Costimulation and Autoimmune Diabetes in BB Rats

Costimulatory signals regulate T-cell activation. To investigate the role of costimulation in autoimmunity and transplantation, we studied the BB rat model of type 1 diabetes. Diabetes-prone BB (BBDP) rats spontaneously develop disease when 55–120 days of age. We observed that two anti-CD28 monoclonal antibodies (mAb) with different functional activities completely prevented diabetes in BBDP rats. Anti-CD154 mAb delayed diabetes, whereas treatment with CTLA4-Ig or anti-CD80 mAb accelerated disease. Anti-CD86 or anti-CD134L mAbs had no effect. Diabetes resistant BB (BBDR) rats are disease-free, but >95% of them develop diabetes after treatment with polyinosinic-polycytidylic acid and an mAb that depletes Treg cells. In the induced BBDR model, anti-CD154 mAb delayed onset of diabetes, whereas CTLA4-Ig, anti-CD134L or either of the anti-CD28 mAbs had little or no effect. In contrast, blockade of the CD134-CD134L pathway was highly effective for preventing autoimmune recurrence against syngeneic islet grafts in diabetic BBDR hosts. Blockade of the CD40-CD154 pathway was also effective, but less so. These data suggest that the effectiveness of costimulation blockade in the treatment of type 1 diabetes is dependent on both the costimulatory pathway targeted and the mechanism of induction, stage, intensity and duration of the pathogenic process.     

Novel explant model to study mechanotransduction and cell-cell communication.

To understand in situ behavior of osteocytes, we characterized a model of osteocytes in their native bone matrix and demonstrated real-time biologic activity of osteocytes while bending the bone matrix. Using 43 male Sprague-Dawley rats, dumbbell-shaped explants were harvested from stainless steel femoral implants after 6-12 weeks and incubated in culture medium or fixed. Sixteen specimens were used to determine bone volume density (BV/TV), volumetric bone mineral density (BMD) and histology for different implantation periods. Osteocyte viability was evaluated by L-lactate dehydrogenase (LDH) activity in 12 cultured explants. Confocal microscopy was used to assess tracer diffusion in three explants and changes in osteocyte pH of a mechanically loaded explant. From 6 to 12 weeks, explant BV/TV and volumetric BMD trended up 92.5% and 101%, respectively. They were significantly and highly correlated. Tissues were uniformly intramembranous and all bone cell types were present. Explants maintained LDH activity through culture day 8. Diffusion at 200 microM was limited to 1,209 Da. Explants appeared capable of reproducing complex bone biology. This model may be useful in understanding osteocyte mechanotransduction in the context of a physiologically relevant bone matrix.     

Overexpression of suppressor of cytokine signalling-5 augments eosinophilic airway inflammation in mice

BACKGROUND: Enhanced expression of the suppressor of cytokine signalling (SOCS)-5 might be of therapeutic benefit for T-helper type 2 (Th2) dominant diseases, as its expression is reported to result in a reduction of Th2 differentiation in vitro due to the inhibition of IL-4 signalling. OBJECTIVE: To investigate the regulatory role of SOCS-5 in vivo, we explored the phenotype of an experimental asthma model developed in SOCS-5 transgenic (Tg) mice. METHODS: The SOCS-5 Tg mice or wild-type (WT) mice were sensitized and repeatedly challenged with ovalbumin (OVA). We examined bronchoalveolar lavage fluid (BALF), lung specimens, and airway hyperresponsiveness (AHR) to methacholine. RESULTS: The production of IFN-gamma by CD4(+) T cells from unprimed SOCS-5 Tg mice was significantly increased in comparison with unprimed wild-type mice, indicating that SOCS-5 Tg mice have a Th1-polarizing condition under natural conditions. However, in an asthma model, significantly more eosinophils in the airways and higher levels of IL-5 and IL-13 in BALF were observed in the SOCS-5 Tg than the wild-type mice. AHR in the asthma model of SOCS-5 Tg was also more enhanced than that of wild-type mice. OVA-stimulated CD4(+) T cells from the primed SOCS-5 Tg mice produced significantly more IL-5 and IL-13 than CD4(+) T cells from wild-type mice. CONCLUSION: Our results demonstrate that the overexpression of SOCS-5 does not inhibit Th2 response, but rather augments the phenotype of the asthma model in vivo. This finding throws into question the therapeutic utility of using enhancement of SOCS-5 expression for Th2-dominant disease.     

