Anti-angiogenic effect of siphonaxanthin from green alga, Codium fragile.

Since anti-angiogenic therapy has becoming a promising approach in the prevention of cancer and related diseases, the present study was aimed to examine the anti-angiogenic effect of siphonaxanthin from green alga (Codium fragile) in cell culture model systems and ex vivo approaches using human umbilical vein endothelial cells (HUVECs) and rat aortic ring, respectively. Siphonaxanthin significantly suppressed HUVEC proliferation (p<0.05) at the concentration of 2.5 μM (50% as compared with control) and above, while the effect on chemotaxis was not significant. Siphonaxanthin exhibited strong inhibitory effect on HUVEC tube formation. It suppressed the formation of tube length by 44% at the concentration of 10 μM, while no tube formation was observed at 25 μM, suggesting that it could be due to the suppression of angiogenic mediators. The ex vivo angiogenesis assay exhibited reduced microvessel outgrowth in a dose dependent manner and the reduction was significant at more than 2.5 μM. Our results imply a new insight on the novel function of siphonaxanthin in preventing angiogenesis related diseases

Japan College of Rheumatology 2009 guidelines for the use of tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, in rheumatoid arthritis

The introduction of biological agents targeting tumor necrosis factor-alpha (TNF-α) has brought about a paradigm shift in the treatment of rheumatoid arthritis (RA). Although these anti-TNF agents have excellent efficacy against RA, a substantial number of patients still show inadequate responses. In Western countries, such patients are already being treated with new classes of antirheumatic drugs such as abatacept and rituximab. Tocilizumab (TCZ) is a humanized monoclonal antibody developed in Japan against the human interleukin-6 (IL-6) receptor. TCZ does not only alleviate the signs and symptoms of RA but also seems to prevent progressive bone and joint destruction. However, there is a concern that TCZ might increase the risk of adverse events such as infections since IL-6 plays a pivotal role in the immune system. Calculating the relative risks of specific adverse outcomes with TCZ use remains difficult, due to insufficient patient numbers enrolled in clinical trials to date. This review presents tentative guidelines for the use of TCZ for RA patients prepared by the Japan College of Rheumatology and based on results of clinical trials in Japan and Western countries. The guidelines are intended as a guide for postmarketing surveillance and clinical practice, and will be revised periodically based on the surveillance

Basement Membrane beneath Serous Mesothelial Cells Contains α1(IV), α2(IV), α5(IV), and α6(IV) Chains of Type IV Collagen Demonstrated by Chain-specific Monoclonal Antibodies

Serous membrane (SM) covers inner surface of abdominal, thoracic and pericardial cavities, aswell as outer surface of organs inside the cavities. It consists of surface mesothelial cells andloose connective tissue. Between them, a thim layer of basement membrane (BM) is located. Type IVcollagen is major constituent of BM, and consists of 6 different a(IV) chains, a1(IV) through a6(IV).Chain-specific functions are assumed by a chain-specific manner of localization. The a(IV) chaincomposition of skin, covering outer surface of the body, is demonstrated to have a1(IV), a2(IV), a5(IV),and a6(IV) chains, whereas that of SM, covering inner surface of the body, is yet to be analyzed. Abdominal wall, small intestine, thoracic wall, lung, pericardium and epicardium of humanmaterials were used in this study. Chain-specific monoclonal antibodies (mAbs) used were H11(for a1), H22 (for a2), H31 (fo a3), H43 (for a4), H53 (for a5) and H63 (for a6). Fresh frozen sectionswere stained with indirect immunofluorescence staining using the mAbs. Four out of six a(IV) chains, a1, a2, a5 and a6, were demonstrated in BM beneath themesothelial cells of all types of SMs, whereas only capillary BM consisted of a1 and a2. Besides,epicardial SM expressed a3 and a4 moderately as extra components. The a(IV) chain composition was same as those of epidermal skin BM. Therefore, these a(IV)chains are designated to be essential for BM covering inside and outside of the body

Effectiveness, safety, and factors associated with the clinical success of endoscopic biliary drainage for patients with hepatocellular carcinoma: a retrospective multicenter study

