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Biomedical subjects

Y Ouchi

Publications and source records attributed to Y Ouchi.

At least 289 records · Page 16Linked to original sources
PubMed1993

Mutational analysis of human lipoprotein lipase by carboxy-terminal truncation.

We have previously reported a Trp382 (TGG)-->stop (TGA) mutation that causes familial lipoprotein lipase (LPL) deficiency. Expression study of the Trp382-->stop mutant showed that the truncated LPL was catalytically inactive with a marked reduction in the expressed mass. To investigate the minimal amino-terminal sequence of human LPL required for an active enzyme, a series of carboxy-terminal (C-terminal) truncated LPLs were expressed in vitro, and the enzyme activity, mass, and LPL mRNA levels were analyzed. The lipolytic activity showed a stepwise reduction between LPL-437 (Cys438-->stop; 68% of normal LPL activity in medium) and LPL-434 (Phe435-->stop; 3%). Without affecting LPL mRNA levels, LPL mass was reduced with the mutants not larger than LPL-437. In terms of specific activity, a significant difference was observed between LPL-436 (Lys437-->stop; 88% of that of normal LPL in medium) and LPL-435 (Val436-->stop; 22%), implying the importance of the role of Val436 in LPL action. Furthermore, our results unexpectedly showed that LPL-446 (Ser447-->stop), which is considered to be a common polymorphic form of LPL, exhibited higher activity than normal LPL (185% in medium). These results demonstrate that the C-terminal region of human LPL is closely associated with the expression of enzyme mass and catalytic activity.

Amino Acid Sequence↗
PubMed1992

Vitamin K2 modulates proliferation and function of osteoblastic cells in vitro.

A human osteosarcoma cell line, HOS TE85 cells, and a mouse osteoblastic cell line, MC3T3-E1 cells, were cultured for 3 days in a medium containing various concentrations of menaquinone-4 (vitamin K2). As a result, the proliferation of HOS cells was suppressed by vitamin K2 in a dose dependent manner up to 56% of control by 10(-7)M of vitamin K2 and that of MC3T3-E1 cells was suppressed to 84% of control by 10(-6)M of vitamin K2. Vitamin K2 increased alkaline phosphatase activity in both kinds of cells. Warfarin counteracted the effect of vitamin K2 on osteoblastic cell proliferation. Our results show that vitamin K2 modulates proliferation and function of osteoblastic cells by some mechanisms including gamma-carboxylation system.

Animals↗
PubMed1992

Characteristics of steroid hormone receptors in cultured MC3T3-E1 osteoblastic cells and effect of steroid hormones on cell proliferation.

We examined the binding characteristics of three kinds of steroid hormones--estrogen, androgen, and glucocorticoid--in cultured MC3T3-E1 mouse osteoblastic cells by whole-cell binding assay. The binding studies revealed the presence of a single class of high-affinity binding sites for [3H]17 beta-estradiol, [3H]mibolerone (a synthetic androgen), and [3H]triamcinolone acetonide (a synthetic glucocorticoid). The numbers of binding sites for these steroid hormones were found to be 4534 +/- 819, 14312 +/- 1884, and 24898 +/- 655 sites/cell; and the Kd values were 8.57 +/- 0.62 x 10(-10) M, 1.12 +/- 0.19 x 10(-9) M, and 6.08 +/- 1.24 x 10(-10) M, respectively. We also examined the effects of steroid hormones on the proliferation of MC3T3-E1 cells. 17 beta-estradiol significantly stimulated the proliferation of the cells (130-150% of control). Dihydrotestosterone also significantly stimulated the proliferation of the cells (115% of control); the effect was, however, much less potent than that of 17 beta-estradiol, although the number of binding sites was approximately three times more than that of 17 beta estradiol. Triamcinolone acetonide and dexamethasone had no effect on cell proliferation. These results suggest that estrogen and androgen act directly on osteoblastic cells through a receptor-mediated mechanism, and that androgen is much less potent than estrogen in stimulating the proliferation of MC3T3-E1 osteoblastic cells.

Animals↗
PubMed1992

Genetic and environmental factors of bone mineral density indicated in Japanese twins.

