Publications by authors named "Koichi Murakami"

76 Publications

A RUNX-CBFβ-driven enhancer directs the Irf8 dose-dependent lineage choice between DCs and monocytes.

Nat Immunol 2021 03 18;22(3):301-311. Epub 2021 Feb 18.

Department of Immunology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.

The transcription factor IRF8 is essential for the development of monocytes and dendritic cells (DCs), whereas it inhibits neutrophilic differentiation. It is unclear how Irf8 expression is regulated and how this single transcription factor supports the generation of both monocytes and DCs. Here, we identified a RUNX-CBFβ-driven enhancer 56 kb downstream of the Irf8 transcription start site. Deletion of this enhancer in vivo significantly decreased Irf8 expression throughout the myeloid lineage from the progenitor stages, thus resulting in loss of common DC progenitors and overproduction of Ly6C monocytes. We demonstrated that high, low or null expression of IRF8 in hematopoietic progenitor cells promotes differentiation toward type 1 conventional DCs, Ly6C monocytes or neutrophils, respectively, via epigenetic regulation of distinct sets of enhancers in cooperation with other transcription factors. Our results illustrate the mechanism through which IRF8 controls the lineage choice in a dose-dependent manner within the myeloid cell system.
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http://dx.doi.org/10.1038/s41590-021-00871-yDOI Listing
March 2021

A longitudinal study on enteric virus contamination in bivalves along the coast of Ibaraki Prefecture, Japan.

J Food Prot 2021 Jan 7. Epub 2021 Jan 7.

Gunma Paz Daigaku Daigakuin Professor Department of Health Sciences 1-7-1, Tonyamachi JAPAN Takasaki-shi 3700006.

During the 2014-2018 seasons, we conducted a longitudinal study involving enteric virus surveillance in bivalves, including natural oysters and clams harvested in Ibaraki Prefecture, Japan. Some norovirus (NoV) contaminations were detected in natural oysters, while no enteric virus was found in clams. NoV detected in oysters were of the genotypes GII.4 and GII.6, which are closely related genetically to the NoV strains prevalent in humans. We found low level of enteric virus contamination in bivalves collected along the coast of Ibaraki Prefecture. The possibility of food poisoning caused by these viruses appears low, and few cases of infectious disease have been observed in the surrounding area. The harvest timing was more related to detection of enteric viruses than the harvest area. Our results highlighted the fact that contamination of bivalves by enteric viruses may depend upon the prevalence of human diarrhea and illness.
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http://dx.doi.org/10.4315/JFP-20-353DOI Listing
January 2021

OGT Regulates Hematopoietic Stem Cell Maintenance via PINK1-Dependent Mitophagy.

Cell Rep 2021 Jan;34(1):108579

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan. Electronic address:

O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is a unique enzyme introducing O-GlcNAc moiety on target proteins, and it critically regulates various cellular processes in diverse cell types. However, its roles in hematopoietic stem and progenitor cells (HSPCs) remain elusive. Here, using Ogt conditional knockout mice, we show that OGT is essential for HSPCs. Ogt is highly expressed in HSPCs, and its disruption induces rapid loss of HSPCs with increased reactive oxygen species and apoptosis. In particular, Ogt-deficient hematopoietic stem cells (HSCs) lose quiescence, cannot be maintained in vivo, and become vulnerable to regenerative and competitive stress. Interestingly, Ogt-deficient HSCs accumulate defective mitochondria due to impaired mitophagy with decreased key mitophagy regulator, Pink1, through dysregulation of H3K4me3. Furthermore, overexpression of PINK1 restores mitophagy and the number of Ogt-deficient HSCs. Collectively, our results reveal that OGT critically regulates maintenance and stress response of HSCs by ensuring mitochondrial quality through PINK1-dependent mitophagy.
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http://dx.doi.org/10.1016/j.celrep.2020.108579DOI Listing
January 2021

Quantification of Joint Space Width Difference on Radiography Via Phase-Only Correlation (POC) Analysis: a Phantom Study Comparing with Various Tomographical Modalities Using Conventional Margin-Contouring.

J Digit Imaging 2021 Feb 2;34(1):96-104. Epub 2020 Dec 2.

Faculty of Health Sciences, Hokkaido University, North-12 West-5, Kita-ku, Sapporo, 060-0812, Japan.

Several visual scoring methods are currently used to assess progression of rheumatoid arthritis (RA) on radiography. However, they are limited by its subjectivity and insufficient sensitivity. We have developed an original measurement system which uses a technique called phase-only correlation (POC). The purpose of this study is to validate the system by using a phantom simulating the joint of RA patients.A micrometer measurement apparatus that can adjust arbitrary joint space width (JSW) in a phantom joint was developed to define true JSW. The phantom was scanned with radiography, 320 multi detector CT (MDCT), high-resolution peripheral quantitative CT (HR-pQCT), cone beam CT (CBCT), and tomosynthesis. The width was adjusted to the average size of a women's metacarpophalangeal joint, from 1.2 to 2.2 mm with increments of 0.1 mm and 0.01 mm. Radiographical images were analyzed by the POC-based system and manual method, and images from various tomographical modalities were measured via the automatic margin detection method. Correlation coefficients between true JSW difference and measured JSW difference were all strong at 0.1 mm intervals with radiography (POC-based system and manual method), CBCT, 320MDCT, HR-pQCT, and tomosynthesis. At 0.01 mm intervals, radiography (POC-based system), 320MDCT, and HR-pQCT had strong correlations, while radiography (manual method) and CBCT had low correlations, and tomosynthesis had no statistically significant correlation. The smallest detectable changes for radiography (POC-based system), radiography (manual method), 320MDCT, HR-pQCT, CBCT, and tomosynthesis were 0.020 mm, 0.041 mm, 0.076 mm, 0.077 mm, 0.057 mm, and 0.087 mm, respectively. We conclude that radiography analyzed with the POC-based system might sensitively detect minute joint space changes of the finger joint.
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http://dx.doi.org/10.1007/s10278-020-00406-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887106PMC
February 2021

Establishment of a High-risk MDS/AML Cell Line YCU-AML1 and its Xenograft Model Harboring t(3;3) and Monosomy 7.

Hemasphere 2020 Oct 17;4(5):e469. Epub 2020 Sep 17.

