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Masaaki Inaba

Publications and source records attributed to Masaaki Inaba.

At least 109 records · Page 6Linked to original sources

Inflammation and bone resorption as independent factors of accelerated arterial wall thickening in patients with rheumatoid arthritis.

OBJECTIVE: We recently reported that rheumatoid arthritis (RA) patients had increased intima-media thickness (IMT) of the common carotid artery (CCA). The present longitudinal study was performed to determine whether the change in arterial thickness was accelerated in RA patients and to determine which factor was important in the progression of arterial wall changes. METHODS: We studied 62 female RA patients with stable disease activity and 63 healthy female controls. IMT of the CCA was measured twice by high-resolution B-mode ultrasonography. The second examination was performed 18-36 months after the first, and changes were expressed as millimeters of increase per year. Baseline examinations included blood markers of inflammation and urinary calcium excretion (expressed as the calcium-to-creatinine ratio). RESULTS: RA patients showed a significantly greater increase in IMT of the CCA compared with controls. In univariate analyses of the RA patient data, the C-reactive protein (CRP) level correlated with the increase in CCA IMT. Other markers of inflammation (the erythrocyte sedimentation rate and white blood cell and platelet counts) also showed significant positive associations with the annual increase in CCA IMT in multiple regression models when adjusted for age, smoking status, blood pressure, and serum cholesterol level. The urinary calcium-to-creatinine ratio was also significantly associated with an increase in CCA IMT. Moreover, both the CRP level and the urinary calcium-to-creatinine ratio were significantly and independently associated with the increase in IMT of the CCA. CONCLUSION: Patients with RA have a higher rate of increase in thickening of the arterial wall. Inflammation and calcium mobilization are factors closely associated with the accelerated arterial wall changes.

Arteriosclerosis↗

Successful treatment of multicentric reticulohistiocytosis with alendronate: evidence for a direct effect of bisphosphonate on histiocytes.

We describe the case of a 44-year-old Japanese woman with severe nodular erythematous skin lesions and arthritis mutilans who was admitted for further treatment of multicentric reticulohistiocytosis. Skin and synovial biopsies showed heavy infiltration with tartrate-resistant acid phosphatase-positive histiocytes and multinucleated giant cells. Immunohistochemical analysis showed that some of the mononuclear cells in the skin were positive for RANKL. After 1 month of Alendronate, an aminobisphosphonate, given at a dosage of 10 mg once a week intravenously for the first 6 weeks and then once a month thereafter, the arthritis and skin nodules improved, and the remission has continued for more than 2 years. The findings in this patient suggest that osteoclast-like multinucleated giant cells differentiate locally in the skin from infiltrating histiocytes with the help of RANKL-positive stromal cells and that alendronate acts directly on cells of monocyte/macrophage lineage in humans. Thus, alendronate should be added to the list of drugs for the treatment of multicentric reticulohistiocytosis.

Adult↗

Arterial wall stiffness is associated with peripheral circulation in patients with type 2 diabetes.

The prevalence of peripheral vascular disease (PVD) in diabetic patients is manyfold higher than that of age- and sex-matched nondiabetic subjects. This study was designed to evaluate the relationship between quantitatively determined peripheral circulation in the lower extremities and arterial wall thickness or stiffness in 68 patients with type 2 diabetes. Peripheral circulation during treadmill-exercise was monitored by transcutaneous oxygen tension (TcPO2) and was expressed as percentage of post-exercise TcPO2 adjusted by that of pre-exercise (TcPO2 index). Arterial wall thickness (intima-media thickness; IMT) and stiffness (stiffness beta) were measured by ultrasonography. TcPO2 index was negatively (r=-0.350, P=0.0007) correlated with stiffness beta, not with IMT, of the femoral artery. In patients without insulin therapy (n=52), both fasting plasma insulin concentration (r=-0.323, P=0.0023) and HOMA IR, an insulin resistance index, (r=-0.281, P=0.0084) were negatively correlated with TcPO2 index. Multiple regression analyses showed that association of stiffness beta of the femoral artery or HOMA IR with the TcPO2 index was independent of other factors including age, smoking index, ankle brachial pressure index and IMT of femoral artery. Thus, arterial wall stiffness of femoral artery appears to be a major determinant of peripheral circulation in patients with type 2 diabetes.

