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Biomedical subjects

Y Ouchi

Publications and source records attributed to Y Ouchi.

At least 253 records · Page 14Linked to original sources

Progression of atrophy of the corpus callosum with deterioration of cerebral cortical oxygen metabolism after carotid artery occlusion: a follow up study with MRI and PET.

In cerebrovascular disease, progression of brain atrophy may reflect an increase in ischaemic changes. The purpose of this study was to determine whether atrophy of the corpus callosum progresses in association with a deterioration in cerebral cortical oxygen metabolism after occlusion of the carotid artery. Magnetic resonance imaging and PET were used to serially evaluate six patients with occlusion of the unilateral internal carotid artery at intervals ranging from 12 to 50 months. One patient had no symptoms, one had a transient ischaemic attack, and four had a minor stroke. All patients had presented at most only subcortical lesions at the first evaluation. During follow up, no patient showed extension of subcortical lesions or recurrent stroke. The initial total callosal area:skull area ratio for the patients was significantly less than that for 14 age matched normal control subjects. The yearly decrease of callosal size in the patients, which differed significantly from zero and exceeded that in the controls, was significantly correlated with the deterioration in mean cerebral cortical oxygen metabolism. Three of the four patients who showed significant progression of callosal atrophy presented deterioration in haemodynamic states as well. It is concluded that in some patients atrophy of the corpus callosum progresses after occlusion of the carotid artery even in the absence of any overt episode of stroke, and that this atrophy is associated with deterioration in cerebral cortical oxygen metabolism. An increase in cerebral morphological changes with deterioration in cerebral metabolism related to ischaemia may occur after occlusion of the carotid artery, even in the absence of symptoms.

Aged↗

Inhibitory effects of insulin on cytosolic Ca2+ level and contraction in the rat aorta. Endothelium-dependent and -independent mechanisms.

To determine the mechanism of the inhibitory effect of insulin on vascular tone, contraction was measured simultaneously with endothelial and smooth muscle cytosolic Ca2+ level ([Ca2+]i) in the isolated rat aorta. Insulin (200 mU/mL) increased endothelial [Ca2+]i and decreased resting muscle tone. The removal of endothelium abolished the effects of insulin. In the aorta precontracted with norepinephrine, insulin (3 to 120 mU/mL) induced concentration-dependent inhibition of contraction. The relaxant effect followed the increase in endothelial [Ca2+]i and decrease in smooth muscle [Ca2+]i. The relaxant effect was attenuated by removal of endothelium or by the addition of 10(-5) mol/L NG-monomethyl-L-arginine but not by 10(-5) mol/L indomethacin. In the absence of endothelium, the relaxant effect of insulin followed the decrease in smooth muscle [Ca2+]i. These results suggest that insulin inhibits vascular contraction by dual mechanisms in the isolated rat aorta: (1) Insulin acts on vascular endothelium by increasing endothelial [Ca2+]i and releasing NO, which decreases smooth muscle [Ca2+]i and the Ca2+ sensitivity of the contractile elements. (2) Insulin also directly acts on smooth muscle and decreases smooth muscle [Ca2+]i.

Animals↗

Improved skin blood flow and cutaneous temperature in the foot of a patient with arteriosclerosis obliterans by vasopressin V1 antagonist (OPC21268). A case report.

A seventy-four-year-old woman with arteriosclerosis obliterans, diabetes mellitus, and hypertension was admitted for the treatment of intermittent claudication and coldness and pain in the right lower extremity. After the administration of a vasopressin V1 antagonist, OPC21268, the symptoms were markedly improved. Furthermore, blood flow in the dorsalis pedis artery and the cutaneous temperature in the right foot increased in response to acute and chronic administration of OPC21268. OPC21268 may be a new useful therapeutic tool for the treatment of arteriosclerosis obliterans.

Aged↗

[Compliance with prescriptions and adverse drug reactions in the elderly].

