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K Yanagawa

Publications and source records attributed to K Yanagawa.

30 records · Page 2Linked to original sources

[Brain MRI findings in patients with initial cerebral thrombosis and the relationship between incidental findings, aging and dementia].

To estimate the relationship between aging, dementia and changes observed on magnetic resonance imaging (MRI) seen in elderly patients with cerebral thrombosis, MRI findings in 103 patients with an initial stroke event (thrombosis group) were compared with those of 37 patients with hypertension/diabetes (high risk group) and 78 patients without those disorders (low risk group). In addition to the causative lesions in the thrombosis group, periventricular hyperintensities (PVH), spotty lesions (SL), silent infarctions (SI), ventricular dilatation (VD), and cortical atrophy (CA) were analyzed in these groups. Infarctions located in the internal capsule/corona radiata were the most frequent causative lesion. Compared to the low risk group, a high incidence of patchy/diffuse PVH, SI, and severe CA was seen in both the thrombosis group and the high risk group. Widespread PVH and multiple SL increased with age in the thrombosis group, while severe CA was seen in each group. SI and VD tended to increase after age 60, though they were not significant. Dementia, diagnosed in 40 out of 78 patients, increased with age. Multivariate analysis revealed the degree of the effects of MRI findings on dementia to be marked in PVH, brain atrophy, causative lesions, and SL, in that order. These results indicated that diffuse PVH and brain atrophy, developing with age, promoted dementia in the elderly with vascular lesions. Moreover, they suggested that a variety of silent brain lesions recognized on MRI other than infarction can affect symptoms in the elderly.

Aged↗

Binding of [3H]KF17837S, a selective adenosine A2 receptor antagonist, to rat brain membranes.

The potential of 8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-[3H] methylxanthine ([3H]Kf17837S) as a highly selective antagonist radioligand for the adenosine A2A receptor was examined and compared with the properties of the adenosine A2A receptor agonist radioligand 2-[p-(2-[3H]carboxyethyl)phenethylamino]-5'-N-ethyl- carboxamidoadenosine ([3H]CGS21680). [3H]KF17837S specific binding to rat striatal membranes was saturable and reversible. Saturation studies showed that the binding of [3H]KF17837S occurred at a single site, with high affinity (Kd, 7.1 +/- 0.91 nM) and limited capacity (Bmax, 1.3 +/- 0.23 pmol/mg of protein). Adenosine receptor antagonist ligands competed with the binding of 1 nM [3H]KF17837S with the following order of activity: CGS15943 > KF17837S > N-[2-(dimethylamino)ethyl]-N-methyl- 4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)benzenesul fonamide > or = xanthine amine congener > 8-cyclopentyl-1,3-dipropylxanthine > 8-(noradamantan-3-yl)-1,3-dipropylxanthine > caffeine. Adenosine receptor agonists inhibited [3H] KF17837S binding in the following order: 5'-N-ethylcarboxamidoadenosine > or = CGS21680 > 2-phenylaminoadenosine > or = (R)- N6-phenylisopropyladenosine > N6-cyclopentyladenosine > (S)- N6-phenylisopropyladenosine. The Ki values of the antagonists for [3H]KF17837S binding and the rank order of potency were similar to those for [3H]CGS21680 binding. The affinities of the agonists were lower with [3H]KF17837S binding than with [3H] CGS21680 binding. However, a strong positive correlation (r = 0.98) was observed between the pharmacological profiles for these two radioligand assays. The inhibition curve for CGS21680 was best fitted to a two-component binding model and addition of GTP shifted the inhibition curve to the right, suggesting that [3H]KF17837S labeled two agonist coupling states. Other pharmacological agents had negligible affinities for the [3H]KF17837S binding site. Autoradiographic study of [3H]KF17837S binding using rat brain sections revealed that the binding site was highly enriched in the striatal region. These data indicate that [3H] KF17837S labels the adenosine A2A receptor in rat brain.

Adenosine↗

[Effect of long-term lithium treatment on serotonin syndrome in rats].

Brain 5-HT receptors are reported to play an important role in the therapeutic effect of Li in manic-depressive illness. In the present study we examined the effect of Li on 5-HT syndrome which is postulated to be the physiological response of 5-HT1 receptors. Intraperitoneal injection of the 5-HT receptor agonist 5-MeODMT elicited 5-HT syndrome in a dose-dependent manner. Then the incidence of 5-HT syndrome elicited by 2 mg/kg of 5-MeODMT was measured in animals under long-term Li treatment. Four out of six abnormal behaviors of the 5-HT syndrome, i.e. forepaw treading, resting tremor, rigidity, and head weaving, were significantly increased by the 9-day treatment with Li. On the 17th day of Li treatment, the incidence of all six behaviors, including hindlimb abduction and straub tail, were significantly enhanced. This Li-induced supersensitivity of 5-HT1 receptor-mediated behaviors inconsistent with the previous reports of the down-regulation of 5-HT1 receptors measured by receptor binding assay. The reason for this discrepancy is obscure. Further examination of the effect of Li on the signal-transduction system from the receptor to the behavior will be necessary.

Animals↗

Changes in antioxidative mechanisms in elderly patients with non-insulin-dependent diabetes mellitus. Investigation of the redox dynamics of alpha-tocopherol in erythrocyte membranes.

BACKGROUND: Recently, it has been suggested that the onset and aggravation of diabetes are closely related to free radicals. Also, vitamin E is a lipophilic free radical scavenger that is localized mainly in biomembranes. OBJECTIVE: The purpose of this study was to clarify the defensive mechanisms against oxidative stress by investigating the differences in the redox dynamics of alpha-tocopherol in plasma and erythrocyte membranes between elderly patients with non-insulin-dependent diabetes mellitus (NIDDM) and healthy elderly subjects. METHODS: Total, alpha-, beta-, gamma- and delta-tocopherol and alpha-tocopherolquinone concentrations were determined by high-performance liquid chromatography with a redox detection mode using a series of four coulometric working electrodes. RESULTS: The alpha-tocopherolquinone/alpha-tocopherol ratio in plasma and erythrocyte membranes was not different between the two groups. Both the alpha-tocopherol concentrations in erythrocyte membranes and ratio of alpha-tocopherol in erythrocyte membranes to alpha- tocopherol in plasma was significantly lower in elderly NIDDM patients than in healthy subjects. CONCLUSION: These findings suggest that alpha-tocopherol is used normally in both plasma and erythrocyte membranes and alpha-tocopherol uptake in erythrocyte membranes is significantly decreased in elderly NIDDM patients. The functional disorder of the antioxidative activity of alpha-tocopherol in erythrocyte membranes due to impairment of this transfer mechanism may be associated with the pathogenesis of NIDDM.

Aged↗

The antiproliferative effect of HGF on hepatoma cells involves induction of apoptosis with increase in intracellular polyamine concentration levels.

Hepatocyte growth factor (HGF) induced apoptosis and decreased the DNA synthesis in Hep G2 cells. In the HGF group interleukin-1 converting enzyme, ornithine decarboxylase (ODC) activity and intracellular polyamine concentrations were increased compared to those of the control group. Administration of the ODC inhibitor decreased polyamine concentration, and inhibited apoptotic changes in the cells. These changes were reversed by exogenous addition of polyamine. These findings suggest that one of the mechanisms by which HGF exerts its antiproliferative effect is induction of apoptosis and that increase in intracellular polyamine concentration may be one of the triggers of cell death.

Apoptosis↗