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Biomedical subjects

Y Ouchi

Publications and source records attributed to Y Ouchi.

At least 271 records · Page 15Linked to original sources

[Therapeutic policy for elderly hypertensives in Japan--a questionnaire survey of specialists].

In order to clarify the therapeutic policy for hypertension in the elderly, we mailed a questionnaire to 147 specialists in Japan and received 123 replies. The upper age limit for antihypertensive treatment was considered to be 80-85 years old by about 50% of the specialists, but the other 50% did not consider an upper age limit. The range of the systolic blood pressure (BP) for which drug treatment was indicated in those without cardiovascular complications was considered to be increased with age, being 160 mmHg and higher in those aged 60-69, 160-170 mmHg and higher in those aged 70-79, and 170-180 mmHg and higher in those aged 80-89, while the level of diastolic BP requiring treatment was considered to be 90-95 mmHg and higher in all age ranges. The goal of BP control was considered to be less than 150/90 mmHg in those aged 60-69, and less than 160/90 mmHg in those aged 70-79 by the majority of the specialists, and to be higher in those aged 80-90, i.e. less than 170-180/95-100 mmHg by more than 20% of the specialists. As the initial selection of antihypertensive regimen, calcium antagonists followed by angiotensin I-converting enzyme inhibitors (ACEI) were selected by the majority, while diuretics, beta-blockers and alpha 1 blockers were chosen by the minority.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Altered energy metabolism in Alzheimer's disease].

To evaluate the energy metabolic status of Alzheimer's disease, we examined the cerebral arteriovenous differences of glucose, oxygen, lactate, pyruvate, ketone bodies, and free fatty acids and N-isopropyl-p-(123I) iodoamphetamine (IMP) single-photon emission computed tomography in 5 patients with Alzheimer's disease (4 male and 1 female patients; mean age of 64.80 +/- 8.47 years). Compared with 5 age matched normal control subjects (4 males and 1 female; mean age of 63.20 +/- 10.76 years), the patients showed significantly decreased regional cerebral blood flow only in the parietotemporal region. The global cerebral glucose metabolic rate (CMRGlu) had significantly low value, whereas the global cerebral oxygen metabolic rate (CMRO2) was not changed. The metabolic ratio (CMRO2/CMRGlu) was significantly elevated to 9.73 in the patients with Alzheimer's disease, compared with 5.50 in the normal controls. The cerebral metabolic rates of ketone bodies and free fatty acids were unchanged. The cerebral pyruvate output was significantly decreased. The cerebral lactate output became negative, but the decrease did not reach statistical significance. We concluded that the markedly elevated metabolic ratio suggests an altered energy metabolism in Alzheimer's disease.

Aged↗

Genomic binding-site cloning reveals an estrogen-responsive gene that encodes a RING finger protein.

Estrogen receptor (ER)-binding fragments were isolated from human genomic DNA by using a recombinant ER protein. Using one of these fragments as a probe, we have identified an estrogen-responsive gene that encodes a putative zinc finger protein. It has a RING finger motif present in a family of apparent DNA-binding proteins and is designated estrogen-responsive finger protein (efp). efp cDNA contains a consensus estrogen-responsive element at the 3' untranslated region that can act as a downstream estrogen-dependent enhancer. Moreover, efp is regulated by estrogen as demonstrated at both the mRNA and the protein level in ER-positive cells derived from mammary gland. These data suggest that efp may represent an estrogen-responsive transcription factor that mediates phenotypic expression of the diverse estrogen action. Thus, the genomic binding-site cloning may be applicable for isolation of the target genes of other transcription factors.

Amino Acid Sequence↗

Vascular smooth muscle cells as target for estrogen.

