Therapeutic effect of 5-FC on YCD modified murine P388 leukemia in vivo

Cytosine deaminases (CDs) in bacteria andfungi are found to deaminate prodrug 5 - FC intocytotoxic agent 5 - FU .Yeast CD (YCD) is clonedfrom Saccharomyces cerevisiae.It has been shownpreviously that YCD was more efficient inconversing5 - FC than bacterial CD(b CD) [1-3 ] .As anovel suicide gene therapy system,YCD/ 5 - Fcsystem may be promising in cancer therapy andprevention of graft versus host disease.In thepresent study,we established a P388/ DBA murineleukemia model by infusin…     

心房颤动与炎症及慢性幽门螺旋杆菌感染相关性研究

目的探讨心房颤动(简称房颤)与炎症及慢性幽门螺旋杆菌(Hp)感染的关系。方法选取66例房颤患者为房颤组(其中阵发性房颤44例,慢性房颤22例),另取同期住院的阵发性室上性心动过速(简称室上速)患者67例作为对照组,用间接ELISA法测定血清Hp-IgG抗体,速率散射免疫比浊法测定C反应蛋白(CRP),比较两组Hp-IgG抗体,CRP的差异并分析HP抗体滴度与房颤及其它相关因素的关系。结果房颤组与对照组的Hp-IgG阳性率Hp-IgG对数值均无差异(P均>0.05)。房颤组CRP中位数较对照组高(1.17mg/dlvs0.65mg/dl,P<0.05)。结论房颤与慢性Hp感染不相关,与炎症相关。     

Monoclonal antibody production to human and bovine 2′:3′-cyclic nucleotide 3′-phosphodiesterase (CNPase): high-specificity recognition in whole brain acetone powders and conservation of sequence between CNP1 and CNP2

Monoclonal antibodies against human and bovine 2′:3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) were generated by fusing FOX-NY myeloma cells with spleen cells from RBF/Dn mice previously immunized with the purified brain antigens. The enzyme isolated from bovine brain was quite basic, with an isoelectric point of 9.71 and both the bovine and human enzymes consisted of a closely spaced doublet at approximately 44 and 46 kDa on SDS-PAGE. Six monoclonals were identified as strongly recognizing the enzyme on both ELISA plates and on immunoblots of whole brain protein. Four monoclonals very weakly cross-reacted with guinea pig myelin basic protein. In contrast with two previous reports, some of our monoclonal antibodies did immunostain 2 or 3 protein bands in peripheral nerve, two bands closely corresponding to those immunostained in central nervous system (CNS) myelin, the Wolfgram protein fraction and in acetone powders of whole brain. Each of the 6 monoclonals reacting strongly on immunoblots recognized the enzyme in from 2 to 5 of the species examined (human, bovine, rat, mouse and rabbit). In addition, all 6 monoclonals that immunostained the enzyme in whole brain, myelin and Wolfgram protein immunoblots recognized both CNP1 (44 kDa) and CNP2 (46 kDa). The two closely spaced protein bands observed on SDS-PAGE and previously stained on immunoblots of CNS CNPase using polyvalent rabbit anti-bovine CNPase antisera, and now different monoclonal antibodies, appear to be immunologically related and to contain highly conserved sequences.     

Expression of epithelial matrix molecules collagen and laminin and corresponding integrins in chronic wounds

Re-epithelialization of cutaneous wounds is a coordinated process of proliferation and migration of keratinocytes at the wound edge. The study objective was to identify the differences in epidermal morphology, keratinocyte proliferation and matrix molecules (laminin 1, laminin 5, type IV collagen) and their specific integrin (α3, α6) expression in biopsies of meshed split thickness grafted and chronic wounds. The mean mitotic index of keratinocytes (ratio of cell cycle associated antigen Ki-67 expressing keratinocytes to basal keratinocytes) was highest in chronic wounds (38.7%) compared to acute wounds (22.25%, range 5.7% to 54%). The mean thickness of the hyper-proliferative epithelium at the wound edge of chronic wounds was 0.69 mm compared to 0.15 mm at the wound margin of split thickness grafted wounds. Both chronic wounds and skin grafted wounds exhibited strong laminin 5 immunoreactivity at the basal side of the epithelium, which extended under the most forward keratinocytes. Laminin 1 and type IV collagen immunoreactivity did not extend to the wound margin in either skin grafted or chronic wounds. In both transplanted skin and chronic wounds, the integrin sub-units α3 and α6 exhibited a strong pericellular immunoreactivity on the leading keratinocytes of the wound margin. Our data demonstrates that the proliferation of keratinocytes and the expression of associated integrins are not impaired in chronic wounds. Presented at the 33rd Congress of the Association of German Plastic Surgeons, Germany, 18–21 September, 2002.     

Asymmetric dimethyl-arginine (ADMA) response to inflammation in acute infections.