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Japan.

Acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) with both inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and monosomy 7 defines an extremely aggressive myeloid cancer whose molecular pathogenesis and optimal therapeutic strategy still remain unclear. We established a new MDS/AML cell line, YCU-AML1, and its patient-derived xenograft (PDX) model from a high-risk MDS patient who later transformed into AML harboring both t(3;3)(q21;q26.2) and monosomy 7. YCU-AML1 cells propagated in co-culture system with stromal cells in granulocyte macrophage colony-stimulating factor (GM-CSF)-dependent manner. CD34 bone marrow cells derived from our PDX model showed high and low expression. Moreover, mutational profile of our MDS/AML model was consistent with recently published mutational spectrum of myeloid malignancies with inv(3)/t(3;3). These data suggest that YCU-AML1 cells and its MDS/AML model strongly mimics a high-risk human myeloid cancer with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and monosomy 7 in terms of both clinical phenotype and molecular basis. We believe our model can be used as a feasible tool to further explore molecular pathogenesis and novel treatment strategy of high-risk MDS/AML with t(3;3)(q21;q26.2) and monosomy 7.
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http://dx.doi.org/10.1097/HS9.0000000000000469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643909PMC
October 2020

Detailed Molecular Interactions of Favipiravir with SARS-CoV-2, SARS-CoV, MERS-CoV, and Influenza Virus Polymerases In Silico.

Microorganisms 2020 Oct 20;8(10). Epub 2020 Oct 20.

Department of Microbiology, Yokohama City University School of Medicine, Yokohama, Kanagawa 236-0004, Japan.

Favipiravir was initially developed as an antiviral drug against influenza and is currently used in clinical trials against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (COVID-19). This agent is presumably involved in RNA chain termination during influenza virus replication, although the molecular interactions underlying its potential impact on the coronaviruses including SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) remain unclear. We performed in silico studies to elucidate detailed molecular interactions between favipiravir and the SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza virus RNA-dependent RNA polymerases (RdRp). As a result, no interactions between favipiravir ribofuranosyl-5'-triphosphate (F-RTP), the active form of favipiravir, and the active sites of RdRps (PB1 proteins) from influenza A (H1N1)pdm09 virus were found, yet the agent bound to the tunnel of the replication genome of PB1 protein leading to the inhibition of replicated RNA passage. In contrast, F-RTP bound to the active sites of coronavirus RdRp in the presence of the agent and RdRp. Further, the agent bound to the replicated RNA terminus in the presence of agent, magnesium ions, nucleotide triphosphate, and RdRp proteins. These results suggest that favipiravir exhibits distinct mechanisms of action against influenza virus and various coronaviruses.
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http://dx.doi.org/10.3390/microorganisms8101610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589801PMC
October 2020

Coinfection with Human Norovirus and Escherichia coli O25:H4 Harboring Two Chromosomal blaCTX-M-14 Genes in a Foodborne Norovirus Outbreak in Shizuoka Prefecture, Japan.

J Food Prot 2020 Sep;83(9):1584-1591

Department of Microbiology, Shizuoka Institute of Environment and Hygiene, 4-27-2 Kitaando, Aoi-ku, Shizuoka, Shizuoka 420-8637, Japan.

Abstract: Hospital-acquired infections caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are a global problem. Healthy people can carry ESBL-producing E. coli in the intestines; thus, E. coli from healthy people can potentially cause hospital-acquired infections. Therefore, the transmission routes of ESBL-producing E. coli from healthy persons should be determined. A foodborne outbreak of human norovirus (HuNoV) GII occurred at a restaurant in Shizuoka, Japan, in 2018. E. coli O25:H4 was isolated from some of the HuNoV-infected customers. Pulsed-field gel electrophoresis showed that these E. coli O25:H4 strains originated from one clone. Because the only epidemiological link among the customers was eating food from this restaurant, the customers were concurrently infected with E. coli O25:H4 and HuNoV GII via the restaurant food. Whole genome analysis revealed that the E. coli O25:H4 strains possessed genes for regulating intracellular iron and expressing the flagellum and flagella. Extraintestinal pathogenic E. coli often express these genes on the chromosome. Additionally, the E. coli O25:H4 strains had plasmids harboring nine antimicrobial resistance genes. These strains harbored ESBL-encoding blaCTX-M-14 genes on two loci of the chromosome and had higher ESBL activity. Multilocus sequence typing and fimH subtyping revealed that the E. coli O25:H4 strains from the outbreak belonged to the subclonal group, ST131-fimH30R, which has been driving ESBL epidemics in Japan. Because the E. coli O25:H4 strains isolated in the outbreak belonged to a subclonal group spreading in Japan, foods contaminated with ESBL-producing E. coli might contribute to spreading these strains among healthy persons. The isolated E. coli O25:H4 strains produced ESBL and contained plasmids with multiple antimicrobial resistance genes, which may make it difficult to select antimicrobials for treating extraintestinal infections caused by these strains.

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http://dx.doi.org/10.4315/JFP-20-042DOI Listing
September 2020

Molecular pharmacology of ciclesonide against SARS-CoV-2.

J Allergy Clin Immunol 2020 08 13;146(2):330-331. Epub 2020 Jun 13.

Department of Microbiology, Yokohama City University School of Medicine, Kanagawa, Japan.

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http://dx.doi.org/10.1016/j.jaci.2020.05.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293530PMC
August 2020

Contrasting Results from Two Commercial Kits Testing for the Presence of Clostridium perfringens Enterotoxin in Feces from Norovirus-Infected Human Patients.

Clin Lab 2020 May;66(5)

Background: Detection of Clostridium perfringens enterotoxin (CPE) is critical for disease surveillance; however, commercial testing kits produce contrasting results.

Methods: We examined the cause of the differing results from a reversed passive latex agglutination (RPLA) assay (PET-RPLA Toxin Detection Kit) and an enzyme-linked immunosorbent assay (C. perfringens Enterotoxin ELISA Kit) using 73 human norovirus-positive fecal samples from gastroenteritis patients across 22 episodes in Japan.

Results: CPE was detected in 39/73 samples using the RPLA method; however, ELISA-based examination of 10 RPLA-positive samples produced negative results. Moreover, cpe was not detected in any of the RPLA-positive (n = 32) or -negative (n = 5) samples, and C. perfringens was only isolated from one RPLA-positive sample.

