1型糖尿病自身抗原研究进展

自身免疫是1型糖尿病发病的重要机制.1型糖尿病自身抗原的发现为疾病的发病机制及临床诊治开拓了视野.胰岛素、谷氨酸脱羧酶65、胰岛细胞瘤相关抗原2等是已发现的1型糖尿病主要的自身抗原.近年来,1型糖尿病自身抗原如嗜铬粒蛋白A、胰岛淀粉样多肽、锌转运体8、胰-十二指肠同源盒因子1备受重视.该文就1型糖尿病自身抗原的研究进展进行综述.     

1型糖尿病免疫学发病机制与免疫干预的研究现状

1型糖尿病是一种T细胞介导的胰岛β细胞选择性破坏的自身免疫性疾病。自身抗原免疫耐受丧失,免疫调节失衡,胰岛自身抗原反应性T细胞克隆活化及Th1、Th2细胞及其细胞因子失衡,启动、维持和加速自身免疫性胰岛炎,导致糖尿病发生。近年来免疫学防治成为1型糖尿病的研究热点。     

免疫药物治疗胰岛残存胰岛β细胞研究进展

1型糖尿病患者胰岛β细胞功能和数量均降低,即使早期使用胰岛素,也不能避免严重并发症发生.免疫治疗不同于以往的替代疗法,侧重于重建机体病态T细胞和免疫调节效应的平衡,抑制针对胰岛β细胞的自身免疫反应,增强胰岛β细胞对自身免疫的耐受.目前,多种免疫药物已经被批准用于治疗1型糖尿病,如抗CD3单克隆抗体、GAD-alum等.     

自身免疫多腺体综合征、1型糖尿病、自身免疫甲状腺病与白细胞抗原-Ⅱ类基因研究进展

自身免疫多腺体综合征(APS)是指由自身免疫引起的以多内分泌腺功能受损为主要表现的综合征,共分3型,1型糖尿病(T1DM)并自身免疫甲状腺病(AITD)为APSⅢ型最常见的类型。白细胞抗原(HLA)是T1DM和AITD的主要遗传因素之一,现将近几年国内外关于APS、T1DM和AITD基因型相关的研究进展作一综述。     

儿童及青少年1型糖尿病患者甲状腺抗体和功能的改变

1型糖尿病 (type 1diabetesmellitus ,T1DM)与自身免疫性甲状腺疾病 (autoimmunethyroiddiseases,AITD)均属于器官特异性自身免疫性疾病。许多文献报告二者存在一定的联系 ,T1DM患者常常出现甲状腺自身抗体 [甲状腺过氧化物酶抗体 (TPO Ab)和甲状腺球蛋白抗体 (TG Ab) ]及甲状腺功能的改变 ,而AITD患者胰岛细胞抗体 (IC Ab)及谷氨酸脱羧酶抗体 (GAD Ab)亦明显升高。国内外近几年关于儿童及青少年 1型糖尿病患者甲状腺自身免疫性改变的研究情况如下。1　儿童及青少年T1DM患者甲状腺自身免疫性改变的发生率1.1　血清甲状腺自身抗…     

特异性免疫治疗机制的研究进展

特异性免疫治疗是治疗过敏性疾病的最有效方法,至今已有90多年的历史.其机制尚未明确,早期的研究重点集中于循环抗体和效应细胞,目前主要集中于免疫治疗对T细胞的作用及由此引起的一系列细胞因子的变化、CD4+调节性T细胞亚群、修饰抗原递呈细胞诱导免疫耐受、免疫效应细胞募集机制、单克隆技术支持下的重组变应原、变应原DNA疫苗、变应原耦联佐剂.     

重症肌无力的免疫治疗

重症肌无力(myasthenia gravis,MG)是一种T细胞依赖、抗体介导的自身免疫病。患者血清中抗乙酰胆碱受体(AChR)抗体等自身抗体滴度升高。MG免疫治疗目前主要有两大类,一是对免疫系统有广泛作用的免疫疗法如皮质激素等;二是针对MG发病有关的特异性免疫细胞或细胞因子等,面对全身其他免疫功能影响较小的免疫治疗方法。     

特异性免疫治疗机制的研究进展

特异性免疫治疗是治疗过敏性疾病的最有效方法,至今已有90多年的历史.其机制尚未明确,早期的研究重点集中于循环抗体和效应细胞,目前主要集中于免疫治疗对T细胞的作用及由此引起的一系列细胞因子的变化、CD4+调节性T细胞亚群、修饰抗原递呈细胞诱导免疫耐受、免疫效应细胞募集机制、单克隆技术支持下的重组变应原、变应原DNA疫苗、...     