ER mRNA was detected as 6.0 kb band by Northern blot analysis in vascular smooth muscle cells (VSMC) derived from rat aorta. The presence of ER mRNA in VSMC was confirmed by reverse transcriptase-polymerase chain reaction using specific primers for rat ER cDNA. In addition, the immunocytochemistry of ER was performed in VSMC using a monoclonal anti-ER antibody which recognizes DNA-binding domain of ER. The immunoreactivity was distributed in the cytoplasm as well as in the nuclei. Thus, the expression of ER in VSMC was demonstrated at both the protein and the mRNA level. Furthermore, the expression of c-fos mRNA in VSMC was found up-regulated by 17 beta-estradiol treatment within 30 min. The observation that VSMC possess ER and respond to estrogen supports the idea that estrogen may directly influence vascular cell system through the ER.

Animals↗

Effect of calcitonin gene-related peptide on cytosolic free Ca2+ level in vascular smooth muscle.

The effect was investigated of calcitonin gene-related peptide (CGRP) on the cytosolic free Ca2+ level ([Ca2+]i) in rat aortic smooth muscle. The rat aortic spiral strip preparations without endothelium were treated with fura 2. The ratio of fluorescences (R340/380), an index of [Ca2+]i, emitted from smooth muscle was serially measured by a fluorescent spectrophotometer when excited by two wavelengths (340 and 380 nm). The tension of the preparations was measured simultaneously. CGRP produced cumulative decreases both in the tension and in R340/380 increased by norepinephrine. These reductions were significantly counteracted by the post-addition of CGRP-(8-37), a CGRP receptor antagonist (10(-6) M). The pretreatment with CGRP (10(-6.5) M) also significantly inhibited the norepinephrine-induced increase both in the tension and in R340/380. These effects of CGRP were significantly augmented by the pretreatment with 3-isobutyl-1-methylxanthine, and were significantly inhibited by the pretreatment with Rp diastereomer of adenosine cyclic 3',5'-phosphorothioate. Dibutyryl cyclic AMP (10(-3.5) M) elicited the effects similar to CGRP. These results suggest that the decrease in [Ca2+]i is involved in the vasodilator action of CGRP and that the decrease in [Ca2+]i might be attributed to cyclic AMP production stimulated by CGRP.

1-Methyl-3-isobutylxanthine↗

Callosal atrophy parallels decreased cortical oxygen metabolism and neuropsychological impairment in Alzheimer's disease.

OBJECTIVE: To evaluate the relationship of corpus callosum atrophy to cerebral cortical oxygen metabolism and cognitive function in patients with Alzheimer's disease. DESIGN: Prospective clinicoradiologic correlation with magnetic resonance imaging and positron emission tomography. SETTING: A university hospital. PATIENTS, PARTICIPANTS: Ten right-handed male patients with Alzheimer's disease, aged 46 to 70 years (mean +/- SD 57 +/- 6 years), and 14 age- and sex-matched right-handed control subjects. MAIN OUTCOME MEASURES: The midsagittal corpus callosum areas (on T1-weighted magnetic resonance images), cerebral metabolic rate of oxygen (measured with positron emission tomography using the oxygen-15 steady-state technique), and the IQs of the Wechsler Adult Intelligence Scale. RESULTS: Compared with control subjects, the patients had significantly decreased callosal areas with a posterior predominance of the degree of atrophy. The area of anterior and posterior halves of the corpus callosum had a significant correlation with the value of oxygen metabolism in the frontal and parietotemporo-occipital association cortices, respectively. The total area of the corpus callosum was significantly related to the total and verbal IQs of the Wechsler Adult Intelligence Scale. CONCLUSION: Atrophy of corpus callosum reflects the severity and pattern of cortical damage associated with hypometabolism and cognitive impairment in Alzheimer's disease.

Aged↗

Immunohistochemical detection and northern blot analysis of estrogen receptor in osteoblastic cells.

Expression of estrogen receptor (ER) was studied in MC3T3-E1 cells (mouse osteoblastic cell line), HOS TE85 cells (human osteosarcoma cell line), and primary osteoblastic cells derived from mouse calvaria with immunohistochemical techniques. The staining of ER was readily detectable in MC3T3-E1 cells, HOS TE85 cells, and primary osteoblastic cells by using a monoclonal anti-ER antibody that recognizes the DNA binding domain of ER. The immunoreactivity was distributed in the cytoplasm as well as in the nuclei. 17 beta-Estradiol (10(-8) M) did not alter this staining pattern. The expression of ER was confirmed by Northern blot analysis using rat ER cDNA probe, which revealed a 6.5 kb band in MC3T3-E1 cells and a 6.2 kb band in HOS TE85 cells. The mRNA level of ER was not altered by 17 beta-estradiol (10(-8) M). The immunohistochemical studies showed that ER was not detectable in all cells but in a small population of each cell type. This study is the first report to demonstrate the presence of ER immunohistochemically, and our results suggest the heterogeneity of ER expression among osteoblastic cells.

