On the Stylohyoid Bone of Naumann's Elephant (Elephas naumanni MAKIYAMA) from Lake Nojiri

The find of the hyoid bone in fossil state has been very rarely reported hitherto. Recently, a part of Proboscidean hyoid bone was unearthed from the bottom sediments at Lake Nojiri, central Japan. That is identified as the stylohyoid bone of Naumann's elephant (Elephas naumanni MAKIYAMA) which is commonly known from the Late Pleistocene deposits in Japan. Comparing the present specimen with the hyoid bones of Asiatic, African and fossil elephants, it is distinguishable in having some peculiar characteristics, viz. the presence of the angulus of the posterior ramus etc.

Variations in amount of TSST-1 produced by clinical methicillin resistant Staphylococcus aureus (MRSA) isolates and allelic variation in accessory gene regulator (agr) locus

<p>Abstract</p> <p>Background</p> <p><it>Staphylococcus aureus </it>(S. aureus) is an important pathogen associated with both nosocomial and community-acquired infections and its pathogenicity is attributed to its potential to produce virulence factors. Since the amount of toxin produced is related to virulence, evaluating toxin production should be useful for controlling S. aureus infection. We previously found that some strains produce relatively large amounts of TSST-1; however, no reports have described the amount of TSST-1 produced by clinical isolates.</p> <p>Methods</p> <p>Amounts of TSST-1 produced by clinical methicillin resistant S. aureus (MRSA) isolates were measured by Western blotting. We determined their accessory gene regulator (<it>agr</it>) class by PCR and investigated whether TSST-1 production correlates with variations in the class and structure of the <it>agr</it>.</p> <p>Results</p> <p>We found that 75% of surveyed MRSA isolates (n = 152) possessed the <it>tst </it>gene and that 96.7% belonged to <it>agr </it>class 2. The concentrations of TSST-1 secreted into culture supernatants by 34 strains measured by Western blotting differed 170-fold. Sequencing the entire <it>agr </it>locus (n = 9) revealed that some had allelic variations regardless of the amount of TSST-1 produced whereas sequencing the <it>sar</it>, sigma factor B and the <it>tst </it>promoter region revealed no significant changes.</p> <p>Conclusion</p> <p>The amounts of TSST-1 produced by clinical MRSA isolates varied. The present results suggest that TSST-1 production is not directly associated with the <it>agr </it>structure, but is instead controlled by unknown transcriptional/translational regulatory systems, or synthesized by multiple regulatory mechanisms that are interlinked in a complex manner.</p

NADase as a target molecule of in vivo suppression of the toxicity in the invasive M-1 group A Streptococcal isolates

<p>Abstract</p> <p>Background</p> <p>NAD-glycohydrolase (NADase) secreted by M-1 group A streptococcal (GAS) isolates are suspected as one of the virulence factors to cause severe invasive disease including streptococcal toxic shock-like syndrome (STSS). M-1 GAS strains were divided into three groups based on NADase activity: high activity, low activity and no activity in our previous report.</p> <p>Results</p> <p>The representative high activity isolates taken from STSS patients showed higher virulence compared with isolates from the low activity group, when used to infect mice. The knockout mutant of the <it>nga </it>gene, which encodes NADase also showed reduced virulence in a mouse infection study. The cloned <it>nga </it>gene was able to significantly complement the lost virulence. In addition, the solution containing purified recombinant IFS, which is an inhibitor of NADase, partially rescued mice infected with <it>S. pyogenes</it>.</p> <p>Conclusions</p> <p>These results indicate that NADase is important for the virulence of <it>S. pyogenes </it>in vivo and is the potential target to suppress the virulence.</p

Transmission of bacterial infections to healthcare workers during intubation and respiratory care of patients with severe pneumonia

Exposure of healthcare workers to patients with rapidly fatal infections invariably raises concerns regarding the risk of occupational acquisition. We describe acquisition of Streptococcus pyogenes by 2 nurses from a patient with fatal pneumonia and review previously reported cases of transmission of bacterial pathogens from patients with pneumonia to healthcare workers

Effect of cyclic bis(3′–5′)diguanylic acid and its analogs on bacterial biofilm formation

