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1.
Gastric Cancer ; 27(4): 722-734, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38668819

RESUMEN

BACKGROUND: The EORTC QLQ-STO22 (QLQ-STO22) is a firmly established and validated measure of health-related quality of life (HRQoL) for people with gastric cancer (GC), developed over two decades ago. Since then there have been dramatic changes in treatment options for GC. Also, East Asian patients were not involved in the development of QLQ-STO22, where GC is most prevalent and the QLQ-STO22 is widely used. A review with appropriate updating of the measure was planned. This study aims to capture HRQoL issues associated with new treatments and the perspectives of patients and health care professionals (HCPs) from different cultural backgrounds, including East Asia. METHODS: A systematic literature review and open-ended interviews were preformed to identify potential new HRQoL issues relating to GC. This was followed by structured interviews where HCPs and patients reviewed the QLQ-STO22 alongside new issues regarding relevance, importance, and acceptability. RESULTS: The review of 267 publications and interviews with 104 patients and 18 HCPs (48 and 9 from East Asia, respectively) generated a list of 58 new issues. Three of these relating to eating small amounts, flatulence, and neuropathy were recommended for inclusion in an updated version of the QLQ-STO22 and covered by five additional questions. CONCLUSIONS: This study supports the content validity of the QLQ-STO22, suggesting its continued relevance to patients with GC, including those from East Asia. The updated version with additional questions and linguistic changes will enhance its specificity, but further testing is required.


Asunto(s)
Calidad de Vida , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/psicología , Neoplasias Gástricas/terapia , Femenino , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Anciano , Comparación Transcultural , Adulto
2.
Niger J Clin Pract ; 25(3): 255-260, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35295045

RESUMEN

Aims and Background: This study evaluated the effect of C-factor on the bond strength of a resin composite to floor and wall dentin using various adhesive systems. Materials and Methods: Four dentin substrates (flat wall, flat floor, cavity wall, or cavity floor) were prepared on human molars. Each specimen was restored with one of three adhesives; Clearfil SE Bond, Single Bond, or Clearfil tri-S Bond followed by buildup or filling using Z100 resin composite. The specimen was cut perpendicular to the bonded surface parallel to the floor or wall to obtain beams after light curing at 24,000 mJ/cm2. The microtensile bond strength to wall specimens or the cavity floor was determined. Data were analyzed. Results: All adhesive systems exhibited the highest bond strength to flat wall group (p < 0.05). The bond strength to the cavity group was significantly lower than that to the respective flat group regardless of the bonding system (p < 0.05). There was no significant difference in bond strength with Clearfil SE Bond and Clearfil tri-S Bond between the cavity wall and cavity floor (p > 0.05). Conclusion: The findings suggested that the strength of bonding to the cavity floor and cavity wall was affected by C-factor regardless of the adhesive system. Bonding to flat wall was higher than flat floor regardless of the adhesive system. Self-etching system provided uniform bond to the cavity wall and cavity floor dentin. However, total etching system reduced bond to the cavity floor than to the cavity wall.


Asunto(s)
Adhesivos , Recubrimientos Dentinarios , Dentina , Humanos , Ensayo de Materiales , Resistencia a la Tracción
3.
Clin Exp Immunol ; 202(3): 308-320, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32880930

RESUMEN

Although increasing evidence demonstrates the association between intestinal dysbiosis and pancreatic diseases such as chronic pancreatitis and pancreatic cancer, it remains largely unknown whether intestinal dysbiosis is involved in the immunopathogenesis of autoimmune pancreatitis (AIP). Recently, we found that intestinal dysbiosis mediates experimental AIP via the activation of plasmacytoid dendritic cells (pDCs), which can produce interferon (IFN)-α and interleukin (IL)-33. However, candidate intestinal bacteria, which promote the development of AIP, have not been identified. Fecal samples were obtained from type 1 AIP patients before and after prednisolone (PSL) treatment and subjected to 16S ribosomal RNA sequencing to evaluate the composition of intestinal bacteria. Induction of remission by PSL was associated with the complete disappearance of Klebsiella species from feces in two of the three analyzed patients with type 1 AIP. To assess the pathogenicity of Klebsiella species, mild experimental AIP was induced in MRL/MpJ mice by repeated injections of 10 µg of polyinosinic-polycytidylic acid [poly(I:C)], in combination with oral administration of heat-killed Klebsiella pneumoniae. The AIP pathology score was significantly higher in MRL/MpJ mice that received both oral administration of heat-killed K. pneumoniae and intraperitoneal injections of poly(I:C) than in those administered either agent alone. Pancreatic accumulation of pDCs capable of producing large amounts of IFN-α and IL-33 was also significantly higher in mice that received both treatments. These data suggest that intestinal colonization by K. pneumoniae may play an intensifying role in the development of type 1 AIP.


