��ϸ����ֲ��HLA���ͺ�ֲ��֤�ݼ��

近年来,随着造血干细胞移植(HSCT)在血液系统疾病治疗中的广泛应用,HLA配型和植入证据的检测越来越细化,人们的认识也日益深入。1造血干细胞移植的HLA配型1.1HLA系统主要组织相容性基因组(MHC)在人类亦称人类白细胞抗原系统(HLA),其抗原决定簇位于第6号染色体短臂上,HLA分子可分为Ⅰ、Ⅱ、Ⅲ类,其中Ⅰ、Ⅱ类基因产物(抗原)直接参与移植免疫反应,Ⅲ类抗原起间接作用。HLA-Ⅰ类主要包括HLA-A、B、C位点,Ⅱ类主要包括HLA-DR、DP、DQ位点。在DR中可以识别9种DRB,每个个体都有DRB1或(和)另一种DRB。一般认为HLA-A,B和DRB…     

人类白细胞抗原-Ⅰ基因多态性与急性淋巴细胞白血病的相关性

目的对急性淋巴细胞白血病(ALL)患儿进行人类白细胞抗原(HLA)基因多态性分型,寻找ALL的易感基因。方法采用特异性寡核苷酸探针杂交(PCR/SSO)法,对ALL患儿和健康对照组进行HLA-A、B基因分型。结果ALL患儿HLA-A01基因位点较健康对照组明显升高[χ2=4.947P=0.026,相对危险率(RR)=10.20]、A02基因位点较对照组降低(χ2=4.187P=0.041,RR=3.13)、A33基因位点较对照组降低(χ2=4.403P=0.036,RR=0.21)。结论HLA-A01、A33与小儿ALL有遗传相关性,其中A01为ALL发生的危险因素;而HLA-A33基因对儿童ALL有遗传拮抗作用。     

����������Ⱥ�Ц�-L������ȩ��ø�����̬���о�

目的探讨辽宁地区粘多糖贮积症Ⅰ型(MPS-Ⅰ)患者及正常人群中α-L艾杜糖醛酸酶(IDUA)基因的多态性分布情况。方法采用PCR、RFLP和DNA测序的方法检测1999年10月至2002年2月辽宁地区20例MPS-Ⅰ型患儿以及120名正常人群中IDUA基因的多态性分布情况。结果发现辽宁地区MPS-Ⅰ型患儿及正常人群中IDUA基因存在4种多态性位点R105Q、L118、A314和A361T;位于外显子Ⅲ的多态性位点L118在MPS-Ⅰ型患者中的频率为45%,而在正常人群中的频率为18%。结论辽宁地区人群中IDUA基因存在4种多态性位点R105Q、L118、A314和A361T,其中L118在MPS-Ⅰ型患儿和正常人群中出现的频率具有明显的差异。     

维生素D受体基因Fok Ⅰ、Taq Ⅰ多态性与女性婴幼儿佝偻病的相关性

目的 研究维牛素D受体(VDR)基因FokⅠ、TaqⅠ多态性分布及其与女性婴幼儿维生素D缺乏性佝偻病的关系,探讨其临床意义.方法 选择男性婴幼儿58例为佝偻病男童组,女性婴幼儿佝偻病60例为佝偻病女童组;健康男、女性婴幼儿62、58例分别为健康对照男童组及女章组;应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析等技术测定各组VDR基因Fok Ⅰ、Taq Ⅰ多态性,分别比较4组VDR基因Fok Ⅰ、Taq Ⅰ多态性分布频率.采用SPSS 13.0软件进行统计学分析.结果 佝偻病女童组与各对照组间比较,VDR的Taq Ⅰ基因型和等位基因分布频率均无显著性差异(Pa＞0.05).Fok Ⅰ基因型和等位基因分布频率在佝偻病女童组与健康对照女童组和健康对照男章组比较均有显著性差异(P=0,0,0.001,0.002);佝偻病女童组与佝偻病男童组比较无显著性差异(P＞0.05).结论 VDR基因部分位点多态性可能与女性婴幼儿佝偻病显著相关;VDR基因多态性在婴幼儿佝偻病中无性别差异.     

