白细胞介素33在支气管哮喘中的作用及其研究现状

支气管哮喘(哮喘)是一种复杂的异质性疾病,多以2型反应为主.近年来随着科技发展人们对哮喘的病理生理学机制有了长足的认识,气道上皮细胞来源的细胞因子白细胞介素33(interleukin 33,IL-33)在哮喘的发生和发展中发挥重要作用.本文立足于IL-33,结合其本身的生物学特点和发挥作用的靶细胞,综述IL-33在哮喘的气道炎症和气道重塑中的作用.     

白介素33与支气管哮喘

白介素33(IL-33)是2005年被发现的一个新的白介素家族成员.1989年ST2首先被Tominaga[1]鉴定为IL1受体超家族的一个成员.后来Baekkevold等从高壁内皮细胞中分离得到IL-33分子[2],而且该分子定位于高壁内皮细胞的核内,故最初被称为“高壁内皮细胞来源的核因子”.直到2005年Schmitz等[3]发现高壁内皮细胞来源的核因子是ST2的特异性配体,并重新命名为IL-33.从那以后人们对IL-33的生物学特征有了更深入的了解.IL-33与ST2结合,诱导Th2细胞因子的产生,从而参与支气管哮喘等Th2相关疾病.本文就IL-33的分子结构、表达、生物学活性及其目前在支气管哮喘发病机制中的作用综述如下.     

Th2细胞因子与支气管哮喘发病机制的研究进展

支气管哮喘(简称哮喘)是由多种细胞和细胞因子参与的肺部慢性炎症性疾病.发病机制尚未完全清楚.目前认为Th1/Th2反应失衡导致Th2细胞过度激活是其重要的免疫学机制之一.Th2细胞产生的多效性细胞因子白介素4(IL-4)、IL-5和IL-13在此过程中发挥巨大作用,与哮喘发病密切相关.     

上皮源性细胞因子与支气管哮喘

支气管哮喘(简称哮喘)是全球最常见的慢性气道炎症性疾病之一.慢性气道炎症是哮喘的内在发病机制,炎症细胞在气道的局部聚集、炎症介质和细胞因子的释放促使气道炎症发生.上皮源性细胞因子是免疫活性细胞的效应因子,其免疫调节功能在哮喘发病机制中处于中心地位.在人类肺组织及免疫细胞中,细胞因子的表达增高,从而导致肺部变态反应性疾病的发生.近年来利用哮喘发病机制中细胞因子作为靶点进行靶向治疗哮喘已成为未来哮喘治疗研究的主要热点.本文主要就上皮源性细胞因子中IL-25、IL-33及胸腺基质淋巴细胞生成素的结构和功能进行介绍,并对其与哮喘的关系作一简单综述.     

IL-36的最新研究及其在支气管哮喘中的作用

IL-36细胞因子家族在2000年代初被确定为IL-1细胞因子家族一个新的亚家族,其包括3个激动剂IL-36α、IL-36β和IL-36γ,以及IL-36受体拮抗剂(IL-36Ra)和IL-38。IL-36较传统IL-1家族成员具有更强的免疫调节与免疫激活作用,是T淋巴细胞和树突状细胞的强效调节剂,其通过参与效应细胞的活化、抗原提呈以及刺激促炎因子的产生,从而在免疫反应中发挥着巨大作用。IL-36细胞因子在皮肤和肠道的上皮屏障组织以及免疫细胞中的表达最为显著,而在肺组织细胞中的作用也正在研究。支气管哮喘是一种常见的慢性炎症性疾病,近年来我国儿童哮喘的患病率呈上升趋势,主要表现为支气管炎症和可逆性气流受限。哮喘被认为是一种Th2细胞疾病,其发病机制为IgE产生增加,嗜酸性粒细胞渗入,以及细胞因子释放增多。IL-36作为新近的研究热点,已被证实在肺部疾病中发挥重要作用,如肺结核病、特发性肺纤维化及慢性阻塞性肺疾病等,而其在支气管哮喘发病过程中的作用正在被发掘。因此,本文综述了IL-36生物学的最新知识及其在支气管哮喘中的发病机制,并讨论了针对IL-36受体及其信号通路治疗支气管哮喘的可能性...     

白介素33与支气管哮喘

白介素33（IL-33）是2005年被发现的-个新的白介素家族成员。1989年ST2首先被Tominaga鉴定为IL-1受体超家族的-个成员。后来Baekkevold等从高壁内皮细胞中分离得到IL-33分子嘲,而且该分子定位于高壁内皮细胞的核内,故最初被称为“高壁内皮细胞来源的核因子”。直到2005年Schmitz等嘲发现高壁内皮细胞来源的核因子是ST2的特异性配体,并重新命名为IL-33。从那以后人们对IL-33的生物学特征有了更深入的了解。II,-33与ST2结合,诱导Th2细胞因子的产生,从而参与支气管哮喘等Th2相关疾病。本文就IL-33的分子结构、表达、生物学活性及其目前在支气管哮喘发病机制中的作用综述如下。     

2型固有淋巴细胞在过敏性疾病发生中的作用

过敏性疾病尤其是支气管哮喘(简称哮喘)一直被认为是由Th2细胞介导的炎症反应.近期研究发现,2型固有淋巴细胞(type-2 innate lymphoid cell,ILC2)作为一种先天性免疫细胞,同样参与哮喘发生的始动环节.该细胞可产生Th2型细胞因子IL-13、IL-5从而应答受损上皮组织释放的IL-33及IL-25,不仅仅作用于固有免疫的初级阶段,还介导获得性免疫相关功能,这使得先天性及获得性两种免疫系统之间存在了某种特殊的联系,也给研究过敏性哮喘发生机制带来了新的思路.     

金水宝胶囊对支气管哮喘患者几种免疫细胞因子的影响

支气管哮喘是一种慢性炎症性气道疾病,免疫因素在哮喘的发病过程中发挥重要作用。以往认为辅助性T淋巴细胞Th1/Th2比例失衡是哮喘发病的重要机制。近年发现了一种以产生IL-17为主要细胞因子的Th17细胞,在哮喘的发病机制中同样具有重要作用,IL-17对于中性粒细胞参与的支气管哮喘气道炎症、气道高反应、气道重塑均发挥重要作用,有可能成为治疗哮喘的有意义的靶目标[1-3]。对支气管     

老年支气管哮喘患者IL-18、IL-12水平的变化及临床意义

目的 探讨老年支气管哮喘患者外周血白细胞介素18(IL-18)和IL-12的变化及其在哮喘发病机制中的作用.方法 采用ELISA法检测42例老年支气管哮喘患者及26例正常对照组检测血清中IL-18及IL-12水平.结果 支气管哮喘发作期患者的血浆IL-12明显高于正常对照组(P<0.01),IL-18明显高于正常对照组(P<0.01).结论 IL-18、IL-12参与了老年支气管哮喘发作期的发病机制,IL-18、IL-12在Th1/Th2细胞因子网络失衡的发病机制中起重要的调节作用.     

吸入糖皮质激素对哮喘患者Th1/Th2细胞因子网络影响

支气管哮喘(哮喘)是一种慢性气道炎症疾病,多种炎性细胞和炎性介质参与其过程。目前认为T辅助淋巴细胞两个功能性亚群Th1／Th2相关细胞因子在哮喘发病中发挥重要作用。我们对哮喘患者白细胞介素-5(IL-5)、白细胞介素-8(IL-8)r-干扰素(IFN-r)水平进行检测,探讨吸入糖皮质激素对哮喘患者Th1／Th2细胞因子的影响。     

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.