肺表面活性物质蛋白B基因多态性与新生儿呼吸窘迫综合征易感性的相关性研究

目的：研究肺表面活性物质蛋白（SP）B基因单核苷酸多态性分布以及与新生儿呼吸窘迫综合征（RDS）的关系。方法：选择88例RDS早产儿和未并发RDS的早产儿103例作为研究对象,采用DNA提取试剂盒提取DNA,应用聚合酶联反应-限制性片段长度多态性技术检测SP-B-18A/C、SP-B 1580C/T两个位点的单核苷酸多态性,分析两个位点多态性与RDS的关系。结果：SP-B -18A/C、SP-B 1580C/T两个位点在病例组和对照组中均存在多态性,与未并发RDS的早产儿对照组比较,RDS患儿SP-B 1580C/T位点基因型以CC型明显增多,（χ2=12.26,P0.05）。结论：SP-B 1580 位点C/T多态性与RDS有关,SP-B 1580C/T可能是RDS的易感基因,携带SP-B 1580位点C等位基因的个体患RDS的风险增加。SP-B-18A/C与RDS无关。     

武汉汉族新生儿肺表面活性物质蛋白B基因多态性频率分布

目的了解武汉汉族新生儿肺表面活性物质蛋白B(SP-B)基因多态性频率分布。方法采用PCR-限制性片段长度多态性分析技术和基因测序技术对武汉汉族新生儿286例(男205例,女81例)进行SP-B 1580C/T位点基因型频率检测,并将武汉汉族新生儿SP-B 1580C/T等位基因频率与德国高加索人、美国白种人及日本人比较。结果武汉汉族新生儿SP-B 1580位点基因型CC、CT、TT频率分别为44.8%、47.6%和7.6%,等位基因C和T频率分别为68.5%和31.5%;不同性别、出生体质量、胎龄新生儿SP-B 1580位点的基因型及等位基因频率比较均无统计学差异。武汉汉族新生儿SP-B 1580等位基因频率与德国高加索人和美国白种人相比均有统计学差异(Pa<0.01),但与日本人比较差异无统计学意义。结论武汉汉族新生儿SP-B 1580基因型及等位基因频率在不同性别、出生体质量、胎龄中无明显关联。不同种族人群SP-B 1580C/T基因多态性分布存在明显差异。     

肺泡表面活性物质蛋白B基因多态性与支气管肺发育不良易感性的关系

目的 了解肺泡表面活性物质蛋白B(SPB)-18A/C和SPB 1580C/T基因多态性与支气管肺发育不良(BPD)易感性的关系.方法 应用聚合酶链反应-限制性片段长度多态分析技术及基因测序技术检测57例BPD患儿及103例同胎龄无BPD早产儿的SPB-18及SPB 1580基因多态性,比较2组SPB-18及SPB 1580基因型和基因分布的差异.结果 1.SPB-18A/C基因型在BPD组与对照组AA、AC、CC基因型频率分别为14.0%、45.6%、40.4%和4.9%、31.1%、64.1%;A等位基因增加新生儿患BPD的风险:AC/CC与AA/CC 的OR值分别为2.3(95%CI 1.2~4.7,P=0.02)和4.7(95%CI 1.4~16.2,P=0.01);2.SPB 1580C/T基因型在对照组和BPD组TT、CT、TT分布分别为6.8%、45.6%、47.6%和12.3%、40.4%、47.4%,对照组和BPD组比较差异无统计学意义(χ2=1.50, P＞0.05).结论 中国武汉汉族人中SPB-18基因多态性是BPD的危险因素,基因型为AA者是BPD易感人群.SPB 1580 C/T基因多态性与BPD发病无明显相关性.     