Conclusions: An ELISA-based testing approach may be more reliable than RPLA assays for CPE detection from human fecal samples. These findings may also be applicable to the detection of other foodborne diseases.
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http://dx.doi.org/10.7754/Clin.Lab.2019.190801DOI Listing
May 2020

Food Workers as a Reservoir of Extended-Spectrum-Cephalosporin-Resistant Strains in Japan.

Appl Environ Microbiol 2020 06 17;86(13). Epub 2020 Jun 17.

Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo, Japan

Dissemination of extended-spectrum-cephalosporin (ESC)-resistant , especially extended-spectrum-β-lactamase (ESBL)-producing , is a concern worldwide. Here, we assessed carriage by food workers in Japan to clarify the prevalence of ESC-resistant harboring We then characterized the genetic features, such as transposable elements, of -harboring plasmids using whole-genome sequencing. A total of 145,220 stool samples were collected from food workers, including cooks and servers from several restaurants, as well as food factory workers, from January to October 2017. Isolated salmonellae were subjected to antimicrobial susceptibility testing (disk diffusion method), and whole-genome sequencing was performed for strains harboring Overall, 164 isolates (0.113%) were recovered from 164 samples, from which we estimated that at least 0.113% (95% confidence interval [CI]: 0.096 to 0.132%) of food workers may carry Based on this estimation, 3,473 (95% CI = 2,962 to 4,047) individuals among the 3,075,330 Japanese food workers are likely to carry Of the 158 culturable isolates, seven showed resistance to ESCs: three isolates harbored and produced AmpC β-lactamase, while four ESBL-producing isolates harbored ( = 1, serovar Senftenberg) or ( = 3, serovar Haardt). was chromosomally located in the Haardt isolates, which also contained IS, while the Senftenberg isolate contained an IncFIA(HI1)/IncHI1A/IncHI1B(R27) hybrid plasmid carrying along with IS This study indicates that food workers may be a reservoir of ESBL-producing and associated genes. Thus, these workers may contribute to the spread of via plasmids or mobile genetic elements such as IS Antimicrobial-resistant bacteria arise in farm environments through imprudent use of antimicrobials. Subsequently, these antimicrobial-resistant strains, such as extended-spectrum-β-lactamase (ESBL)-producing , may be transmitted to humans via food animal-derived products. Here, we examined carriage among food handlers in Japan. Overall, 164 of 145,220 fecal samples (0.113%) were positive for Among the 158 tested isolates, four were identified as ESBL-producing isolates carrying ESBL determinants or In all cases, the genes coexisted with IS, regardless of whether they were located on the chromosome or on a plasmid. Our findings suggest that food workers may be a reservoir of ESBL-producing strains and could contribute to the spread of resistance genes from farm-derived to other bacterial species present in the human gut.
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http://dx.doi.org/10.1128/AEM.00072-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301857PMC
June 2020

Truncated Class 1 Integron Gene Cassette Arrays Contribute to Antimicrobial Resistance of Diarrheagenic .

Biomed Res Int 2020 31;2020:4908189. Epub 2020 Jan 31.

Kawasaki City Institute for Public Health, 3-25-13 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan.

Class 1 integrons (c1-integrons) are associated with multidrug resistance in diarrheagenic (DEC). However, little is known about gene cassettes located within these c1-integrons, particularly truncated c1-integrons, in DEC strains. Therefore, the aims of the present study were to reveal the relationship between antimicrobial resistance and the presence of truncated c1-integrons in DEC isolates derived from human stool samples in Japan. A total of 162 human stool-derived DEC isolates from Japan were examined by antimicrobial susceptibility testing, PCR-based gene detection, and next-generation sequencing analyses. Results showed that 44.4% (12/27) of c1-integrons identified in the DEC isolates harbored only 1 (an element of c1-integrons) and were truncated by IS, Tn, or IS-group insertion sequences. No difference in the frequency of antimicrobial resistance was recorded between intact and truncated c1-integron-positive DEC isolates. Isolates containing intact/truncated c1-integrons, particularly enteroaggregative isolates, were resistant to a greater number of antimicrobials than isolates without c1-integrons. and were the most prevalent antimicrobial resistance genes in the intact/truncated c1-integrons examined in this study. Therefore, gene cassettes located within these intact/truncated c1-integrons may only play a limited role in conferring antimicrobial resistance among DEC. However, DEC harboring truncated c1-integrons may be resistant to a greater number of antimicrobials than c1-integron-negative DEC, similar to strains harboring intact c1-integrons.
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http://dx.doi.org/10.1155/2020/4908189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013361PMC
November 2020

Molecular Evolution of the Protease Region in Norovirus Genogroup II.

Front Microbiol 2019 14;10:2991. Epub 2020 Jan 14.

Graduate School of Health Sciences, Gunma Paz University, Takasaki, Japan.

Noroviruses are a major cause of viral epidemic gastroenteritis in humans worldwide. The protease (Pro) encoded in open reading frame 1 (ORF1) is an essential enzyme for proteolysis of the viral polyprotein. Although there are some reports regarding the evolutionary analysis of norovirus GII-encoding genes, there are few reports focused on the region. We analyzed the molecular evolution of the region of norovirus GII using bioinformatics approaches. A time-scaled phylogenetic tree of the region constructed using a Bayesian Markov chain Monte Carlo method indicated that the common ancestor of GII diverged from GIV around 1680 CE [95% highest posterior density (HPD), 1607-1749]. The GII region emerged around 1752 CE (95%HPD, 1707-1794), forming three further lineages. The evolutionary rate of GII region was estimated at more than 10 substitutions/site/year. The distribution of the phylogenetic distances of each genotype differed, and showed genetic diversity. Mapping of the negative selection and substitution sites of the Pro structure showed that the substitution sites in the Pro protein were mostly produced under neutral selection in positions structurally adjacent to the active sites for proteolysis, whereas negative selection was observed in residues distant from the active sites. The phylodynamics of GII.P4, GII.P7, GII.P16, GII.P21, and GII.P31 indicated that their effective population sizes increased during the period from 2005 to 2016 and the increase in population size was almost consistent with the collection year of these genotypes. These results suggest that the region of the norovirus GII evolved rapidly, but under no positive selection, with a high genetic divergence, similar to that of the RNA-dependent RNA polymerase () region and the region of noroviruses.
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http://dx.doi.org/10.3389/fmicb.2019.02991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971112PMC
January 2020

Flagellum expression and swimming activity by the zoonotic pathogen Escherichia albertii.

