We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000011929 .).

Immune attacks are key issues for cell transplantation. To assess the safety and the immune reactions after iPS cells-derived retinal pigment epithelium (iPS-RPE) transplantation, we transplanted HLA homozygote iPS-RPE cells established at an iPS bank in HLA-matched patients with exudative age-related macular degeneration. In addition, local steroids without immunosuppressive medications were administered. We monitored immune rejections by routine ocular examinations as well as by lymphocytes-graft cells immune reaction (LGIR) tests using graft RPE and the patient’s blood cells. In all five of the cases that underwent iPS-RPE transplantation, the presence of graft cells was indicated by clumps or an area of increased pigmentation at 6 months, which became stable with no further abnormal growth in the graft during the 1-year observation period. Adverse events observed included corneal erosion, epiretinal membrane, retinal edema due to epiretinal membrane, elevated intraocular pressure, endophthalmitis, and mild immune rejection in the eye. In the one case exhibiting positive LGIR tests along with a slight fluid recurrence, we administrated local steroid therapy that subsequently resolved the suspected immune attacks. Although the cell delivery strategy must be further optimized, the present results suggest that it is possible to achieve stable survival and safety of iPS-RPE cell transplantation for a year.

Uniaxial compression tests have been conducted on Oshima granite under various constant axial strain rates ranging from 10−8 to 10−4. The results showed that the strength and the acoustic emission rate increased exponentially with increasing strain rate. The inelastic volumetric strain rate defined by the differentiation with respect to the stress increased with decreasing strain rate. The redistribution of microcracks due to subcritical crack growth was considered theoretically, and the equations derived from the theory were compared with the experimental results. The agreement between the theoretical and experimental results shows that stress corrosion plays not only a major role in the brittle creep under constant load but also dominates the strain rate effects on strength and dilatancy observed in the constant strain rate loadings.

The purpose of this study was to examine the effects of a heavy-resistance exercise protocol known to dramatically elevate immunoreactive growth hormone (GH) on circulating insulin-like growth factor I (IGF-I) after the exercise stimulus. Seven men (23.1 +/- 2.4 yr) volunteered to participate in this study. Each subject was asked to perform an eight-station heavy-resistance exercise protocol consisting of 3 sets of 10 repetition maximum resistances with 1-min rest between sets and exercises followed by a recovery day. In addition, a control day followed a nonexercise day to provide baseline data. Pre- and postexercise (0, 15, and 30 min) blood samples were obtained and analyzed for lactate, creatinine kinase, GH, and IGF-I. Postexercise values for lactate and GH were significantly (P < 0.05) elevated above preexercise and resting baseline values. The highest mean GH concentration after the heavy-resistance exercise protocol was 23.8 +/- 11.8 micrograms/l, observed at the immediate postexercise time point. Significant increases in creatine kinase were observed after the exercise protocol and during the recovery day. No significant relationships were observed between creatine kinase and IGF-I concentrations. No significant changes in serum IGF-I concentrations were observed with acute exercise or between the recovery and control days. Thus, these data demonstrate that a high-intensity bout of heavy-resistance exercise that increases circulating GH did not appear to affect IGF-I concentrations over a 24-h recovery period in recreationally strength-trained and healthy young men.

Mannan-binding protein (MBP) is Mannan-binding protein (MBP),1 also called mannose-binding protein (MBP) or mannan-binding lectin, is a Ca 2ϩ -dependent (C-type) serum lectin and an important serum component associated with innate immunity (1-4). Human MBP is a homo-oligomer of an ϳ31-kDa subunit, each subunit containing a carbohydrate recognition domain followed by a short neck region on the COOH-terminal side and a collagen-like domain followed by a short cysteine-rich region on the NH 2 -terminal side. Three subunits form a structural unit, and MBP normally consists of two to six structural units joined through disulfide bonds at the amino termini, the whole molecular mass being ϳ200 -600 kDa (5, 6).The carbohydrate specificity of MBP is rather broad (it binds to mannose, N-acetylglucosamine, and fucose) in accordance with the fact that MBP binds to the cell surfaces of a wide variety of pathogens (7,8). MBP exhibits complement-dependent bactericidal activity, i.e. the Escherichia coli K12 and B strains, which have exposed N-acetylglucosamine and L-glycero-D-mannoheptose residues, respectively, are killed by MBP with the aid of complement (8). In addition, 1-deoxymannojirimycin (an ␣-mannosidase inhibitor)-treated baby hamster kidney cells, which have high mannose type oligosaccharides exposed on their surfaces, are also killed by MBP with the aid of complement (9). This complement activation pathway is called the lectin pathway (10). MBP has also been shown to function as a direct opsonin (11) and to prevent virus infection (12, 13). 1 The abbreviations used are: MBP, mannan-binding protein; AAL, A. aurantia lectin; CID, collision-induced dissociation; ConA, concanavalin A; FACS, fluorescence-activated cell sorter; FCS, fetal calf serum; FITC, fluorescein 4-isothiocyanate; Fuc, fucose; Hex, hexose; HexNAc, N-acetylhexosamine; HPLC, high performance liquid chromatography; LA, lectin affinity; LacNAc, N-acetyllactosamine; LCA, Lens culinaris lectin; Le, Lewis antigen; LTA, Lotus tetragonolobus lectin; mAb, monoclonal antibody; MALDI, matrix-assisted laser desorption/ ionization; MLO, MBP ligand oligosaccharides; MLO-A1, MBP ligand oligosaccharide-acidic fraction (monosialylated); MLO-N, MBP ligand oligosaccharide-neutral fraction; MS, mass spectrometry; MS/MS, tandem mass spectrometry; nano-ESI, nanoelectrospray ionization; PA, 2-aminopyridine; PBS, phosphate-buffered saline; PHA-E4, P. vulgaris erythroagglutinating lectin; PHA-L4, P. vulgaris leukoagglutinating lectin; PNA, peanut lectin; TOF, time-of-flight. All of the sugar residues have the D configuration except fucose, which has the L configuration.