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Renal function significantly influences the appropriate warfarin dosage. However, studies investigating the impact of genetic factors on warfarin dosage, considering renal function, are limited. This study aimed to assess the role of genetic polymorphisms in VKORC1, CYP2C9, CYP2C19, CYP4F2, GGCX, and APOE in warfarin dosage adjustment considering renal function. A total of 108 outpatients receiving warfarin treatment with controlled prothrombin time-targeted international normalized ratio (1.5-3.0) were included. Patient data, warfarin dosage, and laboratory results were collected from electronic medical records. Each SNP [VKORC1 rs9923231, CYP2C9 rs1057910, CYP4F2 rs2108622, CYP2C19* 2 (rs4244285) and* 3 (rs4986893), GGCX rs699664 and rs12714145, and APOE rs7421] was analyzed. Multiple regression analysis revealed estimated glomerular filtration rate as the most significant factor influencing warfarin dose (p <0.001) (ß = -0.445). VKORC1 rs9923231 AA, CYP4F2 rs2108622 CT/TT, GGCX rs12714145 CT/TT, and CYP2C9 rs1057910 AC carriers were associated with warfarin dose (p <0.001, 0.015, 0.020, 0.038 and ß = -0.317, 0.191, -0.188, -0.162, respectively); however, other genes showed no significant association. In conclusion, after adjusting for renal function, genetic factors of VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs12714145, and CYP2C9 rs1057910 were found to contribute to warfarin dosage, having impact in that order. In contrast, the contribution of other genes to warfarin dosage was absent or negligible.
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Anticoagulantes , Polimorfismo de Nucleótido Simple , Warfarina , Humanos , Warfarina/administración & dosificación , Femenino , Masculino , Anticoagulantes/administración & dosificación , Anciano , Persona de Mediana Edad , Pueblo Asiatico/genética , Japón , Relación Normalizada Internacional , Relación Dosis-Respuesta a Droga , Tasa de Filtración Glomerular , Vitamina K Epóxido Reductasas/genética , Anciano de 80 o más Años , Familia 4 del Citocromo P450/genética , Genotipo , Adulto , Pueblos del Este de AsiaRESUMEN
BACKGROUND: The Shock Index (SI), defined as heart rate divided by systolic blood pressure, is reportedly an early surrogate indicator for postpartum hemorrhage (PPH). However, most previous studies have used clinical data of women who delivered vaginally. Therefore, we aimed to evaluate the SI pattern during cesarean delivery and determine its usefulness in detecting PPH. METHODS: This was a single-center retrospective study using the clinical data of women (nâ¯=â¯331) who underwent cesarean delivery under spinal anesthesia at term between 2018 and 2021. We assessed the SI pattern stratified by total blood loss and evaluated the predictive performance of each vital sign in detecting PPH (total blood loss ≥1000â¯mL) based on the area under the receiver operating characteristic curve (AUROC). RESULTS: At 10-15â¯min after delivery, the mean SI peaked between 0.84 and 0.90 and then decreased to a level between 0.72 and 0.77, which was similar to that upon entering the operating room. Among 331 women, 91 (27.5%) were diagnosed with PPH. There was no correlation between SI and total blood loss (rsâ¯=â¯0.02). The SI had low ability to detect PPH (AUROC 0.54, 95% confidence interval 0.47 to 0.61), which was similar to other vital signs (AUROCs 0.53-0.56). CONCLUSION: We determined the pattern of SI during cesarean delivery. We found no correlation between SI and total blood loss. Unlike in vaginal delivery, the prognostic accuracy of SI for PPH detection in cesarean delivery was low.
