HIV/AIDS患者B7-H1的表达特点及与疾病进展关系研究

目的 研究HIV/AIDS患者外周血mDC及不同亚群T淋巴细胞B7-H1及PD-1的表达水平,分析其与疾病进展的相关性,探讨B7-H1及PD-1信号通路在HIV感染中的作用.方法 采集中国医科大学附属第一医院艾滋病研究所红丝带门诊36例未经抗病毒治疗的HIV/AIDS患者(无症状HIV组、AIDS组)及20名健康对照组...     

前臂远端 1/3 和 1/10部位骨密度测量及临床意义

目的探讨前臂远端 1/3 和 1/10部位骨密度 ( BMD) 的变化规律 , 为骨质疏松症 ( OP) 的诊断治疗和预防提供科学依据 . 方法采用双能 X线骨密度仪 ( DEXA) 测定 1 863例健康人前臂远端 1/3 和 1/10部位的 BMD, 年龄范围 20～ 84岁 , 按 5岁一个年龄组进行统计分析 . 结果男、女 1/3部位骨峰值均在 40～ 44岁年龄组 , 男、女 1/10部位骨峰值分别为 30～ 34岁 , 25～ 29岁年龄组 . 前臂远端 1/3 和 1/10部位 BMD及 OP患病率也不同 ; 女性 45～ 54岁 1/10部位比 1/3部位显示更高的 OP患病率 ( P< 0.01). 结论女性围绝经期测量前臂远端 1/10部位 BMD可更早的发现 OP. 同时测定 1/3 和 1/10部位 BMD, 可较全面反映全身 ( 包括皮质骨和松质骨 ) 的骨量水平 , 有助于 OP的诊断和防治 .     

Diagnostic evaluation of a new combined HIV p24 antigen and anti-HIV1/2/O screening assay

To evaluate a new fourth generation assay for simultaneous detection of antibodies to the human immunodeficiency virus (HIV) 1 and 2 and HIV p24 antigen in daily routine we tested 675 sera obtained from 673 patients and compared the results to conventional antibody tests. In 546 uninfected patients the rate of unspecific reactivities was slightly higher in the new screening assay as compared to conventional antibody assays (1.1% vs. 0.4%). All 121 sera derived from patients with known HIV infection were detected correctly. In six patients from whom sera were obtained during early seroconversion the fourth generation ELISA was positive in three cases, while conventional third generation tests still were negative. In patients negative for HIV antibodies and low amounts of p24 antigen less than 100 pg/ml also the fourth generation ELISA remained negative. Thus, this new assay permits earlier detection of HIV infection and reduces the diagnostic window. It is a reliable tool for routine diagnosis of HIV, especially in blood donors and patients with high risk behavior.     

p16,E6/E7蛋白与宫颈癌及癌前病变相关性的研究进展

宫颈癌是女性最常见的、发病率较高、但完全可以通过筛查早期发现并进行有效防治的恶性肿瘤。在宫颈病变中,高危型HPV病毒的持续感染是导致其发生发展的明确病因,近年来,p16,HPV E6/E7蛋白在明确宫颈病变的发病机制、诊断、临床分流等方面的作用备受关注。     

Screening for germline mutations of the p53 gene in familial breast cancer patients

Abstract. The constitutive DNA from members of four families showing predisposition to breast cancer was amplified by PCR in the region of exons 5, 6, 7 and 8 of the p53 proto-oncogene. Single-strand conformation polymorphism (SSCP) gels were used to compare patient DNA with mutant and wild-type control samples. No cases of anomalous mobility were observed in samples from the susceptible families. The lack of inherited mutations was confirmed for exons 5 and 7 by solid-phase DNA sequencing. The results lend further support to the view that inherited mutations in p53 alleles are not a significant contributor to breast cancer predisposition and it is not, therefore, clinically worthwhile to screen predisposed or potentially predisposed families for germline mutations in the p53 gene.     

