Health-related quality of life of predialysis patients with chronic renal failure.

Background: Health-related quality of life (HQOL) of predialysis patients with chronic renal failure (CRF) has received less attention than that of dialysis patients. We investigated changes in SF-36 over 1 year and examined associations between clinical parameters and SF-36 in predialysis CRF patients.

Methods: Subjects were 471 predialysis CRF patients.

Prediction of bone mineral density from vitamin D receptor polymorphisms is uncertain in representative samples of Japanese Women. The Japanese Population-based Osteoporosis (JPOS) Study.

Background: Vitamin D receptor (VDR) gene polymorphisms have been inconsistently associated with bone mineral density (BMD). To precisely evaluate the associations between three VDR gene polymorphisms and BMD, we performed a large-scale representative study of the Japanese female population.

Methods: Fifty women were randomly selected from each of the 5-year age stratified populations (15-79 years) in each of the three municipalities examined, as a part of the Japanese population-based osteoporosis (JPOS) baseline study in 1996.

Ultrasound bone densitometry of the calcaneus, determined with Sahara, in healthy Japanese adolescents: Japanese Population-based Osteoporosis (JPOS) Study.

To establish the reference values for quantitative ultrasound (QUS) indices (speed of sound [SOS]), and broadband ultrasonic attenuation [BUA]) in healthy Japanese adolescents, and to evaluate the effects of age and body size on QUS in comparison with their effects on bone mineral density (BMD), 632 healthy adolescents aged 12 through 17 years recruited from a larger cohort study (Japanese Population-based Osteoporosis [JPOS] Study), were examined in terms of bone mass measurements by QUS at the calcaneus (Sahara; Hologic) and by dual-energy X-ray absorptiometry at the distal one-third radius and ultradistal forearm. We present sex- and age-specific mean values of the QUS and BMD indices. BMD increased significantly up to 17 years of age in males and up to 16 years in females.

Effect of orally administered shao-yao-gan-cao-tang (Shakuyaku-kanzo-to) on muscle cramps in maintenance hemodialysis patients: a preliminary study.

Muscle cramps are one of the most common complications of hemodialysis (HD), and often are a source of great pain in spite of various clinical measures. The traditional herbal medicine, shao-yao-gan-cao-tang (Japanese name: Shakuyaku-kanzo-to), consists of equal amounts of paeony and licorice roots, and has been used in Japan and China for muscle pain or skeletal muscle tremors. To determine whether this medicine is able to prevent frequent and unendurable muscle cramps in patients undergoing HD, Shakuyaku-kanzo-to at 6 g per day was prospectively administered for 4 weeks to five patients on HD who were suffering from frequent muscle cramps.

Pathogenesis of nephrogenic diabetes insipidus by aquaporin-2 C-terminus mutations.

Background: We previously reported three aquaporin-2 (AQP2) gene mutations known to cause autosomal-dominant nephrogenic diabetes insipidus (NDI) (Am J Hum Genet 69:738, 2001). The mutations were found in the C-terminus of AQP2 (721delG, 763 to 772del, and 812 to 818del). The wild-type AQP2 is a 271 amino acid protein, whereas these mutant genes were predicted to encode 330 to 333 amino acid proteins due to the frameshift mutations leading to the creation of a new stop codon 180 nucleotides downstream.

Critical role of cyclin D1 nuclear import in cardiomyocyte proliferation.

Mammalian cardiomyocytes irreversibly lose their capacity to proliferate soon after birth, yet the underlying mechanisms have been unclear. Cyclin D1 and its partner, cyclin-dependent kinase 4 (CDK4), are important for promoting the G1-to-S phase progression via phosphorylation of the retinoblastoma (Rb) protein. Mitogenic stimulation induces hypertrophic cell growth and upregulates expression of cyclin D1 in postmitotic cardiomyocytes.

ATF3 inhibits doxorubicin-induced apoptosis in cardiac myocytes: a novel cardioprotective role of ATF3.

Activating transcription factor (ATF) 3, a member of the ATF/cyclic adenosine monophosphate (cAMP)-responsive element binding protein (ATF/CREB) family of transcription factors, is induced by a wide range of stress stimuli. Although the ATF3 homodimer is known to repress transcription of several genes, its precise biological roles are still unclear. In this study, we investigated the functional role of ATF3 in doxorubicin (DOX=adriamycin)-treated neonatal rat cardiac myocytes.

Expression of aquaporin-1 in the peritoneal tissues: localization and regulation by hyperosmolality.

Objective: The purpose of this study was to determine the localization of the aquaporin-1 (AQP1) water channel in peritoneal tissues and the effect of hyperosmolality on the peritoneal expression and function of AQP1.

Methods: Immunohistochemical localization of AQP1 was identified in rat peritoneal tissues. Cultured rat peritoneal mesothelial cells (RPMCs) were exposed to hyperosmolality by adding 4% glucose to the culture medium.

Effects of L-threo-3,4-dihydroxyphenylserine on orthostatic hypotension in hemodialysis patients.