肺表面活性物质蛋白 B、C 基因变异与蒙古族早产儿 呼吸窘迫综合征相关性研究

目的研究肺表面活性物质蛋白(SP)B、SP-C基因外显子4(exon4)区域基因变异与蒙古族早产儿呼吸窘迫综合征(RDS)的相关性。方法选择住院治疗的无血缘关系的蒙古族RDS早产儿50例(男31例,女19例),同期、同民族和同群体中无血缘关系的非RDS早产儿50例为对照组(男27例,女23例),分别用聚合酶链式反应(PCR)基因多态性分析和基因检测技术对SP-B、SP-C基因exon4区域基因进行测序,并比较两组患儿SP-B基因exon4区域1580位点基因变异及基因型频率、SP-C基因exon4区域c.571C A(T138N)位点基因变异及基因型频率的差异。结果检测出SP-B基因exon4区域1580位点基因变异,RDS组14例,变异率为28%,非RDS组11例,变异率为22%,两组差异无统计学意义(χ2=0.480,P 0.05)。RDS组1580位点CC、TT、CT基因型频率分别为16%、72%和12%,非RDS组则分别为10%、78%和12%;RDS组C等位基因频率为22%、T等位基因频率为78%,非RDS组则分别为16%、84%;两组间基因型频率差异无统计学意义(χ~2=1.170,P 0.05)。检测出SP-C基因exon 4区域c.571 C A(T 138 N)位点基因变异,RDS组41例,变异率为82%,非RDS组6例,变异率为12%,两组间差异有统计学意义(χ~2 =49.177,P 0.05)。RDS组c.571C A(T138N)位点CC、AA、AC三种基因型频率分别为18%、50%和32%,非RDS组分别为88%、8%和4%;RDS组C等位基因频率为34%、A等位基因频率为66%,非RDS组则分别为90%、10%,两组间A等位基因型频率的差异有统计学意义(χ~2=66.553,P 0.05)。结论携带SP-C基因exon 4区域c.571 C A(T 138 N)位点A等位基因的蒙古族早产儿患RDS的风险更高,而SP-B基因exon 4区域1580位点基因变异与蒙古族早产儿发生RDS无关。     

支气管肺发育不良与遗传因素的相关分析

目的探讨肺表面蛋白A(SPA)和肺表面蛋白B(SPB)基因多态性与支气管肺发育不良(BPD)的相关性。方法运用PCR-限制性片段长度多态性(RFLP)和基因测序方法检测BPD组(51例)和对照组(103例)新生儿的SPA1AA50G/C、SPA1AA219C/T、SPB-18A/C、SPB1580C/T基因型频率和等位基因频率。结合临床参数,运用χ2检验、Fisher’s精确概率法及多因素Lo-gistic回归分析统计学方法分析与BPD发病有关的危险因素。结果 SPA1AA219C/T和SPB1580C/T等位基因和基因型频率在BPD组和对照组中比较差异无统计学意义,而SPA1AA50等位基因G、基因型GG和GC及SPB-18等位基因A、基因型AA和AC分布频率在BPD组中明显高于对照组,差异均有统计学意义(Pa<0.05)。临床参数中,BPD组出生体质量、胎龄、经鼻持续正压通气(CPAP)、机械通气、出生后应用地塞米松、颅内出血和PDA与对照组比较差异均有统计学意义(Pa<0.05)。多因素Logistic回归分析显示,BPD与CPAP、出生后应用地塞米松、颅内出血、SPA1AA50基因型GG和GC及SPB-18基因型AA、AC无关,而与机械通气和PDA呈正相关,与出生体质量、胎龄呈负相关。结论 SPA1AA50G/C、SPB-18A/C不是BPD发病的遗传易感基因。机械通气和PDA是BPD的高危因素,出生体质量和胎龄是其保护因素。     

SP-B 外显子4（T131I）位点与蒙古族新生儿呼吸窘迫综合征相关性研究

目的探讨SP-B外显子4(T131I)位点与内蒙古西部地区新生儿呼吸窘迫综合征(NRDS)易感性的关系。方法采用病例对照研究方法,选择于2009年9月-2016年2月住院诊断为NRDS的蒙古族早产儿86例作为病例组,选择同期未发生NRDS的蒙古族早产儿86例作为对照组。应用聚合酶链反应-单链构象多态(PCR-SSCP)分析技术及基因测序技术检测SP-B基因exon4区域上有无突变,以及T131I位点的基因型、等位基因分布。结果在所有研究对象中,SP-B基因exon 4区域无突变发生,T131I位点基因型均可检出3种基因型,即CC、CT、TT,病例组所占比例分别为58.1%、27.9%、14.0%,对照组分别为40.7%、43.0%、16.3%,两组基因型分布的差异无统计学意义(χ2=5.57,P=0.062);病例组C等位基因频率为80.2%,高于对照组(64.0%),差异有统计学意义(χ~2=11.33,P0.001)。结论 SP-B基因外显子4(T131I)位点基因多态性可能是蒙古族NRDS易感基因之一。     