儿童系统性红斑狼疮与HLA基因单倍型和基因型的相关性及家系分析

目的 探讨HLA基因连锁不平衡情况对儿童SLE发病的影响,以期发现HLA基因在SLE发病中的作用。方法 53例SLE患儿,其中40例有父母资料,35例HLA-DRB*15阳性的SLE患儿,其中有父母资料者27例,78名健康对照儿童,43名有父母资料,及1个SLE大家系作为研究对象,应用微量淋巴毒实验,序列特异性引物聚合酶链反应方法,分析了研究对象的HLA-I类抗原A、B位点,HLA-Ⅱ类基因。DRBI位点的多态性。根据实测的单倍型及基因型情况与正常对比,分析了SLE患儿与HLA-A、B、DR单倍型及基因型的相关性,并分析了DRB1*15阳性的SLE患儿其DRB1*15基因来自父母的垂直传递情况。结果 (1)患儿比正常对照单倍型种类少,患儿与对照共有单倍型较少。单倍型A9B40DRB1*15频率在SLE患儿中较对照高,SLE大家系的研究中,也恰恰表现为A9B40DRB1*15单倍型与患病相连锁。(2)SLE患儿基因型以DRB1*09／DRB1*15及DRB1*03／。DRB1*15多见。(3)在父母携带DRB1*15基因相同的情况下,SLE患儿的DRB1*15基因来源于父亲者较正常对照多。结论 SLE发病不仅与单个HLA基因有关,而且与HLA的某些基因组合相关,由此可见SLE多发位点的致病作用有叠加性。SLE患儿DRB1*15来自父亲者较对照组多,其机理及意义尚不清楚,可能与HLA的遗传模式有关。     

Clara细胞分泌蛋白10基因G38A多态性与5岁以下喘息患儿的相关性

目的探讨5岁以下喘息患儿Clara细胞分泌蛋白10(CC10)基因G38A位点多态性与喘息发病机制的关系。方法随机选取于本院就诊的5岁以下反复喘息患儿120例,分为有特应质高危因素的喘息Ⅰ组(n=67)(湿疹45例,父母或父母一方有哮喘病史13例,变应性鼻炎5例,变应性皮炎4例)和无特应质高危因素的喘息Ⅱ组(n=53);对照组为本院外科近期无感染疾病史、择期进行手术的术前患儿(n=55)。采用PCR-限制性片段长度多态性分析对喘息组和对照组患儿CC10 G38A位点基因型频率和等位基因频率进行检测,比较3组间CC10 G38A位点基因型频率和等位基因频率。结果喘息Ⅰ组、喘息Ⅱ组和对照组3种基因型AA、GA、GG分布频率分别为20.9%、44.8%、34.3%,9.4%、32.1%、58.5%、9.1%、31.0%、60.0%;喘息Ⅰ组和喘息Ⅱ组CC10基因G38A位点基因型频率比较差异有统计学意义(P<0.05);喘息Ⅰ组和对照组CC10基因G38A位点基因型频率比较差异亦具有统计学意义(P<0.05)。喘息Ⅰ组、喘息Ⅱ组和对照组38A和38G等位基因频率分别为43.3%、56.7%,25.5%、74.5%,24.5%、75.5%;喘息Ⅰ组和喘息Ⅱ组、喘息Ⅰ组和对照组比较差异均有统计学意义(Pa<0.05)。结论喘息患儿与哮喘存在相同的基因分布频率,发生哮喘的危险性高;对于CC10基因具有A等位基因的喘息患儿应密切关注。     

糖皮质激素在儿童特发性缺血性中风治疗中的作用

目的　观察糖皮质激素在治疗儿童特发性缺血性中风中的作用。方法　对 2 2例患儿采取对照开放式研究 ,分为加用糖皮质激素组和不用组两组 ,并对其临床效果进行评估。结果　试验组治疗前后神经功能缺损改善度较对照组有显著性差异 (P <0 .0 5 ) ,应用糖皮质激素治疗儿童特发性缺血性中风临床疗效明显优于未使用的患儿。结论　糖皮质激素可能从病因上治疗儿童特发性缺血性中风 ,提示本病可能是一种免疫性血管炎     

广西地区儿童维生素D受体基因Fok Ⅰ位点多态性分布研究

目的 了解维生索D受体基因Fok Ⅰ位点多态性在广西地区儿童中的分布.方法 应用聚合酶链反应-限制性片段长度多态性技术和基因测序技术,检测268名广西地区儿童的维生索D受体基因Fok Ⅰ位点多态性.结果 维生素D受体基因型FF、Ff、ff在研究人群的分布频率分别为29.85%、48.13%、22.02%,F、f等位基因频率为54.66%和45.34%.结论 中国广西地区儿童维生素D受体基因Fok Ⅰ多态性分布频率有其自身的特点.     

上海市哮喘儿童与β2-肾上腺素能受体基因多态性的关系

目的 探讨β2-肾上腺素能受体(β2AR)基因多态性与上海市儿童哮喘的关系.方法 2005年11月-2007年1月本院儿科住院及门诊哮喘患儿57例.男34例,女23例;年龄(4.98±2.78)岁.根据哮喘发作程度分为间歇和轻度发作组(36例)、中重度发作组(21例).同期门诊健康体检儿童62例为健康对照组.男30例,女32例;年龄(5.30±3.40)岁.抽取各组儿童清晨空腹肘静脉血3mL.应用序列特异引物PCR(SSP-PCR)技术,对哮喘组和健康对照组儿童β2AR精氨酸(Arg)16甘氨酸(Gly)和谷氨酰胺(Gln)27谷氨酸(Glu)位点基因多态性进行分析,采用化学发光免疫方法测定各组儿童血清总IgE水平.应用SPSS 10.0软件进行统计学分析.结果 1)哮喘和健康对照组儿童Arg16Gly位点等位基因、基因型频率(x2=0.449,1.396 Pa>0.05)及Gln27Glu位点等位基因、基因型频率(x2=1.315,1.544 Pa>0.05)比较差异均无显著性意义.2)16位点Gly16纯合子在中重度哮喘中的分布显著高于间歇和轻度发作组(x2=7.049 P<0.05);27位点各基因型在间歇和轻度发作组与中重度发作组中的分布比较无显著差异(x2=1.265 P>0.05).3)哮喘组各位点基因型血清总IgE水平比较差异无显著性意义(F=0.105,0.10 Pa>0.05).结论 β2AR Gly16纯合子基因型与上海市儿童哮喘的严重程度相关,可能是严重哮喘的重要遗传因素.     