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BACKGROUND: Immune checkpoint inhibitors are a standard therapy in metastatic urothelial carcinoma (UC). Long-term follow-up is necessary to confirm durability of response and identify further safety concerns. PATIENTS AND METHODS: In KEYNOTE-045, patients with metastatic UC that progressed on platinum-containing chemotherapy were randomly assigned 1:1 to receive pembrolizumab or investigator's choice of paclitaxel, docetaxel, or vinflunine. Primary endpoints were progression-free survival per RECIST version 1.1 by blinded independent central review (BICR) and overall survival. In KEYNOTE-052, cisplatin-ineligible patients with metastatic UC received first-line pembrolizumab. The primary endpoint was objective response rate per RECIST version 1.1 by BICR. RESULTS: A total of 542 patients (pembrolizumab, n = 270; chemotherapy, n = 272) were randomly assigned in KEYNOTE-045. The median follow-up was 62.9 months (range 58.6-70.9 months; data cut-off 1 October 2020). At 48 months, overall survival rates were 16.7% for pembrolizumab and 10.1% for chemotherapy; progression-free survival rates were 9.5% and 2.7%, respectively. The median duration of response (DOR) was 29.7 months (range 1.6+ to 60.5+ months) for pembrolizumab and 4.4 months (range 1.4+ to 63.1+ months) for chemotherapy; 36-month DOR rates were 44.4% and 28.3%, respectively. A total of 370 patients were enrolled in KEYNOTE-052. The median follow-up was 56.3 months (range 51.2-65.3 months; data cut-off 26 September 2020). The confirmed objective response rate was 28.9% (95% confidence interval 24.3-33.8), and the median DOR was 33.4 months (range 1.4+ to 60.7+ months); the 36-month DOR rate was 44.8%. Most treatment-related adverse events for pembrolizumab in either study were grade 1 or 2 and manageable, which is consistent with prior reports. CONCLUSION: With â¼5 years of follow-up, pembrolizumab monotherapy continued to demonstrate durable efficacy with no new safety signals in patients with platinum-resistant metastatic UC and as first-line therapy in cisplatin-ineligible patients. CLINICAL TRIAL REGISTRY AND ID: With ClinicalTrials.gov NCT02256436 (KEYNOTE-045); https://clinicaltrials.gov/ct2/show/NCT02256436 and NCT02335424 (KEYNOTE-052); https://clinicaltrials.gov/ct2/show/NCT02335424.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Carcinoma de Células Transicionales/tratamiento farmacológico , Cisplatino/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Estudios de Seguimiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
The differential cross sections of the Σ^{-}pâΛn reaction were measured accurately for the Σ^{-} momentum (p_{Σ}) ranging from 470 to 650 MeV/c at the J-PARC Hadron Experimental Facility. Precise angular information about the Σ^{-}pâΛn reaction was obtained for the first time by detecting approximately 100 reaction events at each angular step of Δcosθ=0.1. The obtained differential cross sections show a slightly forward-peaking structure in the measured momentum regions. The cross sections integrated for -0.7≤cosθ≤1.0 were obtained as 22.5±0.68 [statistical error(stat.)] ±0.65 [systematic error(syst.)] mb and 15.8±0.83(stat)±0.52(syst) mb for 470
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In this study, a method for estimating the half-value layer (HVL) and effective energy (Eeff) by imaging the luminescence from a polyethersulfone (PES) resin with rotating irradiation of X-rays in a computed tomography scanner was developed. The luminescence of the PES resin was imaged using a charge-coupled device camera. The PES-HVL was determined from the luminance attenuation profile corresponding to the X-ray attenuation within the resin. The PES-HVLs for tube potentials of 80-135 kVp were converted into Eeff values and were compared to those of a conventional lead-covered case method. The Eeff obtained using the proposed luminescence imaging method agreed within ~3.9% of that obtained using the conventional method. Moreover, dose simulations based on the X-ray spectrum calculated from the HVLs were performed using a poly(methyl methacrylate) phantom with a diameter of 16 cm. The simulated doses based on the luminescence imaging method agreed with the in-phantom dosimetry within ~9%.
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Luminiscencia , Tomografía Computarizada por Rayos X , Fantasmas de Imagen , Polímeros , Sulfonas , Tomógrafos Computarizados por Rayos X , Rayos XRESUMEN
This study investigated the potential of olanexidine gluconate as environmental disinfectant against enveloped viruses in the suspension test and three non-porous surface tests. In the suspension test, olanexidine gluconate showed immediate virucidal activity. In addition, non-porous surface tests demonstrated that, although the immediate effect of aqueous formulations was weak, the final virucidal efficacy outcompeted that of ethanol for disinfection. Furthermore, the effectiveness of olanexidine gluconate persisted even after drying on environmental surfaces. This study demonstrated the potential usage of olanexidine gluconate formulations as an environmental disinfectant in the infection control of enveloped viruses.
