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Biomedical subjects

Masaaki Inaba

Publications and source records attributed to Masaaki Inaba.

At least 91 records · Page 5Linked to original sources
PubMed2004

C-reactive protein is a significant predictor of vascular calcification of both aorta and hand arteries.

Although evidence has accumulated indicating a close relationship between inflammation and atherosclerosis, the relationship between inflammation and vascular calcification in patients with chronic renal failure is unclear. In the present study, the relationship between C-reactive protein (CRP) and vascular calcification in dialysis patients was examined. Vascular calcification of the aorta and hand arteries of 512 hemodialysis patients without significant infection (age 58.8 +/- 10.1 y; 305 men, 207 women) were examined by roentgenography of the lateral abdomen and hands, respectively. Patients with a mean CRP level greater than 1.0 mg/L (n = 254) were older than those with a CRP level less than or equal to 1.0 mg/L (n = 258) and had a longer duration of dialysis, lower serum albumin level, and higher phosphate level ( P < .01, P < .05, P < .001, and P < .01, respectively). Prevalence of vascular calcification of aorta and hand arteries in the former group was significantly higher than in the latter (65.0% versus 43.8% for aorta, P < .0001; and 25.0% versus 14.7% for hand arteries, P < .01). In a multivariate logistic regression analysis adjusted for age, hemodialysis duration, sex, levels of calcium and phosphate, and presence of diabetes, CRP level was a significant predictor for the presence of aortic calcification (odds ratio for highest versus lowest quartile, 2.669; 95% confidence interval, 1.539-5.421, P = .0010) and of calcification of hand arteries (odds ratio, 2.243; 95% confidence interval, 1.039-4.841; P = .0395). In conclusion, the present study shows that increased levels of CRP are significantly associated with the presence of vascular calcification in both aorta and hand arteries (ie, with both atheromatous and medial forms of calcification), indicating evidence for a relationship between inflammation and vascular calcification in hemodialysis patients.

Aortic Diseases↗
PubMed2004

Roles of metabolic and endocrinological alterations in atherosclerosis and cardiovascular disease in renal failure: another form of metabolic syndrome.

Patients with end-stage renal disease have markedly increased risk for death from cardiovascular disease. Renal failure is associated with multiple metabolic and endocrinologic abnormalities, and these alterations are involved in advanced atherosclerosis and high cardiovascular risk. Increased insulin resistance index by homeostasis model assessment (HOMA-IR), a simple index of insulin resistance, was an independent predictor of cardiovascular mortality in nondiabetic patients on maintenance hemodialysis. Renal failure impairs lipoprotein metabolism leading to the atherogenic lipoprotein profile characterized by increased triglyceride-rich remnant lipoproteins such as intermediate-density lipoprotein, an independent factor of increased aortic stiffness. Non-high-density lipoprotein cholesterol, the sum of cholesterol of intermediate-density lipoprotein and other apoB-containing lipoproteins, is an independent factor associated with increased arterial thickness and a predictor of cardiovascular death in hemodialysis patients. The risk for cardiovascular death in hemodialysis patients is associated closely with hypertension and malnutrition, but not with obesity. The constellation of insulin resistance, dyslipidemia, hypertension, and malnutrition in renal failure suggests the presence of another type of metabolic syndrome promoting cardiovascular disease. In addition, vitamin D deficiency and abnormalities in calcium, phosphate, and parathyroid hormone levels increase the death risk from cardiovascular disease in renal failure. It is expected that treatment of these metabolic and endocrinologic alterations would improve the survival of patients with renal failure.

Arteriosclerosis↗
PubMed2004

Increased arterial stiffening and thickening in the paretic lower limb in patients with hemiparesis.

