Antigen receptor nonresponsiveness in chronic lymphocytic leukemia B cells

B chronic lymphocytic leukemia (B-CLL) are clonal populations of mIgM+ or mIgM+/mIgD+ CD5+ B cells that appear to be arrested in the follicular mantle-zone B-cell stage. Functional analyses have shown two groups of B-CLL that can be distinguished based on their capacity to proliferate in response to B-cell antigen receptor complex (BCR) cross- linking. To investigate the molecular basis for this phenomenon, we have analyzed both architecture and functional properties of BCR complexes on these two groups of B-CLL. Both groups were found to express structurally similar BCR. However, protein tyrosine kinase (PTK) activity associated with and specific for BCR constituents was strongly diminished in nonresponsive B-CLL. Moreover, the PTK-dependent assembly of Shc/Grb2 complexes, which may couple the BCR to p21ras, was absent in these B-CLL. Finally, of all PTKs tested, the expression of PTK syk was found to be considerably lower in nonresponsive B-CLL. Thus, absence of mitogenic responses upon BCR cross-linking in particular B-CLL was found to be strictly correlated with diminished induction of BCR-associated PTK activity and lower levels of PTK syk. Because nonresponsive B-CLL closely resembles tolerant autoreactive B cells both functionally and biochemically, distinction between B-CLL with respect to functional properties in vitro may be determined by differences in antigen encounter in vivo.     

血管成形术和支架辅助血管成形术治疗颅内动脉粥样硬化的报告标准（上）

背景和目的颅内动脉粥样硬化可造成众多患者发生缺血性卒中。过去10年间血管内治疗技术已经取得突破性进展,能够开展颅内动脉粥样硬化性狭窄的血管内治疗。采用血管成形术和支架辅助阻管成形术治疗颅内动脉粥样硬化性狭窄的患者例数不断增加。但是鉴于目前血管成形术和支架辅助血管成形术治疗狭窄性和闭塞性颅内动脉粥样硬化仍缺乏普遍认可的临床和放射学评估以及皿管内治疗技术及预后的规范,此文就是提供该方面报告标准、术语和书面定义的共识性建议。报告摘要报告标准是在技术评价委员会、神经介入外科学会、介入放射学会、美国神经外科医师协会和神经外科医师代表大会的脑血管外科分会、美国神经科学会的卒中和介入神经病学分会的联合写作组共同起草完成。对1997年1月-2007年12月间,美国国立图书馆医学文献数据库（PubMed）进行计算机检索,旨在确定已发表的狭窄性颅内动脉粥样硬化的神经介入治疗中,能用作质量评价基准的资料。我们尽可能地确定影响神经介入治疗成功及并发症可能性的危险调节变量。对狭窄性和闭塞性颅内动脉粥样硬化进行麻管内治疗的临床试验设计中,不同临床和技术问题可能影响血管内治疗的疗效,此文章为这些问题提供相关的理论基础。该指南中包括对血管内治疗试验报告标准的建议。虽然制定规范和标准主要是出于研究用途,但是这也将有助于临床实践,还适用于所有相关的出版物。结论总之,报告标准提出的建议将有助于构建有效的研究数据库,同时促进产生科学可靠的研究结果,使相似研究之间或内部能够进行可靠的比较。存某些情况下,为报告和出版的一致性,本文中的定义可能是写作组专家的共识性建议。这些建议将促使不同研究组的结果具有直接可比性。     

利用常规心电图鉴别长QT综合征的基因类型

一、引言和背景　　近年来 ,先天性长 QT综合征 ( long QT syn-drome,LQTS)的临床和基础研究在国际上取得了突破性进展。截止目前 ,已从 5个致病基因上鉴定出1 77个基因突变点 ,包括 KVLQTI( LQT1) 42 % ,HERG( LQT2 ) 45% ,SCN5A( LQT3 ) 8% ,KCNE1( LQT5) 3 %和 KCNE2 ( LQT6) 2 % [1] 。LQTS在遗传学上的多样性和复杂性又给临床诊治带来困难。基于目前的技术条件 ,对于一个临床上确诊的 LQTS家系 ,找出其病变基因一般需要 1～ 3年的时间 ,而且费用昂贵 ,其阳性检出率也只有 50 %左右。为了加速实验室的基因检出率…     

血管紧张素原基因5''''端启动子区A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压的相关性

目的分析血管紧张素原基因启动子区A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压的相关性.方法实验于2005-08/2006-01在北京华大实验室完成.选取对象均为生活在内蒙古乌拉特后旗的蒙古族牧民,三代血亲内无其他民族.采用基因测序技术对内蒙古蒙古族人群中107例原发性高血压患者和108例正常对照者进行A-20C和A-6G基因分型,观察高血压组和正常对照组不同基因型的分布和等位基因频率的差异.结果①两组受试者在性别、年龄及吸烟、饮酒、体质量指数和l临床化验检查指标有较好的匹配(P均＞0.05).②两组血管紧张素原基因A-20C位点AA,AC,CC基因型频率比较差异无显著性意义(高血压组分别为0.51,0.29,0.20;正常对照组分别为0.49,0.28,0.23,x2=0.395,P=0.529).A,C等位基因频率比较差异无显著性意义(高血压组分别为0.65,0.35;正常对照组分别为0.63,0.37,x2=0.015,P=0.904).③两组血管紧张素原基因A-6G位点AA,AG,GG基因型频率比较差异无显著性意义(高血压组分别为0.50,0.33,0.17;正常对照组分别为0.55,0.34,0.11,x2=1.924,P=0.165).A,G等位基因频率比较差异无显著性意义(高血压组分别为0.66,0.34;正常对照组分别为0.72,0.28,x2=1.728,P=0.189).④高血压组协同存在血管紧张素原基因A-20C基因型CC时,血管紧张素原基因A-6G基因型GG频率稍高于正常对照组,但差异无显著性意义(x2=2.395,P=0.122,OR=7.52,95%CI 0.014～1.250),高血压组G等位基因明显高于正常对照组(分别为0.37,0.22,x2=4.658,P=0.034),携带该等位基因的蒙古族人群发生原发性高血压的相对危险度升高(OR=2.80,95%CI.087～7.271).结论血管紧张素原基因A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压相关,并可能具有协同作用.     