Cyclic bis(3′–5′)diguanylic acid (cyclic-di-GMP) functions as a second messenger in diverse species of bacteria to trigger wide-ranging physiological changes. We measured cyclic-di-GMP and its structural analogs such as cyclic bis(3′–5′)guanylic/adenylic acid (cyclic-GpAp), cyclic bis(3′–5′)guanylic/inosinic acid (cyclic-GpIp) and monophosphorothioic acid of cyclic-di-GMP (cyclic-GpGps) for effects on the biofilm formation of Staphylococcus aureus and Pseudomonas aeruginosa. We constructed a knockout mutant of SA0701, which is a GGDEF motif protein relevant to diguanylate cyclase from S. aureus 2507. We confirmed that the biofilm formation of this mutant (MS2507ΔSA0701) was reduced. Cyclic-di-GMP corresponding to physiological intracellular levels given in the culture recovered the biofilm formation of MS2507ΔSA0701, whereas its analogs did not, indicating that unlike a previous suggestion, cyclic-di-GMP was involved in the positive regulation of the biofilm formation of S. aureus and its action was structurally specific. At a high concentration (200 μM), cyclic-di-GMP and its analogs showed suppression effects on the biofilm formation of S. aureus and P. aeruginosa, and according to the quantification study using costat analysis, the suppression potential was in the order of cyclic-di-GMP, cyclic-GpGps, cyclic-GpAp and cyclic-GpIp, suggesting that the suppression effect was not strictly specific and the change of base structure quantitatively affected the suppression activity

Changes in anemia management and hemoglobin levels following revision of a bundling policy to incorporate recombinant human erythropoietin

In April 2006, Japan's health insurance system instituted a bundling policy that included recombinant human erythropoietin (rHuEPO) in outpatient hemodialysis therapy. To evaluate outcomes of this, we analyzed a prospective cohort of hemodialysis patients in the Japan Dialysis Outcomes and Practice Patterns Study, in 53 facilities using prevalent cross-sections of 1584 patients before and 1622 patients after the rHuEPO reimbursement change. Patient data included hemoglobin levels, iron management profiles, and anemia treatment with rHuEPO and intravenous iron. No significant differences were found in pre- or post-policy cross-sections for hemoglobin distributions or the percentage of patients prescribed rHuEPO. Among patients receiving rHuEPO, the mean dose significantly decreased by 11.8 percent. The percentage of patients prescribed intravenous iron over 4months significantly increased; however, the mean dose of iron did not significantly change. Thus, this bundling policy was associated with reduced rHuEPO doses, increased intravenous iron use, and stable hemoglobin levels in Japanese patients receiving hemodialysis

Protective Effect of Hainosankyuto, a Traditional Japanese Medicine, on Streptococcus pyogenes Infection in Murine Model

BACKGROUND: Streptococcus pyogenes (S. pyogenes) causes various serious diseases including necrotizing fasciitis and streptococcal toxic shock syndrome. One serious problem observed recently with S. pyogenes therapy is attenuation of the antibiotic effect, especially penicillin treatment failure and macrolide resistance. Hainosankyuto, a traditional Japanese medicine based on ancient Chinese medicine, has been used for treatment of infectious purulent diseases in Japan. In this study, we investigated the protective and therapeutic efficacy of Hainosankyuto against S. pyogenes-skin infection. METHODOLOGY/PRINCIPAL FINDINGS: A broth microdilution method revealed that Hainosankyuto did not show a direct anti-bacterial effect against S. pyogenes. Force-feeding Hainosankyuto to infected mice for 4 consecutive days increased the survival rate and reduced the size of local skin lesions compared with mice fed PBS. Although we did not find the significant recovery of survival rate in Hainosankyuto administration only after S. pyogenes infection, the sizes of ulcer lesion were significant smaller after Hainosankyuto administration compared with mice fed PBS. No difference was observed in the anti-bacterial effect of Hainosankyuto between macrolide-susceptible and -resistant strains. Blood bactericidal assay showed that the survival rate of S. pyogenes using the blood from Hainosankyuto-treated mice was lower than that using the blood from untreated mice. We also found increased levels of IL-12, IFN-γ and a decreased level of TNF-α in the serum of S. pyogenes-infected mice treated with Hainosankyuto. Mouse peritoneal macrophage from Hainosankyuto-treated mice had significant phagocytic activity and increased mRNA levels of IL-12, IFN-γ and decreased mRNA level of TNF-α compared with control macrophage. CONCLUSIONS/SIGNIFICANCE: Hainosankyuto increased survival rate after S. pyogenes infection and up-regulated both blood bactericidal activity and macrophage phagocytic activity through modulation of inflammatory cytokines. Our data also suggest Hainosankyuto may be useful for the treatment of S. pyogenes infection more prophylactically than therapeutically

環境アポトジェンを含む環境汚染化学物質の作用動態解析と化学生態学的防除法の開発研究プロジェクト

プロジェクト研究報告概要集　　戦略的研究基盤形成支援事業プロジェクト　研究代表者:土戸哲明　研究担当者:池内俊彦・下家浩二・上里新一・吉田宗弘・福永健治・安原裕紀・長谷川喜衛・岩木宏明・老川典夫・松村吉

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection