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Biomedical subjects

H Morii

Publications and source records attributed to H Morii.

At least 91 records · Page 5Linked to original sources

Expression of matrix Gla protein (MGP) in an in vitro model of vascular calcification.

To investigate the role of matrix Gla protein (MGP), which can bind mineral ions through gamma-carboxylated glutamic acid residues, in vascular calcification, we examined the expression of MGP in an in vitro calcification model by using bovine vascular smooth muscle cells (BVSMC). The expression of MGP mRNA was decreased during BVSMC calcification and its levels were inversely correlated with the quantities of BVSMC calcification. MGP mRNA expression was restored to the level of uncalcified control by inhibiting BVSMC calcification with bisphosphonates. These data suggest that the expression of MGP gene is modulated in the development of vascular calcification.

Alendronate↗

A novel ether core lipid with H-shaped C80-isoprenoid hydrocarbon chain from the hyperthermophilic methanogen Methanothermus fervidus.

A new ether lipid core (designated as FU) was found in Methanothermus fervidus total lipid. Comparison with caldarchaeol showed lower mobility of FU on TLC and smaller molecular weight (m/z 1298) by 2 mass units on FAB-MS. Treatment of FU with HI followed by displacement with silver acetate afforded long chain alcohol acetate (ROAc), which was further saponified with mild alkali to its free alcohol (ROH). ROH is the long chain alcohol prepared from FU. The molecular weights of ROAc and ROH were shown by MS to be 1354 and 1186, respectively. These results suggested that the molecular formula of ROH was C80H162O4, and ROH had four hydroxyl groups, and one molecule of ROH was bound with two molecules of glycerol by four ether linkages. Because FU was not oxidized by NaIO4 and specific rotation [alpha]D of FU coincided with that of caldarchaeol, it seems that the ether linkages of FU are formed with hydroxyl groups of the sn-2 and sn-3 positions of each glycerol moiety. The structure of FU was suggested to be a modified caldarchaeol in which two hydrocarbon chains are bridged with a covalent bond. Although a few points remain to be elucidated before the final conclusion can be reached on the structure of FU due to difficulty in complete structure determination done even with every approach currently available, the most possible position of the bridge in FU hydrocarbon was proposed from the data of EI-MS of ROAc and 1H-NMR of FU. The hydrocarbon chain looks like H-shaped C80 isoprenoid.

Ether↗

Growth-inhibitory effect of a high glucose concentration on osteoblast-like cells.

Impaired bone formation resulting from a decline of osteoblast activity has been implicated in the pathogenesis of diabetic osteopenia. We examined the effects of high glucose concentration alone, independent of insulin deficiency, on the growth of a human osteoblast-like cell line (MG-63). Sustained exposure to high glucose for 7 days inhibited cell growth in a concentration-dependent manner up to 49.5 mmol/L, as compared with cells cultured with a normal glucose concentration (5.5 mmol/L) or a high mannitol concentration (an iso-osmolar control). Glucose (49.5 mmol/L) attenuated the increment either in DNA content or in [3H]thymidine incorporation induced by insulin-like growth factor I (IGF-I). The IGF-I-induced increase of ornithine decarboxylase (ODC) activity, which plays an important role in cell growth, was also attenuated. The half-life of ODC protein was not shortened by the high glucose culture, but the intracellular content of putrescine (an end product of ODC) was significantly decreased. These changes did not occur in the high mannitol culture, strongly suggesting a specific effect of glucose. In summary, our observations suggest that a high glucose concentration significantly impairs the proliferative response of osteoblastic cells to IGF-I and that the defective cell function caused by sustained exposure to high glucose levels might contribute to impaired bone formation in patients with diabetic osteopenia.

Acetyltransferases↗

Lymphoblastoid interferon-alpha downregulates parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor expression in human osteoblastic cells (Saos-2).

