LHRH药代动力学试验

目的:研究黄体激素释放激素(Luteinizinghormone releasinghormone,LHRH)在大鼠体内的药动学规律。方法:用氯胺T法将125I标记到LHRH分子上(放化纯度96.2%),14只SD大鼠随机分为大剂量、小剂量组,每组7只,分别肌肉注射125I LHRH(小剂量组0.5mg.kg,大剂量组1.00mg.kg),给药后在21个不同时间点逐一取各鼠尾动脉血做放射性测定。结果:大鼠试验结果显示,大剂量组t1/2平均为67.83±20.84h;小剂量组半衰期平均为64.68±22.90h。LHRH的药—时曲线符合二室模型,大剂量LHRH和小剂量LHRH的主要药动学指标差别不大。结论:LHRH在大鼠体内的消除模式为二室模型,为一级动力学消除。     

Genetic segregation of spontaneous erosive arthritis and generalized autoimmune disease in the BXD2 recombinant inbred strain of mice

The BXD2 strain of mice is one of approximately 80 BXD recombinant inbred (RI) mouse strains derived from an intercross between C57BL/6J (B6) and DBA/2J (D2) strains. We have discovered that adult BXD2 mice spontaneously develop generalized autoimmune disease, including glomerulonephritis (GN), increased serum titres of rheumatoid factor (RF) and anti-DNA antibody, and a spontaneous erosive arthritis characterized by mononuclear cell infiltration, synovial hyperplasia, and bone and cartilage erosion. The features of lupus and arthritis developed by the BXD2 mice segregate in F2 mice generated by crossing BXD2 mice with the parental B6 and D2 strains. Genetic linkage analysis of the serum levels of anti-DNA and RF by using the BXD RI strains shows that the serum titers of anti-DNA and RF were influenced by a genetic locus on mouse chromosome (Chr) 2 near the marker D2Mit412 (78 cm, 163 Mb) and on Chr 4 near D4Mit146 (53.6 cm, 109 Mb), respectively. Both loci are close to the B-cell hyperactivity, lupus or GN susceptibility loci that have been identified previously. The results of our study suggest that the BXD2 strain of mice is a novel model for complex autoimmune disease that will be useful in identifying the mechanisms critical for the immunopathogenesis and genetic segregation of lupus and erosive arthritis.     

Limiting dilution analysis of CD4 T-cell cytokine production in mice administered native versus polymerized ovalbumin: directed induction of T-helper type-1-like activation.

Polarized expression of T-helper type-1 (Th1)- or Th2-like patterns of cytokine production frequently correlates with disease outcome. Previously, we have described the long-lived reciprocal regulation of ovalbumin (OVA)-specific IgE (> 95% inhibition) and IgG2a (300-800-fold increased) production following administration of high MW OVA polymers (OVA-POL), in both de novo and ongoing OVA (alum)-induced responses. Here, limiting dilution analysis (LDA) was used to compare precursor frequencies of CD4 T cells producing interferon-gamma (IFN-gamma), interleukin-4 (IL-4) or IL-10 following OVA versus OVA-POL exposure in vivo. Adjuvants were not used, so as to circumvent their impact on measurement of precursor frequencies. We found that the two forms of antigen elicited T-cell activation of comparable intensity, as indicated by equivalent precursor frequencies of clonogenic antigen-specific CD4 T cells. However, they elicited qualitatively different cytokine responses. OVA-POL treatment led to 10-fold higher (mean of six independent LDA experiments) frequencies of IFN-gamma-producing cells, and a mean fivefold lower frequency of IL-10-producing cells, than was observed following in vivo administration of unmodified OVA. Thus, the high MW polymerized form of antigen acted to steer commitment of naive (for this antigen) CD4 T-cell activation from a situation in which IL-10 producers outnumbered IFN-gamma-producing cells by a factor of 4:1 (found in mice administered OVA), to one where IFN-gamma producers dominated by a factor of 11:1 (in mice given OVA-POL), i.e. a qualitative shift in the nature of the OVA-specific response induced from Th2-like to Th1-like. In vivo co-administration of anti-IFN-gamma monoclonal antibody (mAb) abolished the capacity of OVA-POL to preferentially elicit Th1-like dominance. Interestingly, although the ratios of IFN-gamma:IL-4 and IFN-gamma:IL-10 OVA-specific precursor frequencies were strongly increased following OVA-POL exposure (mean 18- and 47-fold higher), the frequency of IL-4-producing CD4 T cells did not differ significantly. The data suggest that this modified antigen promotes in vivo commitment of naive T cells towards a Th1-like response, with consequent inhibition of IgE and enhancement of IgG2a responses, not through direct effects on IL-4 production, but via decreased frequencies of IL-10 and increased frequencies of IFN-gamma-producing OVA-specific CD4 cells. Collectively, the data (1) demonstrate the ability to manipulate commitment of antigen-driven CD4 T-cell populations in naive mice to specific patterns of cytokine gene expression, and (2) provide in vivo evidence of the regulatory role played by IFN-gamma in limiting induction and/or expansion of IL-4- and IL-10-producing CD4 cells to protein allergens.     