To evaluate the effects of genetic and environmental factors on the bone mass, we determined the bone mineral density (BMD) in the total body, the lumbar spine and in the femoral neck in 23 Japanese twin pairs including 21 monozygotic (MZ) pairs, applying dual-energy X-ray absorptiometry. In MZ pairs aged 20-49 years, highly significant intraclass correlation coefficients, ranging from 0.775 to 0.926, were observed at several sites, including the lumbar spine and the femoral neck, which suggests considerable contributions of genetic factors to the BMD. Neither intraclass correlation coefficients nor intrapair differences were found to change with increasing age in the present analysis. In female MZ pairs, exercises both at the present time and in the past were correlated with the BMD at several sites as well as body mass index in multiple regression analyses.

Absorptiometry, Photon↗
PubMed1992

Accuracy and reliability of quantitative measurement of coronary arterial stenosis by videodensitometry on coronary angiogram.

This study was undertaken to investigate the accuracy and reliability of videodensitometry (VDM) in measuring the magnitude of coronary arterial stenosis on coronary angiogram (CAG). CAG taken after administration of sublingual nitroglycerin was analyzed with VDM (XR-70 Coronary Analyzer, Vanguard). The magnitude of stenosis in coronary segments with four different classes of stenosis was consecutively measured 10 times by the same observer, and the values were 89.0 +/- 1.4, 70.9 +/- 2.1, 59.5 +/- 2.5, and 22.8 +/- 3.4%. The coefficients of variation (CVs), indicating intraobserver variability, were low for severe to moderate lesions (1.6, 2.9, and 4.3%, respectively), but was higher for low-grade lesions (14.8%). When the same lesions were measured by 2 observers, the measurements were highly correlated (r = 0.971, p < 0.01). The results of VDM were consistent with those of conventional gross examination for moderate to severe lesions, and the discrepancy was mainly found in low-grade lesions. The magnitude of stenosis of the same lesion was measured from the right and the left anterior oblique views, and the cineangle was found not to affect the results of VDM. Moreover, cardiac cycle did not affect the videodensitometric measurements of % area stenosis. In order to further investigate the accuracy of VDM, the magnitude of stenosis was measured in nine phantom arteries, and the value measured by VDM significantly correlated with the actual stenosis (r = 0.969, p < 0.001). These results indicate that the values of coronary arterial stenosis on CAG measured by VDM are accurate and clinically acceptable, even though variability is somewhat high for low grade lesions. VDM may be useful for evaluation of the outcome of PTCA and the anti-atherogenic action of some agents.

Absorptiometry, Photon↗
PubMed1992

Crossed cerebellar hypoperfusion in unilateral major cerebral artery occlusive disorders.

We evaluated regional blood flow and oxygen metabolism in the cerebral and cerebellar cortices of 15 patients with unilateral major cerebral artery occlusive disorders with PET. These patients showed a cortical blood flow asymmetry in middle cerebral artery distribution. Only subcortical abnormalities were detected on computed tomography. Nine patients showed crossed cerebellar hypoperfusion, a reduction in contralateral cerebellar blood flow, while six did not. No difference in the degree of cerebral blood flow asymmetry existed between the two patient groups. However, oxygen metabolism asymmetry was more pronounced and was more closely matched to blood flow asymmetry in patients with crossed cerebellar hypoperfusion. These findings suggest that a major cause of cerebral cortical blood flow reduction is reduced metabolic demand in patients with crossed cerebellar hypoperfusion. Crossed cerebellar hypoperfusion may have clinical significance as a reflection of the cerebral metabolic state on blood flow images.

Adult↗
PubMed1991

Effect of parathyroid hormone on release of interleukin 1 and interleukin 6 from cultured mouse osteoblastic cells.