Interferon-alpha (IFN-alpha) is a pleiotropic cytokine that modulates the cellular functions of both osteoblastic and osteoclastic lineages. It remains unclear whether IFN-alpha regulates the expression of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor, which is a major target molecule regulating skeletal metabolism. In this study, we examined the effect of IFN-alpha on the expression of PTH/PTHrP receptor in human osteoblastic cells (Saos-2). IFN-alpha inhibited the expression of PTH/PTHrP receptor gene in both a time- and dose-dependent manner. The mRNA level was decreased to 61.1% of that of the untreated control by 48 h treatment with 6000 U/mL of IFN-alpha. IFN-alpha also decreased cAMP response to PTH(1-34) in a dose-dependent manner and significantly depressed expression of the receptor protein. However, IFN-alpha did not exert any effect on other osteoblastic markers, such as alkaline phosphatase (ALP) activity, cAMP response to prostaglandin E2 (PGE2), and secretion of bone gla-protein (BGP) and bone sialoprotein (BSP). Finally, IFN-alpha decreased PTH/PTHrP receptor mRNA to 60.7% that of control in the presence of actinomycin D. These data suggest that IFN-alpha downregulates the expression of PTH/PTHrP receptor and its signaling without affecting other osteoblastic markers, and that IFN-alpha regulates its gene expression mainly by decreasing the stability of its mRNA.

Alkaline Phosphatase↗

Expression of the leptin receptor in human leukaemic blast cells.

The leptin receptor is a member of the cytokine receptor superfamily, and is expressed in CD34 haemopoietic stem cells. We examined expression of the leptin receptor in fresh human leukaemia cells. Northern blot analysis showed the leptin receptor was expressed in leukaemic cells from patients with acute myeloblastic leukaemia, acute lymphoblastic leukaemia and chronic myeloid leukaemia (CML). In CML, higher expression was observed in blast crisis than in chronic phase. The expression of leptin receptor decreased during in vitro differentiation of leukaemic blast cells. It appeared that expression of the leptin receptor was associated with immature leukaemic blast cells. Our findings may indicate the possibility that leptin has some role in leukaemia.

Acute Disease↗

Plasma leptin level and its relationship with body composition in hemodialysis patients.

Leptin is a newly found hormone secreted by adipocytes that regulates food intake, thermogenesis, and body fat. We measured plasma leptin levels in 103 patients with chronic renal failure treated by hemodialysis and 167 age- and gender-matched healthy control subjects to examine the impact of renal failure on plasma leptin levels and the influence of leptin on body composition measured by dual-energy X-ray absorptiometry. Hemodialysis patients showed a significant decrease in both body fat mass and lean body mass compared with those of the control subjects. Plasma leptin was significantly elevated in the hemodialysis group over the controls. In both groups, leptin was higher in female than male subjects, and it correlated positively with percent body fat. The subjects were divided into six categories according to percent body fat, and plasma leptin levels were compared between the two groups in the same category. Leptin of hemodialysis patients was significantly higher than that of the control subjects in the percent body fat categories of 30 or greater, whereas there was no statistically significant difference in leptin concentrations in the lower percent body fat categories. This was also true in the comparison in each gender, and leptin levels in female subjects showed a more remarkable difference between the hemodialysis and control groups in obese categories. Multiple regression analysis in all subjects indicated that plasma leptin levels were independently affected by percent body fat, plasma insulin concentration, gender, and renal failure. The positive impact of renal failure on leptin remained significant in the subjects with percent body fat of 30 or greater in the multiple regression model, whereas it was no longer significant in the remaining lean subjects. In multiple regression analysis of factors affecting fat mass index and lean mass index, leptin level was selectively associated with fat mass index, but not with lean mass index, regardless of percent body fat ranges. These results indicate that renal failure is an important factor affecting plasma leptin levels, especially in obese female subjects, and that hyperleptinemia was closely related to fat mass but not to lean body mass in hemodialysis patients.

Body Composition↗

Intermediate-density lipoprotein as an independent risk factor for aortic atherosclerosis in hemodialysis patients.

Patients with chronic renal failure often show accumulation of intermediate-density lipoprotein (IDL). Because recent studies have emphasized the atherogenicity of IDL in the general population, we evaluated the relationship between this lipoprotein and aortic atherosclerosis in uremic patients treated with hemodialysis. Aortic pulse wave velocity (PWV) was measured as a noninvasive index of sclerotic change of aorta in 205 hemodialysis patients and 184 age- and gender-matched healthy subjects. Fasting plasma lipoproteins were fractionated by ultracentrifugation into very low-density lipoprotein (VLDL), IDL, LDL, and HDL. Plasma lipoprotein (a) (Lp(a)) was measured by a latex immunoturbidimetric assay. Aortic PWV was significantly higher in the hemodialysis patients than in the control subjects. The hemodialysis group showed a significant increase in VLDL and IDL cholesterol, whereas their LDL and HDL cholesterol were lower than the control levels. Lp(a) levels did not differ between the two groups. In the hemodialysis population, VLDL, IDL, and LDL cholesterol correlated positively with aortic PWV adjusted for age, gender, smoking, and BP, whereas Lp(a) did not. Multiple regression analyses indicated that plasma triglycerides, independent of HDL cholesterol, had a significant association with aortic PWV in the hemodialysis patients but not in the control subjects. Further analyses revealed that aortic PWV in the hemodialysis patients had a significant and independent association with IDL cholesterol, whereas aortic PWV in the control subjects had significant and independent associations with HDL cholesterol and Lp(a). These results demonstrate that IDL is the lipoprotein fraction most closely associated with aortic PWV in the hemodialysis patients.

