ISSN:0031-3998    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ThePAX6gene is a paradigm for our understanding of the molecular genetics of mammalian eye development. Twelve years after its identification it is one of the most intensively studied genes, both in terms of its diverse and complex functions during oculogenesis and its role in an ever-increasing variety of human congenital eye malformations. The PAX6 field has benefited greatly from the continued input of clinicians, human geneticists and developmental biologists. This review summarizes the latest data on thePAX6mutation spectrum and recent insights intoPax6function from the mouse.

ISSN:0031-3998    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Current nonhuman models for bronchopulmonary dysplasia have not included perinatal infection. We studied the effects of antenatalUreaplasma urealyticum(Uu) infection in the 125-d immature baboon. Ten 125-d gestation (term = 185 d) baboon dams were delivered after intra-amniotic inoculation withUu. Serial blood and tracheal aspirate samples were analyzed forUucolony-forming units, IL-6, IL-8, and cell counts. Physiologic parameters were serially recorded. Lung histology was examined after 14 d of ventilation and compared with unexposed controls. AllUu-exposed animals had >4 × 102CFU in tracheal aspirate at 24 h. Four of nineUuanimals remained heavily colonized [(+)Uu] at necropsy (>6 × 103). Five animals had negative or low tracheal colony-forming units. AllUuanimals had significant increases for white blood cells, IL-6, and IL-8 in amniotic and fetal lung fluid. Compared with controls, (+)Uuanimals had significantly higher fraction of inspired oxygen, airway pressures, oxygenation index, and ventilation efficiency index between 48 and 240 h and had significantly elevated tracheal IL-6 and IL-8 concentrations between 72 and 240 h. Compared with controls (−)Uuanimals had significantly better oxygenation index and ventilation efficiency index scores between 48 and 144 h. Lung histopathology in bothUugroups showed more severe bronchiolitis and interstitial pneumonitis compared with controls. Two patterns of disease were observed afterUuperinatal infection. Persistent colonization manifested a picture consistent with acute pneumonitis, worse lung function from 2 to 10 d, and prolonged elevated tracheal cytokines. Colonized animals that subsequently clearedUufrom the lung demonstrated early improved lung function compared with unexposed controls yet still manifested mixed bronchiolitis and interstitial pneumonitis at necropsy. Inherent immune system responses may determine outcome of perinatalUreaplasmacolonization.

ISSN:0031-3998    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Partial liquid ventilation (PLV) with perfluorocarbons has been considered as an alternative therapy for severe inflammatory lung disease. The present study was performed to test whether PLV influences bacterial growth and lung histology in a rabbit model of congenital pneumonia caused by group B streptococci. Near-term newborn rabbits were tracheotomized, inoculated via the airways with group B streptococci, and subsequently ventilated for 5 h with either PLV or conventional ventilation. At 30 min after group B streptococci administration, animals in the PLV group (n= 16) received 30 mL/kg body weight of perfluorocarbon (PF 5080) via the tracheal tube. Evaporative losses were substituted with 20 mL/kg perfluorocarbon at hourly intervals. Identical volumes of air were injected in control animals at the same times (n= 15). The number of colony-forming units in left lung homogenate, evaluated at the end of the experiments, tended to be lower in PLV-treated animals than in controls (6.8 × 109versus6.4 × 1010colony-forming units/g body weight;p= 0.06). Comparison of these numbers with the colony-forming units injected at the beginning of the experiments revealed a reduction in bacterial number in the PLV group and proliferation in the controls (−2.2 × 108versus+5.6 × 1010colony-forming units/g body weight;p< 0.05). Histologic examination demonstrated less inflammation and more homogeneous lung expansion in PLV-treated animals. Two animals in the PLV group had focal interstitial emphysema. Our results suggest that PLV with PF 5080 reduces bacterial proliferation in experimental group B streptococcal pneumonia.

ISSN:0031-3998    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The objective of this study was to obtain insight into bone formation and resorption in children with newly diagnosed untreated acute lymphoblastic leukemia (ALL). In 23 consecutive children with ALL, a bone biopsy was taken from the crista iliaca posterior under ketamine anesthesia, together with the diagnostic marrow aspiration, before any treatment was given. Histomorphometric assessment was done of bone volume, bone area, trabecular thickness, osteoid volume, osteoid area, osteoid width, number of osteoblasts, erosion area, and number of osteoclasts. Data were analyzed in age groups under and over 10 y and compared with biopsies from 15 children, obtained during the work-up for other malignancies (only patients without bone marrow involvement were included). In ALL patients, bone volume and trabecular thickness were decreased in children <10 y. In patients >10 y, these parameters were not significantly different from the controls; bone densitometry showed no significant loss of bone in patients >10 y as well. Numbers of osteoblasts and osteoid surface occupied with osteoblasts were reduced in both age groups, as was the number of resorbing osteoclasts. No indications of osteomalacia were found. Childhood ALL results in a reduced number of both osteoblasts and osteoclasts, with a subsequent reduced osteoid formation and reduced bone resorption. This leads to a reduced bone volume and trabecular thickness, especially in younger children. In adolescents, the disturbance of bone (re)modeling is less serious, probably because of the strong stimulus on bone formation of sex hormones. The skeletal impairment at diagnosis is potentially reversible.

