P17 Pharmacology in the integrated course ＂Basic Medical Sciences＂ in Zhejiang University School of Medicine

According to traditional teaching mode, the courses in preclinical medicine including pharmacology are separately run. This mode causes a series of disadvantages including loose connection between knowledge in different disciplines and weak ability to bridge basic preclinical knowledge and clinical practice. In order to overcome the disadvantages and promote the teaching efficiency, we constructed a new integrated course-Course of Basic Medical Sciences, which includes 6 traditional courses, anatomy, histology and embryology, physiology, pathology, pathophysiology and pharmacology. We integrated these courses based on the human organ systems and according to the principle-＂ From macro to micro, From morphological to functional, From normal to abnormal and From disease to drug therapy＂ and published the series of textbook in 2004. The contents of pharmacology are taught just after pathology and pathophysiology in every organ system. In comparison with the traditional teaching mode, teachers of pharmacology need not spend a lot of time to review preceding knowledge of anatomy and histology, physiology, pathophysiology and pathology. This is helpful in saving time and improving the teaching efficiency.     

人类DNA分型研究进展

聚合酶链式反应技术克服了以往ＤＮＡ多态性检测技术的缺点，引起了ＤＮＡ多态性检测的一次革命。本文从扩增片段碱基序列多态性、扩增片段患联重复序列多态性和随机扩增的多态性ＤＮＡ等多方面，系统地综述了近年来聚合酶链式反应技术在ＤＮＡ分型研究中的进展。     

人类细胞遗传学命名的国际体制(1978) ISCN(1978) 人类细胞遗传学命名常务委员会的报告(续)

2.4.命名符号为了描述人类染色体及其畸变,提出了一个命名符号的体制,这些符号的目录列于表3。表3 符号和缩写术语表。根据需要这些缩写术语可配合使用。那些在正文中已详细说明的术语,在括号中列有参考节段。其它术语按Rieger等(1976) 提出的定义。     

Study of severe hepatitis treated with a hybrid artificial liver support system

Artificial liver support system (ALSS) has been used to treat hepatic failure and has significantly decreased the mortality. TECA hybrid artificial liver support system (TECA-HALSS), which combines the hollow fiber bioreactor with a plasma exchange circuit, was used to assess the efficacy, safety and feasibility in treating severe hepatitis patients. The hybrid artificial liver support system (HALSS) consists of a bioreactor containing more than 5 x10(9) porcine hepatocytes and plasma exchange device. Fifteen patients with severe hepatitis were treated with this hybrid system. All patients experienced a reduction in symptoms such as fatigue, abdominal distention or ascites. After each treatment serum total bilirubin decreased markedly while prothrombin activity increased. There were ten patients whose progress of hepatocyte necrosis was stopped after HALSS treatment, and finally they recovered completely. One patient received liver transplantation after HALSS therapy and survived. No serious adverse events were noted in the fifteen patients.     

一例46，XX，t（2;10）（q23;q22），t（4;12）（q35;q2103）

一例４６，ＸＸ，ｔ（２；１０）（ｑ２３；ｑ２２），ｔ（４；１２）（ｑ３５；ｑ２１０３）龙志高李麓芸夏家辉患者女，３５岁。智力正常，结婚５年，自然流产１次。体查：生长发育正常，表型正常。细胞遗传学检查：外周血淋巴细胞培养，Ｇ显带，核型为４６，ＸＸ，ｔ（...     

APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity

We report that the tumor neurosis factor homolog APRIL (a proliferation-inducing ligand) stimulates in vitro proliferation of primary B and T cells and increases spleen weight due to accumulation of B cells in vivo. APRIL functions via binding to BCMA (B cell maturation antigen) and TACI (transmembrane activator and CAML-interactor) and competes with TALL-I (also called BLyS or BAFF) for receptor binding. Soluble BCMA and TACI specifically prevent binding of APRIL and block APRIL-stimulated proliferation of primary B cells. BCMA-Fc also inhibits production of antibodies against keyhole limpet hemocyanin and Pneumovax in mice, indicating that APRIL and/or TALL-I signaling via BCMA and/or TACI are required for generation of humoral immunity. Thus, APRIL-TALL-I and BCMA-TACI form a two ligands-two receptors pathway involved in stimulation of B and T cell function.     

