Syndecan-1和乙酰肝素酶在胃癌淋巴结转移中的相互作用

胃癌的侵袭和转移涉及多个步骤，其中穿越由细胞外基质和基底膜组成的屏障是必不可少的一步。该屏障主要由两种成分构成：一是结构蛋白，二是糖氨聚糖，后者的主要成分是硫酸乙酰肝素蛋白多糖(HSPG)。乙酰肝素酶(HPA)基因编码的蛋白质是惟一降解HSPG硫酸肝素(HS)侧链的核苷内切酶。我们先前的研究显示，HPA mRNA表达与胃癌淋巴结转移有关，且可能通过与CD44v6和基质金属蛋白酶(MMP)-7的协同作用参与胃癌的侵袭转移。     

乙酰硫酸肝素在造血系统及免疫系统中的作用

乙酰硫酸肝素是一种线性多糖,广泛存在于细胞表面和细胞外基质中,并在此与生长因子、生长因子结合蛋白、细胞外蛋白酶、蛋白酶抑制剂、化学物质和黏附蛋白相互作用.乙酰硫酸肝素在造血系统及免疫系统中的重要作用已引起了学者们的广泛重视,对乙酰硫酸肝素合成调控和功能研究有了很大进展.现将近年来对乙酰硫酸肝素在造血调控以及免疫学方面作用的研究进展综述如下.     

肝素酶:一种新的广谱的肿瘤转移相关抗原在中晚期肿瘤免疫治疗中的作用研究进展

肝素酶(Hpa)是裂解硫酸乙酰肝素蛋白多糖的唯一酶类,能破坏细胞外基质及基底膜,参与肿瘤血管生成,与肿瘤的侵袭转移密切相关.目前的研究表明,Hpa在大多数中晚期肿瘤中都有表达,尤其在转移性肿瘤中强表达,而Hpa表达的下调可以抑制肿瘤细胞的转移,提示Hpa可以作为一种广谱的肿瘤转移相关抗原用于中晚期肿瘤的免疫治疗.Hpa疫苗的开发可望为中晚期肿瘤的治疗开辟新的途径.本文详细综述了Hpa的结构与功能、对肿瘤转移的促进作用及其机制、以及其作为肿瘤转移相关抗原用于中晚期肿瘤免疫治疗的可能性.     

乙酰肝素酶与动脉粥样硬化

动脉粥样硬化是致死率较高的常见心血管疾病,乙酰肝素酶是能够裂解细胞外膜中硫酸乙酰蛋白多糖上侧链乙酰肝素的一种内切性β-D-葡萄糖醛酸糖苷酶,且其非酶活性也在许多正常生理活动或病理疾病中发挥作用。研究表明乙酰肝素酶与动脉粥样硬化的形成和进展有着紧密的联系。本文综述了乙酰肝素酶损伤内皮、促凝、诱导炎症因子及脂质聚集等作用,并阐述其在动脉粥样硬化发生发展中的作用及机制。     

乙酰肝素酶在肿瘤侵袭转移和血管生成中的作用

侵袭和转移是肿瘤重要的生物学特征，而细胞外基质(extracenular matrix，ECM)的降解和新生血管的形成则是促进肿瘤侵袭转移的关键因素。乙酰肝素酶(heparanase，HJPSE)是新近克隆出来的一种基质降解酶，可降解ECM和基底膜(basement membrance，BM)中的硫酸乙酰肝素(heparan sulfate，HS)，在肿瘤细胞的侵袭转移和血管生成过程中发挥着重要作用。     

肝素酶基因在肺腺癌中的表达及临床病理学意义

肿瘤转移的两个必备条件为瘤细胞侵犯基底膜(BM)与细胞外基质(ECM)和肿瘤血管的生成。BM及ECM的重要成分之一为硫酸肝素蛋白多糖(HSPGs)，其作用酶为肝素酶。为从分子水平上了解肺癌侵袭转移的机制，进一步探讨控制侵袭转移的方法，从而改善患者预后，提高生存率，我们采用逆转录聚合酶链反应(RT—PCR)技术研究肺腺癌组织中肝素酶基因的表达及临床病理学意义。     

乙酰肝素酶促进脑缺血后血管发生

乙酰肝素酶(heparanase,Hpa)是哺乳动物体内唯一能降解硫酸乙酰肝素蛋白多糖的β-D-葡萄糖醛酸内切酶.研究证实,Hpa可促进多种病理生理学过程的血管发生,但有关脑缺血后Hpa表达和作用的研究仍然较少.文章重点介绍了Hpa与脑缺血后血管发生的关系.     

乙酰肝素酶靶向治疗心肌梗死的前景

<正>乙酰肝素酶(HPSE)是一种内切性β-D-葡萄糖醛酸糖苷酶,是哺乳动物细胞中唯一可以切割细胞表面的硫酸乙酰肝素侧链的酶,参加细胞外重塑。HPSE涉及多种生理过程如胚胎植入,组织修复和炎症过程;病理致病过程主要包括肿瘤的进展和肾脏疾病。HPSE在多种恶性肿瘤病理发展过程中呈现高表达、高活性状态,有可能成为一个抗肿瘤治疗     

以乙酰肝素酶为靶点的肿瘤治疗研究进展

肿瘤的侵袭转移是导致肿瘤患者死亡的主要原因，寻找引发肿瘤细胞侵袭与转移的因素并进行有效阻断是治疗肿瘤的重要方法之一。肿瘤细胞要实现侵袭和转移首先要穿越由细胞外基质（extmcellularmatrix，ECM）及基底膜（basement menbrane，BM）组成的屏障。该屏障主要由Ⅳ胶原（collagen Ⅳ）、层黏连蛋白（laminin）以及硫酸乙酰肝素蛋白多糖（heparan sul fate proteogycans，HSPGs）等构成，     

肝素酶与胃癌侵袭转移的关系

胃癌是人类最常见的恶性肿瘤之一,位居消化道肿瘤之首。多年来,胃癌的发生发展及其侵袭转移一直是众多学者研究的热点。肝素酶(Hpa)是一类βD糖苷内切酶(endoβDglucuronidase),它既可存在于正常组织,也表达于多种恶性肿瘤细胞表面,以水解的方式降解组织屏障中的糖蛋白成分硫酸乙酰肝素糖蛋白(HSPGs),释放HSPGs结合的生物活性分子,促进细胞的侵袭和转移,诱导肿瘤血管生成,降低肿瘤患者的生存率。此文就Hpa与胃癌侵袭转移的关系作一综述。     

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。     

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。     

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。     

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.