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Biomedical subjects

Y Ouchi

Publications and source records attributed to Y Ouchi.

At least 235 records · Page 13Linked to original sources
PubMed1996

Augmented contractile function and abnormal Ca2+ handling in the aorta of Zucker obese rats with insulin resistance.

To investigate the role of hyperinsulinemia/insulin resistance in vasomotor tone regulation, we studied the effects of vasoactive substances on tension and intracellular free calcium concentration ([Ca2+]i) of aortic smooth muscle derived from rats that were made hyperinsulinemic by insulin infusion and from Zucker obese rats with insulin resistance. The tension and [Ca2+]i of fura 2-loaded aortic strip preparations without endothelium were simultaneously measured by using a fluorimeter. Ten male Wistar rats received a continuous subcutaneous infusion of insulin (18 nmol x kg(-1) x day(-1)) for 2 weeks with osmotic minipumps (INS group). A control group of 10 rats received vehicle. The plasma immunoreactive insulin concentration in the INS group increased to 930 +/- 54 pmol/l. The increase in [Ca2+]i and tension by KCl and phenylephrine (PE) were lower in the INS group without alteration of the [Ca2+]i-tension relationship. The responses to serotonin (5-HT) in the INS group were similar to those in the control group. In contrast, responses to KCl, PE and 5-HT were markedly enhanced in Zucker obese rats compared with those in Zucker lean rats. The pretreatment of aortic preparations from lean rats with Bay K8644 significantly enhanced the responses to KCl to the level observed in the preparations from obese rats; however, Bay K 8644 failed to affect the responses to KCl in obese rats. These results suggest that enhanced vascular contractile responses to vasoactive substances, possibly due to altered function of the voltage-dependent Ca2+ channel in vascular smooth muscle, may play an important role in the pathogenesis of hypertension in the insulin resistance syndrome.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1996

Increased spontaneous production and generation of superoxide anion by blood neutrophils in patients with asthma.

Spontaneous production and PMA- and opsonized zymosan- stimulated generation of superoxide anion by blood cells in asthmatic patients were compared with those in normal volunteers and chronic obstructive pulmonary disease (COPD) patients using a lucigenin-dependent chemiluminescence method. Superoxide anion generation by 100 microl of blood in patients with asthma and/or COPD was significantly greater than that in normal subjects [asthma: 5684 +/- 253 chemiluminescence (CL); COPD: 4994 +/- 240 CL; normal: 2543 +/- 213CL]. This is consistent with the increased superoxide generation per leukocyte (PMN) in these patients (Asthma: 1.56 +/- 0.08 CL/PMN; COPD: 1.31 +/- 0.08 CL/PMN; normal: 0.83 +/- 0.07 CL/PMN. However, spontaneous production of superoxide by individual PMNs was increased only in asthmatic patients, compared with that in normal subjects (Asthma: 0.14 +/- 0.02 CL/PMN; COPD: 0.07 +/- 0.01 CL/PMN; normal: 0.07 +/- 0.01 CL/PMN. These results indicate that the respiratory burst is enhanced in both asthmatic patients and COPD patients, and that superoxide production by resting neutrophils is also increased in asthmatic patients, but not in COPD patients, compared with normal subjects.

Adult↗
PubMed1996

[Undergraduate teaching of geriatric medicine in western countries--literature review].

To help plan for the future of undergraduate education in geriatric medicine in Japan, we reviewed the literature concerning undergraduate teaching of geriatric medicine in western countries. Undergraduate teaching in geriatric medicine in the UK is well developed: 22 of 25 universities have a full department of geriatric medicine. Training in geriatric medicine is mandatory in almost all universities. In contrast, geriatric medicine is an elective in most universities in the US. There is a shortage of geriatric medicine faculty in the US, which is similar to the situation in Japan. Clinical and basic research in geriatric medicine and gerontology should be encouraged to attract persons into this field.

Education, Medical, Undergraduate↗
PubMed1996

[Use of a micturition-monitoring device in elderly inpatients].

