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.     

一对一责任助产加笑气吸入用于分娩镇痛的疗效观察

目的探讨一对一责任助产加笑气吸入对分娩镇痛的疗效。 方法将576例产妇随机分为观察组和对照组．每组288例，两组均采用一对一责任助产及其他产科处理措施，观察组同时给予笑气吸入．观察两组的产痛程度、产程时间、分娩方式、笑气对新生儿的影响、产后出血及尿潴留等。 结果观察组无痛分娩率达95．8％．而对照组则为0（P〈0．01），观察组的产程时间短于对照组（P〈0．01）。 结论笑气吸入分娩镇痛产程时间短，对母婴均无不良影响，加一对一责任助产．是一种理想的分娩方法，值得产科临床推广使用。     

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.     

树突状细胞激活的肿瘤浸润性淋巴细胞体外对自体肝癌细胞杀伤活性的研究

目的探讨树突状细胞(DC)激活的肿瘤浸润性淋巴细胞(TIL)体外对自体肝癌细胞杀伤活性.方法从肝癌患者外周血获取DC,应用粒/巨噬细胞集落刺激因子(GM-CSF)、白细胞介素-4(IL-4)和肿瘤抗原激活DC,然后用DC来激活TIL,观察TIL在体外对自体肝癌细胞的杀伤活性.结果DC激活的TIL具有很高的对自体肝癌细胞杀伤活性,杀伤率为(89.39±3.05)%,明显高于未经DC激活的TIL、CD激活的T淋巴细胞和未经DC激活的T淋巴细胞对自体肝癌细胞的杀伤率.结论肝癌患者外周血DC能诱导TIL产生高效而特异的抗肝癌免疫.     

脐血LAK细胞生物学特性影响因素的研究

采集２３名产妇的脐带血和８名正常成人的外周血制备ＬＡＫ细胞，随机分为４组，在培养第３，５，７，１４天，分别利用ＭＴＴ法和＾１２５Ｉ－ＵｄＲ释放法对４组ＬＡＫ细胞的增殖力和杀伤活性进行了测定，同时用细胞毒方法测定培养７天的ＬＡＫ细胞的免疫表型。结果发现，在不同培养时间，脐血来源的ＬＡＫ细胞增殖力显著高于成人血ＬＡＫ细胞（Ｐ〈０．０５或Ｐ〈０．０１），成人血清组，脐血血清组，红细胞组ＬＡＫ细胞增殖力有     

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.     

Hyperprolactinemia inhibits natural killer (NK) cell functionin vivo and its bromocriptine treatment not only corrects it but makes it more efficient

We studied NK cell function in eight patients with pathological hyperprolactinemia by measuring⁵¹Cr release by K562 cells exposed to their mononuclear cells and found it decreased compared to normal controls (P<0.01). Bromocriptine (BrC) treatment corrected NK function but also made it more efficient at 12:1 than at 25:1 or 50:1 effector:target ratios (ANOVA;P=0.01). The study of NK cell function in agarose revealed that its decrease in hyperprolactinemia is due to their low active binding to target cells, active killing, and recycling capacity. BrC tended to correct them but also increased recycling capacity to levels higher than those of controls (P<0.05). Sequential studies in three hyperprolactinemic patients before and after BrC showed correction of NK function within 1 week but its increased efficiency at the 12:1 effector:target ratio required 8 weeks. We conclude that hyperprolactinemia decreases NK cell function. BrC corrects this by decreasing prolactin levels but also makes NK function more efficient by increasing the capacity of NK cells to recycle after killing.     

Effects of N-acetylcysteine on bacterial clearance

Abstract. The aim of this study was to investigate whether the oxygen radical scavenger N -acetylcysteine ( N -AC) impairs bacterial clearance, thus predisposing the host to increased risk of disease. Blood clearance of Escherichia coli and organ colonization were investigated in anaesthetized rabbits after pretreatment with N -AC (250 mg kg^-1 body weight, n = 16) and in sham-operated animals ( n = 12). To enable quantification of the clearance process, defined numbers of exogenous E. coli [1.3 times 108 colony-forming units (CFUs)] were injected intravenously. Parameters monitored were kinetics of bacterial elimination from the blood, and polymorphonuclear leucocyte (PMN) oxidative burst activity. Samples of liver, kidney, spleen and lung were collected for bacterial counts. Compared with controls, pretreatment with N -AC resulted in delayed bacterial elimination from blood and higher organ colonization with increased numbers of E. coli in liver, lung and kidney ( P < 0.05). N -AC treatment was associated with a suppressed PMN oxidative burst activity. Impaired bacterial clearance and enhanced organ colonization in N -AC-treated animals correlated with reduced oxidative burst activity, suggesting impaired granulocyte-dependent bacterial killing due to N -AC application.     

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。