Different costimulation signals used by CD4(+) and CD8(+) cells that independently initiate rejection of allogenic hepatocytes in mice

The current study evaluated the role of CD40/CD40 ligand (CD40L) and CD28/B7 costimulation signals during alloimmune responses independently mediated by CD4(+) or CD8(+) T cells. Allogeneic hepatocytes were transplanted into CD8 or CD4 knock out (KO) mice under cover of costimulatory blockade. Rejection of FVB/N (H-2(q)) hepatocytes occurred by day 10 posttransplant in untreated CD8 or CD4 KO (H-2(b)) mice. Treatment of CD8 or CD4 KO mice with anti-CD40L monoclonal antibody (mAb; MR1) resulted in significant prolongation of hepatocyte survival indicating that CD40/CD40L interactions were critical in both CD4(+) and CD8(+) T-cell initiated hepatocyte rejection. Anti-CD40L mAb also prolonged hepatocyte survival in B-cell KO (H-2(b)) mice, indicating that the efficacy of CD40/CD40L blockade in preventing hepatocyte rejection was B-cell (and antibody) independent. In contrast, treatment with CTLA4 fusion protein (CTLA4Ig), prolonged hepatocyte survival in CD8 KO but not CD4 KO mice, showing that CD28/B7 interactions were important in CD4(+) but not CD8(+) T-cell initiated hepatocyte rejection. Under selected circumstances, such as in CD40 KO mice, both CD4(+) and CD8(+) T cells mediate hepatocyte rejection in the absence of CD40/CD40L costimulation and without a significant contribution from CD28/B7 costimulation signals. These results highlight the disparate roles of CD40/CD40L and CD28/B7 costimulation signals in CD4(+) versus CD8(+) T-cell mediated immune responses to allogeneic hepatocytes. The CD4(+) T-cell independent, CD40L-sensitive, CD28/B7-independent pathway of CD8(+) T-cell activation in response to transplantation antigens is novel.     

炎性相关细胞因子和心肌梗死微循环再灌注状态的关系

目的　观察急性心肌梗死 (AMI)患者梗死相关血管 (IRA)开通前后炎性细胞因子的动态变化及其与心肌组织水平灌注状态的关系。方法　 (1)测定 8例健康人和 2 2例AMI患者急诊冠状动脉介入治疗术 (PCI)前即刻 ,术后 12、2 4h ,血浆白细胞介素 (IL) 1β、肿瘤坏死因子 (TNF)α、IL 10的变化。 (2 )按照再灌注后 2h心电图ST段回落是否 >70 % ,将 2 2例AMI患者分为 :A组 (ST回落≥ 70 % )12例和B组 (ST回落 <70 % ) 10例 ,比较两组患者IL 1β、TNFα、IL 10的变化幅度。 结果　 (1)治疗前A、B两组AMI患者血浆TNFα、IL 10略高于健康对照组 ,但差异无统计学意义 (P >0 0 5 ) ;而IL 1β显著高于健康对照组 (P <0 0 5 ) ;再灌注后 12、2 4hA、B两组血浆IL 1β和TNFα均较术前显著增高 (P <0 0 1,P <0 0 5 ) ,B组血浆IL 10较术前显著增高 (P <0 0 5 ) ,A组则无此变化 (P >0 0 5 )。 (2 )A、B两组间比较 ,治疗前TNFα、IL 1β、IL 10差异均无显著性 (P >0 0 5 ) ;成功PCI、IRA血流达TIMI 3级者 ,B组患者血浆IL 1β、TNFα、IL 10 ,在再灌注 12h显著高于A组 (P <0 0 1,P <0 0 5 ,P <0 0 5 ) ,再灌注 2 4h ,IL 1β、IL 10仍然高于A组 (P <0 0 5 )。 (3)A、B两组患者抗炎因子IL 10的升高幅度均显著低于致炎     

顽固性室性早搏的导管标测与射频消融治疗

采用射频导管消融术对症状明显、药物无效的１０例顽固性室性早搏（简称室早）进行治疗。将消融电极送至右室流出道区域，以Ｓ１Ｓ１或ＲＳ２早搏刺激标测到与体表１２导联心电图记录的自发室早ＱＲＳ波群图形完全相同，并且激动标测时自发室早的局部电图较体表心电图ＱＲＳ波群提前３０ｍｓ以上的部位为消融靶点。以室早在放电后１０ｓ内消失，维持稳定窦性心律３０～６０ｍｉｎ为即刻成功标准。９例患者经１０～２０Ｗ、消融６０～１８０ｓ，早搏和短阵室速完全消失；１例失败。平均随访１１个月，未服任何抗心律失常药物症状消失，复查心电图和动态心电图，９例中８例无早搏、１例为偶发室早，均无并发症。提示射频导管消融术是治疗某些右室流出道早搏的可行方法。     

