严重急性呼吸综合征患者尸解肺标本的病理改变和致病机制研究

目的研究严重急性呼吸综合征（SARS）患者尸解肺标本的病理改变和致病机制。方法观察了2003年4-7月期间死于SARS的6例患者的肺标本,并采用光镜、电镜、Masson三色染色和免疫组织化学染色方法（EnVision法）进行研究。结果肺标本的病理形态改变：（1）6例的双肺均可见到弥漫性实变病灶,肺重量明显增加;（2）6例均可见到弥漫性肺泡损伤,包括透明膜形成、肺泡腔内水肿／出血、纤维素沉积和肺泡上皮细胞脱屑,AE1／AE3免疫组织化学染色显示肺泡上皮细胞的完整性明显破坏;（3）Ⅱ型肺泡上皮细胞轻度增生,有一定异型性,细胞体积增大,胞质呈双染性和颗粒状,胞质内可见小脂肪空泡聚集（5／6）;（4）6例中有5例可见巨细胞在肺泡内浸润,巨细胞大多AEl／AE3阳性（5／6）,少数CD68阳性（2／6）;（5）组织学形态和免疫组织化学染色证实肺泡腔内和肺泡间隔内有多量巨噬细胞浸润（6／6）;（6）6例中有5例可见巨噬细胞噬红细胞象;（7）6例中有5例可见肺纤维化,包括肺泡间隔和肺间质增宽（5／6）、肺泡腔内渗出物机化（6／6）和胸膜增厚（4／6）。Masson三色染色证实胶原纤维明显增生,免疫组织化学染色显示大多数为Ⅲ型胶原。光镜和免疫组织化学染色显示5例有明显的成纤维细胞／肌纤维母细胞增生灶;（8）5例可见支气管黏膜鳞状上皮化生;（9）6例患者均可见血栓;（10）2例同时合并其他感染,1例合并细菌感染,另1例合并真菌感染。此外,电镜发现在肺泡上皮细胞和肺血管内皮细胞的胞质内有冠状病毒样颗粒。结论SARS冠状病毒直接损伤肺泡上皮细胞、巨噬细胞明显浸润和成纤维细胞／肌纤维母细胞显著增生在SARS的致病机制中起重要作用。     

荧光定量PCR检测活检组织EB病毒感染的临床意义

目的　建立检测EBV感染的新方法并观察EBV与鼻咽癌的关系。方法　鼻咽部活检组织和石蜡包埋标本6 6例 ,采用荧光定量聚合酶链反应 (FQ -PCR)和原位杂交 (ISH)两种方法检测EBV ,其检测结果与病理诊断对照。结果 :FQ-PCR检测EBV -DNA阴性 5 2例 ,其中 5 1例为炎性病变 ,另 1例为腺癌 ;EBV -DNA阳性 14例 ,其中 13例为鳞状细胞癌 ,另 1例虽为炎症。但部分上皮细胞呈不典型增生。ISH检测EBV阳性 4 9例 ,其中 4 7例为炎性病变 2例为癌。EBV阳性 17例 ,其中 12例为癌 ,5例为炎性病变。FQ -PCR和ISH检测EBV结果 ,经卡方检测差异无显著性 (P >0 .0 5 )。结论　EBV感染与鼻咽癌有高度相关性。FQ -PCR检测EBV具有方法简单、快速、定量准确等优点。     

Systemic administration of rIL-12 induces complete tumor regression and protective immunity: response is correlated with a striking reversal of suppressed IFN-{gamma} production by anti-tumor T cells

Unfractionated spleen cells taken from tumor-bearing mice 2weeks after tumor implantation contained tumor-primed T cellswhich produced cytokines including IL-2 and IFN- when culturedin vitro. With progressive tumor growth this initial lymphokine-producingcapacity decreased. Here, we investigated the ability of IL-12to (I) restore suppressed IFN- production, (II) cause tumorregression and (II) induce anti-tumor protective immunity. Additionof rIL-12 to spleen cell cultures from 4- to 10-week-old tumor-bearingmice resulted in a striking enhancement in the production ofIFN- compared with cultures of these cells in the absence ofrIL-12 or of normal spleen cells in the presence of rIL-12.Five I.p. injections of rIL-12 into mice bearing s.c. tumorsinduced complete tumor regression. This was found when rIL-12was given at early (1–2 weeks), intermediate (4–5weeks) or even late (7 weeks) stages of tumor growth. Furthermore,IL-12-treated mice which rejected the primary tumor exhibitedcomplete resistance to a rechallenge with the same tumor butdid not reject a second syngenetic tumor. Immunohistochemicalanalyses following IL-12 treatment revealed that CD4⁺ and CD8⁺T cells infiltrate the tumor. More importantly, IFN- mRNA expressionwas observed in fresh tumor masses from tumor-bearing mice receivingIL-12 treatment The importance of IFN- was further demonstratedby the observation that the systemic administration of anti-IFN-mAb prior to IL-12 treatment completely abrogated the anti-tumoreffect of IL-12. Thus, these results indicate that administrationof modest levels of rIL-12 to tumor-bearing mice results intumor regression through mechanisms involving reversal of suppressedIFN- production by anti-tumor T cells and the establishmentof a tumor-specific protective immune response.     

