Comprehensive genetic analysis of overlapping syndromes of RAS/RAF/MEK/ERK pathway

Background: Germline mutations in several members of RAS/RAF/MEK/ERK pathway cause clinically similar genetic disorders, including Noonan syndrome (NS), Costello syndrome (CS) and cardio‐facio‐cutaneous syndrome (CFC). Each of these syndromes has a wide spectrum of molecular etiology. The aim of the present study was to conduct a comprehensive genetic analysis of RAS/RAF/MEK/ERK pathway in these syndromes. Methods: Three patients with NS and two patients with CS/CFC were examined. Peripheral blood samples were collected from all patients as well as from 100 healthy Japanese volunteers. The protein phosphatase, non‐receptor type II (PTPN11), KRAS, HRAS, NRAS, BRAF, RAF1, Son of Sevenless (SOS1) and MEK1genes were analyzed. Results: In a patient with a severe Noonan phenotype, a rare PTPN11 mutation was detected: A to G transition at position 172, causing an N58D substitution within the N‐SH2 domain. In a CS/CFC patient no HRAS mutations were found, but a novel SOS1 missense mutation was found: A to G transition at position 473, causing a T158A substitution within domain of histone‐like fold (HF). Conclusions: A case mimicking CS with SOS1 T158A substitution, which has not been reported previously in CS, revealed the complex relationship between the genotype and phenotype of overlapping syndromes of the RAS/RAF/MEK/ERK pathway.     

Concentrations of LTB4, LTC4, LTD4 and LTE4 in bronchiolitis due to respiratory syncytial virus

Fifty-five infants with bronchiolitis due to respiratory syncytial virus were evaluated for the presence of leukotriene B₄, C₄, D₄ and E₄ in nasopharyngeal secretions. An attempt was made to correlate concentrations of leukotrienes to arterial oxygen tension. Forty participants received conventional therapy consisting primarily of aerosolized albuterol and occasional aminophylline therapy. The other 15 individuals received ribavirin therapy in addition to conventional therapy, and leukotriene concentrations were compared among individuals in these groups. RSV infection was documented by standard methods, and leukotrienes were measured by reverse-phase high pressure liquid chromatography. The leukotriene detected most commonly was LTC₄ (up to 83% of subjects); LTD₄ and LTB₄ were present in approximately 30% of individuals. The mean partial pressure of oxygen was found to be lower in those individuals with detectable LTB₄ than in those without detectable LTB₄ (p < 0.025), and an overall inverse correlation of LTB₄ concentrations with initial pO₂ values was observed (r = 0.318, p < 0.05). The presence and quantity of other leukotrienes did not correlate with the severity of illness. During the first week of illness, the concentration of leukotrienes declined sharply in ribavirin recipients. Individuals receiving conventional therapy during the same time interval exhibited stable or increasing leukotriene concentrations. These observations suggest that LTB₄ may be important in the pathogenesis of bronchiolitis, and that ribavirin therapy may inhibit leukotriene release in the respiratory tract.     

Limb/pelvis-hypoplasia/aplasia syndrome--further delineation of phenotype

We report a case of Al-Awadi/Raas-Rothschild syndrome, an autosomal recessive disorder manifesting at an early gestation as hydrops as a result of congenital high airway obstruction.     

Survival of Cr51-labelled Red Cells from New-born Infants1

Summary
The survival of Cr⁵¹-labelled placental red cells of 10 full-term and 6 premature infants was studied after transfusion to adult recpients. The mean apparent half-life of the red cells from full-term infants was found to be 22.8 days, and that of red cells from premature infants 15.8 days (cf. 27.5 days for red cells from adults). Results obtained by others using the differential agglutination method have indicated a longer life span than that corresponding to the Cr⁵¹ half-times above mentioned. The most probable explanation of this difference seems to be that Cr⁵¹ is eluted more rapidly from fetal red cells than from red cells of adults. This hypothesis is corroborated by the results of experiments in vitro on intact red cells.     

