Expression of the heparin-binding growth factor midkine in the cerebrospinal fluid of patients with neurological disorders.

OBJECTIVE: This study was to clarify the roles of midkine (MK) in the brain. METHODS: We determined cerebrospinal fluid MK levels in patients with neurological disorders by enzyme-linked immunoassay and immunostained autopsied brain samples in patients with meningitis. RESULTS: MK levels were 0.37+/-0.21 ng/ml in controls (n=46, mean +/- S.D.), 0.67+/-0.19 ng/ml in patients with cerebral infarction (n=8), 1.78+/-1.32 ng/ml in patients with meningitis (n=25; ANOVA and post-hoc Fisher's PLSD test, p<0.0001), 0.31+/-0.25 ng/ml in patients with human T-lymphotrophic virus type I-associated myelopathy/tropical spastic paraparesis (n=29), and 0.42+/-0.17 ng/ml in patients with amyotrophic lateral sclerosis (n=8). The regression equations were Y=0.005X+0.498 (Y, CSF MK level; X, cell number) and Y=0.007X+0.326 (Y, MK level; X, protein level) for all CSF samples. Autopsy brain samples from patients with meningitis expressed MK weakly in mononuclear cells on immunohistochemical examination. Western blot and polymerase chain reaction analyses showed that leukocytes were MK positive. CSF MK levels were not high in patients with cerebral infarction but were increased in patients with meningitis. CSF MK levels were high in normal controls, compared to those of other cytokines. MK was expressed in choroid plexus of normal brain and released there. CONCLUSION: Our findings suggested that MK may maintain normal adult brain as a neurotrophic factor, and that MK may be released from leucocytes in brain of patients with meningitis as an immunological mediator.

Precedence of the shift of body-fat distribution over the change in body composition after menopause.

AIM: This study investigated the sequence of certain phenomena after menopause: decrease in bone mineral density (BMD), change in body composition (lean and fat components), and the shift toward upper body fat distribution. METHODS: Subjects were 188 postmenopausal women aged 50-65 years old. They were divided into four subgroups based on 4-year increments in age. Regularly menstruating women (n = 51) aged 50-53 years old served as controls. Age, height, weight, and years since menopause were recorded. Body fat mass, percentage of body fat (%fat), lean body mass (LBM), lumbar spine (L2-4), total body BMD, and the trunk-leg fat mass ratio were measured by dual-energy X-ray absorptiometry. RESULTS: In postmenopausal women (n = 42) aged 50-53 years, BMD was lower compared to age-matched controls (P < 0.05), while other variables did not differ. Trunk-leg fat mass ratio in women aged 54-57 years or more was significantly higher than that in control. LBM was significantly lower while percentage fat was significantly higher in women aged 58-61 years old or more. CONCLUSION: An initial event during the menopausal process is BMD loss, which is followed by body fat distribution shift, then LBM loss and reciprocal increase in body fat mass.

Difference in the relative contribution of lean and fat mass components to bone mineral density with generation.

AIM: To investigate whether the relative contribution of body composition (lean and fat mass component) to bone mineral density (BMD) differs depending on generation or menopause. METHODS: Subjects were 302 premenopausal women aged 30-49 years old and 197 postmenopausal women aged 50-69 years old. They were classified into four subgroups with 10-year increments. Age, height, weight and years since menopause (YSM) were recorded. Lumbar spine (L2-4), total body BMD, body fat mass, lean body mass (LBM), and the percentage of body fat (%fat) were measured using dual-energy X-ray absorptiometry. The correlation of body composition with BMD was investigated. RESULTS: The mean age at menopause was 50.2 +/- 4.1 years old. On Pearson's correlation test, LBM was positively correlated with BMD of the two sites in all groups. In a group aged 60-69 years, both the %fat and body fat mass were correlated with BMD. On multiple regression analysis, LBM was the principal BMD determinant in women aged less than 60 years, while body fat mass and percentage fat were the principal BMD determinants in women aged 60-69 years. Mean %fat in the group aged 60-69 years was 35.5 +/- 7.3%, which was significantly higher than that in the group aged 50-59 years (33.0 +/- 6.7%, P < 0.05). CONCLUSION: Although LBM still influences BMD up to 10 years after menopause, the body fat mass initially influences BMD after 60 years of age. These difference may be attributable to certain aging-related factor(s).