RESUMEN
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-CBFß-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.
Asunto(s)
Linaje de la Célula , Subunidades alfa del Factor de Unión al Sitio Principal/metabolismo , Subunidad beta del Factor de Unión al Sitio Principal/metabolismo , Células Dendríticas/metabolismo , Elementos de Facilitación Genéticos , Factores Reguladores del Interferón/metabolismo , Monocitos/metabolismo , Células Progenitoras Mieloides/metabolismo , Animales , Antígenos Ly/genética , Antígenos Ly/metabolismo , Células de la Médula Ósea , Células Cultivadas , Subunidades alfa del Factor de Unión al Sitio Principal/genética , Subunidad beta del Factor de Unión al Sitio Principal/genética , Células Dendríticas/inmunología , Epigénesis Genética , Femenino , Regulación del Desarrollo de la Expresión Génica , Factores Reguladores del Interferón/deficiencia , Factores Reguladores del Interferón/genética , Masculino , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Ratones Noqueados , Monocitos/inmunología , Células Progenitoras Mieloides/inmunología , Fenotipo , Transducción de SeñalRESUMEN
O-linked N-acetylglucosamine transferase (OGT) critically regulates wide variety of biological processes such as gene expression, metabolism, stress response, signaling and proteostasis. In adult hematopoiesis, OGT is crucial for differentiation of B and T cells and the maintenance of hematopoietic stem cells (HSCs). However, a role for OGT in fetal liver (FL) hematopoiesis remains unknown. To investigate a role for OGT in FL hematopoiesis, we conditionally disrupted OGT in hematopoietic cells in developing FLs. Hematopoietic specific disruption of OGT resulted in embryonic lethality in late stage of gestation due to severe anemia and growth retardation. OGT loss led to profound reduction of differentiating erythroid cells and erythroid progenitors in FLs due to massive apoptosis. In addition, clonogenic capacity of FL cells was severely impaired by OGT loss. Interestingly, expression of BCL-XL, a well-known inhibitor of apoptosis in FL cells, dramatically decreased, and the levels of reactive oxygen species (ROS) were increased in OGT-deficient FL cells. Overexpression of Bcl-xL and reduction of ROS significantly restored the colony formation of OGT-deficient FL cells. This study revealed a novel role for OGT during embryogenesis, which ensures survival of FL hematopoietic cells partly by regulating Bcl-xL and oxidative phosphorylation.
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N-Acetilglucosaminiltransferasas , Fosforilación Oxidativa , Ratones , Animales , Especies Reactivas de Oxígeno/metabolismo , Diferenciación Celular , N-Acetilglucosaminiltransferasas/genética , Hígado/metabolismoRESUMEN
PURPOSE: We describe the epidemiology of invasive Haemophilus influenzae disease (IHD) among adults in Japan. METHODS: Data for 200 adult IHD patients in 2014-2018 were analyzed. The capsular type of H. influenzae was determined by bacterial agglutination and polymerase chain reaction (PCR), and non-typeable Haemophilus influenzae (NTHi) was identified by PCR. RESULTS: The annual incidence of IHD (cases per 100,000 population) was 0.12 for age 15-64 years and 0.88 for age ≥ 65 years in 2018. The median age was 77 years, and 73.5% were aged ≥ 65 years. About one-fourth of patients were associated with immunocompromising condition. The major presentations were pneumonia, followed by bacteremia, meningitis and other than pneumonia or meningitis (other diseases). The case fatality rate (CFR) was 21.2% for all cases, and was significantly higher in the ≥ 65-year group (26.1%) than in the 15-64-year group (7.5%) (p = 0.013). The percentage of cases with pneumonia was significantly higher in the ≥ 65-year group than in the 15-64-year group (p < 0.001). The percentage of cases with bacteremia was significantly higher in the 15-64-year group than in the ≥ 65-year group (p = 0.027). Of 200 isolates, 190 (95.0%) were NTHi strains, and the other strains were encapsulated strains. 71 (35.5%) were resistant to ampicillin, but all were susceptible to ceftriaxone. CONCLUSION: The clinical presentations of adult IHD patients varied widely; about three-fourths of patients were age ≥ 65 years and their CFR was high. Our findings support preventing strategies for IHD among older adults, including the development of NTHi vaccine.