变应性哮喘特异性免疫治疗进展

从儿童支气管哮喘(哮喘)发病、诊断、临床表型、预后、综合防治等方面论述哮喘与过敏的关系.因在治疗方面,抗原特异性免疫治疗是目前哮喘、鼻炎综合防治措施之一,并列入主要指导性的文献,了解特异性免疫治疗的背景、定义、机制、疗效、安全性、存在问题、研究进展等,对变应性哮喘的防治十分重要.     

变应原特异性免疫治疗

变应原特异性免疫治疗是唯一可以改变变态反应性疾病进程的治疗方法,随着近年来变应原制剂质量及标准化程度的提高,使其不良反应更小、更适合临床应用.由于儿童患者正处于生长发育期,其免疫系统发育尚未完全,是接受变应原特异性免疫治疗的最佳时期,治疗效果较成人好.皮下注射的变应原特异性免疫治疗经多年的实践和研究,疗效公认;而目前已逐渐成熟的舌下脱敏治疗和皮下注射脱敏治疗的疗效一样,并得到儿童的喜爱.寻找到引起患者临床症状的主要变应原,用该抗原进行脱敏治疗方可达到预期的治疗目的.     

Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: First results of ETA®

There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Methods. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC^® (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. Results. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (≥ 30 kU/I) or specific IgE (≥ 0.35 kUA/I) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Discussion. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the development of asthma in specifically sensitised infants with atopic dermatitis.     

Resurgence of measles in Singapore: profile of hospital cases

OBJECTIVE: To ascertain the profile of cases of measles seen at a general hospital during a recent outbreak that occurred despite a measles vaccination program. METHODOLOGY: A retrospective study from January 1991 to March 1998. All patients with measles (ICD code 055. 9) seen at the emergency unit or as inpatients were included. RESULTS: There were 87 cases identified. The diagnosis was clinical in all and proven serologically in 71%. Eighty-five per cent of the cases occurred between January 1997 and March 1998. There was a bi-modal age distribution with peaks in the very young (相似文献   

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孤独症谱系障碍(autistic-spectrum disorders,ASDs)近年来患病率逐年攀升至1%左右,其症状往往伴随终生,成为严重威胁儿童健康和发展的神经发育性疾患;注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)是儿童期最常见的精神障碍,国内报道患病率为4.13%～5.83%,其症状可延续至青少年期,甚至到成年期[1]。这两类精神障碍在成年期的临床表现、共患病、治疗策略和预后与儿童期有哪些不同呢?本文通过回顾相     

EXCITING NEW TREATMENT APPROACHES FOR PATHYPHYSIOLOGIC MECHANISMS OF SICKLE CELL DISEASE

During the past several decades, our understanding of the complex pathophysiology of vasoocclusion associated with sickle cell disease has improved greatly. Interaction of genes, hemoglobin molecules, red cell membrane and metabolic changes, cell-cell interactions and cell-plasma interactions, red cell adhesion to vascular endothelium, activation of coagulation, and vascular reactivity play a role in vaso occlusion. Penicillin prophylaxis of pneumococcal infections and appropriate use of blood transfusions and other supportive measures improved survival of sickle cell patients. Hydroxyurea made a major impact on sickle cell therapy when it was shown to decrease acute painful episodes, acute chest syndrome, and the need for blood transfusion in adults. Significant experience in the use of hydroxyurea has been accumulated in older children. The benefits and risks of hydroxyurea for younger children and long-term risks in all patients will be evaluated in future investigations. Other promising therapies include butyrate compounds, clotrimazole, magnesium supplementation, poloxamer 188, antiadhesion agents, anticoagulant approaches, and nitric oxide. Hemopoietic transplantation remains the only curative therapy. However, several transgenic mouse models are available for studies of gene therapy or other treatment approaches on biochemical, cellular, and pathologic effects of mutant genes.     

Infiltrations of Epstein-Barr virus-carrying cells in granular lymphocyte-proliferative disorders corresponding to chronic active Epstein-Barr virus infection

A 21-year-old man with granular lymphocyte-proliferative disorders (GLPD) associated with chronic active Epstein-Barr virus (EBV) infection is described. Chromosomal analyses revealed several clonal abnormalities and two of them were mainly repetitious. High copy numbers of monoclonal EBV genome were also detected in the proliferative large granular lymphocytes (LGLs), indicating the monoclonal expansion of EBV-infected LGLs. The patient had an indolent course for several years, and there was no evidence of infiltrations of his bone marrow until the end stage. At autopsy, microscopic studies revealed marked infiltrations of LGL in the liver and spleen, and the infiltrating cells were NK-cell immunophenotype. The infiltrated LGLs showed latency I.     