Adult↗

Decrease in glomerular filtration rate in Japanese patients with type 2 diabetes is linked to atherosclerosis.

OBJECTIVE: We assessed the effects of atherosclerosis on the glomerular filtration rate (GFR) in patients with type 2 diabetes and who had micro- or normoalbuminuria. RESEARCH DESIGN AND METHODS: A total of 61 Japanese patients with type 2 diabetes were recruited from inpatients of Osaka City University Hospital. They ranged in age from 40 to 69 years (28 men and 33 women). Each subject collected a 24-h urine sample for quantitative analysis of albumin. Absence of albuminuria was defined as a urinary albumin excretion level of <30 mg/24 h (n = 36) and microalbuminuria as a level of 30-300 mg/24 h. The GFR was estimated using 99mTc diethylenetriamine pentaacetic renogram method. As indexes of atherosclerosis, we measured the intimal-medial thickness (IMT) and distensibility of the carotid artery using high-resolution B-mode ultrasonagraphy and an echo-tracking system. We measured the resistance index (RI) of the renal interlobar arteries by pulsed Doppler sonography. RESULTS: The clinical characteristics of type 2 diabetic patients with and without microalbuminuria did not differ except for duration of diabetes, which was longer in the patients with microalbuminuria. GFR also did not differ between the patients with and without microalbuminuria. GFR was significantly correlated with the patient's age (r = -0.256, P < 0.05), carotid IMT (r = -0.326, P < 0.05), carotid stiffness beta (r = -0.449, P < 0.001), and renal arterial RI (r = -0.365, P < 0.05). In multiple regression analysis, independent factors associated with GFR were carotid IMT (R2 = 0.108, P = 0.0102), carotid stiffness beta (R2 = 0.208, P = 0.0003), and renal artery RI (R2 = 0.130, P = 0.0043). CONCLUSIONS: The decline in GFR in type 2 diabetic patients in the early stages of nephropathy may be due in part to atherosclerosis.

Adult↗

Stiffness indexes beta of the common carotid and femoral arteries are associated with insulin resistance in NIDDM.

OBJECTIVE: To investigate the association between arterial wall stiffness indexes beta of the common carotid artery (CCA) and the femoral artery (FA) and insulin resistance in NIDDM subjects in a cross-sectional study. RESEARCH DESIGN AND METHODS: We evaluated the arterial stiffness indexes beta of CCA and FA using an ultrasonic phase-locked echo-tracking system in 60 NIDDM subjects attending the diabetes center in Osaka City University Hospital, compared with 120 age- and sex-matched control subjects. Insulin sensitivity indexes were evaluated using a euglycemic-hyperinsulinemic clamp. RESULTS: Stiffness indexes beta of both CCA and FA were significantly higher in NIDDM subjects than in control subjects (CCA 18.1 +/- 0.9 vs. 11.7 +/- 0.3, respectively, P < 0.001; FA 35.7 +/- 2.3 vs. 23.7 +/- 0.8, respectively, P < 0.001). The mean insulin sensitivity index in NIDDM subjects was 4.69 +/- 0.29 mg.kg-1.min-1.mU-1.l. The stiffness indexes beta of both CCA and FA were inversely correlated with insulin sensitivity indexes (CCA r = -0.393, P = 0.002; FA r = -0.329, P = 0.010), as well as with age, duration of diabetes, and mean blood pressure. In stepwise multiple regression analyses, insulin sensitivity index and duration of diabetes were identified as significant independent variables for stiffness indexes beta in both CCA and FA (CCA R2 = 0.249, P = 0.0003; FA R2 = 0.336, P < 0.001). CONCLUSIONS: Arterial stiffness indexes beta of CCA and FA were associated with insulin resistance in NIDDM subjects.

Adult↗

Sympathetic function test of vasoconstrictor changes in foot arteries in diabetic patients.