肺表面活性物质蛋白B基因多态性与新生儿呼吸窘迫综合征易感性的研究

目的 探讨肺泡表面活性物质蛋白B（SPB）基因多态性与新生儿呼吸窘迫综合征易感性的关系。方法 收集华中科技大学同济医学院附属同济医院的新生儿呼吸窘迫综合征（NRDS）诊断病例为病例组,并按1∶2比例收集胎龄和出生体重相匹配的无明显感染症状早产儿为对照组。应用聚合酶链反应 限制性片段长度多态（PCR RFLP）分析技术及基因测序技术检测SPB 18A/C及SPB1580C/T多态性,观察两组间基因型频率和等位基因频率的差异。并复习文献比较本研究汉族与其他种族人群等位基因频率的差异。结果 2008至2010年NRDS组91例,对照组182名进入分析。 ①SPB－18A/C基因在NRDS组AA,AC,CC基因型频率分别为11.0%、40.7%和48.4%,对照组分别为6.6%、31.3%和62.1%;两组基因型频率差异无统计学意义（P>0.05）;NRDS组A等位基因频率显著高于对照组（31.3% vs 22.3%）。②SPB1580C/T基因在NRDS组TT、TC和CC基因型频率分别为5.5%、63.7%和45.1%,对照组分别为30.8%、6.6%和48.4%;两组基因型频率差异无统计学意义（P>0.05）;NRDS组C等位基因频率显著高于对照组（79.1% vs 70.9%）。③本研究汉族人、美国人、巴西人和丹麦人SPB1580等位基因C频率分别为79%、35%、41%和46%,差异有统计学意义（P<0.05）,与日本人群等位基因C频率（72%）差异无统计学意义（P>0.05）;本研究汉族人、巴西人、美国人和丹麦人SPB－18等位基因A频率分别为31%、58%、57%和61%,差异有统计学意义（P<0.05）。结论 本研究汉族人群SPB－18A/C及SPB1580C/T基因多态性是NRDS的危险因素。不同种族人群SPB1580C/T和SPB－18A/C基因多态性分布存在明显差异。     

内蒙古西部地区汉族新生儿呼吸窘迫综合征与SP-B外显子7区域R236C位点的相关性研究

目的通过检测和分析肺表面活性物质蛋白B基因外显子7(exon7)区域上是否存在基因变异,探讨其与内蒙古西部地区汉族新生儿呼吸窘迫综合征(NRDS)发病的关系。方法采用病例对照研究方法,选择祖上三代都居住在内蒙古西部地区的汉族NRDS患儿47例作为病例组,选择同民族和同群体中未发生NRDS的新生儿47例为对照组。通过PCR基因分析技术检测SP-B基因外显子7区域上有无突变,以及SP-B外显子7(R236C)位点的基因型、等位基因分布。结果在内蒙古西部地区汉族新生儿中,SP-B基因外显子7区域无突变发生;SP-B外显子7(R236C)位点基因型均可检出两种基因型(CC、CT),两组中均未检出TT基因型。病例组CC和CT基因型频率分别为72%和28%,C等位基因频率为85%,T等位基因频率为15%。对照组此两种基因型分别为85%和15%,C等位基因频率为93%,T等位基因频率为7%。病例组与对照组此位点基因多态性相比等位基因及基因型频率在两组之间差异无统计学意义(P0.05)。结论内蒙古西部地区汉族NRDS患儿的SP-B基因第7外显子未发现基因突变。未发现SP-B基因外显子7(R236C)位点基因多态性与该地区汉族NRDS的发生有明显相关性。     