Cytochrome B558 Component of O-2M Generating Oxidase in the Neutrophils From Patients With Chronic Granulomatous Disease

Cytochrome b₅₅₈ is probably a component of an electron transport chain which is called NADPH oxidase. Cytochrome b₅₅₈ from the neutrophils of two male patients with chronic granulomatous disease (CGD) and their parents was studied. One of the CGD patients had decreased amounts of cytochrome b₅₅₈, The α-band of light absorption of cytochrome b₅₅₈ at 558 nm was found as a trace, and the peak of the γ-band was shifted to 420 nm, whereas the normal γ-band is at 426 nm. Intermediate amounts of cytochrome b₅₅₈ were present in his mother, whereas his father had a normal amount. Another patient had normal peaks of α- and γ-bands of cytochrome b₅₅₈. Thus, abnormalities in NADPH oxidase of the two patients were different.     

Pediatric RadiologyContinuing Medical Education Activity

Pediatric Radiology CME Activity

Pediatric Radiology Continuing Medical Education Activity     

NeOProM: Neonatal Oxygenation Prospective Meta-analysis Collaboration study protocol

Background  

The appropriate level of oxygenation for extremely preterm neonates (<28 weeks' gestation) to maximise the greatest chance of survival, without incurring significant morbidity, remains unknown. Infants exposed to lower levels of oxygen (targeting oxygen saturations of <90%) in the first weeks of life are at increased risk of death, cerebral palsy, patent ductus arteriosus, pulmonary vascular resistance and apnoea, whilst those maintained in higher levels of oxygen (targeting oxygen saturations of >90%) have been reported to have greater rates of morbidity including retinopathy of prematurity and chronic lung disease. In order to answer this clinical dilemma reliably, large scale trial evidence is needed.     

哮喘患儿诱导痰液中NO3^—／No2^—含量的变化及其意义

探讨儿童哮喘诱导痰液中一氧化氮(NO)代谢终产物硝酸盐/亚硝酸盐(NO-3/NO-2)含量的变化及临床意义,采用3%高渗盐水雾化吸入诱导患儿咳痰,0.1%DTT和PBS缓冲液裂解痰液,应用硝酸酶还原法和荧光酶标法分别测定诱导痰液中NO-3/NO-2和嗜酸性粒细胞阳离子蛋白(ECP)含量,便携式肺功能仪测定肺通气功能.结果表明,稳定期、轻度和中、重度发作期患儿诱导痰液中NO-3/NO-2浓度较对照组显著增高,P<0.05;ECP含量较对照组显著增高,P<0.05;不同时期哮喘患儿各组间诱导痰液中NO-3/NO-2含量和ECP均有显著性差异,P<0.05.哮喘患儿诱导痰液中NO-3/NO-2和ECP含量与1秒钟用力呼气容积占预计值百分比(FEV1.0%)呈显著负相关,r=-0.512,P<0.01;而NO-3/NO-2含量与痰液中ECP浓度呈显著正相关r=0.607,P<0.01.提示NO参与了儿童哮喘的发生和发展,诱导痰液中NO-3/NO-2水平可反映气道炎症的变化,可用于儿童哮喘病情监测及指导药物治疗.     

儿童1型糖尿病TH1/TH2免疫应答状况研究

目的研究儿童1型糖尿病T     

Effect of PaCO2 and Haemoglobin Concentration on Day to Day Variation of CBF in Preterm Neonates

Pryds, O. and Greisen, G. (Department of Neonatology, Rigshospitalet, Copenhagen, Denmark). Effect of P_aCO₂ and haemoglobin concentration on day to day variation of CBF in preterm neonates. Acta Paediatr Scand, Suppl 360: 33, 1989.
The CBF was measured on the first three days of life in 22 mechanically ventilated, preterm neonates (mean gestational age 29.5 weeks) with simultaneous recordings of arterial carbon dioxide tension (P_aCO₂), arterial oxygen tension (P_aO₂), haemoglobin concentration (Hgb), haemoglobin oxygen saturation and mean arterial blood pressure (MABP). CBF ± tended to increase slightly with age. The intra-individual variation of CBF ± was positively related to changes in P_aCO₂ (p=0.0004) and inversely related to changes in Hgb (p=0.029). Neither P_aO₂ nor MABP achieved a significant relation to changes in CBF ± Thus, the mean CBF ±-CO₂ reactivity was calculated to 22.1 % per kPa whereas CBF increased by a mean of 11.9% per mM decrease of Hgb thereby providing a constant oxygen delivery to the brain. It is concluded that P_aCO₂ and Hgb have the expected effect on CBF ± in preterm neonates even during respiratory distress shortly after birth.