Comprehensive Analysis of Inflammatory Immune Mediators in Vitreoretinal Diseases

Inflammation affects the formation and the progression of various vitreoretinal diseases. We performed a comprehensive analysis of inflammatory immune mediators in the vitreous fluids from total of 345 patients with diabetic macular edema (DME, n = 92), proliferative diabetic retinopathy (PDR, n = 147), branch retinal vein occlusion (BRVO, n = 30), central retinal vein occlusion (CRVO, n = 13) and rhegmatogenous retinal detachment (RRD, n = 63). As a control, we selected a total of 83 patients with either idiopathic macular hole (MH) or idiopathic epiretinal membrane (ERM) that were free of major pathogenic intraocular changes, such as ischemic retina and proliferative membranes. The concentrations of 20 soluble factors (nine cytokines, six chemokines, and five growth factors) were measured simultaneously by multiplex bead analysis system. Out of 20 soluble factors, three factors: interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in all groups of vitreoretinal diseases (DME, PDR, BRVO, CRVO, and RRD) compared with control group. According to the correlation analysis in the individual patient's level, these three factors that were simultaneously increased, did not show any independent upregulation in all the examined diseases. Vascular endothelial growth factor (VEGF) was significantly elevated in patients with PDR and CRVO. In PDR patients, the elevation of VEGF was significantly correlated with the three factors: IL-6, IL-8, and MCP-1, while no significant correlation was observed in CRVO patients. In conclusion, multiplex bead system enabled a comprehensive soluble factor analysis in vitreous fluid derived from variety of patients. Major three factors: IL-6, IL-8, and MCP-1 were strongly correlated with each other indicating a common pathway involved in inflammation process in vitreoretinal diseases

Chondroitin sulfate N-acetylgalactosaminyltransferase-1 is required for normal cartilage development

CS (chondroitin sulfate) is a glycosaminoglycan species that is widely distributed in the extracellular matrix. To understand the physiological roles of enzymes involved in CS synthesis, we produced CSGalNAcT1 (CS N-acetylgalactosaminyltransferase 1)-null mice. CS production was reduced by approximately half in CSGalNAcT1-null mice, and the amount of short-chain CS was also reduced. Moreover, the cartilage of the null mice was significantly smaller than that of wild-type mice. Additionally, type-II collagen fibres in developing cartilage were abnormally aggregated and disarranged in the homozygous mutant mice. These results suggest that CSGalNAcT1 is required for normal CS production in developing cartilage

腎生検を行った蛋白漏出性腎疾患の犬2例，猫1例における比較検討

高度蛋白尿を呈す犬2例，猫1例について腎生検を行い，病理学的変化，治療経過および予後を比較した。　病理学的変化は，病変なし（糸球体微小変化型病変の疑い），膜性増殖性糸球体腎炎（MPGN），巣状分節性硬化（FSGS）の疑いであった。MPGNの症例は急性経過をとり死亡し，他の2例は長期生存した。　生存した2症例にはACEI （アンギオテンシン変換酵素阻害剤）およびシクロスポリンによる治療を行った。UPCの推移や治療反応は一様ではなかった。　獣医療域において蛋白漏出性腎疾患には多様な病態が含まれていることが示唆され，糸球体障害の種類や障害の程度の把握などに腎生検が有益であった。　一方で臨床症状と生検結果に沿った適切な薬剤の選択には更なる検討が必要であり，今後は症例数を重ねて更なる検討が必要であると考えられた。A cat and two dogs with severe proteinuria underwent renal biopsy for pathological diagnosis, and their clinical outcome and prognosis were compared. Their pathological findings were all different: no abnormality (suspected of minimal change glomerular disease); membranoproliferative glomerulonephritis (MPGN) and suspected focal segmental glomerulosclerosis. The dog with MPGN died in an acute course. They were treated with angiotensin-converting enzyme inhibitor and cyclosporine. The urine protein-to-creatinine ratio and response to treatment were not consistent in these cases. These results suggest that protein-losing nephropathy may present various pathological forms in small animalsand thus renal biopsy is essential for understanding the pathological process of the disease. Further research is needed to determine the best drug of choice based on the clinical symptoms and biopsy results

A Project to Design and Build the Magnets for a New Test Beamline, the ATF2, at KEK

In order to achieve the high luminosity required at the proposed International Linear Collider (ILC), it is critical to focus the beams to nanometer size with the ILC Beam Delivery System, and to maintain the beams collisions with a nanometer-scale stability. To establish the technologies associated with this ultra-high precision beam handling, a special beamline has been designed and built as an extension of the existing extraction beamline of the Accelerator Test Facility at KEK, Japan. The ATF provides an adequate ultra-low emittance electron beam that is comparable to the ILC requirements; the ATF2 mimics the ILC final focus system to create a tightly focused, stable beam. There are 37 magnets in the ATF2, 29 quadrupoles, 5 sextupoles and 3 bends. These magnets had to be acquired in a short time and at minimum cost, which led to various acquisition strategies; but nevertheless they had to meet strict requirements on integrated strength, physical dimensions, compatibility with existing magnet movers and beam position monitors, mechanical stability and field stability and quality. This paper will describe how 2 styles of quadrupoles, 2 styles of sextupoles, one dipole style and their supports were designed, fabricated, refurbished or modified, measured and aligned by a small team of engineers from 3 continents

Effect of In Ovo Administration of Branched-Chain Amino Acids on Embryo Growth and Hatching Time of Chickens

The effect of various branched-chain amino acids (BCAA : isoleucine, leucine, valine) on embryo growth and the hatching time of fertilized eggs of chickens was examined. Before the onset of egg incubation, one of BCAA was injected into fertilized eggs. The amount of each BCAA administrated into eggs was equal to 1% of each amino acid exits in the egg. On day 14 of incubation, the weight of embryos was measured. On day 21, the hatching time was recorded, and body weight of chicks at birth was measured. The in ovo administration of BCAA increased the weight of whole embryo compared to the control. Compared to the control, the in ovo administration of leucine and valine significantly accelerated the hatching time. There were no significant differences in body weight of newly hatched chicks among all treatments. It was concluded that the in ovo administration of BCAA, especially leucine and valine, could accelerate embryo growth resulting in the acceleration of hatching time of chicks