老年缺血性脑卒中患者白细胞介素1受体拮抗剂基因多态性研究

目的探讨白细胞介素1受体拮抗剂基因内含子2的变数串联重复(VNTR)多态性与老年缺血性脑卒中的关系。方法选择老年缺血性脑卒中患者112例作为脑卒中组,选择同期年龄和性别相匹配的健康志愿者或其他疾病住院的患者105例作为对照组,通过PCR和琼脂糖凝胶电泳来确定其基因型。结果脑卒中组患者A2等位基因频率低于对照组(4.9% vs 10.5%,χ~2=4.78,P=0.029),A1A2+A2A2基因型的频率也较对照组低(9.8% vs20.0%,χ~2=4.47.P=0.035)。结论白细胞介素1受体拮抗剂内含子2基因VNTR多态性与老年缺血性脑卒中有关,其A2等位基因对脑卒中可能有保护作用。     

白细胞介素-1α基因启动子-889C/T和白细胞1受体拮抗剂第2内含子VNTR基因多态性与脑梗死关系的研究

目的研究白细胞介素1α(IL1α)基因启动子889C/T多态性和白细胞介素1受体拮抗剂(IL1Ra)第2内含子可变数目串联重复(VNTR)多态性及血清水平与脑梗死的关系。方法采用聚合酶链反应限制性片段长度多态性(PCRRFLP)技术,检测155例脑梗死患者和170例健康对照者的IL1α(889C/T)和IL1Ra(VNTR)基因型,同时采用酶联免疫吸附试验(ELISA)检测脑梗死患者和对照者的血清IL1水平。结果脑梗死组血清IL1水平显著高于对照组(P<001),IL1α基因889C/T基因型频率和等位基因频率在脑梗死组和对照组比较差异有显著性(P<005),等位基因频率的相对风险分析发现,T等位基因携带者患脑梗死的风险是C等位基因的2029倍(OR=2029,95%CI1207~3410);IL1Ra基因型频率和等位基因频率在脑梗死组和对照组比较差异有显著性(P<005),与健康对照组比较,不携带IL1RaⅡ的基因型患脑梗死的相对风险度增加1853倍(OR=1853,95%CI1010~3398),携带IL1RaⅡ的基因型的脑梗死患者血清IL1Ra水平显著高于不携带者〔(142532±32392)pg/ml,(129634±29236)pg/ml,P<001〕。结论IL1α(889C/T)和IL1Ra(VNTR)基因多态性与脑梗死的发病具有相关性,其中T等位基因可能是脑梗死发病的遗传易感基因;携带IL1RaⅡ基因的个体可能通过促进IL1Ra的高度表达而对脑梗死具有保护作用     

冠心病患者白细胞介素-1受体拮抗剂基因多态性的研究

目的　探讨白细胞介素 1受体拮抗剂基因 (IL 1RN)内含子 2可变数串联重复多态性(VNTR)和外显子 2 ( + 80 0 6T/C)多态性与冠心病 (CHD)的相关关系 ,以及各基因型对CHD患者血清白细胞介素 1受体拮抗剂 (IL 1Ra)水平的影响。方法　采用聚合酶链反应 (PCR)和PCR RFLP的方法 ,分析 2 4 5例CHD患者和 2 36例健康对照者的IL 1RN(VNTR)和IL 1RN( + 80 0 6T/C)基因型 ,并从CHD患者中随机选择 5 5例 (携带IL 1RN Ⅱ或IL 1RN C者 2 5例 ,不携带者 30例 ) ,利用酶联免疫吸附实验检测其血清IL 1Ra水平。结果　与健康对照组相比 ,不携带IL 1RN Ⅱ或IL 1RN C基因型者患CHD的相对风险度增加 1 91倍 (OR =1 91,95 %CI =1 12～ 3 2 4 ) ;而与心绞痛组相比 ,其患心肌梗死的相对风险度增加 4 15倍 (OR =4 15 ,95 %CI=1 5 0～ 11 4 5 )。携带IL 1RN Ⅱ或IL 1RN C基因型的CHD患者血清IL 1Ra水平显著高于不携带者 (P <0 0 1)。IL 1RN Ⅱ总是伴随着IL 1RN C的出现而出现。结论　IL 1RN(VNTR)和IL 1RN( + 80 0 6T/C)多态间存在完全连锁不平衡 ;其基因型与CHD的发生、发展及该疾病的严重程度密切相关 ;IL 1RN C和IL 1RN Ⅱ可能共同通过促进IL 1Ra的表达而具有保护作用     

