A promoter polymorphism of lamin A/C gene is an independent genetic predisposition to arterial stiffness in a Japanese general population (the Tanno and Sobetsu study).

Aim: We examined the hypothesis that there is a positive, independent association between polymorphisms of lamin A/C gene (LMNA) and arterial stiffness in Japanese.

Methods: The subjects were 261 men (mean age, 64.4+/-0.

The impact of diabetes mellitus on vitamin D metabolism in predialysis patients.

Although diabetes mellitus (DM) disturbs bone metabolism, little is known concerning its effects on laboratory abnormalities in chronic kidney disease-mineral and bone disorders (CKD-MBD). We extracted data for 602 patients from the Osaka Vitamin D Study in patients with CKD (OVIDS-CKD), an observational study enrolling predialysis outpatients. No enrolled patients received vitamin D, bisphosphonate, estrogen or raloxifene.

[Sampling and early measure devised to deal with high-risk patients].

To evaluate high-risk group in the elderly is very important. Elderly itself is high-risk, and elderly patients show higher frequencies of cardiovascular diseases, falling and fracture, dementia and impairment of activity of daily life (ADL). To evaluate high-risk for cardiovascular diseases, arterial stiffness measured by pulse wave velocity and atherosclerosis measured by carotid-echography are very useful.

Prevention of osteoporosis by angiotensin-converting enzyme inhibitor in spontaneous hypertensive rats.

A recent analysis of clinical studies suggests that angiotensin-converting enzyme (ACE) inhibitors might reduce bone fractures. In this study, we examined whether an ACE inhibitor might attenuate osteoporosis in a hypertensive rat model. In spontaneous hypertensive rats (SHRs), estrogen deficiency induced by ovariectomy (OVX) resulted in a significant increase in osteoclast activation as assessed by the tartrate-resistant acid phosphatase (TRAP) activity in the tibia, accompanied by a significant decrease in bone density evaluated by dual-energy X-ray absorptiometry and an increase in urinary deoxypyridinoline.

Effect of interleukin-6 receptor blockage on renal injury in apolipoprotein E-deficient mice.

Hyperlipidemia has been demonstrated to be associated with renal disease, yet the mechanism of renal injury is still poorly understood. Inflammation that occurs with the hyperlipidemia has been considered to play an important role in development of glomerular injury. In the present study, we investigated the role of interleukin-6 (IL-6), a key inflammatory molecule, on renal injury in apolipoprotein E-deficient (ApoE(-/-)) mice with severe hypercholesterolemia.

Genetic basis of hypertension for the development of tailored medicine.

Similar to a tsunami wave, a new surge of genome-wide association studies in common complex diseases has succeeded in identifying the causative genetic risk factors of hypertension. The current status of genomic studies in hypertension, however, remains disorganized, and there are no clear solutions in sight. One possible reason for this disorganization is the small effect of each genetic variant on the predisposition to hypertension.

Kid-1 participates in regulating ERK phosphorylation as a part of the circadian clock output in rat kidney.

Circadian clock genes play a role for the regulation of cell cycle, but the factors connecting clock to cell cycle are not fully understood. We found that mRNA of Kid-1--a zinc-finger-type transcriptional repressor was localized to cortical and juxtamedullary segments of tubules but not to glomeruli in the rat kidney. Kid-1 mRNA showed robust circadian oscillation with a peak at ZT16.

Validation of Abeta1-40 administration into mouse cerebroventricles as an animal model for Alzheimer disease.

Valid animal models for a specific human disease are indispensable for development of new therapeutic agents. The conclusions drawn from animal models largely depend on the validity of the model. Several studies have shown that administration of Abeta into the brain causes some of the pathological events observed in Alzheimer disease (AD).

Elevation of plasma beta-amyloid level by glucose loading in Alzheimer mouse models.

With the emergence of a promising approach to treat Alzheimer disease (AD) targeting the beta-amyloid (Abeta) pathway, it is necessary to establish new diagnostic biomarkers that enable the antemortem diagnosis of AD. Although plasma Abeta has been suggested as a non-invasive biomarker, its significance has been inconclusive. Thus, it is important to improve the diagnostic potential of plasma Abeta.

The CXCL12 (SDF-1)/CXCR4 axis is essential for the development of renal vasculature.

CXC chemokine ligand 12 (CXCL12; stromal cell-derived factor 1) is a unique homeostatic chemokine that signals through its cognate receptor, CXCR4. CXCL12/CXCR4 signaling is essential for the formation of blood vessels in the gastrointestinal tract during development, but its contribution to renal development remains unclear. Here, we found that CXCL12-secreting stromal cells surround CXCR4-positive epithelial components of early nephrons and blood vessels in the embryonic kidney.

A candidate gene approach to genetic prognostic factors of IgA nephropathy--a result of Polymorphism REsearch to DIstinguish genetic factors Contributing To progression of IgA Nephropathy (PREDICT-IgAN).

Background: Renal prognosis of IgA nephropathy (IgAN) is affected by environmental and genetic factors. Other studies demonstrated that some atherosclerotic disease-related genes were significantly associated with renal prognosis.

Methods: The Polymorphism REsearch to DIstinguish genetic factors Contributing To progression of IgAN (PREDICT-IgAN) was a multicentre retrospective observational study to investigate associations between progression of IgAN (a 50% increase of serum creatinine level and slope of eGFR) and a hundred atherosclerotic disease-related gene polymorphisms, mainly single nucleotide polymorphisms (SNPs) in 320 IgAN patients who had more than a normal range of urinary protein (> or =0.