Asunto(s)
Bacteriemia , Infecciones por Haemophilus , Meningitis , Humanos , Lactante , Anciano , Japón/epidemiología , Infecciones por Haemophilus/epidemiología , Infecciones por Haemophilus/microbiología , Haemophilus influenzae , Meningitis/complicaciones , Bacteriemia/epidemiología , Bacteriemia/complicacionesRESUMEN
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.
Asunto(s)
Articulación Metacarpofalángica , Tomografía Computarizada por Rayos X , Femenino , Articulaciones de los Dedos , Humanos , Fantasmas de Imagen , RadiografíaRESUMEN
Dissemination of extended-spectrum-cephalosporin (ESC)-resistant Salmonella, especially extended-spectrum-ß-lactamase (ESBL)-producing Salmonella, is a concern worldwide. Here, we assessed Salmonella carriage by food workers in Japan to clarify the prevalence of ESC-resistant Salmonella harboring blaCTX-M We then characterized the genetic features, such as transposable elements, of blaCTX-M-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 Salmonella strains harboring blaCTX-M Overall, 164 Salmonella 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 Salmonella 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 Salmonella Of the 158 culturable isolates, seven showed resistance to ESCs: three isolates harbored blaCMY-2 and produced AmpC ß-lactamase, while four ESBL-producing isolates harbored blaCTX-M-14 (n = 1, Salmonella enterica serovar Senftenberg) or blaCTX-M-15 (n = 3, S. enterica serovar Haardt). blaCTX-M-15 was chromosomally located in the S Haardt isolates, which also contained ISEcp1, while the S Senftenberg isolate contained an IncFIA(HI1)/IncHI1A/IncHI1B(R27) hybrid plasmid carrying blaCTX-M-14 along with ISEcp1 This study indicates that food workers may be a reservoir of ESBL-producing Salmonella and associated genes. Thus, these workers may contribute to the spread of blaCTX-M via plasmids or mobile genetic elements such as ISEcp1IMPORTANCE Antimicrobial-resistant Salmonella bacteria arise in farm environments through imprudent use of antimicrobials. Subsequently, these antimicrobial-resistant strains, such as extended-spectrum-ß-lactamase (ESBL)-producing Salmonella, may be transmitted to humans via food animal-derived products. Here, we examined Salmonella carriage among food handlers in Japan. Overall, 164 of 145,220 fecal samples (0.113%) were positive for Salmonella Among the 158 tested isolates, four were identified as ESBL-producing isolates carrying ESBL determinants blaCTX-M-15 or blaCTX-M-14 In all cases, the genes coexisted with ISEcp1, 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 Salmonella to other bacterial species present in the human gut.
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Antibacterianos/farmacología , Cefalosporinas/farmacología , Reservorios de Enfermedades/microbiología , Farmacorresistencia Bacteriana , Industria de Alimentos , Infecciones por Salmonella/epidemiología , Salmonella/aislamiento & purificación , Adulto , Humanos , Japón/epidemiología , Persona de Mediana Edad , Salmonella/efectos de los fármacos , Infecciones por Salmonella/microbiología , Adulto JovenRESUMEN
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.