Carboxymethyl-histaminocarbonylmethylamylose as a mimetic system of chymotrypsin in the catalytic hydrolysis of esters

A new type of polysaccharide host, carboxymethyl-histaminocarbonylmethylamylose ( 2b ), containing carboxylic, imidazolyl and hydroxyl groups in the backbone, was used as a mimetic system for chymotrypsin in the catalytic hydrolysis of 3-acetoxy-N-dodecylpyridinium iodide ( 1 ). The substrate is located in the hydrophobic cavity of the amylose helix. The apparent saturation, the entropy-favored kinetics and the pronounced catalytic efficiency (9 times higher than that of a system consisting of the same concentration of carboxymethylamylose and histamine) show that 2b is a good enzyme model in which the definite binding site, active center and self-organization characteristics are present. Most distinctly, the pH-rate constant profile of the hydrolysis of 1 and 2b is of bell-type and has an optimum at pH 7,98, which is very close to 7,90 for chymotrypsin. In conclusion, the charge relay mechanism is also involved in the catalytic effect of 2b .     

认知疗法治疗强迫症的对照研究

目的　探讨认知疗法治疗强迫症的疗效。方法　对 6 0例符合 CCMD-2 -R诊断标准 ,且 Y-BOCS量表评分≥ 1 6分的强迫症病人 ,随机分到认知治疗组 ( 30例 )和氯丙咪嗪组 ( 30例 ) ,两组在氯丙咪嗪常规治疗的同时 ,其中一组加用认知治疗 ,共治疗 8周。在治疗前、后两组均进行临床疗效评估和 Y-BOCS量表评分。结果　认知治疗组痊愈 1 1例、显效 1 6例、有效 3例。氯丙咪嗪组痊愈 6例、显效 1 4例、有效 1 0例。两组痊愈和显效比较有显著差异 ( P<0 .0 5 )。 Y-BOCS量表减分率 :认知治疗组 5 4 .90 % ,氯丙咪嗪组 4 2 .33% ,两组比较有显著差异 ( P<0 .0 5 )。结论　认知疗法配合药物治疗强迫症比单用氯丙咪嗪治疗强迫症疗效更好     

肾脏微血管内的压力分布与ANP的作用

本实验在40只大鼠经伺服零测压技术测定的肾脏微血管内压力分布及其ANP的作用均随血管树各段的口径变化而改变。分析小球前各段血管的压力降所占动脉总压降的比例得知:小叶间动脉占总压降的88％。肾小球毛细血管和出球小动脉亦具有较大的压力降。正常对照情况下,肾小球前血管内的压力分布与内径呈直线相关(r=0.869,n=65,P<0.01),其回归方程为平均压()=34.71±0.798×血管内径(D)。给ANP后肾小球前血管内的压力与内径仍呈直线相关(r=0.931,P<0.01),回归方程式为()=38.53+0.765D,其曲线右上移。本文结果提示,肾小球前微血管内压力分布与血管内径密切相关。小叶间动脉的阻力较大。     

升压治疗急性脑缺血再灌注损伤保护作用的实验研究

目的:探讨升压治疗局灶性脑缺血的保护作用及治疗的维持时间。方法:采用大鼠局灶性脑缺血再灌注模型,40只大鼠随机分为五组:模型对照组(A)、升压维持15min组(B)、维持45min组(C)、维持90min组(D)和120min组(E),观察各组神经功能评分、脑梗死体积和病理学改变。结果:神经功能缺损评分B、C、D组明显低于A组;B、C、D、E各组脑梗死体积明显低于A组,C、D、E组明显低于B组;各治疗组组织病理学改变比对照组轻,B组最轻。结论:缺血3h再灌注时,升压维持时间在2h以内对脑损伤有保护作用,升压最佳维持时间是15min。     

LHRH药代动力学试验

目的:研究黄体激素释放激素(Luteinizinghormone releasinghormone,LHRH)在大鼠体内的药动学规律。方法:用氯胺T法将125I标记到LHRH分子上(放化纯度96.2%),14只SD大鼠随机分为大剂量、小剂量组,每组7只,分别肌肉注射125I LHRH(小剂量组0.5mg.kg,大剂量组1.00mg.kg),给药后在21个不同时间点逐一取各鼠尾动脉血做放射性测定。结果:大鼠试验结果显示,大剂量组t1/2平均为67.83±20.84h;小剂量组半衰期平均为64.68±22.90h。LHRH的药—时曲线符合二室模型,大剂量LHRH和小剂量LHRH的主要药动学指标差别不大。结论:LHRH在大鼠体内的消除模式为二室模型,为一级动力学消除。