ISSN:0031-3998    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Apolipoprotein E (APOE) regulates cholesterol and fatty acid metabolism, and may mediate synaptogenesis during neurodevelopment. To our knowledge, the effects of APOE4 isoforms on infant development have not been studied. This study was nested within a cohort of mother-infant pairs living in and around Mexico City. A multiple linear regression model was constructed using the 24-mo Mental Development Index (MDI) of the Bayley Scale as the primary outcome and infant APOE genotype as the primary risk factor of interest. Regression models stratified on APOE genotype were constructed to explore effect modification. Of 311 subjects, 53 (17%) carried at least one copy of the APOE4 allele. Mean (SD) MDI scores among carriers with at least one copy of APOE4 were 94.1 (14.3) and among E3/E2 carriers were 91.2 (14.0). After adjustment for covariates, APOE4 carrier status was associated with a 4.4 point (95% confidence interval: 0.1-8.7;p= 0.04)higher24-mo MDI. In the stratified regression models, the negative effects for umbilical cord blood lead level on 24-mo MDI score was approximately 4-fold greater among APOE3/APOE2 carriers than among APOE4 carriers. These results suggest that subjects with the E4 isoform of APOE may have advantages over those with the E2 or E3 isoforms with respect to early life neuronal/brain development.

ISSN:0031-3998    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Gradually it is getting clear that motor development – in particular balance control – in so-called “low-risk” preterm infants often differs from that in full-term infants. However, little is known on the etiology and pathophysiology of these problems. The aim of this study was to evaluate postural behavior during reaching by means of kinetic and kinematic measurements. Preterm infants (n= 32) without cerebral palsy were investigated longitudinally at the corrected ages of 4 and 6 mo. Thirteen age-matched full-term infants served as controls. Cognitive and motor development were assessed by means of the quality of General Movements (GMs) at 4 mo and Bayley scales at 6 and 12 mo. The infants were lying supine on a forceplate reaching for a toy and the kinetics of the total body’s Center of Pressure (COP) was measured in cranial-caudal and medial-lateral direction. The analysis focused on COP displacement,Vmaxand oscillatory changes of the COP displacement during reaching. The kinematic analysis of reaching focused on movement units,Vmaxand a compound kinematic variable reflecting the quality of reaching. The results showed that preterm infants showed a remarkable “still” postural behavior, which differed significantly from the mobile COP behavior of the full-term infants. More “still” postural behavior at 6 mo was associated with a better quality of reaching movements and with normal GMs at 4 mo. We concluded that “still” postural behavior is an adequate postural strategy of preterm infants. But it might be that this postural behavior is an indicator of later dysfunction.

ISSN:0031-3998    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Phosphorylase kinase-deficient liver glycogenosis manifests in infancy with hepatomegaly, growth retardation, and elevated plasma aminotransferases and lipids. It can be caused by mutations in three different genes of phosphorylase kinase subunits:PHKA2,PHKB, andPHKG2.It is usually a benign condition, often with complete resolution of symptoms during puberty. A minority of patients displays a more severe phenotype with symptomatic fasting hypoglycemia and abnormal liver histology that may progress to cirrhosis. Three patients with liver cirrhosis in childhood analyzed previously all hadPHKG2mutations. This suggested that this genotype may generally cause a more severe clinical manifestation, but to datePHKG2mutations have been identified in only seven patients. Here, we report mutation analysis in three new patients with liver phosphorylase kinase deficiency and recurrent hypoglycemia, liver fibrosis, and lack of glucagon response but no overt cirrhosis. In all three patients,PHKG2mutations were found (H89fs[insC], E157K, D215N, W300X). Three of these mutations are novel, bringing the total number of distinct humanPHKG2mutations to 11, found in 10 patients. We conclude that liver phosphorylase kinase deficiency with a severe phenotype, with or without cirrhosis, is indeed often caused byPHKG2mutations. These patients require active measures to maintain normoglycemia (raw cornstarch, nocturnal tube feeding), which may also alleviate growth retardation and the development of abnormal liver histology.

ISSN:0031-3998    

出版商:OVID    

年代:2003

数据来源: OVID