Nobutoshi Kawamura

Anti-neurofascin antibody in patients with combined central and peripheral demyelination

Objectives: We aimed to identify the target antigens for combined central and peripheral demyelination (CCPD). Methods: We screened target antigens by immunohistochemistry and immunoblotting using peripheral nerve tissues to identify target antigens recognized by serum antibodies from selected CCPD and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) cases. We then measured the level of antibody to the relevant antigen in 7 patients with CCPD, 16 patients with CIDP, 20 patients with multiple sclerosis, 20 patients with Guillain-Barré syndrome, 21 patients with other neuropathies, and 23 healthy controls (HC) by ELISA and cell-based assays using HEK293 cells. Results: At the initial screening, sera from 2 patients with CCPD showed cross-like binding to sciatic nerve sections at fixed intervals, with nearly perfect colocalization with neurofascin immunostaining at the node and paranode. ELISA with recombinant neurofascin revealed significantly higher mean optical density values in the CCPD group than in other disease groups and HC. Anti-neurofascin antibody positivity rates were 86% in patients with CCPD, 10% in patients with multiple sclerosis, 25% in patients with CIDP, 15% in patients with Guillain-Barré syndrome, and 0% in patients with other neuropathies and HC. The cell-based assay detected serum anti-neurofascin antibody in 5 of 7 patients with CCPD; all others were negative. CSF samples examined from 2 patients with CCPD were both positive. In anti-neurofascin antibody–positive CCPD patients, including those with a limited response to corticosteroids, IV immunoglobulin or plasma exchange alleviated the symptoms. Conclusion: Anti-neurofascin antibody is frequently present in patients with CCPD. Recognition of this antibody may be important, because patients with CCPD who are antibody positive respond well to IV immunoglobulin or plasma exchange.

Case–control study of risk of Parkinson's disease in relation to hypertension, hypercholesterolemia, and diabetes in Japan

This case-control study investigated the associations of a history of hypertension, hypercholesterolemia, and diabetes mellitus with the risk of Parkinsons disease (PD) in Japan. Included were 249 cases within 6 years of onset of PD. Controls were 368 inpatients and outpatients without a neurodegenerative disease. Data on the vascular risk factors and confounders were obtained from a self-administered questionnaire. The vascular risk factors were defined based on drug treatment. Adjustment was made for sex, age, region of residence, pack-years of smoking, years of education, leisure-time exercise, body mass index, dietary intake of energy, cholesterol, vitamin E, alcohol, and coffee and the dietary glycemic index. The proportions of hypertension, hypercholesterolemia, and diabetes mellitus prior to the onset of PD were 23.7%, 9.6%, and 4.0%, respectively, in cases. Hypertension, hypercholesterolemia, and diabetes mellitus were significantly associated with a decreased risk of PD: the adjusted ORs were 0.43 (95% CI: 0.29-0.64), 0.58 (95% CI: 0.33-0.97), and 0.38 (95% CI: 0.17-0.79), respectively. No significant differences were observed in the association of vascular risk factors with the risk of PD between men and women. We found evidence of significant inverse associations of hypertension, hypercholesterolemia, and diabetes mellitus with the risk of PD in Japan. Further well-designed investigations of the association of vascular risk factors with the risk of PD are needed, particularly large-scale prospective studies in Asia.

Dietary fat intake and risk of Parkinson's disease: A case-control study in Japan

The present case-control study examined the relationship between dietary intake of individual fatty acids and the risk of Parkinsons disease (PD) in Japan. Included were 249 cases within 6 years of onset of PD. Controls were 368 inpatients and outpatients without a neurodegenerative disease. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Compared with arachidonic acid intake in the first quartile, consumption of that in the fourth quartile was significantly related to an increased risk of PD: the adjusted odds ratio between extreme quartiles was 2.09 (95% confidence interval: 1.21-3.64, P for trend=0.008). Cholesterol intake was also significantly positively associated with the risk of PD: the adjusted odds ratio between extreme quartiles was 1.78 (95% confidence interval: 1.04-3.05, P for trend=0.01). Consumption of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, and linoleic acid and the ratio of n-3 to n-6 polyunsaturated fatty acid intake were not associated with PD. Higher consumption of arachidonic acid and cholesterol may be related to an increased risk of PD.