Asunto(s)
Infecciones por Caliciviridae , Enterotoxinas/análisis , Ensayo de Inmunoadsorción Enzimática , Heces/química , Pruebas de Fijación de Látex , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/microbiología , Infecciones por Caliciviridae/fisiopatología , Niño , Diarrea , Ensayo de Inmunoadsorción Enzimática/métodos , Ensayo de Inmunoadsorción Enzimática/normas , Heces/microbiología , Femenino , Microbioma Gastrointestinal/fisiología , Humanos , Pruebas de Fijación de Látex/métodos , Pruebas de Fijación de Látex/normas , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Zoonotic pathogen Escherichia albertii has been identified as the cause of several human disease outbreaks; however, factors such as the general symptoms and incubation period of E. albertii infection have yet to be defined. Therefore, we aimed to determine the unique aspects of E. albertii outbreaks in Japan and to examine the genetic characteristics of the causative pathogen. We studied all known E. albertii 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 E. albertii 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 E. albertii 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 E. albertii 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 E. albertii strains were classified into four of the five known phylogroups. Therefore, we determined that multiple E. albertii 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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Infecciones por Enterobacteriaceae/epidemiología , Escherichia/genética , Escherichia/patogenicidad , Sistemas de Secreción Tipo III/genética , Brotes de Enfermedades , Infecciones por Enterobacteriaceae/microbiología , Enfermedades Transmitidas por los Alimentos/microbiología , Genoma Bacteriano , Genotipo , Humanos , Japón/epidemiología , Filogenia , Factores de Virulencia/genética , Enfermedades Transmitidas por el Agua/microbiologíaRESUMEN
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 S = -0.385, P < 0.001, r S = -0.458, P < 0.0001, respectively), but not with the f and D* values (r S = -0.010, P = 0.936, r S = -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.
Asunto(s)
Artritis/diagnóstico por imagen , Artritis/patología , Articulaciones de la Mano/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Membrana Sinovial/diagnóstico por imagen , Adulto , Anciano , Proliferación Celular , Femenino , Articulaciones de la Mano/patología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Membrana Sinovial/patologíaRESUMEN
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/mm2 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 cDWI2000 based on b values of 400-1000 s/mm2 (rs = 0.405, p < 0.01). The area under the curve of cDWI2000 based on b values of 400-1000 s/mm2 (0.762) was larger than that of ADC values (0.570-0.608) when comparing low versus high contrast enhancement grades. Both cDWI1800 (200-1000) and cDWI2000 (400-1000) demonstrated high sensitivity and specificity in visual assessment (84.6% and 66.7%, respectively). The cDWI2000 based on b values of 400-1000 s/mm2 may be useful for noninvasive differentiation of synovial proliferation from joint effusion in hand arthritis.
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Artritis/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Articulaciones de la Mano/diagnóstico por imagen , Membrana Sinovial/diagnóstico por imagen , Sinovitis/diagnóstico por imagen , Adulto , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
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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Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/virología , Norovirus/genética , Norovirus/inmunología , Filogenia , Adolescente , Niño , Preescolar , Brotes de Enfermedades , Gastroenteritis/epidemiología , Gastroenteritis/virología , Humanos , Lactante , Recién Nacido , Japón/epidemiología , Estaciones del Año , Adulto JovenAsunto(s)
Antineoplásicos , Tumores del Estroma Gastrointestinal , Neoplasias del Recto , Humanos , Recto/cirugía , Recto/patología , Tumores del Estroma Gastrointestinal/cirugía , Tumores del Estroma Gastrointestinal/patología , Terapia Neoadyuvante , Neoplasias del Recto/patología , Pelvis/patología , Antineoplásicos/uso terapéuticoRESUMEN
The number of reported cases of infections due to Capnocytophaga species (spp.) is limited. We herein describe four cases developing bacteremia due to Capnocytophaga spp. during neutropenia after chemotherapy for hematological malignancies. At the onset of bacteremia, 3 of the 4 patients had oral mucositis, and 2 were co-infected with other bacteria. Two patients developed bacteremia while receiving fluoroquinolone as prophylaxis against bacterial infection. Bacteremia resolved with administration of antimicrobial agents in all patients and no recurrences were observed thereafter. The emergence of fluoroquinolone-resistant or beta-lactamase-producing Capnocytophaga spp. has recently been reported. Therefore, Capnocytophaga spp. could be causative pathogens in breakthrough and refractory infections under fluoroquinolone prophylaxis and empiric therapy, respectively, for febrile neutropenia. Capnocytophaga spp. should be recognized as one of the causative pathogens of febrile neutropenia. Furthermore, accumulation of cases and susceptibility data are required to establish an optimal treatment protocol.
