弥漫性泛细支气管炎人类白细胞抗原易感基因的研究

目的 研究弥漫性泛细支气管炎患者人类白细胞抗原(HLA)易感基因的位点.方法 选择1999年11月至2006年3月的24例弥漫性泛细支气管炎患者为患者组,比较其临床特点,采用t检验比较红霉素治疗前、后实验室数据的变化.另选53名健康志愿者为对照组.采用寡核苷酸微阵列基因芯片对HLA-A、HLA-B,DR位点进行检测,采用SAS 6.12软件对疾病的相关性进行卡方检验评估,筛选我国弥漫性泛细支气管炎患者HLA易感基因.P＜0.05为差异有统计学意义.结果 患者组HLA-A2频率为20.83%(5/24),对照组为66.04%(35/53),两组频率比较差异有统计学意义(X2=13.52,P＜0.01);HLA-A2频率与弥漫性泛细支气管炎呈负相关(比值比=0.12);而患者组HLA-A11频率为58.33%(14/24),对照组为26.42%(14/53),两组频率比较差异有统计学意义(X2=7.27,P＜0.01);HLA-A11与弥漫性泛细支气管炎呈正相关(比值比=3.9);但在HLA-B位点的检测中未发现弥漫性泛细支气管炎患者有易感基因.尽管患者组在HLA-B54、HLA-B55、HLA-B56的频率分别为12.5%(3/24)、16.67%(4/24)、8.33%(2/24),高于对照组的频率[5.66%(5/53)、3.78%(2/53)、3.78%(2/53)],经统计处理两组频率比较差异无统计学意义(X2分别为1.08、3.82、0.70;P均＞0.05);此外,患者组HLA-DRB5 *010/020频率为37.5%(9/24),对照组为16.98%(9/53),两组频率比较差异有统计学意义(X2=3.88,P＜0.05),必须考虑病例数较少所造成的误差.结论 弥漫性泛细支气管炎HLA易感基因主要位于HLA-Ⅰ类分子A和B位点之间,但HLA-A2可能是中国弥漫性泛细支气管炎发病率相对较低的因素.     

弥漫性泛细支气管炎和慢性鼻窦炎的相关性研究进展

弥漫性泛细支气管炎（DPB）是一种呼吸性细支气管区域的慢性炎症性疾病,主要发病于东亚地区,多合并或既往有慢性鼻窦炎,属于鼻窦支气管综合征（SBS）的一种,遗传可能是DPB发病及其与慢性鼻窦炎有相关性的基础,其中最引人注目的是有关人类白细胞抗原（HLA）的研究,该文就DPB与HLA及慢性鼻窦炎的相关性作一综述。     

Childhood diffuse panbronchiolitis: a case report

Diffuse panbronchiolitis (DPB) is a chronic, potentially life-threatening lower respiratory tract disease that is particularly common in Japanese people. If left untreated, it progresses to bronchiectasis, respiratory failure, and death. Lack of familiarity with DPB in the non-Far East may result in a failure to correctly diagnose and treat this disorder. We describe a child with DPB. We suggest that DPB is a sinopulmonary disease that is not exclusive to the Asian population and to adults. Its clinical and radiological features should be better known by pediatric pulmonary physicians.     

弥漫性泛细支气管炎气道黏液高分泌的研究进展

弥漫性泛细支气管炎是一种小气道慢性炎症性疾病，气道黏液高分泌即痰液增多是该病主要临床表现之一。其黏液高分泌的机制至今尚不清楚，相关研究表明与绿脓杆菌、中性粒细胞、炎症介质及黏蛋白基因的多态性有关。另外，大环内酯类抗生素对弥漫性泛细支气管炎的气道高分泌有显著治疗作用。     

铜绿假单胞菌与弥漫性泛细支气管炎发病机制

弥漫性泛细支气管炎(diffuse panbronchiolitis,DPB)是一种小气道慢性弥漫性疾病,其确切病因不甚明确,部分学者认为DPB的发病与铜绿假单胞菌感染有关,铜绿假单胞菌多种毒力因子如杀白细胞素、外毒素A、内毒素、弹性蛋白酶和鞭毛蛋白等在引起DPB气道感染损伤过程中有着重要的作用,同时铜绿假单胞菌密度感应信号系统参与调节这些毒力因子的基因表达过程.     