溃疡性结肠炎的白细胞介素(IL)-1β、IL-1受体拮抗剂、IL-4基因多态性

目的研究溃疡性结肠炎(UC)病人的白细胞介素(IL)-1β、IL-1受体拮抗剂(IL-1RA)、IL-4基因多态性,并分析其与抗中性粒细胞胞质抗体(ANCA)及临床分型的关系.方法用PCR-限制性片段长度多态性方法和序列特异性引物-PCR方法分别对81例UC病人和114例健康者进行IL-1β和IL-1RA、IL-4基因多态性分析.结果 UC组IL-4 的RP2基因频率明显高于对照组(29.0% 对11.8%,P=0.000 02),而对照组RP1基因频率明显高于UC组(88.2% 对71.0%,P=0.000 02),UC组RP1.2、RP2.2基因型的优势比值分别为2.71 (95%CI, 1.39～5.31),9.04 (95%CI, 1.05～203.29);2组IL-1β、IL-1RA各基因频率比较差异均无显著性 (P＞0.05);ANCA(+)组和ANCA(-)组UC病人IL-4的 RP1、RP2基因频率显著不同,差异有显著性 (P值均<0.05).结论中国汉族UC病人与IL-4内含子3的基因多态性相关联,UC病人IL-4 RP1基因频率明显降低,而RP2基因频率明显增加,与正常人的差异发生在 ANCA(+) UC病人;中国汉族UC病人与IL-1β、IL-1RA基因多态性无关联.     

白细胞介素1受体拮抗剂在动脉粥样硬化中的作用

动脉粥样硬化是一个复杂的过程,炎症反应贯穿其发生、发展的全过程。白细胞介素1受体拮抗剂作为内源性白细胞介素1的拮抗剂,在动脉粥样硬化形成和发展过程中起着非常重要的作用,可抑制动脉粥样硬化的发展。应用人重组白细胞介素1受体拮抗剂进行治疗可阻止动脉粥样硬化的进展,提高对冠心病的治疗效果。而对白细胞介素1受体拮抗剂基因的分析有望在早期即可筛查出易感人群,从而达到早期预防、早期治疗的目的。     

白细胞介素—1受体拮抗剂基因多态性在正常人群中的…

目的：了解白细胞介素－１受体拮抗剂（ＩＬ－１ｒａ）基因多态性在中国正常人群中的分布及其与不同种族比较的特点。 方法：用ＰＣＲ方法对９８名正常人群ＩＬ－１ｒａ基因ＶＮＴＲ多态性进行了观察，并结合文献进行了不同种族间的分析比较。 结果：中国正常人群以ＩＬ１ＲＮ＾＊１等位基因发生频率最高，ＩＬ１ＲＮ＾＊２等位基因次之，与英国白种人相比，中国人ＩＬ１ＲＮ＾＊１等位基因的发生频率明显高于英国人，而英国人ＬＩ     

IL-1α基因启动子-889C/T和IL-1Ra第2内含子VNTR基因型及血清水平与2型糖尿病的相关性研究

目的　研究白细胞介素 1α(IL 1α)基因启动子 889C/T多态性和白细胞介素 1受体拮抗剂 (IL 1Ra)第 2内含子可变数目串联重复(VNTR)多态性及血清水平与 2型糖尿病 (T2DM)的相关关系。方法　采用聚合酶链反应 限制性片段长度多态性 (PCR RFLP)技术 ,检测 1 35例T2DM患者和 1 4 0例健康对照者的IL 1α( 889C/T)和IL 1Ra(VNTR)基因型 ,同时采用ELISA检测T2DM患者和对照者的血清IL 1水平。结果　T2DM组血清IL 1水平显著高于对照组 (P <0 0 1 ) ,IL 1α基因 889C/T基因型频率和等位基因频率在T2DM组和对照组比较差异有显著性 (P <0 0 5) ,等位基因频率的相对风险分析发现 ,T等位基因携带者患T2DM的风险是C等位基因的 2 0 2 3倍 (OR =2 0 2 3 ,95 %CI:1 1 4 7～ 3 567) ;IL 1Ra基因型频率和等位基因频率在T2DM组和对照组比较差异有显著性 (P <0 0 5) ,与健康对照组比较 ,不携带IL 1RaⅡ的基因型患 2型DM的相对风险度增加 2 0 2 5倍 (OR =2 0 2 5 ,95 %CI :1 0 33～ 3 967) ,携带IL 1RaⅡ的基因型的T2DM患者血清IL 1Ra水平显著高于不携带者〔(1 4 2 6 2 5± 32 4 31 ) pg/mlVS (1 2 99 56± 2 93 47) pg/ml,P <0 0 1〕。 结论　IL 1α( 889C/T)和IL 1Ra(VNTR)基因多态性与T2DM的发病具有相关性 ,其     