儿童特发性间质性肺疾病与肺表面活性物质-B基因多态性的相关性研究

目的 探讨肺表面活性物质(surfactant protein,SP)-B外显子4(T131I)位点的基因多态性与儿童特发性间质性肺疾病的相关性.方法 收集2013年10月至2016年9月在深圳市儿童医院和广西医科大学附属第一医院住院诊断为特发性间质性肺疾病的患儿共67例为病例组,选择同期与特发性间质性肺疾病无关的因呼吸道感染在深圳市儿童医院住院的102例患儿为对照组,采用SP-B全外显子和侧翼区高通量测序法对所有病例采集的标本进行检测,分析外显子4(T131I)位点的基因型和等位基因分布.结果 病例组和对照组SP-B基因外显子 4(T131I)位点的基因型均可检出3 种,CC、CT及TT型,病例组所占比例分别为67.16%、25.37%、7.46%,对照组分别为56.86%、35.29%、7.84%,两组基因型分布的差异无统计学意义(χ2=1.981,P=0.371);病例组C等位基因频率为79.85%,对照组为74.51%,差异无统计学意义(χ2=1.288,P=0.256).对照组SP-B基因外显子 4(T131I)位点的基因突变频率为43.14%(44/102),与人类基因组千人人群数据库基因突变频率平均值52.00%比较,差异无统计学意义(P>0.05);与欧洲千人人群数据库基因突变频率53.88%、南亚千人人群数据库基因突变频率45.50%和美洲整体人群数据库基因突变频率41.93%比较,差异无统计学意义(P>0.05),而与东亚千人人群数据库基因突变频率26.39%和非洲千人人群数据库基因突变频率80.18%比较,差异有统计学意义(P<0.05).结论 SP-B 基因外显子4(T131I)位点的基因多态性与儿童特发性间质性肺疾病易感性不存在相关性,外显子4(T131I)位点的基因突变频率与种族人群和地域具有一定的差异性.     

白细胞介素-8-251A/T和781C/T基因多态性与呼吸道合胞病毒毛细支气管炎的相关性

目的 探讨白细胞介素-8(IL-8)-251A/T和781C/T基因多态性与呼吸道合胞病毒(RSV)毛细支气管炎易感性的关系.方法 应用聚合酶链反应-限制性酶切片段长度多态性技术检测150例RSV毛细支气管炎患儿和120例健康对照儿童血IL-8-251A/T和781C/T的单核苷酸多态性(SNP),分析其基因型、等位基因型的分布,并对2个SNP位点进行连锁和单体型分析.结果 1.病例组和健康对照组均发现IL-8-251A/T位点基因多态性,均可见AA、AT和TT 3种基因型;其中病例组AA、AT、TT基因型频率分别为12.0%、56.7%、31.3%,A、T等位基因频率分别为40.3%、59.7%;健康对照组AA、AT、TT基因型频率分别为7.5%、54.2%、38.3%,A、T等位基因频率分别为34.6%、65.4%;病例组IL-8-251A/T基因型及等位基因频率与健康对照组比较,差异均无统计学意义(x2=2.373,1.875 P0.05).2.病例组和健康对照组均发现IL-8 781C/T位点基因多态性,均可见CC、CT、TT3种基因型;其中病例组CC、CT、TT基因型频率分别为38.7%、40.7%、20.6%,C、T等位基因频率分别为59.0%、41.0%;健康对照组CC、CT、TT基因型频率分别为40.8%、41.7%、17.5%,C、T等位基因频率分别为61.7%、38.3%,二组基因型及等位基因频率比较,差异均无统计学意义(x2=0.442,0.396 P0.05).3.IL-8-251A和781C是连锁的(D'=0.348±0.019,r2=0.114 P<0.05).4.病例组AC单体型频率显著增加(x2=9.047 P<0.05).结论 IL-8-251A和781C形成的AC单体型与RSV毛细支气管炎易感性相关,即部分RSV毛细支气管炎的易感基因可能存在于含有AC单体型的基因片段或与该段基因紧密连锁.     

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.     

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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.     

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.     

