Induction of Experimental Antiphospholipid Antibody Syndrome in PL/J Mice Following Immunization With β2GPI

PROBLEM: Immunization with β₂-glycoprotein I (β₂GPI) induces antiphospholipid antibodies (aPL) in normal mice and rabbits. Recently we reported early onset of autoimmunity in MRL/++ mice following immunization with β₂GPI. There is a close association between aPL with thrombosis, recurrent fetal loss, and intrauterine growth retardation. In this study we evaluated the effect of β₂GPI-induced aPL on pregnancy outcomes in an inbred strain of mice (PL/J). METHOD: Three groups of seven-week-old female PL/J mice (12 per group) were studied. Group A was immunized with β₂GPI and group B with ovalbumin; group C was not immunized. After two booster injections, the mice were tested for aPL, anti-DNA by ELISA, and for ANA by indirect immunofluorescence. Platelet count and pregnancy outcomes were studied at the age of 14 weeks. RESULTS: The aPL and anti-DNA levels were higher at 12 and 14 weeks in group A; the optical densities (OD) were 1.72±0.6 and 0.699±0.25 for group A, 0.091 ±0.040 and 0.230±0.47 for group B, and 0.0435±0.003 and 0.119±0.026 for group C (comparing group A with groups B and C combined, P<0.001). ANA titers rose in groups A and B by age, but they were significantly higher at 14 weeks in group A. The mean titers were 1/286, 1/90, and 1/16 for A, B, and C, respectively (P<0.001). The platelet counts were not significantly different among the three groups. The litter size was significantly smaller in group A, as evidenced by the numbers of viable fetuses among the mice that became pregnant in each group: 0.75, 2.45, and 5.5 in groups A, B, and C, respectively. Seven pregnant mice in group A had complete resorption, seven pregnant mice in group B showed focal (partial) resorption areas, and only one mouse in group C had complete resorption of the embryos, as shown by histopathological studies, although the fecundity rate was similar in the three groups. CONCLUSION: Our data suggest a pathogenic role for β₂GPI-induced aPL in the development of experimental models of APS in PL/J mice.     

人重组C3片段通过IL-2自分泌效应对CTLL-2细胞产生促增殖作用

目的研究补体Ｃ３片段的体外生物学活性及其作用机理，进一步探讨Ｃ３片段与免疫细胞的关联。方法利用重组ＤＮＡ技术表达纯化Ｃ３活性片段（命名为Ｃ３３），观察其对ＩＬ－２依赖性的小鼠杀伤性Ｔ细胞株ＣＴＬＬ－２细胞的促增殖效应，并通过抗体封闭途径和分子杂交技术研究Ｃ３３作用的机理。结果发现Ｃ３３蛋白对ＣＴＬＬ－２细胞具有明显的促增殖作用，并呈剂量依赖关系；这一作用能够部分地被抗小鼠ＣＤ１１ｂ抗体所封闭，能够完全被抗小鼠ＩＬ－２抗体所封闭；分子杂交显示Ｃ３３蛋白能够明显刺激ＣＴＬＬ－２细胞的ＩＬ－２ｍＲＮＡ表达。结论人重组Ｃ３片段Ｃ３３可通过ＩＬ－２的自分泌效应对ＣＴＬＬ细胞产生促增殖作用，补体受体ＣＲ３参与这一作用。     

模拟医学生物化学实验血清标本的探讨

用蛋白胨、三油酸甘油酯、鼠肝、葡萄糖等材料模拟血清标本,通过测定该血清中蛋白、血脂、谷丙转氨酶、血糖以及部分物理参数,探讨了模拟血清从外观和实验项目上满足实验教学的可行性。结果表明,模拟血清实用、简便易得,既能解决医学生物化学实验教学标本来源困难问题,又能防止实验室污染和节省大量实验经费。     

Efficacy I: a new method for estimating relative efficacy of full agonists via a newly defined efficacy related parameter

A new method for estimating relative efficacies and relative intrinsic efficacies of agonists is described. Relative efficacy is estimated by employing a newly defined efficacy related parameter (e^ES) and it may be estimated without prior knowledge of efficacy values or the value of the equilibrium dissociation constants, K_A, of agonist-receptor complexes. The parameter e^ES is directly related to efficacy (e) and is defined as the ratio of maximal stimulus to maximal effect of an agonist. The value of e^ES indicates whether or not spare receptors are present for a particular agonist–effector system. The e^ES values of agonists are estimated by utilizing submaximal concentration–effect curves determined with fixed agonist-competitive antagonist concentration combinations and choosing a suitable reference (height of an agonistic concentration–effect curve) to which the height of the stimulus concentration–effect curves of the agonist may be compared. In addition to e^ES, other new agonist–effector parameters, namely S_Em/S_m and φ_min, were also defined.     

