儿童急性白血病细胞周期蛋白D1表达的研究

目的 　探讨细胞周期蛋白D1 (cyclinD1 )的表达与儿童急性白血病 (AL)的关系。方法 　采集 50例初发或复发的儿童AL患者 (AL组 )和 2 6例完全缓解AL(AL-CR组 )患者作为病例组 ,2 3例非肿瘤性疾病患者作为对照组。运用超敏SP免疫组织化学法 ,检测骨髓细胞中cyclinDl的表达情况。结果 　cyclinD1阳性率在AL、AL-CR和对照组中分别为 56 %、3 85%和 0 ,AL组明显高于AL -CR组和对照组 (P <0 0 1 ) ;AL组中的高危AL和标危AL阳性率分别为 86 36 %、32 1 4 % ,两者有显著差异 (P <0 0 1 )。结论　cyclinD1在儿童AL患者的表达率较高 ,它可能与AL的发病有关 ,而且可作为预后和疗效观察的指标。     

儿童急性白血病Notch1和Jagged1的基因表达

目的：探讨儿童急性白血病（AL）骨髓或外周血单个核细胞中Notch1和Jagged1基因表达及其在AL发病中的可能作用。方法：收集2009年2月至2011年7月初诊的47例AL患儿和20例正常或非恶性血液病儿童（对照组）骨髓或外周血单个核细胞,采用二步法半定量逆转录聚合酶链反应（RT-PCR）方法检测骨髓或外周血中Notch1和Jagged1基因表达情况。47例AL患儿中,急性淋巴细胞白血病（ALL）32例,其中B-ALL 26例,T-ALL 6例;急性髓细胞白血病（AML）15例。结果：ALL组及AML组Notch1基因阳性率高于对照组,差异均有统计学意义（P<0.05）。T-ALL患儿Notch1 基因表达水平高于B-ALL患儿,差异有统计学意义（P<0.01）。ALL组及AML组Jagged1基因阳性率与对照组比较差异无统计学意义,但ALL组及AML组Jagged1表达水平均高于对照组,差异有统计学意义（P<0.05）。结论：Notch1在儿童不同类型ALL中的表达有明显差异,T-ALL 患儿中的Notch1表达明显高于B-ALL患儿;在儿童AL细胞中,普遍存在Notch1信号的活化;Notch1在AML儿童中异常表达,提示Notch1在AML儿童中也起着重要作用。Jagged1在ALL及AML儿童中异常表达,但需要收集更多资料论证。     

急性白血病患儿骨髓细胞环氧合酶-2和survivin表达及其意义

目的探讨环氧合酶-2(COX-2)和survivin蛋白在儿童急性白血病(AL)中的表达及意义。方法应用免疫组织化学链霉亲和素-生物素-过氧化物酶(SABC)法检测2006年6～11月收治42例AL患儿骨髓细胞中COX-2和survivin的表达,对照组为10例非恶性血液病且骨髓正常儿童。结果AL患儿COX-2和survivin表达阳性率分别为52.4%和45.2%,与对照组比较差异有显著性(Pa<0.05)。其中32例急性淋巴细胞白血病(ALL)COX-2和survivin的表达阳性率分别为46.9%和40.6%,与对照组比较差异有显著性(Pa<0.05)。ALL高危组和中低危组COX-2阳性表达率分别为54.5%和42.8%,二组比较差异无统计学意义(Pa>0.05)。AL42例COX-2与survivin表达均为阳性16例,均为阴性17例,COX-2和survivin蛋白表达呈正相关(r=0.579P<0.001)。COX-2阴性组初次完全缓解率高于阳性组(93.3%和66.7%),差异有显著性(P<0.05)。结论1.COX-2蛋白在儿童AL中表达增高;2.COX-2与抗凋亡因子survivin共同参与AL发展,二者可能起协同作用;3.COX-2高表达可能与儿童AL预后有关。     