Age Factors↗

Association of muscle glycogen synthase polymorphism with insulin resistance in type 2 diabetic patients.

The aim of the present study is to investigate whether Met416Val (M416V) polymorphism of glycogen synthase (GYS1) gene is associated with insulin resistance in type 2 diabetes. In 100 type 2 diabetic subjects (66 men and 34 women), the M416V polymorphism of GYS1 gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) as previously reported, and insulin resistance was assessed by euglycemic hyperinsulinemic clamp represented as M/I value, the mean of glucose infusion rate (M value) adjusted by steady state plasma insulin level. The means of age and body mass index (BMI) of the subjects were 53.1+/-11.6 (SD) years and 23.3+/-3.5 kg/m2. The allele frequencies of M416V polymorphism were 82.0% for MM, 16.0% for MV, and 2.0% for VV, and subjects were subsequently divided into V(+) group (n=18) and V(-) group (n=82) according to the presence or absence of V allele. There were no significant differences in age, BMI, blood pressure, fasting plasma glucose or insulin levels or glycosylated hemoglobin (HbA1c) levels between the V(+) and V(-) groups. No significant differences in either M or M/I value were found between the V(+) and V(-) groups (M value, 5.06+/-2.20 v 5.12+/-2.04 mg x kg(-1) x min(-1), P=.841; M/I value, 5.24+/-3.07 v 5.39+/-2.87 mg x kg(-1) x min(-1) x mU(-1) x L, P=.576). BMI showed the strongest independent contribution to M/I value, but the presence of V allele did not in multiple regression analysis. In conclusion, the M416V polymorphism of GYS1 gene is not associated with insulin resistance in type 2 diabetes.

Adult↗

Decrease in carotid intima-media thickness in hypothyroid patients after normalization of thyroid function.

OBJECTIVE: This case-control study was carried out to assess whether levothyroxine (L-T4) replacement might cause regression of the enhanced atherosclerosis seen in hypothyroid patients. PATIENTS AND METHODS: Intima-media thickness (IMT) in the common carotid artery (CCA) was measured from digitalized still images taken during scanning by high-resolution ultrasonography as an indicator of early atherosclerosis. Thirty-five hypothyroid patients were examined for their CCA IMT before and 1 year after normalization of thyroid function by L-T4 replacement. As control, 35 healthy subjects were enrolled from among the participants in a local health-check programme conducted at the Osaka City University Hospital. RESULTS: Basal CCA IMT was significantly higher in hypothyroid patients [0.635 +/- 0.018 (mean +/- SE) mm] than in control subjects (0.559 +/- 0.021 mm, P < 0.005). After 1 year of euthyroidism, 34 out of 35 patients showed a significant decrease of CCA IMT, to 0.552 +/- 0.015 mm (P < 0.0001), a level comparable to normal controls. CCA IMT change was closely associated with basal levels of total cholesterol (r = -0.472, P= 0.0031), low-density lipoprotein (LDL) cholesterol (r = -0.441, P= 0.0076) and the total/HDL cholesterol ratio (r =-0.435, P= 0.0057), but not with any of the other variables measured except for age (r = -0.353, P= 0.0296). CONCLUSIONS: This study demonstrated that L-T4 treatment might have the potential to reverse the progression of atherosclerosis in hypothyroid patients. Furthermore, it suggests that increased levels of LDL cholesterol and the total/HDL cholesterol ratio have an important role in the increased common carotid intima-media thickness in hypothyroid patients.

