| 1. |
Justin B Schaal, Yoshihiro Eriguchi, Dat Q Tran, Patti A Tran, Chase Hawes, Anthony E Cabebe, Kaitlyn Pike, Katie Trinh, André J Ouellette, Michael E Selsted, A host-directed macrocyclic peptide therapeutic for MDR gram negative bacterial infections., Scientific reports, 10.1038/s41598-021-02619-y, 11, 1, 23447-23447, 2021.12, The emergence of infections by carbapenem resistant Enterobacteriaceae (CRE) pathogens has created an urgent public health threat, as carbapenems are among the drugs of last resort for infections caused by a growing fraction of multi-drug resistant (MDR) bacteria. There is global consensus that new preventive and therapeutic strategies are urgently needed to combat the growing problem of MDR bacterial infections. Here, we report on the efficacy of a novel macrocyclic peptide, minimized theta-defensin (MTD)-12813 in CRE sepsis. MTD12813 is a theta-defensin inspired cyclic peptide that is highly effective against CRE pathogens K. pneumoniae and E. coli in vivo. In mouse septicemia models, single dose administration of MTD12813 significantly enhanced survival by promoting rapid host-mediated bacterial clearance and by modulating pathologic cytokine responses, restoring immune homeostasis, and preventing lethal septic shock. The peptide lacks direct antibacterial activity in the presence of mouse serum or in peritoneal fluid, further evidence for its indirect antibacterial mode of action. MTD12813 is highly stable in biological matrices, resistant to bacterial proteases, and nontoxic to mice at dose levels 100 times the therapeutic dose level, properties which support further development of the peptide as a first in class anti-infective therapeutic.. |
| 2. |
Hiromu Tanaka, Ho Lee, Atsuho Morita, Ho Namkoong, Shotaro Chubachi, Hiroki Kabata, Hirofumi Kamata, Makoto Ishii, Naoki Hasegawa, Norihiro Harada, Tetsuya Ueda, Soichiro Ueda, Takashi Ishiguro, Ken Arimura, Fukuki Saito, Takashi Yoshiyama, Yasushi Nakano, Yoshikazu Mutoh, Yusuke Suzuki, Koji Murakami, Yukinori Okada, Ryuji Koike, Yuko Kitagawa, Katsushi Tokunaga, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga, Clinical Characteristics of Patients with Coronavirus Disease (COVID-19): Preliminary Baseline Report of Japan COVID-19 Task Force, a Nationwide Consortium to Investigate Host Genetics of COVID-19., International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 10.1016/j.ijid.2021.09.070, 113, 74-81, 2021.12, BACKGROUND AND DESIGN: The coronavirus disease (COVID-19) pandemic is having a devastating effect worldwide. Host genome differences between populations may influence the severity of COVID-19. The Japan COVID-19 Task Force is conducting host genome analysis of hospitalized patients with COVID-19 from more than 70 institutions nationwide in Japan. This report describes the clinical characteristics of patients enrolled to date. RESULTS: The median (interquartile range) age of the 1674 patients included in the analysis was 59 (45-71) years, and more than half of the patients (66.2%) were male. Less than half of the patients (41.2%) had severe disease. The case fatality rate was 3.2%. CONCLUSIONS: Since this is a hospital-based study, the number of severe cases was relatively high, but the case fatality rate was relatively low, when compared to that of other countries. In the future, we will continue to enroll patients and conduct genome analyses of patients with COVID-19.. |
| 3. |