More than 100,000 people suffer from functional urinary incontinence in Japan. To improve the quality of life of these people, we tested a device for monitoring micturition by means of a thin-layer membrane sensor in a diaper. The device was tested in elderly inpatients, and associated changes in the wordload of the nursing staff were also recorded. The device was beneficial because the precise micturition time was easily obtained and thus the daily pattern of micturition became obvious. With the use of this device, the time during which the patients wore wet diapers was shorter than with the conventional system of scheduled changes. However, the increase in the frequency of diaper changed doubled the workload of the nursing staff. In conclusion, improving the quality of life with regard to urinary incontinence entails an increase in the workload of the nursing staff; efficient distribution of that work may require some staff members to devote all their time to changing diapers.

Aged↗
PubMed1996

[Guidelines on treatment of hypertension in the elderly, 1995--a tentative plan for comprehensive research projects on aging and health-- Members of the Research Group for "Guidelines on Treatment of Hypertension in the Elderly", Comprehensive Research Projects on Aging and Health, the Ministry of Health and Welfare of Japan].

We propose the following guidelines for treatment of hypertension in the elderly. 1. Indications for Treatment. 1) Age: Lifestyle modification is recommended for patients aged 85 years and older. Antihypertensive therapy should be limited to patients in whom the merit of the treatment is obvious. 2) Blood pressure: Systolic BP > 160 mmHg, diastolic BP > 90 approximately 10 mmHg. Systolic BP < age + 100 mmHg for those aged 70 years and older. Patients with mild hypertension (140-160/ 90-95 mmHg) associated with cardiovascular disease should be considered for antihypertensive drug therapy. 2. Goal of Therapy for BP: The goal BP in elderly patients is higher than that in younger patients (BP reduction of 10-20 mmHg for systolic BP and 5-10 mmHg for diastolic BP). In general, 140-160/< 90 mmHg is recommended as the goal. However, lowering the BP below 150/85 should be done with caution. 3. Rate of Lowering BP: Start with half the usual dose, observe at the same dose for at least four weeks, and reach the target BP over two months. Increasing the dose of antihypertensive drugs should be done very slowly. 4. Lifestyle Modification: 1) Dietary modification: (1) Reduction of sodium intake is highly effective in elderly patients due to their high salt-sensitivity. NaCl intake of less than 10 g/day is recommended. Serum Na+ should be occasionally measured. (2) Potassium supplementation is recommended, but with caution in patients with renal insufficiency. (3) Sufficient intake of calcium and magnesium is recommended. (4) Reduce saturated fatty acids. Intake of fish is recommended. (2) Regular physical activity: Recommended exercise for patients aged 60 years and older: peak heart rate 110/minute, for 30-40 minutes a day, 3-5 days a week. (3) Weight reduction. (4) Moderation of alcohol intake, smoking cessation. 5. Pharmacologic Treatment: 1) Initial drug therapy. First choice: Long-acting (once or twice a day) Ca antagonists or ACE inhibitors. Second choice: Thiazide diuretics (combined with potassium-sparing diuretic). 2) Combination therapy. (1) For patients without complications, either of the following is recommended. i) Ca antagoinst + ACE inhibitor, ii) ACE inhibitor + Ca antagonist (or low-dose diuretics), iii) diuretic + Ca antagonist (or ACE inhibitor), iv) beta-blockers, alpha 1-blockers, alpha + beta blockers can be used according to the patho-physiological state of the patient. (2) For patients with complications. Drug(s) should be selected according to each complication. 3) Relatively contraindicated drugs. beta-Blockers and alpha 1-blockers are relatively contraindicated in elderly patients with hypertension in Japan. Centrally acting agents such as reserpine, methyldopa and clonidine are also relatively contraindicated beta-Blockers are contraindicated in patients with congestive heart failure, arteriosclerosis obliterans, chronic obstructive pulmonary disease, diabetes mellitus (or glucose intolerance), or bradycardia. These conditions are often present in elderly subjects. Elderly subjects are susceptible to alpha 1-blocker-induced orthostatic hypotension, since their baroreceptor reflex is diminished. Orthostatic hypotension may cause falls and bone fractures in the elderly.

Aged↗
PubMed1996

Effects of estrogen on atherosclerosis formation and serum nitrite/nitrate concentrations in cholesterol-fed ovariectomized rabbits.