乌苯美司的药物动力学及对实验性肿瘤转移的治疗作用

目的：探讨乌苯美司对小鼠药物动力学及与实验性肿瘤转移治疗活性间的关系。方法：用放射免疫法测定小鼠在不同给药途径下的乌苯美司血清药物动力学及观察乌苯美司对黑色素瘤肺转移模型的治疗活性。结果：乌苯美司ｉｖ的Ｔ１２较短，初始血药浓度较高。ｉｖ和ｉｍ给药后的曲线下面积较大；ｐｏ及ｉｐ则较小。不同给药途径对实验性肿瘤转移均有治疗作用。结论：乌苯美司的血清Ｔ１２较短，其治疗活性取决于冲击和高剂量的给药方式。     

评价酶联免疫检测血清CYFRA21—1对非小细胞肺癌的诊断价值

目的评价检测ＣＹＦＲＡ２１┐１对非小细胞肺癌的诊断价值。方法用ＥＬＩＳＡ法测定７０例肺癌（ＬＣ）其中４７例非小细胞肺癌（ＮＳＣＬＣ），３例小细胞肺癌（ＳＣＬＣ）和２０例未分型肺癌、６４例肺部良性疾病患者及４０例健康人血清ＣＹＦＲＡ２１┐１浓度。试验的诊断性能用相对操作特征（ＲＯＣ）分析法估测之。结果测得全阈诊断准确率（ＯｖｅｒａｌＤｉａｇ┐ｎｏｓｔｉｃＡｃｃｕｒａｃｉｅｓ）ＬＣ为０．７５、ＮＳＣＬＣ为０．７６，ＳＱＣ为０．８３，ＡＤＥ为０．６７和ＳＣＬＣ为０．３８。在相应于特异性为０．９５的界定值３．４７μｇ／Ｌ处，各型的灵敏度分别为ＳＱＣ０．６２，ＬＣ０．５３，ＮＳＣＬＣ０．５１，ＡＤＥ０．４８和ＳＣＬＣ０．００。结论结果显示ＣＹＦＲＡ２１┐１是ＮＳＣＬＣ较灵敏和特异的一个标志物。未观察到ＴＮＭ各期间该标志物的平均水平有明显的差异；然而异常升高水平的患者的比例随病期的进展而显著增加，提示一系列检测ＣＹＦＲＡ２１┐１水平可能有助于监查ＮＳＣＬＣ患者的疗效。     

EFFECT OF SOME TRICYCLIC AND NONTRICYCLIC ANTIDEPRESSANTS ON [3H]IMIPRAMINE BINDING AND SEROTONIN UPTAKE IN RAT CEREBRAL CORTEX AFTER PROLONGED TREATMENT

Chronic administration of different antidepressant drugs reduced the number of [3H]imipramine [( 3H]IMI) binding sites in rat cerebral cortex. In the same experimental conditions, fluvoxamine and dothiepin, as well as desmethylimipramine, induced an increase in the maximal velocity of high affinity serotonin (5HT) uptake in cortical slices, whereas citalopram and viloxazine were ineffective in this regard. Our results indicate that even if 5HT uptake and [3H]IMI binding sites are located on the same nerve terminals, they are differently modulated. Increased Vmax of the 5HT uptake process could be due to a rebound phenomenon after withdrawal from drugs that acutely inhibit 5HT uptake. The effect on [3H]IMI sites might be explained through either the agonist properties of the drugs towards these sites or the involvement of mechanisms still unknown.     

Enhancement of performance by methyl β-carboline-3-carboxylate, in learning and memory tasks

Benzodiazepines are known to induce a profound anterograde amnesia in man. In this report, it is shown that methyl β-carboline-3-carboxylate (β-CCM), an inverse agonist of the benzodiazepine receptor, has the opposite effect; it enhances performance in learning and memory tasks. Three different learning models were used: habituation to a new environment and passive avoidance in mice and imprinting in chicks. The opposite effects of both β-CCM and the benzodiazepine diazepam were blocked by administration of the benzodiazepine receptor antagonist Ro 15-1788, provicling evidence that the benzodiazepine receptor is involved in these effects.     

Macrolide–lincosamide–streptogramin B resistance phenotypes and genotypes among Staphylococcus aureus clinical isolates in Japan

In total, 269 methicillin-resistant Staphylococcus aureus (MRSA) and 434 methicillin-susceptible S. aureus (MSSA) isolates were investigated to determine their macrolide-lincosamide-streptogramin B (MLS(B)) resistance phenotypes and genotypes. The constitutive phenotype (61.3% in MRSA, 1.3% in MSSA) and erm(A) gene predominated among the 261 erythromycin-resistant MRSA isolates, while the inducible phenotype (38.7% in MRSA, 94.0% in MSSA) and erm(C) gene were more prevalent among the 150 erythromycin-resistant MSSA isolates. There was a higher incidence of the MLS(B) inducible phenotype compared with other countries, perhaps because MLS(B) antibiotics are not recommended as first-line agents against S. aureus in Japan.     

High-Performance Liquid Chromatographic (HPLC) Assay Using Fluorescence Detection for the Simultaneous Determination of Gallopamil and Norgallopamil in Human Plasma

Gallopamil is a calcium-channel antagonist with reported activity in experimental animals three to five times higher than that of verapamil. An automated high-performance liquid chromatographic (HPLC) method with fluorescence detection is described for the simultaneous determination of gallopamil and its metabolite norgallopamil in plasma. Gallopamil was well resolved from norgallopamil and other metabolites, allowing simultaneous quantitation of both drugs. The detection limit for both gallopamil and norgallopamil was 0.9 ng/ml. This method has been successfully used for the determination of gallopamil and norgallopamil following the administration of 25-, 37.5-, and 50-mg oral doses of drug.