Keane K Y Lai, Xiaohui Hu, Keisuke Chosa, Cu Nguyen, David P Lin, Keith K Lai, Nobuo Kato, Yusuke Higuchi, Sarah K Highlander, Elizabeth Melendez, Yoshihiro Eriguchi, Patrick T Fueger, Andre J Ouellette, Nyam-Osor Chimge, Masaya Ono, Michael Kahn, p300 Serine 89: A Critical Signaling Integrator and Its Effects on Intestinal Homeostasis and Repair., Cancers, 10.3390/cancers13061288, 13, 6, 2021.03, Differential usage of Kat3 coactivators, CBP and p300, by β-catenin is a fundamental regulatory mechanism in stem cell maintenance and initiation of differentiation and repair. Based upon our earlier pharmacologic studies, p300 serine 89 (S89) is critical for controlling differential coactivator usage by β-catenin via post-translational phosphorylation in stem/progenitor populations, and appears to be a target for a number of kinase cascades. To further investigate mechanisms of signal integration effected by this domain, we generated p300 S89A knock-in mice. We show that S89A mice are extremely sensitive to intestinal insult resulting in colitis, which is known to significantly increase the risk of developing colorectal cancer. We demonstrate cell intrinsic differences, and microbiome compositional differences and differential immune responses, in intestine of S89A versus wild type mice. Genomic and proteomic analyses reveal pathway differences, including lipid metabolism, oxidative stress response, mitochondrial function and oxidative phosphorylation. The diverse effects on fundamental processes including epithelial differentiation, metabolism, immune response and microbiome colonization, all brought about by a single amino acid modification S89A, highlights the critical role of this region in p300 as a signaling nexus and the rationale for conservation of this residue and surrounding region for hundreds of million years of vertebrate evolution.. |
| 4. |
Kaitlin Skrypek, Steven Balog, Yoshihiro Eriguchi, Kinji Asahina, Inhibition of Stearoyl-CoA Desaturase Induces the Unfolded Protein Response in Pancreatic Tumors and Suppresses Their Growth., Pancreas, 10.1097/MPA.0000000000001737, 50, 2, 219-226, 2021.02, OBJECTIVE: Pancreatic ductal adenocarcinoma is the fourth-leading cause of cancer death in the United States, and there is an urgent need for effective therapies. Stearoyl-CoA desaturase (SCD) is an enzyme localized in the endoplasmic reticulum and generates monounsaturated fatty acid from saturated fatty acid. In this study, we examined the role of SCD in pancreatic cancer. METHODS: We isolated epithelial cell adhesion molecule-positive pancreatic tumors from the Pdx1Cre;LSL-KrasG12D mouse and formed organoids in Matrigel. Using a SCD inhibitor, A939572, we tested its effects on growth and cell death in tumor organoids, tumors developed in the Pdx1Cre;LSL-KrasG12D mouse, and a human pancreatic ductal adenocarcinoma cell line, PANC-1. RESULTS: A939572 treatment rapidly induced degeneration of mouse tumor organoids and activated the unfolded protein response (UPR). Cotreatment of oleic acid, but not stearic acid, reduced the UPR in the organoids and rescued the inhibitory effect of the SCD inhibitor on their growth. Administration of A939572 to Pdx1Cre;LSL-KrasG12D mice caused cell death in early pancreatic tumors, but not in acini or islets. The SCD inhibitor induced the UPR in PANC-1 and suppressed their growth but did not induce cell death. CONCLUSIONS: The inhibition of the SCD enzyme causes an UPR and cell death in early pancreatic tumors.. |
| 5. |
Yong Chong, Hideyuki Ikematsu, Naoki Tani, Yoko Arimizu, Haruka Watanabe, Yukako Fukamachi, Akiko Yonekawa, Sho Iwasaka, Ruriko Nishida, Yoshihiro Eriguchi, Noriko Miyake, Shinji Shimoda, Yoji Nagasaki, Nobuyuki Shimono, Koichi Akashi, Clinical significance of SARS-CoV-2-specific IgG detection with a rapid antibody kit for COVID-19 patients., Influenza and other respiratory viruses, 10.1111/irv.12802, 15, 1, 13-18, 2021.01, BACKGROUND: The longitudinal observation of the detection of antibody responses to SARS-CoV-2 using antibody kits during the clinical course of COVID-19 is not yet fully investigated. OBJECTIVES: To understand the significance of the detection of anti-SARS-CoV-2 antibodies, particularly IgG, using a rapid antibody kit, during the clinical course of COVID-19 patients with different severities. METHODS: Sixty-three serum samples from 18 patients (5 asymptomatic and 13 symptomatic patients) were retrospectively examined using a commercial SARS-CoV-2 