The PDZ-binding domain is essential for the dendritic targeting of 5-HT2A serotonin receptors in cortical pyramidal neurons in vitro

The 5-HT(2A) serotonin receptor represents an important molecular target for atypical antipsychotic drugs and for most hallucinogens. In the mammalian cerebral cortex, 5-HT(2A) receptors are enriched in pyramidal neurons, within which 5-HT(2A) receptors are preferentially sorted to the apical dendrites. In primary cortical cultures, 5-HT(2A) receptors are sorted to dendrites and not found in the axons of pyramidal neurons. We identified a sorting motif that mediates the preferential targeting of 5-HT(2A) receptors to the dendrites of cortical pyramidal neurons in vitro. We constructed green fluorescent protein-tagged 5-HT(2A) receptors wherein potential sorting motifs were disrupted, and subsequently employed either the Semliki Forest virus or calcium phosphate for the transient expression of recombinant 5-HT(2A) receptors in cultured cortical pyramidal neurons. Using dual-labeling immunofluorescent confocal microscopy, we quantified the axonal and dendritic sorting patterns of endogenous and recombinant 5-HT(2A) receptors. We discovered that disruption of the PDZ-binding domain of the 5-HT(2A) receptor greatly attenuates the dendritic targeting of 5-HT(2A) receptors without inappropriately sorting 5-HT(2A) receptors to axons. The PDZ-binding domain is therefore a necessary signal for the preferential targeting of the 5-HT(2A) receptor to the dendritic compartment of cultured cortical pyramidal neurons, the first such role ascribed to this protein-protein interaction motif of any G protein-coupled receptor.     

Interferon-gamma is an autocrine mediator for dendritic cell maturation

Maturation of dendritic cells (DC) is critical for efficient antigen presentation and initiation of an immune response. Interferon-gamma (IFN-gamma) is an important Th1 cytokine. In this study, we investigated the role of IFN-gamma in DC maturation using either IFN-gamma receptor deficient- or IFN-gamma overexpression-models. We showed that immature DC generated in vitro from bone marrow (BM) progenitor cells produced low level of IFN-gamma. After LPS stimulation, DC produced more IFN-gamma, and IFN-gamma productions were at comparable levels among C57BL/6 mice-derived DC (C57BL/6 DC), wild-type 129 mice-derived DC (129 DC) and IFN-gamma receptor deficient 129 mice-derived DC (IFN-gammaR-/-DC). We found that IFN-gammaR-/-DC exhibited decreased expression of CD54, CD86, reduced capacity to secrete IL-1beta and IL-12p70, and impaired capacity to stimulate alloreactive T cells and to drive Th1 differentiation. Transfection of IFN-gamma gene into DC promoted DC to express higher CD40, CD54, CD80, CD86, CCR7 and I-Ab, secrete more IL-1beta and IL-12p70, and more potently activate both CD4 and CD8 T cells. These data suggest that IFN-gamma signaling pathway is important for the maturation of DC in an autocrine fashion.     

A novel locus for autosomal dominant nonsyndromic hearing loss identified at 5q31.1-32 in a Chinese pedigree

 Hearing impairment is an extremely heterogeneous disorder. A total of 35 loci and 17 related genes for autosomal dominant nonsyndromic hearing loss have been identified. In a Chinese pedigree characterized by autosomal dominant inheritance with bilateral, postlingual, progressive, and sensorineural nonsyndromic hearing impairment, the putative disease gene locus was localized to chromosome 5q31.1-32 by a genome-wide scan. Fine mapping indicated that the disease gene was located within an 8.8-cM region between markers D5S2056 and D5S638, with a maximum two-point logarithm of differences (LOD) score of 6.89 (θ = 0) at D5S2017. By the candidate gene approach, mutation screening of the DIAPH1 and POU4F3 genes at 5q31 was performed. No mutation was found, suggesting that this is a novel deafness locus, which has been named DFNA42. Received: May 8, 2002 / Accepted: October 1, 2002     

真核生物RNA聚合酶Ⅱ启动子的计算机预测

启动子是基因组序列中靠近基因转录起始位点的区域，是影响基因表达的重要功能单位之一。除实验方法发现或验证序列的启动子外，现已经有多种启动子序列的计算机预测方法，如位点比重阵列(PWM)、隐马尔柯夫模型(HMM)、神经网络、低聚复合物和CpG岛等。本文综述了现有真核生物基因启动子序列的生物信息研究技术。