Background Only a few reports have assessed the effectiveness of endoscopic biliary drainage (EBD) in hepatocellular carcinoma (HCC) patients with obstructive jaundice and liver dysfunction. Methods This was a retrospective study based on the clinical databases from the Okayama University Hospital and 10 affiliated hospitals. All patients received EBD for jaundice or liver dysfunction. The indication for EBD was aggravation of jaundice or liver dysfunction with intrahepatic bile duct (IHBD) dilation. The technical and clinical success rate, complications, factors associated with clinical failure, and survival duration were evaluated. Results A total of 107 patients were enrolled in this study. Technical success was achieved in 105 of 107 patients (98.1%). Clinical success was achieved in 85 of 105 patients (81%). Complications related to endoscopic retrograde cholangiography (ERC) occurred in 3 (2.8%) patients. Child–Pugh class C (odds ratio 3.90, 95% confidence interval [CI] 1.47–10.4, p = 0.0046) was the only factor associated with clinical failure, irrespective of successful drainage. The median survival duration was significantly longer in patients with clinical success than in those without clinical success (5.0 months vs. 0.93 months; hazard ratio [HR] 3.2, 95% CI 1.87–5.37). HCC Stage I/II/III (HR 0.57, CI 0.34–0.95, p = 0.032), absence of portal thrombosis (HR 0.52, CI 0.32–0.85, p = 0.0099), and clinical success (HR 0.39, CI 0.21–0.70, p = 0.0018) were significant factors associated with a long survival. Conclusions EBD for obstructive jaundice and liver dysfunction in patients with HCC can be performed safely with a high technical success rate. Clinical success can improve the survival duration, even in patients expected to have a poor prognosis

Development of an adaptation scale for university students with developmental disorders (including the tendency): Extraction of the items

We developed an adaptation scale for university students with developmental disorders. 1) Subjects comprised 62 university students with developmental disorders (including tendency) who consulted the health support room at University A from April, 2010 to April, 2015. We obtained data regarding issues and situations reported by the students themselves. 2) We obtained data regarding issues reported by university staff. 3) We retrospectively examined behavioral problems and psychiatric symptoms. On the basis these data, we made the adaptation scale. The tool which evaluates the annoyance in the campus life, psychiatric symptoms, coping behavior, and social support is useful for 1) integrated evaluation, 2) common understanding of the supporters, 3) visualization of difficult concepts, and 4) grasping of the change

Fluorescent probes for the analysis of DNA strand scission in base excision repair

We have developed fluorescent probes for the detection of strand scission in the excision repair of oxidatively damaged bases. They were hairpin-shaped oligonucleotides, each containing an isomer of thymine glycol or 5,6-dihydrothymine as a damaged base in the center, with a fluorophore and a quencher at the 5′- and 3′-ends, respectively. Fluorescence was detected when the phosphodiester linkage at the damage site was cleaved by the enzyme, because the short fragment bearing the fluorophore could not remain in a duplex form hybridized to the rest of the molecule at the incubation temperature. The substrate specificities of Escherichia coli endonuclease III and its human homolog, NTH1, determined by using these probes agreed with those determined previously by gel electrophoresis using 32P-labeled substrates. Kinetic parameters have also been determined by this method. Since different fluorophores were attached to the oligonucleotides containing each lesion, reactions with two types of substrates were analyzed separately in a single tube, by changing the excitation and detection wavelengths. These probes were degraded during an incubation with a cell extract. Therefore, phosphorothioate linkages were incorporated to protect the probes from nonspecific nucleases, and the base excision repair activity was successfully detected in HeLa cells

Activation of Src Mediates PDGF-Induced Smad1 Phosphorylation and Contributes to the Progression of Glomerulosclerosis in Glomerulonephritis