This study was undertaken to examine the possibility that parathyroid hormone promotes the production of interleukin 1 and 6 in MC3T3-E1 osteoblastic cells derived from mouse calvaria. The cells were incubated in serum-free medium with or without synthetic human parathyroid hormone(1-34). The concentrations of interleukin 1 and 6 in the culture medium were determined by using specific bioassay. The cells cultured without parathyroid hormone for 24 hr released both of interleukins, and parathyroid hormone stimulated the release in a dose-dependent manner. When the cells were cultured with 10(-6) M parathyroid hormone, the release of both interleukins from the cells remained higher than control up to 144 hr. These results suggest that interleukin 1 and 6 release stimulated by parathyroid hormone may be involved in the bone resorbing activity of the hormone.

Animals↗
PubMed1991

Biological activity of 1 alpha, 25-dihydroxyvitamin D derivatives--24-epi-1 alpha, 25-dihydroxyvitamin D-2 and 1 alpha,25-dihydroxyvitamin D-7.

Biological activity of 24-epi-1 alpha,25-dihydroxyvitamin D-2 (24-epi-1,25(OH)2D2) and 1 alpha,25-dihydroxyvitamin D-7 (1,25(OH)2D7), the 22,23-dihydro derivative of the former compound, was investigated. Both of the vitamin D derivatives stimulated intestinal calcium transport and calcium mobilization from bones in rats; however, the effect was about 50% of that of 1 alpha,25-dihydroxyvitamin D-3 (1,25(OH)2D3). On the other hand, 24-epi-1,25(OH)2D2 and 1,25(OH)2D7 inducement of HL-60 human leukemia cell differentiation was comparable to that of 1,25(OH)2D3. Accordingly, the differentiation-inducing activity of 24-epi-1,25(OH)2D2 and 1,25(OH)2D7 was much greater than their ability to stimulate calcium metabolism. In contrast to 1,25(OH)2D3, 24-epi-1,25(OH)2D2 and 1,25(OH)2D7 exerted little hypercalcemic activity in mice. These results suggest that both vitamin D derivatives will be useful as anti-tumor agents.

Alkaline Phosphatase↗
PubMed1991

Effects of vitamin D2 analogs on calcium metabolism in vitamin D-deficient rats and in MC3T3-E1 osteoblastic cells.

The effects of 1 alpha-hydroxyvitamin D2 on calcium metabolism in vivo and of 1 alpha, 25-dihydroxyvitamin D2, which is an active metabolite of 1 alpha-hydroxyvitamin D2, on bone metabolism in vitro was studied and compared with that of 1 alpha-hydroxyvitamin D3 or 1 alpha,25-dihydroxyvitamin D3. 1 alpha-Hydroxyvitamin D2 and 1 alpha-hydroxyvitamin D3 was equally potent in stimulating intestinal calcium transport by using the everted sac method and of calcium mobilization from bone in vitamin D-deficient rats. On the other hand, the hypercalcemic activity of 1 alpha-hydroxyvitamin D2 was much lower than that of 1 alpha-hydroxyvitamin D3 in normal mice and rats. 1 alpha,25-Dihydroxyvitamin D2 and 1 alpha,25-dihydroxyvitamin D3 stimulated alkaline phosphatase activity in osteoblastic MC3T3-E1 cells and bone resorption in newborn mouse calvaria maintained in organ culture. These results show that 1 alpha-hydroxyvitamin D2 as well as 1 alpha-hydroxyvitamin D3 promote calcium absorption and may accelerate bone remodelling via direct action on osteoblasts. In addition, they suggest that 1 alpha-hydroxyvitamin D2 may be more useful than 1 alpha-hydroxyvitamin D3 for the treatment of senile osteoporosis, because hypercalcemia is one of the major side effects of 1 alpha-hydroxyvitamin D3.

Alkaline Phosphatase↗
PubMed1991

Calcium requirement in elderly Japanese women.

In order to evaluate calcium requirements (RC) in Japanese elderly women, a calcium balance study was carried out in 9 osteoporotics (73.9 +/- 2.7 years old, mean +/- SE) and 9 normal elderly women (67.0 +/- 2.5 years old). Diet containing 700 mg/day of calcium were given for at least 1 week. Then, diets containing approximately 700 mg/day (722.5 +/- 91.9 mg/day) of calcium in the 1st week and 1,474 mg/day of calcium in the 2nd week were served. The amount of calcium intake to maintain zero balance, defined as daily RC, was 550.4 +/- 50.0 and 648.8 +/- 44.7 mg/day in normal and osteoporotic subjects, respectively. There was no statistically significant difference between these two groups. Although the recommended daily allowance (RDA) for the adult Japanese is 600 mg/day, our study suggests that RDA in the elderly Japanese should be 847 mg.