Dietary intake of antioxidant vitamins and risk of Parkinson's disease: a case-control study in Japan.

Background:  Antioxidant vitamins are expected to protect cells from oxidative damage by neutralizing the effects of reactive oxygen species. However, epidemiological evidence regarding the associations between antioxidant vitamin intake and Parkinson’s disease (PD) is limited and inconsistent. We investigated the relationship between dietary intake of selected antioxidant vitamins, vegetables and fruit and the risk of PD in Japan using data from a multicenter hospital‐based case–control study.

Dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and risk of Parkinson's disease: a case-control study in Japan.

Increased homocysteine levels might accelerate dopaminergic cell death in Parkinsons disease (PD) through neurotoxic effects; thus, increasing intake of B vitamins involved in the regulation of homocysteine metabolism might decrease the risk of PD through decreasing plasma homocysteine. However, epidemiological evidence for the association of dietary B vitamins with PD is sparse, particularly in non-Western populations. We conducted a hospital-based case-control study in Japan to examine associations between dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and the risk of PD. Patients with PD diagnosed using the UK PD Society Brain Bank criteria (n 249) and controls without neurodegenerative diseases (n 368) were recruited. Dietary intake during the preceding month was assessed at the time of study recruitment using a validated, self-administered, semi-quantitative, comprehensive diet history questionnaire. After adjustment for potential dietary and non-dietary confounding factors, intake of folate, vitamin B12 and riboflavin was not associated with the risk of PD (P for trend = 0.87, 0.70 and 0.11, respectively). However, low intake of vitamin B6 was associated with an increased risk of PD, independent of potential dietary and non-dietary confounders. Multivariate OR (95 % CI) for PD in the first, second, third and fourth quartiles of vitamin B6 were 1 (reference), 0.56 (0.33, 0.94), 0.69 (0.38, 1.25) and 0.48 (0.23, 0.99), respectively (P for trend = 0.10). In conclusion, in the present case-control study in Japan, low intake of vitamin B6, but not of folate, vitamin B12 or riboflavin, was independently associated with an increased risk of PD.

Characterization of IgG4 anti-neurofascin 155 antibody-positive polyneuropathy.

To investigate anti‐neurofascin 155 (NF155) antibody‐positive chronic inflammatory demyelinating polyneuropathy (CIDP).

Intake of Japanese and Chinese teas reduces risk of Parkinson’s disease

Studies that have addressed the association between the intake of coffee or caffeine and Parkinsons disease (PD) were conducted mainly in Western countries. Little is known about this relationship in an Asian population. Therefore, we performed an assessment of the association of the intake of coffee, other caffeine-containing beverages, and caffeine with the risk of PD in Japan. The study involved 249 PD cases and 368 control subjects. Information on dietary factors was obtained through a self-administered diet history questionnaire. Adjustment was made for sex, age, region of residence, educational level, pack-years of smoking, body mass index, the dietary glycemic index, and intake of cholesterol, vitamin E, β-carotene, vitamin B(6,) alcohol, and iron. Intake of coffee, black tea, and Japanese and Chinese teas was significantly inversely associated with the risk of PD: the adjusted odds ratios in comparison of the highest with the lowest quartile were 0.52, 0.58, and 0.59, respectively (95% confidence intervals = 0.30-0.90, 0.35-0.97, and 0.35-0.995, respectively). A clear inverse dose-response relationship between total caffeine intake and PD risk was observed. We confirmed that the intake of coffee and caffeine reduced the risk of PD. Furthermore, this is the first study to show a significant inverse relationship between the intake of Japanese and Chinese teas and the risk of PD.

Dietary intake of metals and risk of Parkinson's disease: a case-control study in Japan.

