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B Mihara

Publications and source records attributed to B Mihara.

At least 37 records · Page 2Linked to original sources

Morphometry of structural preservation of tunica media in aged and hypertensive human intracerebral arteries.

BACKGROUND AND PURPOSE: Medial smooth muscle cell necrosis has been reported as a lesion that may precede angionecrosis, which is a major cause of not only hypertensive brain hemorrhage but also lacunar infarct. We morphometrically studied a loss of smooth muscle cells in the media of cerebral arteries in relation to clinical risk factors. METHODS: The lateral striate, ie, perforating arteries and the medullary arteries in the subcortical white matter of the temporal lobe (100 to 400 microns in diameter) were histologically investigated in 121 autopsied brains. Medial area was measured quantitatively, and the number of nuclei of smooth muscle cells in the area was calculated in 1210 cross-sectional arteries of histological sections. The influence on the structural (ie, smooth muscle cell) preservation of the tunica media (ratio of number of smooth muscle cell nuclei to medial area [N-MA ratio]) of age, blood pressure, serum lipids, and presence of absence of extracerebral severe atherosclerosis was investigated. RESULTS: The N-MA ratio decreased slightly with age in both arteries. A reverse correlation between N-MA ratio and age was seen in groups both with and without hypertension. The mean N-MA ratio in the hypertensive group was significantly lower than that of the nonhypertensive group (P < .001) in all decades of life. The mean N-MA ratio of the perforating arteries was slightly lower than that of the medullary arteries in both groups. Severe atherosclerosis of the internal carotid arteries, even with hypertension, mitigated a decrease of the N-MA ratio, which was as slight as that in the nonhypertensive group. Serum cholesterol in this group was higher than in both the conventional hypertensive group (P < .005) and the nonhypertensive group (P < .001). CONCLUSIONS: Although both hypertension and age were significant risk factors for medial smooth muscle cell necrosis, hypertension was relatively more significant. Medial smooth muscle cells of the perforating arteries in the basal ganglia were more vulnerable than those of the medullary arteries. Cerebral small arteries in subjects with severe atherosclerosis of the carotid and major cerebral arteries (hypertension in eight of nine subjects) may have been protected from extensive loss of medial smooth muscles presumably because of both high serum cholesterol and decreased wall tensile stress associated with reduced blood perfusion due to severe atherosclerotic stenosis.

Adolescent↗

Immobilization stress induces alterations of second-messenger systems in the gerbil brain.

The effects of immobilization stress on the cerebral second messenger (adenylate cyclase and phosphoinositide) were investigated autoradiographically in mongolian gerbils. After 10 min (10-min stress group, n = 7), or after 6 h (6-h stress group, n = 7) of fixation on a flat board while supine, in vitro autoradiography was performed using [3H]forskolin (3H-FK) and [3H]phorbol-12,13-dibutyrate (3H-PDBu) as specific ligands to identify the distribution of adenylate cyclase and protein kinase C, respectively. In another group of 7 gerbils (control group), the same autoradiographic procedure was performed immediately after the animals were removed from the cage. In the 10-min stress group, FK binding was significantly decreased in the hypothalamus and amygdala, but significantly increased in the basal ganglia including the caudate-putamen and globus pallidus. FK binding in the 6-h stress group tended to increase throughout the brain, rising significantly in the basal ganglia. PDBu binding in either stress group did not change significantly compared to the control group in any region except the hippocampal CA3 region of the 6-h stress group. Under immobilization stress, the adenylate cyclase system may undergo time-dependent and regionally specific changes, while the phosphoinositide system remains relatively stable.

Adenylyl Cyclases↗

Reduction in second-messenger ligand binding sites after brain ischemia--autoradiographic Bmax and Kd determinations using digital image analysis.