Interprofessional education about patient decision support in specialty care

Specialty care involves services provided by health professionals who focus on treating diseases affecting one body system. In contrast to primary care - aimed at providing continuous, comprehensive care - specialty care often involves intermittent episodes of care focused around specific medical conditions. In addition, it typically includes multiple providers who have unique areas of expertise that are important in supporting patients' care. Interprofessional care involves multiple professionals from different disciplines collaborating to provide an integrated approach to patient care. For patients to experience continuity of care across interprofessional providers, providers need to communicate and maintain a shared sense of responsibility to their patients. In this article, we describe challenges inherent in providing interprofessional patient decision support in specialty care. We propose ways for providers to engage in interprofessional decision support and discuss promising approaches to teaching an interprofessional decision support to specialty care providers. Additional evaluation and empirical research are required before further recommendations can be made about education for interprofessional decision support in specialty care.     

Doppler-derived mitral deceleration time: an early strong predictor of left ventricular remodeling after reperfused anterior acute myocardial infarction

BACKGROUND: The relation between remodeling and left ventricular (LV) diastolic function has not yet been fully investigated. The aim of this study was to determine whether early assessment of Doppler-derived mitral deceleration time (DT), a measure of LV compliance and filling, may predict progressive LV dilation after acute myocardial infarction (AMI). METHODS AND RESULTS: Fifty-one patients (aged 61+/-11 years; 6 women) with anterior AMI successfully treated with direct coronary angioplasty underwent 2-dimensional and Doppler echocardiographic examinations within 24 hours of admission, at days 3, 7, and 30 and 6 months after the index infarction. Mitral flow velocities were obtained from the apical 4-chamber view with pulsed Doppler. End-diastolic volume index (EDVI) and end-systolic volume index (ESVI) were calculated with the Simpson's rule algorithm. Patients were divided according to the DT duration assessed at day 3 in 2 groups: group 1 (n=33) with DT >130 ms and group 2 (n=18) with DT 相似文献   

Peripheral blood harvest of unaffected CD34+ CD38- hematopoietic precursors in paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) arises from somatic mutation of a bone marrow progenitor that disrupts glycosylinositol phospholipid (GPI) anchoring of cell surface proteins. We recently characterized the expression of GPI-anchored decay acclerating factor (DAF) and CD59 during hematopoietic development in PNH marrow. We found that, although a subset of early hematopoietic precursors identified by the CD34+CD38- phenotype exhibits normal DAF and CD59 expression, DAF and CD59 are absent on the majority of CD34+CD38- cells. Pluripotent CD34+CD38- hematopoietic stem cells normally circulate in the peripheral blood and can be collected by apheresis, cryopreserved, and later used for reconstitution of hematopoiesis. In this study, we examined the phenotypes of CD34+ cells that are released into the blood of PNH patients. Analyses of apheresis samples from three affected individuals showed discrete populations of circulating DAF+CD59+CD34+ and DAF-CD59- CD34+ cells. Variable proportions of CD34+CD38- cells were present within the peripheral blood CD34+ cells of each patient, but in all three cases the DAF+CD59+CD34+CD38- cell subset subset. Because CD34+ cells lacking CD38 antigen are highly enriched for self-renewing hematopoietic stem cells, these findings indicate that apheresis samples can serve as a source of unaffected stem cells for autologous marrow transplantation of PNH patients.     

Thalidomide as salvage therapy for chronic graft-versus-host disease

Thalidomide has been reported to be an effective agent for treatment of chronic graft-versus-host disease (CGVHD). To determine the efficacy of this agent in patients with refractory CGVHD a total of 80 patients who failed to respond to prednisone (PSE) or PSE and cyclosporine (CSA) were treated with thalidomide. Sixteen patients (20%) had a sustained response, 9 with a complete remission and 7 with a partial response. Twenty-nine patients (36%) had thalidomide discontinued because of side effects, which included sedation, constipation, neuritis, skin rash, and neutropenia. Side effects were reversible with drug discontinuation except for mild residual neuritis in one case. Rashes and neutropenia have not previously been reported as thalidomide side effects when used for CGVHD treatment. We conclude thalidomide is immunosuppressive and active in the treatment of CGVHD. A high incidence of reversible side effects limited dose intensity and reduced the number of patients who could benefit from treatment.     

Marrow transplantation from unrelated donors for treatment of hematologic malignancies: effect of mismatching for one HLA locus

One hundred twelve patients less than 36 years old received marrow grafts from unrelated donors as treatment for hematologic malignancy. Seventy donor/recipient pairs were phenotypically identical for HLA-A, - B, and -D, while 42 had a "minor" disparity at one HLA locus. There was an increase in the risk of acute graft-versus-host disease (GVHD) in patients receiving HLA-partially matched grafts compared with those receiving HLA-matched grafts (51% v 36% probability of grades III-IV acute GVHD). However, in this cohort of patients, there was no significant difference in survival (at 1.5 years, 46% v 51% for good- risk patients, 44% v 30% for poor-risk patients). This finding suggests that some degree of HLA disparity can be tolerated in young patients transplanted from unrelated donors for malignant disease, thus making transplantation an option available to larger numbers of patients.