Metals are involved in several important functions in the nervous system. Zinc and iron are increased and copper is decreased in the substantia nigra in Parkinsons disease (PD). However, epidemiological evidence for the association of dietary intake of metals with the risk of PD is limited. We investigated the relationship between metal consumption and the risk of PD in Japan using data from a multicenter hospital-based case-control study. Included were 249 cases within 6 years of onset of PD based on the UK PD Society Brain Bank clinical diagnostic criteria. Controls were 368 inpatients and outpatients without a neurodegenerative disease. Information on dietary factors was collected using a self-administered diet history questionnaire. Higher intake of iron, magnesium, and zinc was independently associated with a reduced risk of PD: the adjusted OR in the highest quartile was 0.24 (95% CI: 0.10-0.57, P for trend=0.0003) for iron, 0.33 (95% CI: 0.13-0.81, P for trend=0.007) for magnesium and 0.50 (95% CI: 0.26-0.95, P for trend=0.055) for zinc. There were no relationships between the intake of copper or manganese and the risk of PD. Higher intake of iron, magnesium, and zinc may be protective against PD.

Dietary glycemic index is inversely associated with the risk of Parkinson's disease: a case-control study in Japan.

OBJECTIVE High glycemic index (GI) or glycemic load (GL) carbohydrates might be expected to decrease the risk of Parkinsons disease (PD) by an insulin-induced increase in brain dopamine. We conducted a hospital-based case-control study in Japan to examine associations between dietary GI and GL and other dietary carbohydrate variables, including intake of available carbohydrate and dietary fiber, and PD. METHODS Patients with PD diagnosed using the U.K. Parkinsons Disease Society Brain Bank criteria (n=249) and controls without neurodegenerative diseases (n=368) were recruited. Dietary intake during the preceding month was assessed at the time of study recruitment using a validated, self-administered, semiquantitative, comprehensive diet history questionnaire. RESULTS After adjustment for potential dietary and non-dietary confounding factors, dietary GI was significantly inversely associated with the risk of PD. Multivariate odds ratios (95% confidence intervals) for PD in the first, second, third, and fourth quartiles of dietary GI were 1.00 (reference), 1.03 (0.64-1.66), 0.68 (0.41-1.15), and 0.61 (0.34-1.09), respectively (P for trend=0.04). Conversely, no significant association was observed for other dietary carbohydrates, including dietary GL (P for trend=0.77), available carbohydrate intake (P for trend=0.28), or dietary fiber intake (P for trend=0.73). CONCLUSION This preliminary case-control study based on current dietary habits found an independent inverse relation between dietary GI and PD. Considering the plausibility of the putative mechanism, further investigation using a case-control design with accurate assessment of past dietary habits or a prospective design is warranted.

Genetic polymorphisms involved in dopaminergic neurotransmission and risk for Parkinson's disease in a Japanese population

BackgroundParkinsons disease (PD) is characterized by alterations in dopaminergic neurotransmission. Genetic polymorphisms involved in dopaminergic neurotransmission may influence susceptibility to PD.MethodsWe investigated the relationship of catechol-O-methyltransferase (COMT), monoamine oxidase B (MAOB), dopamine receptor (DR) D2 and DRD4 polymorphisms and PD risk with special attention to the interaction with cigarette smoking among 238 patients with PD and 369 controls in a Japanese population.ResultsSubjects with the AA genotype of MAOB rs1799836 showed a significantly increased risk of PD (odds ratio (OR) = 1.70, 95% confidence interval (CI) = 1.12 - 2.58) compared with the AG and GG genotypes combined. The AA genotype of COMT rs4680 was marginally associated with an increased risk of PD (OR = 1.86, 95% CI = 0.98 - 3.50) compared with the GG genotype. The DRD2 rs1800497 and DRD4 rs1800955 polymorphisms showed no association with PD. A COMT -smoking interaction was suggested, with the combined GA and AA genotypes of rs4680 and non-smoking conferring significantly higher risk (OR = 3.97, 95% CI = 2.13 - 7.41) than the AA genotype and a history of smoking (P for interaction = 0.061). No interactions of smoking with other polymorphisms were observed.ConclusionsThe COMT rs4680 and MAOB rs1799836 polymorphisms may increase susceptibility to PD risk among Japanese. Future studies involving larger control and case populations and better pesticide exposure histories will undoubtedly lead to a more thorough understanding of the role of the polymorphisms involved in the dopamine pathway in PD.