Carotid Artery Diseases↗

Non-high-density lipoprotein cholesterol (non-HDL-C) as a predictor of cardiovascular mortality in patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease (ESRD) often show lipid abnormalities that may promote atherosclerosis. Although the standard lipid marker is low-density lipoprotein cholesterol (LDL-C) in official recommendations, the need of fasting blood sampling has prevented routine screening for plasma lipids in hemodialysis patients. METHODS: We therefore evaluated the power of non-high-density lipoprotein cholesterol (non-HDL-C) in predialysis (non-fasting) serum as a predictor of cardiovascular mortality in a cohort of 525 hemodialysis patients. RESULTS: During the mean follow-up of 64 months, 120 deaths, including 44 fatal cardiovascular events, occurred. Patients in the highest tertile of non-HDL-C (137 to 285 mg/dL) had a significantly higher risk for cardiovascular mortality (HR, 3.065; 95% CI, 1.357 to 6.925; P = 0.007) [correction] in a univariate Cox analysis. The association between non-HDL-C and cardiovascular mortality remained significant in multivariate Cox models, which included HDL-C, age, gender, duration of hemodialysis, blood pressure, presence of diabetes mellitus, serum albumin, C-reactive protein, and body mass index. CONCLUSION: Non-HDL-C in predialysis serum was a significant and independent predictor of cardiovascular mortality in hemodialysis patients. Non-HDL-C may be a useful marker for risk assessment in routine practice, although predictive powers of this and the standard fasting LDL-C should be compared in future studies.

Adult↗

Intima-media thickness of carotid artery predicts cardiovascular mortality in hemodialysis patients.

BACKGROUND: Cardiovascular disease is the leading cause of death in patients with end-stage renal disease (ESRD). Previous studies showed that patients with ESRD had increased intima-media thickness of the carotid artery (CA-IMT). In the present study, we examined whether CA-IMT would predict cardiovascular mortality in patients with ESRD. METHODS: The cohort consisted of 438 patients with ESRD treated with hemodialysis. CA-IMT was measured by high-resolution B-mode ultrasonography. RESULTS: During the follow-up period of 30 months, 82 deaths, including 44 cardiovascular fatal events, occurred. Compared with those with CA-IMT less than 1.0 mm, those with moderately increased CA-IMT (1.0 to 2.0 mm) and those with severely increased CA-IMT (>or=2.0 mm) showed a significantly greater risk for death from cardiovascular causes; odds ratios were 3.17 (95% confidence interval [CI], 1.41 to 7.17; P = 0.005) and 10.20 (95% CI, 3.67 to 28.3; P < 0.0001), respectively, in a multivariate Cox analysis including age, sex, duration of hemodialysis therapy, presence of diabetes mellitus, blood pressure, body mass index, and high-density lipoprotein and non-high-density lipoprotein cholesterol levels as covariates. Conversely, CA-IMT was not significantly associated with noncardiovascular mortality. CONCLUSION: These results indicate that increased CA-IMT is an independent predictor of cardiovascular mortality in the hemodialysis population.

Adult↗

Body fat mass in hemodialysis patients.

BACKGROUND: Changes in body fat mass in a large number of hemodialysis patients is unknown. METHODS: Body fat mass and lean body mass were measured by dual x-ray absorptiometry (DXA) in 561 patients with hemodialysis duration less than 180 months (62.3 +/- 11.5 years old; mean +/- SD). RESULTS: Fat mass tended to increase during the first 3 years of hemodialysis, and it tended to decrease thereafter. Between hemodialysis duration and the fat mass index, there was a significant positive correlation within the first 36-month period of hemodialysis (r = 0.124; P < 0.05; n = 245), and a significant negative correlation during the period of 36 to 180 months. (r = -0.192; P < 0.001; n = 316). There was no tendency of change in the lean body mass index. CONCLUSION: Considering the results together with the authors previous prospective study results, which show significant fat mass increase in the first year of hemodialysis, the present cross-sectional study may suggest that fat mass gradually increases in the first 3 years and decreases thereafter. Fat mass is suggested to be a nutritional parameter in hemodialysis patients.

Absorptiometry, Photon↗

Relationship between parathyroid gland size and responsiveness to maxacalcitol therapy in patients with secondary hyperparathyroidism.

