Lysosome is a primary organelle in B cell receptor-mediated apoptosis: an indispensable role of Syk in lysosomal function

To investigate the mechanism of B cell receptor (BCR)-mediated apoptosis, we utilized immature B cell lines, DT40 and WEHI-231. In both cell lines, BCR-crosslinking caused the increase in lysosomal pH with early apoptotic changes characterized by chromatin condensation and phosphatidylserine exposure. This increase was detected in c-Abl-deficient DT40 cells but not in Syk-deficient cells, which corresponded to the fact that the former cells but not the latter revealed BCR-induced apoptosis. In contrast, BCR-crosslinking caused no apparent change in mitochondrial transmembrane potential. Therefore, the lysosomal change might be a primary event in BCR-induced apoptosis in DT40 cells. The increased activity of cathepsin B and apoptosis-preventing effect of a cathepsin inhibitor suggested a significant role of lysosomal enzymes in this apoptosis. By microscopic studies, lysosomes of wild-type DT40 cells fused to BCR-carrying endosomes became enlarged and accumulated one another. In contrast, these changes of lysosomal dynamics did not occur in Syk-deficient cells but transfer of wild-type Syk restored the lysosomal changes and apoptosis. These results demonstrated that the lysosomal change accompanied with the activation of lysosomal enzymes is a primary step in BCR-crosslinking-mediated apoptosis and Syk is responsible for this step through the fusion of BCR-carrying endosomes to lysosomes.     

Generation of sheep X (sheep X mouse) heterohybridoma cell line expressing the beta-1 integrin membrane molecule

Sheep are an important biological model in such diverse areas as immunology and reproductive biology. The limitation of sheep as an experimental model is the absence of reliable cell lines. To establish cell lines that express functional sheep membrane molecules, we produced a sheep x mouse heterohybridoma by fusion of sheep efferent lymph T cells with the murine myeloma cell line NS1. A cloned heterohybridoma fusion partner was selected by treatment with 8-azaguanine. The resulting cell line HL1/385 was selected for hypoxanthine/aminopterin/thymidine (HAT) sensitivity and growth efficiency. The HL1/385 cell line was used as a back-fusion partner into lectin-stimulated efferent T lymphocytes. The back-fusion approach produced more than 50 heterohybrid cell lines with high growth efficiency. The expression of physiological levels of the sheep beta-1 integrin cell surface molecule on the HT4/6 cell line was stable for months in culture. These results suggest that somatic heterohybrids may provide a reliable source of cell lines for sheep studies in vitro.     

催经止孕药Ru-486的临床药代动力学

应用高效液相色谱法(HPLC)研究了抗孕激素药,Ru-486的临床药代动力学。六名志愿受试者,一次口服Ru-486 50毫克后测得该药的药代动力学各项参数,血药半寿期t 1/2 33.0小时,一级消除速率常数Kel 0.021 hr~(-1),血药表观容积Vd 120.1 Liter,体内血药总廓清率Cl2.5 Liter/hr,药-时曲线下面积Auc 19825.1 ng/ml/hr。实验表明,服药后一小时血药浓度迅即达高峰,随后转入消除期,血浆药物浓度在消除相的头4～8小时消除较快,而后逐渐减慢,持续24小时,到48小时血药浓度已较低(0.15±0.07μg/ml)。     

Sexualisierte Gewalt in der Erfahrung Jugendlicher: Ergebnisse einer repräsentativen Befragung

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Seit 1998 erhebt die Bundeszentrale für gesundheitliche Aufklärung (BZgA) im Rahmen ihrer Repräsentativbefragung...     

FAM19A4基因启动子甲基化检测在宫颈癌及其癌前病变筛查的研究

宫颈癌是最常见的妇科恶性肿瘤之一。目前人乳头瘤病毒(HPV)检测及细胞学检查是宫颈癌及其癌前病变(CCPL)的主要筛查手段。由于上述传统筛查方法,仍然存在对CCPL漏诊的风险,因此寻找有效识别CCPL的特异性分子标志物,具有重要临床意义。对具有序列相似性家族19成员A4(FAM19A4)基因启动子甲基化定量检测,可有效检出CCPL组织,较传统筛查方法有较高特异度,有望成为CCPL筛查的特异性分子标志物。笔者拟就FAM19A4基因启动子甲基化定量检测,在CCPL筛查中应用的最新研究现状进行阐述,旨在为进一步推进CCPL筛查方法的开发,提供思路。     

Effects of establishing a financing scheme for outpatient care on inpatient services: empirical evidence from a quasi-experiment in China

The European Journal of Health Economics - The relationship between outpatient and inpatient care is central to the current healthcare reform debate especially in developing countries. Despite the...     

充血性心力衰竭病人甲状腺素水平的变化

目的　为探讨充血性心力衰竭 (CHF)患者甲状腺素水平及其与预后的关系。方法　观测了 2 5例CHF患者 (治疗组 )治疗前后及同期 3 0例健康体检者 (对照组 )血浆甲状腺激素水平的变化。结果　治疗组T3水平明显低于对照组 ,且治疗组T3水平随心功能的恶化而降低 ,随治疗好转而回升 ,而T4 则明显波动。结论　CHF患者心功能与T3浓度有密切关系 ,还可降低外周血管阻力 ,减轻心脏后负荷     

Safety and efficacy of magnetic resonance imaging-guided focused ultrasound neurosurgery for Parkinson’s disease: a systematic review

Neurosurgical Review - Magnetic resonance imaging-guided focused ultrasound (MRgFUS) neurosurgery is a new option for medication-resistant Parkinson’s disease (PD), but its safety and...