This study was to examine the effects of estrogen replacement on atherosclerosis formation in ovariectomized cholesterol-fed rabbits. We also examined serum levels of nitrite/nitrate, stable metabolites of nitric oxide, to investigate the involvement of nitric oxide. Female New Zealand White rabbits were ovariectomized and divided into 3 groups; 1) fed a normal diet (ND group, n=5), 2) fed a 1% cholesterol diet (CD group, n=6), or 3) fed a 1% cholesterol diet and received estrogen replacement (CD+E group, n=7). After 3 months, the rabbits were sacrificed to examine atherosclerosis formation. Atherosclerosis was not observed in ND. The oil red 0 positive area in the aorta was significantly greater in CD than in CD+E (CD, 17.3+/-2.2; CD+E, 9.3+/-0.8%, p<0.05). Stenosis of the coronary artery was also significantly greater in CD than in CD+E (CD, 30.6+/-9.7; CD+E, 6.7+/-2.9%, p <0.05). There was no significant difference in serum lipids between CD and CD+E. Serum nitrite/nitrate levels were significantly lower in CD than in ND (ND, 37.6+/-3.6; CD, 25.3+/-3.1 microM, p<0.05). There was a non-significant trend towards higher nitrite/nitrate levels after estrogen replacement (CD+E, 34.4+/-3.8 microM, p=0.08 vs. CD). These results suggest that direct actions on vascular wall including nitric oxide production contribute to the anti-atherogenic effects of estrogen.

Animals↗
PubMed1996

Expression of immunoreactive activin A protein in remodeling lesions associated with interstitial pulmonary fibrosis.

The expression of activin A, one of the transforming growth factor-beta supergene family, was studied in various pulmonary conditions associated with interstitial pulmonary fibrosis (3 cases with diffuse alveolar damage, 6 cases with idiopathic pulmonary fibrosis, and 1 case with pulmonary fibrosis associated with rheumatoid arthritis) using immunohistochemical techniques on paraffin-embedded sections. Controls consisted of 10 cases with normal pulmonary parenchyma, and 2 cases with primary pulmonary hypertension and 1 case with secondary pulmonary hypertension were also studied. The lung specimens from normal parenchyma weakly expressed immunoreactive activin A on the bronchiolar epithelium. In marked contrast, all of the specimens from cases with diffuse alveolar damage and interstitial pulmonary fibrosis demonstrated strong expression of activin A on metaplastic epithelium, hyperplastic smooth muscle cells, desquamated cells, and alveolar macrophages. Pulmonary arteries from patients with primary or secondary pulmonary hypertension showed abundant immunoreactive activin A on smooth muscle cells. These findings suggest a potential role for this growth factor, activin A, in the pathogenesis of pulmonary tissue remodeling associated with interstitial pulmonary fibrosis.

Activins↗
PubMed1996

Altered energy metabolism in Alzheimer's disease.

To evaluate the energy metabolism in Alzheimer's disease (AD), the cerebral arteriovenous differences of oxygen, glucose, lactate, pyruvate, ketone bodies and free fatty acids, and regional cerebral blood flow (rCBF) were examined in 7 patients with Alzheimer's disease (AD). The ratio of oxygen and glucose molar utilization was significantly elevated to 9.86 in AD, compared with 5.63 for 7 age matched controls. Single-photon emission computed tomography revealed that the patients had significantly decreased rCBF only in the parietotemporal region. The glucose extraction fraction and global cerebral metabolic rate of glucose were significantly decreased, whereas the global cerebral metabolic rate of oxygen was slightly decreased. However, the elevated oxygen/glucose utilization ratio is not due to the oxygenation of ketone bodies or free fatty acids, because the cerebral metabolic rates of these substrates did not alter. We concluded that the marked elevated value of the oxygen/glucose utilization ratio suggests an altered energy metabolism in AD.

Aged↗
PubMed1995

Modulation of endothelium-dependent flow-mediated dilatation of the brachial artery by sex and menstrual cycle.