Overcoming surfactant inhibition with polymers

Inhibition of the function of pulmonary surfactant in the alveolar space is an important element of the pathophysiology of many lung diseases, including meconium aspiration syndrome, pneumonia and acute respiratory distress syndrome. The known mechanisms by which surfactant dysfunction occurs are (a) competitive inhibition of phospholipid entry into the surface monolayer (e.g. by plasma proteins), and (b) infiltration and destabilization of the surface film by extraneous lipids (e.g. meconium-derived free fatty acids). Recent data suggest that addition of non-ionic polymers such as dextran and polyethylene glycol to surfactant mixtures may significantly improve resistance to inhibition. Polymers have been found to neutralize the effects of several different inhibitors, and can produce near-complete restoration of surfactant function. The anti-inhibitory properties of polymers, and their possible role as an adjunct to surfactant therapy, deserve further exploration.     

How well are we doing? – Metabolic control in patients with diabetes

OBJECTIVE: To compare the present level of metabolic control in children and adolescents with insulin-dependent diabetes mellitus (IDDM) attending Brisbane paediatric diabetes clinics with published overseas data. METHODOLOGY: Blood HbA1c concentrations, population characteristics, current treatment practices and short-term complications were recorded in all patients, aged 19 years and under, attending the diabetes clinics of the two Brisbane Children's Hospitals or the private practice of one of the authors (MJT) in the first quarter of 1998. RESULTS: Two hundred and sixty-eight patients were assessed (M/F 142/126). Ages ranged from 1 to 19 years (mean 11. 2 years); duration of IDDM was 0-16 years (mean 4.4 years); and 141 (53%) were pubertal. Of those aged less than 13 years, only 4% had more than two injections daily. Insulin doses (U/kg/day) rose with increasing age. Larger doses were required in regimens involving more than two injections per day than those involving one to two injections per day. Ketoacidosis or severe hypoglycaemia in the last 3 months were reported in eight (2.7%) and 17 (6.3%) of patients, respectively. Mean HbA1c (+/- SD) was 8.6 +/- 1.4% (range 5.2-14.0%), with 33% of children having a HbA1c concentration < 8%. HbA1c concentrations were significantly related (P < 0.05) to insulin dose and to duration of diabetes, but not to severe hypoglycaemia, ketoacidosis, age, frequency of injections, or number of clinic visits per year. Mean HbA1c concentration was significantly higher (P < 0.05) in those children in puberty (8.7 +/- 1.5%) than in those not in puberty (8.5 +/- 1.2%). CONCLUSION: Only 33% of patients had a HbA1C concentration less than 8% and 6.3% had a severe hypoglycaemic episode in the 3 months. These results are similar to published overseas data.     

MAINTENANCE OF DIFFERENTIATED FUNCTION OF THE SURFACTANT SYSTEM IN HUMAN FETAL LUNG TYPE II EPITHELIAL CELLS CULTURED ON PLASTIC

We report a simplified culture system for human fetal lung type II cells that maintains surfactant expression. Type II cells isolated from explant cultures of hormone-treated lungs (18-22 wk gestation) by collagenase + trypsin digestion were cultured on plastic for 4 days in serum-free medium containing dexamethasone (Dex, 10 nM) + 8-bromo-cAMP (0.1 mM) + isobutylmethylxanthine (0.1 mM) or were untreated (control). Surfactant protein (SP) mRNAs decreased markedly in control cells between days 1 and 4 of culture, but mRNA levels were high in treated cells on day 4 (SP-A, SP-B, SP-C, SP-D; 600%, 100%, 85%, 130% of day 0 content, respectively) . Dex or cAMP alone increased SP-B, SP-C, and SP-D mRNAs and together had additive effects. The greatest increase in SP-A mRNA occurred with cAMP alone. Treated cells processed pro-SP-B and pro-SP-C proteins to mature forms and had a higher rate of phosphatidylcholine (PC) synthesis (2-fold) and higher saturation of PC (~34% versus 27%) than controls. Only treated cells maintained secretagogue-responsive phospholipid synthesis. By electron microscopy, the treated cells retained lamellar bodies and extensive microvilli. We conclude that Dex and cAMP additively stimulate expression of surfactant components in isolated fetal type II cells, providing a simplified culture system for investigation of surfactant-related, and perhaps other, type II cell functions.