SAHG, a comprehensive database of predicted structures of all human proteins

Most proteins from higher organisms are known to be multi-domain proteins and contain substantial numbers of intrinsically disordered (ID) regions. To analyse such protein sequences, those from human for instance, we developed a special protein-structure-prediction pipeline and accumulated the products in the Structure Atlas of Human Genome (SAHG) database at http://bird.cbrc.jp/sahg. With the pipeline, human proteins were examined by local alignment methods (BLAST, PSI-BLAST and Smith–Waterman profile–profile alignment), global–local alignment methods (FORTE) and prediction tools for ID regions (POODLE-S) and homology modeling (MODELLER). Conformational changes of protein models upon ligand-binding were predicted by simultaneous modeling using templates of apo and holo forms. When there were no suitable templates for holo forms and the apo models were accurate, we prepared holo models using prediction methods for ligand-binding (eF-seek) and conformational change (the elastic network model and the linear response theory). Models are displayed as animated images. As of July 2010, SAHG contains 42 581 protein-domain models in approximately 24 900 unique human protein sequences from the RefSeq database. Annotation of models with functional information and links to other databases such as EzCatDB, InterPro or HPRD are also provided to facilitate understanding the protein structure-function relationships

Effect of Ranirestat, a New Aldose Reductase Inhibitor, on Diabetic Retinopathy in SDT Rats

Purpose. To evaluate the effect of ranirestat, a new aldose reductase inhibitor (ARI), on diabetic retinopathy (DR) in Spontaneously Diabetic Torii (SDT) rats. Methods. The animals were divided into six groups, normal Sprague-Dawley rats (n=8), untreated SDT rats (n=9), ranirestat-treated SDT rats (0.1, 1.0, and 10 mg/kg/day, n=7, 8, and  6, resp.), and epalrestat-treated SDT rats (100 mg/kg/day, n=7). Treated rats received oral ranirestat or epalrestat once daily for 40 weeks after the onset of diabetes. After the eyes were enucleated, the retinal thickness and the area of stained glial fibrillary acidic protein (GFAP) were measured. Results. The retinas in the untreated group were significantly thicker than those in the normal and ranirestat-treated (0.1, 1.0, and 10 mg/kg/day) groups. The immunostained area of GFAP in the untreated group was significantly larger than that in the normal and ranirestat-treated (1.0 and 10 mg/kg/day) groups. There were no significant differences between the untreated group and epalrestat-treated group in the retinal thickness and the area of stained GFAP. Conclusion. Ranirestat reduced the retinal thickness and the area of stained GFAP in SDT rats and might suppress DR and have a neuroprotective effect on diabetic retinas

Cut-Off Value of Medial Meniscal Extrusion for Knee Pain

Purpose. Medial meniscal extrusion (MME) has attracted attention as an index of knee pain in conjunction with clinical symptoms that could be more useful than the diagnosis of knee osteoarthritis on X-ray. However, the size of MME that would cause knee pain has not been clarified. The aim of the present study was to investigate the cut-off value of MME for knee pain. Methods. A total of 318 knees were evaluated. The presence of current or past knee pain was confirmed by interview. Next, MME was measured using vertical sonographic images of the medial joint spaces during weightbearing. Results. Overall, 71 knees were painful (P-group), and 247 knees were not (N-group). MME was 5.9 ± 1.8 mm in the P-group and 2.9 ± 1.5 mm in the N-group (P<0.0001). Analysis of the receiver operating characteristic curve showed that the cut-off value of MME for knee pain was 4.3 mm, with sensitivity of 0.8451 and specificity of 0.8502. In addition, 64% of knees without pain cases at the time of examination whose MME exceeded this cut-off value had past knee pain. Conclusions. The sensitivity and specificity of MME for knee pain were very high with a cut-off value of 4.3 mm