Klotho suppresses TNF-alpha-induced expression of adhesion molecules in the endothelium and attenuates NF-kappaB activation.

Klotho is a senescence suppressor protein that, when overexpressed, extends the lifespan of mice. Klotho-disrupted mice exhibit atherosclerosis and endothelial dysfunction, which led us to investigate the effect of the Klotho protein on vascular inflammation, particularly adhesion molecule expression. In this study, human umbilical vein endothelial cells (HUVECs) were preincubated with Klotho protein and then exposed to tumor necrosis factor-alpha (TNF-alpha) or vehicle.

Fluvastatin improves osteoporosis in fructose-fed insulin resistant model rats through blockade of the classical mevalonate pathway and antioxidant action.

Feeding rats with a high-fructose diet induced insulin resistance, leading to hypertension or metabolic disorders. Although hypertension is known to accelerate osteoporosis, it is not obvious whether insulin resistance would accelerate osteoporosis. In this study, we evaluated whether osteoporosis might accelerate in fructose-fed rats (FFR), and examined the effect of fluvastatin through a blockade of the mevalonate pathway and an antioxidant action.

Negative effects of anemia on quality of life and its improvement by complete correction of anemia by administration of recombinant human erythropoietin in posttransplant patients.

Background: Anemia is a common complication in posttransplant patients (posttransplant anemia: PTA). We tested the hypothesis that targeting hemoglobin (Hb) over 13.3 g/dl by administration of recombinant human erythropoietin (rHuEPO-ad) has positive impact on quality of life (QOL).

[Angiotensin (1-7) receptor].

Mas, which was protooncogene, first detected in vivo by tumorigenic properties originating from rearrangement of its 5'-flanking region was identified as a functional receptor for angiotensin (1-7) and provide a clear molecular basis for the physiological actions of this biologically active peptide. Angiotensin (1-7) is mainly produced from angiotensin II by angiotensin converting enzyme 2, homologue of angiotensin converting enzyme. Many investigations suggested angiotensin (1-7) via Mas receptor might play protective effects on hypertensive complications, such as renal dysfunction and cardiovascular diseases, competed with angiotensin II and its type 1 receptor.

Relationship between the achieved blood pressure and the incidence of cardiovascular events in Japanese hypertensive patients with complications: a sub-analysis of the CASE-J trial.

Various guidelines for hypertension specify that the target blood pressure (BP) should be below 140/90 mm Hg and that strict control is recommended for patients with cardiovascular risk factors. We examined the relationship between the achieved BP and the incidence of cardiovascular events in hypertensive patients with complications as a sub-analysis of the Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial. A total of 4703 patients were evaluated for efficacy in the CASE-J trial.

Severe adverse effects of 5-fluorouracil in S-1 were lessened by haemodialysis due to elimination of the drug.

S-1 and cisplatin are used as one of the first-line chemotherapies for gastric cancer in Japan. The plasma concentration of 5-fluorouracil (5-FU) is increased in patients with renal dysfunction because gimeracil in S-1 inhibits the degradation of 5-FU and about 50% of gimeracil is excreted in the urine. We describe a 35-year-old man with acute kidney injury while taking S-1 and cisplatin for advanced gastric cancer and who presented severe adverse effects of 5-FU.

Usefulness of bone resorption markers in hemodialysis patients.

Although bone biopsy is a golden standard in the diagnosis of renal osteodystrophy, it is invasive and repetitive evaluation of bone status by this method is practically impossible. Non-invasive evaluation by bone metabolic markers such as serum cross-linked N-telopeptide of type I collagen (NTX) might give us additional information which cannot be obtained only by measurements of parathyroid hormone (PTH). These days, bone resorption marker, serum tartrate-resistant acid phosphatase (TRAP5b) was reported to be correlated with histomorphometric parameters of bone resorption in a bone biopsy study enrolling hemodialysis (HD) patients.

Macrophage inflammatory protein-1beta induced cell adhesion with increased intracellular reactive oxygen species.

Unlabelled: To investigate the role of macrophage inflammatory protein-1 beta (MIP-1beta) in the development of atherosclerosis, we designed an in vitro study to elucidate the mechanisms of monocyte-endothelium adhesion via intracellular reactive oxygen species (ROS). Angiotensin II (AngII) was used as a positive control. Furthermore, we examined the efficacy of MIP-1beta as a predictor of stroke and cardiovascular events in hypertensive patients.

Active vitamin D and its analogue, 22-oxacalcitriol, ameliorate puromycin aminonucleoside-induced nephrosis in rats.

Background: Recent studies have demonstrated that podocyte injury, which results in proteinuria, leads to tubulointerstitial fibrosis. Although some studies have revealed that vitamin D administration protects renal structure and function in mesangial cell proliferative and/or excessive matrix productive models, the effects of vitamin D on podocyte injury have remained uncertain.

Methods: In this study, we examined whether administration of active vitamin D (calcitriol) or its analogue, 22-oxacalcitriol (maxacalcitol), is preventative in podocyte injury using the puromycin aminonucleoside nephrosis model with neither mesangial proliferation nor matrix accumulation.

Fas promoter region gene polymorphism is associated with an increased risk for myocardial infarction.

A growing body of evidence has shown that Fas-mediated apoptosis is involved in atherosclerosis progression. Recent studies have revealed that a single nucleotide polymorphism (SNP) in the Fas promoter region (-670G/A) influences Fas expression. Here, we investigated whether -670G/A SNP influences the incidence of myocardial infarction (MI) by examining a comparison between MI patients (n=154) and control subjects (n=462) in a Japanese population.