Junko Ikeda

Prevalence and risks of dementia in the Japanese population : RERF's adult health study Hiroshima subjects

OBJECTIVES: To study the prevalence rate of dementia and its subtypes in Japan and to investigate the relationship of risk factors, such as demographic features and disease history, to the prevalence of Alzheimers disease or vascular dementia.

Endothelial markers and adhesion molecules in acute ischemic stroke—sequential change and differences in stroke subtype

The progress of a stroke concerns the activation of endothelial cells and platelets. We measured the plasma activities of von Willebrand factor (vWf) and the serum levels of soluble thrombomodulin (sTM) as endothelial markers, and the plasma concentrations of soluble P-selectin (sP-selectin) and soluble E-selectin (sE-selectin) as adhesion molecules during the acute (within 48 h from onset) and subacute (after 1 month from the onset) phases of 52 consecutive patients with acute ischemic stroke and 86 age-matched control subjects. The plasma vWf activities and levels of sP-and sE-selectins in stroke patients were significantly elevated compared with those in controls during both the acute and subacute phases. The serum levels of sTM in stroke patients were significantly higher than those in controls only during the subacute phase. In atherothrombotic infarction, the vWf activities and the levels of sP-selectin, markers for endothelial and platelet activation, remained higher until the subacute phase compared with controls, and the concentrations of sTM, a marker for endothelial injury, were increased during the subacute phase compared with during the acute phase. In lacunar infarction, the levels of sTM and sE-selectin of patients were higher only during the acute phase than controls. These findings suggest that the endothelial cell damage might be maintained until the subacute phase in atherothrombotic infarction, whereas it is remarkable only during the acute phase in lacunar infarction. The evaluation of endothelial markers and adhesion molecules would represent the pathophysiological states of stroke and may provide useful information for the treatment of the ischemic infarction.

Incidence of dementia, Alzheimer disease, and vascular dementia in a Japanese population: Radiation Effects Research Foundation adult health study.

Objective: To determine the age-, sex-, and subtype-specific incidence of dementia and to assess the effect of education level on the incidence in a Japanese population. Methods: 2,286 dementia-free subjects, aged ≧60 years, were followed for 5.9 years through biennial two-phase examinations. Results: 206 cases of dementia were newly diagnosed based on DSM IV. The incidence per 1,000 person-years was 12.0 for men and 16.6 for women. Based on NINCDS-ADRDA criteria, 80 cases of probable Alzheimer disease (AD) and 50 cases of possible AD were diagnosed. Based on NINDS-AIREN criteria, 36 cases of probable vascular dementia (VaD) and 40 cases of possible VaD were diagnosed. Age and education showed the most statistically significant effects for all dementia. Probable AD showed the most remarkable increase with age and decreased with increasing education level (p = 0.001). Probable VaD showed significant effects of sex (p = 0.033) and sex-age interaction (p = 0.048), but not education (p = 0.26). Conclusion: AD was the predominant type of dementia in this recent incidence study conducted in Japan, suggesting a reduction in VaD and an increase in AD. Age, sex, and education effects differed by dementia subtype.

Clonal Expansion of Double-Positive Intraepithelial Lymphocytes by MHC Class I-Related Chain A Expressed in Mouse Small Intestinal Epithelium

Expression of a distant homologue MHC class I molecule, MHC class I-related chain A (MICA), has been found to be stress inducible and limited to the intestinal epithelium. This nonclassical MHC molecule is associated with various carcinomas in humans. To understand the biological consequences of MICA expression in the gut, we generated transgenic (Tg) mice (T3b-MICA Tg) under the control of the T3b promoter. The T3b-MICA Tg mice expressed MICA selectively in the intestine and had an increased number of TCRαβ CD4CD8αα, double-positive (DP) intraepithelial lymphocytes (IELs) in the small bowel. These MICA-expanded DP IELs exhibited a bias to Vβ8.2 and overlapped motifs of the complementarity-determining region 3 region among various Tg mice. Hence, the overexpression of MICA resulted in a clonal expansion of DP IELs. Studies in model of inflammatory bowel disease showed that transgenic MICA was able to attenuate the acute colitis induced by dextran sodium sulfate administration. Therefore, this unique in vivo model will enable investigation of possible influences of stress-inducible MICA on the gut immune surveillance.