应用合成肽研究柯萨奇B病毒衣壳蛋白VP1的共同抗原表位

对柯萨奇B4病毒(CVB4)衣壳蛋白VPl保守区的亲水性和二级结构进行分析和预测,选择可能代表优势抗原表位的肽段进行合成(VPl-l肽,RIYF KPKHVK AYV),并截取了该肽段的前12个残基(VPI-2肽)用同样方法进行合成.用VP1-1肽免疫家兔制备出高效价抗体,应用酶联免疫吸附法(ELISA)检测,这些抗体与CVBI-6病毒均有结合反应,VP1-1肽与型特异性CVB1-6抗体均有良好的结合反应,表明VP1-1肽是CVB的共同抗原表位.用VP1-1肽检测心肌炎患者血清CVBIgM抗体,阳性率在40%左右.     

Activation of CD8+ T cells by allogeneic class II-deficient B-cell lines derived from patients with bare lymphocyte syndrome

The major histocompatibility complex (MHC) class II antigens (Ags) are known to carry the major stimulating determinants of the primary mixed lymphocyte reactions (MLR). We investigated the mechanism of generating HLA class I-directed alloreactive T-cells in primary MLR. With the use of class II-deficient EBV-transformed B-lymphoblastoid cell lines (B-LCLs) derived from patients with bare lymphocyte syndrome (BLS), we have demonstrated in the present study that class I disparity alone can trigger primary MLR in the absence of exogenous IL-2. The CD8+ T cells were primary MLR-responsive cells, and the CD4+ T cells seem to play no role in primary MLR when class II alloantigens are not involved in stimulation. Addition of autologous macrophages did not influence the primary MLR response. The primary MLR was completely blocked by anti-class I or anti-CD8 antibodies but not by anti-class II or anti-CD4 antibodies. The MLC-generated CD8+ T cells exhibited cytolytic activity as well as proliferative responses. The proliferative response of the CD8+ T cells was specifically directed against class I antigens, demonstrated by proliferative assays; and the helper-independent CD8+ T cells were generated only when the activation of CD4+ T cells did not occur. This observation suggests that functional recruitment of T-cell receptor (TCR) repertoire is under active regulation, and the suppression of CD8+ T-cell helper recruitment appears to be dictated by the CD4+ T-cell subset. Further analysis of the primed T-cell specificities showed that alloreactivity of the CD8+ T cells was mostly accounted for by the HLA-B Ags.(ABSTRACT TRUNCATED AT 250 WORDS)     