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Biguanidas/farmacología , Desinfectantes/farmacología , Glucuronatos/farmacología , Control de Infecciones/métodos , Envoltura Viral/efectos de los fármacos , Virus/efectos de los fármacos , Biguanidas/química , Línea Celular , Desinfectantes/química , Desinfección/normas , Microbiología Ambiental , Glucuronatos/química , Humanos , Pruebas de Sensibilidad Microbiana , Virus/clasificaciónRESUMEN
In an emulsion-counter hybrid experiment performed at J-PARC, a Ξ^{-} absorption event was observed which decayed into twin single-Λ hypernuclei. Kinematic calculations enabled a unique identification of the reaction process as Ξ^{-}+^{14}Nâ_{Λ}^{10}Be+_{Λ}^{5}He. For the binding energy of the Ξ^{-} hyperon in the Ξ^{-}-^{14}N system a value of 1.27±0.21 MeV was deduced. The energy level of Ξ^{-} is likely a nuclear 1p state which indicates a weak ΞN-ΛΛ coupling.
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With the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), a high-speed and convenient detection technology should be at the forefront of medical care worldwide. This study evaluated the usefulness of GeneSoC, a compact, high-speed reciprocal flow quantitative reverse transcription polymerase chain reaction system, for the detection of SARS-CoV-2. The results support the use of this system for the rapid identification of SARS-CoV-2. This approach can contribute to the strategic selection of initial management strategies for patients with COVID-19.
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Betacoronavirus/genética , Betacoronavirus/aislamiento & purificación , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/genética , Neumonía Viral/diagnóstico , Neumonía Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , COVID-19 , Humanos , Japón , Pandemias , SARS-CoV-2 , Sensibilidad y EspecificidadRESUMEN
The aim of this study was to develop a head-chest phantom that could mimic the physique of a Japanese 0.5-year-old child and to investigate the current status of exposure dose in infant head computed tomography examinations in Japan. The phantom was produced by machine processing, and radiophotoluminescence glass dosemeters were installed in the phantom for dose measurement. Organ doses were measured for seven different head scan protocols routinely used in three hospitals. In this study, the average dose of the brain and lens within the scan region was equivalent to that measured using infant phantoms in previous studies. In contrast, the doses of both salivary glands and thyroid glands adjacent to the scan region were 1.4-1.8 times higher than those in previous studies. Expansion of the scan area accompanied by a transition of the scan mode from non-helical to helical may have resulted in the differences in organ doses.
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Cabeza/efectos de la radiación , Fantasmas de Imagen , Dosis de Radiación , Dosimetría Termoluminiscente , Tórax/efectos de la radiación , Tomografía Computarizada por Rayos X , Carga Corporal (Radioterapia) , Diseño de Equipo , Cabeza/diagnóstico por imagen , Humanos , Lactante , Japón , Tórax/diagnóstico por imagenRESUMEN
AIM: To assess whether Epstein-Barr virus (EBV) reactivation is triggered by persistent apical periodontitis-related microbes using in vitro and ex vivo methodologies. METHODOLOGY: Surgically removed human periapical granulomas (n = 50) and healthy gingival tissues (n = 10) were analysed to determine the presence of EBV and seven persistent apical periodontitis-related microbes. In addition, real-time polymerase chain reaction was used to detect the mRNA expression of BZLF-1, an immediate-early gene of EBV. Expression of latent membrane protein (LMP)-1 and ZEBRA, an early lytic protein of EBV encoded by BZLF-1, was also examined using triple-colour immunofluorescence staining. n-Butyric acid produced by the microbes was quantified, and luciferase assays were performed in association with bacterial lysates. In addition, Daudi cells were cultured with bacterial lysates, and the expression levels of BZLF-1 mRNA and ZEBRA protein were determined. RESULTS: EBV DNA and BZLF-1 mRNA were detected in 47 out of 50 periapical granulomas, but not in healthy gingival tissues. The EBV DNA copy number and the number of Fusobacterium nucleatum were significantly positively correlated with BZLF-1 expression in periapical granulomas. The number of Prevotella intermedia was slightly correlated with BZLF-1 expression; however, the other microbes were not. CD79a-positive B cells in periapical granulomas, but not those in healthy gingival tissues, expressed both LMP-1 and ZEBRA. n-Butyric acid production was the highest in F. nucleatum and the lowest in P. intermedia. Enterococcus faecalis, Candida albicans and the other tested microbes did not produce n-butyric acid. An F. nucleatum lysate exhibited significantly increased BZLF-1-luciferase activity in the same manner of commercial butyric acid, whereas P. intermedia did not. F. nucleatum also induced the expression of BZLF-1 mRNA and ZEBRA protein by Daudi cells, indicating that EBV reactivation was induced. CONCLUSION: Among the persistent apical periodontitis-related bacteria that were tested, F. nucleatum most strongly reactivated latent EBV, whereas E. faecalis and C. albicans as well as the other microbes did not.