LUTEINIZING HORMONE RECEPTOR MUTATIONS IN DISORDERS OF SEXUAL DEVELOPMENT AND CANCER

Human male sexual development is regulated by chorionic gonadotropin (CG) and luteinizing hormone (LH). Aberrant sexual development caused by both activating and inactivating mutations of the human luteinizing hormone receptor (LHR) have been described. All known activating mutations of the LHR are missense mutations caused by single base substitution. The most common activating mutation is the replacement of Asp-578 by Gly due to the substitution of A by G at nucleotide position 1733. All activating mutations are present in exon 11 which encodes the transmembrane domain of the receptor. Constitutive activity of the LHR causes LH releasing hormone-independent precocious puberty in boys and the autosomal dominant disorder familial male-limited precocious puberty (FMPP). Both germline and somatic activating mutations of the LHR have been found in patients with testicular tumors. Activating mutations have no effect on females. The molecular genetics of the inactivating mutations of the LHR are more variable and include single base substitution, partial gene deletion, and insertion. These mutations are not localized and are present in both the extracellular and transmembrane domain of the receptor. Inactivation of the LHR gives rise to the autosomal recessive disorder Leydig cell hypoplasia (LCH) and male hypogonadism or male pseudohermaphroditism. Severity of the clinical phenotype in LCH patients correlates with the amount of residual activity of the mutated receptor. Females are less affected by inactivating mutation of the LHR. Symptoms caused by homozygous inactivating mutation of the LHR include polycystic ovaries and primary amenorrhea.     

A profile of respiratory symptoms in urban and rural South Australian school children

This report describes the cross-sectional analyses of data from the first year of a longitudinal study using questionnaire and respiratory function data over a 5 year period from a sample of rural South Australian school children. The cumulative or lifetime prevalences of respiratory symptoms were estimated in 825 rural and 1261 urban school children aged between 5 and 15 years in order to determine if the prevalence rates differed between rural and urban school children. The study found the overall cumulative prevalence of asthma and/or wheezy breathing (AWB) to be 24.1% in the rural school children compared to 27.6% in the urban school children. Most children developed AWB symptoms before the age of 7 years, with 20% reporting moderately severe symptoms and 10% having more than one attack per fortnight. The cumulative prevalence of bronchitis, loose/rattly cough (BLRC) differed significantly between the rural school children (34.1%) and urban school children (47.9%). The BLRC symptoms preceded the development of AWB in many cases. Urban school children also reported a higher prevalence of atopic conditions.     

Personality profiles and heart rate variability (vagal tone) in children with recurrent abdominal pain

The aim of the study was to explore psychological factors and autonomic activity in children with recurrent abdominal pain and to compare them with those in a control group of healthy children. The Personality Inventory for Children was used for assessment of developmental, emotional and psychosocial factors in 25 children with recurrent abdominal pain (age, 7-15 y). Parasympathetic and sympathetic functions in these children and in 23 healthy control subjects (age, 7-13 y) were also investigated, non-invasively using a computerized polygraph. Vagal tone (parasympathetic function) was indexed by calculation of respiratory sinus arrhythmia in beats/min. Skin conductance (sympathetic function) was recorded by the constant current method. On the Personality Inventory for Children, 16 patients had high scores on somatic concern. Several patients had scores in the clinical range for depression, withdrawal and anxiety, but the mean scores for these personality profile scales were well within the normal range of healthy children. Interestingly, there was a spike on the L (Lie)-scale for most of the patients and 15 patients had scores above or close to the clinical cut-off value. As compared with the scores in healthy children, vagal tone and sympathetic tone were normal. Conclusion: Many children with recurrent abdominal pain have scores in the clinical range for depression, withdrawal, anxiety and L-scale indicating coping problems, denial and a trend towards somatic concern that may contribute to the evolution of abdominal pain. Autonomic nerve activity was not disturbed in these children.     

Hauttemperaturen verschiedener Körperoberflächenareale des Rumpfes bei Säuglingen

Summary In two groups of infants (3–53 weeks old) skin temperatures were controlled in different areas of the trunk—i.e.: regions of sternum, lungs, heart, liver, spleen, kidneys—at different room-temperatures (group I: 21–25°C; group II: 29–32°C). Rectal temperatures of some probands in both groups also had been controlled simultaneously. A definite change in the reaction to heat was proofed in different periods of the first year of life. In higher environmental temperatures the skin temperature was almost constant at every controll-point of the skin, even in older infants. In lower environmental temperatures the skin temperatures lowered continuously with age till 7. to 9. moth. From 10. to 12. month the lowering of skin temperature discontinued. The rectal temperatures were relatively constant in all infants. Only in infants from 7. to 12. month, whose skin temperatures were controlled in lower as well as in higher environmental temperatures, a tendency to higher rectal temperatures was proofed in warmer environmental temperatures.The significance of these results is discussed.

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Untersuchungen mit Unterstützung durch die Deutsche Forschungsgemeinschaft.