COL9A1基因在单纯性马蹄内翻足中的表达及其多态性分析

目的：COL9A1 基因是位于单纯性马蹄内翻足（ICTEV）易感区域(6q12-13)的已知基因。本研究探讨 COL9A1 基因在 ICTEV 患者中的表达及其单核苷酸多态 (SNP) 位点在ICTEV 和正常人中的分布情况。方法：应用免疫组化方法检测 25 例 ICTEV 患儿及 5 例正常对照组肌肉及肌腱组织中 COL9A1 的表达;应用限制性片段长度多态性技术结合测序法,分析 118 例 ICTEV 患者及 100 名正常人 COL9A1 基因的 2 个 SNP位点基因型。结果：88%（22/25）的 ICTEV 患者 COL9A1蛋白表达阳性,明显高于正常对照组。位于 COL9A1 基因编码区的 SNP 位点 rs1135056 的基因型频率和等位基因频率在两组人群中的分布差异有统计学意义（P<0.05）：ICTEV 组 G 等位基因频率高于对照组;与对照组相比,AA 基因型频率降低,AG、GG 基因型频率增高。结论：COL9A1 基因在 ICTEV 中高表达,rs1135056多态位点G等位基因和ICTEV的发生相关。     

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   

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.     

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.     

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.

---

---

Untersuchungen mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Psychopathologie du syndrome d’Asperger et « aspérigisation » de la société contemporaine

The author has attempted here to point out, just for a start, the characteristics of Asperger syndrome from the point of view of psychopathology through a rereading of Hans Asperger's original paper (1944). This thesis merits reevaluation, if for no other reason than to fill the gaps in operational diagnostics based on the DSM. It is found by rereading that Asperger's view of the principal disturbances of autistic psychopathy include a “disturbance of natural evidence” or a “crisis of common sense”. This question of natural evidence that he evokes with regard to autistic psychopathy corresponds to W. Blankenburg's natural evidence, which constitutes a key concept for comprehending schizophrenia in the form poor-symptom (“symptomarme Schizophrenie”) that he observes in the speech of his patient Anne Rau. One can deduce from this that in terms of fundamental disturbances, Asperger syndrome and this “symptom-poor” schizophrenia overlap at the level of loss of natural evidence. It is moreover possible to classify Asperger syndrome among the disturbances of spacing in the sense meant by the evolutionary psychiatry of A. Stevens and J. Price. The author then develops our comprehension of Asperger syndrome from the point of view of the perspective proposed by the notion of resilience in people with Asperger syndrome and of the possibility for them, through these mechanisms of adaptation, to find in the organization of the personality of the “as if” type a position of relative equilibrium. They concur or overlap in the creation of crutches, of borrowed personalities secondarily legitimated by the reaction of the socius. This will end up in the production of inventions and œuvres (works). Clearly, one rarely encounters several cases that one could consider pertinently to be “successful” Asperger syndrome. Finally, the author notes that one can find a sort of isomorphism between Asperger syndrome and contemporary society when he proposes the term “asperigisation” to characterize our society, given that the equilibrium between emotion and logic is strongly disturbed in these patients, in whom logic undergoes hypertrophy while emotion is impoverished. From this perspective, the author hopes to suggest reasons for the increase in the number of cases of Asperger syndrome in the clinical setting and in society in general in our contemporary era.     

Bibliometric data: a disaster for many non-American biomedical journals

Bibliometric data published by the Institute of Scientific Information in Philadelphia (ISI), and which was previously discussed in Acta Paediatrica , has increasingly been used despite all the relevant and severe criticism that has been raised against this method of evaluating individual research results and grading scientific journals. It is obvious that the present trend regarding the use of bibliometric data as a basis for priorities and funding of research and for the promotion of individual scientists favours American-oriented research projects at the expense of those that are based on concepts of predominantly European relevance.

Conclusion: For the future of non-American research, it is important that no single super-power, i.e. the USA, should dominate scientific priorities. The condition for efficient European competition is that European Centres with high levels of competence for creative research and training of scientists from all over the world are established. In addition, it is important that the results of European research are published in prestigious European journals, as was the situation before World War II.     

�¶�֢��ϵ�ϰ���ע��ȱ�ݶද�ϰ������ڵ�ת��

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     

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.     

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.