HA117编码蛋白、P-gp和bcl-2在儿童急性白血病中的表达及意义

目的 探讨HA117编码蛋白、B细胞白血病/淋巴瘤-2（bcl-2）和P-糖蛋白（P-gp）在急性白血病（AL）患儿骨髓单个核细胞中的表达及临床意义.方法 通过免疫组织化学（SP）方法检测37例AL患儿中HA117编码蛋白、bcl-2、P-gp的表达情况,以15例非恶性血液病患儿为对照.结果 （1）AL组患儿HAll7编码蛋白、bcl-2及P-gp的阳性表达率分别为64.86％、62.16％和37.84％;AL组HA117编码蛋白表达阳性率明显高于对照组（P =0.033）;三种蛋白在急性髓细胞白血病组和急性淋巴细胞白血病组表达阳性率差异无显著性.（2）HA117编码蛋白在初诊组表达阳性率明显高于对照组（P =0.021）,而完全缓解组与对照组比较差异无显著性（P =0.098）.（3）AL患儿HAll7编码蛋白与bcl-2的表达水平呈正相关性（P=0.0001,r=0.593）.结论 新基因HA117可能参与了儿童AL的耐药机制,对儿童AL的预后有一定的预示作用,并在肿瘤的发生、发展和耐药中可能与抗凋亡基因bcl-2存在协同作用.     

同源盒基因HOXA9在儿童急性白血病中的表达及其临床意义

目的：研究同源盒基因HOXA9在儿童急性白血病（AL）患儿骨髓单个核细胞中的表达,并探讨其临床意义。方法：采用RT-PCR方法检测46例不同时期AL患儿HOXA9 mRNA的表达水平,以15例特发性血小板减少性紫癜（ITP）患儿作为对照。结果：46例AL患儿（52份骨髓标本）HOXA9基因阳性表达率为63%,其中急性髓细胞白血病(AML)组阳性表达率（86%）明显高于急性淋巴细胞白血病（ALL）组（35%）及对照组（13%）（P<0.05）; AML组HOXA9 mRNA表达水平明显高于ALL组及对照组（P<0.05）。HOXA9在各型儿童AML中表达不同,mRNA相对表达水平依次为：M5型＞M4型＞M1和（或）M2型,而在M3型中未检测到表达。HOXA9在AML患儿高危组中的阳性表达水平较高。AML患儿初治组HOXA9基因阳性表达率及mRNA水平明显高于缓解组和对照组（P<0.05）,而缓解组与对照组比较差异无统计学意义;未缓解组HOXA9基因表达显著高于缓解组和对照组（P<0.05）。结论：HOXA9基因高表达与AL的发生相关;AML患儿HOXA9基因表达水平明显高于ALL患儿。HOXA9基因高表达者与白血病危险程度有关,且提示预后不良。因此,HOXA9基因有望成为儿童AL诊断、治疗及判断预后的一个靶点。     

细胞外信号调节激酶-1、细胞周期蛋白D1表达与儿童急性白血病关系研究

目的探讨细胞外信号调节激酶_1(ERK1)、细胞周期蛋白D1(cyclinD1)的表达与儿童急性白血病(AL)的关系。方法50例儿童AL(AL组)和26例AL完全缓解(AL_CR组)患儿为病例组,23例非肿瘤性疾病患儿为对照组,采用超敏SP免疫组织化学法,检测各组骨髓细胞中ERK1、cyclinD1的表达情况。结果AL组ERK1、cyclinD1阳性率分别为68.00%和56.00%,明显高于AL_CR组(3.85%,3.85%)和对照组(0,0)(P<0.01);高危AL患儿中阳性率分别为90.91%、86.36%,明显高于标危AL患儿(P<0.01);16例AL患儿化疗前ERK1、cyclinD1阳性率分别为75.00%、68.75%,化疗缓解后阳性率均为0(P<0.01);AL组中ERK1、cyclinD1表达相同(χ2=2.5,P>0.05)。结论AL患儿ERK1、cyclinD1表达率较高,可作为近期疗效的观察指标;ERK1与cyclinD1过度表达相同,可能在AL发生发展过程中有协同作用。     

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目的探讨细胞周期蛋白D3、E的表达与儿童急性白血病(AL)的关系。方法采用免疫组织化学法,对广西医科大学第一附属医院儿科2002年1月至2004年5月收治的50例初发或复发儿童AL,其中急性淋巴细胞白血病(ALL)30例(高危ALL12例,标危ALL18例),急性非淋巴细胞白血病(ANLL)20例,和26例完全缓解AL(AL CR)患儿,以及23例同期住院的非恶性疾病患儿(对照组),检测其骨髓细胞中细胞周期蛋白D3、E的表达情况。结果AL组中细胞周期蛋白D3、E阳性率分别为54%和46%,高于AL CR组和对照组(P<0.01);在ALL和ANLL间差异无显著性(P>0.05)。高危ALL细胞周期蛋白D3阳性率明显高于标危ALL(P<0.01)。化疗前细胞周期蛋白D3、E表达阳性率明显高于化疗缓解后(P<0.01)。细胞周期蛋白D3、E在AL组中的表达呈正相关(r=0.5298,P<0.01)。结论细胞周期蛋白D3、E与儿童AL发病有关,它们的表达存在相关性,可作为疗效观察的指标;细胞周期蛋白D3可能与患儿不良预后有关。     

