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This study revealed that the absence of histamine in histidine decarboxylase gene-knockout (HDC(-/-)) mice resulted in delayed cutaneous wound healing and that exogenously administered histamine compensated this process. With the overproduction of histamine in HDC gene-transgenic mice, the healing was accelerated compared to the HDC(+/+) mice. These results indicate that histamine positively accelerated the cutaneous wound healing. Macrophage recruitment and angiogenesis at the wound edge were specifically impaired in HDC(-/-) mice, and histamine-treated wounds in HDC(-/-) mice demonstrated increased macrophage recruitment and angiogenesis. The amount of basic fibroblast growth factor (bFGF) in protein level at the wound edge was higher in HDC(+/+) mice, especially on the 3rd and 5th day of wound healing compared to those in HDC(-/-) mice. Topically administered SU5402, a specific antagonist to fibroblast growth factor receptor-1 tyrosine kinase, to the wound surface suppressed the wound healing in HDC(+/+) mice but not in HDC(-/-) mice. Moreover, SU5402 reduced macrophage recruitment and angiogenesis in HDC(+/+) mice. From these observations, it was concluded that the accelerated wound-healing activity of histamine was mediated by the activity of bFGF, which leads to angiogenesis, and macrophage recruitment in the wound-healing process.

No abstract

PVI RESULTSThe median ages at diagnosis of CP, assignment of Gross Motor Function Classification System (GMFCS) level, cognitive assessment, and MRI were 2 years (range 5mo-8y), 6 years (2y 8mo-19y), 6 years (1y 4mo-19y), and 7 years (10mo-30y) respectively. MRI included normal findings (41.9%), periventricular leukomalacia, hypomyelination, and porencephaly ⁄ periventricular venous infarction. The frequency of patients in GMFCS levels III to V and intellectual disability did not differ between those with normal and abnormal MRI findings. Patients with normal MRI findings had significantly fewer epileptic episodes than those with abnormal ones (p=0.001).INTERPRETATION Varied MRI findings, as well as the presence of severe motor dysfunction and intellectual disability (despite normal MRI), suggest that patients born at term with spastic diplegia had heterogeneous and unidentified pathophysiology.

The role of endosomal pH in neurite formation, one of the principal processes of neuronal differentiation, is unknown. This study shows that the neuron-enriched Na+/H+ exchanger NHE5 potently acidifies recycling endosomes and regulates TrkA trafficking, NGF-TrkA signaling, and neurite outgrowth.

To determine the epidemiological, clinical, and genetic characteristics of congenital hypomyelinating leukodystrophies, including Pelizaeus-Merzbacher disease (PMD), we conducted a nationwide epidemiological survey in Japan. A two-step survey targeting all medical institutions specializing in pediatric neurology and childhood disability (919 institutes) in Japan was performed. Detailed information was collected for 101 patients (86 males and 15 females) with congenital hypomyelinating leukodystrophies. The prevalence of congenital hypomyelinating disorders was 0.78 per 100,000 people (0-19 years old), and the incidence was 1.40 per 100,000 live births. Molecular testing was performed in 75 % of patients, and PLP1 gene abnormalities were observed in 62 %. The incidence of PMD with PLP1 mutations was estimated to be 1.45 per 100,000 male live births and that for congenital hypomyelinating disorders with unknown cause to be 0.41 per 100,000 live births. Patients with PLP1 mutations showed a higher proportion of nystagmus and hypotonia, both of which tend to disappear over time. Our results constitute the first nationwide survey of congenital hypomyelinating disorders, and provide the epidemiological, clinical, and genetic landscapes of these disorders.

Background: Mutations of proteolipid protein 1 (PLP1) induce endoplasmic reticulum (ER) stress. Results: PLP1 mutants deplete some chaperones from the ER and induce fragmentation of the Golgi apparatus (GA). Conclusion: These changes affect clinical pathology in disease-causing mutations of PLP1. Significance: This work provides a novel insight involving global changes of organelles in pathogenesis of ER stress-related diseases.

The neuron-enriched Na+/H+ exchanger NHE5 is expressed in C6 glioma cells, acidifies recycling endosomes, and modulates cell surface abundance of receptor tyrosine kinases MET and EGFR. NHE5 depletion impairs MET recycling and facilitates degradation, thereby impairing cell migration and polarity.