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Herpesvirus Humano 4 , Periodontitis Periapical , Encía , Humanos , Tejido Periapical , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: Emerging evidence suggests that stemness in cancer cells is a cause of drug resistance or metastasis and is an important therapeutic target. PR [positive regulatory domain I-binding factor 1 (PRDI-BF1) and retinoblastoma protein-interacting zinc finger gene (RIZ1)] domain containing 14 (PRDM14), that regulates pluripotency in primordial germ cell, has reported the overexpression and function of stemness in various malignancies, suggesting it as the possible therapeutic target. However, to our knowledge, there have been no reports on the expression and function of PRDM14 in colorectal cancer (CRC). Therefore, we investigated the expression and the role of PRDM14 in CRC. METHODS: We performed immunohistochemistry evaluations and assessed PRDM14 expression on 414 primary CRC specimens. Colon cancer cell lines were subjected to functional and stemness assays in vitro and in vivo. RESULTS: We found that PRDM14 positive staining exhibited heterogeneity in the CRC primary tumor, especially at the tumor invasion front. The aberrant expression of PRDM14 at the invasion front was associated with lymph node metastasis and disease stage in patients with CRC. Furthermore, the multivariate analysis revealed high PRDM14 expression as an independent prognostic factor in the patients with Stage III CRC. Overexpression of PRDM14 enhanced the invasive, drug-resistant and stem-like properties in colon cancer cells in vitro and tumorigenicity in vivo. CONCLUSION: Our findings suggest that PRDM14 is involved in progression and chemoresistance of CRC, and is a potential prognostic biomarker and therapeutic target in the CRC patients.
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Adenocarcinoma/genética , Neoplasias Colorrectales/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ARN/genética , Factores de Transcripción/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenoma/genética , Adenoma/metabolismo , Adenoma/patología , Anciano , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Proteínas de Unión al ADN/metabolismo , Resistencia a Antineoplásicos/genética , Femenino , Fluorouracilo/farmacología , Humanos , Inmunohistoquímica , Irinotecán/farmacología , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Trasplante de Neoplasias , Oxaliplatino/farmacología , Pronóstico , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción/metabolismo , Carga TumoralRESUMEN
Background: It is not known whether perioperative chemotherapy, compared with adjuvant chemotherapy alone, improves disease-free survival (DFS) in patients with upfront resectable colorectal liver metastases (CLM). The aim of this study was to estimate the impact of neoadjuvant 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX) on DFS in patients with upfront resectable CLM. Methods: Consecutive patients who presented with up to five resectable CLM at two Japanese and two French centres in 2008-2015 were included in the study. Both French institutions favoured perioperative FOLFOX, whereas the two Japanese groups systematically preferred upfront surgery plus adjuvant chemotherapy. Inverse probability of treatment weighting (IPTW) and Cox regression multivariable models were used to adjust for confounding. The primary outcome was DFS. Results: Some 300 patients were included: 151 received perioperative chemotherapy and 149 had upfront surgery plus adjuvant chemotherapy. The weighted 3-year DFS rate was 33·5 per cent after perioperative chemotherapy compared with 27·1 per cent after upfront surgery plus adjuvant chemotherapy (hazard ratio (HR) 0·85, 95 per cent c.i. 0·62 to 1·16; P = 0·318). For the subgroup of 165 patients who received adjuvant FOLFOX successfully (for at least 3 months), the adjusted effect of neoadjuvant chemotherapy was not significant (HR 1·19, 0·74 to 1·90; P = 0·476). No significant effect of neoadjuvant chemotherapy was observed in multivariable regression analysis. Conclusion: Compared with adjuvant chemotherapy, perioperative FOLFOX does not improve DFS in patients with resectable CLM, provided adjuvant chemotherapy is given successfully.