Asunto(s)
Antibacterianos/uso terapéutico , Bacteriemia/microbiología , Capnocytophaga/aislamiento & purificación , Neoplasias Hematológicas/tratamiento farmacológico , Recurrencia Local de Neoplasia/microbiología , Neutropenia/microbiología , Adulto , Bacteriemia/diagnóstico , Bacteriemia/tratamiento farmacológico , Capnocytophaga/efectos de los fármacos , Neoplasias Hematológicas/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neutropenia/diagnóstico , Neutropenia/tratamiento farmacológico , Adulto JovenRESUMEN
BACKGROUND: To confirm the hypothesis that Salmonella enterica subspecies enterica serovar (S.) Infantis has higher basic reproductive rates in chicks compared with other Salmonella serovars, 1-day-old specific-pathogen-free chicks (n = 8) were challenged simultaneously with S. Infantis and S. Typhimurium per os. Challenged chicks (Group A) were then housed with non-infected chicks (Group B, n = 4) for 6 days (from 2 to 8 days of age). Group B birds were then housed with other non-infected birds (Group C, n = 4), which were then transferred to cages containing a further group of untreated chicks (Group D, n = 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 Salmonella from bowel and liver samples were enumerated. RESULTS: Both serovars were isolated from all groups except the control group. S. Typhimurium was isolated at a greater frequency than S. 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. S. Typhimurium, but not S. 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 S. Infantis in chicken flocks may explain why this serovar is predominant in broiler chickens.
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Antivirales/farmacología , Betacoronavirus/efectos de los fármacos , Endorribonucleasas/antagonistas & inhibidores , Glucocorticoides/farmacología , Pregnenodionas/farmacología , Proteínas no Estructurales Virales/antagonistas & inhibidores , Replicación Viral/efectos de los fármacos , Antivirales/química , Antivirales/metabolismo , Betacoronavirus/enzimología , Betacoronavirus/genética , Sitios de Unión , COVID-19 , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/virología , Endorribonucleasas/química , Endorribonucleasas/genética , Endorribonucleasas/metabolismo , Expresión Génica , Glucocorticoides/química , Glucocorticoides/metabolismo , Humanos , Simulación de Dinámica Molecular , Pandemias , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/virología , Pregnenodionas/química , Pregnenodionas/metabolismo , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Estructura Secundaria de Proteína , ARN Polimerasa Dependiente del ARN/química , ARN Polimerasa Dependiente del ARN/genética , ARN Polimerasa Dependiente del ARN/metabolismo , SARS-CoV-2 , Homología Estructural de Proteína , Termodinámica , Proteínas no Estructurales Virales/química , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismoRESUMEN
[Aim] To determine genotypes of Mycobacterium tuberculosis strains in Fukuoka Prefecture, Japan. [Methods] A total of 296 isolates from 296 tuberculosis patients is tested using 24-locus variable-number tandem- repeat (VNTR) typing. We also determined whether these isolates and a further 10 were Beijing lineage. [Results] The 296 isolates were classified into 264 VNTR types, and re-classified into 25 clusters when each cluster was defined as isolates being identical to VNTR types in 24 regions, or in 23 regions with the exception of one hypervariable region. Two clusters were shown to be identical to that of the Kansai regional epidemic. Regarding regional diversity, hypervariable regions showed relatively higher variation of isolate types. The Beijing lineage accounted for 78.1% of all isolates, which was similar to the value obtained from Kobe (78.5% in 2009) in the Kansai region. [Discussion] Six isolates from Fukuoka Prefecture over- lapped with those from Kansai region with respect to domi- nant VNTR type, while clusters from Fukuoka Prefectural isolates were unique, which may be a feature of Fukuoka prefectural isolates. [Conclusion] These data are likely to be useful for public health measures in the area.
