Search

Ken Ogino,1 Maho Oishi,1 Akio Oishi,1 Satoshi Morooka,1 Masako Sugahara,1 Norimoto Gotoh,1,2 Masafumi Kurimoto,3 Nagahisa Yoshimura1 1Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, 2Center for Genomic Medicine, Kyoto University, 3Department of Ophthalmology, Kyoto Katsura Hospital, Kyoto, JapanPurpose: To describe the peripheral autofluorescence images and clinical features of patients with retinal dystrophy who showed radial fundus autofluorescence (FAF) at the posterior pole.Methods: The authors retrospectively reviewed pooled wide-field FAF images of 711 patients with retinal dystrophy and 56 family members.Results: Eleven eyes of seven women exhibited radial FAF at the posterior pole. Wide-field FAF showed extension of the radial pattern to the periphery in all eyes except one. One woman showed radial hyper-FAF only in the periphery, not at the posterior pole. These eight individuals were X-linked retinitis pigmentosa patients or carriers. The tapetal-like reflex was not observed in their color fundus photographs. The peripheral visual field showed wedge-shaped restriction in some individuals.Conclusion: Wide-field FAF imaging can depict radial FAF not only at the posterior pole but also in the periphery in X-linked retinitis pigmentosa carriers. The authors therefore agree with previous reports that radial FAF may be a hallmark of X-linked retinitis pigmentosa. Keywords: X-linked retinitis pigmentosa, radial pattern, wide-field fundus autofluorescence, RPGR gene

Background:Pancreatic cancer has a poor prognosis because of its high refractoriness to chemotherapy and tumour recurrence, and these properties have been attributed to cancer stem cells (CSCs). MicroRNA (miRNA) regulates various molecular mechanisms of cancer progression associated with CSCs. This study aimed to identify the candidate miRNA and to characterise the clinical significance.Methods:We established gemcitabine-resistant Panc1 cells, and induced CSC-like properties through sphere formation. Candidate miRNAs were selected through microarray analysis. The overexpression and knockdown experiments were performed by evaluating the in vitro cell growth and in vivo tumourigenicity. The expression was studied in 24 pancreatic cancer samples after laser captured microdissection and by immunohistochemical staining.Results:The in vitro drug sensitivity of pancreatic cancer cells was altered according to the miR-1246 expression via CCNG2. In vivo, we found that miR-1246 could increase tumour-initiating potential and induced drug resistance. A high expression level of miR-1246 was correlated with a worse prognosis and CCNG2 expression was significantly lower in those patients.Conclusions:miR-1246 expression was associated with chemoresistance and CSC-like properties via CCNG2, and could predict worse prognosis in pancreatic cancer patients. [ABSTRACT FROM AUTHOR]

Naturally shed deciduous teeth are potentially useful as a biomarker of environmental exposure. To assess the prenatal environment of child, we tried to present the neonatal line on the elemental maps and investigate the trace elements in pre- and post-natally formed tooth enamel using micro-PIXE. Generally, the neonatal line is observed more clearly in the tooth from child who has some difficulties at birth. In this study, five deciduous teeth from five children with developmental disorders were used for analysis. Seven trace elements (, , , , , , and ) were detected in enamel of all five teeth. The line, it was thought neonatal line, was observed on the elemental map of and in the tooth from the child with serious birth complications. In order to compare the elemental concentration between pre- and post-natal enamel, concentration variation of elements were projected along the line perpendicular to the neonatal line. Lower concentration in prenatal enamel was observed. By tracing the location of neonatal line on the other elemental maps, the concentrations of detected trace elements were compared in the same way. The differences of concentration of these trace elements between pre- and post-natal enamel were not clear because of much statistic variation. We could determine the trace elemental profiles and concentrations around the neonatal line in the enamel from the child with serious birth complications. [ABSTRACT FROM AUTHOR]

PurposeThe 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.MethodsHighly 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 >26.00 mm or refractive errors >−6.0 diopters) Japanese patients with CNV who were 50 years of age (mean age±standard deviation of 62.7±6.3 years) and 170 highly myopic patients without CNV who were 50 years old (62.3±7.1 years) were studied. The differences in the genotypic distributions for the three SNPs between the two groups were tested with the Trend χ2 test, and logistic regression analyses were performed for age and gender adjustment.ResultsNo significant difference was detected in the distribution of the three SNPs, rs10490924 (P>0.1), rs11200638 (P>0.1), and rs1061170 (P>0.5), between the two groups even after adjustments for age and gender differences.ConclusionThe genetic risk factors of AMD related to these SNPs do not contribute significantly to the development of CNV in a highly myopic elderly Japanese population. [ABSTRACT FROM AUTHOR]

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. Tumourigenesis was analysed using sorted cells and total RNA was subjected to gene expression profiling and gene set enrichment analysis (GSEA).Results: We showed that several breast cancer cell lines have a small population of CD24(-/low)/CD44(+) cells in which TICs may be enriched, and confirmed the properties of TICs in a xenograft model. GSEA revealed that CD24(-/low)/CD44(+) cell populations are enriched for genes involved in transforming growth factor-beta, tumour necrosis factor, and interferon response pathways. Moreover, we found the presence of nuclear factor-kappaB (NF-kappaB) activity in CD24(-/low)/CD44(+) cells, which was previously unrecognised. In addition, NF-kappaB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) prevented tumourigenesis of CD24(-/low)/CD44(+) cells in vivo.Conclusion: Our findings suggest that signalling pathways identified using GSEA help to identify molecular targets and biomarkers for TIC-like cells. [ABSTRACT FROM AUTHOR]