Aged↗
PubMed1991

Effect of nifedipine on the progression of coronary atherosclerosis in humans. Analysis of coronary angiogram by videodensitometry.

This study was conducted retrospectively to elucidate whether the long-term use of nifedipine is effective against the progression of coronary atherosclerosis in humans. Twenty-nine subjects with ischemic heart disease, on whom repeated coronary angiographic examinations (CAG) were performed, were randomly selected. Sixteen subjects were on nifedipine therapy (40 mg/day; NIF group, age 53 +/- 2) and 13 subjects not on nifedipine therapy served as the control group (C group, age 58 +/- 3). No significant differences were observed in clinical backgrounds, including the interval between CAG, between the 2 groups. The lesions with 25 to 75% stenosis on the first CAG were defined as the regions of interest (ROI), and the magnitude of stenosis was quantitatively measured by videodensitometry for each ROI on the first and the second CAG. The magnitude of stenosis showed a small increase (54.1 +/- 2.6 to 58.6 +/- 3.3%: N.S.) for 37 ROIs in the C group. In contrast, it showed a significant decrease (52.5 +/- 3.8 to 46.2 +/- 4.3%: p less than 0.05) for 33 ROIs in the NIF group. The trend was more apparent in the left coronary artery. The change in the mean value for ROIs in each subject produced similar results. These results suggest that the long-term use of nifedipine might be effective in retarding the progression of coronary atherosclerosis in humans. However, a prospective study should be performed to confirm this.

Coronary Angiography↗
PubMed1991

[Aortic pulse wave velocity in patients with coronary atherosclerosis--a comparison with coronary angiographic findings].

This study was conducted to investigate the relationship between aortic pulse wave velocity (PWV) and coronary atherosclerosis. We measured PWV in 105 subjects (84 males and 21 females; age 59 +/- 0.5) who received coronary angiographic examination (CAG). PWV was measured by simultaneous recording of pulse waves from the left carotid and the left femoral arteries, electrocardiogram and phonocardiogram. The subjects were classified into 4 groups according to the number of major coronary arteries having stenosis, that is, N group with normal CAG, 1 vessel disease (VD) group, 2VD group and 3VD group. The PWV value was significantly greater only in 3VD group (n = 10, age 63 +/- 3.6, PWV 10.0 +/- 0.88 m/sec) than that in N group (n = 18, age 53 +/- 2.0, PWV 8.0 +/- 0.34 m/sec). No significant difference was observed between PWV value in N group and that in all patients with coronary artery stenosis (n = 87, age 60 +/- 2.0, PWV 8.9 +/- 0.2 m/sec). To further investigate the relationship between PWV values and CAG findings, we used a CAG score which means the sum of the points assigned to each coronary artery segment (American Heart Association) according to the severity of stenosis (0, 1, 2, 3, and 4 for normal, less than 49% stenosis, 50 to 74% stenosis, 75 to 99% stenosis, and complete occlusion, respectively). The PWV values significantly correlated with the CAG score and also with age by a simple regression analysis. Multivariate analysis, however, revealed that PWV values did no longer correlate with CAG score. PWV values still significantly correlated with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

The role of calcium and magnesium in the development of atherosclerosis. Experimental and clinical evidence.