Changes in serum macrophage-related factors in patients with chronic inflammatory demyelinating polyneuropathy caused by intravenous immunoglobulin therapy

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a slowly progressive or recurrent neuropathy accompanied by infiltration of macrophages in the peripheral nerves. Macrophage colony-stimulating factor (M-CSF) and monocyte chemoattractant protein-1 (MCP-1) are a macrophage-related cytokine and chemokine, respectively. Although, intravenous immunoglobulin (IVIg) infusion therapy has been used for treating CIDP patients, not all CIDP patients have responded to IVIg infusion therapy. To determine the mechanisms of the action of IVIg, we examined serum M-CSF and MCP-1 levels during and after IVIg infusion therapy in 19 CIDP patients treated with IVIg (0.4 g/kg/day for 5 days). Ten of the 19 patients (52.6%) responded to IVIg therapy. Both M-CSF and MCP-1 concentrations in IVIg responders were significantly higher on day 1 postinfusion than those in nonresponders, but decreased to their pretreatment values on day 5 postinfusion. The results suggest that immunomodulation through M-CSF and MCP-1 is involved in the mechanisms underlying the effect of IVIg infusion therapy in CIDP patients.

Elevation of serum soluble E‐selectin and antisulfoglucuronyl paragloboside antibodies in amyotrophic lateral sclerosis

Immunological abnormality is often found in amyotrophic lateral sclerosis (ALS). Antibodies to sulfoglucuronyl paragloboside (SGPG) were reported in ALS, although the pathogenetic significance of the antibodies is still unknown. We have already demonstrated that SGPG, a unique glycolipid, is present in both peripheral nerve and vascular endothelial cells. To investigate whether serum anti‐SGPG antibodies would participate in activation and/or injury of endothelial cells in ALS, we examined serum anti‐SGPG antibodies in association with serum soluble E‐ and P‐selectins, which are markers of activated endothelial cells, in 25 patients with ALS and 14 age‐matched patients with other neurological diseases (ONDs) using the microtiter‐ELISA method. Seven out of 25 ALS patients had anti‐SGPG antibodies. Levels of sE‐selectin were significantly higher in patients with ALS (48.5 ± 23.4 ng/ml) compared with ONDs (24.0 ± 11.8 ng/ml) (P < 0.005). Four out of seven ALS patients with anti‐SGPG antibodies had concomitantly high sE‐selectin levels. The mean sE‐selectin levels were higher in patients with anti‐SGPG antibodies (61.9 ± 25.2 ng/ml) than in those without anti‐SGPG antibodies (43.3 ± 21.1 ng/ml). Anti‐SGPG antibodies may take part in the activation and/or injury of endothelial cells. The increased expression of E‐selectin may be related to an immunological process in some ALS patients.

Therapeutic effects of intensive inpatient rehabilitation in advanced Parkinson's disease

The importance of rehabilitation therapy in Parkinsons disease is well recognized. However, the effects of an inpatient rehabilitation program for advanced Parkinsons disease have not been fully investigated.

Amelioration of Persistent, Non-Ketotic Hyperglycemia-Induced Hemichorea by Repetitive Transcranial Magnetic Stimulation

Diabetic hemichorea-hemiballism with non-ketotic hyperglycemia is usually a benign syndrome. Here, we report a 78-year-old woman with persistent hemichorea (HC) for longer than 1 year with a recurrence after rapid correction of hyperglycemia. Following the disappearance of the characteristic T1 hyperintensity at 3 months after onset, an MRI demonstrated T2* hypointensity and atrophic changes in the contralateral striatum, suggesting irreversible neuronal loss and some vascular proliferation. The electrophysiological examination using transcranial magnetic stimulation revealed significantly shorter cortical silent periods (CSPs) on the contralateral primary motor cortex (M1), possibly in relation to cortical hyperexcitability. We have applied 10 daily sessions of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the contralateral M1 to reduce the hyperexcitability. The HC was suppressed during and for several minutes after rTMS with prolongation of CSPs. After rehabilitation therapy, the patient was able to walk independently with a walker. We suggest that the combination of low-frequency rTMS and rehabilitation therapy may be a possible choice in medically refractory involuntary movements.

Endothelial cell activation and/or injury in multiple sclerosis comparative analysis with endothelial markers and adhesion molecules

101 A Comparative Study of MMP and TIMP-2 Production in Rat and Human Foetal CNSVaseular Endothdial Cell Lines K.A. Harkness,Royal Hallamshire Hospital, U.K., M.N. Woodroofe, Sheffield Hallam University, U.K., J.D. Sussman, G.A.B, Davies-Jones, RoyaIHallcu~sh~Hosp~tal, UX. 104 Interferon-b Induces Release of Soluble Adhesion Molecules from Human Cerebral Endothelial Cells B. Kallmann, V. Hum m el, K. Toyka, P, Rieckmann, Umver~ity of Wuerzburg, Germany