Papers by Yoshiki Nishizawa
The role of albumin in bone metabolism was studied in Nagase analbuminemic (NA) rats. Serum calci... more The role of albumin in bone metabolism was studied in Nagase analbuminemic (NA) rats. Serum calcium (Ca), inorganic phosphate (Pi) and magnesium (Mg) concentrations did not differ between female NA and control Sprague-Dawley (SD) rats at the time of ovariectomy (ovx), although serum ionized Ca was significantly lower in NA rats than in SD rats. Serum parathyroid hormone (PTH) and
Background—Recent genetic animal models reveal important roles of platelet P-selectin on progress... more 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 (n517; 235 male and 282 female), including 187 with type 2 diabetes, 184 with hypertension, and 366 with hyperlipidemia, were enrolled in the study.
cAMP and cGMP are known to suppress vascular smooth muscle cell (SMC) proliferation. In this stud... more cAMP and cGMP are known to suppress vascular smooth muscle cell (SMC) proliferation. In this study, our aim was to delineate the molecular mechanism underlying cAMP and cGMP suppression of cell cycle transition in human SMCs. cAMP inhibits both platelet-derived growth factor-stimulated cyclin-dependent kinase (cdk) 2 and cdk4 activation through upregulation of the cdk2 inhibitor p27 Kip1 and downregulation of
was investigated in each group. QUICKI was strongly corre- lated with Clamp-IR in all groups (r 0... more was investigated in each group. QUICKI was strongly corre- lated 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
Hyperthyroid patients exhibit accelerated bone loss by increased bone turnover, and normalization... more Hyperthyroid patients exhibit accelerated bone loss by increased bone turnover, and normalization of thyroid function is associated with a significant attenuation of increased bone turnover, followed by an increase in bone mineral density. However, of patients with Graves' disease (GD) maintained on antithyroid drug (ATD) treat- ment, some exhibit persistent suppression of TSH long after normal- ization of their serum
Atherosclerosis, 2010
ObjectiveReceptor for advanced glycation end-products (RAGE) has been shown to be involved in car... more ObjectiveReceptor for advanced glycation end-products (RAGE) has been shown to be involved in cardiovascular diseases. We examined the involvement of RAGE in atherosclerosis under non-diabetic status, and its relation to the effect on adiposity.
Abstract—Proliferation and,avb3 integrin‐ dependent,migration of vascular smooth,muscle,cells are... more Abstract—Proliferation and,avb3 integrin‐ dependent,migration of vascular smooth,muscle,cells are suppressed,on polymerized,type I collagen. To identify genes specifically regulated in human,smooth,muscle cells by polymerized collagen, we used the suppressive subtraction hybridization technique. Compared with smooth muscle cells cultured on monomer collagen, polymerized collagen suppresses the following: (1) a number of other extracellular matrix proteins, including fibronectin, thrombospondin-1, tenascin-C, and cysteine-rich protein 61;
Biochemical and Biophysical Research Communications, 2005
Cancer cells in solid tumors are challenged by various microenvironmental stresses, including hyp... more Cancer cells in solid tumors are challenged by various microenvironmental stresses, including hypoxia, and cancer cells in hypoxic regions are resistant to current cancer therapies. To investigate the mechanism of resistance to hypoxia in cancer cells, we examined mouse Lewis lung carcinoma (LLC) cells, which died due to necrosis at high density under hypoxic but not under normoxic conditions. Levels
Background. Renal failure results in deficiency of active vitamin D3 that has diverse effects on ... more Background. Renal failure results in deficiency of active vitamin D3 that has diverse effects on metab- olism and organ functions. Treatment with active forms of vitamin D3 ameliorates abnormalities in bone and mineral metabolism, cardiac function, immune response and others. We hypothesized that treatment with vitamin D3 may be beneficial for survival in patients with end-stage renal disease (ESRD). Methods.
Endothelial dysfunction has been implicated in the pathogenesis of diabetic microangiopathies suc... more Endothelial dysfunction has been implicated in the pathogenesis of diabetic microangiopathies such as retinopathy and nephropathy as well as macrovascular diseases. The aim of the current study was to determine whether endothelial function in the retinal and renal arteries is impaired in type 2 diabetes mellitus. We examined the effects of an intravenous infusion of L-arginine and a sublingual administration
Magnesium research : official organ of the International Society for the Development of Research on Magnesium
Serum magnesium (Mg) levels have been associated with muscle performance in the general populatio... more Serum magnesium (Mg) levels have been associated with muscle performance in the general population. We hypothesized that serum Mg would be associated with muscle quality in hemodialysis patients. A total of 310 patients were examined (age: 58 ± 12 years, hemodialysis duration: 6.4 ± 6.0 years, 60.6% men, and 36.1% diabetics). Arm lean mass was measured by dual energy X-ray absorptiometry (DXA) on the dominant side. Arm muscle quality was defined as the ratio of the handgrip strength to the arm lean mass of the same side (kg/kg). Serum Mg was 1.15 ± 0.16 mmol/L (2.8 ± 0.4 mg/dL), being higher than the reference range of normal subjects. There was a significant negative correlation between muscle quality and age (r = -0.326, p<0.0001) and duration of hemodialysis (r = -0.253, p<0.0001). The muscle quality of the diabetics was significantly lower than that of the non-diabetics (p<0.001). There was a significant, positive correlation between muscle quality and serum Mg (r = 0.1...