Environ Microbiol Rep 2020 02 25;12(1):92-96. Epub 2019 Dec 25.

Kyushu University, Fukuoka, Fukuoka, Japan.

Flagella are the well-known structural appendages used by bacteria for motility. Although generally reported to be non-motile, the enteropathogenic bacterial species Escherichia albertii produces flagella intermittently. We found that E. albertii expressed flagella under specific environmental conditions. After several generations (involving 4 to 12-h incubations), six of the twelve strains we investigated displayed swimming motility in various aquatic environments, including pond water containing nutrients from pigeon droppings (10% suspension) as well as in 20 × -diluted tryptic soy broth. The most significant motility determinant was a temperature between 15 and 30 °C. At 20 °C in the 10% pigeon-dropping suspension, microscopic observations revealed that some cells (1%-95% of six strains) showed swimming motility. Electron microscopy showed that the E. albertii cells expressed flagella. Lower concentrations of some substrates (including nutrients) may be of secondary importance for E. albertii flagella expression. Interestingly, the non-motile strains (n = 6/12) contained pseudogenes corresponding to essential flagella structural proteins. After being released from its host into surface water, E. albertii may express flagella to move toward nutrient sources or new hosts.
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http://dx.doi.org/10.1111/1758-2229.12818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003939PMC
February 2020

Clinical characteristics of human herpesvirus-6 myelitis after allogeneic hematopoietic stem cell transplantation and its favorable outcome by early intervention.

Bone Marrow Transplant 2020 05 21;55(5):939-945. Epub 2019 Nov 21.

Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.

After allogeneic hematopoietic stem cell transplantation (HSCT), human herpesvirus-6 (HHV-6) can cause serious central nervous system (CNS) disorder and typically presents as encephalitis. Another manifestation of HHV-6 is myelitis, which has not been fully evaluated. In this study, we retrospectively analyzed 19 patients who developed HHV-6 myelitis after allogeneic HSCT. Median onset was 20 days after transplantation (range, 13-31), with a cumulative incidence of 4.1% at day 40 after transplantation. Median age at transplant was 50 years (range, 17-61). Median copy number of HHV-6 DNA was 3000 copies/ml in cerebrospinal fluid (CSF; range, 200-100,000). The most common symptoms were pruritus, pain of the extremities/back, and numbness. Three patients subsequently developed encephalitis in the clinical course of myelitis; their HHV-6 copy numbers in CSF had been higher than 10,000 copies/ml at the onset of myelitis. Antiviral agents were initiated shortly after onset in all patients, resulting in recovery. These results suggest that myelitis would be an important subtype of HHV-6-associated CNS disorders after allogeneic HSCT, whose prognosis could be favorable by an early intervention. Transplant physicians should recognize early posttransplant neurological symptoms such as pruritus, pain, or numbness as possible signs of HHV-6 myelitis, which could also progress to encephalitis.
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http://dx.doi.org/10.1038/s41409-019-0755-2DOI Listing
May 2020

O-antigen biosynthesis gene clusters of : their diversity and similarity to gene clusters and the development of an O-genotyping method.

Microb Genom 2019 11;5(11)

Department of Microbiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.

is a recently recognized human enteropathogen that is closely related to . In many Gram-negative bacteria, including , O-antigen variation has long been used for the serotyping of strains. In , while eight O-serotypes unique to this species have been identified, some strains have been shown to exhibit genetic or serological similarity to known / O-serotypes. However, the diversity of O-serotypes and O-antigen biosynthesis gene clusters (O-AGCs) of remains to be systematically investigated. Here, we analysed the O-AGCs of 65 strains and identified 40 O-genotypes (EAOgs) (named EAOg1-EAOg40). Analyses of the 40 EAOgs revealed that as many as 20 EAOgs exhibited significant genetic and serological similarity to the O-AGCs of known / O-serotypes, and provided evidence for the inter-species horizontal gene transfer of O-AGCs between and . Based on the sequence variation in the gene among the 40 EAOgs, we developed a multiplex PCR-based O-genotyping system for (EAO-genotyping PCR) and verified its usefulness by genotyping 278 strains from various sources. Although 225 (80.9 %) of the 278 strains could be genotyped, 51 were not assigned to any of the 40 EAOgs, indicating that further analyses are required to better understand the diversity of O-AGCs in and improve the EAO-genotyping PCR method. A phylogenetic view of strains sequenced so far is also presented with the distribution of the 40 EAOgs, which provided multiple examples for the intra-species horizontal transfer of O-AGCs in .
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http://dx.doi.org/10.1099/mgen.0.000314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927306PMC
November 2019

Epidemiological Aspects of Outbreaks in Japan and Genetic Characteristics of the Causative Pathogen.

Foodborne Pathog Dis 2020 02 11;17(2):144-150. Epub 2019 Oct 11.

Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo, Japan.

Zoonotic pathogen has been identified as the cause of several human disease outbreaks; however, factors such as the general symptoms and incubation period of infection have yet to be defined. Therefore, we aimed to determine the unique aspects of outbreaks in Japan and to examine the genetic characteristics of the causative pathogen. We studied all known outbreaks that occurred in Japan up until 2015, which consisted of five confirmed outbreaks and one putative outbreak (Outbreaks 1-6). Outbreaks were re-examined based on personal communications between researchers in prefectural and municipal public health institutes, and through examination of any published study conducted at the time. Draft genome sequences of outbreak-associated isolates were also generated. The most common symptom displayed by patients across the six episodes was watery diarrhea (>80%), followed by abdominal pain (50-84%) and fever (37.0-39.5°C) (26-44%). The estimated average incubation period of infection was 12-24 h. We assumed that most of the outbreaks were foodborne or waterborne, with restaurant foods, restaurant water, and boxed lunches being the suspected transmission vehicles. Three of the six outbreak-associated isolates possessed intact ETT2 regions, while the remaining isolates contained disrupted ETT2-encoding genes. Virulence gene screening revealed that more than half (44/70) of the tested genes were present in all 5 strains examined, and that each of the strains contained more than 1 gene from 14 out of the 21 groups of virulence genes examined in this study. The five strains were classified into four of the five known phylogroups. Therefore, we determined that multiple genotypes in Japan have the potential to cause outbreaks of diarrhea, abdominal pain, and/or fever following infection of a human host.
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http://dx.doi.org/10.1089/fpd.2019.2654DOI Listing
February 2020

Computed diffusion-weighted imaging for differentiating synovial proliferation from joint effusion in hand arthritis.