We performed a survey concerning prescriptions in the elderly to investigate the influence of ageing on compliance and the occurrence of adverse drug reactions. First, we surveyed 222 outpatients attending at our department (average 70.2 y.o.). The physicians in change examined the account of remaining medicines, and we analyzed the relationship between the compliance with prescriptions, age, diseases and medicines. Secondly, we surveyed 282 inpatients (average 68.0 y.o.). We compared the number of prescriptions before hospitalization, at discharge and 6 months after discharge. We also examined the frequency of adverse drug reactions. The number of medicines, which were prescribed for both in- and outpatients, increased according to age. However, no ageing effect on the number of prescriptions per disease was found. The average number of prescriptions per patient at discharge significantly increased compared to that before hospitalization. The average number of prescriptions of the elderly (above 65 y.o.) admitted at emergency case was significantly more than regularly admitted elderly (p < 0.01). The rate of proper medication taking was significantly higher in the elderly than in the young (p < 0.05). The total percentage of adverse drug reactions among inpatients was 18.8%. Among the patients aged above 60 y.o., the frequency of adverse drug reactions increased according to age. Increased number of the prescribed medicines might be involved in the cause of increased adverse drug reactions in the elderly.

Adult↗

Effect of an intracerebroventricularly administered vasopressin V1 antagonist on blood pressure and heart rate in deoxycorticosterone-salt hypertensive rats.

It is well known that peripheral vasopressin (VP) is essential for the development and maintenance of DOC-salt hypertension. It is, however, still unclear whether central VP is involved in this type of hypertension. Therefore, the aim of this study was to clarify the role of central VP in the regulation of blood pressure in DOC-salt hypertension. In order to examine this issue, three series of investigations were performed. First, a novel vasopressin V1 antagonist (OPC21268) was administered intravenously to DOC-salt hypertensive rats, and mean arterial blood pressure (MABP) and heart rate (HR) were recorded. Second, the concentration of VP in the perfusate of microdialysis of cerebrospinal fluid (CSF) was determined in DOC-salt hypertensive and control rats. Finally, intracerebroventricular (i.c.v.) administration of a V1 antagonist was performed in DOC-salt hypertensive rats to determine the central mechanism of hypertension. Intravenous administration of a V1 antagonist had no effect on MABP and HR. There was no difference in VP in the perfusate of CSF between DOC-salt hypertensive and control rats. I.c.v. administration of a V1 antagonist significantly decreased MABP and HR in a dose-dependent manner in DOC-salt hypertensive rats (P < 0.05-0.01). These results suggest that central VP is involved in the maintenance of DOC-salt hypertension, and the mechanism is, in part, mediated by upregulation of the V1 receptor.

Animals↗

Demonstration of activin-A in arteriosclerotic lesions.

We previously reported that follistatin, an activin-binding protein, is produced in arteriosclerotic lesions. Here, the expression of activin-A which promotes the growth of vascular smooth muscle cells was examined in arteriosclerotic lesions of WHHL (Watanabe heritable hyperlipidemic) rabbits. Activin-A mRNA was detected in normal aorta by reverse transcriptase-polymerase chain reaction using specific primers for activin-A cDNA and was increased remarkably in arteriosclerotic lesions. In addition, using the cloned rabbit activin-A cDNA, RNA probe was prepared and in situ hybridization histochemistry was performed. Activin-A transcripts were detected abundantly in neointima of the diseased artery. Furthermore, immunohistochemistry also detected activin-A at the protein level. These observations suggest that activin-A is a cytokine expressed in arteriosclerotic lesions and might be involved in the pathogenesis of atherosclerosis.

Activins↗

Parathyroid hormone-related protein reduces cytosolic free Ca2+ level and tension in rat aortic smooth muscle.