白细胞介素-6基因多态性对冠心病发病易感性的影响及其机制

目的了解白细胞介素-6（IL-6）基因-597G／A及-572C／G多态性对冠心病（CHD）发病易感性的影响及其影响机制。方法 应用聚合酶链反应．限制性片段长度多态性（PCR-RFLP）分析方法,测定245例CHD患者和260例正常对照者的IL-6基因型,探讨其与CHD的相关关系;观察基因型对血清IL-6水平的影响,并采用logistic回归分析法了解基因型与CHD其他危险因素间的相互作用。结果 两组研究对象中-597位点均仅发现GG基因型。-572C／G基因型和等位基因频率在两组间存在明显统计学差异（P均〈0．01）,CHD组GG基因型和G等位基因频率均显著高于对照组（P均〈0．01）;CG、GG基因型人群患CHD的风险分别为CC基因型人群的1．46倍（95％CI：1．01～2．10,P〈0．05）和5．19倍（95％CI：1．69～15．89,P〈0．01）;不同基因型患者间血清IL-6水平无统计学差异（P〉0．05）;-572C／G基因型与总胆固醇、甘油三酯间存在一定的交互作用,OR值分别为1．76（95％CI：1．05～3．16,P〈0．05）、2．51（95％CI：1．04～6．45,P〈0．05）。结论 IL-6基因-597G／A多态性可能与中国汉族人群CHD发病易感性无关,而-572C／G多态性可能是该人群CHD发病的易感基因之一,其可能通过对组织IL-6水平的影响及与血脂的协同作用参与CHD的发生。     

白细胞介素-1α、4、6基因多态性与Graves病的关系

本研究分析了中国山东地区汉族人群Grayes病患者与健康对照者白细胞介素-1α、4、6基因多态性。结果表明Graves病患者白细胞介素4(-590)c／t基因型和t等位基因频率均低于健康对照组。     

IL-1基因多态性与Hp感染后胃癌易感性的研究

目的 研究白细胞介素1B基因（IL-1B）启动子区域-31位点和-511位点及白细胞介素1受体拮抗剂基因（IL-1RN）多态性在我国北方人群胃癌患者与胃炎患者中的分布，探讨各基因型与胃癌的相关性。方法 收集126例胃癌患者与125例慢性胃炎患者（对照组）的外周血标本和流行病学资料，提取基因组DNA；IL-1RN基因采用PCR方法直接测定，IL-1B-31基因采用PCR-CTPP方法，IL-1B-511基因采用PCR-RFLP的方法进行基因分型。通过快速尿素酶、^14C呼气试验及Hp血清IgG抗体的方法检测Hp感染。结果 IL-1RN有5种基因型，分别为1／1、1／3、1／4、1／2和2／2型，其出现频率在胃癌组中分别为76．19％、4．76％、6．35％、11．90％和0．79％；在对照组分别为76．00％、4．00％、4．80％、13．60％和1．60％。各基因型在胃癌组和对照组中分布差异无统计学意义。IL-1B-31位点有3种基因型C／C、C／T和T／T型，在胃癌组中的频率分别为12．70％、47．62％和39．68％；在对照组中的频率分别为28．00％、48．80％和23．20％。与C／C型相比较，携带T／T基因型者胃癌发生的风险增加，OR=3．772（95％CI=1．786-7．966）。IL-1B-511位点有3种基因型C／C、C／T和T／T型，在胃癌组中的频率分别为19．20％、56．80％和24．00％；在对照组中的频率分别为23．38％、49．19％和27．42％。各基因型在胃癌组和对照组中分布差异无统计学意义。结论 IL-1B基因启动子区域-31位点的基因多态性可能与国人胃癌易感性相关；尚未有证据表明IL-1RN和IL-1B-511位点的基因多态性与国人胃癌易感性相关。     

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.