风湿性心脏炎HLA—DR分子表达量的改变

目的　了解风湿性心脏炎 (rheumaticcarditis,RC)外周血淋巴细胞表面HLA DR分子的表达量 ,以探讨HLA DR分子在外周血淋巴细胞表面的表达量在RC发病机制中的意义 ,为RC的诊断和防治提供新的途径。方法　选取门诊及住院确诊风湿性心脏炎者 33例 ,单纯风湿性关节炎 2 1例 ,风心病静止期组 36例 ,链球菌感染后状态组 16例 ,正常对照组 43例。分别予A组 β型溶血性链球菌 (GAS)膜抗原及GM CSF刺激其淋巴细胞 ,另设空白对照 ,参照RandallEllisMorris的cell ELISA方法 ,检测淋巴细胞表面HLA DR的表达情况 ,以OD/cell为单位表示。HLA DR表达量以均数±标数差表示 ,用方差分析其差异 ,P <0 0 5为统计学显著标准。结果　①心脏炎组HLA DR分子表达量明显高于其他各组 (P <0 0 5 ) ,而关节炎组较非活动期组亦有明显增高 (P<0 0 5 )。②加入膜抗原及GM CSF后各样本的HLA DR的表达量均有增加。加入膜抗原刺激者 ,心脏炎组的增加量较其他各组明显大 ,而关节炎组和风心病静止期组增加量与正常对照组及链球菌感染后状态组相比亦有显著差别 (P <0 0 5 )。结论　①对HLA DR分子表达量的检测有助于对风湿热不同型别及不同病期的诊断和监测风湿性心脏炎的活动情况。②膜抗原与HLA DR分子对风湿性心脏炎发病及发展起了重要     

系统性红斑狼疮骨髓T细胞活化及其与病情活动的相关性分析

目的 探讨系统性红斑狼疮（SLE）患者骨髓T淋巴细胞的活化状态及多种活化的T细胞亚群与疾病活动指标之间的相关性。方法 SLE患者11例（其中活动期6例，非活动期5例）和健康对照8名。应用流式细胞术比较活动期和非活动期SLE患者骨髓T细胞CD25、人类白细胞抗原（HLA）-DR的表达。用直线相关分析活化T细胞亚群与SLE疾病活动性评分（SLEDAI）、尿蛋白定量（24h）、血清补体C3、C4的相关性。结果 活动期SLE、非活动期SLE与正常对照相比骨髓T细胞CD25、HLA—DR的表达，差异均无统计学意义（P〉0．05）。活动期SLE骨髓T细胞HIJA—DR^＋、CD4^＋HLA—DR^＋、CD8^＋HLA—DR^＋的表达均明显高于正常对照外周血（P〈0．05）。11例SLE患者骨髓CD3^＋HLA—DR^＋、CD4^＋HLA—DR^＋细胞与C3之间均呈显著负相关（r=-0．682，r=-0．675，P均〈0．05）；CD3^＋HLA—DR^＋、CD8^＋-HLA—DR^＋细胞与尿蛋白定量（24h）之间均呈显著正相关（r=-0．712，r=-0．688，P均〈0．05）。活动期SLE骨髓CD3^＋HLA—DR^＋、CD8^＋HLA—DR^＋细胞与C3之间均呈显著负相关（r=-0．943，r=-0．829，P均〈0．05）。结论 活动期SLE患者骨髓T细胞活化明显高于正常对照外周血，且骨髓中活化的T细胞与疾病活动指标相关。     

甲氨蝶呤及环磷酰胺联合用药对类风湿关节炎患者外周血淋巴细胞凋亡的影响

目的 探讨甲氨蝶呤（MTX）和环磷酰胺（CTX）及两者联合治疗对类风湿关节炎（RA）患者外周血淋巴细胞凋亡的影响。方法 入选活动期RA患者30例，随机分为3组（单用MTX组、单用CTX组及联合用药组），Annexin V-FITC及碘化丙锭（PI）双标记RA患者外周血淋巴细胞，应用流式细胞术检测MTX、CTX及联合组治疗前后外周血淋巴细胞凋亡的变化；同时以10例健康志愿者外周血淋巴细胞凋亡情况为正常对照。结果 活动期RA患者外周血淋巴细胞早期凋亡率与正常人比较差异无统计学意义（P〉0．05）。单用MTX及单用CTX组患者用药后较用药前外周血淋巴细胞早期凋亡率均明显增加，差异均有统计学意义（P〈0．05）；联合用药后外周血淋巴细胞早期凋亡率较单用MTX、CTX组明显增加，差异有统计学意义（P〈0．05）。RA患者基线外周血淋巴细胞早期凋亡率与疾病活动指数（DAS）28、血沉（ESR）、C反应蛋白（CRP）疾病活动指标间无相关性。结论 MTX联合CTX治疗能更加有效地诱导RA患者外周血淋巴细胞凋亡。     