黑色素瘤特异性抗原基因在儿童急性白血病中的表达及初步应用

目的探讨急性白血病(AL)儿童骨髓及外周血单个核细胞(MNC)中黑色素瘤特异性抗原(PRAME)基因表达情况,以及用于微小残留病监测的临床意义。方法釆用半定量逆转录聚合酶链反应(RT-PCR)方法检测31例初发、6例复发、10例完全缓解期AL儿童骨髓及外周血PRAME mRNA的表达情况,同时检测10例非血液系统恶性疾病患儿骨髓、5例正常成人外周血中PRAME mRNA的表达情况,分析该基因与疗效、预后之间的关系。结果 37例初发及复发AL病例中15例PRAME mRNA表达阳性(40.5%),其中在急性淋巴细胞白血病(ALL)组、急性髓系白血病(ANLL)组的阳性率分别为37.9%、50.0%,两组比较差异无显著性(P0.05)。在初发组及复发组的表达率分别为38.7%、50.0%,两组比较差异无显著性(P0.05)。10例完全缓解期及15例对照组病例中PRAME mRNA表达均阴性。PRAME基因表达阳性的患儿完全缓解率(CR)显著低于表达阴性的患儿(CR率分别为60.0%,90.99%,P=0.042)。随访1例初诊PRAME基因表达阳性的ALL患儿,经化学治疗达完全缓解后PRAME基因表达转阴。结论 PRAME基因可在AL患儿中呈阳性表达,并可随疾病的缓解情况逐渐降低或转阴。因此,PRAME基因作为儿童AL的一个重要基因标记物,动态监测其表达水平在评估疗效、判断预后、预测复发方面有一定的意义。     

细胞外信号调节激酶-1的表达与儿童急性白血病近期疗效关系的研究

目的 探讨细胞外信号调节激酶-1（extracelluar signal-regulated kinase-1，ERK1）的表达与儿童急性白血病（AL）的关系。方法 50例儿童AL（AL组）和26例完全缓解AL（AL-CR组）患者为病例组，23例非肿瘤性疾病患者为对照组。采用超敏SP免疫组织化学法，检测病例组、对照组骨髓细胞中ERKI的表达情况。结果 ERKI阳性率在AL组为68％，明显高于AL-CR组和对照组（P〈0．01）：在高危AL中阳性率分别为90．91％，明显高于标危AL（P〈0．01）。16例化疗前ERKI阳性率为75％，化疗缓解后阳性率为0（P〈0．01）。结论 AL患者ERKI的过度表达率较高，可作为近期疗效观察的指标。     

急性白血病患儿mdr1基因定量表达的研究

目的应用新型MGB探针的实时荧光定量聚合酶链反应(FQ-PCR)分析方法,研究mdr1 mRNA在K562细胞系和其耐药细胞系K562/A02细胞及急性白血病(AL)患儿细胞中的表达水平。方法运用Taq Man-MGB探针,以含有目的基因mdr1cDNA的质粒pHaMDR1/A为阳性模板,设立实时FQ-PCR反应体系,研究mdr1 mRNA在不同类型、不同分期AL患儿白血病细胞中的表达;并就AL患儿初治组、难治复发组、完全缓解组分别与正常对照组比较其mdr1 mRNA表达率和表达量,且在AL患儿3组间再作mdr1 mRNA表达率及其表达量比较,数据均作统计学处理。结果初治和完全缓解期AL患儿mdr1 mRNA表达阳性率和表达水平均较正常对照组升高。难治复发组AL患者白血病细胞mdr1 mRNA表达阳性率和表达水平较其他AL各组明显升高;AL完全缓解患者维持期化疗的随访观察中,部分患儿mdr1 mRNA表达量渐升高,尤其是复发AL患儿升高更显著。结论AL患儿化疗耐药的发生与mdr1 mRNA表达有较密切的联系,应用Taq Man-MGB荧光探针进行实时FQ-PCR检测人类mdr1基因在AL细胞中表达,可为AL患儿个体化化疗方案的合理制定、化疗疗效和预后判断及针对性逆转由于mdr1基因表达导致的多药耐药提供有价值的实验室依据。     

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.