The effect of parathyroid hormone-related protein (PTHrP) on cytosolic free Ca2+ level ([Ca2+]i) and tension in rat aortic smooth muscle was investigated with special reference to the role of production and action of cyclic AMP. Rat aortic spiral strip preparations without endothelium were treated with the acetoxymethyl ester of fura 2, and the ratio of fluorescences (R340/380), an index of [Ca2+]i, emitted from smooth muscle, was measured. The tension of the preparations was simultaneously measured. PTHrP-(1-34) produced concentration-dependent decreases both in the tension and in R340/380 increased by phenylephrine (10(-7) M). These effects were significantly inhibited by pretreatment with either PTHrP-(7-34) (10(-6) M), a PTHrP receptor antagonist, or with Rp diastereomer of adenosine cyclic 3',5'-phosphorothioate (RpcAMPS; 10(-4) M), a cyclic AMP-dependent protein kinase inhibitor. Dibutyryl cyclic AMP (10(-5)-10(-3.5 M) elicited effects similar to those of PTHrP-(1-34). PTHrP-(1-34) was found to significantly elevate aortic cAMP level, measured by specific radioimmunoassay, after 5 min incubation with PTHrP-(1-34). These results suggest that the decrease in [Ca2+]i is involved in the vasodilator action of PTHrP, and that the decreases both in tension and in [Ca2+]i might be attributed to cyclic AMP production stimulated by PTHrP.

Animals↗

Scopolamine abolishes cerebral blood flow response to somatosensory stimulation in anesthetized cats: PET study.

The effect of the cholinergic blocker, scopolamine on the cerebral blood flow (CBF) response to vibrotactile stimulation of a fore paw was studied using high-resolution positron emission tomography and H2 15O in 5 pentobarbital-anesthetized cats. Before scopolamine injection, the CBF response to the stimulation was found in the contralateral somatosensory cortex (mean ratio (contralateral/ipsilateral) control: stimulated 1.02 +/- 0.02: 1.17 +/- 0.05; P < 0.01). After intravenous injection of scopolamine (0.35 mg/kg), the CBF response was abolished. However, the cerebral metabolic rate of glucose (CMRGlu) response to the same stimulation was unchanged after scopolamine injection in the same cats. We concluded that scopolamine abolishes the CBF response but not neuronal response to stimulation. We suggest that cholinergic mechanisms may play an important role for mediating CBF coupling to neuronal activity during physiological stimulation.

Anesthesia↗

Immunocytochemical detection of parathyroid hormone-related protein in vascular endothelial cells.

The expression of parathyroid hormone-related protein (PTHrP) in cultured endothelial cells derived from bovine carotid artery was immunocytochemically investigated. The cells showed positive immunoreactivity for PTHrP abundantly in cytoplasm. PTHrP-like immunoreactivity was found in all endothelial cells under investigation. Negative control prepared with non-immune rabbit serum or with the antiserum preabsorbed with PTHrP showed no significant staining, indicating the specificity for immunostaining. Addition of 10% fetal calf serum to serum-deprived endothelial cells did not significantly increase PTHrP-like immunoreactivity. These results suggest that endothelial cells express PTHrP constitutively and PTHrP may act as a new class of endothelium-derived relaxing factor.

Animals↗

Do variations in hip geometry explain differences in hip fracture risk between Japanese and white Americans?

Despite lower femoral neck bone mass, Japanese women have a substantially lower incidence of hip fracture than North American whites. Reasons for this discrepancy were sought in a study of 57 Japanese and 119 white American women aged 50-79. All women were in good health. Bone mineral content (BMC) in the femoral neck, femoral neck length (NL), femoral neck angle (theta), cross-sectional moment of inertia (CSMI), safety factor (SF), and fall index (FI) were calculated using dual x-ray absorptiometry. Height and weight were greater in Americans than in Japanese (1.62 versus 1.52 m; p < 0.0001 and 66.0 versus 49.4 kg; p < 0.0001, respectively). Mean BMC in the femoral neck and CSMI were greater in Americans than in Japanese (3.91 versus 3.02 g; p < 0.0001 and 0.99 versus 0.57 cm4; p < 0.0001, respectively). NL was longer in Americans (5.6 versus 4.4 cm; p < 0.0001) and theta was larger in Americans (130 versus 128 degrees; p < 0.01), whereas SF and FI were less in Americans than in Japanese (3.41 versus 5.12; p < 0.0001 and 1.00 versus 1.40; p < 0.0001, respectively). These results indicate that despite lower bone mass, Japanese women have lower risks of structural failure in the femoral neck, attributable primarily to shorter femoral necks and, to a lesser degree, a smaller femoral neck angle. Geometric characteristics of the femoral neck in Japanese women are associated with their lower hip fracture risk, and the measurement of proximal femoral geometry, combined with bone mass, may provide further clinical information about the risk of hip fracture.