BACKGROUND: Estrogen has been reported to augment endothelium-dependent vasodilatation. The role of endogenous ovarian hormones in modulating endothelium-dependent vasodilatation, however, remains to be determined. The purpose of the present study was to investigate the effects of sex and menstrual cycle on endothelium-dependent flow-mediated vasodilatation. METHODS AND RESULTS: Seventeen female volunteers 25.1 +/- 0.8 years old and 17 age-matched male volunteers were examined. We measured brachial artery diameters noninvasively using a 7.5-MHz ultrasound machine at rest, during reactive hyperemia, and after sublingual nitroglycerin administration. All female subjects were studied three times each, in three different phases of one menstrual cycle (M, menstrual phase; F, follicular phase; and L, luteal phase). Flow-mediated diameter (D) increase (%FMD; delta D/D x 100) in M, when serum estradiol level was low (121.9 +/- 12.5 pmol/L), was 11.22 +/- 0.58%, and the value was comparable to that in male subjects (10.60 +/- 0.75%). %FMD increased in F (18.20 +/- 0.81%, P < .01 versus M) and L (17.53 +/- 0.74%, P < .01 versus M), when serum estradiol level was high (F, 632.0 +/- 74.5 and L, 533.8 +/- 33.4 pmol/L, P < .01 versus M). Endothelium-independent vasodilatation by nitroglycerin increased in both F and L. However, the increment was smaller than that of %FMD. CONCLUSIONS: Endothelium-dependent vasodilatation varies during the menstrual cycle. The endogenous estradiol may be involved in this menstrual cycle-related vasodilatation.

Adult↗
PubMed1995

Association of estrogen receptor dinucleotide repeat polymorphism with osteoporosis.

We investigated the association between dinucleotide (thymine-adenine) repeat polymorphism lying upstream of human estrogen receptor (ER) gene and bone mineral density (BMD) as well as biochemical markers for bone metabolism in 144 healthy postmenopausal Japanese women. The genotype was classified into 'A' through 'R' according to the number of the repeats, from 10 to 27. BMD was expressed in Z score (a deviation from the weight-adjusted average BMD of each age using the standard deviation as a unit). The people having genotype C (12 repeats of thymine-adenine) allele (n = 15) had significantly lower Z score of spine BMD (mean +/- SD; -1.11 +/- 1.3 vs. -0.06 +/- 1.2; p < 0.01) and of total body BMD (-0.58 +/- 1.0 vs. 0.31 +/- 0.9; p < 0.01) than those without this genotype (n = 129). They also had significantly higher levels of serum intact osteocalcin, urinary pyridinoline, and urinary deoxypyridinoline. These results suggest that genetic variation at the ER locus may be associated with some determinants for BMD and bone metabolism in postmenopausal women.

Aged↗
PubMed1995

17 beta-Estradiol inhibits Ca2+ influx and Ca2+ release induced by thromboxane A2 in porcine coronary artery.

BACKGROUND: We wished to investigate the possible mechanism of the protective effect of estrogen replacement on coronary atherosclerosis observed in postmenopausal women. METHODS AND RESULTS: Cytosolic Ca2+ concentration ([Ca2+]i) and contraction were measured simultaneously in fura 2-loaded porcine coronary arterial strips stimulated by the thromboxane A2 analogue U46619 and high-K+ depolarization in the presence and absence of 17 beta-estradiol. Pretreatment with 17 beta-estradiol (30 nmol/L to 30 mumol/L) inhibited the sustained elevation of [Ca2+]i and the sustained contraction induced by 300 nmol/L U46619. Higher concentrations of 17 beta-estradiol (1 to 100 mumol/L) also inhibited the U46619-induced transient increase in [Ca2+]i and contraction in the absence of extracellular Ca2+. In the strips precontracted by 90 mmol/L K+, 17 beta-estradiol (30 mumol/L) inhibited the increases in [Ca2+]i and contraction to resting levels. In contrast, 30 mumol/L 17 beta-estradiol only partially inhibited the U46619-induced sustained contraction, despite complete inhibition of the sustained increase in [Ca2+]i. Verapamil (10 mumol/L) also strongly inhibited the sustained increase in [Ca2+]i induced by 300 nmol/L U46619, with a partial inhibition of the U46619-induced sustained contraction. A subsequent addition of 30 mumol/L 17 beta-estradiol did not show an additional inhibitory effect on either the [Ca2+]i or the tension after the addition of verapamil. 17 beta-Estradiol (10 mumol/L) also inhibited the increase in [Ca2+]i and the contraction induced by cumulative addition of Ca2+ in the strips pretreated with 90 mmol/L K+. However, 17 beta-estradiol did not change the slope of the [Ca2+]i-tension curves. 17 beta-Estradiol (10 mumol/L) had no effect on the levels of cAMP and cGMP in the coronary strips. CONCLUSIONS: 17 beta-Estradiol inhibits the contraction of coronary vascular smooth muscle mainly inhibiting Ca2+ influx without changing Ca2+ sensitivity of contractile elements. The Ca2+ channel blocker-like action of 17 beta-estradiol may explain at least a part of the antiatherosclerotic effect of estrogen.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Age-related decrease in the effect of parathyroid hormone-related protein on cytosolic free calcium level and tension in rat aortic smooth muscle.