OBJECTIVE: We studied the relationship between vasoconstrictor changes in foot arteries (pedal, metatarsal, and digital arteries) and autonomic neuropathy in diabetic patients to estimate the degrees of sympathetic dysfunction. RESEARCH DESIGN AND METHODS: Sixty-two patients and nineteen age-matched control subjects were studied. The resistance index (RI) and pulsatility index (PI) were measured as vascular hemodynamic parameters using Doppler sonography, and the increases in these hemodynamic parameters (%RI and %PI) from rest to a deep breath were measured as indexes of the degrees of sympathetic vasoconstrictor function. Cardiovascular autonomic function tests (AFTs) were performed and the score was compared to %RI and %PI values obtained. RESULTS: Of the 62 diabetic patients, 51 had various degrees of autonomic neuropathy. Both %RI and %PI in the diabetic patients were significantly less than those in the control subjects for all foot arteries tested (all P < 0.001). There were strongly inverse correlations between the %RI and %PI of foot arteries and the AFT score (r = -0.556 to -0.846, P < 0.0001). The %RI of the digital artery was the most strongly correlated with AFT score (r = -0.846, P < 0.0001) among foot arteries tested. The abnormality of sympathetic vasoconstriction was detectable in the majority of the diabetic patients with the early phase of autonomic neuropathy (%RI: 89.5%; %PI: 94.5%). CONCLUSIONS: We conclude that the %RI of the digital artery is a useful and reliable sympathetic function test of early phase in diabetic patients.

Adult↗

QT interval prolongation in the patients receiving maintenance hemodialysis.

QT prolongation is associated with a poor prognosis in patients with various diseases. The pathogenesis of the long QT syndrome is not well understood and little is known about the QT interval in the patients receiving maintenance hemodialysis. We evaluated changes in the QTc interval and investigated factors that contribute to its prolongation in 42 patients receiving maintenance hemodialysis. We also examined the association between the QTc interval and ventricular arrhythmias on 24-h ambulatory electrocardiograms. Comparison of standard 12-lead electrocardiograms of 42 patients and of 30 healthy controls matched for age and sex showed that the QTc interval in the patients was significantly prolonged (432.6 +/- 24.9 vs 402.0 +/- 21.0 ms, p <0.001). Multivariate analysis using stepwise multiple regression identified diabetes mellitus and the ejection fraction measured by echocardiography as independent risk factors for QTc prolongation. The QTc interval was significantly prolonged in patients with complex VPCs (couplets or salvos) (n = 13, 447.9 +/- 14.4 ms) on 24 h ambulatory ECG compared with simple VPCs (none or occasional) (n = 29, 425.6 +/- 25.8 ms) (p = 0.03). In conclusion, the QTc interval was prolonged in patients receiving maintenance hemodialysis and QTc prolongation was associated with complex VPCs. Decreased myocardial contractility and diabetes mellitus contributed to QTc prolongation.

Arrhythmias, Cardiac↗

[Treatment of osteoporosis by active vitamin D].

Supplementation of active vitamin D has been thought to be reasonable for those who convert insufficiently vitamin D to active form, especially for senile persons. Treatment of osteoporosis by vitamin D are accepted as not only supplementation of vitamin D but also direct activation of bone turnover. Several previous clinical trials suggest active vitamin D prevents fractures more effectively rather than the increase of the bone mass. The calcium intake of Japanese people is less than that of Western countries, and many of Japanese have the vitamin D receptor genotype which is more responsive to vitamin D. Therefore, it is probable that active vitamin D is more effective for Japanese than Western people.

Calcitriol↗

[Ipriflavone].

Ipriflavone (7-isopropoxyisoflavone), a non-hormonal isoflavone derivative, is currently used in several countries for prevention and treatment of postmenopausal osteoporosis. This compound is devoid of estrogenic activity in humans, but increases the activity of estrogens. Ipriflavone has been shown to be effective in reducing bone turnover rate mainly through an inhibition of bone resorption, and has been effect to stimulate of bone formation. Inhibitory effect of ipriflavone on bone resorption has been demonstrated both directly by the activation of mature osteoclast and the formation of new osteoclasts by stimulating estrogen-induced calcitonin secretion by thyroids in vivo. There are some evidence that ipriflavone has direct effect on bone formation. Several clinical studies have demonstrated that bone mineral density (BMD) was increased or maintained in patients treated with ipriflavone. Recently, a large multicentral study, Ipriflavone Multicenter European Fracture Study (IMEFS), was designed in order to investigate the efficacy of ipriflavone on the prevention of vertebral and the effect on BMD in women with postmenopausal osteoporosis.

Bone Remodeling↗