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Biomedical subjects

Hideki Tahara

Publications and source records attributed to Hideki Tahara.

At least 55 records · Page 3Linked to original sources
PubMed2004

Arterial stiffness in predialysis patients with uremia.

BACKGROUND: Hemodialysis patients have advanced arterial wall stiffening as shown by increased aortic pulse wave velocity (PWV), an independent predictor of cardiovascular mortality. We compared aortic PWV of uremic patients before starting hemodialysis treatment with that of patients on maintenance hemodialysis. METHODS: The subjects were 71 patients with end-stage renal disease (ESRD) before starting hemodialysis (predialysis group), 144 patients on maintenance hemodialysis, and 140 healthy control subjects. These three groups were all nondiabetic and comparable in age and gender. RESULTS: The hemodialysis group had greater aortic PWV than the healthy subjects, and the predialysis patients showed a still higher value than the hemodialysis group. Multiple regression analysis in the total subjects revealed that the presence of renal failure was significantly associated with increased aortic PWV independent of age, gender, blood pressure, body mass index, smoking, high-density lipoprotein (HDL) and nonhigh-density lipoprotein (non-HDL) cholesterol levels. In contrast, hemodialysis was associated with decreased aortic PWV independent of renal failure and the other factors. Further analyses in the combined uremic patients again indicated the favorable impact of hemodialysis on aortic PWV independent of the classical risk factors, use of antihypertensive medications, including angiotensin-converting enzyme inhibitors and calcium channel blockers, hematocrit, serum calcium, phosphorus, parathyroid hormone levels, and the use of calcium carbonate. Insulin resistance using homeostasis model assessment (HOMA-IR) was associated with increased aortic PWV. CONCLUSION: Aortic stiffening was present in uremic patients before starting hemodialysis treatment and no adverse effect of hemodialysis was observed, suggesting the important roles of renal failure and/or metabolic alterations secondary to renal failure in arterial stiffness in patients with uremia.

Aged↗
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

[Target range of PTH in uremia].

Skeletal resistance to parathyroid hormone (PTH) is well defined in patients with chronic renal failure. Recently, with the increased frequency of development of adynamic bone disease (ABD), it has been suggested that higher PTH is needed to maintain bone turnover in uremia. It has very recently been argued that the optimal PTH level for maintenance of skeletal bone remodeling may be insufficient to prevent the extraskeletal complications of cardiovascular systems. Furthermore, conventional intact PTH assay detects (7-84) PTH in addition to (1-84) PTH and overestimate the actual activity of circulating PTH molecules in uremic patients. Thus, target range of PTH in uremic patients should be set by careful considerations.

Humans↗
PubMed2004

[Osteomalacia and vitamin D deficiency in hemodialyzed patients].

Aluminum accumulation in plasma and tissues is a well-described complication among patients undergoing hemodialysis. Although the ratio of aluminum-induced osteomalacia has been decreasing year by year, there are still considerably many problems in such patients. Sources of aluminum now include food, drugs, and cooking tools. Besides, iron and strontium accumulations also induce osteomalacia. Early and accurate diagnosis of such metal toxicities is important because effective therapy is available.

Aluminum↗
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

Interaction of AP-1 and the ctgf gene: a possible driver of chondrocyte hypertrophy in growth cartilage.

The expression of the connective tissue growth factor ( ctgf) gene increases along with the differentiation of growth cartilage cells, and the highest expression is observed in the hypertrophic stage. Similarly, recent reports demonstrated c- fos expression in chondrocytes in the early hypertrophic zone of growth cartilage, and suggested that the c- fos gene may play a crucial role in the regulation of hypertrophic differentiation. A chondrocytic human cell line, HCS-2/8, is known to retain a variety of chondrocytic phenotypes. When such cells were kept overconfluent, they expressed increasing levels of c- fos transcripts along a time course phenotypically similar to that of hypertrophic differentiation. Moreover, by using a competitive electromobility-shift assay, we found that AP-1, a Fos/Jun heterodimer, in HCS-2/8 was capable of binding not only to a typical AP-1-binding DNA fragment but also to the enhancer fragment of the ctgf gene. Based on the findings above, we hypothesize that, prior to hypertrophic differentiation, AP-1-related oncogenes are activated and that their gene products subsequently activate ctgf gene expression, which might eventually induce hypertrophy.