Changes in forskolin (FK) and phorbol 12,13-dibutyrate (PDBu) binding were evaluated in relation to local cerebral blood flow (CBF) after 6-h unilateral carotid artery occlusion in the gerbil striatum employing a quantitative autoradiographic method, which permitted these three parameters to be measured in the same brain. CBF was measured by the [14C]iodoantipyrine method at the end of the experiment. [3H]FK and [3H]PDBu were utilized as specific ligands to assess the activity of adenylate cyclase (AC) and protein kinase C (PKC), respectively. A saturation study was undertaken to measure the Kd (dissociation constant) and Bmax (maximal binding capacity) of each ligand by digital image processing of sequential autoradiograms employing pixel-by-pixel Scatchard analysis. The Bmax values of FK and PDBu were significantly decreased on the ischemic side, but the reduction in Bmax of FK was greater than that of PDBu. The K4 of each ligand remained unchanged. The FK binding underwent a progressive decline as CBF fell below 30 ml/100 g/min. The PDBu binding showed only a gradual decline in parallel with the CBF reduction. These findings suggest that a reduction in CBF below 30 ml/100 g/min for 6 h may induce a remarkable suppression of the AC system with less significant inhibition of the PKC system in the striatum.

Adenylyl Cyclases↗

Inhibition of nitric oxide synthesis impairs autoregulation of local cerebral blood flow in the rat.

The effect of intravenous administration of NG-monomethyl-L-arginine (L-NMMA, 30 mg kg-1), a specific inhibitor of nitric oxide (NO) synthesis, on the autoregulation of local cerebral blood flow (LCBF) was examined in the rat using the [14C]iodoantipyrine autoradiographic method. LCBF was significantly lower in various superficial regions such as the cerebral cortices and cerebellar cortex and in several deep brain regions in animals with haemorrhagic hypotension induced after L-NMMA infusion (the L-NMMA + HEM group) compared with animals without haemorrhagic hypotension after L-NMMA infusion (the L-NMMA group). The present findings suggest that NO synthesis may play a crucial role in the autoregulation of LCBF in response to a reduction in blood pressure in the cerebral cortices, cerebellar cortex and several deep brain regions.

Animals↗

[Alteration of inositol 1,4,5-trisphosphate receptor binding after 6-hour hemispheric ischemia in the gerbil brain].

Inositol 1,4,5-trisphosphate (IP3) has recently been known to play vital roles as one of the second messengers to control intracellular metabolism of calcium ion. Therefore, alterations of IP3 receptor binding and local cerebral blood flow (1CBF) were evaluated at 6 hours after occlusion of the right common carotid artery in the gerbil brain. The autoradiographic method developed in our laboratory enabled us to measure both parameters in the same brain. Animals attaining more than 5 in their ischemic scores, which were assessed at 1 hour after the occlusion, were utilized. LCBF was measured by the 14C-iodoantipyrine method at the end of the experiment. After frozen brains were cut into serial slices on a cryostat, the IP3 receptor binding was evaluated in vitro by using 3H-inositol 1,4,5-trisphosphate as the ligand. LCBF fell below 10 ml/100 g/min in most of the cerebral regions on the occluded side. In contrast a significant reduction in IP3 binding was noted only in the hippocampus CA1 on the occluded side. The IP3 binding tended to decrease when the values of 1CBF were reduced below 20 ml/100 g/min in this region. These findings suggest that the selective alteration of IP3 receptor binding in the hippocampus CA1 may be closely associated with the selective vulnerability of this region to ischemia.

Animals↗

Alteration of second-messenger ligand binding following 2-hr hemispheric ischemia in the gerbil brain.