IgM/IgG antibody kit. PCR positivity of patient samples was also examined as a marker of current SARS-CoV-2 infection. RESULTS: IgG antibodies were detected in all cases in this study. The IgG detection rates reached 100.0% in samples collected on day 13 or later. IgG seropositivity after an initial negative status was observed in 13 patients (3/5 asymptomatic and 10/13 symptomatic cases). Interestingly, the persistence of both PCR and IgG positivity was detected in seven cases, of which three were asymptomatic. The longest overlap duration of the PCR and IgG positivity was 17 days in asymptomatic status. CONCLUSIONS: SARS-CoV-2-specific IgG production can be detected in all infected individuals, using a rapid antibody kit, irrespective of clinical status. However, these findings suggest that, in some infected individuals, particularly those with asymptomatic status, the presence of virus-specific IgG antibodies does not imply prompt viral clearance.. |
| 6. |
Virginia Basso, Dat Q. Tran, Justin B. Schaal, Patti Tran, Yoshihiro Eriguchi, Diana Ngole, Anthony E. Cabebe, A. young Park, Paul M. Beringer, André J. Ouellette, Michael E. Selsted, Rhesus Theta Defensin 1 Promotes Long Term Survival in Systemic Candidiasis by Host Directed Mechanisms, Scientific reports, 10.1038/s41598-019-53402-z, 9, 1, 2019.12, Invasive candidiasis is an increasingly frequent cause of serious and often fatal infections in hospitalized and immunosuppressed patients. Mortality rates associated with these infections have risen sharply due to the emergence of multidrug resistant (MDR) strains of C. albicans and other Candida spp., highlighting the urgent need of new antifungal therapies. Rhesus theta (θ) defensin-1 (RTD-1), a natural macrocyclic antimicrobial peptide, was recently shown to be rapidly fungicidal against clinical isolates of MDR C. albicans in vitro. Here we found that RTD-1 was rapidly fungicidal against blastospores of fluconazole/caspofungin resistant C. albicans strains, and was active against established C. albicans biofilms in vitro. In vivo, systemic administration of RTD-1, initiated at the time of infection or 24 h post-infection, promoted long term survival in candidemic mice whether infected with drug-sensitive or MDR strains of C. albicans. RTD-1 induced an early (4 h post treatment) increase in neutrophils in naive and infected mice. In vivo efficacy was associated with fungal clearance, restoration of dysregulated inflammatory cytokines including TNF-α, IL-1β, IL-6, IL-10, and IL-17, and homeostatic reduction in numbers of circulating neutrophils and monocytes. Because these effects occurred using peptide doses that produced maximal plasma concentrations (Cmax) of less than 1% of RTD-1 levels required for in vitro antifungal activity in 50% mouse serum, while inducing a transient neutrophilia, we suggest that RTD-1 mediates its antifungal effects in vivo by host directed mechanisms rather than direct fungicidal activity. Results of this study suggest that θ-defensins represent a new class of host-directed compounds for treatment of disseminated candidiasis.. |
| 7. |
Yoshihiro Eriguchi, Kiminori Nakamura, Yuki Yokoi, Rina Sugimoto, Shuichiro Takahashi, Daigo Hashimoto, Takanori Teshima, Tokiyoshi Ayabe, Michael E. Selsted, André J. Ouellette, Essential role of IFN-γ in T cell-associated intestinal inflammation, JCI Insight, 10.1172/jci.insight.121886, 3, 18, 2018.09, Paneth cells contribute to small intestinal homeostasis by secreting antimicrobial peptides and constituting the intestinal stem cell (ISC) niche. Certain T cell-mediated enteropathies are characterized by extensive Paneth cell depletion coincident with mucosal destruction and dysbiosis. In this study, mechanisms of intestinal crypt injury have been investigated by characterizing responses of mouse intestinal organoids (enteroids) in coculture with mouse T lymphocytes. Activated T cells induced enteroid damage, reduced Paneth cell and