CTLA-4 gene polymorphism is associated with predisposition to coeliac disease

BACKGROUND: Susceptibility to coeliac disease is strongly associated with particular HLA class II alleles. However, non-HLA genetic factors are likely to be required for the development of the disease. Among candidate genes is the CTLA-4 (cytotoxic T lymphocyte associated) gene located on chromosome 2q33 in humans, which encodes a cell surface molecule providing a negative signal for T cell activation. AIMS: To investigate CTLA-4 exon 1 polymorphism (position 49 A/G) in patients with coeliac disease. PATIENTS: 101 patients with coeliac disease and 130 healthy controls. METHODS: Allele specific hybridisation and restriction enzyme digestion of polymerase chain reaction amplified genomic DNA. RESULTS: The A allele of the CTLA-4 position 49 polymorphism was found on 82.2% of chromosomes in patients with coeliac disease compared with 65.8% in controls (p < 0.0001), mostly in the homozygous form (68.3% in patients versus 47.7% in controls; odds ratio (OR) 2.36, 95% confidence interval (CI) 1.37 to 4.06, p = 0.002). Four patients only had the G/G genotype compared with 21 controls (OR 0.21, CI 10.07 to 0.64, p = 0.002). These differences were maintained when subjects were stratified according to the HLA class II phenotype, in particular when patients and controls were matched for the presence of the predisposing HLA DQB1*02 (DQ2) allele or HLA-DQA1*0501/DQB1*02 heterodimer. CONCLUSION: The CTLA-4 gene polymorphism is a non-HLA determinant that predisposes to coeliac disease. Whether it directly contributes to disease susceptibility or represents a marker for a locus in linkage disequilibrium with CTLA-4 needs further investigation.     

弥漫性泛细支气管炎12例临床分析

目的探讨弥漫性泛细支气管炎(DPB)的临床特征及红霉素治疗效果。方法回顾性分析2010-10~2015-06接受红霉素治疗的12例DPB患者的临床资料,包括临床症状及体征、影像学表现、实验室检测指标,观察红霉素治疗过程及结果。结果 12例DPB患者的平均发病年龄为(59.2±10.4)岁,从发病到确诊时间平均(9.3±7.4)年。12例胸部CT均表现为小叶中央性结节,12例肺功能均提示阻塞性通气功能障碍及血气分析提示低氧血症,1例冷凝集试验阳性。既往被误诊为慢性阻塞性肺疾病(COPD)6例,支气管哮喘1例,支气管扩张症4例,粟粒型肺结核1例。通过红霉素治疗,10例DPB患者临床症状改善;2例患者出现复发,经再次红霉素治疗后临床症状改善。结论 DPB易被误诊,应提高对其认识。红霉素治疗DPB有效,患者耐受性好。     

弥漫性泛细支气管炎2例临床分析并文献复习

目的 探讨弥漫性泛细支气管炎(DPB)的临床特点及治疗.方法 回顾性分析我院2例确诊为DPB患者的临床特点及治疗,并复习相关文献.结果 2例均以慢性咳嗽、咳痰伴活动后气促为主诉,肺部听诊均闻及湿啰音,HLA-B54均阳性,但冷凝集试验均阴性,肺功能均以阻塞性通气功能障碍为主;1例经病理确诊,胸部影像见典型弥漫小叶中心性结节影,但无慢性鼻窦炎病史,口服阿奇霉素0.25g,隔日1次,治疗12个月后肺部病灶明显吸收;1例经临床确诊,胸部影像见典型弥漫结节影伴支气管扩张和间质性肺纤维化,既往有慢性鼻窦炎病史,口服阿奇霉素0.25 g,隔日1次,治疗7个月后肺部病灶明显吸收;2例患者初期均长期误诊.结论 2例患者具有DPB典型临床表现,但某些特征有别于一般日本DPB患者,2例病例均显示长期口服小剂量阿奇霉素治疗DPB效果显著.     