胰腺癌患者血浆K-ras和p53基因突变检测的研究

目的　检测胰腺癌患者血浆K ras和p5 3基因突变情况 ,初步分析其诊断价值。方法　本研究包括胰腺癌组 2 4例、其他疾病组 14例和健康对照组 2 1例。提取血浆DNA ,采用突变富集PCR RFLP法检测K ras基因第 12密码子突变 ,PCR SSCP 银染法检测p5 3基因第 5～ 8外显子突变。结果　 2 4例胰腺癌患者中 17例血浆检测到K ras突变 ,3例检测到p5 3突变 ;2 1例健康对照者血浆中均未检测到K ras和p5 3突变 ;在 38例疑为胰腺肿瘤患者中 ,血浆K ras突变诊断胰腺癌的敏感性为 70 % ,特异性为 86 % ,阳性预测值为 90 % ,阴性预测值为 6 3%。结论　本研究提示通过胰腺癌患者血浆标本检测K ras和p5 3基因突变是可行的。血浆K ras突变分析有助于胰腺癌的诊断。     

Antiviral activity and safety of aplaviroc with lamivudine/zidovudine in HIV-infected, therapy-naive patients: the ASCENT (CCR102881) study

BACKGROUND: This Phase IIb study explored the antiviral activity and safety of the investigational CCR5 antagonist aplaviroc (APL) in antiretroviral-naive patients harbouring R5-tropic virus. METHODS: One hundred and forty-seven patients were randomized 2:2:1 to one of two APL dosing regimens or efavirenz (EFV). All dosage arms were administered twice daily and in combination with lamivudine/zidovudine (3TC/ZDV; Combivir, COM). Efficacy, safety, and pharmacokinetic parameters were assessed. RESULTS: This study was prematurely terminated due to APL-associated idiosyncratic hepatotoxicity. The primary endpoint of the study was the proportion of patients with plasma HIV-1 RNA <400 copies/ml who remained on randomized treatment through week 12. Of the 147 patients enrolled, 145 patients received one dose of treatment and were included in the intention-to-treat population. The proportion of patients with HIV-1 RNA <400 copies/ml at week 12 was 53%, 50% and 66% in the APL 600 mg twice daily, APL 800 mg twice daily, and EFV arms, respectively. Common clinical adverse events (AEs) were diarrhoea, nausea, fatigue and headache. APL demonstrated non-linear pharmacokinetics with high interpatient variability. In addition to the hepatic findings, there was an apparent dose-response relationship in the incidence of diarrhoea. CONCLUSIONS: Whereas target plasma concentrations of APL were achieved, the antiviral activity of APL as the third agent in a triple drug regimen did not appear to be comparable to EFV in this treatment-naive patient population.     

Wasting and malnutrition in patients with HIV/AIDS

It is important for healthcare professionals caring for HIV-infected individuals to understand the relationship among nutrition, HIV infection, and the immune system. Progressive weight loss is a major component of the clinical syndrome in persons with HIV infection and AIDS. Weight loss occurs for a variety of reasons, which, when recognized, may be preventable or treatable. Malnutrition occurring with weight loss may adversely affect the function of the immune system and further impair the infected individual's ability to avoid or recover from infection. Nursing interventions in nutritional care, outlined in this article, can help these clients improve both the quantity and quality of their lives.     

Medicines information and adherence in HIV/AIDS patients

BACKGROUND: Providing written medicines information is being legislated in an increasing number of countries worldwide, with the patient information leaflet (PIL) being the most widely used method for conveying health information. The impact of providing such information on adherence to therapy is reportedly unpredictable. Therapy for human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and related opportunistic infections usually involves polytherapy and complex regimens, both of which are risk factors for non-adherence. The objective of this study was to assess the impact of medicines information on adherence to chronic co-trimoxazole therapy in low-literate HIV/AIDS patients. METHODS: Two different PILs were designed for co-trimoxazole tablets and were available in both English and isiXhosa. Participants were randomly allocated to a control group (receiving no PIL), group A (receiving a "complex PIL") and group B (receiving a "simple PIL" incorporating pictograms). At the first interview, demographic data were collected and the time, date and day that the participant would take his/her first tablet of the month's course was also documented. In a follow-up interview adherence to therapy was assessed using two methods; self-report and tablet count. RESULTS: The medicines information materials incorporating simple text and pictograms resulted in significantly improved adherence to therapy in the short term, whereas a non-significant increase in adherence was associated with the availability of the more complex information. This was shown by both the self-reported assessment as well as the tablet count. CONCLUSION: This research suggests that appropriately designed written material can have a positive impact in improving adherence and, together with verbal consultation, are essential for enabling patients to make appropriate decisions about their medicine taking.     

Epitopes at the proteolytic cleavage sites of HIV-1-gp120 and RSV-F protein share a sequence homology: comparative studies with virus-induced and antipeptide antibodies.

