CiteULike: jyuh's Osawa

Calcium and phosphorus control in patients undergoing hemodialysis: from the view-points of activities of daily living.

Y Osawa — 2008-06-30T01:53:56-00:00

Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy, Vol. 11 Suppl 1 (October 2007)

To determine the compliance with the JSDT guidelines and activities of daily living (ADLs), phosphorus levels, calcium levels and Barthel index of patients under maintenance hemodialysis therapy in Shinrakuen hospital at December 2005 were evaluated. Of 369 patients, 28.7 % were controlled in the range of JSDT guidelines both phosphorus and calcium. Administration of sevelamer hydrochloride were low both in number of patients and also of using dose. Barthel index were higher in the patients with high phosphorus levels and low calcium level. Patients mortality at February 2007 was highest in the group of low phosphorus and high calcium levels in which the ADLs were the lowest. Concerned about vascular complication, patients in the group with target level or higher level of calcium and phosphorus were frequently noted.

Visualizing Spatiotemporal Dynamics of Multicellular Cell-Cycle Progression

Asako Sakaue-Sawano — 2008-02-08T16:32:00-00:00

Cell, Vol. 132, No. 3. (8 February 2008), pp. 487-498.

Summary The cell-cycle transition from G1 to S phase has been difficult to visualize. We have harnessed antiphase oscillating proteins that mark cell-cycle transitions in order to develop genetically encoded fluorescent probes for this purpose. These probes effectively label individual G1 phase nuclei red and those in S/G2/M phases green. We were able to generate cultured cells and transgenic mice constitutively expressing the cell-cycle probes, in which every cell nucleus exhibits either red or green fluorescence. We performed time-lapse imaging to explore the spatiotemporal patterns of cell-cycle dynamics during the epithelial-mesenchymal transition of cultured cells, the migration and differentiation of neural progenitors in brain slices, and the development of tumors across blood vessels in live mice. These mice and cell lines will serve as model systems permitting unprecedented spatial and temporal resolution to help us better understand how the cell cycle is coordinated with various biological events.

The forkhead transcription factor FoxO1 regulates proliferation and transdifferentiation of hepatic stellate cells.

M Adachi — 2008-01-19T07:20:23-00:00

Gastroenterology, Vol. 132, No. 4. (April 2007), pp. 1434-1446.

BACKGROUND & AIMS: The Forkhead box gene, group O (FoxO) family of Forkhead transcription factors is phopsphorylated and inactivated by the phosphatidylinositol 3-kinase (PI3K)/AKT pathway and regulates a variety of cellular functions. Hepatic stellate cells (HSCs) play a crucial role in liver fibrosis. A fibrotic stimulus causes HSCs to transdifferentiate from a quiescent phenotype to a collagen-producing myofibroblast-like phenotype and to proliferate. METHODS: Mutation/deletion mutants of FoxO1 were introduced into primary rat, mouse, and immortalized human HSCs and assessed for activation, proliferation, and signal transduction. The role of FoxO1 in experimental liver fibrosis was assessed in FoxO1(+/-) and FoxO1(+/+) mice. RESULTS: Platelet-derived growth factor (PDGF) or insulin phosphorylates FoxO1 and induces FoxO1 translocation from the nuclei to the cytosol via the PI3K/AKT pathway in HSCs. Constitutively active FoxO1 inhibits proliferation via cell cycle arrest at the G1 phase, whereas dominant-negative FoxO1 enhances proliferation of HSCs even in the presence of the PI3K inhibitor LY294002. In addition, the phosphorylation of FoxO1 is increased during transdifferentiation of HSCs. The transdifferentiation is also inhibited by constitutively active FoxO1 and is accelerated by dominant-negative FoxO1. FoxO1 directly induces the expression of p27(kip1) and manganese superoxide dismutase (MnSOD). After bile duct ligation for 3 weeks, FoxO1(+/-) mice are more susceptible to liver fibrosis, consistent with our in vitro results. CONCLUSIONS: FoxO1 plays a crucial role in the transdifferentiation and proliferation of HSCs in liver fibrosis. Hyperinsulinemia inactivates FoxO1 in HSCs, resulting in HSC activation and may result in the fibrosis in nonalcoholic fatty liver disease.