Background: Orthostatic hypotension (OH) is a serious complication observed in hemodialysis (HD) patients after HD as well as during the interdialytic period. L-Threo-3,4-dihydroxyphenylserine (L-DOPS) is a nonphysiological neutral amino acid that is directly converted to the neurotransmitter norepinephrine by aromatic L-amino acid decarboxylase.

Methods: A placebo-controlled double-blind study for 4 consecutive weeks and a long-term study (24-52 weeks) were conducted to evaluate the efficacy of L-DOPS for OH after HD.

Human CLC-KB gene promoter drives the EGFP expression in the specific distal nephron segments and inner ear.

Human CLC-KB has been identified as a kidney-specific member of the CLC chloride channel family, and mutations of the human CLC-KB gene are known to cause Bartter syndrome type III. A precise understanding of the localization of this channel in the human kidney is imperative to our understanding of the pathophysiology, but this has remained unclear due to the high homology between human CLC-KB and CLC-KA, another kidney-specific member of the same family. The high intraspecies homology also rules out an exact correlation of the human isoforms (CLC-KA and CLC-KB) to the mouse and rat isoforms (CLC-K1 and CLC-K2, respectively).

Fas-ligand and perforin expression in infiltrating cytotoxic T lymphocytes in the liver of chronic hepatitis C.

Cytotoxic T cells (CTLs) are believed to play an important role in the pathogenesis of chronic hepatitis C based on histological findings of the liver and in vivo experiments. Fas-ligand-Fas and perforin dependent pathways are two major killing systems when CTLs induce their target-cell death. Thus, the present study attempts to determine whether these pathways are activated, and if they are, how they are related in chronic hepatitis C.

CLC-3 deficiency leads to phenotypes similar to human neuronal ceroid lipofuscinosis.

Background: CLC-3 is a member of the CLC chloride channel family and is widely expressed in mammalian tissues. To determine the physiological role of CLC-3, we generated CLC-3-deficient mice (Clcn3-/- ) by targeted gene disruption.

Results: Together with developmental retardation and higher mortality, the Clcn3-/- mice showed neurological manifestations such as blindness, motor coordination deficit, and spontaneous hyperlocomotion.

Clinical effects of L-threo-3,4-dihydroxyphenylserine on orthostatic hypotension in hemodialysis patients.

Orthostatic hypotension is one of the major factors interfering with everyday activities in hemodialysis patients, but there has been no effective agent for treating it. In order to clarify the clinical effects of L-threo-3,4-dihydroxyphenylserine (L-DOPS) on orthostatic hypotension of hemodialysis patients, we conducted a randomized, double-blind comparative trial. 149 regular hemodialysis patients with orthostatic hypotension were randomly allocated to three groups and L-DOPS at doses of 400 mg, 200 mg or placebo was orally administrated to each group 30 min before starting every hemodialysis for 4 weeks.

Titin mutations as the molecular basis for dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a heterogeneous cardiac disease characterized by ventricular dilatation and systolic dysfunction. Recent genetic studies have revealed that mutations in genes for cardiac sarcomere components lead to DCM. The cardiac sarcomere consists of thick and thin filaments and a giant protein, titin.

Gene transfer of Smad7 using electroporation of adenovirus prevents renal fibrosis in post-obstructed kidney.

Background: Unilateral ureteral obstruction (UUO) leads to interstitial fibrosis of the obstructed kidney, and TGF-beta is considered to play an important role in this fibrotic process. Smad7 has been recently identified as an antagonist of TGF-beta signaling. To investigate whether this novel molecule can be exploited for therapy of renal fibrosis, we determined the effect of exogenous Smad7, introduced by a recombinant adenovirus vector combined with in vivo electroporation (EP), on UUO-induced renal fibrosis in rats.

Analysis of NaCl transport in thin ascending limb of Henle's loop in CLC-K1 null mice.

To characterize the nature of NaCl transport in the thin ascending limb (tAL), we examined the transport properties of Na(+) and Cl(-) using in vitro microperfusion of the tAL in CLC-K1 null mice. In the presence of a transmural NaCl concentration gradient (100 mM higher in the lumen), the transepithelial diffusion voltage (V(d)) was 15.5 +/- 1.

Intrarenal and cellular localization of CLC-K2 protein in the mouse kidney.

CLC-K2, a kidney-specific member of the CLC chloride channel family, is thought to play an important role in the transepithelial Cl(-) transport in the kidney. This consensus was first reached shortly after it was demonstrated that the mutations of the human CLCNKB gene resulted in Bartter's syndrome type III. To clarify the pathogenesis, the exact intrarenal and cellular localization of CLC-K2 by immunohistochemistry of the Clcnk1-/- mouse kidney were investigated by use of an anti-CLC-K antibody that recognized both CLC-K1 and CLC-K2.

Prognosis of anti-hepatitis C virus antibody-positive patients on regular hemodialysis therapy.

The prevalence of hepatitis C virus (HCV) infection is high in patients who are on chronic hemodialysis, but the role of HCV infection and HCV-related liver disease in the mortality of these patients has not been shown. Therefore, we conducted a prospective cohort study of 1470 patients who were on chronic hemodialysis (17 to 89 yr old) from 16 dialysis centers in Japan. Among them, 276 patients (18.