The alterations of second-messenger ligand binding and cerebral blood flow (CBF) were evaluated in the gerbil brain after 2-h unilateral common carotid artery occlusion. [3H]Forskolin (FK) and [3H]phorbol-12,13-dibutyrate (PDBu) were used as specific ligands for adenylate cyclase (AC) and protein kinase C (PKC) activity estimation, respectively. CBF was determined at the end of the experiment by the [14C]iodoantipyrine method. A quantitative autoradiographic method permitted simultaneous measurement of the three parameters in the same brain. The levels in the caudate-putamen, globus pallidus, and hippocampus were analyzed. The animals were divided into three groups: Group 1 with severe ischemia (CBF in the lateral nuclei of the thalamus (CBFt) less than 50 ml/100 g/min), Group 2 with mild ischemia (CBFt greater than or equal to 50 ml/100 g/min), and the Sham Group. The PDBu binding revealed a statistically significant increase in the caudate-putamen, lateral nuclei of the thalamus and hippocampus (CA1 and CA3 regions and dentate gyrus) on the ischemic side in Group 1 as compared to that in Group 2 and the Sham Group. In contrast, the FK binding did not show any significant changes in any of the regions. These data and our previous findings for 6-h ischemia suggest that (1) PKC translocation to the cell membrane may occur at the early ischemic phase in particular regions including the caudate-putamen, lateral nuclei of the thalamus and hippocampus, with the translocated PKC gradually diminishing during the subsequent ischemic period; and (2) the suppression of the AC system observed in 6-h ischemia may not appear in the early ischemic phase.

Adenylyl Cyclases↗

Animal species differences in erythrocyte aggregability.

Species differences in erythrocyte aggregability were investigated employing our whole blood erythrocyte aggregometer. Blood was sampled from seven species, including humans and anesthetized (30 mg/kg pentobarbital) animals. The erythrocyte aggregation rates were the following (in s-1): cats, 0.213 +/- 0.027 (means +/- SD); dogs, 0.164 +/- 0.027; men, 0.112 +/- 0.025; rats, 0.111 +/- 0.005; domestic rabbits, 0.049 +/- 0.021; and mongolian gerbils, 0.034 +/- 0.015. Domestic fowls did not exhibit erythrocyte aggregograms like those seen in the other species. Statistical analysis revealed significant differences among the erythrocyte aggregation rates of the different species (multiple-comparisons with an overall significance level of 0.05) except between men and rats and between rabbits and gerbils. No single factor which is known to accelerate the erythrocyte aggregation rate (hematocrit, fibrinogen, etc.) was correlated with the erythrocyte aggregation rate except the globulin concentration in the blood. The failure to detect erythrocyte aggregation in domestic fowls was probably attributable to their erythrocyte shape. These results suggest that each species has its own proper tendency for erythrocyte aggregation. This factor must be taken into consideration when the blood circulation is discussed among different animal species.

Animals↗

Inhibition of nitric oxide synthesis induces a significant reduction in local cerebral blood flow in the rat.

The effect of intravenous administration of NG-monomethyl-L-arginine (L-NMMA, 30 mg/kg), a specific inhibitor of nitric oxide synthesis, on local cerebral blood flow (lCBF) was examined in the rat using the [14C]iodoantipyrine autoradiographic method. L-NMMA induced a statistically significant reduction in lCBF in the cerebral cortices as well as in various deep structures of the brain. This reduction in lCBF was accompanied by a clear increase in mean arterial blood pressure, suggesting that the cerebral resistance vessels constricted significantly beyond the autoregulatory response following L-NMMA administration. These findings indicate that the basal cerebral circulation may be closely related to nitric oxide production.

Animals↗

Autoradiographic analysis on second-messenger systems and local cerebral blood flow in ischemic gerbil brain.

Alterations of the second-messenger systems, adenylate cyclase (AC) and protein kinase C (PKC), and local cerebral blood flow (lCBF) were evaluated during experimental cerebral ischemia in gerbils employing a quantitative autoradiographic method, which permitted these three parameters to be measured in the same brain. Ischemia was induced by occlusion of the right common carotid artery for 6 h. Animals attaining more than 5 in their ischemic scores were utilized for further experiments. At the end of ischemia, lCBF was measured by the [14C]iodoantipyrine method. The AC and PKC activities were estimated by the autoradiographic technique developed in our laboratory using [3H]forskolin (FK) and [3H]phorbol-12,13-dibutyrate (PDBu), respectively. The lCBF fell below 10 ml/100 g/min in most cerebral regions on the ligated side. The greatest reduction in FK binding was noted in the olfactory tubercle, caudate-putamen, and globus pallidus, followed by the hippocampus and cerebral cortices. The FK binding tended to be low at lCBF less than 20 ml/100 g/min in the cerebral cortices. However, the PDBu binding was relatively well preserved in each cerebral structure, and no significant correlation between lCBF and PDBu binding was noted in the cerebral cortices. The AC system may thus be vulnerable to ischemic insult over extensive brain regions, while the PKC system may be relatively resistant to ischemia.