Antecedentes: Se desconoce si la quimioterapia perioperatoria en comparación con la quimioterapia adyuvante sola mejora la supervivencia libre de enfermedad (diseasefree survival, DFS) en pacientes con metástasis hepáticas de origen colorrectal (colorectal liver metastases, CLM) resecables de inicio. El objetivo de este estudio fue estimar el impacto de la neoadyuvancia con 5fluorouracilo, leucovorina y oxaliplatino (FOLFOX) sobre la DFS en pacientes con CLM resecables desde el principio. Métodos: Se incluyeron pacientes consecutivos que presentaban hasta cinco CLM resecables en dos centros japoneses y dos centros franceses entre 2008 a 2015. Ambas instituciones francesas favorecían FOLFOX perioperatorio, mientras que los dos grupos japoneses utilizaban sistemáticamente la cirugía de entrada y quimioterapia adyuvante. Se utilizaron la probabilidad inversa del tratamiento ponderado (Inverse Probability of Treatment Weighting, IPTW) y el modelo multivariable de regresión de Cox para ajustar por factores de confusión. El resultado primario fue la DFS. Resultados: Se incluyeron 300 pacientes (grupo de quimioterapia perioperatoria n = 151 y grupo de cirugía de entrada más quimioterapia adyuvante n = 149). La DFS a los 3 años ponderada fue del 33% después de quimioterapia perioperatoria versus 27% tras cirugía de entrada (cociente de riesgos instantáneos, hazard ratio HR: 0,85; i.c. del 95% (0,621,16); P = 0,32). Cuando se consideró el subgrupo de pacientes que (n = 165) de manera efectiva (al menos 3 meses) recibieron FOLFOX adyuvante, el efecto ajustado de la quimioterapia neoadyuvante no fue significativo (HR: 1,19 (0,741,90); P = 0,48). No se observó un efecto significativo de la quimioterapia neoadyuvante en el análisis de regresión multivariable. Conclusión: En comparación con la quimioterapia adyuvante, el FOLFOX perioperatorio no mejora la DFS en CLM resecables siempre y cuando la quimioterapia adyuvante se administre de forma efectiva.
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Quimioterapia Adyuvante/tendencias , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/cirugía , Neoplasias Hepáticas/secundario , Periodo Perioperatorio/tendencias , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Francia/epidemiología , Hepatectomía/métodos , Humanos , Japón/epidemiología , Leucovorina/administración & dosificación , Leucovorina/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/uso terapéutico , Oxaliplatino/administración & dosificación , Oxaliplatino/uso terapéutico , Estudios Retrospectivos , Complejo Vitamínico B/administración & dosificación , Complejo Vitamínico B/uso terapéuticoRESUMEN
OBJECTIVE: Dermatomyositis (DM) is an idiopathic inflammatory myopathy which often involves the lungs. DM is likely to be associated with aberrant T- and B-cell activation in the pathogenesis because of the proven effectiveness of T- and B-cell-targeted treatments. Assuming that the aberrant activation is reflected by biases in the lymphocyte subset repertoires, we aimed to elucidate these biases, especially in relation to clinical features of DM. METHOD: Based on the immunophenotyping standardized by the Human Immunology Project Consortium, untreated 13 DM patients, including seven patients with interstitial lung disease (ILD), and 18 age-matched healthy donors (HDs) were examined for proportions of peripheral blood lymphocyte subsets. Six DM patients were examined before and after successful induction of remission. RESULTS: Naïve CD4+ T cells and naïve B cells were more abundant, while there were fewer naïve CD8+ T cells, central memory CD8+ T cells, effector memory CD4+ T cells, Th1 cells, Tfh cells, and memory B cells in DM patients than in HDs. When the patients were subgrouped according to the presence of ILD, the lymphocyte subset repertoires in the patients with ILD contributed to the statistical differences in all the biased lymphocyte subset proportions. After treatment, transitional B cells vanished and there was an increase in memory B cells. CONCLUSION: The lymphocyte subset repertoires in the DM patients were biased, and were associated with the presence of ILD and disease activity of DM.