BACKGROUND: Although vitamin D has been reported to be useful in the treatment of patients with secondary hyperparathyroidism, it is not effective in some of them. The goal of this study was to see whether a relationship could be found between maxacalcitol responsiveness and parathyroid gland size. METHODS: Parathyroid gland size was measured by ultrasonography in 25 patients with secondary hyperparathyroidism [serum intact parathyroid hormone (PTH) >300 pg/ml, 58.1 +/- 2.8 years old, 15 males and 10 females], who were treated with maxacalcitol. Patients were divided into two groups according to the mean value of the maximum diameter of the glands: group S with a diameter <11.0 mm and group L with a diameter >or =11.0 mm. Between the two groups there were no significant differences in serum intact PTH, calcium or phosphate level or duration of haemodialysis. RESULTS: Mean (+/- SE) maximal diameter of detectable parathyroid glands was 11.0 +/- 0.7 mm before treatment. At 4-24 weeks after administration of maxacalcitol, intact PTH concentrations decreased significantly in group S (from 546 +/- 39 to 266 +/- 34 pg/ml at 24 weeks; P < 0.01), but did not significantly change in group L (from 481 +/- 39 to 403 +/- 49 pg/ml at 24 weeks). At 24 weeks after maxacalcitol administration, the number of detectable parathyroid glands was significantly decreased in group S (from 2.2 +/- 0.3 to 1.8 +/- 0.4; P < 0.05), but not in group L. Serum calcium increased significantly in group L (from 9.6 +/- 0.2 to 10.2 +/- 0.3 mg/dl; P < 0.05), but not in group S. There was a significant correlation between reduction in PTH and parathyroid gland size (r = -0.42, P < 0.05). CONCLUSIONS: These results indicate that the responsiveness to maxacalcitol therapy of secondary hyperparathyroidism is dependent on parathyroid gland size and that the simple measurement of maximum parathyroid gland diameter by ultrasonography may be useful for predicting responsiveness to maxacalcitol treatment.

Antimetabolites↗

Preferential stiffening of central over peripheral arteries in type 2 diabetes.

Arterial stiffness affects cardiac functions, peripheral circulation, and cardiovascular mortality. We examined whether arterial stiffness in different regions is equally affected by diabetes and other factors. The subjects were 161 patients with type 2 diabetes and 129 healthy subjects comparable in age and sex. Arterial stiffness was evaluated by measuring pulse wave velocity (PWV) in the heart-carotid, heart-brachial, heart-femoral, and femoral-ankle segments using an automatic device. The diabetic patients had greater PWV than the healthy subjects in the four arterial regions, and the effect of diabetes on PWV was greater in the heart-carotid and heart-femoral segments (central) than in the heart-brachial and femoral-ankle regions (peripheral). PWV increased with age in the four arterial regions, and the effect of age on PWV was greater in the central than in peripheral arteries. In multiple regression analysis, age and systolic blood pressure had significant impacts on PWV of the four regions, whereas diabetes was significantly associated only with PWV of the central arteries. In contrast, sex was associated with PWV of the peripheral arteries. Thus, type 2 diabetes had greater impact on PWV of the central arteries, and different factors were involved in PWV among different arterial regions.

Adult↗

Intrarenal hemodynamic changes after captopril test in patients with type 2 diabetes: a duplex Doppler sonography study.

OBJECTIVE: ACE inhibitors are known to be effective in preventing the progression of diabetic nephropathy. Activation of the renin-angiotensin system (RAS) is reported to contribute to intrarenal hemodynamic abnormality in diabetic patients. We examined whether RAS blockade by captopril induces intrarenal hemodynamic changes in normotensive patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The patients ranged in age from 40 to 65 years (20 men and 20 women). A total of 15 age- and sex-matched healthy individuals served as control subjects. Resistive index (RI) of interlobar arteries was examined by duplex Doppler sonography before and after the oral captopril (25 mg) test. RESULTS: At baseline, no significant differences in RI values or plasma renin activity (PRA) were seen between the patients and healthy subjects. In healthy subjects, the RI values after the captopril test were significantly higher than baseline values (P < 0.01). However, in patients with type 2 diabetes, both with normoalbuminuria and microalbuminuria, RI values after the test were significantly lower than baseline values (P < 0.001). There were significant negative correlations between DeltaRI value and HbA1c (r = -0.458, P < 0.005) and between DeltaRI value and baseline PRA in diabetic patients (r = -0.339, P < 0.05). Multiple regression analysis showed that HbA1c and baseline PRA significantly and independently affected the magnitude of decrease in RI values after captopril administration in diabetic patients (R2 = 0.391, P < 0.0001). CONCLUSIONS: These results indicate that the intrarenal RAS may be activated in diabetic patients, that such activation may be affected by poor glycemic control, and that blockade of RAS activation by ACE inhibitor reduces intrarenal vascular resistance in diabetic patients. The results emphasize the beneficial effects of ACE inhibition in improving intrarenal hemodynamics in diabetic patients.

Adult↗

Factors affecting progression of renal failure in patients with type 2 diabetes.

OBJECTIVE: Hyperglycemia and hypertension are known to be risk factors for the development of proteinuria in patients with diabetes. Little is known, however, about predictors of progression of renal failure in diabetic patients. RESEARCH DESIGN AND METHODS: We investigated factors affecting progression of renal failure by measuring the doubling of serum creatinine (s-Cr) as an end point in a cohort of 85 type 2 diabetic patients with chronic renal insufficiency/failure (s-Cr >1.5 and <3.7 mg/dl, 61 +/- 11 years old, 51 men and 34 women, mean s-Cr 2.3 +/- 0.6 mg/dl). RESULTS: The survey period (mean +/- SD) was 14.2 +/- 10.8 months. The cumulative incidence of the end point in patients with insulin therapy (n = 41) was significantly lower than that in patients without it (n = 44) (P = 0.0022, P values by log-rank test). Multivariate Cox analysis revealed insulin therapy (hazard ratio [HR] 0.435, 95% CI 0.252-0.750, P = 0.0027), serum albumin (0.484, 284-0.823, P = 0.0074), mean blood pressure (1.023, 1.004-1.043, P = 0.017), and hemoglobin (0.841, 0.728-0.972, P = 0.0194) to be independent and significant predictors of progression to renal failure, whereas HbA(1c) or serum cholesterol were not. CONCLUSION: In type 2 diabetic patients with renal failure, hypoalbuminemia, anemia, higher mean blood pressure, and lack of use of insulin predict rapid progression of renal failure, but HbA(1c) does not, and insulin therapy may be possibly an indicator of the delay in progression of renal failure.

Age of Onset↗

Arterial wall thickness is associated with insulin resistance in type 2 diabetic patients.

The aim of the present study was to investigate the independent association of the intimal-medial thickness of carotid and femoral arteries (CA-IMT and FA-IMT), a marker of atheroscelosis, with insulin resistance in type 2 diabetic patients. We evaluated CA-IMT and FA-IMT by high-resolution ultrasonography and insulin resistance determined by euglycemic hyperinsulinemic clamp in 119 type 2 diabetic subjects, 71 males and 48 females (age, 54 +/- 12 (SD) years). In simple regression analyses, CA-IMT and FA-IMT were significantly inversely correlated with insulin sensitivity index (CA-IMT, r = -0.225, p = 0.010; FA-IMT, r = -0.186, p = 0.043, respectively). Multiple regression analysis was performed with the logarithm of CA-IMT or FA-IMT as a dependent variable and insulin sensitivity index as an independent variable along with known clinical risk factors. Insulin sensitivity index exhibited a significant independent contribution to log (CA-IMT) (beta = -0.204, p = 0.033) and to log (FA-IMT) (beta = -0.237, p = 0.010) in these models (CA-IMT, R(2) = 0.347, p < 0.0001; FA-IMT, R(2) = 0.398, p < 0.0001, respectively). In conclusion, insulin resistance is associated with both CA-IMT and FA-IMT in type 2 diabetic patients, suggesting that it is an independent risk factor for the development of atherosclerosis in type 2 diabetes.

Adolescent↗

[Renal osteodystrophy with diabetic bone disease].