HLA-DR4等位基因与类风湿关节炎疗效的关系

目的：探讨对类风湿关节炎（RA）联合使用改善病情抗风湿药（DMARDs）的疗效与易感HLA－DR4基因携带的关系。方法 测定RA患者HLA－DR4携带频率,并作病程、关节功能及红细胞沉降率（ESR）、C反应蛋白（CRP）、类风湿因子（RF）比较分析后,分别于阳性者及阴性者联用甲氨蝶呤（MTX）、柳氮磺吡啶（SASP）及氯奎（CQ）等DMARDs,并观察疗效。结果 HLA－DR4携带使患者ESR、CRP及RF值升高,使RA病情复杂化,给联合治疗带来困难,表现在控制症状及生化指标恢复正常值的时间上,HLA－DR4阳性组比HLA－DR4阴性组显著延迟;在RF值恢复正常方面,HLA－DR4阳性组比HLA－DR4阴性组病例显著减少,上述两方面与RA预后密切相关。在药物的副作用方面,两组差异无显著性。结论 HLA－DR4可作为判断RA治疗的重要预后指标。     

葡萄糖-6-磷酸异构酶mRNA在RA患者外周血单个核细胞中的表达及意义

目的探讨葡萄糖-6-磷酸异构酶（glucose-6-phosphate isomerase，GPI）mRNA在类风湿关节炎（RA）患者外周血单个核细胞（PBMCs）中的表达及其与RA疾病活动性的关系。方法对30例RA活动期患者、30例RA缓解期患者、30例其他风湿性疾病患者及30名健康体检者，采用反转录聚合酶链反应（RT—PCR）半定量检测PBMCs中GPImRNA的表达水平。结果RA活动期患者GPImRNA的表达水平明显高于RA缓解期患者、其他风湿性疾病患者及正常对照组（P〈0．05），在RA活动组和RA缓解组，差异亦有统计学意义（P〈0．05）。结论GPImRNA在部分RA患者中高表达，其可能在RA发病机制中起作用，并与疾病的活动性相关。     

外周血单个核淋巴细胞表面IL-21受体表达与类风湿关节炎的相关性

目的探讨外周血单个核淋巴细胞表面IL-21受体（IL-21R）在类风湿关节炎（RA）发生过程中的作用。方法收集32例RA患者（观察组）和22例健康成人（对照组）外周血标本,分离外周血单个核淋巴细胞,采用流式细胞仪检测CD4^＋、CD8^＋细胞、B细胞和NK细胞表面IL-21R的表达。结果观察组IL-21R表达水平明显高于对照组（P〈0．05）。药物治疗症状控制后,IL-21R表达水平明显下降（P〈0.05）。结论RA患者外周血单个核淋巴细胞表达IL-21R水平明显升高,提示IL-21R在RA的病情进展中起重要作用,其机制可能为诱导关节滑膜炎症病变、参与关节滑膜组织及全身的免疫病理损伤。     

类风湿关节炎患者外周血高迁移率族蛋白1表达

目的通过检测类风湿关节炎（RA）患者外周血单个核细胞（PBMC）、血浆中高迁移率族蛋白1（HMGB1）表达,为寻找治疗RA的新靶点提供依据。方法采集38例活动期RA患者、24例相对稳定期RA患者和20例健康对照者外周血。RT．PCR检测PBMC HMGB1mRNA表达,Western blot检测PBMC、血浆HMGB1蛋白表达。结果与相对稳定期RA患者、健康对照者相比,活动期RA患者PBMC HMGB1mRNA表达水平差异无统计学意义（F=1．23,P〉0．05）,而HMGB1蛋白表达水平下降（F=70．91,P〈0．01）,血浆HMGB1水平显著增高（P〈0．001）。相对稳定期RA患者与健康对照者之间差异无统计学意义（P〉0．05）。活动期RA患者血浆HMGB1水平与ESR（r．=0．478。P〈0．001）、C-反应蛋白（rs=0．574,P〈0．05）呈正相关。结论HMGB1与RA发病密切相关,并可能成为新的治疗靶点。     

