Long-term in vivo expression of a murine adenosine deaminase gene in rhesus monkey hematopoietic cells of multiple lineages after retroviral mediated gene transfer into CD34+ bone marrow cells

Retroviral mediated gene transfer into stem cells has been proposed as therapy for many inherited hematopoietic diseases. Deficiency of the enzyme adenosine deaminase (ADA) results in depletion of T lymphocytes, causing severe combined immunodeficiency syndrome (SCIDS). In this report, we describe retroviral mediated gene transfer of a murine ADA cDNA into Rhesus monkey hematopoietic stem cells. Immunoselected CD34+ bone marrow cells were exposed to medium containing the ADA retrovirus during culture on a stromal cell line engineered to express the transmembrane form of stem cell factor. After infusion of autologous, transduced cells into irradiated recipients, gene transfer was observed in all three monkeys. The ADA provirus was detected in 2% of circulating granulocytes and T cells from 100 days post-transplantation to longer than 1 year and in B cells from 250 days post-transplantation and beyond. Mouse ADA activity was detected in peripheral blood cells at approximately 3% the activity of monkey ADA. Thus, we have shown gene transfer into repopulating cells that contribute to all hematopoietic lineages with persistent gene expression. These data provide support for the use of stem cell targeted gene transfer for therapy of ADA deficiency.     

Serum levels of CD8 antigen in childhood lymphoid malignancies: a possible indicator of increased suppressor cell activity in poor-risk patients

Serum concentrations of CD8 antigen were measured at diagnosis with an enzyme-linked immunoassay in children with acute lymphoblastic leukemia (n = 344) or non-Hodgkin's lymphoma (n = 65). All patients had detectable levels of the serum antigen, which in its soluble nonreduced form appeared to be a 52-Kd homodimer as compared with the 66-Kd surface membrane component on most thymocytes and on a subset of functionally distinct T cells (suppressor/cytotoxic). Increased serum levels of CD8 in leukemia patients were significantly related to recognized high-risk prognostic features: high leukocyte count, large liver and spleen size, high serum lactic dehydrogenase level, T-cell immunophenotype, presence of a mediastinal mass, pseudodiploid karyotype, DNA index less than 1.16, and chromosomal translocation. Children with serum CD8 levels greater than or equal to 450 U/mL were more likely to fail treatment than were those with lower levels (P = .002), even in the group with non-T-cell leukemia (P = .003). In a multivariate analysis, serum CD8 antigen contributed independent prognostic information beyond that conveyed by age, leukocyte count, and race (P = .02). High serum CD8 antigen levels also correlated with advanced stages of disease in children with non-Hodgkin's lymphoma or B- cell leukemia. Children with higher serum CD8 antigen levels (greater than or equal to 700 U/mL) had a poorer treatment outcome (P = .003), even after results were adjusted for disease stage and serum lactic dehydrogenase level (P = .05). Measurement of serum levels of CD8 antigen not only has important prognostic value in childhood lymphoid malignancies but also could be useful in assessing the immunoregulatory role of T cells in patients with cancer.     

汉、苗、侗族大学生的人格比较

目的:考察汉、苗、侗族大学生的人格差异。方法:于2006-04/05在凯里学院采用分层随机抽样法抽取文科和理科各年级大学生进行测查,被试年龄为18～22岁的少数民族聚居地区大学生。采用大五人格问卷简式量表考察贵州省汉族、苗族、侗族大学生的人格特点。该量表测量外向性、情绪稳定性、宜人性、责任性和开放性五种人格特征。在大学生群体中,整体量表Cronbach'sα系数为0.75,表明此量表在大学生群体中具有较好的测量学指标。问卷施测采用班级集体施测的方式,测试时统一指导语。依照本次接受测验的学生总体分数计算各个维度的百分位数(25%,75%),百分位>75%属于得分较高,>25%且<75%属于中等得分,<25%属于得分较低。结果:共发放问卷1000份,回收有效问卷871份。①女生宜人性得分高于男生,开放性和责任性得分低于男生(女生:53.48±8.92,46.15±8.39,46.57±9.70;男生:52.34±9.25,48.35±9.24,47.69±8.65,P<0.05,P<0.01)。②二年级学生情绪稳定性得分高于三年级学生(31.77±11.36,29.41±11.53,P<0.05);三年级学生宜人性、责任性和开放性得分高于一、二年级学生(三年级:54.27±9.12,48.95±9.10,49.07±8.73;二年级:52.27±8.79,46.30±8.83,46.63±8.66;一年级:53.11±9.36,46.52±9.68,46.23±8.96,P<0.05,P<0.01,P<0.001)。③文科学生情绪稳定性得分高于理科学生,责任性得分低于理科学生(文科:31.56±11.40,46.45±9.23;理科:30.04±11.11,47.77±9.24,P<0.05)。④ANOVA比较结果发现,在五个维度中,汉族和苗族大学生的责任性、宜人性得分明显高于侗族大学生(责任性:47.72±9.70,47.66±8.72,45.55±9.35;宜人性:53.64±9.36,53.24±8.89,51.84±8.97,P<0.01,P<0.05),汉族苗族大学生差异不显著。结论:大学生人格特征在性别、年级、专业变量上存在部分差异,不同民族大学生的各维度人格特征得分有差异。     

Epidemiologic background of blood donors with antibody to human T-cell lymphotropic virus. Transfusion Safety Study Group

We interviewed 51 blood donors in four major US metropolitan areas subsequently found to have had antibodies to human T-cell lymphotropic virus (anti-HTLV) in late 1984-early 1985. Sixteen donors (31%) reported that they or a sexual contact had a history of blood transfusion. Twelve donors (24%) reported that they or a sexual contact used intravenous drugs. Ten donors (20%) were blacks born in the southeastern US. Four of the male donors (15%) reported homosexual contact. The most common characteristic was an association with Japan or the Caribbean basin (61%). These results show a broader variation of epidemiologic backgrounds than anticipated.     

