Polymorphisms of the human platelet alloantigens HPA-1, HPA-2, HPA-3, and HPA-4 in ischemic stroke

Polymorphism in human platelet antigen (HPA)-1 and HPA-3 (GPIIb/IIIa), HPA-2 (GPIb/IX), HPA-4 (GPIIIa), and HPA-5 (GPIa/IIa) was investigated in 329 stroke patients and 444 matched control subjects. HPA genotyping was done by PCR-SSP method. Lower HPA-1a (P < 0.001) and higher HPA-1b (P < 0.001) allele frequencies were seen in patients than control subjects, and homozygosity for HPA-1b (P < 0.001) alleles was more prevalent in stroke cases than in controls. The allele and genotype distributions of the other HPA polymorphic variants were similar between cases and controls. Select HPA combined genotypes comprising the 2121 (Pc = 0.008) and 2221 (Pc = 0.018) genotypes, which were positively associated, and the 1111 (Pc < 0.001), which was negatively associated with stroke, thereby conferred a disease susceptibility and protective nature to these genotype combinations. Multivariate analysis confirmed the negative association of the 1111 (P < 0.001) and the positive association of the 2121 (P = 0.017) combined genotypes with stroke, after adjustment for a number of covariates. This is the first evidence demonstrating differential association of the common 4 HPA gene variants and specific HPA genotype combinations with stroke.     

Evidence for HLA class II susceptible and protective haplotypes for osteomyelitis in pediatric patients with sickle cell anemia

We investigated the association of human leukocyte antigen (HLA) class II alleles and haplotypes with the pathogenesis of sickle cell anemia (SCA) osteomyelitis. SCA patients comprised 42 patients with osteomyelitis and 150 patients without osteomyelitis; HLA-DRB1* and HLA-DQB1* genotyping was performed by polymerase chain reaction-sequence-specific priming (SSP). DRB1*100101 (P value corrected for the number of different alleles tested, Pc=0.003) was positively associated with osteomyelitis. At the haplotype level, DRB1*100101-DQB1*050101 (Pc=0.001) was more prevalent among patients, while DRB1*030101-DQB1*0201 (Pc=0.020) and DRB1*040101-DQB1*0302 (Pc=0.039) were more prevalent among SCA controls, thereby conferring disease susceptibility or protection to these haplotypes, respectively. These results show that specific HLA haplotypes influence SCA osteomyelitis risk and that specific HLA types may serve as markers for identifying SCA patients at high risk for osteomyelitis.     

Autoimmune Type 1 Diabetes Genetic Susceptibility Encoded by Human Leukocyte Antigen DRB1 and DQB1 Genes in Tunisia

Human leukocyte antigen (HLA) class II genes contribute to the genetic susceptibility to type 1 diabetes (T1D), and susceptible alleles and haplotypes were implicated in the pathogenesis of T1D. This study investigated the heterogeneity in HLA class II haplotype distribution among Tunisian patients with T1D. This was a retrospective case control study done in Monastir in central Tunisia. The subjects comprised 88 T1D patients and 112 healthy controls. HLA-DRB1 and -DQB1 genotyping was done by PCR-sequence-specific priming. Significant DRB1 and DQB1 allelic differences were seen between T1D patients and controls; these differences comprised DRB1*030101 and DQB1*0302, which were higher in T1D patients than in control subjects, and DRB1*070101, DRB1*110101, DQB1*030101, and DQB1*060101, which were lower in T1D patients than in control subjects. In addition, the frequencies of DRB1*030101-DQB1*0201 and DRB1*040101-DQB1*0302 were higher in T1D patients than in control subjects, and the frequencies of DRB1*070101-DQB1*0201 and DRB1*110101-DQB1*030101 haplotypes were lower in T1D patients than in control subjects. Multiple logistic regression analysis revealed the positive association of DRB1*030101-DQB1*0201 and DRB1*040101-DQB1*0302 and the negative association of only DRB1*070101-DQB1*0201 haplotypes with T1D. Furthermore, a significantly increased prevalence of DRB1*030101-DQB1*0201 homozygotes was seen for T1D subjects than for control subjects. Our results confirm the association of specific HLA-DR and -DQ alleles and haplotypes with T1D in Tunisians. The identification of similar and unique haplotypes in Tunisians compared to other Caucasians highlights the need for evaluating the contribution of HLA class II to the genetic susceptibility to T1D with regard to haplotype usage and also to ethnic origin and racial background.Type 1 (insulin-dependent) diabetes (T1D) is the most prevalent form of diabetes in children and young adults (12, 17) and results from autoimmune CD4⁺ and CD8⁺ T-cell-directed destruction of insulin-producing pancreatic ß islet cells, leading to irreversible hyperglycemia and related complications (4, 22). In addition to environmental factors, there is a strong genetic component to T1D pathogenesis, of which the human leukocyte antigen (HLA) locus, in particular the class II region (DR and DQ), account for 40 to 50% of T1D familial clustering (13, 30). This was evidenced by the enrichment of DR3, DR4, DQ2, and DQ8, and the lower prevalence of DR15 or DQ6.2 alleles among T1D patients, thereby assigning a susceptible or protective role for these alleles in T1D pathogenesis, respectively (3, 16, 21).The fact that not all carriers of a specific high-risk DR or DQ variant develop the disease and the strong linkage disequilibrium between select DRB1 and DQB1 alleles (28) indicate that the pathogenesis of T1D results from the complex interaction between several genes within the class II region, in which specific DRB1-DQB1 haplotypes contribute to disease susceptibility. Accordingly, the enrichment or decreased prevalence of select DRB1-DQB1 haplotypes in T1D patients imparts disease susceptibility or protection, respectively (3, 18, 24). This susceptibility or protection effect disappears when a different DRB1 or DQB1 allele replaces the specific allele in the haplotype (29). The contribution of specific HLA haplotypes toward T1D susceptibility depends on the ethnic/racial background (26), which was highlighted by the positive association of DRB1*030101-DQB1*0201 and DRB1*040101-DQB1*0302 haplotypes with T1D among Caucasians (3, 16) compared to DRB1*0405-DQB1*0401 and DRB1*0901-DQB1*0303 haplotypes and T1D in Japanese (18), while DRB1*1501-DQB1*0602 appeared to be protective of T1D in all populations (3, 16, 18). This indicates that association of a specific class II allele and DRB1-DQB1 haplotype with T1D must be evaluated in the context of the specific ethnic/racial background (26).We previously reported an association between HLA DRB1 and DQB1 alleles and haplotypes in Tunisian T1D patients (n = 50) and control subjects (n = 50) and identified two susceptible haplotypes (DRB1*030101-DQB1*0201 and DRB1*040101-DQB1*0302), but no protective haplotypes (27). Using haplotype estimation and regression analysis, here, we extend our investigation of HLA class II and T1D risk on a large sample size by confirming the association of these haplotypes and identified an additional T1D-protective haplotype.     