Binding Sites↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2003

Quantitative insulin sensitivity check index and the reciprocal index of homeostasis model assessment in normal range weight and moderately obese type 2 diabetic patients.

OBJECTIVE: To investigate whether the quantitative insulin sensitivity check index (QUICKI) and the reciprocal index of homeostasis model assessment (1/HOMA-IR) derived from fasting plasma glucose and insulin level are excellent surrogate indices of insulin resistance in both normal range-weight and moderately obese type 2 diabetic and healthy subjects. RESEARCH DESIGN AND METHODS: The association between QUICKI or 1/HOMA-IR and insulin resistance index assessed by euglycemic-hyperinsulinemic clamp (clamp-IR) was investigated in 121 type 2 diabetic and 29 healthy subjects recruited from among 120 (age 55 +/- 11, 48 +/- 15, and 52 +/- 15 years [means +/- SD], respectively). Type 2 diabetic subjects were divided into groups of 76 normal range-weight and 45 moderately obese subjects (BMI 21.4 +/- 2.3 vs. 27.2 +/- 2.2 kg/m(2), P < 0.0001). RESULTS: QUICKI and 1/HOMA-IR were significantly lower in the moderately obese group than in the normal range-weight type 2 diabetic and healthy groups (n = 120) (QUICKI, 0.338 +/- 0.030, 0.371 +/- 0.037, and 0.389 +/- 0.041, respectively, P < 0.0001; 1/HOMA-IR, 0.50 +/- 0.33, 0.92 +/- 0.55, and 1.24 +/- 0.82, P < 0.0001). QUICKI was strongly correlated with clamp-IR in normal range-weight, moderately obese type 2 diabetic, and healthy subjects (r = 0.641, 0.570, and 0.502, respectively; all subjects, r = 0.608, P < 0.01) and 1/HOMA-IR exhibited correlations comparable to those of QUICKI with clamp-IR (r = 0.637, 0.530, and 0.461, respectively; all subjects, r = 0.589, P < 0.001). In multiple regression models including QUICKI or 1/HOMA-IR as an independent variable, the estimation formula accounted for 55% of the variability of clamp-IR for the group of all type 2 diabetic subjects (R(2) = 0.547 and 0.551, respectively, P <or= 0.0001). CONCLUSIONS: QUICKI and 1/HOMA-IR were highly correlated with clamp-IR, with comparable coefficients in both normal range-weight and moderately obese type 2 diabetic patients and nondiabetic subjects. The latter can probably be applied clinically in view of its convenience.

Adult↗
PubMed2002

Thoracoscopic excision for ectopic mediastinal parathyroid tumor.

Ectopic parathyroid adenoma or hyperplasia in the mediastinum are seen in a percentage of patients with hyperparathyroidism and have generally been treated by conventional open surgery. However, due to recent improvements in the ability of diagnostic imaging such as 99mTc-methoxyisobutylisonitrile (MIBI) scintigraphy to identify these lesions, we have been obtaining favorable results from thoracoscopic excision of mediastinal parathyroid tumors. In thoracoscopic surgery, three to four trocars were inserted between the fourth and seventh ribs from a lateral approach. Based on diagnostic imaging, tumors were identified and excised by the shortest possible route. Surgery time for four consecutive patients ranged from 50 to 140 min, and hemorrhage volumes were small. No intra- or postoperative complications were observed, and the postoperative course for these patients has been uneventful. Analgesia was required only a few times for each patient. In the most recent patient, radioisotope-navigated thoracoscopic excision was performed using 99mTc-MIBI. When thoracoscopic excision was combined with radioisotope navigation, tumor identification took less time, cutting the surgery time in half and ultimately placing less stress on the patient.

Adult↗
PubMed2002

Advanced atherosclerosis in predialysis patients with chronic renal failure.

