Differential activity of interferon-α8 promoter is regulated by Oct-1 and a SNP that dictates prognosis of glioma

We have previously reported that the single nucleotide polymorphism (SNP) rs12553612 in IFNA8 is associated with better overall survival of glioma patients with the AA-genotype compared with patients with the AC-genotype. As rs12553612 is located in the IFNA8 promoter, we hypothesized that the A-allele allows for an enhanced IFNA8 promoter activity compared with the C-allele. Reporter assays in the human monocyte derived THP-1 cell line demonstrated a superior promoter activity of the A-allele compared with the C-allele. Electrophoretic mobility shift assays (EMSA) further demonstrated that the A-genotype specifically binds to more nuclear proteins than the C-genotype, including the transcription factor Oct-1. Further, co-transfection of plasmids encoding Oct-1 and the reporter constructs revealed that Oct-1 enhanced the promoter activity with the A- but not the C-allele. Taken together, our data demonstrate that the A-allele in the rs12553612 SNP, which is associated with better glioma patient survival, allows for IFNA8 transcription by allowing for Oct-1 binding, which is absent in patients with C allele, and suggests a molecular mechanism of IFNA8 mediated immune-surveillance of glioma progression

Localization of S100C immunoreactivity in various human tissues.

Using 2-dimensional gel electrophoresis, we previously demonstrated that the S100C protein remarkably decreased after immortalization of normal human fibroblasts, and that this protein caused growth inhibition of human tumor cells when forcibly expressed in these cells, suggesting that S100C plays a significant role in tumor suppression. The present study was carried out to determine what type of human tissues express S100C protein, and, subsequently, whether the S100C content in these tissues changes after normal cells have been transformed into cancer cells. We found that ductal cells in various tissues were positively stained with the S100C protein. In comparison, epithelial cells in digestive organs such as the stomach, small intestine, and colon were not stained as strongly. When 14 pairs of human normal and cancerous tissues were stained with the antibody, decreases in the staining levels of S100C were observed in 6 kinds of cancerous tissues--from the bronchus, mammary duct, renal tubule, prostate, uterus, and testis--in comparison with staining in their normal counterparts. These results suggest that S100C is a new tumor marker protein, the expression of which significantly decreases after malignant transformation of human tissues.</p

Pandemic (H1N1) 2009–associated Pneumonia in Children, Japan

To describe clinical aspects of pandemic (H1N1) 2009 virus–associated pneumonia in children, we studied 80 such children, including 17 (21%) with complications, who were admitted to 5 hospitals in Japan during August–November 2009 after a mean of 2.9 symptomatic days. All enrolled patients recovered (median hospitalization 6 days). Timely access to hospitals may have contributed to favorable outcomes