Adenylyl Cyclases↗

Effects of lesioning of the substantia innominata on autoregulation of local cerebral blood flow in rats.

Recently, accumulated data have suggested that the nucleus basalis magnocellularis, i.e., the substantia innominata (SI), may represent the primary source of central cholinergic innervation in the rat cortical vasculature. We therefore examined the effects of unilateral lesion of the SI on the autoregulation of local CBF (lCBF) during induced hypotension in rats. Male Wistar rats were divided into three groups. The animals of groups 1 and 2 received an injection of 5 micrograms of ibotenate into the right SI stereotaxically. At 7 days after the injection, the lCBF was measured by the [14C]iodoantipyrine technique in the awake state. Group 1 was used as the normotensive group (MABP = 113.1 +/- 12.2 mm Hg). Group 2 formed the hypotensive group, and the lCBF was measured during hypotension (MABP = 80.0 +/- 5.5 mm Hg) induced by hemorrhage. Group 3, the sham-operated normotensive group, received vehicle injection into the right SI at 7 days prior to the lCBF measurement. In group 1, lCBF was significantly lower in the frontal, parietal, temporal, and striate cortices on the lesioned side compared to that on the contralateral side. In group 2, lCBF was significantly decreased in the cortices on the lesioned side, but there was no significant difference in magnitude of the lCBF reduction between groups 1 and 2. Group 3 exhibited no hemispheric asymmetries in lCBF. These findings suggest that the SI exerts an influence on cortical lCBF, but does not play a role in the autoregulation of lCBF during hypotension.

Animals↗

Two types of abnormal somatosensory evoked potentials in chronic cerebellar ataxias.

To investigate subclinical sensory impairment in spinocerebellar degenerations, median nerve somatosensory evoked potentials (SEPs) were examined in 16 patients with chronic cerebellar ataxia who were originally diagnosed by clinical neurologists as having olivopontocerebellar atrophy (OPCA). Two types of abnormal SEP patterns were found in six patients. Two patients had the SEP pattern of peripheral neuropathy, which was also detected by peripheral sensory nerve conduction studies. Four patients had abnormal SEPs seen in patients with the lesions in the central nervous system (dorsal column, medial lemniscus). Magnetic resonance imaging (MRI) showed multiple sclerosis (MS). It is possible that clinically diagnosed OPCA sometimes includes a similar form of Friedreich's ataxia with subclinical sensory fiber neuropathy detected by SEPs and peripheral sensory conduction studies. In cases of lesions in the central nervous system demonstrated by both SEPs and MRI, there must be a follow-up in order to make a final diagnosis. In those cases, an alternative diagnosis of MS must be considered when the temporal profile of symptoms and signs characteristic of MS is observed.

Adult↗

[Anticardiolipin antibody in cerebral infarction].

We investigated the anticardiolipin antibody (ACA) in a series of patients with cerebral infarction without systemic lupus erythematosus (SLA). Clinical and laboratory data were assessed from a series of 250 non-SLE patients with cerebral infarction who visited our clinic from 1988 to 1990. The concentration of anticardiolipin IgG antibody was measured by an enzyme-linked immunosorbent assay technique. An elevated ACA level was defined as one which was greater than 3 standard deviations above the mean level for normal controls. We examined the CT findings and risk factors for stroke such as hypertension, diabetes mellitus, hyperlipidemia and cardiac disease. Laboratory data such as the platelet count, the presence of lupus anticoagulant and a biologic false-positive test for syphilis were also investigated. Among the 250 patients with infarction, IgG ACA was detected in 22 (8.8%). There was no significant difference in incidence of ACA between the patients with cerebral thrombosis and those with cerebral embolism. On CT scan, multiple cerebral infarcts were noted in 18 of the 22 patients. As regards the location of the infarct, the cerebral cortex together with the basal ganglia was more common than isolated lesions of the cortex or basal ganglia. Concerning the risk factors for stroke, hypertension was noted in 12, diabetes mellitus in 2, hyperlipidemia in 2 and cardiac disease in 2. Lupus anticoagulant and thrombocytopenia were not detected in any of the cases. A biologic false-positive test for syphilis was observed in one case. Dementia was present in 12 of the 22 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The mechanical filtration coefficient (Lp) of the cell membrane of cultured glioma cells (C6).