弥漫性泛细支气管炎9例临床分析

目的 增强对弥漫性泛细支气管炎(DPB)临床特征的认识及诊断. 方法 收集南京医科大学第一附属医院呼吸科9例曾被误诊的DPB患者,通过实验室检查、肺功能及动脉血气检查、影像学检查等分析其临床特点. 结果 所有患者均有慢性咳嗽、咳痰、活动后气促的症状,合并副鼻窦炎.9例患者用阿奇霉素(500mg/d),联合抗生素、氧疗和对症、支持疗法等方法治疗后症状均有明显改善、痰量减少,肺部高分辨CT提示明显好转. 结论 DPB具有一定的临床特异性,只有正确地认识及诊断才能改善其预后.     

Kartagener's综合征伴泛细支气管炎临床病理分析

目的探讨Kartagener’s综合征(KS)合并泛细支气管炎的临床病理学特征。方法分析8例Kartagener’s综合征合并泛细支气管炎患者的临床资料和组织形态特点。结果Kart-agener’s综合征是一种罕见的遗传性疾病,它的特点是支气管扩张症、副鼻窦炎以及内脏转位。以呼吸道为首发症状,常合并弥漫性泛细支气管炎(DPB)。病理形态特点为终末细支气管和呼吸性细支气管管壁增厚,慢性炎细胞浸润。其中2例透射电镜检查1例为纤毛的内侧臂缺失,1例纤毛畸形,融合成团。结论Kartagener’s综合征合并泛细支气管炎值得引起临床注意,影像及肺活检有助于对本病的诊断。     

Clinical efficacy of the FLUTTER device for airway mucus clearance in patients with diffuse panbronchiolitis

Abstract Expectoration of mucus is important in preventing the development of airway inflammation in patients with diffuse panbronchiolitis (DPB). To evaluate the clinical efficacy of the FLUTTER device in clearing mucus from the airways of patients with DPB who have difficulty expectorating, we assessed pulmonary function and symptoms in patients treated with FLUTTER. Eight patients in a stable clinical condition with DPB were included in the study. The study was divided into two consecutive, 1-week periods. The initial week was an observation week. During the following week, patients used FLUTTER four times daily. Expectorated sputum was collected in a container and weighed every day during 2 weeks. Pulmonary function, partial oxygen pressure and partial carbon dioxide pressure in arterial blood were measured in all patients on the last day of the observation week and the FLUTTER treatment week. A symptom score for difficulty of expectoration was determined by questionnaire. A pneumothorax developed in one patient during using FLUTTER. The mean daily sputum weight and peak expiratory flow rate increased significantly after treatment with FLUTTER ( P < 0.04 and P< 0.02, respectively). Symptom score improved significantly after using FLUTTER ( P < 0.02). We conclude that the use of FLUTTER is effective in clearing mucus from the airways. However, the development of a pneumothorax may complicate use of the procedure in some cases.     

红霉素对弥漫性泛细支气管炎治疗作用的实验研究

目的探讨红霉素治疗弥漫性泛细支气管炎的作用机理。方法40只健康雄性SD大鼠随机分为三组：正常对照组、模型组和红霉素治疗组。红霉素治疗组于置管后7d按50mg／kg／a给予口服红霉素。实验60d后观察肺组织病理变化,应用ELISA方法测定血清与肺匀浆中TNF-α、IL-8的含量。结果血清中TNF-α、IL-8的含量三组 间无统计学差异（P〉0．05）;模型组肺匀浆中TNF—α及IL-8的含量较对照组明显增高（P〈0．05）,红霉素治疗组比模型组上述指标明显下降（P〈0．05）。结论细胞因子TNF-α、IL-8的释放可能与弥漫性泛细支气管炎的发病有关;红霉素治疗弥漫性泛细支气管炎可能是通过抑制细胞因子TNF-α、IL-8的释放而起作用的。     

Genetic analysis of HLA class II alleles and susceptibility to Type 1 (insulin-dependent) diabetes mellitus in Japanese subjects

Summary Although HLA-DQB1 alleles encoding aspartic acid at position 57 (Asp-57) are protective against Type 1(insulin-dependent) diabetes mellitus in Caucasians, most Japanese Type 1 diabetic patients carry at least one Asp-57 DQB1 allele. We analysed the DRB1, DQA1 and DQB1 genes of 99 Japanese patients and 86 control subjects with polymerase chain reaction and sequence-specific oligonucleotide hybridization. We found that (1) the DQA1*0301 allele was significantly increased in Type 1 diabetic patients (RR 7.8,pc < 0.0001); (2) the DRB1*0405 (Dw15) allele, which is a subtype of DR4 haplotype, was significantly increased in DR4-positive patients (RR 12.0,pc < 0.001); and (3) although the DRw8-DQw8 haplotype was positively associated with Type 1 diabetes, the DRBl*0406-DQw8 haplotype was decreased in the diabetic patients. These data indicate that DRB 1 and DQA1 genes also confer susceptibility to Type 1 diabetes in Japanese.     

