冠状动脉不稳定斑块中平滑肌细胞和炎性细胞PCNA阳性及TUNEL阳性细胞分布特点

目的　探讨增殖细胞核抗原 (PCNA)的表达和细胞凋亡在人冠状动脉不稳定斑块中的作用。方法　取人冠状动脉不稳定斑块标本 2 3例 ,采用免疫组织化学技术SP法检测细胞PCNA表达原位末端标记法 (TUNEL)检测细胞凋亡。结果　纤维帽区与肩部炎性细胞PCNA表达显著高于其余二区 ;脂核区平滑肌细胞、炎细胞TUNEL阳性细胞数明显高于其余三个区。纤维帽和肩部中平滑肌细胞和炎细胞PCNA阳性表达大于TUNEL阳性细胞数 (P <0 0 5;P <0 0 1) ;脂核内TUNEL阳性细胞明显大于PCNA阳性表达细胞 (P <0 0 1)。结论　冠状动脉不稳定斑块内细胞凋亡主要发生在斑块脂核周围 ,炎细胞的增殖主要发生在斑块的肩部     

替米沙坦对脑出血急性应激性胃黏膜病变大鼠胃黏膜细胞增殖和凋亡的影响

目的探讨血管紧张素Ⅱ受体拮抗剂替米沙坦对脑出血急性应激性胃黏膜病变大鼠胃黏膜细胞增殖和凋亡的影响。方法健康成年SD大鼠96只,随机分为假手术组、脑出血组、替米沙坦组,每组32只,各组再分为1、2、3和5d4个时间点,每个时间点8只大鼠。制作脑出血大鼠模型,大体观察胃黏膜病变并计算溃疡指数;HE染色光镜下观察胃黏膜组织形态学改变;免疫组织化学法检测胃黏膜增殖细胞核抗原(PCNA)蛋白的表达;TUNEL检测胃黏膜凋亡细胞。结果与假手术组比较,脑出血组大鼠1、2、3和5d胃黏膜溃疡指数明显增大、PCNA表达明显减少、TUNEL凋亡细胞明显增多(P<0.01)。与脑出血组比较,替米沙坦组大鼠1、2、3和5d胃黏膜溃疡指数明显减小、PCNA表达增多、TUNEL凋亡细胞减少(P<0.05)。结论替米沙坦能够减小脑出血急性应激性胃黏膜病变大鼠胃黏膜溃疡指数、增加PCNA表达、减少TUNEL凋亡细胞,减轻应激性胃黏膜病变。     

萎缩性胃炎胃黏膜组织细胞增殖与凋亡的实验研究

目的　研究热盐水灌胃导致的大鼠萎缩性胃炎胃黏膜组织中的凋亡细胞、增殖细胞和bcl 2、Fas表达状态 ,以探讨长期热咸饮食与慢性萎缩性胃炎 (CAG)发生的关系。方法　采用脱氧核糖核酸转移酶介导等缺口末端标记 (TUNEL)技术及免疫组织化学染色技术。细胞凋亡时DNA含量分析采用流式细胞检测技术。结果　 (1 )TUNEL检测细胞凋亡显示 :在热盐水所致的大鼠CAG中凋亡细胞数明显增多 ,在黏膜全层均可见到 ,呈弥漫性分布。CAG中凋亡细胞指数显著高于正常大鼠胃黏膜 (P <0 0 5) ;(2 )免疫组化法检测凋亡相关基因和增殖细胞核抗原 (PCNA)显示 :bcl 2、Fas及PCNA在热盐水灌胃所致的CAG中的表达率显著高于正常胃黏膜 (P <0 0 5) ;热盐水灌胃不同时间大鼠胃黏膜中bcl 2、Fas蛋白表达率随灌胃时间延长而逐渐增加 ,在 4、8、1 2周 (CAG出现 )时bcl 2蛋白表达率分别为 1 2 5 %、1 6 7%、76 5 % ,Fas蛋白表达率分别为 1 8 7%、2 2 2 %、64 7%。 (3)流式细胞检测显示 :CAG时 ,在G0 /G1 峰前可见一个亚G0 /G1 峰 ,也即凋亡细胞峰出现 ,而在正常胃黏膜时未显示亚G0 /G1 峰。结论　热盐水灌胃可导致大鼠胃黏膜组织细胞增殖和细胞凋亡异常 ,其调控基因在热盐水所致的大鼠CAG发生中起重要作用     

