无环鸟苷亲脂性前体药物脂质体的制备及体外抗病毒活性(英文)

本文通过将无环鸟苷(acyclovir,简称ACV)2’位羟基分别与月桂酰氯或棕榈酰氯进行酯化反应,制得亲脂性前体药物无环鸟苷月桂酸酯和无环鸟苷棕榈酸酯(分别简称为C₁₂-ACV和C₁₆-ACV),使脂质体包封率从ACV的29.9%提高到C₁₂-ACV的95.6%和C₁₆-ACV的97.1%;漏泄实验表明在4℃透析60h后,一半以上的ACV从脂质体中漏泄,而C₁₂-ACV和C₁₆-ACV的滞留率分别为70%和80%;体外抗疱疹病毒的试验中,在最低试验浓度0.044μmol/L时,ACV不显示抗病毒活性,而C₁₆-ACV脂质体抑制细胞病变率达75%,说明前体药物通过与脂质体脂膜的结合增加了药物的进入细胞能力,从而提高了ACV的抗病毒能力。     

中药材龟板和鳖甲中DNA的提取与扩增

中药材龟板和鳖甲中ＤＮＡ的提取与扩增王亚明，周开亚，吴平，徐珞珊（南京师范大学生物系，南京２１００９７；中国药科大学生药学研究室，南京２１０００９）龟鳖类药材在我国使用历史悠久，具补阴益气的功效。《中国药典》（１９９０年版）规定龟甲（龟板）的原动物为...     

Development of hatching blastocysts from immature human oocytes following in-vitro maturation and fertilization using a co-culture system

Recently, in-vitro maturation (IVM) of immature human oocytes recovered from non-stimulated follicles has been applied in the treatment of infertility. However, in previous reports, very few embryos cultured in conventional medium have reached the expanded blastocyst stage following in-vitro maturation and fertilization (IVM/IVF). The objective of this study was to investigate whether the developmental competence of human embryos following IVM/IVF could be enhanced by the use of a human ampullary cell co-culture system. Immature human oocytes were aspirated from small follicles at Caesarean section and then cultured in medium containing human menopausal gonadotrophin for 36 to 48 h, followed by insemination. Zygotes were randomly cultured either in conventional culture medium alone or in the co-culture system. Of 48 embryos cultured in conventional medium alone, all arrested at the 2-16- cell stage on day 3 after insemination. Of 46 embryos cultured in the co-culture system, 26 embryos (56.5%) arrested at the 2-16-cell stage. Six embryos (13%) developed to the morula stage. Fourteen embryos (30.4%) developed to expanded blastocysts and two blastocysts were hatching on day 7 after insemination. We conclude that co-culture significantly enhances the development of blastocysts in embryos resulting from IVM/IVF.      

Relationship between HLA-DRB1 and DQ alleles and the genetic susceptibility to type 1 diabetes

Objective　To study the relationship between human leukocyte antigen (HLA)-DRB1 and DQ alleles and the genetic susceptibility of type 1 diabetes in North Chinese children. Methods　Polymerase chain reaction (PCR) techniques were used to amplify the second exon of DRB1 and DQ alleles, after which sequence specific olignucleotide probe (SSOP) dot blot hybridization techniques were used to analyze the amplified products. Results　DRB1*0301, DQA1*0301, DQB1*0201 alleles and DRB1*0301-DQA1*0501-DQB1*0201 haplotype were significantly increased in patients, while DQA1*0103 and DQB1*0601 alleles were significantly increased in controls. The distribution of DR4 and DR9 haplotypes in patients and controls were not significantly different, but DR3/DR4 and DR4/DR9 heterozygotes were significantly increased in patients. Conclusions　DRB1*0301, DQA1*0301 and DQB1*0201 confer susceptibility while DQA1*0103 and DQB1*0601 confer protection to type 1 diabetes. DRB1*0301-DQA1*0501-DQB1*0201 haplotype offers a predisposition to type 1 diabetes in North Chinese. Although the distribution of DR4 and DR9 in patients and controls had no significant difference, DR3/DR4 and DR3/DR9 heterozygotes were significantly increased in patients, showing that the susceptive effects of DR3 and DR4 or DR4 and DR9 haplotypes could be added up.     

恶性肿瘤患者血清与尿液中一氧化氮含量测定

0 引言一氧化氮（Nitric oxide,NO）是一种具有活跃生物化学性质的无机小分子. NO对许多肿瘤细胞和微生物有细胞毒性［1］,为探讨NO与肿瘤的关系,我们检测了119例恶性肿瘤患者血清及尿液中的NO.     