Lgr5+ ISC mRNA levels, and induced Paneth cell death through a caspase-3/7-dependent mechanism. IFN-γ mediated these effects, because IFN-γ receptor-null enteroids were unaffected by activated T cells. In mice, administration of IFN-γ induced enteropathy with crypt hyperplasia, villus shortening, Paneth cell depletion, and modified ISC marker expression. IFN-γ exacerbated radiation enteritis, which was ameliorated by treatment with a selective JAK1/2 inhibitor. Thus, IFN-γ induced Paneth cell death and impaired regeneration of small intestinal epithelium in vivo, suggesting that IFN-γ may be a useful target for treating defective mucosal regeneration in enteric inflammation.. |
| 8. |
Eduardo R. Cobo, Ravi Holani, France Moreau, Kiminori Nakamura, Tokiyoshi Ayabe, Jennifer R. Mastroianni, Yoshihiro Eriguchi, Andre Ouellette, Kris Chadee, Entamoeba histolytica Alters Ileal Paneth Cell Functions in Intact and Muc2 Mucin Deficiency, Infection and Immunity, 10.1128/IAI.00208-18, 86, 7, 2018.07, Enteric α-defensins, termed cryptdins (Crps) in mice, and lysozymes secreted by Paneth cells contribute to innate host defense in the ileum. Antimicrobial factors, including lysozymes and β-defensins, are often embedded in luminal glycosylated colonic Muc2 mucin secreted by goblet cells that form the protective mucus layer critical for gut homeostasis and pathogen invasion. In this study, we investigated ileal innate immunity against Entamoeba histolytica, the causative agent of intestinal amebiasis, by inoculating parasites in closed ileal loops in Muc2+/+ and Muc2−/− littermates and quantifying Paneth cell localization (lysozyme expression) and function (Crp secretion). Relative to Muc2+/+ littermates, Muc2−/− littermates showed a disorganized mislocalization of Paneth cells that was diffusely distributed, with elevated lysozyme secretion in the crypts and on villi in response to E. histolytica. Inhibition of E. histolytica Gal/GalNAc lectin (Gal-lectin) binding with exogenous galactose and Entamoeba histolytica cysteine proteinase 5 (EhCP5)-negative E. histolytica had no effect on parasite-induced erratic Paneth cell lysozyme synthesis. Although the basal ileal expression of Crp genes was unaffected in Muc2−/− mice in response to E. histolytica, there was a robust release of proinflammatory cytokines and Crp peptide secretions in luminal exudates that was also present in the colon. Interestingly, E. histolytica-secreted cysteine proteinases cleaved the proregion of Crp4 but not the active form. These findings define Muc2 mucin as an essential component of ileal barrier function that regulates the localization and function of Paneth cells critical for host defense against microbes.. |
| 9. |
Y. Eriguchi, K. Nakamura, D. Hashimoto, S. Shimoda, N. Shimono, K. Akashi, T. Ayabe, T. Teshima, Decreased secretion of Paneth cell α-defensins in graft-versus-host disease, Transplant Infectious Disease, 10.1111/tid.12423, 17, 5, 702-706, 2015.10, Background: Intestinal microbial ecology is actively regulated by Paneth cell-derived antimicrobial peptides, α-defensins. Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (SCT). We previously demonstrated that Paneth cells are targeted by GVHD, and their expression of antimicrobial peptide α-defensins is impaired, leading to a loss of physiological diversity among the microflora and development of bloodstream infection. Herein, we evaluated whether fecal levels of α-defensins could be surrogate marker of intestinal dysbiosis. Methods: We directly measured α-defensin cryptdin-1 (Crp1) in fecal pellets of mice with GVHD by using a novel enzyme-linked immunosorbent assay. Results: Fecal levels of Crp1 were significantly decreased in mice with GVHD but unchanged in mice without GVHD after SCT. These were correlated with intestinal flora diversity. Conclusion: We demonstrate a link between reduced secretion of Paneth cell α-defensins and dysbiosis of intestinal flora in GVHD. Fecal levels of α-defensins could be surrogate markers for intestinal microbial homeostasis.. |
| 10. |
Yoshihiro Eriguchi, Hidetaka Uryu, Kiminori Nakamura, Sonoko Shimoji, Shuichiro Takashima, Hiromi Iwasaki, Toshihiro Miyamoto, Nobuyuki Shimono, Daigo Hashimoto, Koichi Akashi, Tokiyoshi Ayabe, Takanori Teshima, Reciprocal expression of enteric antimicrobial proteins in intestinal graft-versus-host disease, Biology of Blood and Marrow Transplantation, 10.1016/j.bbmt.2013.07.027, 19, 10, 1525-1529, 2013.10, We recently demonstrated that expression of α-defensins, the major antimicrobial peptides produced by Paneth cells, was severely suppressed in mice with graft-versus-host disease (GVHD). In this study, we found that antibacterial lectin, regenerating islet-derived IIIγ (RegIIIγ) was upregulated in villous enterocytes, thus demonstrating the reciprocal control of enteric antimicrobial proteins in GVHD. Upregulation of RegIIIγ was mediated by a mechanism independent upon radiation-induced intestinal tract damage. MyD88-mediated signaling in intestinal epithelium was required for RegIIIγ upregulation in GVHD and antibiotic therapy downregulated RegIIIγ expression. These results suggest that MyD88-mediated sensing of the intestinal microbes disregulated in GVHD induces RegIIIγ upregulation in GVHD and argue a role for RegIIIγ in the pathogenesis of GVHD.. |
| 11. |
S. Shimoji, K. Kato, Y. Eriguchi, K. Takenaka, H. Iwasaki, T. Miyamoto, Y. Oda, K. Akashi, T. Teshima, Evaluating the association between histological manifestations of cord colitis syndrome with GVHD, Bone Marrow Transplantation, 10.1038/bmt.2013.44, 48, 9, 1249-1252, 2013.09, Cord colitis syndrome (CCS) is a recently proposed clinical entity characterized by a persistent diarrheal illness after cord blood transplantation (CBT), which is not caused by GVHD or CMV colitis. CCS is histologically characterized by chronic active colitis with granulomatous inflammation and Paneth cell metaplasia suggesting chronicity. However, the specificity of these pathological features to CCS remains to be validated. We conducted a retrospective study of 49 patients who had diarrhea and underwent diagnostic colonoscopy with biopsy following allogeneic hematopoietic SCT. None of the patients met the clinical criteria for CCS. Chronic active colitis with granulomatous inflammation and Paneth cell metaplasia was present in 12/33 (36%) patients with biopsy-proven GVHD, 4/6 (67%) patients with CMV colitis and 2/15 (13%) patients with nonspecific colitis. In patients with GVHD and/or CMV colitis, these pathological features were present in 4/8 (50%) patients after CBT and in 11/26 (42%) patients undergoing BMT or PBSCT. These results demonstrate that chronic active colitis with granuloma and Paneth cell metaplasia is not only a specific feature of CCS but also is present in GVHD and CMV colitis, irrespective of stem cell source.. |
| 12. |
Yoshihiro Eriguchi, Shuichiro Takashima, Hideyo Oka, Sonoko Shimoji, Kiminori
Nakamura, Hidetaka Uryu, Shinji Shimoda, Hiromi Iwasaki, Nobuyuki Shimono,
Tokiyoshi Ayabe, Koichi Akashi, and Takanori Teshima, Graft-versus-host disease disrupts intestinal microbial ecology by inhibiting Paneth cell production of α-defensins
, Blood, doi:10.1182/blood-2011-12-401166, 120, 1, 223-231, 2012.07, 同種造血幹細胞移植は様々な血液疾患に対して根治的な治療方法である。移植片対宿主病（Graft-versus-host disease ：GVHD）と感染症は、この造血幹細胞移植の厄介な合併症であり、GVHDと感染症は互いに影響を与えていると推測されている。本研究では、GVHDと感染症の相互関係をマウスモデルにより解析した。
αディフェンシンは、病原菌に対し殺菌活性があり、共生菌に対しては活性を有さない選択的抗菌活性を持った抗菌ペプチドである。Paneth細胞は、このαディフェンシンを分泌することにより腸内細菌叢を制御している。我々は、Paneth細胞がGVHDの標的となり、腸管でのαディフェンシンの発現が減少することを発見した。
腸内細菌叢の分子生物学的解析では、GVHD発症マウスで腸内細菌叢の多様性が減少する一方で、正常細菌叢では0.1％にも満たず、敗血症の病因となる大腸菌が異常増殖することを示した。この細菌叢の変化は、GVHD発症マウスにのみみられ、移植前処置である放射線照射による腸管障害とは無関係であり、菌叢の変化の度合いはGVHDの重症度と有意に相関した。また、大腸菌に抗菌活性のあるポリミキシンBの経口投与は、大腸菌の異常増殖を抑え、GVHDを軽減した。
これらの結果は、GVHD発症により正常腸内細菌叢から、病原菌が爆発的に増加した異常細菌叢へと変移する新規のメカニズムと、今まで認識されていなかったGVHDと同種造血幹細胞移植後に発症する感染症との関連を明らかにした。
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| 13. |
Noriko Miyake, Masako Kadowaki, Yoriko Sato, Yoshihiro Eriguchi, Yoji Nagasaki, Yukiko Harada, Yujiro Uchida, Nobuyuki Shimono, Influence of inoculum size on MICs for methicillin-susceptible Staphylococcus aureus and methicillin-resistant Staphylococcus aureus on in vitro, Japanese Journal of Antibiotics, 64, 4, 231-237, 2011.08, Using 49 clinical methicillin-susceptible Staphylococcus aureus isolates (MSSA) and 54 clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates, we examined the change of MIC using five different inocula (2.5-4×10 2cfu/spot - 2.5-4×10 6cfu/spot). We found the big change of the MIC with the increase of the inoculum size in ampicillin against MSSA, and the change was small in cefazolin, meropenem, ciprofloxacin. For anti-MRSA antibiotics, we found the small change with the increase of the inoculums size in vancomycin and arbekacin, and the middle change in teicoplanin and linezolid against MSSA and MRSA. The data from this study suggest that in serious and high inocula infections caused by S. aureus, the presence of an inoculum effect should be considered in curing.. |
| 14. |
Yujiro Uchida, Tomomi Mochimaru, Yuiko Morokuma, Makiko Kiyosuke, Masako Fujise, Fujiko Eto, Yoshihiro Eriguchi, Yoji Nagasaki, Nobuyuki Shimono, Dongchon Kang, Clonal spread in Eastern Asia of ciprofloxacin-resistant Escherichia coli serogroup O25 strains, and associated virulence factors, International Journal of Antimicrobial Agents, 10.1016/j.ijantimicag.2009.12.012, 35, 5, 444-450, 2010.05, A significant problem in the field of infectious diseases is the increase in fluoroquinolone (FQ)-resistant Escherichia coli. Although mutation of strains and clonal dissemination are supposed to be the cause of this increase, little is known about the prevalence of this organism. We investigated 219 FQ-resistant E. coli strains in Japan and nine Asian countries by serotyping and genotyping. Seventy-one strains (32.4%) were serogroup O25, which was prevalent in South Korea, China and Japan, especially in the southwest part of Japan. Aerobactin, a virulence factor in uropathogenic and avian pathogenic E. coli, was associated with the presence of FQ-resistant O25 strains of E. coli. Seven of the seventy-one FQ-resistant E. coli O25 had extended-spectrum β-lactamase genes (six CTX-M-14 and one SHV-12), however, we were unable to find any E. coli O25-ST131 clone that produced CTX-M-15, which was previously reported to have emerged across continents. These data demonstrate that a clonal group of FQ-resistant and virulent E. coli recently became prevalent at least in East Asia and suggest that this might become a public health problem because the strains may acquire resistance to other antimicrobial agents.. |
| 15. |
Yoriko Maehara, Yoji Nagasaki, Masako Kadowaki, Yoshihiro Eriguchi, Noriko Miyake, Yujiro Uchida, Koji Nagafuji, Nobuyuki Shimono, Hematological unit invasive aspergillosis epidemiology, Kansenshōgaku zasshi. The Journal of the Japanese Association for Infectious Diseases, 10.11150/kansenshogakuzasshi.84.176, 84, 2, 176-181, 2010.03, Invasive aspergillosis (IA) is a major cause of morbidity and mortality among the immunocompromised, especially those undergoing hematopoietic stem cell transplantation. With spore inhalation the usual infection route, such subjects must be protected from environmental spore contamination, necessitating measures such as high-efficiency particulate air (HEPA) filtration. In April 2006, we implemented a new transplantation unit with HEPA filtration. We retrospectively evaluated its efficacy for hospitalized transplantation unit subjects whose sera were tested for aspergillus galactomannan antigen between April 2004 and March 2007. Subjects numbered 265 (973 samples) categorized as definite, probable, or possible. The earliest IA onset date was when symptoms, positive radiological findings, or positive galactomannan antigen tests occurred, based on revised European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) definitions. We classified cases when IA occurred over 10 days after admission as hospital-acquired. No such cases were detected after November 2005 and IA incidence decreased significantly after the new unit began being used. Results suggest that the new unit and HEPA filtration helped eliminate nosocomial IA.. |