Asunto(s)
ADN Bacteriano/genética , Mycobacterium tuberculosis/genética , Tuberculosis , Genotipo , Humanos , Japón/epidemiología , Repeticiones de Minisatélite , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis/epidemiologíaRESUMEN
Achromobacter xylosoxidans (A. xylosoxidans) is a non-fermentative gram-negative rod. This organism is reportedly a causative pathogen of bacteremia mainly in patients with hematological disorders. However, only one case of cellulitis due to A. xylosoxidans associated with hematological malignancy has been reported. An 80-year-old man developed cellulitis and subsequent bacteremia due to A. xylosoxidans during bortezomib therapy for multiple myeloma. Although his condition was serious enough to require intensive care, he fully recovered with appropriate antimicrobial agents and supportive care. The isolate was broadly resistant to antimicrobial agents, including cefepime, amikacin, and ciprofloxacin. Therefore, the identification and selection of appropriate antimicrobial agents were considered to have contributed to the successful outcome in this case. Physicians should recognize A. xylosoxidans as a possible pathogen causing cellulitis and secondary bacteremia, as well as being aware of its broad resistance to antimicrobial agents.
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Achromobacter denitrificans/aislamiento & purificación , Antineoplásicos/uso terapéutico , Bortezomib/uso terapéutico , Celulitis (Flemón)/tratamiento farmacológico , Mieloma Múltiple/tratamiento farmacológico , Achromobacter denitrificans/efectos de los fármacos , Anciano de 80 o más Años , Celulitis (Flemón)/complicaciones , Celulitis (Flemón)/patología , Humanos , Masculino , Mieloma Múltiple/complicaciones , Mieloma Múltiple/patología , Resultado del TratamientoRESUMEN
Microglia are generally considered the immune cells of the central nervous system. Recent studies have demonstrated that under specific polarization conditions, microglia develop into two different phenotypes, termed M1-like and M2-like microglia. However, the phenotypic characteristics of M1-like- and M2-like-polarized microglia and the mechanisms that regulate polarization are largely unknown. In this study, we characterized lipopolysaccharide-treated M1-like and IL-4-treated M2-like microglia and investigated the mechanisms that regulate phenotypic switching. The addition of M2-like microglial conditioned medium (CM) to primary neurons resulted in an increase in neurite length when compared with neurons treated with M1-like microglial CM, possibly because of the enhanced secretion of neurotrophic factors by M2-like microglia. M1-like microglia were morphologically characterized by larger soma, whereas M2-like microglia were characterized by long processes. M2-like microglia exhibited greater phagocytic capacity than M1-like microglia. These features switched in response to polarization cues. We found that expression of interferon regulatory factor 7 (IRF7) increased during the M2-like to M1-like switch in microglia in vitro and in vivo. Knockdown of IRF7 using siRNA suppressed the expression of M1 marker mRNA and reduced phosphorylation of STAT1. Our findings suggest that IRF7 signaling may play an important role in microglial polarization switching.
Asunto(s)
Polaridad Celular/fisiología , Factor 7 Regulador del Interferón/metabolismo , Microglía/metabolismo , Neuronas/metabolismo , Animales , Polaridad Celular/efectos de los fármacos , Células Cultivadas , Regulación hacia Abajo/efectos de los fármacos , Factor 7 Regulador del Interferón/deficiencia , Lipopolisacáridos/toxicidad , Ratones , Ratones Endogámicos C57BL , Microglía/citología , Microglía/efectos de los fármacos , Factores de Crecimiento Nervioso/metabolismo , Neuritas/efectos de los fármacos , Fenotipo , Fosforilación/efectos de los fármacos , ARN Interferente Pequeño , Factor de Transcripción STAT1/genética , Transducción de Señal/efectos de los fármacosRESUMEN