Rheumatol Int 2019 Dec 27;39(12):2111-2118. Epub 2019 Aug 27.

Faculty of Health Sciences, Hokkaido University, North-12 West-5, Kita-ku, Sapporo, 060-0812, Japan.

The objective of this study is to investigate computed DWI (cDWI) as an alternative method to contrast-enhanced MRI in comparison with directory measured DWI (mDWI) and apparent diffusion coefficient (ADC) for differentiating synovial proliferation from joint effusion. Nine patients suspected with RA (5 women) were included in this study. A radiologist identified region of interest (ROI) based on STIR, and evaluated using a 5-point grading scale of 0 (fluid) to 4 (synovial proliferation) according to the degree of contrast enhancement within the ROI. cDWI was synthesized for b values from 1000 to 2000 at 200 s/mm intervals using the combination of b values at mDWI. In addition to ADC values, contrast ratios were calculated using signal intensity for each ROI on the mDWI and cDWI. Visual assessment by a radiologist was conducted between pairs of STIR image and mDWI or cDWI. ROI grades were most significantly correlated with cDWI based on b values of 400-1000 s/mm (r = 0.405, p < 0.01). The area under the curve of cDWI based on b values of 400-1000 s/mm (0.762) was larger than that of ADC values (0.570-0.608) when comparing low versus high contrast enhancement grades. Both cDWI (200-1000) and cDWI (400-1000) demonstrated high sensitivity and specificity in visual assessment (84.6% and 66.7%, respectively). The cDWI based on b values of 400-1000 s/mm may be useful for noninvasive differentiation of synovial proliferation from joint effusion in hand arthritis.
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http://dx.doi.org/10.1007/s00296-019-04425-2DOI Listing
December 2019

Non-biogroup 1 or 2 Strains of the Emerging Zoonotic Pathogen , Their Proposed Assignment to Biogroup 3, and Their Commonly Detected Characteristics.

Front Microbiol 2019 5;10:1543. Epub 2019 Jul 5.

Professor Emeritus, Kyushu University, Fukuoka, Japan.

, a zoonotic enteropathogen, is responsible for outbreaks of disease in humans. Identifying strains of by phenotypic characterization tests is difficult because of its poorly defined properties. Screening its phenotypic characteristics is, nevertheless, a necessary prerequisite for further genetic analysis of its properties, and species-specific polymerase chain reaction (PCR) analysis can be used to type the pathogen. While two biogroups (1 and 2) have been described, strains with characteristics divergent from both biogroups have been reported worldwide. The aim of the present study was to evaluate the characteristics of non-biogroup 1 or 2 strains, and discern the characteristics common to all of the strains from this study. Altogether, 107/414 field isolates were selected for examination based on pulsed-field gel electrophoresis analysis. The 107 strains were isolated from 92 sources, including humans and pigeon feces, other wild birds, and retail chicken livers. All strains were then examined using various culture-based, biochemical (API 50CHE tests, API Zym test, and others) and molecular (virulence gene screening, multi-locus sequence analysis) testing methods. Our results revealed that all field strains ( = 107) showed non-biogroup 1 or 2 characteristics, with multiple sequence differences. Variations in indole production and the lysine decarboxylase activity profiles among the isolates made identification of very difficult. Therefore, we propose that non-biogroup 1 or 2 of should be assigned to biogroup 3 to make screening of them easier in public health and clinical laboratory settings. Clearly, having group criteria for indole-negative/lysine-positive, indole-positive/lysine-negative, and indole-positive/lysine-positive biogroups 1, 2, and 3 strains, respectively, should provide for more accurate identification of isolates. Based on our findings, we recommend that isolates displaying phenotype mobility-negativity (sulfide-indole-motility medium, 37°C), hydrogen sulfide production-negativity (triple sugar iron medium), acid production-negativity from xylose, negative β-glucuronidase activity properties, and showing indole production and lysine decarboxylase activity profiles in accordance with one of the three biogroups, should be further assessed using an -specific PCR assay.
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http://dx.doi.org/10.3389/fmicb.2019.01543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624678PMC
July 2019

Evaluation of early radiation DNA damage in a fractal cell nucleus model using Geant4-DNA.

Phys Med 2019 Jun 17;62:152-157. Epub 2019 May 17.

CNRS, IN2P3, CENBG, UMR 5797, Gradignan, France; Université de Bordeaux, CENBG, UMR 5797, Gradignan, France. Electronic address:

The advancement of multidisciplinary research fields dealing with ionising radiation induced biological damage - radiobiology, radiation physics, radiation protection and, in particular, medical physics - requires a clear mechanistic understanding of how cellular damage is induced by ionising radiation. Monte Carlo (MC) simulations provide a promising approach for the mechanistic simulation of radiation transport and radiation chemistry, towards the in silico simulation of early biological damage. We have recently developed a fully integrated MC simulation that calculates early single strand breaks (SSBs) and double strand breaks (DSBs) in a fractal chromatin based human cell nucleus model. The results of this simulation are almost equivalent to past MC simulations when considering direct/indirect strand break fraction, DSB yields and fragment distribution. The simulation results agree with experimental data on DSB yields within 13.6% on average and fragment distributions agree within an average of 34.8%.
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http://dx.doi.org/10.1016/j.ejmp.2019.04.010DOI Listing
June 2019

Intravoxel incoherent motion MRI for discrimination of synovial proliferation in the hand arthritis: A prospective proof-of-concept study.

J Magn Reson Imaging 2019 10 31;50(4):1199-1206. Epub 2019 Jan 31.

Faculty of Health Sciences, Hokkaido University, Sapporo, Japan.