抗聚角蛋白微丝蛋白抗体的检测在类风湿关节炎诊断中的意义

目的：探讨抗聚角蛋白微丝蛋白抗体（AFA）对RA诊断的意义，并比较其与抗核周因子抗体（APF），抗角蛋白抗体（AKA）以及HLA－DR4之间的相关性。方法；用免疫印迹法（WB）检测157例类风湿关节炎（RA）血清标本和104例对照血清，包括系统性红斑 狼疮（SLE)、干燥综合征（SS）、骨关节炎（OA）等的AFA。APF和AKA用间接免疫荧光法检测。结果：157例RA病人的AFA敏感性和特异性分别为36．3％、 93．4％，与疾病对照组和正常对照组相比，差异有显著性（P＜0．05）。57例AFA阳性的血清中，其中AKA同时阳性的有36例,重叠为63．2％；APF同时阳性的有38例，重叠率为66．7％；HLA－DR4同时阳性的有36例，重叠率为52．6％。统计学分析证实AFA与AKA、APF及HLA－DR4之间有相关性。结论：AFA对RA具有很高的特异性，可用于RA的临床诊断。AFA与APF、AKA及GLA－DR4有相关性。AFA不能完全替代APF和AKA，三项临床检测可互相补充,提高RA的诊断率。     

系统性红斑狼疮患者外周血单个核细胞c-kit受体表达的研究

目的：探讨系统性红斑狼疮（SLE）患者外周血单个核细胞（PBMC）中c-kit受体的表达及其临床意义。方法：采用免疫荧光标记，流式细胞仪检测SLE患者PBMC的c-kit受体蛋白（CD117）表达，反转录－聚合酶链式反应（RT－PCR）检测其c-kit mRNA的表达水平，并分别与正常人比较。结果：SLE患者PBMC中c-kit受体及其mRNA表达水平与正常组相比显著增高（P＜0．05）；活动期与非活动期相比显著增高（P＜0．05），非活动期SLE患者PBMC的c-kit受体蛋白表达与正常人差异无显著性（P＞0．05），PBMC的c-kit受体蛋白表达与其SLEDAI显著相关（P＜0．01），结论：SLE患者PBMC c-kit受体蛋白水平及其mRNA表达水平均显著高于正常人，且与疾病活动呈正相关，c-kit受体可能在SLE的病程变化中起着重要作用。     

系统性红斑狼疮患者T细胞上Fas受体分子数与治疗效果的相关性

目的 通过定量流式细胞术检测系统性红斑狼疮（SLE）患者T淋巴细胞表面Fas受体的分子数（Fas/T），探讨其对疾病治疗效果的指导作用。方法 36例活动期SLE患者，分别给予泼尼松、甲泼尼龙、环磷酰胺冲击治疗，在入院3d内、出院时（平均住院天数为22．6d）和出院后4周复诊时，采集患者外周血，采用Fas定量流式细胞试剂盒荧光染色，通过流式细胞仪对T淋巴细胞上表达Fas受体分子数（Fas/T）进行检测。结果 活动期SLE患者随着皮质类固醇或免疫抑制剂治疗，到出院时T细胞表面Fas/T呈明显升高；出院后4剧复诊时T细胞表面Fas/T呈下降趋势；各组间差异均有统计学意义（P〈0．05）。SLE患者治疗前后T细胞表面Fas/T与SLE疾病活动指数（SLEDAl）之间，具有明显的相关性（P〈0．05），治疗前后T细胞表面Fas/T与抗dsDNA抗体、C3和C4之间无明显的相关性（P〉0．05）。结论 SLE患者T淋巴细胞表面Fas／T与SLE的活动性呈正相关，可作为一种评价SLE疾病活动性的指标，对临床治疗效果具有一定指导作用。由Fas介导的淋巴细胞凋亡是引起SLE免疫功能紊乱的主要原因，也是判断狼疮活动的重要指标。     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.     

Study of constancy of hydrogen-consuming flora of human colon

The constancy of the hydrogen consuming flora of the human colon was studied in 15 healthy subjects via two measurements obtained 18 to 36 months apart. Hydrogen disappearance rate and the major products of H₂-consuming bacteria, methane and sulfide, were measured during incubation of fecal homogenates with excess hydrogen and sulfate. In 11/15, the hydrogen consumption rate and the predominant hydrogen-consuming pathway (methanogenesis, sulfate reduction, or neither) remained constant. However, major shifts in these pathways were observed in four subjects, with two losing and two gaining the ability to produce methane. Methanogenesis was associated with the highest hydrogen consumption rate. This study demonstrates that clinically unrecognizable, major alterations of the colonic flora occur in healthy subjects. Understanding of the factors responsible for these alterations might allow for therapeutic manipulation of the colonic flora.Supported in part by the Department of Veterans Affairs and NIDDKD RO1 DK 13309-25.