BackgroundEmerging evidences suggest that circulating hematopoietic stem cells (HSCs) affect the pathogenesis of choroidal neovascularization (CNV), however, the roles of HSCs in CNV remain unclear in human population. The current study was designed to investigate the role of HSCs in the pathogenesis of CNV secondary to pathologic myopia (PM).MethodsWe clinically documented 78 patients with CNV in PM, and 35 of 78 patients and 28 age-matched controls were experimentally analysed. Functional analyses of HSCs were performed using an ex vivo culture system.ResultsWe disclosed colony-forming units of endothelial cell (CFU-EC) were markedly lower in patients with bilateral CNV compared to those with unilateral CNV (13.8±3.7 vs 45.9±7.8, P<0.001). Systemic characteristics between both groups showed no significant difference. To identify local ocular factors that may affect the occurrence of CNV, clinical parameters were compared with the following groups in all enrolled subjects: eyes with CNV vs without CNV in unilateral affected patients, and primary affected eyes vs secondary affected eyes in patients with bilateral CNV. However, no statistically significant factors were identified in any of the groups.ConclusionsCirculating HSCs may play a role in the bilateral involvement of CNV in PM patients as one of the systemic factors. Further prospective and longitudinal studies are required.Eye (2009) 23, 718–726; doi:10.1038/eye.2008.192; published online 20 June 2008 [ABSTRACT FROM AUTHOR]

The docking protein FRS2α is a major mediator of fibroblast growth factor (FGF) signaling. However, the physiological role of FRS2α in vivo remains unknown. In this report, we show that Frs2 tv-null mouse embryos have a defect in anterior-posterior (A-P) axis formation and are developmentally retarded, resulting in embryonic lethality by embryonic day 8. We demonstrate that FRS2α is essential for the maintenance of self-renewing trophoblast stem (TS) cells in response to FGF4 in the extraembryonic ectoderm (ExE) that gives rise to tissues of the placenta. By analyzing chimeric embryos, we found that FRS2α also plays a role in cell movement through the primitive streak during gastrulation. In addition, experiments are presented demonstrating that Bmp4 expression in TS cells is controlled by mitogen-activated protein kinase-dependent FGF4 stimulation. Moreover, both the expression of Bmp4 in ExE and activation of Smadl/5 in epiblasts are reduced in FRS2α-null embryos. These experiments underscore the critical role of FRS2α in mediating multiple processes during embryonic development and reveal a potential new link between FGF and Bmp4 signaling pathways in early embryogenesis. [ABSTRACT FROM AUTHOR]

Investigates the role of FRS2 alpha in fibroblast growth factor (FGF) receptor-mediated signal transduction pathway. Characterization of FRS2 alpha-deficient fibroblast; Disruption of FRS2alpha gene; Role of FGF-induced mitogen-activated protein kinase stimulation; Implication for embryogenic development.

Spontaneous cefsulodin-resistant mutants of Pseudomonas aeruginosa PAO4089 were isolated on agar impregnated with 3 mg/l of cefsulodin. This strain does not produce any chromosomal beta-lactamase. The MICs of cefsulodin for the parent and its mutants were 0.78 and 12.5 mg/l, respectively. Complete cross-resistance between cefsulodin and seven other antipseudomonal beta-lactams was noted in the mutants. The mutant gene, designated as pbpB, was mapped by FP5 plasmid-mediated conjugation and found to be near to cys-59 on the PAO chromosome, the gene order being pur-67, oruI, pbpB and cys-59. There were no detectable differences between the parent and its mutants in their outer membrane protein profiles. Penicillin-binding protein assay, by the competition method, with cefsulodin or carbenicillin showed a significant reduction in affinity of PBP3 for these beta-lactams. This PBP is the primary target for cefsulodin in P. aeruginosa. The genetic mechanism by which the cefsulodin-resistant clinical isolates of P. aeruginosa have emerged is discussed. [ABSTRACT FROM AUTHOR]

Decreased susceptibilities to two low Mr beta-lactam antibiotics, CS-533 (a carbapenem; Mr, 339) and CGP31608 (a penem; Mr, 262), were found in imipenem-resistant mutants of Pseudomonas aeruginosa PAO. The diffusion rates of several beta-lactam antibiotics including imipenem, CS-533 and CGP31608 across the proteoliposome membrane reconstituted from the outer membrane of the wild type strain or its imipenem-resistant mutants were determined by the liposome swelling technique. Diffusion rates of imipenem, CS-533 and CGP31608 in the proteoliposomes from outer membranes of the imipenem-resistant strain were found to be 27, 20 and 47%, respectively, of the diffusion rates in proteoliposomes reconstituted from outer membranes of the sensitive parent strain. The SDS-polyacrylamide gel electrophoretogram of outer membrane proteins of the imipenem-resistant strains indicated deletion of protein D2. These results suggested that decreased susceptibilities to imipenem, CS-533 and CGP31608 were due to decreased outer membrane permeability, and that D2 is a protein fraction constituting pores for diffusion of these antibiotics through the P. aeruginosa outer membrane. [ABSTRACT FROM AUTHOR]

Investigates sites of mutations in clinical strains of Pseudomonas aeruginosa and Enterococcus faecium. Materials and methods; Results and discussion.

Abstract: Mono-layered gold nanoparticles just below the surface of silicon oxide film have been formed by a gold negative-ion implantation at a very low-energy, where the deviation of implanted atoms was sufficiently narrow comparing to the size of nanoparticles. Gold negative ions were implanted into SiO2 thin films on Si substrate at energies of 35, 15 and 1keV. The samples were annealed in Ar flow for 1h at 900 or 1000°C. Cross-sectional TEM observation for the implantation at 1keV showed existence of Au nanoparticles aligned in the same depth of 5nm from the surface. The nanoparticles had almost same diameter of 7nm. The nanoparticles were found to be gold single crystal from a high-resolution TEM image. [Copyright &y& Elsevier]