Renal osteodystrophy (ROD) in chronic renal failure (CRF) patients with diabetes mellitus (DM) is characterized by lower degree of secondary hyperparathyroidism and higher prevalence of low turnover bone disorders than that in non-DM CRF patients. Particularly, aplastic bone disease is frequently observed (30 - 40 %). Compared to non-DM CRF patients, serum levels of osteocalcin are significantly decreased, and bone mineral density of trabecular bones is significantly decreased in DM CRF patients. Dietary calcium intake is often less than daily requirement, and hypovitaminosis D is frequently observed. Although persistent hyperglycemic state and impairment of insulin action are major contributors to diabetic osteodystrophy, many factors complicate the feature of DM-CRF. Control of blood glucose levels is the most important to alleviate abnormal bone metabolism in DM-CRF patients, and dietary calcium intake should be normalized. Further, therapeutic strategy of appropriate vitamin D administration should be established, in addition to appropriate exercise therapy, in order to prevent the progression of ROD in DM CRF patients.

English Abstract↗

Increased thickness of the arterial intima-media detected by ultrasonography in patients with rheumatoid arthritis.

OBJECTIVE: To determine whether arterial wall thickening is advanced in rheumatoid arthritis (RA) patients compared with healthy controls by measuring the intima-media thickness (IMT) of the common carotid and femoral arteries, and to evaluate the factors associated with arterial IMT in patients with RA. METHODS: We studied 138 RA patients and 94 healthy controls (matched for age, sex, and other major risk factors for atherosclerosis). IMT was measured on digitized still images of the common carotid and femoral arteries obtained by high-resolution ultrasonography (10-MHz in-line Sectascanner). Laboratory variables relevant to RA activity were measured by routine methods. The degree of RA progression was assessed by scoring (Larsen method) metacarpophalangeal (MCP) joints on hand radiographs. Activities of daily living were determined by a modified Health Assessment Questionnaire (M-HAQ) score, and physical activity levels were assessed by ultrasound measurement of the calcaneus (expressed as the osteo-sono assessment index [OSI] Z score). RESULTS: Common carotid and femoral artery IMTs were significantly higher (P < 0.05) in RA patients (mean +/- SD 0.641 +/- 0.127 and 0.632 +/- 0.125 mm, respectively) compared with controls (0.576 +/- 0.115 and 0.593 +/- 0.141 mm, respectively). Multiple regression analysis revealed a significant association between RA and the common carotid artery IMT. Moreover, the common carotid artery IMT in RA patients was positively associated with disease duration, the MCP joint Larsen score, and the M-HAQ score, and was negatively associated with the calcaneus OSI Z score. No significant association was found between corticosteroid treatment and common carotid artery IMT. CONCLUSION: RA patients exhibited greater thickness of the common carotid and femoral arteries than healthy controls. The duration and severity of RA and decreased activities of daily living, but not corticosteroid treatment, were independently associated with the increased arterial wall thickness.

Adrenal Cortex Hormones↗

Establishment and characterization of OCUT-1, an undifferentiated thyroid cancer cell line expressing high level of telomerase.

BACKGROUND & OBJECTIVES: Undifferentiated thyroid cancer is one of the most aggressive human malignancies, and the prognoses that have been reported are extremely poor. A number of studies have described the clinicopathologic features of this tumor and analyzed its biologic background to explain the extraordinarily aggressive nature of the tumor. Still the mechanism of cellular aggressiveness in undifferentiated thyroid cancer is not yet fully understood. METHODS: We established and characterized an undifferentiated thyroid cancer cell line, OCUT-1, derived from the surgical specimen obtained from a 74-year-old Japanese woman with advanced undifferentiated thyroid cancer. RESULTS: The cell line had already maintained over 100 passages and was stably cultured for more than a year. The cell line was observed to maintain not only its morphologic similarity to the primary cancer cells, but also its aggressive nature, including high proliferative activity, numerous genetic abnormalities, and cytokine production. Further, we have demonstrated the expression of telomerase activity in the cell, which could represent one of the responsible mechanisms for the cellular aggressiveness of this type of tumor. CONCLUSIONS: This cell line might be useful for further study concerning the correlation between telomerase activation and disease progression or anaplastic change in thyroid cancer.

Aged↗