Joint effect of cigarette smoking and CFH and LOC387715/HTRA1 polymorphisms on polypoidal choroidal vasculopathy.

Purpose: To investigate whether the major genetic and environmental risk factors of age-related macular degeneration (AMD)-CFH Y402H and LOC387715 A69S and cigarette smoking-are also associated with polypoidal choroidal vasculopathy (PCV) and whether the associations of CFH Y402H and LOC387715 A69S with PCV are modified by smoking.

Methods: Three hundred seventy-five Japanese patients with PCV and 847 Japanese who served as population-based control subjects, all ≥55 years of age, were studied. CFH Y402H (rs1061170) and LOC387715 A69S (rs10490924) were genotyped with a single-nucleotide polymorphism (SNP) assay.

FRS2α regulates Erk levels to control a self-renewal target Hes1 and proliferation of FGF-responsive neural stem/progenitor cells.

Fibroblast growth factor (FGF) is among the most common growth factors used in cultures to maintain self-renewal and proliferative capabilities of a variety of stem cells, including neural stem cells (NSCs). However, the molecular mechanisms underlying the control by FGF have remained elusive. Studies on mutant mice of FGF receptor substrate 2α (FRS2α), a central mediator for FGF signaling, combined with FRS2α knockdown or gain-of-function experiments, allowed us to dissect the role of FGF signaling for the self-renewal and proliferation of NSCs and to provide novel molecular mechanisms for them.

Collocation-based sparse estimation for constructing dynamic gene networks.

One of the open problems in systems biology is to infer dynamic gene networks describing the underlying biological process with mathematical, statistical and computational methods. The first-order difference equation-based models such as dynamic Bayesian networks and vector autoregressive models were used to infer time-lagged relationships between genes from time-series microarray data. However, two primary problems greatly reduce the effectiveness of current approaches.

CFH and ARMS2 variations in age-related macular degeneration, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation.

Purpose: To seek an association in Japanese individuals between the CFH polymorphisms Y402H and I62V and the ARMS2 polymorphism A69S and age-related macular degeneration (AMD) or its three subtypes: typical (t)AMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP).

Methods: The three polymorphisms were genotyped in a case-control study of 1351 control subjects and 962 patients with AMD.

Results: The three polymorphisms correlated with AMD (Y402H, P = 1.

Theme: oncology--molecular mechanisms determining the efficacy of EGF receptor-specific tyrosine kinase inhibitors help to identify biomarker candidates.

Non-small-cell lung cancer is a major subtype of lung cancer, which is the most common and fatal cancer in the world. Gefitinib (Iressa) and later erlotinib (Tarceva), specific tyrosine kinase inhibitors for EGF receptors (EGFRs), have been demonstrated to be effective for some non-small-cell lung cancer patients and used in clinics as pioneers of molecule-based targeted drugs for cancer. There has been an urgent need to develop biomarkers and to select appropriate patients who should benefit from treatment with these drugs because of the high sensitivity of target cancer cells.

Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration.

We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH (P < 10(-75)), ARMS2 (P < 10(-59)), C2/CFB (P < 10(-20)), C3 (P < 10(-9)), and CFI (P < 10(-6)). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls).

A state space representation of VAR models with sparse learning for dynamic gene networks.

We propose a state space representation of vector autoregressive model and its sparse learning based on L1 regularization to achieve efficient estimation of dynamic gene networks based on time course microarray data. The proposed method can overcome drawbacks of the vector autoregressive model and state space model; the assumption of equal time interval and lack of separation ability of observation and systems noises in the former method and the assumption of modularity of network structure in the latter method. However, in a simple implementation the proposed model requires the calculation of large inverse matrices in a large number of times during parameter estimation process based on EM algorithm.

FRS2beta, a potential prognostic gene for non-small cell lung cancer, encodes a feedback inhibitor of EGF receptor family members by ERK binding.

An adaptor protein FRS2beta inhibits epidermal growth factor-receptor (EGFR) tyrosine kinase without being phosphorylated at tyrosine residues after EGF stimulation. Although binding to ERK appears to be important for this inhibition, the precise molecular mechanisms and the role of FRS2beta in signal transduction mediated by other EGFR family members, as well as its role in human cancer, remain unclear. In this study, we demonstrate that FRS2beta inhibits anchorage-independent cell growth induced by oncogenic ErbB2, another member of EGFR family, and that it inhibits heterodimer formation between EGFR and ErbB2.