3T3 Cells↗

Effects of estrogen replacement on insulin-like growth factor I concentrations in serum and bone tissue and on interleukin 1 secretion from spleen macrophages in oophorectomized rats.

Oophorectomy (OOX) has been known to increase bone turnover, but its precise mechanism is not fully understood. In order to further investigate the mechanism, we determined insulinlike growth factor I (IGF-I) concentrations in serum and bone tissue and interleukin 1 (IL-1) release from spleen macrophages in oophorectomized rats because it has been demonstrated that IGF-I stimulates bone formation and IL-1 stimulates bone resorption. Female 8-week-old Wistar rats were divided into four groups: (1) control, (2) OOX, (3) OOX given estradiol, and (4) control given estradiol. Ten micrograms/kg of 17 beta-estradiol was given daily by subcutaneous injection. After 5 weeks of treatment, IGF-I concentrations in the extract from right femur and in serum were determined by specific radioimmunoassay. IL-1 activity released from lipopolysaccharide (LPS)-stimulated spleen macrophages was determined by bioassay. IGF-I contents in the femur and IGF-I concentrations in serum in oophorectomized rats were significantly higher than those in control rats. Treatment by estradiol inhibited the increase in IGF-I concentrations both in femur and in serum. IL-1 release from LPS-stimulated spleen macrophages in oophorectomized rats was increased, and treatment by estradiol also inhibited the stimulated IL-1 release. The ash weights and the calcium contents of left femur in oophorectomized rats were lower than those in control rats. These results suggest that both IGF-I and IL-1 may be involved in the mechanism of the regulation of bone turnover in oophorectomized rats.

Animals↗

Expression of follistatin, an activin-binding protein, in vascular smooth muscle cells and arteriosclerotic lesions.

Activin-A has a mitogenic effect on vascular smooth muscle cells (SMCs) and is produced by monocyte/macrophage lineage cells. Here, we studied the expression of follistatin, an activin-binding protein, in both A10 cells, a rat aortic SMC line, and vascular SMCs derived from adult rat aorta. Follistatin mRNA was detected in these cells by Northern blot analysis. Ligand blot and immunoblot analyses demonstrated that follistatin was produced in the conditioned medium at a higher level by A10 cells than by SMCs. Furthermore, immunostaining and in situ hybridization of the arteriosclerotic lesions showed that follistatin was highly expressed in the diseased artery, where abnormal proliferation of SMCs occurred. We suggest that follistatin is produced by vascular SMCs and is involved in the course of atherogenesis.

Activins↗

Hemodilution improves cerebral hemodynamics in internal carotid artery occlusion.

BACKGROUND AND PURPOSE: Hemodilution may be a useful form of therapy for patients with carotid occlusive disease and hemodynamic ischemia. Accordingly, we evaluated the effects of hemodilution on cerebral hemodynamics and oxygen metabolism in patients with carotid artery occlusion. METHODS: Using positron emission tomography, we analyzed regional cerebral blood flow, oxygen extraction fraction, oxygen metabolic rate, and blood volume before and after isovolemic hemodilution in five patients with unilateral internal carotid artery occlusion and minor stroke. Hemodilution was accomplished by phlebotomy of 400 mL and infusion of 400 mL of hydroxyethyl starch. RESULTS: Before hemodilution, the patients had a significant decrease in blood flow and oxygen transport along with significantly elevated oxygen extraction fraction in the cerebral hemisphere with carotid artery occlusion compared with six control subjects. After hemodilution, the hematocrit and arterial oxygen content decreased from 41.2% and 18.6 mL/dL to 36.3% and 16.5 mL/dL, respectively. Both cerebral blood flow and oxygen transport were increased and oxygen extraction fraction was decreased without any change in oxygen consumption. The degree of increase in blood flow and oxygen transport was positively correlated with the ratio of oxygen extraction fraction to blood volume before hemodilution. CONCLUSIONS: These findings indicate that hemodilution improves oxygen transport as well as blood flow in patients with internal carotid occlusion and decreased perfusion and that this improvement may be more prominent in patients with a severely compromised hemodynamic state. Thus, hemodilution may be useful in patients with hemodynamic ischemia.