Asunto(s)
Pancreatitis Autoinmune , Microbioma Gastrointestinal , Klebsiella pneumoniae/inmunología , Prednisolona/farmacología , Animales , Pancreatitis Autoinmune/inmunología , Pancreatitis Autoinmune/microbiología , Células Dendríticas/inmunología , Modelos Animales de Enfermedad , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/inmunología , Humanos , Interferón-alfa/inmunología , Interleucina-33/inmunología , Masculino , Inducción de Remisión
4.
Phys Rev Lett ; 124(13): 136404, 2020 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-32302163

RESUMEN

The chiral crystal is characterized by a lack of mirror symmetry and inversion center, resulting in the inequivalent right- and left-handed structures. In the noncentrosymmetric crystal structure, the spin and momentum of electrons are expected to be locked in the reciprocal space with the help of the spin-orbit interaction. To reveal the spin textures of chiral crystals, we investigate the spin and electronic structure in a p-type semiconductor, elemental tellurium, with the simplest chiral structure by using spin- and angle-resolved photoemission spectroscopy. Our data demonstrate that the highest valence band crossing the Fermi level has a spin component parallel to the electron momentum around the Brillouin zone corners. Significantly, we have also confirmed that the spin polarization is reversed in the crystal with the opposite chirality. The results indicate that the spin textures of the right- and left-handed chiral crystals are hedgehoglike, leading to unconventional magnetoelectric effects and nonreciprocal phenomena.

5.
Gastric Cancer ; 23(5): 765-779, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32488651

RESUMEN

BACKGROUND: The literature on the prognostic relevance of signet-ring cell (SRC) histology in gastric cancer (GC) is controversial which is most likely related to inconsistent SRC classification based on haematoxylin-eosin staining. We hypothesised that mucin stains can consistently identify SRC-GC and predict GC patient outcome. METHODS: We performed a comprehensive literature review on mucin stains in SRC-GC and characterised the mucin expression in 851 Caucasian GC and 410 Asian GC using Alcian Blue (AB)-Periodic Acid-Schiff (PAS), MUC2 (intestinal-type mucin), and MUC5AC (gastric-type mucin). The relationship between mucin expression and histological phenotype [poorly cohesive (PC) including proportion of SRCs, non-poorly cohesive (non-PC), or mucinous (MC)], clinicopathological variables, and patient outcome was analysed. RESULTS: Depending on mucin expression and cut-offs, the positivity rates of SRC-GC reported in the literature varied from 6 to 100%. Patients with MUC2 positive SRC-GC or SRC-GC with (gastro)intestinal phenotype had poorest outcome. In our cohort study, PC with ≥ 10% SRCs expressed more frequently MUC2, MUC5AC, and ABPAS (p < 0.001, p = 0.004 and p < 0.001, respectively). Caucasians with AB positive GC or combined ABPAS-MUC2 positive and MUC5AC negative had poorest outcome (all p = 0.002). This association was not seen in Asian patients. CONCLUSIONS: This is the first study to suggest that mucin stains do not help to differentiate between SRC-GC and non-SRC-GC. However, mucin stains appear to be able to identify GC patients with different outcome. To our surprise, the relationship between outcome and mucin expression seems to differ between Caucasian and Asian GC patients which warrants further investigations.