In-Depth Proteomic Profiling of the Normal Human Kidney Glomerulus Using Two-Dimensional Protein Prefractionation in Combination with Liquid Chromatography-Tandem Mass Spectrometry.

Masahito Miyamoto — 2007-08-26T22:57:48-00:00

J Proteome Res (21 August 2007)

The kidney glomerulus plays a pivotal role in ultrafiltration of plasma into urine and also is the locus of kidney disease progressing to chronic renal failure. We have focused proteomic analysis on the glomerulus that is most proximal to the disease locus. In the present study, we aimed to provide a confident, in-depth profiling of the glomerulus proteome. The glomeruli were highly purified from the kidney cortex from a male, 68-year-old patient who underwent nephroureterectomy due to ureter carcinoma. The patient was normal in clinical examinations including serum creatinine and urea levels and liver function, and did not receive any chemotherapy and radiotherapy. The cortical tissue was histologically normal, and no significant deposition of immunoglobulins and complement C3 was observed. We employed a novel strategy of protein separation using 1D (SDS-PAGE) and 2D (solution-phase IEF in combination with SDS-PAGE) prefractionation prior to the shotgun analysis with LC-MS/MS. The protein prefractionation produced 90 fractions, and eventually provided a confident set of identified proteins consisting of 6686 unique proteins (3679 proteins with two or more peptide matches and 3007 proteins with one peptide match), representing 2966 distinct genes. All the identified proteins were annotated and classified in terms of molecular function and biological process, compiled into 1D and 2D protein arrays, consisting of 15 and 75 sections, corresponding to the protein fractions which were defined by MW and pI range, and deposited on a Web-based database (http://www.hkupp.org). The most remarkable feature of the glomerulus proteome was a high incidence of identification of cytoskeleton-related proteins, presumably reflecting the well-developed, cytoskeletal organization of glomerular cells related to their physiological functions. Keywords: human kidney * glomerulus * 2D protein prefractionation * solution-phase IEF * database.

Genetic variations associated with diabetic nephropathy and type II diabetes in a Japanese population.

S Maeda — 2007-08-11T15:48:57-00:00

Kidney Int Suppl, No. 106. (August 2007)

Genetic susceptibility plays an important role in the pathogenesis of diabetic nephropathy and type II diabetes. To identify the genetic polymorphisms associated with diabetic nephropathy and type II diabetes, we performed a genome-wide association study using single-nucleotide polymorphisms as genetic markers. We also analyzed polymorphisms within the genes encoding for the renin-angiotensin system that were considered as candidate genes for diabetic nephropathy susceptibility and the transcription factor 7-like 2 (TCF7L2) as a candidate for type II diabetes, in a large cohort of a Japanese population. A genome-wide association study identified SLC12A3 and engulfment and cell motility 1 gene as the new candidates for diabetic nephropathy and transcription factor-activating protein 2beta as a novel susceptibility gene for type II diabetes; this observation was based on the significant association between the polymorphisms within the genes and the corresponding diseases (P<0.0001). Further, we discovered that the genes encoding the angiotensin-converting enzyme, angiotensinogen, and angiotensin II type I receptor have a significant combinational effect on conferring susceptibility to diabetic nephropathy. Furthermore, TCF7L2 that has been reported as a convincing susceptibility gene for type II diabetes in Caucasian populations was also shown to be associated with type II diabetes in a Japanese population. These genes could be considered as strong susceptibility genes for diabetic nephropathy and type II diabetes in the Japanese, although the new candidates that have been identified by genome-wide screening need to be examined in greater detail by several replication studies.

Combinational effect of genes for the reninangiotensin system in conferring susceptibility to diabetic nephropathy

Osawa — 2007-02-26T09:43:05-00:00

Journal of Human Genetics, Vol. 52, No. 2. (February 2007), pp. 143-151.