Background: Postcontrast-enhanced MRI is currently the reference standard for synovial proliferation in rheumatoid arthritis (RA). However, the technique is somewhat invasive due to the use of gadolinium contrast agents, which may cause severe adverse/side effects. Intravoxel incoherent motion (IVIM) simultaneously permits quantification of perfusion as well as diffusion using a single imaging scan.

Purpose/hypothesis: To test the capability of IVIM MRI for noninvasive discrimination of synovial proliferation in hand arthritis.

Study Type: Prospective.

Subjects: Seven suspected RA patients (three women and four men; mean age, 61 years; range, 26-74 years).

Field Strength/sequence: 3 T/short tau inversion recovery (STIR), IVIM, postcontrast-enhanced MRI.

Assessment: Region of interest (ROI) was identified based on STIR. Contrast-enhanced MRI was evaluated using a 5-point grading scale of 0 (water) to 4 (synovial proliferation) according to the degree of contrast enhancement within the ROI. For each ROI, we calculated the apparent diffusion coefficient (ADC) and IVIM parameters (molecular diffusion coefficient [D], perfusion fraction [f], and perfusion-related diffusion coefficient [D*]). These parameters were subsequently compared with ROI contrast enhancement grades.

Statistical Tests: Spearman's rank correlation test and a receiver operating characteristic (ROC) curve.

Results: A total of 90 ROIs of suspected synovial proliferation and/or joint effusion were identified. ROI grades were correlated with ADC and D values (r = -0.385, P < 0.001, r = -0.458, P < 0.0001, respectively), but not with the f and D* values (r = -0.010, P = 0.936, r = -0.084, P = 0.505, respectively). The area under the curves (AUCs) of D values (0.708-0.888, P = 0.002-0.0002) were slightly larger than those of ADC values (0.692-0.791, P = 0.013-0.001) when comparing low- vs. high-contrast enhancement grades.

Data Conclusion: The IVIM parameter D and ADC may be useful for the noninvasive identification of synovial proliferation in hand arthritis.

Level Of Evidence: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:1199-1206.
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http://dx.doi.org/10.1002/jmri.26660DOI Listing
October 2019

MPEXS-DNA, a new GPU-based Monte Carlo simulator for track structures and radiation chemistry at subcellular scale.

Med Phys 2019 Mar 22;46(3):1483-1500. Epub 2019 Jan 22.

KEK, 1-1, Oho, Tsukuba, Ibaraki, 305-0801, Japan.

Purpose: Track structure simulation codes can accurately reproduce the stochastic nature of particle-matter interactions in order to evaluate quantitatively radiation damage in biological cells such as DNA strand breaks and base damage. Such simulations handle large numbers of secondary charged particles and molecular species created in the irradiated medium. Every particle and molecular species are tracked step-by-step using a Monte Carlo method to calculate energy loss patterns and spatial distributions of molecular species inside a cell nucleus with high spatial accuracy. The Geant4-DNA extension of the Geant4 general-purpose Monte Carlo simulation toolkit allows for such track structure simulations and can be run on CPUs. However, long execution times have been observed for the simulation of DNA damage in cells. We present in this work an improvement of the computing performance of such simulations using ultraparallel processing on a graphical processing unit (GPU).

Methods: A new Monte Carlo simulator named MPEXS-DNA, allowing high computing performance by using a GPU, has been developed for track structure and radiolysis simulations at the subcellular scale. MPEXS-DNA physics and chemical processes are based on Geant4-DNA processes available in Geant4 version 10.02 p03. We have reimplemented the Geant4-DNA process codes of the physics stage (electromagnetic processes of charged particles) and the chemical stage (diffusion and chemical reactions for molecular species) for microdosimetry simulation by using the CUDA language. MPEXS-DNA can calculate a distribution of energy loss in the irradiated medium caused by charged particles and also simulate production, diffusion, and chemical interactions of molecular species from water radiolysis to quantitatively assess initial damage to DNA. The validation of MPEXS-DNA physics and chemical simulations was performed by comparing various types of distributions, namely the radial dose distributions for the physics stage, and the G-value profiles for each chemical product and their linear energy transfer dependency for the chemical stage, to existing experimental data and simulation results obtained by other simulation codes, including PARTRAC.

Results: For physics validation, radial dose distributions calculated by MPEXS-DNA are consistent with experimental data and numerical simulations. For chemistry validation, MPEXS-DNA can also reproduce G-value profiles for each molecular species with the same tendency as existing experimental data. MPEXS-DNA also agrees with simulations by PARTRAC reasonably well. However, we have confirmed that there are slight discrepancies in G-value profiles calculated by MPEXS-DNA for molecular species such as H and H O when compared to experimental data and PARTRAC simulations. The differences in G-value profiles between MPEXS-DNA and PARTRAC are caused by the different chemical reactions considered. MPEXS-DNA can drastically boost the computing performance of track structure and radiolysis simulations. By using NVIDIA's GPU devices adopting the Volta architecture, MPEXS-DNA has achieved speedup factors up to 2900 against Geant4-DNA simulations with a single CPU core.

Conclusion: The MPEXS-DNA Monte Carlo simulation achieves similar accuracy to Monte Carlo simulations performed using other codes such as Geant4-DNA and PARTRAC, and its predictions are consistent with experimental data. Notably, MPEXS-DNA allows calculations that are, at maximum, 2900 times faster than conventional simulations using a CPU.
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http://dx.doi.org/10.1002/mp.13370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850505PMC
March 2019

Decrease in the prevalence of extended-spectrum cephalosporin-resistant Salmonella following cessation of ceftiofur use by the Japanese poultry industry.

Int J Food Microbiol 2018 Jun 17;274:45-51. Epub 2018 Mar 17.