Atherosclerosis has two key components, thickening and stiffening of arterial wall. These parameters are quantified ultrasonographically by IMT (intima-media thickness) and PWV (pulse wave velocity). In the present study, we determined the FA IMT (IMT of the bilateral femoral artery) and PWV of femoral-ankle (PWV fa) and brachial-ankle (PWV ba) segments in order to examine whether the degree of atherosclerosis is different between paretic and non-paretic lower limbs in 24 patients with hemiparesis. The values of PWV fa, PWV ba and FA IMT were all significantly greater on the paretic than the non-paretic side. Furthermore, significant decreases in masses of muscle, bone and fat, determined by dual-energy X-ray absorptiometry, were observed in paretic lower limbs compared with the non-paretic side. PWV fa correlated significantly and negatively with muscle mass ( r =-0.488, P =0.0004) and tended to correlate negatively with BMC (bone mineral content; r =-0.264, P =0.069) when statistical analyses were performed with the paretic and non-paretic sides together. Multiple regression analysis elucidated that the muscle mass was associated significantly with PWV fa and PWV ba, independent of age, duration after cerebrovascular accident, gender, bone and fat mass and FA IMT. The muscle mass was still associated with increased PWV fa and PWV ba when multivariate analysis was conducted independently in the paretic and non-paretic sides. In summary, our results indicated that arterial thickening and stiffening were greater on the paretic than the non-paretic side and suggested that a decrease of muscle mass might be associated with increased arterial stiffening in the paretic lower limb.

Adipose Tissue↗
PubMed2004

Lower risk for cardiovascular mortality in oral 1alpha-hydroxy vitamin D3 users in a haemodialysis population.

BACKGROUND: Renal failure results in deficiency of active vitamin D3 that has diverse effects on metabolism and organ functions. Treatment with active forms of vitamin D(3) ameliorates abnormalities in bone and mineral metabolism, cardiac function, immune response and others. We hypothesized that treatment with vitamin D(3) may be beneficial for survival in patients with end-stage renal disease (ESRD). METHODS: We compared the risk of death between regular users (n = 162) and non-users (n = 80) of oral 1alpha-hydroxyvitamin D3 (alfacalcidol) in a cohort of ESRD patients undergoing haemodialysis for a follow-up of 61 +/- 23 months. The daily dose of alfacalcidol ranged from 0.25 to 1.5 microg, with a median of 0.5 microg. RESULTS: The alfacalcidol users showed a lower risk of death from cardiovascular disease than the non-users in a univariate Cox model [hazards ratio (HR) 0.287, 95% confidence interval (CI) 0.127-0.649, P = 0.003], whereas the risk for death from non-cardiovascular disease was not different between the two groups. Stepwise multivariate Cox analysis showed that cardiovascular mortality was significantly associated with age, presence of diabetes mellitus and treatment with alfacalcidol (HR 0.377, 95% CI 0.246-0.578, P = 0.022). CONCLUSIONS: These results indicate that use of oral alfacalcidol was associated with reduced risk for cardiovascular death in this cohort of ESRD patients. The result of this observational study warrants further randomized controlled trials with 1alpha-hydroxy vitamin D3 to confirm the possibility that such medication improves survival of ESRD patients.

Adjuvants, Immunologic↗
PubMed2004

FGF-23 in patients with end-stage renal disease on hemodialysis.

BACKGROUND: Fibroblast growth factor (FGF)-23 is a recently identified circulating factor which causes renal phosphate wasting disorders. Although the mechanism of regulation of FGF-23 secretion is unknown, plasma FGF-23 level may be regulated or affected by serum phosphate levels because of its hypophosphatemic effect. METHODS: We tested the hypothesis that plasma FGF-23 levels may be increased in hyperphosphatemia in patients with end-stage renal disease (ESRD) on maintenance hemodialysis. We measured plasma FGF-23 levels in 158 male uremic patients on maintenance hemodialysis. Plasma samples were obtained before starting dialysis sessions to determine FGF-23 levels by enzyme-linked immunosorbent assay (ELISA). RESULTS: Plasma FGF-23 level exhibited significant and positive correlations with inorganic phosphate, intact parathyroid hormone (PTH), corrected calcium, and duration of hemodialysis on simple regression analyses. All these associations remained significant in multiple regression analyses. CONCLUSION: Serum phosphate, calcium, and intact PTH could be regulators of FGF-23 levels in uremic patients on maintenance hemodialysis. Our results may provide new insights into the pathophysiologic effects of FGF-23 on calcium-phosphate homeostasis.

