Fumiko Ishizaki

Marked reduction of the Cu/Zn superoxide dismutase polypeptide in a case of familial amyotrophic lateral sclerosis with the homozygous mutation.

We identified a missense mutation of the Cu/Zn superoxide dismutase (SOD) gene (Leu126Ser) in a Japanese family with ALS that included a patient with the homozygous mutation. The content of the Cu/Zn SOD polypeptide in erythrocytes was markedly reduced in the case with the homozygous mutation compared to those with the heterozygous mutation. We speculated that this reduction of the mutant Cu/Zn SOD molecule might be related to the severe clinical phenotype of the case.

Plasma benzylamine oxidase activity in cerebrovascular disease.

The plasma benzylamine oxidase level (BzAO) was determined in 60 patients with different types of acute cerebrovascular disease, such as cerebral bleeding, subarachnoid bleeding and cerebral infarction. Patients with cerebral infarction included both apoplectic and multiple types. A decreased plasma level of the enzyme was found following a stroke in patients with cerebral bleeding, subarachnoid bleeding, and the apoplectic type of cerebral infarction. The BzAO level increased in patients with the multiple type of cerebral infarction. Thus, we postulate that plasma BzAO metabolism is involved in cerebrovascular disease, and that plasma BzAO level varies with the type of cerebral infarction.

Relation of blood serotonin and benzylamine oxidase to clinical symptoms and prognosis in Parkinson's disease.

In 21 parkinsonian patients, we investigated the contents of blood serotonin (5HT) and benzylamine oxidase (BzAO) before and during L-dopa therapy. Then, we studied the patients prospectively, and evaluated the relationship between 5HT and BzAO and the clinical characteristics. The levels of blood 5HT and BzAO varied not only with the treatment, but also with the duration and clinical type of the disease. We postulated that in certain types of Parkinsons disease, the generalized defect of 5HT and enzyme metabolism might primarily exist, and might influence the efficacy of L-dopa therapy and the prognosis of the disease.

PS-63-7 Prolonged QTc intervals in Parkinson's disease — relation to sudden death and autonomic dysfunction

Sudden death has been reported in Parkinsons disease (PD), but the cause of death has not been fully clarified. A prolonged QT interval on the electrocardiogram (ECG) of patients without cardiac dysfunction is an independent risk factor for sudden death regardless of etiology. QT prolongation is believed to be related to cardiac autonomic dysfunction. We suspected that QTc intervals, as well as QT intervals, might be related to the clinical characteristics of PD and to the function of the autonomic nervous system in PD and also postulated a relationship between QTc prolongation and sudden death in PD. We investigated the QTc intervals on the ECGs of 48 PD patients (20 males 28 females) aged 64.5 +/- 9.4 years and 44 controls aged 60.0 +/- 8.2 years, and excluded patients with heart disease. QTc intervals were determined by using ECG-8210, ECAPS12 (Nihon-Kohden). The autonomic nervous system was evaluated by measuring CVR-R and performing orthostatic tests. Since the autonomic nervous system is considered to play an important role in the mechanism of diurnal blood pressure variation (DBPV), we assessed DBPV in 19 PD patients by determining blood pressure automatically every 30 minutes for 24 hours with an ambulatory blood pressure monitor (90202, Space Lab). QTc intervals were significantly longer in the PD patients (412 +/- 26 msec) than in the controls (401 +/- 14 msec) (p < 0.02, t-test). QTc prolongation was significantly correlated with severity according to Hoehn and Yahr stage (r = 0.509, p < 0.001), orthostatic hypotension, and decreased CVR-R ratio but not with duration of PD or treatment. The incidence of QTc prolongation was higher in the PD patients with non-dipper type DBPV than in those with the dipper type. Two of the PD patients died suddenly. Their QTc intervals a year before their death were 451 msec and 470 msec, respectively, suggesting that cardiac dysautonomia may have been involved in the cause of their death. These findings suggest that cardiac autonomic dysfunction is related to the severity of PD, and that it may predispose such patients to cardiac disorders including sudden cardiac death.

Association of changes in neck circumference with cardiometabolic risk in postmenopausal healthy women

AIM Although neck circumference (NC) is thought to predict obesity-related metabolic abnormality, its causal role in cardiometabolic risk is unclear. The aim of this study was to clarify the impact of changes in NC on cardiometabolic risk in healthy postmenopausal women through a community-based longitudinal study. METHODS From a local community in Japan, 63 generally healthy postmenopausal women were recruited. All participants received an assessment of obesity-related anthropometric markers, biochemical parameters, and hemodynamic measures and were followed on average for 3 years. RESULTS At baseline analysis, larger NC was positively associated with atherosclerosis-related markers, brachial-ankle pulse wave velocity (baPWV) and blood pressure, as well as some lipid parameters. After the follow-up period, change in NC was associated with changes in body mass index (BMI), body fat percentage, and waist circumference (WC). Interestingly, significant correlations of change in NC with changes in baPWV and blood pressure were observed, whereas changes in WC and BMI were only associated with changes in low-density lipoprotein cholesterol and/or total cholesterol. In multivariate linear regression analysis, change in NC was significantly associated with changes in baPWV and systolic blood pressure, independent of changes in BMI, WC, and biochemical parameters. In addition, an increase in NC was associated with a 2.69-fold increased odds ratio of accelerated baPWV. CONCLUSIONS Change in NC was independently associated with changes in atherosclerosis-related markers. These observations suggest that NC is an important predictor of the risk of developing obesity-related atherosclerosis in healthy postmenopausal women.