冠状动脉粥样硬化性心脏病易感基因的研究进展

随着冠状动脉粥样硬化性心脏病在全球范围内发病率的日益增高,其所带来的高病死率和高致残率在消耗国家公共资源的同时也阻碍着人们生活质量的提高.面对这一严峻局面,全球科学家都积极致力于其发病机制的研究,从宏观因素到分子水平,以期找到预防和治疗的新方法.随着人类基因组草图绘制的完成为大家开展基因研究提供了更加方便、快捷的平台,大家的目光也更多的聚集于糖尿病、冠状动脉粥样硬化性心脏病等常见多基因复杂疾病基因层面的研究.在这样的大背景下,针对冠状动脉粥样硬化性心脏病易感基因开展的研究亦取得了不俗进展.     

Genetic dissection between silent and clinically diagnosed symptomatic forms of coeliac disease in multiplex families

Background. Coeliac disease has a large variation in clinical outcome. In addition to the classical disease with malabsorption, many individuals have a silent form, in which subjective symptoms are missing but autoantibodies and mucosa lesions are identical to the symptomatic disease.

Aim. To investigate whether differences in HLA DR-DQ genes explain the variation in outcome.

Materials and methods. HLA DQ alleles were determined in 28 multiplex families with sibling pairs in which one had the symptomatic disease but the other had the silent form.

Results. No differences in the distribution of HLA DR-DQ haplotypes could be observed. The clinically diagnosed coeliac disease seemed to have earlier onset than silent coeliac disease.

Conclusions. Results indicate that the major genetic susceptibility locus, HLA DO, does not determine the exact clinical outcome of coeliac disease.     

Genetic susceptibility to Hodgkin's lymphoma associated with the human leukocyte antigen region

Abstract:  Based on the presence of an abundant inflammatory infiltrate, expression of a broad spectrum of cytokines and the professional antigen presenting phenotype of Hodgkin Reed-Sternberg cells it can be anticipated that immunological mechanisms play a major role in the pathogenesis of Hodgkin's lymphoma (HL). Genetic susceptibility to HL probably relates to functionality of the immune system and the large number of associations with the human leukocyte antigen (HLA) region in family and population-based studies supports this relation. In Epstein–Barr virus (EBV) positive HL cases, which usually demonstrate HLA class I expression, HRS cells should be able to present EBV derived antigenic peptides and trigger the immune system. This process depends on the affinity of the HLA binding groove for binding immunogenic peptides and thus on the HLA alleles. It can be anticipated that certain combinations of alleles predispose to or protect from the development of EBV positive HL. In EBV negative HL cases other antigenic peptides, related to malignant transformation, in combination with other HLA alleles may be involved. In addition, differential attraction and activation of inflammatory cells may influence HL subtype. In this article, possible roles of HLA in HL pathogenesis are explored and genetic associations of HLA with HL are reviewed and commented on.     

Genetic predisposition to pancreatic cancer

Pancreatic adenocarcinoma (PC) is the most deadly of the common cancers. Owing to its rapid progression and almost certain fatal outcome, identifying individuals at risk and detecting early lesions are crucial to improve outcome. Genetic risk factors are believed to play a major role. Approximately 10% of PC is estimated to have familial inheritance. Several germline mutations have been found to be involved in hereditary forms of PC, including both familial PC (FPC) and PC as one of the manifestations of a hereditary cancer syndrome or other hereditary conditions. Although most of the susceptibility genes for FPC have yet to be identified, next-generation sequencing studies are likely to provide important insights. The risk of PC in FPC is sufficiently high to recommend screening of high-risk individuals; thus, defining such individuals appropriately is the key. Candidate genes have been described and patients considered for screening programs under research protocols should first be tested for presence of germline mutations in the BRCA2, PALB2 and ATM genes. In specific PC populations, including in Italy, hereditary cancer predisposition genes such as CDKN2A also explain a considerable fraction of FPC.