| 16. |
Yoji Nagasaki, Yoshihiro Eriguchi, Yujiro Uchida, Noriko Miyake, Yoriko Maehara, Masako Kadowaki, Mine Harada, Koichi Akashi, Nobuyuki Shimono, Combination therapy with micafungin and amphotericin B for invasive pulmonary aspergillosis in an immunocompromised mouse model, Journal of Antimicrobial Chemotherapy, 10.1093/jac/dkp175, 64, 2, 379-382, 2009.07, Objectives: Antifungal monotherapy with polyenes, azoles or echinocandins is not always effective for invasive pulmonary aspergillosis (IPA). The main purpose of this study was to evaluate the efficacy of a combination of micafungin and amphotericin B for the primary treatment of IPA in an immunocompromised mouse model. Methods: Female ICR mice were used in all experiments. An immunosuppressive state was induced in mice by an intraperitoneal injection of cyclophosphamide. Mice were intratracheally inoculated with Aspergillus fumigatus conidia, treated with micafungin, amphotericin B or both for 7 days, and were tested for their survival 20 days after the Aspergillus inoculation. Fungal burden in lungs, serum galactomannan index (GMI) and histopathology of lungs, spleen and kidneys were also evaluated. Results: Combination therapy with micafungin and amphotericin B gave excellent survival of infected mice compared with monotherapy with micafungin or amphotericin B alone. Combined therapy reduced the fungal burden in the lungs and the serum GM levels compared with monotherapy or untreated controls, resulting in a significant histological improvement with disappearance of fungi in the lungs. Conclusions: These findings suggest that combination therapy with micafungin and amphotericin B is more effective compared with monotherapy with either of them alone for IPA treatment.. |
| 17. |
Noriko Tsuchimochi, Yujiro Uchida, Yoji Nagasaki, Yoshihiro Eriguchi, Yoriko Maehara, Masako Kadowaki, Nobuyuki Shimono, Combined antibacterial effects of between meropenem and vancomycin, teicoplanin, linezolid, or arbekacin in methicillin-resistant Staphylococcus aureus, Japanese Journal of Chemotherapy, 55, 5, 363-367, 2007.09, In vitro interaction between meropenem(MEPM) and vancomycin(VCM), teicoplanin(TEIC), linezolid (LZD) , or arbekacin(ABK) was studied using the checkerboard technique in 207 clinical isolates of methicillin-resistant Staphylococcus aureus(MRSA) (MIC of MEPM ≧32). Of 207 strains, synergistic or additive action was observed in all strains by combination of MEPM and VCM or TEIC. A combination of MEPM and LZD or ABK showed synergistic or additive 196 strains (94.7%) and 159 strains (76.8%). Antagonism was not observed in any combination of MEPM and VCM, TEIC, or LZD, but 22 strains (10.6%) exhibited antagonism in combination with MEPM and ABK. It is thus important to know both the susceptibility of anti-MRSA agents alone and the combined effects of agents.. |
| 18. |
H. Kuwayama, K. Asaka, T. Sugiyama, Y. Fukuda, N. Aoyama, Y. Hirai, T. Fujioka, Gakuyo Karasawa, Ryo Uyama, Mototsugu Kato, Yuichi Shimizu, Souichi Nakagawa, Ken Nishi, Shigeru Ozasa, Mineo Kudo, Takahiro Kamata, Masao Saito, Naoyuki Kawamura, Masako Tsuyuguchi, Hiroko Ooizumi, Takeaki Kobayashi, Asako Iijima, Tsuyoshi Yabana, Kazuyoshi Yamashita, Youji Harada, Teitetsu Niido, Yuri Yasuda, Yoko Iga, Hajime Kuwayama, Morio Takahashi, Hironobu Takada, Hiroshi Takada, Shigeki Oka, Hiroki Ichimura, Eiko Makino, Kazumasa Miki, Jun Miwa, Yasuo Matsubara, Takashige Tomita, Shigeru Koyama, Nobuhiro Sakaki, Masahiko Takahashi, Haruko Yokoyama, Yuji Koike, Tuyo To, Yoshiharu