Bmx tyrosine kinase has a redundant function downstream of angiopoietin and vascular endothelial growth factor receptors in arterial endothelium.

The Bmx gene, a member of the Tec tyrosine kinase gene family, is known to be expressed in subsets of hematopoietic and endothelial cells. In this study, mice were generated in which the first coding exon of the Bmx gene was replaced with the lacZ reporter gene by a knock-in strategy. The homozygous mice lacking Bmx activity were fertile and had a normal life span without an obvious phenotype. Staining of their tissues using beta-galactosidase substrate to assess the sites of Bmx expression revealed strong signals in the endothelial cells of large arteries and in the endocardium starting between days 10.5 and 12.5 of embryogenesis and continuing in adult mice, while the venular endothelium showed a weak signal only in the superior and inferior venae cavae. Of the five known endothelial receptor tyrosine kinases tested, activated Tie-2 induced tyrosyl phosphorylation of the Bmx protein and both Tie-2 and vascular endothelial growth factor receptor 1 (VEGFR-1) stimulated Bmx tyrosine kinase activity. Thus, the Bmx tyrosine kinase has a redundant role in arterial endothelial signal transduction downstream of the Tie-2 and VEGFR-1 growth factor receptors.

A favorable response to antiparkinsonian treatment in juvenile neuronal ceroid lipofuscinosis.

To study the effect of dopaminergic drugs on the parkinsonism in juvenile neuronal ceroid lipofuscinosis, the authors conducted an open study of 21 patients. According to the motor Unified PD Rating Scale (UPDRS) score, treatment was initiated with either levodopa (n = 10) or selegiline (n = 6). Five patients served as a control group. The UPDRS score after 1 year was compared with the score at onset. Both in the control group and in the selegiline group, the mean UPDRS score increased, whereas in the levodopa group, the mean UPDRS score decreased. The difference between the levodopa group and the control group was significant.

Predicting neurological disorders in infants with extremely low birth weight using the movement assessment of infants.

PURPOSE: The aim of the study was to investigate the predictive value of the Movement Assessment of Infants (MAI) in early detection of neurological disorders in infants with extremely low birth weight (ELBW; <1000 g). METHOD: Thirty-three infants were examined and predictions regarding neurologic status were made at the corrected age of four months using the MAI. Follow-up examinations took place at the corrected age of 12 and 24 months by a pediatric neurologist and a physiotherapist. A neuropsychological assessment using the Bayley Scales of Infant Development was completed at the corrected age of two years. RESULTS: For predicting cerebral palsy (CP), the sensitivity was 64%; specificity 91%, and the positive and negative predictive values were 78% and 84%, respectively. For minor neurological disorders (MND), the value of sensitivity was 44%, specificity 71%, the positive predictive value was 50%, and the negative predictive value was 67%. CONCLUSION: The MAI assessment administered at the corrected age of four months is highly specific in predicting CP in the infants with ELBW.

The Bmx tyrosine kinase is activated by IL-3 and G-CSF in a PI-3K dependent manner.

Cytoplasmic protein tyrosine kinases play crucial roles in signaling via a variety of cell surface receptors. The Bmx tyrosine kinase, a member of the Tec family, is expressed in hematopoietic cells of the granulocytic and monocytic lineages. Here we show that Bmx is catalytically activated by interleukin-3 (IL-3) and granulocyte-colony stimulating factor (G-CSF) receptors. Activation of Bmx required phosphatidylinositol 3-kinase (PI-3K) as demonstrated by the ability of PI-3K inhibitors to block the activation signal. A green fluorescent protein (GFP) tagged Bmx was translocated to cellular membranes upon co-expression of a constitutively active form of PI-3K, further indicating a role for PI-3K in signaling upstream of Bmx. The expression of wild type Bmx in 32D myeloid progenitor cells resulted in apoptosis in the presence of G-CSF, while cells expressing a kinase dead mutant of Bmx differentiated into mature granulocytes. However, Bmx did not modulate IL-3-dependent proliferation of the cells. These results demonstrate distinct effects of Bmx in cytokine induced proliferation and differentiation of myeloid cells, and suggest that the stage specific expression of Bmx is critical for the differentiation of myeloid cells. Oncogene (2000) 19, 4151 - 4158

Does perinatal hypocarbia play a role in the pathogenesis of cerebral palsy?

This study aimed to evaluate the role of hypocarbia as a risk factor for mortality and for cerebral palsy in extremely low birthweight infants. The records for 215 extremely low birthweight children were analysed, grouping the infants into those who died (n = 72), those who had a confirmed diagnosis of cerebral palsy (n = 27) and those without major neurological symptoms at the age of 2 y (n = 116). The analysed risk factors were: birthweight, gestational age, maternal diseases and toxaemia, multiple pregnancy, male gender, respiratory distress syndrome, abnormal neonatal cerebral ultrasound, occurrence of septic infection, and/or at least one episode of systemic hypotension and/or at least two episodes of hypocarbia (<3 kPa) during the neonatal period. The mortality rate was 31% and the rate of cerebral palsy was 17% in the survivors. Hypocarbia was found in 33% of children with cerebral palsy, in 10% of infants who died and in 19% of the healthy controls; the differences were statistically insignificant. Birthweight and gestational age, episodes of systemic hypotension and abnormal ultrasound emerged as risk factors for mortality. Abnormal cerebral ultrasound was the only significant risk factor for cerebral palsy. The role of hypocarbia in the pathogenesis of CP remained indistinct but the distribution of risk factors was different in infants with a mortal outcome and in infants with cerebral palsy.

Neurodevelopment until the adjusted age of 2 years in extremely low birth weight infants after early intervention--a case-control study.

A total of 104 infants with birth weights of less than 1000 grams were enrolled in this prospective case-control study in order to examine the effect of occupational therapy based on sensory integration (SI) and neurodevelopmental therapy (NDT) on neurological development. The children were grouped as matched pairs on the basis of a set of developmental risks assessed at the age of 3 months. The intervention children had a weekly session of 60 minutes of occupational therapy from the corrected age of 6 months up to 12 months. All the children were examined at the corrected age of 3, 6, 9, 12, 18 and 24 months. The neurodevelopment of the cases and the controls did not differ essentially and the only significant difference was found in the social development of the children at the age of 12 months to the advantage of the intervention group. It is concluded that this amount of occupational therapy in at-risk children does not have a relevant effect on neurological development.