Age-related changes in the effect of parathyroid hormone-related protein (PTHrP) on the cytosolic free calcium level ([Ca2+]i) and on the tension in rat aortic smooth muscle were investigated. The possible involvement of cAMP, a second messenger of PTHrP, in such changes was also investigated. Spiral aortic strip preparations without endothelium from 8-weeks, 6-months, and 24-months old rats were treated with fura 2/AM, and the fluorescence ratio R340/380, an index of [Ca2+]i was measured. Simultaneously, the tension of the preparations was measured. PTHrP-(1-34) and dibutyryl cAMP produced concentration-dependent decreases in the tension and in R340/380 in aortas precontracted with phenylephrine (10(-7) M). These effects were significantly lower in the aortas of 24-months old rats than in the vessels of 8-weeks and 6-months old rats. The effects were similar in the aortas of 8-weeks and 6-months old rats. PTHrP-(1-34) concentration-dependently increased cAMP production in vascular smooth muscle cells (VSMCs) from 8-weeks old rats. However, the increase in cAMP production was significantly lower in cultured VSMCs from 6-months and 24-months old rats than in cells from 8-weeks old rats. These results suggest that the reduced cAMP production stimulated by PTHrP and the reduced effects of cAMP with aging might contribute to the age-related changes in the decreases in tension and [Ca2+]i in response to PTHrP in the rat aorta.

Age Factors↗
PubMed1995

Demonstration of isoforms of the estrogen receptor in the bone tissues and in osteoblastic cells.

Expression of isoforms of estrogen receptor (ER) was examined in the bone tissues. Reverse transcriptase-polymerase chain reaction ((RT-PCR) using specific primers for rat ER cDNA was performed with total RNA from rat bone tissues. Then, we sequenced the amplified products after cloning and identified two isoforms of the ER and the wild-type ER. One of the ER mRNA isoforms did not have the region corresponding to exon 4 and the other isoform did not have the region corresponding to both exon 3 and exon 4. These isoforms were designated as ER delta 4 isoform and ER delta 3/4 isoform, respectively. The existence of these isoforms was also confirmed by ROS-17/2.8 osteoblastic osteosarcoma cells. Chloramphenicol acetyltransferase assay showed that these isoforms lost estrogen dependent transactivation activities. We suggest that the ER isoforms may play some roles in the bone metabolism in which estrogen is essential to maintain bone density.

Animals↗
PubMed1995

Corpus callosum atrophy in amyotrophic lateral sclerosis.

Recent studies have suggested widespread involvement of the cerebral regions other than the primary motor cortex in amyotrophic lateral sclerosis. To investigate atrophy of the corpus callosum as a measure of cerebral pathology, we studied 25 right-handed patients with sporadic amyotrophic lateral sclerosis using magnetic resonance imaging. Five patients had cognitive decline or emotional and personality changes. The ratios of mid-sagittal corpus callosum areas to the midline internal skull surface area on T1-weighted images were analysed. Compared with 25 age- and sex-matched right-handed control subjects, the patients had significantly decreased callosal/skull area ratio, with anterior predominance of the degree of atrophy. The patients with cognitive decline or psychiatric symptoms had substantial atrophy of the anterior fourth of the corpus callosum. These findings suggest that atrophy of the corpus callosum, especially in the anterior half, is present in amyotrophic lateral sclerosis, and that severe atrophy in the anterior fourth is associated with cognitive decline and psychiatric symptoms. Callosal atrophy may reflect the widespread distribution of pathological changes in the cerebral cortex, which are accentuated in the frontal cortex.

Adult↗