The mechanical filtration coefficient (Lp) of the membrane of cultured glioma cells was determined from the rate of swelling of the cells. The swelling was induced by exposing the cells to distilled water. Assuming that cells swell in a symmetrical manner, Lp was 2.2 x 10(-8) cm/s.mmHg, or 1.7 x 10(-4) microns/s.cmH2O when calculated from changes of the cell diameter.

Cell Membrane↗

Effect of glycerol on the hemodynamics of acutely induced ischemic area in the cerebral cortex of cats.

The effect of glycerol on the hemodynamics of ischemic areas of the brain was examined. Employing a photoelectric apparatus, the CBV (vol%), mean transit time of blood(s), and CBF (ml/100 g/min) in the cortex of the left ectosylvian gyrus were determined in 16 anesthetized cats before, at 1 hr, and at 2 hr after left MCA occlusion. In 10 cats, 10% glycerol in 5% fructose saline was intravenously administered at a speed of 5 ml/kg/hr at 1 hr after MCA occlusion. The other animals served as the control. In the group given glycerol, the relation between the values of CBF at 1 hr after MCA occlusion (X) and those at 2 hr after MCA occlusion (Y) was curvilinear and could be expressed by the regression curve, Y = 0.04X2 - 0.26X + 7.68 (R2 = 0.86). In the control group without glycerol, however, a linear relation expressed by the equation, Y = 0.76X + 5.96 (R2 = 0.94), was obtained. Comparison between the two relations indicated that glycerol improved the hemodynamics in the mild ischemic area with a relatively higher CBF. Severely ischemic areas showed no improvement.

Animals↗

Enhanced erythrocyte aggregability in occlusive cerebrovascular disease.

We measured the rate of erythrocyte aggregation using our whole-blood aggregometer in 80 patients with occlusive cerebrovascular disease during the acute and chronic phases. We compared the data with values for 38 age-matched healthy controls. Mean +/- SD erythrocyte aggregability of the patients during both the acute phase (0.145 +/- 0.21/sec, n = 35) and the chronic phase (0.139 +/- 0.21/sec, n = 45) was higher than that in the controls (0.123 +/- 0.21/sec, n = 38; p less than 0.01). Erythrocyte aggregability was positively correlated with the plasma concentration of globulin and fibrinogen and inversely correlated with the albumin:globulin ratio. However, these correlations did not necessarily exclude the possibility that some unknown substance(s) released from ischemic tissue might enhance erythrocyte aggregability.

Acute Disease↗

Effects of lesions in the substantia innominata on active avoidance task and cerebral glucose metabolism.

Abnormalities in the central cholinergic system have been reported in Alzheimer disease. The present study was designed to evaluate the effects of the central cholinergic neurons in the substantia innominata on cognitive functions and cerebral metabolism in rats. Forty-nine Wistar rats were trained for an active avoidance task for 5 days. On Day 5, rats which had acquired the avoidance response were divided into two groups. The lesioned group (n = 7) received ibotenic acid in the substantia innominata bilaterally and the sham-operated group (n = 7) received the vehicle only. From Day 8 to 12, the rats were again trained for the avoidance task. On Day 12, the local cerebral metabolic rate for glucose was measured by the 14C-2-deoxyglucose method. The rats in the lesioned group revealed severe deficits in retention and re-acquisition of the active avoidance task. In addition, the glucose metabolism was decreased in the cerebral cortices, especially in the frontal cortex (p less than 0.05). The central cholinergic neurons of the substantia innominata may be closely related to cognitive functions and to glucose metabolism in the cortices.

Animals↗