Mouse model of post-infarct ventricular rupture: time course, strain- and gender-dependency, tensile strength, and histopathology

OBJECTIVE: Recent studies on mice with surgically induced acute myocardial infarction (AMI) have documented the frequent occurrence of ventricular rupture, an event not previously reported in other laboratory species. We have examined the natural history, histopathology and myocardial mechanical strength in mice with AMI. METHODS: AMI was induced by coronary artery occlusion and animals were monitored for fatal events. Gross and histological examinations were undertaken. RESULTS: Rupture occurred in the left ventricular free wall at 2-6 days after AMI. Incidence of rupture in male mice varied among three strains studied (3% for FVB/N, 27% for C57B/6J, and 59% for 129sv, P<0.05) and was lower in female than male mice (23% vs. 59%, P<0.05). Histologically, ruptured hearts had rapid-occurring and severe infarct expansion, multifocal intramural hemorrhage and leucoyte infiltration at the border zone and infarcted zone. In vitro, infarcted left ventricles demonstrated a 50-60% reduction in muscle tensile strength. This reduction preceded the onset of rupture and was related to the time-window of rupture and to infarct size. CONCLUSION: LV wall rupture in the mouse occurs within a narrow time-window after AMI and is strain- and gender-dependent. Infarct expansion, regional hemorrhage with formation of hematoma and leuocyte accumulation are important pathological changes leading to reduced myocardial tensile strength.     

颈动脉支架置入术会取代颈动脉内膜切除术吗?

多年来,颈动脉内膜切除术(CEA)一直被视为重度颈动脉狭窄患者治疗的"金标准",但随着颈动脉支架置入术(CAS)的发展,逐渐使CEA的"金标准"地位受到挑战,甚至有人提出用CAS代替CEA.近年来陆续发表了有关两种治疗方式的对比研究,但对相关研究结果的解读,以及各项研究间的结果却并不一致.文章就这些方面的争议进行了分析.     

支气管镜在儿童呼吸系统疾病应用的安全性研究进展

随着支气管镜技术的不断发展和完善,支气管镜在儿科领域的应用日益广泛.同时,由于儿童自身的特殊性,支气管镜在儿科应用的安全性问题一直都备受关注.与儿童支气管镜诊疗安全性相关的研究及观察也逐渐成为热点.为了降低不良反应和并发症的发生率,术前应仔细评估并进行积极的心理护理.术中应选择适合的麻醉方式、持续给氧、熟练快捷地完成操作并应密切监护患者的生命体征.尤其是对于小年龄组患者更要引起高度重视.为了避免患者发生不必要的医源性感染,还应完善严格执行消毒隔离制度.同时也要保护好医护人员的安全.     

Retransplantation for severe accelerated coronary artery disease in heart transplant recipients

Development of accelerated coronary artery disease (CAD) in the cardiac allograft is one of the major causes of late graft failure in heart transplant recipients. At the Stanford University Medical Center 356 heart transplant procedures were performed in 329 patients by the end of January 1985. Eighty-nine of these patients developed evidence of transplant CAD. Twenty retransplant procedures, including 2 third transplants, were performed in 19 of the 89 patients because of transplant CAD. The graft survival rates after the second transplant were 55%, 25% and 10% after 1, 2 and 5 years, respectively. Nine of these retransplant patients currently survive, the longest for 5.5 years. To examine potential risk factors for development of severe transplant CAD, these 20 retransplant procedures were compared with 113 transplant recipients who had no evidence of transplant CAD on annual coronary arteriograms. An excess of rejection episodes (3 +/- 2 vs 2 +/- 1 episodes/patient, p = 0.02), elevated total cholesterol (266 +/- 78 vs 225 +/- 47 mg/dl, p = 0.002) and higher low-density lipoprotein levels (176 +/- 88 vs 137 +/- 46 mg/dl, p = 0.009) were noted in the transplant CAD retransplant group. Five of 11 retransplant recipients who survived greater than 1 year again developed transplant CAD. Characteristic morphologic features and rapid progression of CAD in the second graft were similar to those in the primary graft.(ABSTRACT TRUNCATED AT 250 WORDS)