BACKGROUND AND METHODS: The endogenous inhibitor of nitric oxide synthase (NOs) asymmetrical dimethyl-arginine (ADMA) has been implicated as a possible modulator of inducible NOs during acute inflammation. We examined the evolution in the plasma concentration of ADMA measured at the clinical outset of acute inflammation and after its resolution in a series of 17 patients with acute bacterial infections. RESULTS: During the acute phase of inflammation/infection, patients displayed very high levels of C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin and nitrotyrosine. Simultaneous plasma ADMA concentration was similar to that in healthy subjects while symmetric dimethyl-arginine (SDMA) levels were substantially increased and directly related with creatinine. When infection resolved, ADMA rose from 0.62 +/- 0.23 to 0.80 +/- 0.18 micromol/l (+29%, P = 0.01) while SDMA remained unmodified. ADMA changes were independent on concomitant risk factor changes and inversely related with baseline systolic and diastolic pressure. Changes in the ADMA/SDMA ratio were compatible with the hypothesis that inflammatory cytokines activate ADMA degradation. CONCLUSIONS: Resolution of acute inflammation is characterized by an increase in the plasma concentration of ADMA. The results imply that ADMA suppression may actually serve to stimulate NO synthesis or that in this situation plasma ADMA levels may not reflect the inhibitory potential of this methylarginine at the cellular level.     

侧脑室注射链脲霉素引起大鼠脑Aβ1-40和Aβ1-42表达增加

目的:探讨大鼠侧脑室注射链脲霉素(Streptozotocin,STZ)阻断脑内胰岛素信号传导与Aβ表达的关系.方法:24只SD大鼠随机等分为手术组和对照组(n=12),手术组双侧侧脑室注入STZ 3 mg/kg,第3日重复此剂量,对照组只手术操作但不注射药物.21 d后,采用免疫组化方法观测各组大鼠大脑皮层和海马区的Aβ1-40和Aβ1-42阳性表达.结果:与对照组相比,手术组皮层、海马Aβ1-40和Aβ1-42阳性细胞明显增多.结论:侧脑室注射STZ可以引起脑内Aβ表达增多,提示胰岛素/胰岛素受体系统障碍与阿尔茨海默病(AD)发病有密切关系.     

冠心病患者CRP水平与肾动脉狭窄的关系

【论文特点介绍】本研究观察了CRP是否可以作为肾动脉粥样硬化狭窄（ARAs）的独立危险因子。通过对危险因素进行多变量Logistic回归分析，结果表明年龄、冠脉病变严重程度、外周血管疾病是ARAS的独立危险因素，而CRP水平、高血压、高脂血症、肾功能不全并非ARAS的独立危险因素。     

Astroglial alterations in rat hippocampus during chronic lead exposure.

The present study was performed in order to follow the response of astroglial cells in the rat hippocampus to chronic low-level lead exposure. The experiments combined immunohistochemistry using anti-glial fibrillary acidic protein (GFAP) antibody and conventional transmission electron microscopy (EM). Chronic administration with drinking water [1 g% w/v (subclinical dose) of lead acetate dissolved in distilled water] was started through the mother's milk when pups were 7 days old. Following weaning, experimental offspring were treated for 3 months with the same concentration of adulterated water. The group of intoxicated animals and their controls were sacrificed by perfusion-fixation at 30, 60, and 90 days of exposure. After 60 days of lead treatment, staining of GFAP-positive cells demonstrated an astroglial transformation from the quiescent to the reactive state, characterized by an increase in GFAP. In control rats no changes in GFAP immunostaining were observed. The intensity of the astroglial response was enhanced after 90 days of lead intoxication, showing an increment of GFAP immunoreactivity. Quantification of these changes was made by computerized image analysis, confirming that the sectional areas of the astroglia in lead-exposed animals were larger than those in controls. These results are consistent with the ultrastructural alterations. Simultaneously with the increment in gliofilaments, intranuclear inclusions were seen in some astrocytes. The mechanisms by which lead affects astrocytes are unknown. Probably the astroglial changes induced by lead intoxication produce microenvironmental modifications that may disturb the neuronal function.     

大肠癌患者血清MMP-9与VEGF水平的变化及意义

目的本文检测血管内皮生长因子(VEGF)和基质金属蛋白酶(MMP-9)在大肠癌患者血清中的水平,探讨其与大肠癌恶性程度、浸润、转移的关系。方法用ELISA法对48例大肠癌患者及40例正常对照者血清VEGF和MMP-9进行检测。结果大肠癌患者血清VEGF、MMP-9的水平分别为(665.8±232.8)ng/L;(532.7±208.9)ug/L。显著高于对照组(391.6±135.2)ng/L;(317.8±132.2)ug/L(P<0.01)。并与组织分化程度、Duke’s分期有关。低分化者及C、D期患者较中、高度分化及A、B期高(P<0.01)。结论大肠癌患者血清VEGF和MMP-9水平增高,与肿瘤的组织分化程度、转移、分期有关,提示VEGF、MMP-9对大肠癌恶性程度的判断有一定的价值。