Absorptiometry, Photon↗

The role of activation of the sympathetic nervous system in the central pressor action of calcitonin gene-related peptide in conscious rats.

The effects of intracerebroventricular (i.c.v.) administration of calcitonin gene-related (CGRP) on blood pressure and heart rate (HR), and the underlying mechanisms were studied in conscious rats. CGRP (0.1-3.0 nmol i.c.v.) increased mean arterial blood pressure (MABP) and HR. CGRP (3.0 nmol i.c.v.) also significantly increased both plasma norepinephrine and epinephrine concentrations. Pretreatment with 16.5 nmol i.c.v. CGRP(8-37), a specific CGRP receptor antagonist, significantly inhibited the i.c.v. CGRP (1.0 nmol)-induced increases in MABP and HR. Phenoxybenzamine inhibited the i.c.v. CGRP-induced increase in MABP, while propranolol suppressed the tachycardiac response to i.c.v. CGRP. Chemical sympathectomy by 6-hydroxydopamine inhibited the increases in MABP and HR produced by i.c.v. CGRP. These results suggest that the central pressor and tachycardiac effects of i.c.v. CGRP are mediated by catecholamine release due to stimulation of sympathetic nervous system activity, possibly via specific CGRP receptors in the central nervous system.

Animals↗

Immunocytochemical identification of androgen receptor in mouse osteoclast-like multinucleated cells.

Expression of androgen receptor (AR) in mouse osteoclast-like multi-nucleated cells (OCs) was examined with immunocytochemical techniques. Murine OCs were obtained by co-culturing mouse osteoblastic cells and bone marrow cells. Three preparations of polyclonal anti-AR antibody which were raised in rabbit against different parts of the human AR were employed for the experiments. Specific staining for AR was demonstrated in the nuclei and the perinuclear area of mouse OCs. This is the first report demonstrating the presence of AR in osteoclast-like cells.

Animals↗

Localization of follistatin, an activin-binding protein, in bone tissues.

We have previously reported that activin-A has a mitogenic effect on osteoblast-like MC3T3-E1 cells and that these cells produce an activin-binding protein, follistatin (Hashimoto, M., Shoda, A., Inoue, S., Yamada, R., Kondo, T., Sakurai, T., Ueno. N., and Muramatsu, M. (1992) J. Biol. Chem. 267, 4999-5004). Activin-A was also detected abundantly in bone matrix tissues and was found to act as an osteoclast differentiation factor. Here, we studied the expression of follistatin in bone tissues by in situ hybridization with a follistatin cRNA probe. Follistatin transcript was detected in the osteoblasts and a fraction of osteocyte population in the developing mouse mandible. Immunohistochemistry using anti-follistatin antibody supported this observation at the protein level. Follistatin mRNA was also detected in the callus of repairing bone after fracture. These findings suggest that activin and follistatin may play significant roles in the bone system in vivo.

Animals↗

Immunohistochemical and in situ hybridisation detection of adenovirus early region 1A (E1A) gene in the microglia of human brain tissue.

To investigate whether brain tissue is infected latently by adenovirus via a monocyte/microglia-mediated entry mechanism, brain tissue resected at necropsy from seven senile subjects (five with senile dementia of Alzheimer type (SDAT) and two subjects without pathological changes) was examined for adenovirus early region 1A (E1A) gene and its expression using in situ hybridisation and immunohistochemical staining. HLA-DR positive, reactive microglial cells in both SDAT and normal brain tissue showed positive hybridisation and immunoreactive expression of adenovirus E1A. Thus there may be monocyte/microglia-mediated entry of adenovirus in the central nervous system which would be a novel and presumably common interaction between brain tissue and adenovirus.