Case-Control Studies↗
PubMed2004

Quantitative insulin sensitivity check index and the reciprocal index of homeostasis model assessment are useful indexes of insulin resistance in type 2 diabetic patients with wide range of fasting plasma glucose.

The purpose of the study was to investigate whether quantitative insulin sensitivity check index (QUICKI) and the reciprocal index of homeostasis model assessment (1/HOMA-IR) are excellent surrogate indexes of insulin resistance in type 2 diabetic patients with various ranges of fasting plasma glucose. One hundred eight type 2 diabetic patients were divided into tertiles according to fasting levels of plasma glucose (FPG) [T1: 4.2 < or = FPG (mmol/liter) < 6.5, n = 36; T2: 6.5 < or = FPG < 8.1, n = 36; T3: 8.1 < or = FPG < or = 11.1, n = 36]. The association between QUICKI or 1/HOMA-IR and insulin resistance index assessed by euglycemic hyperinsulinemic clamp (Clamp-IR) was investigated in each group. QUICKI was strongly correlated with Clamp-IR in all groups (r = 0.615 in T1, r = 0.659 in T2, and r = 0.788 in T3; all subjects, r = 0.691; all P < 0.001). Reciprocal of HOMA-IR also highly correlated with Clamp-IR in all groups (r = 0.600, r = 0.721, and r = 0.730, respectively; all subjects, r = 0.685; all P < 0.001). In conclusion, QUICKI and the reciprocal index of HOMA were highly correlated with Clamp-IR in type 2 diabetic patients with relatively wide ranges of fasting plasma glucose.

Adult↗
PubMed2004

Change in von Willebrand factor and carotid intima-media thickness in hypothyroid patients with normal thyroid function after levothyroxine replacement therapy.

OBJECTIVE: This study examined whether levothyroxine (L-T4) replacement might affect serum markers of endothelium injury, including von Willebrand factor (vWF), factor VIII activity and thrombomodulin (TM), during normalization of increased intima-media thickness (IMT) in the common carotid artery (CCA) in hypothyroid patients after L-T4 replacement therapy. PATIENTS AND METHODS: Thirty-three hypothyroid patients were examined for vWF, factor VIII, TM and CCA IMT before and after 1 year of normalization of thyroid function by L-T4 replacement. CCA IMT was measured from digitized still images taken during scanning by high-resolution ultrasonography as an indicator of early atherosclerosis. RESULTS: Serum factor VIII and vWF increased significantly during 1 year of normalization of thyroid function (from 122.7+/-9.4 to 151.3+/-18.8% (P<0.05) and from 109.9+/-9.6 to 135.2+/-12.4% (P<0.005) respectively), although these values all fell within the respective normal range. Serum TM, in contrast, did not change appreciably in response to L-T4 treatment, moving from 2.57+/-0.15 to 2.74+/-0.18 ng/ml (P=0.086). During 1 year of a euthyroid state, all patients showed a significant decrease in CCA IMT (P<0.0001). Change in serum vWF, but not in factor VIII or TM, showed a positive correlation with that of CCA IMT during L-T4 replacement therapy. Furthermore, the change in serum vWF was significantly and independently associated with change in CCA IMT (r=0.490, P=0.0038). CONCLUSIONS: The present study demonstrated that the improvement of CCA IMT during L-T4 treatment might have the potential to attenuate an elevation of vWF and to attenuate vascular injury by the cardiovascular effects of thyroid hormone in hypothyroid patients.

Biomarkers↗
PubMed2004

[Metabolic bone disease and bone quality].

On the progress of study concerned with pathology of metabolic bone disease such as osteoporosis, it has been known that most of bone strength can be explained by bone volume. As bone volume can be determine by bone mineral density (BMD) with dual-energy X-ray absorptiometry (DXA), it has been widely used for diagnosis of osteoporosis or efficacy of treatment. However, with the advance of bone morphometry, decrease of bone strength or existence of insufficiency fracture is influenced by not only loss of BMD but also deterioration of bone quality especially bone microstructure. In this chapter, we will give an outline of change of bone quality in metabolic bone disease.

Bone Diseases, Metabolic↗
PubMed2004

[SERM & bone metabolism: protective effects of SERM against fracture risk and its long-term beneficial effects].

The Multiple Outcomes of Raloxifene Evaluation (MORE) Trial enrolled 7,705 women with osteoporosis, defined by prevalent vertebral fractures and/or a bone mineral density (BMD) T score at -2.5 or below, who were treated with placebo or raloxifene at a dosage of 60 or 120 mg/day for 3 years. Raloxifene hydrochloride therapy significantly reduces the risk for vertebral fractures at 3 and 4 years administration group. The fact that Raloxifene administration causes the significant 25% reduction in overall risks in postmenopausal women indicate a favorable risk-benefit profile. These data suggested that raloxifene is effective to protect from the occurrence of bone fracture without causing increases of breast cancer and endometrial cancer, and improve overall health conditions in postmenopausal women.

Bone Density↗
PubMed2004

[Osteoporosis and mineral intake].

For prevention against the development of osteoporosis and related fractures, the importance of sufficient intake of calcium and vitamin D has been increasingly recognized. However, due to increasing intake of calcium, the relative intake of magnesium and trace elements, such as zinc and copper has been relatively decreasing and thus been focused in recent years. On this article, we will give an outline of the importance of magnesium and trace elements in the regulation of bone metabolism.

Bone Density↗
PubMed2003

Technical and clinical characterization of the Bio-PTH (1-84) immunochemiluminometric assay and comparison with a second-generation assay for parathyroid hormone.

BACKGROUND: The Bio-Intact parathyroid hormone (1-84) assay (Bio-PTH), a newly developed two-site immunochemiluminometric assay, measures exclusively PTH (1-84) in contrast to second-generation "intact PTH" (I-PTH) assays. We investigated the technical performance and clinical significance of this new assay. METHODS: PTH was measured simultaneously by the Bio-PTH assay and Allegro intact PTH IRMA in sera from Japanese patients with calcium disorders. RESULTS: Measured Bio-PTH in serum was unaffected by six freeze-thaw cycles and was stable at 4 degrees C for 7 days and during storage at -20 or -80 degrees C over 28 days. The calibration curve was linear to 1800 ng/L. The detection limit was 3.9 ng/L. The intra- and interassay imprecision was <2.8% and 3.5%, respectively, for analyte concentrations spanning the range of the calibration curve. Bio-PTH was unaffected by a 1000-fold excess of PTH (7-84), although I-PTH reacted equally with PTH (7-84) and PTH (1-84). Bio-PTH was correlated with I-PTH in healthy individuals (r = 0.953; P <0.0001; n = 26) and in the full population without renal dysfunction (r = 0.994; P <0.0001; n = 62). In 72 volunteers, mean (SD) Bio-PTH was 22.2 (7.1) ng/L, or 62% of the mean I-PTH [36.1 (22.3) ng/L]. This ratio was 51% in hemodialysis patients (n = 177). Mean Bio-PTH was high in patients with primary hyperparathyroidism [121 (85) ng/L; n = 18] and hemodialysis patients [102 (104) ng/L; n = 177], low in idiopathic hypoparathyroidism [5.5 (2.8) ng/L; n = 4], and within 2 SD of the mean for healthy controls in Paget disease of the bone [34 (15) ng/L; n = 9] and bone metastasis [24 (12) ng/L; n = 8]. CONCLUSION: The Bio-PTH assay is sensitive and precise and produces expected results for patients with the studied disorders of calcium metabolism.

Blood Specimen Collection↗
PubMed2003

Preferential reductions of paraarticular trabecular bone component in ultradistal radius and of calcaneus ultrasonography in early-stage rheumatoid arthritis.

Rheumatoid arthritis (RA) is a major cause of secondary osteoporosis and is frequently associated with both paraarticular and generalized osteoporosis. The present study was designed to investigate the preferential sites of reduction of bone mineral density (BMD), in the early stage of RA, with special emphasis on the differential effect of RA on BMD in trabecular and cortical components. The participants (30 RA patients and 26 healthy participants) were all female with disease duration of less than 1 year. BMD in the radius was measured at 4% (ultradistal site) and 20% (midshaft) to the ulnar length proximal to the end of radius by peripheral quantitative computed tomography. BMD in lumbar spine was measured by dual X-ray absorptiometry and the osteo-sono assessment index (OSI) of the calcaneus by ultrasound. RA patients showed lower BMD preferentially in the trabecular component, but not in cortical bone component of the ultradistal radius than age-matched normal controls. Calcaneus OSI was also significantly reduced. The radial midshaft and lumbar spine did not differ significantly between RA patients and normal controls. Trabecular BMD in the ultradistal radius exhibited negative correlations with serum CRP, ESR, and RF, and calcaneus OSI with M-HAQ score. In conclusion, it was suggested that disease activity of RA and impairment of daily physical activity might be a significant determinant of deterioration of bone structure in paraartciular distal radius and calcaneus, respectively, in early-stage RA patients.

Activities of Daily Living↗
PubMed2003

Platelet P-selectin expression is associated with atherosclerotic wall thickness in carotid artery in humans.

BACKGROUND: Recent genetic animal models reveal important roles of platelet P-selectin on progression of atherosclerosis. In the present study, we examine the relation between platelet P-selectin expression and atherosclerotic parameters in 517 subjects. METHODS AND RESULTS: Unrelated subjects (n=517; 235 male and 282 female), including 187 with type 2 diabetes, 184 with hypertension, and 366 with hyperlipidemia, were enrolled in the study. P-selectin expression was determined by whole-blood flow cytometry. Arterial stiffness (stiffness index beta) and arterial wall thickness (intima-media thickness [IMT]) were determined by carotid ultrasound. P-selectin expression was significantly and positively correlated with carotid IMT and stiffness index beta. Multiple regression analyses showed that the association of the percentage of P-selectin-positive platelets with carotid IMT was independent of other clinical factors. Moreover, the percentage of P-selectin-positive platelets was higher in subjects with carotid plaque and was an independent factor associated with occurrence of carotid plaque analyzed by multiple logistic regression analysis. Finally, the percentage of P-selectin-positive platelets was positively associated with age, body mass index, systolic and diastolic blood pressure, and HbA1c and inversely associated with HDL cholesterol. CONCLUSIONS: Platelet P-selectin is independently associated with atherosclerotic arterial wall changes in human subjects.

Age Factors↗
PubMed2003

Blocking of alpha 5 integrin stimulates production of TGF-beta and PAI-1 by human mesangial cells.

Expression of integrin, which mediates cell-matrix interaction, is affected by several cytokines, in particular by transforming growth factor-beta (TGF-beta). However, it is unknown whether, in an opposite way, a specific integrin is involved in cytokine synthesis. We tested this hypothesis. Function-blocking anti-alpha 5 integrin (fibronectin receptor) antibody increased TGF-beta secretion in growth-arrested human mesangial cells (2.3-fold) compared with control IgG or anti-alpha v beta 3 integrin (receptor for several matrix proteins) antibody. It also increased the secretion of plasminogen activator inhibitor-1 (PAI-1), a protein associated with matrix increase, by 3.2-fold. The increase in PAI-1 secretion induced by anti-alpha 5 integrin antibody was not abrogated by anti-TGF-beta neutralizing antibody. These results indicate that function-blocking of anti-alpha 5 integrin stimulates TGF-beta as well as PAI-1 production, suggesting that alpha 5 integrin is involved in fibrotic process. Function-modulation of a specific integrin thus appears to play a role in glomerular remodeling.

Antibodies↗