Laparoscopy-assisted urologic surgery through minilaparotomy

Minimally invasive surgery has gained wide acceptance as a method of reducing postoperative pain and curtailing the convalescence period. We have devised a modified surgical technique of laparoscopy-assisted surgery through minilaparotomy. It is a hybridized form of conventional open and laparoscopic surgery and it combines the benefits of both techniques by reducing postoperative pain and scarring as in laparoscopy, but at the same time maintaining the safety of conventional open surgery. From January 1992 to September 1999, we performed laparoscopy-assisted surgery through minilaparotomy in 167 patients. The operative time for laparoscopy-assisted surgery through minilaparotomy ranged from 79 to 290 minutes (mean 125). There was no conversion to open surgery, no peri- or postoperative complications, and only 3 patients needed a blood transfusion at any stage. Pain was significant on the first day but resolved quickly. All patients resumed consistent oral intake on the second day. All patients commenced ambulation by the second postoperative day and were able to resume full ambulatory activity by the fourth postoperative day. The final would size did not exceed 10 cm in size and all patients expressed satisfaction with their wounds. In conclusion, we believe that laparoscopy-assisted minilaparotomy surgery is a truly minimally invasive technique maintaining the advantages of conventional surgery. Our method could become a first-line approach for simple nephrectomy, living donor nephrectomy and radical nephrectomy, as well as surgery for kidney and ureter stones.     

慢性肾功能不全患者血清及尿液超氧化物歧化酶含量的变化

用放射免疫分析测定７５例肾病患者血清和尿液含铜锌离子超氧化物歧化酶（Ｃｕ－Ｚｎ－Ｓｕｐｅｒｏｘｉｄｅｄｉｓｍｕｔａｓｅ，简称Ｃｕ－Ｚｎ－ＳＯＤ或ＳＯＤ－１）的含量，并与５１名健康人对比。结果显示，慢性肾功能不全（ＣＲＦ）血透组患者血清ＳＯＤ－１含量显著增高（Ｐ＜０．０１），随着血液透析期的延长，其含量有渐升趋势；非血透组略有降低（Ｐ＞０．０５；其它肾病组明显降低（Ｐ＜０．０１）。三组患者尿液ＳＯＤ－１含量呈不同程度增高（Ｐ均＜０．０１），并随着病变的严重程度而增幅更明显，血／尿ＳＯＤ－１比值也随之降低。本文初步分析了这些变化的原因及意义。     

Preparation of poly(amide-imide)s by means of triphenyl phosphite, 1. Aliphatic-aromatic poly(amide-imide)s based on trimellitimide

Aliphatic-aromatic poly(amide-imide)s with high molecular weight (η_inh up to 2,91 dl/g in DMAc/5% LiCl) were synthesized by direct polycondensation reaction of imide-containing dicarboxylic acids and aromatic diamines using triphenyl phosphite in N-methyl-2-pyrrolidone (NMP)/pyridine solution in the presence of metal salts. The factors affecting the reaction of N-(trimellitoyl)glycine and 4,4′-oxydianiline were investigated. The molecular weight of the polymer varied with the amount of metal salts, showing a maximum at a concentration of about 1 wt.-% CaCl₂ or about 2 wt.-% LiCl in the reaction mixture. A monomer concentration of about 0,2 mol/l gave the most favorable result. Among the solvents tested, NMP was most effective. Similarly, polycondensations of several combinations of three imide-diacids with various aromatic diamines were carried out. Solubility, thermal properties, and tensile properties of the polymers are discussed.     

Preparation of graded porous titanium coatings on titanium implant materials by plasma spraying

Graded porous titanium coatings have been deposited on titanium substrates for dental implants by plasma spraying in an argon atmosphere. X-ray diffraction (XRD), scanning electron microscopy (SEM), surface roughness measurement, and tensile strength tests were performed on graded porous coatings. The results showed that Ti(3)O(5) was formed in the outermost surface of the porous coatings due to oxidation. The graded porous coatings consisted of three layers. The outer layer was full of macropores with a surface roughness of approximately 100 microm. The diameter of many macropores reached and even surpassed 150 microm, which could be beneficial for tissue to grow into the coating. The middle layer consisted of a mixture of micropores and macropores. The inner layer was a very dense and tight interface layer that included mechanical, physical, and metallurgical bonding. In tensile strength tests, testing bars peeled off the coatings, because the adhesive agent fractured, but the coatings remained intact.