Favorably tipping the balance between cytopathic and regulatory T cells to create transplantation tolerance

Therapeutic application of broadly reactive anti-T cell antibodies can lead not only to potent immunosuppression but also to profound and long-lived T cell depletion. We reasoned that a strategy that almost exclusively targets activated cytopathic donor reactive T cells and spares immunoregulatory networks might prove to be an exceptionally potent and highly selective means of producing long-term engraftment and tolerance. Herein we show that the combined administration of rapamycin and agonist IL-2- and antagonist IL-15-related cytolytic fusion proteins provides for long-term engraftment/tolerance in exceptionally stringent allotransplant models by (1) limiting the early expansion of activated T cells, (2) preserving and even exaggerating their subsequent apoptotic clearance, and (3) further amplifying the depletion of these activated T cells by antibody-dependent mechanisms, while (4) preserving CD4+CD25+ T cell-dependent immunoregulatory networks.     

大鼠小脑皮质NPY能神经元的形态与分布

目的　研究大鼠小脑皮质内NPY免疫阳性神经元的形态与分布。方法　SD大鼠 10只 ,雌雄不限 ,升主动脉灌注固定 ,开颅取小脑 ,SP免疫组织化学染色。结果　大鼠小脑内NPY免疫阳性神经元分布在皮质的Purkinje细胞层 ,胞体呈梨形或烧瓶状 ,细胞核清晰不染 ,轴突伸向颗粒层 ,树突呈网状伸向分子层 ,突起未见染色。分子层和颗粒层未见阳性细胞 ,但可见神经纤维的存在。结论　小脑Purkinje细胞层内存在NYP阳性神经元。     

Incidence and case-fatality rates resulting from the 1998 enterovirus 71 outbreak in Taiwan

In 1998, an epidemic of hand-foot-and-mouth disease and herpangina caused by enterovirus 71 occurred in Taiwan, leaving many fatalities and severely handicapped survivors in its wake. The reasons this rather common pathogen would cause such a large-scale epidemic remain unknown. A seroepidemiological survey to elucidate the epidemiological characteristics of this outbreak, including its incidence and case-fatality rates was undertaken. Microneutralization tests for antibodies against enterovirus 71 were used to screen four collections of serum samples: 1) 202 specimens taken from individuals > or = 4 years old in 1994; 2) 245 specimens collected from individuals of all ages in 1997; 3) 1,258 specimens collected from individuals of all ages in 1999; and 4) sera samples from a birth cohort of 81 children who had yearly blood samples taken from 1988-98. After the maternal antibody had declined, the seropositive rates began to increase with age. Approximately half of all children aged 6 years or older were enterovirus 71 seropositive. Significantly higher seropositive rates were noted in 1999 than in 1997, in children aged 0.5-3 years. The incidence of enterovirus 71 infection during the epidemic was estimated to be 13-22%, with the higher rates in younger children. The case-fatality rate was highest (96.96 per 100,000) in infants aged 6-11 months, and declined in older children. The results showed that enterovirus 71 is endemic in Taiwan. The apparent lack of large-scale enterovirus 71 activity in the 3 years before 1998 might have been the prelude to the epidemic's appearance in 1998, and might suggest that enterovirus 71 infection will reappear every few years. The lack of a protective antibody in younger children may account for the high incidence and case-fatality rate in this age group.     

Clinical and cytogenetics studies on acute myeloid leukemia with abnormality of chromosome 11

OBJECTIVE: To investigate the incidence of chromosome 11 abnormality in acute myeloid leukemia and its relationship with the clinical aspects and prognosis. METHODS:Conventional cytogenetic analysis of R-band was used to detect the abnormalities of chromosome 11 in 356 acute myeloid leukemia patients. RESULTS: Thirty-four out of 356 patients (9.55%) had abnormalities of chromosome 11, of which 20 (58.8%) involved in 11q23, 7 (19.9%) had translocations involving 11p15, 5 (14.7%) had-11, and the rest had other abnormalities such as +11, and t(11;14). The incidence of 11q23 involvement in M4 and M5 was higher than other subtypes of acute myeloid leukemia (AML). Ten cases with 11q23 abnormality had additional cytogenetic aberrations. In 30 cases treated with chemotherapy, 13 cases acquired complete remission (CR). The CR rate was lower than that of whole cases of acute myeloid leukemia(34.3% versus 64.0%). The CR rate of AML with 11q23 abnormality was lower than that of AML with normal karyotype (25% versus 55.6%). In other 10 patients with additional chromosome aberrations, the CR rate was lower than that of AML with 11q23 alone. In 7 patients with translocations at 11p15, only 3 patients acquired CR, and 2 patients relapsed early. Only 2 patients acquired CR in 5 patients with-11. CONCLUSION: 11q23 was a frequent aberration in chromosome 11 anomaly, which was often detected in M4 and M5. It might be associated with the pathogenesis of acute monolytic leukemia. The patients with chromosome 11 anomaly had poorer prognosis.     