九洲港货运港区的鼠密度调查、及灭鼠效果观察

本文报道了1995年春对九洲港货运港区的鼠密度和灭鼠效果调查，结果鼠密度投药后(4．1％)比投药前(24．6％)有明显下降，灭鼠率达83．3％；根据九洲港货运港区鼠患情况，提出防鼠灭鼠建议。     

溴敌隆的家栖鼠实验室适口性和现场灭鼠效果评价

目的　评价溴敌隆防制家栖鼠的效果。方法　实验室有选择适口性试验 ,现场灭家栖鼠效果考核。结果　在有选择的摄食试验条件下 ,0 .0 0 5 %溴敌隆大米毒饵对褐家鼠和黄胸鼠的毒杀率达 10 0 %和 94 .4 4 % ,摄食系数分别为 0 .6 3和 0 .5 4 ,致死剂量分别为 9.97(0 .0 6～ 2 4 .6 9)和 7.93(5～ 17.6 1)mg/kg。现场灭家栖鼠试验 ,灭鼠率达 86 .4 3%。结论　溴敌隆对家栖鼠毒效髙 ,适口性好 ,具有较好的防制效果     

海南省钩端螺旋体病地理流行病学研究 Ⅰ.自然地理、动物地理区划和流行概况

本文简介海南岛的自然地理、啮齿动物地理区划和社会经济（包括人口数、性别年龄分布、人工植被、耕作习惯等）与钩端螺旋体病发生或流行有关的自然因素．扼要报告自1958─1991年以来各年度该病的发病率与病死率，比较了50─90年代总的发病态势是低→高→低，并略作了分析。     

Spatiotemporal pattern of striatal ERK1/2 phosphorylation in a rat model of L-DOPA-induced dyskinesia and the role of dopamine D1 receptors.

BACKGROUND: We examined the activation pattern of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and its dependence on D1 versus D2 dopamine receptors in hemiparkinsonian rats treated with 3,4-dihydroxyphenyl-L-alanine (L-DOPA). METHODS: 6-Hydroxydopamine-lesioned rats were treated acutely or chronically with L-DOPA in combination with antagonists for D1 or D2 receptors. Development of dyskinesia was monitored in animals receiving chronic drug treatment. Phosphorylation of ERK1/2, mitogen- and stress-activated protein kinase-1 (MSK-1), and the levels of FosB/DeltaFosB expression were examined immunohistochemically. RESULTS: L-DOPA treatment caused phosphorylation of ERK1/2 in the dopamine-denervated striatum after acute and chronic administration. Similar levels were observed in matrix and striosomes, and in enkephalin-positive and dynorphin-positive neurons. The severity of dyskinesia was positively correlated with phospho-ERK1/2 levels. Phosphorylation of ERK1/2 and MSK-1 was dose-dependently blocked by SCH23390, but not by raclopride. SCH23390 also inhibited the development of dyskinesia and the induction of FosB/DeltaFosB. CONCLUSIONS: L-DOPA produces pronounced activation of ERK1/2 signaling in the dopamine-denervated striatum through a D1-receptor-dependent mechanism. This effect is associated with the development of dyskinesia. Phosphorylated ERK1/2 is localized to both dynorphinergic and enkephalinergic striatal neurons, suggesting a general role of ERK1/2 as a plasticity molecule during L-DOPA treatment.     

全国部分城乡家鼠鼠情监测三年结果分析——Ⅰ.鼠种组成及地区分布

对全国部分城乡家鼠鼠情监测三年结果的分析表明:城乡家鼠组成均以三大家鼠(褐家鼠、小家鼠、黄胸鼠)为主,其次为食虫目臭鼩鼱~#和黑线姬鼠。五种主要鼠种在家鼠组成中的数量比基本稳定,但三年中城乡少数鼠种间的顺位有所变化。监测结果亦表明,五种主要鼠种的地区分布是:褐家鼠、小家鼠遍布所有监测的省、市、区,同以往文献中遍布全国的说法一致;黄胸鼠分布于黄河以南;食虫目中的臭鼩鼱分布于华中区以南的广大地区。这在以往文献中均已有记载,但以往文献有关黄胸鼠和臭鼩鼱分布的其他说法,则被证实为不确切的。黑线姬鼠的分布范围已超过以往文献中关于分布于东北、华北及长江流域的说法,但以往文献中关于该鼠种遍及全国的说法是否正确,则有待进一步证实。     

大隆毒饵灭鼠效果的研究

目的 观察大隆毒饵现场灭鼠效果。方法采用粉迹法调查鼠密度，在现场采用饱和投毒法投放大隆灭鼠毒饵。结果投放毒饵20d后，鼠密度由灭鼠前的10．8％-18．2％下降到1．2％-2．0％，灭鼠率为88．9％以上。结论 0．005％大隆毒饵现场大面积灭鼠效果好，使用方便，安全可靠。