X-ray polarimeter with a transmission multilayer.

We fabricated a novel x-ray polarimeter with a transmission multilayer and measured its performance with synchrotron radiation. A self standing multilayer with seven Mo/Si bilayers was installed with an incident angle of 45 degrees in front of a back-illuminated CCD. The multilayer can be rotated around the normal direction of the CCD keeping an incident angle of 45 degrees.

Altered renal proximal tubular endocytosis and histology in mice lacking myosin-VI.

Myosin VI (Myo6) is an actin-based molecular motor involved in clathrin-mediated endocytosis that is highly expressed in the renal proximal tubule brush border. We investigated the renal physiological consequences of loss of Myo6 function by performing renal clearance and physiological measurements on Myo6 functional null Snell's waltzer (sv/sv) and control heterozygous (+/sv) mice. Sv/sv mice showed reduced body weight and elevated blood pressure compared with controls; no differences were observed for glomerular flow rate, urine volume, blood acid-base parameters, and plasma concentrations and urinary excretions of Na(+) and K(+).

Characterization of non-endcapped polymeric ODS column for the separation of triacylglycerol positional isomers.

The characteristics of a non-endcapped polymeric ODS column for the resolution of triacylglycerol positional isomers (TAG-PI) were examined using a recycle HPLC-atmospheric pressure chemical ionization/mass spectrometry system. A pair of TAG-PI containing saturated fatty acids at least 12 carbons was separated. Except for TAG-PI containing elaidic acid, pairs of TAG-PI containing three unsaturated fatty acids were not separated, even by recycle runs.

Prognostic factors of vitreous hemorrhage secondary to exudative age-related macular degeneration.

Purpose: Vitreous hemorrhage (VH) is a rare but serious complication of the eyes with exudative age-related macular degeneration (AMD). This retrospective study was designed to evaluate various clinical factors that may affect the visual prognosis of patients with VH secondary to exudative AMD.

Design: Retrospective case study.

The hemolytic and cytolytic activities of Serratia marcescens phospholipase A (PhlA) depend on lysophospholipid production by PhlA.

Background: Serratia marcescens is a gram-negative bacterium and often causes nosocomial infections. There have been few studies of the virulence factors of this bacterium. The only S.

Gene set enrichment analysis provides insight into novel signalling pathways in breast cancer stem cells.

Background: Tumour-initiating cells (TICs) or cancer stem cells can exist as a small population in malignant tissues. The signalling pathways activated in TICs that contribute to tumourigenesis are not fully understood.

Methods: Several breast cancer cell lines were sorted with CD24 and CD44, known markers for enrichment of breast cancer TICs.

An FGF4-FRS2alpha-Cdx2 axis in trophoblast stem cells induces Bmp4 to regulate proper growth of early mouse embryos.

A variety of stem cells are controlled by the actions of multiple growth factors in vitro. However, it remains largely unclear how growth factors control the proliferation and differentiation of stem cells in vivo. Here, we describe a novel paracrine mechanism for regulating a stem cell niche in early mammalian embryos, which involves communication between the inner cell mass (ICM) and the trophectoderm, from which embryonic stem (ES) cells and trophoblast stem (TS) cells can be derived, respectively.

Analysis of surface whitening of extracted hydrophobic acrylic intraocular lenses.

Purpose: To identify the cause of light scattering on the surface (ie, whitening) of extracted AcrySof intraocular lenses (IOLs).

Setting: Department of Ophthalmology, Dokkyo Medical University, Tochigi, Japan.

Methods: Dislocated IOLs extracted from 3 patients were stored and the IOL surfaces examined under light microscopy.

Effects of three different highly purified n-3 series highly unsaturated fatty acids on lipid metabolism in C57BL/KsJ-db/db mice.

Triglycerides (TG) consisting of highly purified (>97%) n-3 series highly unsaturated fatty acids, eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), were administered to C57BL/KsJ-db/db mice for 4 weeks by pair-feeding to compare their effects on lipid metabolism and to evaluate the effects of DPA on lipid metabolism. The hepatic TG level and total amount was decreased by treatment with DHA and DPA compared to the control. The efficacy of DPA was greater than that of EPA, but less than that of DHA.

A genome-wide association analysis identified a novel susceptible locus for pathological myopia at 11q24.1.