Recently, there has been a marked increase in the number of reports of fluoroquinolone-resistant Campylobacter jejuni and Campylobacter coli. The aim of this study was to evaluate the prevalence of antimicrobial resistance and its genetic determinants in Campylobacter species isolated from meat and human subjects in Fukuoka Prefecture, Japan. Between 2011 and 2013, 55 and 64 isolates were collected from meat (chicken meat and beef liver) and humans, respectively, in this prefecture. Antimicrobial susceptibility tests were conducted using the agar dilution method in accordance with the Clinical and Laboratory Standards Institute guidelines, using the following 11 antimicrobial agents : cephalexin, cefoxitin, nalidixic acid, ciprofloxacin, levofloxacin, tetracycline, minocycline, ampicillin, streptomycin, kanamycin and erythromycin. The susceptibility rates of the isolates to three quinolones (nalidixic acid, ciprofloxacin, levofloxacin) were 43.7%, 41.2%, 40.3%, respectively. All the isolates were multidrug resistant. Whereas 46.9%-51.6% of the human isolates were resistant to one or more of the quinolones, only 32.7%-34.5% of the meat isolates were resistant to one or more of the drugs. DNA sequencing showed that of the 50 quinolone resistant isolates 44 had position 86 isoleucine (Ile) substituted for threonine (Thr) in the GyrA protein (Thr86Ile). This amino acid substitution resulted from ACA to ATA and ACT to ATT mutations of codon 86 in C. jejuni and C. coli, respectively. Furthermore, two of the four C. jejuni isolates lacking the Thr86Ile mutation had combined Ser22Gly-Asn203Ser substitutions, while the remaining two isolates had combined Ser22Gly-Asn203Ser-Ala 206Val substitutions. These four isolates also had cmeABC sequences that differed from the quinolone sensitive C. jejuni ATCC33560(T) strain. In conclusion, C. jejuni and C. coli have relatively high quinolone resistance, and are resistant to other antibiotics. The new combination of amino acid substitutions in the GyrA protein could pose a potential threat to public health in Japan.
Asunto(s)
Antibacterianos/farmacología , Campylobacter coli/efectos de los fármacos , Campylobacter coli/genética , Campylobacter jejuni/efectos de los fármacos , Campylobacter jejuni/genética , Carne/microbiología , Mutación , Campylobacter coli/aislamiento & purificación , Campylobacter jejuni/aislamiento & purificación , Farmacorresistencia Bacteriana/genética , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
A woman in her 40s presented at our department with abdominal fullness. Abdominal computed tomography showed hepatomegaly and ascites, and gastrointestinal endoscopy showed esophageal varices. A diagnosis of Budd-Chiari syndrome (BCS) was confirmed by percutaneous hepatic venography, which detected obstruction of the main hepatic vein. It was treated using percutaneous transluminal angioplasty and metallic stent placement. Rupture of the esophageal varices occurred 5 months later because of the occlusion of the stent lumen; however, she was successfully retreated with further stent placement.
RESUMEN
Using 48,627 samples from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), we present a pan-cancer landscape of driver alterations and their clinical actionability in Japanese patients. Comparison with White patients in Genomics Evidence Neoplasia Information Exchange (GENIE) demonstrates high TP53 mutation frequencies in Asian patients across multiple cancer types. Integration of C-CAT, GENIE, and The Cancer Genome Atlas data reveals many cooccurring and mutually exclusive relationships between driver mutations. At pathway level, mutations in epigenetic regulators frequently cooccur with PI3K pathway molecules. Furthermore, we found significant cooccurring mutations within the epigenetic pathway. Accumulation of mutations in epigenetic regulators causes increased proliferation-related transcriptomic signatures. Loss-of-function of many epigenetic drivers inhibits cell proliferation in their wild-type cell lines, but this effect is attenuated in those harboring mutations of not only the same but also different epigenetic drivers. Our analyses dissect various genetic properties and provide valuable resources for precision medicine in cancer. SIGNIFICANCE: We present a genetic landscape of 26 principal cancer types/subtypes, including Asian-prevalent ones, in Japanese patients. Multicohort data integration unveils numerous cooccurring and exclusive relationships between driver mutations, identifying cooccurrence of multiple mutations in epigenetic regulators, which coordinately cause transcriptional and phenotypic changes. These findings provide insights into epigenetic regulator-driven oncogenesis. This article is featured in Selected Articles from This Issue, p. 695.