BACKGROUND: Atherosclerosis is advanced in hemodialysis patients as shown by increased intima-media thickness of carotid arteries (CA-IMT), although it is not established whether the advanced atherosclerosis results from hemodialysis treatment or from chronic renal failure. The purpose of this study was to evaluate the effects of hemodialysis and renal failure on CA-IMT in patients with chronic renal failure. METHODS: CA-IMT was measured by high-resolution B-mode ultrasonography in 110 patients with chronic renal failure before starting dialysis (CRF group), and compared with CA-IMT of 345 hemodialysis patients (HD group) and 302 healthy control subjects. They were all nondiabetic and the three groups were comparable in age and gender. RESULTS: As compared with the healthy control subjects, the CRF and HD groups had greater CA-IMTs, whereas CA-IMTs of the CRF and HD groups were not statistically different. There was no significant correlation between duration of hemodialysis and CA-IMT in the HD group. Multiple regression analysis in the total subjects indicated that presence of renal failure, but not being treated with hemodialysis, was a significant factor associated with increased CA-IMT independent of age, gender, blood pressure, smoking, high-density lipoprotein (HDL) and non-HDL cholesterol levels. CONCLUSIONS: These results demonstrate that thickening of arterial wall is present in patients with chronic renal failure before starting hemodialysis treatment, and support the concept that advanced atherosclerosis in hemodialysis patients is due not to hemodialysis treatment, but to renal failure and/or metabolic abnormalities secondary to renal failure.

Arteriosclerosis↗
PubMed2002

Antibody to oxidized low-density lipoprotein and cardiovascular mortality in end-stage renal disease.

BACKGROUND: Immune response to oxidized low-density lipoprotein (oxLDL) may modulate the process of atherogenesis and cardiovascular disease. METHODS: We performed a prospective, observational cohort study in 249 patients with end-stage renal disease (ESRD) to examine whether the serum titer of anti-oxLDL antibody can predict cardiovascular mortality. RESULTS: The median anti-oxLDL antibody titer was 320 mU/mL at baseline. During the follow-up (63 +/- 23 months), 72 deaths including 34 cardiovascular deaths occurred. When the subjects were divided into two groups by the median titer, the high titer group showed a lower risk for cardiovascular mortality (P = 0.040 by Kaplan-Meier analysis and log-rank test). Multivariate Cox proportional hazards model indicated that the lower risk of cardiovascular death in the high titer group remained significant (hazard ratio of 0.46, 95%CI 0.23-0.95, P = 0.037) and independent of age, presence of vascular complications, presence of diabetes mellitus, and elevated C-reactive protein. In contrast, anti-oxLDL antibody titer was not associated with non-cardiovascular mortality. CONCLUSIONS: These results demonstrate, to our knowledge for the first time, that serum anti-oxLDL antibody titer is an independent predictor of cardiovascular mortality in a cohort of patients with ESRD.

Adult↗
PubMed2002

Clonal chromosomal defects in the molecular pathogenesis of refractory hyperparathyroidism of uremia.

Indirect X chromosome-inactivation analyses have demonstrated that most parathyroid glands from patients with uremic refractory secondary/tertiary hyperparathyroidism are monoclonal neoplasms. However, little is known regarding the specific acquired genetic abnormalities that must underlie such clonal expansion or the molecular pathogenetic features of this disorder, compared with primary parathyroid adenomas. To address these issues in a uniquely powerful manner, both comparative genomic hybridization (CGH) and genome-wide molecular allelotyping were performed with a large group of uremia-associated parathyroid tumors. As indicated by CGH, one or more chromosomal changes were present in 24% of the tumors, which is markedly different from the value for common sporadic adenomas (72%). Two recurrent abnormalities that had not been previously described for sporadic parathyroid adenomas were noted with CGH, i.e., gains on chromosomes 7 (9%) and 12 (11%). Losses on chromosome 11 occurred in only one of the 46 uremia-associated tumors (2%); the tumor also contained a somatic mutation of the remaining MEN1 allele (221del18). A total of 13% of tumors demonstrated recurrent allelic loss on 18q, with 18q21.1-q21.2 being defined as the putative tumor suppressor-containing region. In conclusion, the powerful combination of genome-wide molecular allelotyping and CGH has identified recurrent clonal DNA abnormalities that suggest the existence and locations of genes important in uremic hyperparathyroidism. In addition, genome-wide patterns of somatic DNA alterations, including disparate roles for MEN1 gene inactivation, indicate that markedly different molecular pathogenetic processes exist for clonal outgrowth in severe uremic hyperparathyroidism versus common parathyroid adenomas.

Adult↗