不同抗溃疡药物对应激性溃疡发生、发展过程中细胞凋亡的影响

背景：研究不同抗溃疡药物在防治应激性溃疡(SU)时，其对胃黏膜细胞学行为的作用是否有助于SU的防治。目的：观察抗溃疡药物奥美拉陛、米索前列醇和铝碳酸镁对SU的疗效，及其对细胞凋亡和与凋亡相关的细胞因子一氧化氮合酶(NOS)表达的影响。方法：水浸—束缚应激(WRS)结束后2h，计算胃黏膜损伤的溃疡指数(UI)；原位末端标记(TUNEL)法检测胃黏膜细胞凋亡；免疫组化法检测神经型NOS(nNOS)和诱导型NOS(iNOS)表达的变化。结果：奥美拉陛(0)组、米索前列醇(M)组和铝碳酸镁(H)组胃黏膜损伤均较生理盐水组显著减轻(P＜0．01)，胃黏膜细胞凋亡发生率均显著降低(P＜0．01)，但0组和M组的效果优于H组。与生理盐水组比较，3组用药组的nNOS表达均显著增加(P＜0．01)，iNOS表达均显著降低(P＜0．01)，M组和H组的nNOS表达升高较0组更为显著(P＜0．05)。结论：奥美拉唑、米索前列醇和铝碳酸镁作用于SU发生的不同环节，可显著抑制细胞凋亡的发生，对SU均有明显防治作用。寻找对细胞有直接保护作用的药物以提高细胞的抗应激能力可能是防治SU的最终途径。     

肺癌组织与细胞凋亡和增殖的关系

目的　探讨肺癌与细胞凋亡和增殖的关系。方法　对 38例肺癌组织及 2 1例肺部良性组织 ,应用 TUNEL 技术对细胞凋亡情况进行检测 ,应用免疫组织化学法对增殖细胞核抗原(PCNA)等进行检测 ,并对细胞凋亡和 PCNA阳性细胞进行计数 ,分别定义凋亡指数和增殖指数。结果　肺癌组织中凋亡指数 [(3.73± 2 .42 ) % ]和增殖指数 [(13.86± 15 .0 5 ) ]%均高于肺部良性组织 [(0 .77± 0 .5 0 ) %、(0 .91± 3.19) % ],P <0 .0 1。结论　细胞凋亡和 PCNA均可作为肺癌的标志物     

iNOS在乙肝肝硬化组织中的表达及与肝细胞增殖凋亡的关系

采用免疫组化法检测诱导型一氧化氮合酶（iNOS）及增殖细胞核抗原（PCNA））在乙肝肝硬化组织（观察组）和正常肝组织（对照组）中的表达,并与TUNEL染色凋亡细胞进行相关性分析。结果观察组iNOS表达阳性率100%,对照组未见iNOS表达,两组iNOS水平有显著差异（P〈0.05）;PCNA阳性细胞数和凋亡细胞数均与iNOS表达呈正相关,P〈0.01。认为iNOS可能参与了肝硬化的发生、发展,机理为促进细胞增殖。     

下丘脑外侧区注射五肽胃泌素对大鼠胃黏膜细胞应激性损伤的影响

目的研究下丘脑外侧区（LHA）注射五肽胃泌素（G5）对应激性胃黏膜细胞损伤的作用及机制。方法将24只SD大鼠随机分为对照组、水浸—束缚应激（WRS组）、G5＋WRS组、溶剂对照＋WRS组各6只。LHA注射G5，制备大鼠WRS模型；用western-blot法检测胃黏膜细胞凋亡及凋亡相关基因c-Jun氨基末端激酶（JNK）磷酸化水平。结果与WRS组及溶剂对照＋WRS组比较，G5＋WRS组应激后胃黏膜细胞损伤明显增加（P〈0．05或〈0．01），caspase-3蛋白表达及JNK磷酸化水平升高（P均〈0．01）。结论LHA内注射G5可加重大鼠应激性胃黏膜细胞损伤，其机制与增加胃黏膜细胞凋亡有关。     