Aged↗

Central neural mechanism contributing to attenuation of angiotensin II-induced hypertension in rats on dietary calcium supplementation.

The effect of dietary calcium (Ca) supplementation on blood pressure (BP) and the central nervous system (CNS) mechanism underlying this effect were studied in angiotensin II (Ang II)-induced hypertensive rats. The effects of dietary Ca (0.5, 2, 4%) on systolic blood pressure (SBP), ionized Ca concentration (Ca++) in cerebrospinal fluid (CSF) and central norepinephrine (NE) turnover were investigated in male Wistar rats receiving subcutaneous infusion of Ang II (100 ng/min). Central NE turnover was studied by measuring 3-methoxy-4-hydroxyphenylglycol (MHPG) concentration in CSF with multiple electrode liquid chromatography. Ang II significantly increased SBP, and dietary Ca dose-dependently attenuated the increase. SBP inversely correlated with Ca++ and MHPG in CSF. Intracerebroventricular injection of CaCl2 more markedly reduced BP in Ang II-treated rats than that in control rats. These results suggest that modulation of central NE turnover possibly caused by the increase in CNS Ca++ is involved in the anti-hypertensive mechanism of dietary Ca supplementation in Ang II-induced hypertensive rats.

Angiotensin II↗

[Successful weaning from mechanical ventilation in an aged subject with severe apneas due to brain damage].

A 73-year-old male was admitted to Tokyo University Hospital due to cardiac arrest secondary to ventricular arrhythmias. Although the patient survived after cardiopulmonary resuscitation, he needed mechanical ventilation. When we tried to wean the patient from mechanical ventilation, we found that he suffered from frequent sleep apneas of over 40 times/hour. To evaluate the severity and frequency of the apneas, we performed polysomnographic study on the patient under assist ventilation. The polysomnographic study revealed that frequency of apneas was very high but the magnitude of desaturation was not so severe during the night. Since we confirmed the lowest SaO2 in this patients was over 90% during day and night, we tried to wean from the patient from the ventilator again and succeeded. The clinical application and usefulness of nocturnal ventilatory monitoring for patients with mechanical ventilation was discussed.

Aged↗

[The importance of the host nutritional and immune status on the prognosis of urinary tract infection in the elderly].

This study was performed to evaluate the role of the nutritional and immune status on the prognosis of urinary tract infections (UTI) in the elderly. 192 patients among the 790 inpatients were diagnosed as UTI. Age-related increase in the prevalence of UTI was accompanied with poor prognosis in the patients with hypoalbuminemia (< 2.6 g/dl) and lymphocytopenia (< 700/mm3). To study the immunologic basis for susceptibility to UTI in the aged further, we compared the T-cell functions between outpatients without serious disease and inpatients with chronic UTI. The absolute numbers of lymphocyte, OKT3 (pan T-cell marker), OKT4 (Helper/Inducer marker) and Interleukin (IL)-2 as well as serum albumin concentration were decreased in the patients with UTI. A prospective study was done to confirm that these nutritional and immunological changes become risk factors in the prognosis of UTI with long-term and low-dose chemotherapy. In the patients continued with bacteriuria (Non-responders, n = 6), serum albumin concentration and IL-2 production were significantly lower than the patients who became free from bacteriuria (Responders, n = 7). These results suggest that poor nutrition-related immune dysfunction contributes to the vulnerability of elderly patients to UTI and becomes risks for he prognosis of UTI.

Adult↗