Infectious Disease Surveillance Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan. Electronic address:

Extended-spectrum cephalosporin (ESC)-resistant Salmonella in chicken meat is a significant food safety concern. We previously reported that the prevalence of ESC-resistant Salmonella in chicken meat, giblets, and processed chicken (chicken meat products) increased in Japan between 2005 and 2010, with 27.9% (17/61) of Salmonella isolated from chicken meat products in 2010 showing resistance to ESC. The aims of the present study were to clarify trends in the prevalence of ESC-resistant Salmonella in chicken meat products in Japan between 2011 and 2015, and to determine the genetic profiles of bla-harboring plasmids, including replicon types, using next-generation sequencing. Our results showed that the prevalence of ESC-resistant Salmonella, mainly consisting of AmpC β-lactamase CMY-2-producing isolates, in chicken meat products had increased to 45.5% (10/22) by 2011. However, following the voluntary cessation of ceftiofur use by the Japanese poultry industry in 2012, the prevalence of ESC-resistant Salmonella steadily decreased each year, to 29.2% (7/24), 18.2% (4/22), 10.5% (2/19), and 10.5% (2/19) in 2012, 2013, 2014, and 2015, respectively. Furthermore, no AmpC β-lactamase CMY-2-producing isolates were identified in 2014 and 2015. However, the prevalence of Salmonella enterica subspecies enterica serovar Manhattan isolates harboring a bla-carrying IncX1 plasmid remained steady even after the cessation of ceftiofur use. Therefore, continuous monitoring of ESC resistance amongst Salmonella isolates from chicken meat products is required for food safety.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2018.03.011DOI Listing
June 2018

Geant4-DNA track-structure simulations for gold nanoparticles: The importance of electron discrete models in nanometer volumes.

Med Phys 2018 May 23;45(5):2230-2242. Epub 2018 Mar 23.

Univ. Bordeaux, CENBG, UMR 5797, Gradignan, France.

Purpose: Gold nanoparticles (GNPs) are known to enhance the absorbed dose in their vicinity following photon-based irradiation. To investigate the therapeutic effectiveness of GNPs, previous Monte Carlo simulation studies have explored GNP dose enhancement using mostly condensed-history models. However, in general, such models are suitable for macroscopic volumes and for electron energies above a few hundred electron volts. We have recently developed, for the Geant4-DNA extension of the Geant4 Monte Carlo simulation toolkit, discrete physics models for electron transport in gold which include the description of the full atomic de-excitation cascade. These models allow event-by-event simulation of electron tracks in gold down to 10 eV. The present work describes how such specialized physics models impact simulation-based studies on GNP-radioenhancement in a context of x-ray radiotherapy.

Methods: The new discrete physics models are compared to the Geant4 Penelope and Livermore condensed-history models, which are being widely used for simulation-based NP radioenhancement studies. An ad hoc Geant4 simulation application has been developed to calculate the absorbed dose in liquid water around a GNP and its radioenhancement, caused by secondary particles emitted from the GNP itself, when irradiated with a monoenergetic electron beam. The effect of the new physics models is also quantified in the calculation of secondary particle spectra, when originating in the GNP and when exiting from it.

Results: The new physics models show similar backscattering coefficients with the existing Geant4 Livermore and Penelope models in large volumes for 100 keV incident electrons. However, in submicron sized volumes, only the discrete models describe the high backscattering that should still be present around GNPs at these length scales. Sizeable differences (mostly above a factor of 2) are also found in the radial distribution of absorbed dose and secondary particles between the new and the existing Geant4 models. The degree to which these differences are due to intrinsic limitations of the condensed-history models or to differences in the underling scattering cross sections requires further investigation.

Conclusions: Improved physics models for gold are necessary to better model the impact of GNPs in radiotherapy via Monte Carlo simulations. We implemented discrete electron transport models for gold in Geant4 that is applicable down to 10 eV including the modeling of the full de-excitation cascade. It is demonstrated that the new model has a significant positive impact on particle transport simulations in gold volumes with submicron dimensions compared to the existing Livermore and Penelope condensed-history models of Geant4.
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http://dx.doi.org/10.1002/mp.12827DOI Listing
May 2018

Detailed genetic analyses of the HN gene in human respirovirus 3 detected in children with acute respiratory illness in the Iwate Prefecture, Japan.

Infect Genet Evol 2018 04 14;59:155-162. Epub 2018 Feb 14.

Infectious Disease Surveillance Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan; School of Medical Technology, Faculty of Health Science, Gunma Paz University, 1-7-1 Tonyamachi, Takasaki-shi, Gunma 370-0006, Japan; Department of Microbiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanagawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan. Electronic address:

We performed detailed genetic analyses of the partial hemagglutinin-neuraminidase (HN) gene in 34 human respirovirus 3 (HRV3) strains from children with acute respiratory illness during 2013-2015 in Iwate Prefecture, Japan. In addition, we performed analyses of the evolutionary timescale of the gene using the Bayesian Markov chain Monte Carlo (MCMC) method. Furthermore, we analyzed pairwise distances and performed selective pressure analyses followed by linear B-cell epitope mapping and N-glycosylation and phylodynamic analyses. A phylogenetic tree showed that the strains diversified at around 1939, and the rate of molecular evolution was 7.6 × 10 substitutions/site/year. Although the pairwise distances were relatively short (0.03 ± 0.018 [mean ± standard deviation, SD]), two positive selection sites (Cys544Trp and Leu555Ser) and no amino acid substitutions were found in the active/catalytic sites. Six epitopes were estimated in this study, and three mouse monoclonal antibody binding sites (amino acid positions 278, 281, and 461) overlapped with two epitopes belonging to subcluster C3 strains. Bayesian skyline plot analyses indicated that subcluster C3 strains have been increasing from 2004, whereas subcluster C1 strains have declined from 2004. Based on these results, Iwate strains were divided into two subclusters and each subcluster evolved independently. Moreover, our results suggested that some predicted linear epitopes (epitopes 3 and 5) are candidates for an HRV3 vaccine motif. To better understand the details of the molecular evolution of HRV, further studies are needed.
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http://dx.doi.org/10.1016/j.meegid.2018.01.021DOI Listing
April 2018

Genetic Analysis of Human Norovirus Strains in Japan in 2016-2017.

Front Microbiol 2018 18;9. Epub 2018 Jan 18.

Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Musashimurayama, Japan.