外源性肾上腺髓质素对肾脏创伤大鼠Th1／Th2的调节作用

目的:观察外源性肾上腺髓质素(adrenomedullin,ADM)对大鼠肾脏创伤后外周血Th1/Th2的调节作用,并了解给药时间对此作用的影响。方法:实验于2005年在兰州大学实验中心进行。将104只Wistar大鼠随机分为4大组:①正常对照组(8只);不打击。②创伤组(32只);自由落体生物撞击仪撞击大鼠脊肋区,间接打击双侧肾脏造成肾脏Ⅰ级损伤。③创伤前注射ADM组(32只);打击同创伤组,打击前10min腹腔注射肾上腺髓质素0.1nmol/kg(终体积0.5mL)。④创伤后注射ADM组(32只):打击同创伤组,打击后10min腹腔注射肾上腺髓质素0.1nmol/kg(终体积0.5mL)。后3组分别在打击后1,6,12,24h各处死8只。采用酶联免疫斑点法测定Th1与Th2阳性率。结果:82只大鼠进入结果分析。①创伤组:Th1细胞在创伤后6h显著增加并达峰值,高于创伤后1h及正常对照组[(0.32±0.07)%,(0.13±0.06)%,(0.16±0.07)%,P<0.05,0.01];Th2各时间点比较均无差异;Th1/Th2在创伤后6h达高峰,创伤后24h降至正常对照组水平。②创伤前注射ADM组:Th1在创伤后6h低应答,在创伤后12h增高并达峰值,高于创伤后6h及正常对照组[(0.32±0.08)%,(0.08±0.06)%,(0.16±0.07)%,P<0.05,0.01];Th2在创伤后6-12h的变化趋势与Th1相同;Th1/Th2创伤后6h达最低,低于该时点创伤组(4.58±3.81,23.44±6.19,P<0.01),随后上升,至创伤后24h达高峰。③创伤后注射ADM组:Th1自创伤后1h逐渐上升,至24h达高峰,高于创伤后1,6h[(0.32±0.10)%,(0.10±0.04)%,(0.17±0.07)%,P<0.05,0.01],Th2细胞各时间点比较均无差异;Th1/Th2于创伤后1,6h接近正常对照组,然后逐渐上升,至创伤后24h达最高,高于正常对照组及该时点创伤组(22.49±12.64,5.33±4.55,4.78±3.15,P<0.01)。结论:①急性创伤早期(以创伤后6h为著),外源性肾上腺髓质素通过抑制Th1优势应答,具有校正Th1/Th2比例失衡的免疫调节作用。②急性创伤后最初6h内,创伤后给予肾上腺髓质素调节Th1/Th2平衡作用明显优于创伤前给药。     

Bacterial meningitis in patients with nasopharyngeal carcinoma

Bacterial meningitis was found in 12 patients with nasopharyngeal carcinoma, accounting for 0.65% of the 1850 patients with the tumour diagnosed between 1981 and 1994 in our hospital. In 11 patients, the time-lag between diagnosis of cancer and the appearance of infection ranged from 9 months to 11 years (mean 57 months) whereas in one patient it was only 5 days. Three patients developed mixed bacterial meningitis. Cerebrospinal fluid culture for bacteria was positive in six patients. Three patients (25%) were bacteraemic. Gram-negative bacilli, especially Pseudomonas aeruginosa, were the most common pathogens. Age, sex and histopathology were not risk factors for infection. Conditions predisposing to meningitis included intracranial invasion of the tumor, neutropenia, otitis media, and neurosurgical procedures. All but two patients had intracranial tumour invasion and erosion of the base of the skull. Local spread of micro-organism to the meninges was more important than haematogenous spread. The overall mortality in our patients was 66.7%, much higher than in patients without cancer.      

疱液在诊断表皮下自身免疫性大疱病中的意义

目的：探讨表皮下自身免疫性大疱病疱液中抗基底膜带（ＢＭＺ）自身抗体的情况及在诊断中的意义。方法：应用非盐裂皮肤及盐裂皮肤间接免疫荧光技术（ＩＦ）检测３８例表皮下自身免疫性大疱病患者疱液和血清中ＩｇＧ、ＩｇＡ、ＩｇＭ、ＩｇＥ及ＩｇＧ亚型ＩｇＧ１～ＩｇＧ４抗ＢＭＺ抗体及滴度，并检测疱液和血清中结合补体Ｃ３的特异性抗ＢＭＺ抗体。结果：（１）疱液和血清中抗ＢＭＺ抗体及滴度和结合补体Ｃ３的特异性抗ＢＭＺ抗体均无显著性差异。（２）大疱性类天疱疮患者的疱液和血清中ＩｇＧ抗ＢＭＺ抗体的亚型分布相同，主要为ＩｇＧ１和ＩｇＧ４。结论：疱液可作为ＩＩＦ检测表皮下大疱病抗ＢＭＺ抗体的另一个有价值的标本来源。