Circulation research, Jan 12, 2002
Inflammatory cells such as macrophages and T lymphocytes play an important role in vascular calci... more Inflammatory cells such as macrophages and T lymphocytes play an important role in vascular calcification associated with atherosclerosis and cardiac valvular disease. In particular, macrophages activated with cytokines derived from T lymphocytes such as interferon-gamma (IFN-gamma) may contribute to the development of vascular calcification. Moreover, we have shown the stimulatory effect of 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) on in vitro calcification through increasing the expression of alkaline phosphatase (ALP), an ectoenzyme indispensable for bone mineralization, in vascular smooth muscle cells. Therefore, we hypothesized that macrophages may induce calcifying phenotype, especially the expression of ALP in human vascular smooth muscle cells (HVSMCs) in the presence of IFN-gamma and 1,25(OH)2D3. To test this hypothesis, we used cocultures of HVSMCs with human monocytic cell line (THP-1) or peripheral blood monocytes (PBMCs) in the presence of IFN-gamma and 1,25(OH)2D3. T...
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation, 2015
Protein-energy wasting plays an important role in the increased risk of mortality from cardiovasc... more Protein-energy wasting plays an important role in the increased risk of mortality from cardiovascular disease in people with end-stage renal disease. Because protein-energy wasting is a condition of imbalance between anabolism and catabolism, endocrine and metabolic alterations that regulate such balance should be the possible target of intervention. Subjects with end-stage renal disease exhibit various changes in thyroid function, gonadal hormones, adrenal androgen, glucose metabolism, dyslipidemia, fatty acid composition, cholesterol absorption, and vitamin D. In this article, we briefly review the association of these alterations with mortality and cardiovascular disease in hemodialysis patients. Although some of them may be the adaptive response to the catabolic condition, these observational data are useful for risk stratification of patients and also for providing new ideas for possible prevention.
Journal of bone and mineral metabolism, Jan 16, 2014
Paget's disease of bone (PDB) is a chronic disorder characterized by localized bone regions with ... more Paget's disease of bone (PDB) is a chronic disorder characterized by localized bone regions with excessive bone turnover. Although oral risedronate (17.5 mg daily for 8 weeks) was recently approved in Japan, its efficacy is not well understood. We retrospectively examined the efficacy of oral risedronate in PDB patients in a clinical setting. Eleven patients whose serum alkaline phosphatase (ALP) level exceeded the upper limit of the normal range were treated. Patients whose ALP levels normalized and remained so for 12 months after therapy initiation were defined as responders. Treatment was repeated if bone pain recurred or if serum ALP levels increased at least 25% above the nadir. Six patients (55%) were responsive to the therapy. A higher prevalence of skull lesions, higher serum calcium levels at treatment initiation and antecedent treatments of bisphosphonates were predictors of resistance against the therapy. Fresh frozen serum samples obtained from some treatment sessions were evaluated for metabolic bone markers such as bone-specific ALP (BAP), type I procollagen N-terminal pro-peptide (PINP), N-treminal crosslinking telopeptide of type I collagen and C-treminal crosslinking telopeptide of type I collagen (CTX). A significant reduction of P1NP preceded that of serum ALP levels in the responders, which was followed by a similar occurrence for BAP and osteocalcin (BGP) levels. A temporary decrease in CTX levels was noted. No significant changes in markers (including ALP level) were observed in non-responder and repeattreatment groups. P1NP levels may be more useful than ALP levels in assessing treatment efficacy. Repeat treatment effectiveness for the repeat-treatment group was limited.
Atherosclerosis, 2014
The receptor for advanced glycation end-products (RAGE) is involved in vascular complications in ... more The receptor for advanced glycation end-products (RAGE) is involved in vascular complications in diabetic patients. Pioglitazone, in contrast to glimepiride, has been shown to be protective against atherosclerotic disorders. In this study, we directly compared the effects of those drugs on RAGE system. Sixty-three type 2 diabetic patients (age 20-80 years, hemoglobin A1c 6.4-10.3%) being treated with sulfonylurea (glimepiride 0.5-2.0 mg/day, glyclazide 20-80 mg/day, glibenclamide 1.25-5.0 mg/day), or with nateglinide or metiglynide were randomly assigned to receive either pioglitazone (n = 31) or glimepiride (n = 32). Levels in plasma of soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE), and RAGE expression in peripheral mononuclear cells were determined at 0, 12, and 24 weeks. Twenty-seven patients in the pioglitazone group (15-30 mg) and 30 in the glimepiride group (0.5-4 mg) completed the 24-week trial. Increases in plasma esRAGE were significantly greater in the piogli...