Satake, Makiyo Machida, Takashi Kawai, Satoru Taira, Kenji Nukaga, Naomi Uemura, Jyunichi Akiyama, Yuko Hiraga, Hitohiko Koizuka, Shigeaki Yasaka, Ryosuke Tajiri, Masao Kobayakawa, Akitaka Takahara, Mika Shimamoto, Hiroshi Murata, Toshihide Okada, Yoshihide Fujiyama, Shigeki Koyama, Masaya Sasaki, Tomoyuki Tsujikawa, Izumi Ishizuka, Kiyoshi Ashida, Hajime Takahashi, Takumi Fukuchi, Naomi Kiyota, Hiroshi Yamashita, Reiko Tsukamoto, Hiroshi Ito, Tomohiro Nishide, Haruki Kato, Takashi Ando, Koichi Terao, Nobuo Aoyama, Daisuke Shirasaka, Takao Tamura, Shunichi Yoshida, Seiichi Hirano, Yoshihiro Fukuda, Kazutoshi Hori, Toshihiko Tomita, Tahashi Sakagami, Kazuhiko Inoue, Mutsumi Hananoki, Norio Miyashima, Hirotsugu Okuda, Kazuhiro Harada, Toshihiro Honda, Masaharu Takeda, Ken Haruma, Toru Hidaka, Hiroaki Oogoshi, Shinji Nagata, Akira Tari, Hiroshi Tani, Hiroshi Mieno, Mitsuhiro Mihara, Yoshihiro Wada, Tomohiko Shimatani, Masaki Inoue, Takashi Kobayashi, Kazuhiko Yamauchi, Makoto Tsugita, Nobutoshi Kuniyoshi, Kazuma Fujimoto, Ryuichi Iwakiri, Hiroyuki Sakata, Seiji Tsunada, Akifumi Ootani, Atsushi Kikkawa, Yoshihiro Eriguchi, Koji Fukuyama, Masahiro Hattori, Tomofumi Tanaka, Kiwamu Hasuda, Hideyo Goto, Toshio Fujioka, Ryugo Sato, Kazunari Murakami, Masaaki Kodama, Tadayoshi Okimoto, Hajime Miyajima, Masami Ono, Tsuyoshi Arita, Syunzo Sato, Hisanori Abe, Rabeprazole-based eradication therapy for Helicobacter pylori
A large-scale study in Japan, Alimentary Pharmacology and Therapeutics, 10.1111/j.1365-2036.2007.03298.x, 25, 9, 1105-1113, 2007.05, Background: Large-scale studies of rabeprazole-based Helicobacter pylori eradication therapy have not been reported in Japan. Aims: To evaluate H. pylori eradication by rabeprazole-based therapy with reference to antibiotic susceptibility, CYP2C19 genotype, and rabeprazole and clarithromycin dosages. Methods: From 35 centres 479 H. pylori-positive patients with gastric or duodenal ulcer were randomized to four treatment groups: Group 1 (10 mg rabeprazole + 750 mg amoxicillin + 200 mg clarithromycin twice daily for 7 days); Group 2 (10 mg, 750 mg, 400 mg); Group 3 (20 mg, 750 mg, 200 mg) and Group 4 (20 mg, 750 mg, 400 mg). Results: Eradication rates were 86% (102 of 119), 89% (97 of 109), 91% (106 of 116) and 90% (104 of 115) for Groups 1-4, respectively. The eradication rate was 95% (360 of 379) for clarithromycin- susceptible strains, and 50% (30 of 60) for clarithromycin-resistant strains. The eradication rates were 88% (332 of 379) and 96% (77 of 80) in extensive metabolizers and poor metabolizers, respectively. Conclusions: Rabeprazole-based therapies achieved 50% eradication of clarithromycin-resistant H. pylori, and even achieved good rates in extensive metabolizers. Accordingly, rabeprazole can be recommended as part of a first-line proton pump inhibitor-based triple therapy for H. pylori.. |
| 19. |
Yoshihiro Eriguchi, Seiji Tsunada, Sadahiro Amemori, Kenichiro Watanabe, Takehiro Fujise, Atsushi Kikkawa, Hibiki Ootani, Akifumi Ootani, Hiroyuki Sakata, Ryuichi Iwakiri, Masanobu Mizuguchi, Kazuma Fujimoto, A case of relapsed ischemic colitis with colon cast-like stripped mucosa, Japanese Journal of Gastroenterology, 103, 10, 1152-1156, 2006.10, An 82-year-old woman who had 5 relapses of ischemic colitis was admitted with sudden lower abdominal pain. Colonoscopic examination performed on the 2nd day revealed colon cast-like stripped colonic mucosa in the lower portion of the descending colon. She was treaed conservatively. After 2 weeks, ischemic colitis healed, with slight residual stenosis. Most reports of colon cast indicated that colon cast was caused by abdominal aneurysm, operation, or external wound. The only predisposing conditions in this case were arteriosclerosis of abdominal aorta and chronic constipation. Arteriosclerosis and chronic constipation might be the important risk factors of ischemic colitis with colon cast and relapsing of ischemic colitis.. |
