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141.
Plasmid DNA encoding transforming growth factor-beta1 suppresses chronic disease in a streptococcal cell wall-induced arthritis model. 总被引:6,自引:0,他引:6
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X Y Song M Gu W W Jin D M Klinman S M Wahl 《The Journal of clinical investigation》1998,101(12):2615-2621
Transforming growth factor beta is a potent immunomodulator with both pro- and antiinflammatory activities. Based on its immunosuppressive actions, exogenous TGF-beta has been shown to inhibit autoimmune and chronic inflammatory diseases. To further explore the potential therapeutic role of TGF-beta, we administered a plasmid DNA encoding human TGF-beta1 intramuscularly to rats with streptococcal cell wall-induced arthritis. A single dose of 300 microg plasmid DNA encoding TGF-beta1, but not vector DNA, administered at the peak of the acute phase profoundly suppressed the subsequent evolution of chronic erosive disease typified by disabling joint swelling and deformity (articular index = 8.17+/-0. 17 vs. 1.25+/-0.76, n = 6, day 26, P < 0.01). Moreover, delivery of the TGF-beta1 DNA even as the chronic phase commenced virtually eliminated subsequent inflammation and arthritis. Both radiologic and histopathologic as well as molecular evidence supported the marked inhibitory effect of TGF-beta1 DNA on synovial pathology, with decreases in the inflammatory cell infiltration, pannus formation, cartilage and bone destruction, and the expression of proinflammatory cytokines that characterize this model. Increases in TGF-beta1 protein were detected in the circulation of TGF-beta1 DNA-treated animals, consistent with the observed therapeutic effects being TGF-beta1 dependent. These observations provide the first evidence that gene transfer of plasmid DNA encoding TGF-beta1 provides a mechanism to deliver this potent cytokine that effectively suppresses ongoing inflammatory pathology in arthritis. 相似文献
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Hitoshi Ogino Nongchana Klangsuk Wu Jin Christopher T. Bowles Magdi H. Yacoub 《Artificial organs》1995,19(6):525-534
Abstract: The dependence of transient pressure characteristics of a ventricular assist device (VAD) on the compliance of its housing and cannulas was investigated in a mock circulation. The peak rate of change of pressure ( dP/dt max ) values was greater in the cannulas than other compartments and was associated with valve closure-induced pressure oscillations. When cannula compliance was increased from 0.0057 to 0.0129 cm3 /mm Hg, these values decreased by ˜20%, and outflow cannula pressure oscillation frequency decreased from 17.5 Hz by 35%. This trend was also apparent in the inflow. A VAD housing compliance increase from 0.0162 to 0.0483 cm3 /mm Hg caused a dP/dt max decrease of 30% in both the blood chamber and the outflow cannula. The effect of this change on the inflow was weaker implying that housing absorbs the energy associated with outflow deceleration more effectively than the inflow. These findings suggest that increasing VAD housing and cannulas compliance can improve hydrodynamic performance. 相似文献
145.
This study examined the immunoregulatory role of recombinant interleukin 4 (IL-4), also known as B-cell stimulating factor 1, on the generation of cytotoxic effector cells from normal and leukaemic human blood mononuclear cells. When tested on cells from normal individuals, the addition of IL-4 to mixed lymphocyte cultures led to a dose-dependent proliferation of T-helper cells (CD3, 4 positive) with a concomitant decrease in phenotypic and functional cytotoxic T cells and natural killer (NK) cells. IL-4 also inhibited the interleukin-2 (IL-2)-induced generation of lymphokine-activated killer (LAK) activity when added at the beginning of mixed lymphocyte culture. When tested on mature leukaemic NK cells, IL-4 also inhibited the ability of IL-2 to induce LAK function using a short-term culture system. These results show that IL-4 acts on both normal and leukaemic cells and suggests that it acts at more than one level during the development of LAK function. 相似文献
146.
目的 :探讨联合菌苗防治肿瘤的作用。方法采用动物体内实验 ,动物为封闭群KM小鼠 ,菌株为 2 6 0 0 3- 2 1、4 482 4 - 3及 932 0 1- 3,瘤种为S180 。所有实验小鼠接种S180 后 ,按随机对照试验设计分成 5组 ,即三个不同的单价菌苗组、一个联合菌苗组及一个对照组 ,同期观察联合菌苗对S180 增长的影响。结果 :三个不同的单价菌苗组及联合菌苗组的平均瘤重均比对照组低 ,联合菌苗组的平均瘤重比单价菌苗组的更低 ,差异均有高度统计学意义 (P <0 .0 1~ 0 .0 0 1) ;三个不同单价菌苗组的抑瘤率分别为 5 0 .6 %、4 8.3%、4 5 .5 % ,联合菌苗组抑瘤率为 75 .0 %。结论 :实验所选用的菌苗能抑制S180 的增长 ,联合菌苗的效果更好 相似文献
147.
Hyung Jee Kim Gilho Lee Dong Hee Kim Suk Jae Lee Duck Ki Yoon Jae Heung Cho 《Urologia internationalis》2002,68(1):44-48
INTRODUCTION: The purpose of this study is to investigate in vitro the effects of serotonin on the rat detrusor. In particular, it examines which drugs inhibit the serotonin-induced detrusor contractions. MATERIALS AND METHODS: Isometric tension changes of isolated rat bladder muscle strips were recorded in an organ bath using a force transducer. Acute effects of serotonin (0.0001-0.01 mM) on resting tension were assessed. Electrical field stimulation (EFS); bethanechol (0.0001-0.01 mM); ATP (1-3 mM)- or KCl (63.5-254 mM)-induced contractions using an application in an organ bath were compared with serotonin-induced contractions. In order to examine the action mechanism of serotonin-induced stimulation, EFS-, bethanechol-, ATP- or KCl-induced contraction on serotonin treatment (0.001 mM) was assessed and serotonin (0.001-0.1 mM) was cumulatively added to the organ bath following preincubation with propranolol, ketanserin, tropisetron, propiverine, sodium nitroprusside or doxazosin. RESULTS: The serotonin-induced response has two phases: an initial transient contraction and a prolonged tonic phase. Serotonin produced a reversible and dose-dependent contraction of the detrusor strips. Responses to bethanechol significantly increased with a concentration of 0.001 mM serotonin (p < 0.05). There was no effect on the responses to ATP, KCl, or EFS on 0.001 mM serotonin. The 5-HT(2) receptor is mainly responsible for serotonin-induced contractions of the detrusor (p < 0.05), while the 5-HT(1) receptor is partially responsible. Doxazosin and propiverine each significantly suppressed the response to serotonin, while sodium nitroprusside and tropisetron each had no effect (p < 0.05). CONCLUSIONS: Because the 5-HT(2) antagonist blocked the effect of serotonin-induced bladder contractions and the stimulation of the adrenoreceptors, the 5-HT(2) antagonist seems to improve lower urinary tract symptoms. 相似文献
148.
Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT1 ) receptors in rabbit aorta and human recombinant AT1 receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'2 = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [125 I]AII binding to rabbit aortic membranes (AT, receptors) and [125 I][Sar1 , Ile8 ]AII binding to human recombinant AT1 receptors in a concentration-dependent manner with IC50 values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [125 I)AII binding to bovine cerebellum membranes (ÀT2 receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT1 receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT1 selective angiotensin receptor antagonist which exerts a competitive antagonism in the [125 I]AII binding assay and insurmountable AT1 receptor antagonism in the functional study. 相似文献
149.
腺病毒介导的HSV—tk基因治疗大鼠脑胶质瘤实验研究 总被引:4,自引:0,他引:4
目的:带有HSV-tk基因的重组腺病毒(AdHCMV-tk)结合核苷类似物(NA)治疗大鼠C6脑胶质瘤。方法:用X-gal染色测定AdHCMV-lacZ转染大鼠C6胶质瘤细胞的效率。用AdHCMV-tk/ACV、GCV离体及活体治疗大鼠C6胶质瘤。结果:AdHCMV-lacZ感染C6细胞效率达100%,AdHCMV-tk感染C6细胞,在病毒感染复数为1000时,GCV和ACV半致死剂量分别为3μg/ml和20μg/ml,Ad-HCMV-tk/ACV治疗大鼠C6胶质瘤模型,大鼠生存期超过90天,而对照组分别为17.0±1.6天(生理盐水组)、14.5±1.3天(AdHCMV-lacZ组),P<0.001。结论:重组腺病毒对靶细胞感染效率可达100%,AdHCMV-tk用GCV的杀伤C6胶质瘤细胞比ACV强,而HSV-tk/ACV用腺病毒介导治疗大鼠脑肿瘤疗效显著。 相似文献
150.
Factors affecting fusion rate in adult spondylolisthesis 总被引:8,自引:0,他引:8
The authors examined factors affecting fusion rate in the surgical treatment of 89 consecutive adult patients with spondylolisthesis. Two factors significantly improved fusion rate: combined anterior and posterior fusion and rigid postoperative immobilization in the cast. In 65 patients with isthmic spondylolisthesis, the fusion rate was raised from 70% when posterior fusion alone was used to 88% when combined anterior and posterior fusion was used. In 20 patients with degenerative spondylolisthesis, frequent use of combined anterior and posterior fusion contributed to a high overall fusion rate of 95%. Among patients with isthmic spondylolisthesis, postoperative cast immobilization resulted in a higher fusion rate of 90% compared with a fusion rate of 63% obtained after brace immobilization. 相似文献