带有蛋白转导结构域的bcr/abl癌蛋白片段表达及其跨膜转运

0　引言　人类免疫缺陷病毒 (human immunodeficiencyvirus,HIV) - 1编码的反式激活蛋白 TAT具有独特的跨膜运转方式 ,而且有转导速度快 ,效率高的特点 ,被称为蛋白转导结构域 (protein transduction domain,PTD) [1 ,2 ] .本研究用PCR扩增了慢性粒细胞白血病慢粒 bcr/ abl融合蛋白的基因片段 ,在其 5′端融合 PTD结构域的编码区后在大肠杆菌中进行了表达 .表达产物经纯化后 ,加入培养的 HL 6 0细胞 ,表达的蛋白可直接进入细胞内 .这一结果为用外源蛋白负载(L oading)免疫细胞提供了新的途径 .1　材料和方法1.1　 DNA重组　人工合…     

Continuous infusion cisplatin and etoposide chemotherapy for cancer of unknown primary site (CUPS) in Taiwan, a region with a high prevalence of endemic viral infections

BACKGROUND: To evaluate the efficacy and toxicity of cisplatin/etoposide continuous infusion chemotherapy for cancer of unknown primary site in Taiwan, a region with a high prevalence of endemic viral infections. METHOD: Between April 1994 and February 1996, 20 patients with a diagnosis of CUPS were treated, including 15 males and five females, of average age 63.3 years (range 41-83 years). Continuous intravenous infusion of etoposide 80 mg/m2 and cisplatin 25 mg/m2 was given for 3 days every 3 weeks. Pretreatment tumor marker and viral serology studies were performed for baseline evaluation. Nearly two-thirds of the patients had poorly differentiated carcinoma. The average number of metastatic sites was 2.65 (range 1-4), with liver and lymph node involvement predominating. RESULTS: The overall response rate was 25% (95% CI 17.7-32.3%); 30.7% for poorly differentiated cancers and 25% for well differentiated cancers. Median survival was 4 months (range 1-12 months), 4.8 months for patients attaining partial response. Toxicity was moderate, grade 3 and 4 neutropenia occurred in 55% and grade 3 and 4 thrombocytopenia in 40%; other toxicities were mild. CA125 and CA199 were elevated in more than 50% of patients. Viral serology studies were not significantly different from those of the indigenous population. CONCLUSION: Etoposide and cisplatin combination chemotherapy has modest activity in patients with extensive CUPS and, at the schedule and dosage given, it is associated with moderate toxicity.      

In vitro killing of neuroblastoma cells by neutrophils derived from granulocyte colony-stimulating factor-treated cancer patients using an anti-disialoganglioside/anti-Fc gamma RI bispecific antibody

Neutrophils isolated from cancer patients treated with granulocyte colony-stimulating factor (G-CSF) express high levels of Fc gamma RI. They exhibited an efficient killing of GD2+ neuroblastoma cells in the presence of an antidisialoganglioside (GD2) mouse monoclonal antibody (MoAb; 7A4, IgG3 kappa). However, this cytotoxicity was totally blocked by human monomeric IgG. In contrast, a bispecific antibody (7A4 bis 22/MDX-260), prepared by chemically linking an F(ab') fragment of 7A4 with an F(ab') fragment of an anti-Fc gamma RI MoAb, 22, which binds outside the Fc binding domain, triggered antibody-dependent cell cytotoxicity, even when neutrophils were preincubated with human monomeric IgG. F(ab')2 22 MoAb abrogated the MDX-260 killing without affecting that of 7A4. The 3G8 MoAb, directed against the Fc gamma RIII binding site, did not inhibit the cytotoxicity induced by either antibody. Thus, these results indicate that G-CSF-activated neutrophils exert their cytotoxic effect against neuroblastoma cells through Fc gamma RI and not Fc gamma RIII, and that the saturation of the high affinity Fc gamma RI by monomeric IgG can be overcome by the use of bispecific antibodies binding epitopes outside the IgG Fc gamma RI binding site. A combined administration of such bispecific antibodies and G-CSF may be, therefore, an efficient therapeutic approach to trigger tumor lysis by cytotoxic neutrophils in vivo.     

Ocular Manifestations in Egyptian Children and Young Adults with Sickle Cell Disease

In sickle cell disease (SCD), ocular lesions result from stasis and occlusion of small eye vessels by sickled erythrocytes. Vaso-occlusive disease of the retina can be responsible for nonproliferative (NPR) and proliferative retinopathy (PR). Patients are often asymptomatic until serious complications arise as, vitreous hemorrhage and retinal detachment. This work aimed to study the frequency and pattern of ocular manifestations in Egyptian children and young adults with SCD. In this cross-sectional study, 40 steady state patients (80 eyes) aged 2–28 years (30 children and 10 young adults) with established diagnosis of SCD (26 with homozygous SS and 14 with S/β thalassemia underwent complete ophthalmic examination with dilated fundoscopy. Fluorescein angiography was performed for patients ≥12 years old. The overall frequency of retinal lesions was 47.5 % (46.2 and 50 % of SS and S/β patients respectively). PR and NPR were evident in 32.5 and 27.5 % of all enrolled patients respectively (five patients having both). Peripheral retinal occlusion was a frequent ocular finding in both groups; the youngest patient showing PR was 15 years old. Older age, longer disease duration and splenectomy were significantly more prevalent among patients with PR. Despite lack of visual symptoms, children and young adults are at risk of PR. Frequency of retinal lesions was comparable in SS and S/β patients. Periodic ophthalmologic examination starting at the age of 12 years is recommended for timely-identification of retinal lesions thus minimizing the risk of sight threatening retinopathy.