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Increased SBP and low milk intake in midlife were associated with VaD detected 25 to 30 years later. Early behavioral control of the risk factors for vascular disease might reduce the risk of dementia.

Regenerative coordination and remodeling of the intramuscular motoneuron network and neuromuscular connections are critical for restoring skeletal muscle function and physiological properties. The regulatory mechanisms of such coordination remain unclear, although both attractive and repulsive axon guidance molecules may be involved in the signaling pathway. Here we show that expression of a neural secreted chemorepellent semaphorin 3A (Sema3A) is remarkably upregulated in satellite cells of resident myogenic stem cells that are positioned beneath the basal lamina of mature muscle fibers, when treated with hepatocyte growth factor (HGF), established as an essential cue in muscle fiber growth and regeneration. When satellite cells were treated with HGF in primary cultures of cells or muscle fibers, Sema3A message and protein were upregulated as revealed by reverse transcription-polymerase chain reaction and immunochemical studies. Other growth factors had no inductive effect except for a slight effect of epidermal growth factor treatment. Sema3A upregulation was HGF dose dependent with a maximum (about 7- to 8-fold units relative to the control) at 10-25 ng/ml and occurred exclusively at the early-differentiation stage, as characterized by the level of myogenin expression and proliferation (bromodeoxyuridine incorporation) of the cells. Neutralizing antibody to the HGF-specific receptor, c-met, did not abolish the HGF response, indicating that c-met may not mediate the Sema3A expression signaling. Finally, in vivo Sema3A was upregulated in the differentiation phase of satellite cells isolated from muscle regenerating following crush injury. Overall, the data highlight a heretofore unexplored and active role for satellite cells as a key source of Sema3A expression triggered by HGF, hence suggesting that regenerative activity toward motor innervation may importantly reside in satellite cells and could be a crucial contributor during postnatal myogenesis.

Risk factors for hip fracture were determined from a Japanese cohort. A cohort of 4573 people (mean age 58.5 ؎ 12.2) who participated in the Adult Health Study in 1978 -1980 were subsequently followed by biennial examinations up to 1992. Fifty-five incident hip fractures not due to traffic accidents were identified by medical records during the follow-up period. Poisson regression analysis showed that baseline low body mass index (BMI), regular alcohol intake, prevalent vertebral fracture, and having five or more children significantly increased the risk of hip fracture, and low milk intake and later age at menarche were marginally associated with increased fracture risk, after multivariable adjustment. Regular alcohol intake doubled the risk of hip fracture (relative risk 1.91, 95% confidence interval 1.07-3.42). Those individuals who had a vertebral fracture had 2.6 times higher risk than those who did not. The risk was 2.5 times higher among women who had five or more children than women with one or two. Body height, health status, marital status, intake of fish, coffee, tea, Japanese tea, smoking, exposure to atomic bomb radiation, and age at menopause were not associated with hip fracture. Relative risk for hip fracture decreased with decreasing number of preventable risk factors (low BMI, low milk intake, and regular alcohol intake). We conclude that many factors, such as BMI, milk intake, alcohol intake, prevalent vertebral fracture, age at menarche, and number of children, are related to the risk of hip fracture, and prevention programs need to focus on reducing preventable risk factors. (J Bone Miner Res 1997;12:998-1004)