Based on the findings presented in this study, we propose the hypothesis that calcium could be a mediator for the development of atherosclerosis. Figure 8 shows a schematic illustration of the hypothesis. The presence of risk factors such as hypertension, hyperlipidemia, and smoking may increase the influx of calcium into vascular ECs. We have shown that reactive oxygen species, which are considered to be a risk factor for the development of atherosclerosis, actually increase [Ca++]i in vascular ECs. Increased intracellular calcium may damage the function of ECs, resulting in platelet aggregation at the damaged site. Increased intracellular calcium may also increase uptake of macromolecules in plasma such as fibrinogen and LDL, eventually forming atherosclerotic plaque. We have also shown that the influx of calcium into vascular ECs is associated with LDL transport across vascular ECs. The pretreatment by nifedipine inhibited both the increase in [Ca++]i and the increase in LDL transport, suggesting that intracellular calcium modulates LDL transport across ECs. Growth factors released from platelets may provoke migration and proliferation of medial SMCs in the aterial intima. It has been reported that migration of SMCs from arterial media to intima is enhanced by the presence of calcium, and can be inhibited by the pretreatment of calcium antagonist. As demonstrated in this study, calcium also plays an important role in the proliferation of SMCs provoked by some kinds of growth factors such as EGF. On the other hand, we found that an increased amount of dietary Mg suppressed the development of atherosclerotic lesions in the aorta of cholesterol-fed rabbits without affecting plasma total cholesterol and HDL-cholesterol concentrations. The mechanism of action might also be related to the calcium entry blocking action. The clinical and nutritional implications of these phenomena should be investigated further. The evidences presented in this study, however, would not be sufficient to fully explain the etiological role of calcium in atherogenesis. Further studies are required to elucidate the mechanism of the contribution of calcium to atherogenesis. The efficacy of calcium antagonist for the prevention of atherosclerosis in humans should also be investigated further.

Animals↗
PubMed1990

Effect of endothelin-1 on pulmonary resistance in rats.

We examined the effect of endothelin-1 (ET-1), a novel 21-residue vasoconstrictor peptide, on pulmonary resistance (RL) in Wistar rats. The lung volume, tracheal flow, and transpulmonary pressure of tracheotomized and paralyzed rats were measured with a fluid-filled esophageal catheter and a pressure-sensitive body plethysmograph. RL was calculated by the method of von Neergaard. The femoral artery was cannulated to measure the mean arterial blood pressure. Intravenous bolus administration of synthetic ET-1 provoked a dose-dependent increase in RL in rats. The bronchoconstricting effect reached maximum at 500 pmol/kg. This bronchoconstriction was observed in less than 5 min, increased up to 15 min, and was sustained for 60 min. ET-1 increased the mean arterial blood pressure in a dose-dependent manner. We conclude that ET-1 is a hitherto unknown potent bronchoconstrictor that has a sustained effect in vivo. The potential physiological and pathophysiological role of this new peptide in the development of respiratory disease warrants further investigation.

Airway Resistance↗
PubMed1990

[An aged case of orthostatic hypotension possibly due to parasympathetic neurodysfunction].

94-year-old male patient, with orthostatic hypotension, possibly due to impairment of vasoconstriction and parasympathetic nervous system dysfunction was reported. This patient experienced faintness and lower muscle weakness on standing. The blood pressure was 180/90 mmHg in a supine position, while it significantly decreased to 100/58 mmHg in an upright position. There was no evidence indicating the presence of organic brain diseases, cardiovascular diseases, and endocrine diseases, plasma catecholamine, renin, aldosterone, and vasopressin levels at rest were within normal range. Thus, the cause of orthostatic hypotension of this patient was unknown. His systolic blood pressure decreased by 70 mmHg, and his diastolic blood pressure also decreased by 25 mmHg in response to a 70 degrees head-up tilting test (170/71-100/46 mmHg). Plasma vasopressin level significantly increased in response to this test (0.62-67.2 pg/ml). Plasma catecholamine levels also increased (Adr 0.01-0.10 ng/ml, Ndr 0.05-0.22 ng/ml). Other autonomic nervous system examinations revealed normal responses to mental arithmetic test, hyperventilation test, cold pressure test, and adrenalin test. However, the results of the carotid occlusion test, acetylcholine test, atropine test, phenylephrine test were considered to be abnormal. From these findings, we concluded that the functions of sympathetic nervous system were almost intact, while the parasympathetic functions were impared in this case. The orthostatic hypotension of the patient as effectively treated with fludrocortisone. This report suggests that impairment of vasoconstriction and parasympathetic neurodysfunction might be involved in the development of orthostatic hypotension in the elderly.

Acetylcholine↗