藻酸双酯钠与蝮蛇抗栓酶-3号对冠心病血液流变学作用的对比观察

对比观察藻酸双酯钠与腹蛇抗栓酶-3号对90例冠心病患者血液流变学作用的影响。结果示:藻酸双酯钠与蝮蛇抗栓酶-3号均能明显改善冠心痛患者血液流变学状态,降低血液粘度。蝮蛇抗栓酶-3号比藻酸双酯钠效果更佳。     

新生物碱——18-羟基喜树碱

自喜树(Camptotheca acuminata Decne)果中分到一个新生物碱,经光谱分析(UV,IR,¹HNMR,MS,CD)推定为18-羟基喜树碱(Ⅰ),同时分得的还有吕宋果内酯,水杨酸和壬二酸。18-羟基喜树碱对P388白血病细胞有细胞毒活性。     

盐酸西布曲明的合成

目的：改进肥胖症治疗药盐酸西布曲明（ｓｉｂｕｔｒａｍｉｎｅ ｈｙｄｒｏｃｈｌｏｒｉｄｅ）的合成方法。方法：以４－氨苄腈为起始原料,经环烃化、Ｇｒｉｇｎａｒｄ反应、还原、Ｅｓｃｈｗｅｉｌｅｒ－ｃｌａｒｋｅ甲基化和成盐等反应合成了盐酸西布曲明。结果：合成产物经熔点、元素分析、红外光谱和核磁共振谱等确证,总收率３６．３％。结论：此合成工艺简便,易于工业化生产。     

中药葛根及其同属植物的资源利用和评价

对我国葛属（ＰｕｅｒａｒｉａＤＣ，）９种和１变种植物进行了调查研究，认为目前国内市售中药葛根的主流品种为野葛Ｐ，ｌｏｂａｔａ（Ｗｉｌｌｄ．）Ｏｈｗｉ和粉葛Ｐ．ｔｈｏｍｓｏｎｉｉ）Ｂｅｎｔｈ．。野葛在我国大部份省区都有分布，资源最为丰富；粉葛在广西载培历史悠久；其他种主要分布在西南地区，并有少数种在当地作中药葛根用。从成分分析结果看，野葛的葛根素（ｐｕｅｒａｒｉｎ）及总黄酮含量显著高于本属其它植物，粉葛次之。除野葛和粉葛外其他种均不宜作葛根药用。峨嵋葛Ｐ．ｏｍｅｉｅｎｓｉｓＷａｎｇｅｔＴａｎｇ是个有争议的种，我们比较了化学成分的含量，其结果与粉葛相近，而与山葛藤有所区别，有待进一步研究。     

Tacrolimus (FK506) versus cyclosporine microemulsion (neoral) as maintenance immunosuppression therapy in kidney transplant recipients

The effects of the calcineurin inhibitors tacrolimus (FK506) and cyclosporine (Neoral) on graft survival, function, and metabolic profile were evaluated in 69 patients receiving Neoral (group 1) and 54 patients receiving FK506 (group 2) for maintenance immunosuppression following kidney transplantation. Recipient and donor demographics and induction therapy were comparable, except for a higher number of sensitized patients in group 2 (n = 13). Acute rejection timing, severity, and infection rates and types were similar in both groups. During hospitalization, at 6 months, and at 1 year following transplantation, no significant differences were noted between groups in fasting glucose, serum cholesterol levels, triglyceride levels, or need for insulin or antihypertensive therapy. Mean serum creatinine levels on discharge (1.42 mg/dL +/- 0.14 vs 1.68 mg/dL +/- 0.3), at 1 month (1.45 mg/dL +/- 0.1 vs 1.39 mg/dL +/- 0.11), 3 months (1.46 mg/dL +/- 0.09 vs 1.32 mg/dL +/- 0.14), and 1 year (1.29 mg/dL +/- 0.08 vs 1.19 mg/dL +/- 0.09), but not at 6 months (1.42 +/- 0.37 vs 1.10 +/- 0.07; P = .001), were comparable between groups. The 1-year patient and graft survival rates were 98.3% for group 1 and 94.5% for group 2. When evaluated for acute rejection, infection, and metabolic differences, we conclude that both tacrolimus and cyclosporine are effective and safe calcineurin inhibitors for short-term use in kidney transplantation. A similar study is proposed to evaluate the long-term effects of both agents.