In the 2016/2017 winter season in Japan, HuNoV GII.P16-GII.2 strains (2016 strains) emerged and caused large outbreaks of acute gastroenteritis. To better understand the outbreaks, we examined the molecular evolution of the gene and region in 2016 strains from patients by studying their time-scale evolutionary phylogeny, positive/negative selection, conformational epitopes, and phylodynamics. The time-scale phylogeny suggested that the common ancestors of the 2016 strains gene and region diverged in 2006 and 1999, respectively, and that the 2016 strain was the progeny of a pre-2016 GII.2. The evolutionary rates of the gene and region were around 10 substitutions/site/year. Amino acid substitutions (position 341) in an epitope in the P2 domain of 2016 strains were not found in pre-2016 GII.2 strains. Bayesian skyline plot analyses showed that the effective population size of the gene in GII.2 strains was almost constant for those 50 years, although the number of patients with NoV GII.2 increased in 2016. The 2016 strain may be involved in future outbreaks in Japan and elsewhere.
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http://dx.doi.org/10.3389/fmicb.2018.00001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778136PMC
January 2018

Phylogeny and Immunoreactivity of Norovirus GII.P16-GII.2, Japan, Winter 2016-17.

Emerg Infect Dis 2018 01;24(1):144-148

During the 2016-17 winter season in Japan, human norovirus GII.P16-GII.2 strains (2016 strains) caused large outbreaks of acute gastroenteritis. Phylogenetic analyses suggested that the 2016 strains derived from the GII.2 strains detected during 2010-12. Immunochromatography between 2016 strains and the pre-2016 GII.2 strains showed similar reactivity.
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http://dx.doi.org/10.3201/eid2401.170284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749477PMC
January 2018

Pulsed-field profile diversities of Enteritidis, S. Infantis, and Corvallis in Japan.

Ital J Food Saf 2017 Aug 29;6(3):6808. Epub 2017 Sep 29.

Department of Health Sciences, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.

The diversity of pulsed-field profiles (PFPs) within non-typhoidal subtypes influences epidemiological analyses of outbreaks. Therefore, determining the PFP diversity of each serovar is important when evaluating current circulating strains. This study examined the PFP diversity of three important public health subspecies serovars, . Enteritidis (n=177), . Infantis (n=205), and . Corvallis (n=90), using pulsed-field gel electrophoresis. Isolates were collected from several sources, primarily from chicken-derived samples, in the Kyushu-Okinawa region of Japan between 1989 and 2005. . Enteritidis isolates displayed 51 distinct PFPs (E-PFPs), with 92 (52.0%) and 32 (18.1%) isolates displaying types E-PFP1 and E-PFP10, respectively. The 205 . Infantis isolates showed 54 distinct PFPs (I-PFPs), with 87 (42.4%) and 36 (17.6%) isolates being I-PFP4 and I-PFP2, respectively. I-PFP18 was the dominant I-PFP of layer chicken isolates across a 5-year period. Fourteen distinct . Corvallis PFPs were detected. Simpson's index results for the genetic diversities of . Enteritidis, . Infantis, and . Corvallis isolates were 0.70, 0.79, and 0.78, respectively. None of the E-PFPs or I-PFPs of layer chicken isolates overlapped with those of broiler chicken isolates, and the dominant clonal lines existed for >10 years. In conclusion, limited PFP diversities were detected amongst . Enteritidis, Infantis, and Corvallis isolates of primarily chicken-derived origins in the Kyushu-Okinawa region of Japan. Therefore, it is important to take into account these limitations in PFP diversities in epidemiological analyses of outbreaks.
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http://dx.doi.org/10.4081/ijfs.2017.6808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641657PMC
August 2017

Simultaneous oral administration of Infantis and Typhimurium in chicks.

Ir Vet J 2017;70:27. Epub 2017 Aug 31.

Department of Animal Science, Tokyo University of Agriculture, Atsugi, Kanagawa 243-0034 Japan.

Background: To confirm the hypothesis that subspecies serovar () Infantis has higher basic reproductive rates in chicks compared with other serovars, 1-day-old specific-pathogen-free chicks ( = 8) were challenged simultaneously with Infantis and Typhimurium . Challenged chicks (Group A) were then housed with non-infected chicks (Group B,  = 4) for 6 days (from 2 to 8 days of age). Group B birds were then housed with other non-infected birds (Group C,  = 4), which were then transferred to cages containing a further group of untreated chicks (Group D,  = 2). A control group consisting of four non-infected chicks was used for comparison. All chickens were humanely sacrificed at 18 days of age, and from bowel and liver samples were enumerated.

Results: Both serovars were isolated from all groups except the control group. Typhimurium was isolated at a greater frequency than Infantis from the bowel samples of chicks from Groups B, C and D, while no differences in colonisation rates were observed between the two serovars in liver samples from Groups B, C and D. Typhimurium, but not Infantis, was immunohistochemically detected in the lamina propria of the cecum and rectum in five birds of Group A. Despite the competitive administration, neither of the two serovars completely excluded the other, and no differences were observed in basic reproductive rates between the two serovars.

Conclusions: These findings, together with data from previous studies, suggest that the initial quantitative domination of Infantis in chicken flocks may explain why this serovar is predominant in broiler chickens.
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http://dx.doi.org/10.1186/s13620-017-0105-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579891PMC
August 2017

Bridging-to-transplant with Azacitidine for Myelodysplastic Syndrome and Acute Myeloid Leukemia, Reduces the Incidence of Acute Graft--host Disease.

Hematol Rep 2017 Jun 15;9(2):7114. Epub 2017 Jun 15.

Division of Hematology, Department of Internal Medicine, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.

Allogeneic stem cell transplantation (allo-SCT) is the only curative option for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Azacitidine (AZA) has a good toxicity profile compared with intensive chemotherapy and can be considered a pre-transplant regimen in elderly patients and in patients with comorbidities. To investigate the impact of pre-transplant AZA on patient outcome after allo-SCT, we conducted a retrospective analysis of AZA pre-treatment followed by allo-SCT in patients with high-risk MDS and AML. Twenty patients who were divided into two groups according to AZA treatment given prior to allo-SCT (AZA non-AZA group, 10 each). Overall survival, event-free survival and incidence of chronic graft--host disease (GVHD) were not significantly different between the two groups. The overall incidence of grade II to IV acute GVHD in the AZA group was significantly lower than that in the non-AZA group (P=0.004). Bridging to transplant with AZA should be considered as an immunomodulator and effective treatment strategy for patients with MDS and AML.
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http://dx.doi.org/10.4081/hr.2017.7114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477469PMC
June 2017