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Dermatomiositis , Inmunosupresores , Enfermedades Pulmonares Intersticiales , Subgrupos Linfocitarios/inmunología , Dermatomiositis/complicaciones , Dermatomiositis/diagnóstico , Dermatomiositis/tratamiento farmacológico , Dermatomiositis/inmunología , Femenino , Humanos , Memoria Inmunológica/efectos de los fármacos , Inmunofenotipificación/métodos , Inmunofenotipificación/estadística & datos numéricos , Inmunosupresores/inmunología , Inmunosupresores/uso terapéutico , Japón , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/inmunología , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Gravedad del PacienteRESUMEN
Differential cross sections and photon-beam asymmetries for the γ[over â]pâπ^{-}Δ^{++}(1232) reaction have been measured for 0.7
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AIM: To determine whether Porphyromonas endodontalis can reactivate latent Epstein-Barr virus (EBV). METHODOLOGY: The concentrations of short-chain fatty acids (SCFAs) in P. endodontalis culture supernatants were determined using high-performance liquid chromatography. A promoter region of BamHI fragment Z leftward open reading frame 1 (BZLF-1), which is a transcription factor that controls the EBV lytic cycle, was cloned into luciferase expression vectors. Then, the luciferase assay was performed using P. endodontalis culture supernatants. Histone acetylation using Daudi cells treated with P. endodontalis culture supernatants was examined using Western blotting. BZLF-1 mRNA and BamHI fragment Z EB replication activator (ZEBRA) protein were also detected quantitatively using real-time polymerase chain reaction (PCR) and Western blotting. Surgically removed periapical granulomas were examined to detect P. endodontalis, EBV DNA, and BZLF-1 mRNA expression using quantitative real-time PCR. Statistical analysis using Steel tests was performed. RESULTS: The concentrations of n-butyric acid in P. endodontalis culture supernatants were significantly higher than those of other SCFAs (P = 0.0173). Using B-95-8-221 Luc cells treated with P. endodontalis culture supernatants, the luciferase assay demonstrated that P. endodontalis induced BZLF-1 expression. Hyperacetylation of histones was also observed with the culture supernatants. BZLF-1 mRNA and ZEBRA protein were expressed by Daudi cells in a dose-dependent manner after the treatment with P. endodontalis culture supernatants. P. endodontalis and BZLF-1 in periapical granulomas were also detected. The expression levels of BZLF-1 mRNA were similar to the numbers of P. endodontalis cells in each specimen. CONCLUSIONS: n-butyric acid produced by P. endodontalis reactivated latent EBV.
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Ácido Butírico/metabolismo , Ácido Butírico/farmacología , Herpesvirus Humano 4/efectos de los fármacos , Herpesvirus Humano 4/metabolismo , Porphyromonas endodontalis/metabolismo , Adolescente , Adulto , Anciano , Línea Celular , Relación Dosis-Respuesta a Droga , Ácidos Grasos Volátiles/metabolismo , Ácidos Grasos Volátiles/farmacología , Femenino , Regulación Viral de la Expresión Génica/efectos de los fármacos , Encía/patología , Herpesvirus Humano 4/genética , Histonas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/biosíntesis , Transactivadores/genética , Transactivadores/metabolismo , Factores de Transcripción/metabolismo , Replicación Viral , Adulto JovenRESUMEN
We report on the first observation of γ rays emitted from an sd-shell hypernucleus, _{Λ}^{19}F. The energy spacing between the ground state doublet, 1/2^{+} and 3/2^{+} states, of _{Λ}^{19}F is determined to be 315.5±0.4(stat)_{-0.5}^{+0.6}(syst) keV by measuring the γ-ray energy of the M1(3/2^{+}â1/2^{+}) transition. In addition, three γ-ray peaks are observed and assigned as E2(5/2^{+}â1/2^{+}), E1(1/2^{-}â1/2^{+}), and E1(1/2^{-}â3/2^{+}) transitions. The excitation energies of the 5/2^{+} and 1/2^{-} states are determined to be 895.2±0.3(stat)±0.5(syst) and 1265.6±1.2(stat)_{-0.5}^{+0.7}(syst) keV, respectively. It is found that the ground state doublet spacing is well described by theoretical models based on existing s- and p-shell hypernuclear data.