, and THV performance remained stable at 1 year. 相似文献
69.
High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis 总被引:1,自引:0,他引:1
Shevchenko YL Novik AA Kuznetsov AN Afanasiev BV Lisukov IA Kozlov VA Rykavicin OA Ionova TI Melnichenko VY Fedorenko DA Kulagin AD Shamanski SV Ivanov RA Gorodokin G 《Experimental hematology》2008,36(8):922-928
High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (auto-HSCT) is a new and promising approach to the treatment of multiple sclerosis (MS) patients because currently there are no effective treatment methods for this disease. In this article, we present results of a prospective clinical study of efficacy of HDIT + auto-HSCT in MS patients. The following treatment strategies were employed in the study: "early," "conventional," and "salvage/late" transplantation. Fifty patients with various types of MS were included in this study. No toxic deaths were reported among 50 MS patients; transplantation procedure was well-tolerated by the patients. The efficacy analysis was performed in 45 patients. Twenty-eight patients achieved an objective improvement of neurological symptoms, defined as at least 0.5-point decrease in the Expanded Disability Status Scale (EDSS) score as compared to the baseline and confirmed during 6 months, and 17 patients had disease stabilization (steady EDSS level as compared to the baseline and confirmed during 6 months). The progression-free survival at 6 years after HDIT + auto-HSCT was 72%. Magnetic resonance imaging data were available in 37 patients before transplantation showing disease activity in 43.3%. No active, new, or enlarging lesions were registered in patients without disease progression. In conclusion, HDIT + auto-HSCT suggests positive results in management of patients with different types of MS. Identification of treatment strategies based on the level of disability, namely "early," "conventional," and "salvage/late" transplantation, appears to be feasible to improve treatment outcomes. 相似文献
70.
Gregoric ID Cohn WE Akay MH La Francesca S Myers T Frazier OH 《Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital》2008,35(2):184-185
The CentriMag left ventricular assist system can be used for perioperative or postcardiotomy circulatory support of the failing heart. The device resides at the patient's bedside, and the cannulae are usually inserted through a midline sternotomy, with the inflow cannula in the left ventricle or right superior pulmonary vein and the outflow cannula in the aorta. In a patient whose chest has been closed and who has a delayed need for temporary mechanical support, a less invasive method of left ventricular assist device cannula insertion is preferred. In these cases, the CentriMag cannulae can be inserted through a right minithoracotomy with the inflow cannula in the right superior pulmonary vein and the outflow cannula in the aorta, with no heparinization. Herein, we describe this approach in a patient who experienced postcardiotomy cardiogenic shock after aortocoronary bypass surgery. This technique may facilitate ambulation and recovery in selected patients. 相似文献