基因组序列CGR图形表示的多重分形分析

为了更好地描述基因组序列CGR(chaos-game representation)图形的分形特征,引入多重分形理论进行分析。通过研究3种概率集对标度不变性范围的影响,选取出标度不变性最好的概率集,计算光滑的广义维数谱和多重分形谱。结果表明:以相对概率组成概率集时标度不变性最好,而且标度不变性随尺度变化可被分为3个不同的区域,这反映了基因组序列不同长度的序列片段有不同的分布规律。可见,多重分形方法可以用于描述基因组序列CGR图形的分形特征。     

用糖基化磷脂酰肌醇B7-1锚定肿瘤细胞膜进行免疫治疗

目的 研制抗肿瘤免疫治疗的新疫苗.方法 用蛋白转化法将B7-1锚定在肿瘤细胞膜上,免疫C57BL-6小鼠后,一组小鼠取脾细胞进行T细胞扩增和细胞毒T淋巴细胞(CTL)功能检测,另一组小鼠进行肿瘤细胞接种试验.结果 用GPI-B7-1修饰的肿瘤细胞膜免疫小鼠后诱发了肿瘤特异性T细胞扩增和CTL.且该疫苗有一定的保护小鼠免受肿瘤细胞侵袭的作用.结论 GPI蛋白转化法为人类抗肿瘤免疫治疗提供了新的、有效的修饰肿瘤细胞膜的方法.     

血小板活化因子受体拮抗剂的抗内毒素肝损伤作用研究

本文研究了血小板活化因子受体拮抗剂ＢＮ５２０２１及ＢＮ５０７３９的抗大鼠内毒素肝损伤的作用。结果表明ＢＮ５２０２１及ＢＮ５０７３９能使内毒素所致的肝线粒体膜磷脂降解及溶血磷脂的聚集，脂质过氧化反应的增强以及机体抗氧化能力的降低得到明显改善，提示ＢＮ５２０２１及ＢＮ５０７３９是两种强有效的抗内毒素肝损伤的药物，用于内毒素肝损伤的治疗。     

广州4194份脐带血HLA-A、B、DRB1等位基因型和单倍型频率研究

目的 对广州脐血库10年来保存的脐血人类白细胞抗原(human leukocyte antigen,HLA)等位基因及单倍型分布特征进行分析.方法 采用单克隆板,序列特异引物聚合酶链反应,PCR序列特异性寡核苷酸探针和DNA测序分型方法对广州脐血库内4194份脐带血进行HIA-A、B、DRB1等位基因分型.用Arlequm软件计算HLA基因频率和单倍型频率.结果 在广州脐血库中,HLA-A、B、DRB1等位基因型分别有18,43,13种.累积频率>50%的显著高频率等位基因是:A*11,A*02,A*24,A*33,B*40,B*15,B*46,B*13,DRB1*12,DRB1*15,DRB1*09,DRB1*04;最常见的单倍型为:A2-B46、B6-DR9、A11-DR12、A2-B6-DR9.结论 广州脐血库脐血捐献者HIA-A、B、DRB1等位基因型及单倍型分布具有典型南方人群的特点,此资料有助于为临床移植寻找合适匹配的供受对.     

Sephadex—G50微柱凝胶血型试剂的研制和应用

目的 研制卡式微柱凝胶血型试剂并应用于血型血清学试验。方法 以Sephadex-G50超细凝胶为分子筛载体，制备成中性微柱凝胶试剂卡、特异性凝胶试剂卡及coomb’s凝胶试剂卡并用于血型鉴定、配血试验、抗体筛选和鉴定，对1000名献血者ABO及Rh（D）血型进行鉴定，其中A型272例、B型279例、B3亚型1例、0型437例、AB型11例；Rh（D）阴性2例，Rh（D）阳性998例；对100例输血前检查标本进行配血试验；以Coomb＇s凝胶试剂卡对抗-D、-C、-c、-E、-e、-Jk^a、-Jk^b、-Fy^a、-Di^a等9个抗体分别与谱红细胞反应做特异性抗体鉴定试验：同时以瑞士进口的DiaMed同类产品及常规的血型血清学试管法同步比较。结果 研制的卡式微柱凝胶血型试剂与瑞士进口的DiaMed同类产品比较，检验结果、敏感性、特异性无明显差别。结论 研制的卡式微柱凝胶试剂适用于血型鉴定、配血试验、抗体筛选和鉴定等血型血清学检查，该试剂制备具有成本低、工艺简单的优点，具有较好的推广应用和开发价值。     

糖尿病患者心理健康状况的多因素Logistic回归分析

目的探讨糖尿病患者心理健康状况的影响因素。方法对山西省4个地区8个调查点的2132名城乡居民，其中包括139名糖尿病患者，进行问卷调查，了解其一般情况以及情绪状况、社会支持等社会心理因素。结果单因素分析发现，糖尿病患者的焦虑情绪高于非糖尿病者，对社会支持中的家庭资源的利用也不及非糖尿病者；多因素发现，影响糖尿病患者心理健康状况的因素有地区、性别、年龄、经济收入、焦虑以及抑郁等；结论糖尿病患者心理健康状况的影响因素既涉及地区、性别、年龄、经济收入等一般状况，也与患者的情绪障碍的社会支持有密切关系。临床应根据不同的影响因素进行有效牙心理干预。