Platelet-derived growth factor (PDGF) plays critical roles in mesangial cell (MC) proliferation in mesangial proliferative glomerulonephritis. We showed previously that Smad1 contributes to PDGF-dependent proliferation of MCs, but the mechanism by which Smad1 is activated by PDGF is not precisely known. Here we examined the role of c-Src tyrosine kinase in the proliferative change of MCs. Experimental mesangial proliferative glomerulonephritis (Thy1 GN) was induced by a single intravenous injection of anti-rat Thy-1.1 monoclonal antibody. In Thy1 GN, MC proliferation and type IV collagen (Col4) expression peaked on day 6. Immunohistochemical staining for the expression of phospho-Src (pSrc), phospho-Smad1 (pSmad1), Col4, and smooth muscle α-actin (SMA) revealed that the activation of c-Src and Smad1 signals in glomeruli peaked on day 6, consistent with the peak of mesangial proliferation. When treated with PP2, a Src inhibitor, both mesangial proliferation and sclerosis were significantly reduced. PP2 administration also significantly reduced pSmad1, Col4, and SMA expression. PDGF induced Col4 synthesis in association with increased expression of pSrc and pSmad1 in cultured MCs. In addition, PP2 reduced Col4 synthesis along with decreased pSrc and pSmad1 protein expression in vitro. Moreover, the addition of siRNA against c-Src significantly reduced the phosphorylation of Smad1 and the overproduction of Col4. These results provide new evidence that the activation of Src/Smad1 signaling pathway plays a key role in the development of glomerulosclerosis in experimental glomerulonephritis

A Case of Cholesterol Crystal Embolization with Hemorrhagic Intestinal Ulcer

Cholesterol crystal embolization (CCE) is a rare systemic embolism caused　by formation of cholesterol crystals from atherosclerotic plaques. CCE usually occurs during　vascular manipulation such as vascular surgery or endovascular catheter manipulation, or　due to anticoagulation or thrombolytic therapy. We report a rare case of localized intestinal　ulcer with active hemorrhage caused by spontaneous CCE. An 83-year-old man with a history　of hypertension and diabetes was treated with a percutaneous coronary intervention (PCI)　for myocardial infarction. Melena occurred eight days after PCI. An abdominal computed　tomography revealed small intestinal ulcer, extravasation of the gastrointestinal tract and　bleeding in the abdominal cavity. The patient was diagnosed as bleeding from the small　intestinal ulcer, so an emergency laparotomy was performed. Partial resection of the small　intestine was performed. A histopathological examination indicated that small intestine　obstruction was caused by CCE. A histopathological examination indicated that small intestinal　obstruction was caused by CCE. Therefore, in cases of intestinal obstruction after vascular　manipulation, CCE should also be considered

SP7 Inhibits Osteoblast Differentiation at a Late Stage in Mice

RUNX2 and SP7 are essential transcription factors for osteoblast differentiation at an early stage. Although RUNX2 inhibits osteoblast differentiation at a late stage, the function of SP7 at the late stage of osteoblast differentiation is not fully elucidated. Thus, we pursued the function of SP7 in osteoblast differentiation. RUNX2 induced Sp7 expression in Runx2−/− calvarial cells. Adenoviral transfer of sh-Sp7 into primary osteoblasts reduced the expression of Alpl, Col1a1, and Bglap2 and mineralization, whereas that of Sp7 reduced Bglap2 expression and mineralization at a late stage of osteoblast differentiation. Sp7 transgenic mice under the control of 2.3 kb Col1a1 promoter showed osteopenia and woven-bone like structure in the cortical bone, which was thin and less mineralized, in a dose-dependent manner. Further, the number of processes in the osteoblasts and osteocytes was reduced. Although the osteoblast density was increased, the bone formation was reduced. The frequency of BrdU incorporation was increased in the osteoblastic cells, while the expression of Col1a1, Spp1, Ibsp, and Bglap2 was reduced. Further, the osteopenia in Sp7 or Runx2 transgenic mice was worsened in Sp7/Runx2 double transgenic mice and the expression of Col1a1 and Bglap2 was reduced. The expression of Sp7 and Runx2 was not increased in Runx2 and Sp7 transgenic mice, respectively. The expression of endogenous Sp7 was increased in Sp7 transgenic mice and Sp7-transduced cells; the introduction of Sp7 activated and sh-Sp7 inhibited Sp7 promoter; and ChIP assay showed the binding of endogenous SP7 in the proximal region of Sp7 promoter. These findings suggest that SP7 and RUNX2 inhibit osteoblast differentiation at a late stage in a manner independent of RUNX2 and SP7, respectively, and SP7 positively regulates its own promoter