非小细胞肺癌Bcl-2基因蛋白表达及其与细胞凋亡和增殖的关系

目的探讨非小细胞肺癌Bcl-2蛋白表达与细胞凋亡和增殖的关系。方法采用SAB免疫组化法检测43例非小细胞肺癌及20例癌旁正常肺组织石蜡包埋标本Bcl-2蛋白及增殖细胞核抗原（PCNA）表达;用TUNEL法检测细胞凋亡。结果肺癌组织Bcl-2蛋白的表达显著高于癌旁肺组织,P〈0．05;肺癌组织中凋亡指数和增殖指数均明显高于癌旁正常肺组织,P〈0．01,Bcl-2表达阳性的肺癌组织细胞凋亡指数明显低于Bcl-2表达阴性组,P〈0．05;高细胞凋亡、增殖指数提示肺癌预后不良,P〈0．05。结论肺癌存在Bcl-2表达上调,Bcl-2异常表达在肺癌发生过程中可能起重要作用。     

胃癌细胞凋亡相关基因、PCNA与细胞凋亡的关系

目的探讨细胞凋亡相关基因、增殖细胞核蛋白(PCNA)与胃癌细胞凋亡的相关性。方法采用原位末端标记法及免疫组化技术,检测115例胃癌及癌前病变患者和正常人胃黏膜上皮细胞凋亡指数bcl-2、bax、PCNA的表达。结果正常人、浅表性胃炎、萎缩性胃炎、不典型增生、胃癌的细胞凋亡指数分别为(4.58±1.92)%、(10.14±2.56)%、(24.6±35.19)%、(19.35±4.04)%、(19.81±4.66)%;bcl-2蛋白表达分别为0、18.5%、20.3%、44.6%、58.5%;bax蛋白表达分别为20.4%、51.5%、55.2%、27.6%、16.8%;PCNA分别为(3.93±1.02)%、(13.58±4.65)%、(20.16±4.89)%、(24.30±4.44)%、(39.79±6.37)%、(54.79±10.6)%。结论胃黏膜癌变过程中,起初三个阶段细胞凋亡指数、bcl-2、bax和PCNA同时增加,而至萎缩性胃炎后,细胞凋亡指数、bax表达显著减少,bcl-2、PCNA表达显著增加,说明以上因素在胃癌演变过程中可能起重要作用。     

NiTi放射性支架置入兔腹主动脉后对平滑肌细胞增殖和凋亡的影响

目的　观察NiTi放射性支架对平滑肌细胞增殖和凋亡的影响。方法　在 76只家兔腹主动脉中分别置入放射与非放射性支架。用免疫组化法和TUNEL法观察放射性支架对平滑肌细胞增殖和凋亡的影响。结果　 (1) 2周时放射与非放射性组新生内膜面积无显著差异 (P >0 0 5 ) ,1个月和 3个月时放射支架组新生内膜面积小于非放射性组 (P <0 0 1) ;(2 )PCNA法测定平滑肌细胞增殖显示放射性组在各时间点PCNA表达低于非放射性组 (P <0 0 5 ) ;(3)TUNEL法测定放射性组平滑肌细胞凋亡与对照组相比在 2周和 1个月时有显著差异 (P<0 0 5 ) ,在 3个月时两组平滑肌细胞凋亡无显著差异 (P >0 0 5 )。结论　 (1)放射性支架可减少支架置入术后支架内新生内膜面积。 (2 )放射性支架可抑制血管平滑肌细胞增殖。 (3)放射性支架促进血管平滑肌细胞凋亡     

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.     

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.     

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.     

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。     

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.     

Angiographic diagnosis of the degree of serosal invasion of carcinoma of the colon

Angiography using Prostaglandin El^® was performed on 38 patients with carcinoma of the colon in order to diagnose the degree of serosal cancer invasion. The findings at angiography were classified into four groups:1) AG-S3, abnormal change (irregularity and/or encasement) up to marginal vessels; 2) AG-S2, abnormality up to vasa recta; 3) AG-S1, abnormality of penetrating branches of vasa recta within the wall of the colon; and 4) AG-S0, no distinct findings of abovementioned vessels. These angiographic findings were compared with both macroscopic and microscopic serosal cancer invasion. Angiographic diagnosis is in accord with the macroscopic findings in 84.2 percent of cases. Angiographic diagnosis is in accord with the microscopic findings in 32.4 percent of cases. Macroscopic findings confirm the angiographic diagnosis precisely but the conflict with microscopic findings should not be overlooked. This may be the result of inflammatory change, adhesion, and fibrosis around carcinoma of the colon.     

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.