ツシマ デントウ ハッコウ ショクヒン 「センダンゴ」 ノ カク チイキ ニ オケル セイゾウ ホウホウ

長崎県対馬市は南北に長い島であり,対馬のそれぞれの農家ではサツマイモを原料とした固有の伝統保存食品である『せんだんご』を小規模に製造している。 せんだんごは,水で戻し,捏ねた生地を麺状に加工して茹であげ『ろくべえ麺』として食される。 ろくべえは,原料であるサツマイモ単体では生じ得ない食感を有していることから,せんだんごの製造工程に着目した。 せんだんごの製造には,"芋を腐らせる(発酵させる)"工程,それを丸めて数ヶ月に及ぶ軒下での"寒晒し"の工程があることから,島内各地域の「せんだんご製造農家」を訪問し,製造方法の調査を行った。 その結果,これら両工程にはカビなどの微生物が繁殖しており,黒色カビが繁殖した場合は味が悪くなるという理由からその部位が破棄され,白色や青色カビが繁殖した部位の製造が続行される。 このことから微生物の働きがあってせんだんごとなり,さらにろくべえ麺特有の食感が与えられると推察した。 さらに,せんだんご製造に重要な働きをすると考えられる微生物を特定するにあたり,数年にわたり島内の調査を重ねた結果,基本的にはせんだんご製造工程には3段階の発酵工程(発酵1(浸漬),発酵2(棚板に広げて発酵),発酵3(ソフトボール大の塊で発酵))と洗浄・成型工程の2工程4区分に分けられることが確認された。Sendango is an indigenous preserved food derived from sweet potato that is traditionally made in Tsushima, Japan located between the Korean Peninsula and Kyushu. The local people process a noodle called Rokube from Sendango and eat it with soup, fish or chicken. Rokube has a unique texture similar to konyaku, and unlike that of cooked sweet potato. There are two or three fermentation processes involved in Sendango production; therefore, we inferred that the unique texture of Rokube may result from the fermentation process. Sendango is manufactured in several farmhouses on the island ; however, the manufacturing process varies among districts. We investigated each local Sendango manufacturing process and determined the microorganisms involved in fermentation. The investigation of Sendango manufacturing procedures was carried out in three towns, Toyotama, Izuhara, and Mitsushima, by interviews and observations between December and February each year from 2008 to 2011. The processes consist of three main fermentations. In Fermentation-1 (F1), sliced or smashed sweet potatoes were soaked in cold water for 7-10 days. Gas production and film formation were observed during F1. In Fermentation-2 (F2), the soaked sweet potato pieces were piled to a thickness of 5-20cm for 20-30 days. Intense propagation of filamentous fungi was observed during F2. In fermentation-3 (F3), softball-sized lumps were formed on the sticky sweet potato by fungi. The sweet potatoes were left outside for approximately 1 month. The lumps gradually hardened by drying. Many fungal mycelia were observed on the surface of potatoes and inside the lumps during F3. The three aforementioned fermentation processes were used for Sendango production in two towns (Toyotama and Izuhara). In Izuhara, smashed sweet potatoes were placed in sandbags knit with plastic strings, and the bags were soaked in the flowing river water. The sandbags collected from the river water were left on the river bank for 20 days. F2 was carried out in sandbags. In Mitsushima, Sendango production consisted of two fermentation processes, F1 and F3. The fermentation process occurs over a long time period. The propagation of filamentous fungi was particularly intense during F2 and F3. It is thought that filamentous fungi are indispensable for Sendango production. We characterized the microorganisms participating in Sendango production based on this investigation

Efficacy and Safety of Intravitreal Aflibercept Treat-and-Extend Regimens in Exudative Age-Related Macular Degeneration: 52- and 96-Week Findings from ALTAIR : A Randomized Controlled Trial.

PURPOSE:To evaluate efficacy and safety of intravitreal injections of aflibercept (IVT-AFL) treat-and-extend (T&E) dosing regimens in treatment-naïve patients with exudative age-related macular degeneration (AMD).METHODS:Adults aged at least 50 years old with exudative AMD and best-corrected visual acuity (BCVA) of 73-25 Early Treatment Diabetic Retinopathy Study (ETDRS) letters were included. Patients received three monthly doses of IVT-AFL 2 mg. At week 16, patients were randomized 1:1 to IVT-AFL T&E with either 2- or 4-week adjustments. The primary endpoint was mean change in BCVA from baseline to week 52. Outcomes were assessed at weeks 52 and 96.RESULTS:Baseline characteristics were comparable between the groups (n = 123 each). Over 52 weeks, mean number of injections was 7.2 and 6.9 and mean last injection interval was 10.7 and 11.8 weeks, for the 2- and 4-week groups, respectively. From baseline, mean change in BCVA was + 9.0 and + 8.4 letters (week 52) and + 7.6 and + 6.1 letters (week 96); mean change in central retinal thickness was - 134.4 µm and - 126.1 µm (week 52) and - 130.5 µm and - 125.3 µm (week 96). Last injection interval before week 52 was at least 12 weeks in 42.3% and 49.6% of patients and 56.9% and 60.2% before week 96. Over 96 weeks, mean number of injections was 10.4 (both groups). The safety profile of IVT-AFL was consistent with previous reports.CONCLUSIONS:IVT-AFL administered using two different T&E regimens for treatment-naïve exudative AMD improved functional and anatomic outcomes at week 52 and outcomes were maintained to week 96. Outcomes were similar between the 2- and 4-week groups.TRIAL REGISTRATION:ClinicalTrials.gov identifier, NCT02305238