PLOS ONE, 2015
Fatigue is a predictor of cardiovascular events in patients with end-stage renal disease (ESRD) u... more Fatigue is a predictor of cardiovascular events in patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment. We hypothesized that multinutritional support would improve quality of life, fatigue symptoms, and potential quantitative measures including endocrine, immune and autonomic functions in patients with ESRD undergoing hemodialysis. Two hundred and two hemodialysis patients were randomly assigned to receive active treatment (containing vitamin B1, vitamin B2, niacin, vitamin B6, vitamin B12, folic acid, vitamin C, carnitine, coenzyme Q10, naïve galacto-oligosaccharide, and zinc) or placebo after each dialysis session for 12 weeks. The patients and attending physicians were blinded to the treatment, and 172 patients (86 in each group) completed the study. Fatigue was evaluated via fatigue questionnaire at 0, 4, and 12 weeks. To assess human herpes virus (HHV) 6 and 7 reactivation, numbers of viral DNA copies were determined in saliva by polymerase chain reaction at weeks 0 and 12. Autonomic function was determined via measurement of beat-to-beat variation by using acceleration plethysmography. Clinical characteristics, changes in fatigue, quality of life score, endocrine functions, and laboratory data did not differ significantly between the two groups. Several parameters of heart rate variability significantly increased after nutritional treatment compared to placebo. Nutritional drink for 12 weeks significantly suppressed HHV7 DNA copy numbers. Similarly, HHV6 DNA copy numbers tended to be decreased by treatment but without reaching statistical significance. Nutritional supplementation may modulate immune and autonomic dysfunction in ESRD patients undergoing hemodialysis.
Biological trace element research, 2011
Trace element disturbance is often observed in hemodialysis patients. While trace element concent... more Trace element disturbance is often observed in hemodialysis patients. While trace element concentrations have been reported in blood samples from hemodialysis patients, they have not been well investigated in scalp hair. In the present study, 22 trace elemental concentrations were measured by inductively coupled plasma-atomic emission spectrometry in the scalp hair of 80 male hemodialysis patients and compared with those of 100 healthy male subjects. In hemodialysis patients, the concentrations of beryllium, arsenic, magnesium, chromium, manganese, iron, selenium, molybdenum, iodine, vanadium, and cobalt were significantly higher than those in healthy subjects, while lead, mercury, copper, germanium, and bromine were significantly lower than those in the former group. No significant differences were observed for lithium, aluminum, cadmium, zinc, boron, or nickel. There were significant positive correlations between the duration of hemodialysis and the magnesium and manganese concent...
Pediatrics international : official journal of the Japan Pediatric Society, 2006
Local force distribution supporting the bodyweight of infants with Down syndrome (DS) appears to ... more Local force distribution supporting the bodyweight of infants with Down syndrome (DS) appears to be different from that of healthy controls. The purpose of the present study was to establish methods to assess this force distribution and to allow therapeutic evaluation of neurological development in DS infants prior to walking. Contact pressure distribution patterns in supine and prone positions were measured by photoelastic methods and were compared between DS infants and healthy controls. The DS group included eight subjects, seven with regular trisomy 21, and one with a Robertson translocation. The controls consisted of 14 neonates, four 4-month-old infants and eight 7-month-old infants. In both groups, head loading ratio decreased as age advanced but the decrement was less in the test group than in the control group. When the bodyweight loading ratios were measured in two different lying positions, that is, prone and supine, the ratios for prone generally tended to be smaller tha...
Nihon rinsho. Japanese journal of clinical medicine, 2005
Clinical calcium, 2005
Bio-intact parathyroid hormone (Bio-PTH) assay, which measures exclusively intact PTH (1-84) mole... more Bio-intact parathyroid hormone (Bio-PTH) assay, which measures exclusively intact PTH (1-84) molecule, provides a better assay for estimating parathyroid function in hemodialysis (HD) patients, whereas intact PTH (I-PTH) assay cross-react with PTH (7-84) as well as PTH (1-84). We have found that PTH (7-84) accumulated into serum of hemodialysis patients due probably to its impaired excretion into urine. We have reported that parathyroid gland size is one of major predictor for vitamin D responsiveness in secondary hyperparathyroidism. Therefore, we investigated whether serum Bio-PTH, in comparison with serum I-PTH, may provide a relevant assay to estimate parathyroid function as evidence by its correlation with parathyroid gland size on ultrasound examination.
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Papers by Yoshiki Nishizawa