The proteolytic cleavage sites of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein precursor gp160 and the fusion protein of respiratory syncytial virus (RSV) show a sequence homology. To study this homology two synthetic peptides corresponding to HIV-1-env-gp160-aa 507-518 (KAKRRVVQREKR) and RSV-F2-aa 130-136 (SKKRKRR) were synthesized. Human serum samples from HIV-positive or RSV-positive collections recognized the appropriate peptide in 90.6 or 37.2% respectively. No cross-reactivity towards the nonhomologous peptide could be monitored in both serum collections. In contrast, antipeptide antibodies raised against both peptides demonstrate a high degree of cross-reactivity. These data indicate that the high specificity of the virus-induced antibodies may be a result of strong conformational restrictions at the proteolytic cleavage site of both proteins. Moreover, these observations are important for diagnostic purposes. Synthetic peptides are a valuable tool for HIV antibody screening. Our data provide information concerning the specificity of antigen-antibody interaction on a highly immunogenic HIV-1 epitope.     

6例Wiskott-Aldrich综合征患儿的临床特点和基因分析

目的 分析6例Wiskott-Aldrich综合征(WAS)患儿的临床特点、实验室检测指标改变特征及基因突变,探讨其临床与病理意义。方法 用流式细胞术检测WAS患儿T细胞亚群;免疫浊度法分析患儿免疫球蛋白;全血分析仪检测患儿外周血白细胞、红细胞及血小板等;用PCR结合直接测序方法分析患儿及其父母WAS蛋白(WASP)基因。结果 患儿均反复感染及发生湿疹,临床评分为3或4分。患儿血小板计数均减少伴平均血小板体积减少,均有轻中度贫血,白细胞计数有所升高;骨髓检查示巨核细胞数正常或轻度增加,伴成熟障碍,产血小板能力下降。患儿CD3+T细胞减少,CD4+/CD8+比值紊乱,CD19+及CD16+ CD56+细胞均正常;患儿IgA均增高,IgG大多数增高,1例IgM增高。6例患儿中发现了6种基因突变:10250 C→T,6783 C→G,10216-10221插入G,9964缺失T,10192-10203缺失GCCTGCCGGGG 与10052-10059缺失GCTACTG。后5种为新的突变;例1、2、3、4患儿的母亲为相应突变携带者,而P5与P6患儿母亲不携带相应的突变,属散发性病例。除6783C→G(Y102stop)位于外显子3,其余突变位于外显子10,均为无义、小插入或缺失突变。结论 本组WAS患儿血小板计数减少伴小血小板,免疫功能紊乱;基因突变均为缺失、插入及无义突变,其临床表型与基因突变类型有一定关系;患儿都曾被误诊为原发免疫性血小板减少症,鉴别诊断具有重要意义。     

Influenza and its vaccination in HIV1-AIDS patients.

Influenza vaccination of HIV1-seropositive subjects generally protects against specific flu, especially if the patients have not reached a too-advanced stage. Influenza vaccination, as spontaneous influenza, can increase viral load or induce a rebound at a PCR-imperceptible phase of HIV1. Recombinant canarypox vectors encoding HIV1 antigens can stimulate HIV1-specific cytotoxic T lymphocytes.     

Nucleocytoplasmic Shuttling of the TACC Protein Mia1p/Alp7p Is Required for Remodeling of Microtubule Arrays during the Cell Cycle

Microtubule arrays are remodeled as cells proceed through the cell cycle. It is important to understand how remodeling is regulated in time and space. In fission yeast, the conserved microtubule associated TACC/TOG complex plays an important role in organizing microtubules throughout the cell cycle. Here we show that this complex undergoes nucleocytoplasmic shuttling through the nuclear import and export signals located in the TACC protein Mia1p/Alp7p. When the Crm1p-dependent nuclear export signal of Mia1p is disabled, Mia1p accumulates in the nucleus while its partner protein Alp14p/TOG is restricted to the cytoplasm. This leads to defects in assembly of both interphase arrays and the mitotic spindle. Artificial targeting of Alp14p to the nucleus partially rescues the mitotic spindle defects caused by lack of Mia1p nuclear export. Interestingly, the nuclear export sequence of Mia1p appears to overlap with the Alp14p binding site. We propose that intricate regulation of the subcellular distribution of TACC/TOG complexes drives microtubule array remodeling as cells progress through the cell cycle.