Myopia is one of the most common ocular disorders worldwide. Pathological myopia, also called high myopia, comprises 1% to 5% of the general population and is one of the leading causes of legal blindness in developed countries. To identify genetic determinants associated with pathological myopia in Japanese, we conducted a genome-wide association study, analyzing 411,777 SNPs with 830 cases and 1,911 general population controls in a two-stage design (297 cases and 934 controls in the first stage and 533 cases and 977 controls in the second stage).

Efficacy of ophthalmic nonsteroidal antiinflammatory drugs in suppressing anterior capsule contraction and secondary posterior capsule opacification.

Purpose: To evaluate the efficacy of ophthalmic nonsteroidal and steroidal antiinflammatory drugs in preventing anterior capsule contraction and secondary posterior capsule opacification (PCO) using an experimental cataract model.

Setting: Department of Ophthalmology, Dokkyo Medical University, Tochigi, Japan.

Methods: Eight-week-old albino rabbits weighing about 2 kg each had phacoemulsification and intraocular lens implantation.

ARMS2/HTRA1 and CFH polymorphisms are not associated with choroidal neovascularization in highly myopic eyes of the elderly Japanese population.

Purpose: The purpose of this study was to investigate whether the genetic risk factors of age-related macular degeneration (AMD) are associated with the development of choroidal neovascularization (CNV) in highly myopic eyes of elderly Japanese.

Methods: Highly myopic elderly Japanese patients with and without CNV were genotyped for three AMD-associated single nucleotide polymorphisms (SNPs), namely rs10490924 (A69S) of ARMS2, rs11200638 of HTRA1, and rs1061170 (Y402H) of complement factor H (CFH), with the TaqMan SNP assay. One hundred and eighty-three unrelated highly myopic (axial lengths>26.

Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms.

Acquired uniparental disomy (aUPD) is a common feature of cancer genomes, leading to loss of heterozygosity. aUPD is associated not only with loss-of-function mutations of tumour suppressor genes, but also with gain-of-function mutations of proto-oncogenes. Here we show unique gain-of-function mutations of the C-CBL (also known as CBL) tumour suppressor that are tightly associated with aUPD of the 11q arm in myeloid neoplasms showing myeloproliferative features.

Classification of OprD sequence and correlation with antimicrobial activity of carbapenem agents in Pseudomonas aeruginosa clinical isolates collected in Japan.

A total of 99 clinical isolates of metallo-ss-lactamase-negative Pseudomonas aeruginosa collected in Japan between 1998 and 2001 were studied for their susceptibilities to carbapenem agents and corresponding oprD gene mutations. The OprD sequence of each strain was grouped into two major classes, based on the pattern of alterations. Eighty strains (80.

The FRS2 family of docking/scaffolding adaptor proteins as therapeutic targets of cancer treatment.

Background: There are two members--FRS2alpha and FRS2beta--in the fibroblast growth factor receptor substrate 2 (FRS2) family of docking/scaffolding adaptor proteins. These proteins function downstream of certain kinds of receptor tyrosine kinases (RTKs) that are important for tumorigenesis. FRS2alpha acts as a control centre for fibroblast growth factor receptor signalling and encourages tumorigenesis, while FRS2beta regulates EGFR signalling negatively, and might have a tumour suppressive role.

Increased prevalence and clonal dissemination of multidrug-resistant Pseudomonas aeruginosa with the blaIMP-1 gene cassette in Hiroshima.

Objectives: The aim of this study was to evaluate the dissemination of metallo-beta-lactamase (MBL)-encoding genes among multidrug-resistant (MDR) Pseudomonas aeruginosa isolates recovered from major hospitals in the Hiroshima region.

Methods: During July to December from 2004 to 2006, a surveillance of eight major hospitals in the Hiroshima region identified 387 non-duplicate isolates resistant to imipenem (MIC >or= 16 mg/L). They were screened for resistance to amikacin (MIC >or= 64 mg/L) and ciprofloxacin (MIC >or= 4 mg/L) and MBL-encoding genes.

Pseudomonas aeruginosa Las quorum sensing autoinducer suppresses growth and biofilm production in Legionella species.

Bacteria commonly communicate with each other by a cell-to-cell signalling mechanism known as quorum sensing (QS). Recent studies have shown that the Las QS autoinducer N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C(12)-HSL) of Pseudomonas aeruginosa performs a variety of functions not only in intraspecies communication, but also in interspecies and interkingdom interactions. In this study, we report the effects of Pseudomonas 3-oxo-C(12)-HSL on the growth and suppression of virulence factors in other bacterial species that frequently co-exist with Ps.