Adenoviridae↗

Role of central vasopressin in cardiovascular regulation: effect of dehydration and sex.

The present study was performed to evaluate the role of central vasopressin in cardiovascular regulation. First, a novel vasopressin V1 antagonist (OPC21268) was injected intracerebroventricularly in conscious rats. In water-deprived animals, the mean arterial blood pressure (MABP) and heart rate were significantly decreased compared with euhydrated control rats. There was, however, no significant difference in the concentration of vasopressin in the perfusate of cerebrospinal fluid between groups. Second, vasopressin was intracerebroventricularly injected in male and female homozygous Brattleboro rats. The increase in MABP was greater in males than in females. These results suggest that central vasopressin is involved in blood pressure regulation in pathophysiological states.

Animals↗

Callosal atrophy in patients with lacunar infarction and extensive leukoaraiosis. An indicator of cognitive impairment.

BACKGROUND AND PURPOSE: It is unclear why only some patients with lacunar infarction and radiological evidence of diffuse white matter abnormalities have dementia. The purpose of this study is to investigate the value of callosal atrophy as an indicator of cognitive impairment. METHODS: We used magnetic resonance imaging to evaluate 11 right-handed male patients with lacunar infarction and extensive white matter hypodensities on computed tomography (8 with dementia and 3 without dementia). The midsagittal corpus callosum area on T1-weighted images was compared with the IQ determined by the Wechsler Adult Intelligence Scale. The relation between these parameters and cerebral oxygen metabolism measured with positron emission tomography was also evaluated in the 8 patients with dementia. RESULTS: All patients showed diffuse high-intensity areas in the bilateral hemispheric white matter on T2-weighted images. Compared with 19 age- and sex-matched right-handed normal control subjects, the patients had a significantly smaller callosal area. The severity of callosal atrophy, which varied from mild to severe, was significantly related to the total IQ. In the 8 demented patients, the total callosal area was significantly correlated with the mean level of oxygen metabolism in the cerebral white matter. CONCLUSIONS: In patients with lacunar infarction and diffuse white matter abnormalities, the presence of callosal atrophy may indicate cognitive impairment. Callosal atrophy may reflect the severity and extent of white matter damage associated with a decrease in oxygen metabolism, which may determine the severity of intellectual decline.

Adult↗

Cell cycle-dependent expression of estrogen receptor and effect of estrogen on proliferation of synchronized human osteoblast-like osteosarcoma cells.

Dual fluoroimmunohistochemical staining of estrogen receptor (ER) and bromodeoxyuridine was performed in a human osteoblastic osteosarcoma cell line, HOS TE85 cells. ER immunoreactivity was observed preferentially in the nuclei of the cells that were bromodeoxyuridine positive. ER expression at various phases of the cell cycle was investigated in HOS TE85 cells, which were synchronized at the G1/S phase boundary by intermittent exposure to thymidine and hydroxyurea. ER immunoreactivity became detectable in the S phase, decreased in the G2/M and G1 phases, and then reappeared in the S phase of the next cell cycle. Western blot analysis also showed that ER protein exists in these cells and increases in the S phase. Moreover, Northern blot analysis demonstrated that the expression of ER messenger RNA increases in the early S phase, gradually decreases during the progress of the cell cycle, and increases again in the S phase of the subsequent cell cycle. Interestingly, 17 beta-estradiol (10(-8) M) increased cell number and [3H]thymidine incorporation into DNA in the synchronized HOS TE85 cells, whereas this effect was not observed in the nonsynchronized HOS TE85 cells. The present studies suggest that the cell cycle-dependent regulation may contribute to the heterogeneity of ER expression in osteoblastic cells.

Animals↗