Asunto(s)
Pueblo Asiatico/estadística & datos numéricos , Carcinoma de Células en Anillo de Sello/patología , Neoplasias Esofágicas/patología , Mucina-1/metabolismo , Neoplasias Gástricas/patología , Población Blanca/estadística & datos numéricos , Anciano , Carcinoma de Células en Anillo de Sello/etnología , Carcinoma de Células en Anillo de Sello/metabolismo , Carcinoma de Células en Anillo de Sello/terapia , Estudios de Cohortes , Terapia Combinada , Neoplasias Esofágicas/etnología , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias Gástricas/etnología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/terapia , Tasa de Supervivencia
6.
Mol Psychiatry ; 23(3): 639-647, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-28115744

RESUMEN

Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10-9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (Pbest=5.8 × 10-10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (Pbest=1.9 × 10-9), TRANK1 (Pbest=2.1 × 10-9) and ODZ4 (Pbest=3.3 × 10-9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', Pbest~10-29, R2~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' Pbest~10-13, R2~0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.


Asunto(s)
Trastorno Bipolar/genética , Adulto , Proteínas de Ciclo Celular/genética , Citocinas/genética , delta-5 Desaturasa de Ácido Graso , Ácido Graso Desaturasas/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Humanos , Japón/epidemiología , Masculino , Glicoproteínas de Membrana/genética , Persona de Mediana Edad , Herencia Multifactorial/genética , Factores de Transcripción NFI/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleótido Simple/genética
7.
Mol Psychiatry ; 22(3): 430-440, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27240532

RESUMEN

Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (<100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio=3.04, P=9.3 × 10-9, 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novo CNVs (e.g., MBD5 deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novo CNVs and variable expressivity of CNVs.


Asunto(s)
Esquizofrenia/genética , Adulto , Estudios de Casos y Controles , Hibridación Genómica Comparativa/métodos , Variaciones en el Número de Copia de ADN/genética , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Japón , Masculino , Polimorfismo de Nucleótido Simple/genética
8.
Occup Med (Lond) ; 68(6): 370-377, 2018 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-29897506

RESUMEN

BACKGROUND: Mental disorders and suicide resulting from overwork or work-related stress have become major occupational health issues worldwide, particularly in Asian countries. However, no studies have reported incidence rates of mental disorders and suicide by sex, age group and industry, using a national database containing all cases involving compensation in Asian countries. AIMS: The present study examined incidence rates of occupational mental disorders and suicide by sex, age group and industry using a database containing all cases involving compensation for mental disorders and suicide in Japan over a 5-year period. METHODS: Cases involving compensation for mental disorders and suicide in Japan between January 2010 and March 2015 were analysed. Incidence rates over the 5-year study period were calculated by sex, age group and industry. RESULTS: In total, 1990 cases involving compensation for mental disorders and suicide (619 women and 1371 men) between January 2010 and March 2015 were analysed. The incidence rate involving compensation was higher in employees aged between 30 and 39 years. In men, incidence rates were higher in 'accommodation/eating/drinking services', 'information/communication' and 'scientific research, professional and technical services'. In these industries, incidence rates were particularly high for those aged 29 years or younger. CONCLUSIONS: Our findings highlight the importance of promoting mental health support for younger employees and increasing awareness of their working conditions. Differences in incidence rates by sex, age and industry should be taken into consideration in the development of a national policy and industry- and age-specific preventive measures for overwork-related mental disorders and suicide.


Asunto(s)
Trastornos Mentales/etiología , Suicidio/psicología , Carga de Trabajo/psicología , Carga de Trabajo/normas , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Incidencia , Japón/epidemiología , Masculino , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Salud Laboral , Estrés Laboral/complicaciones , Estrés Laboral/psicología , Suicidio/estadística & datos numéricos
9.
Ann Oncol ; 28(8): 1876-1881, 2017 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-28486692

RESUMEN

BACKGROUND: Neoadjuvant chemotherapy (NAC) is a promising method of improving the survival of resectable gastric cancer. Cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) are both effective against metastatic gastric cancer. This report clarified the impact of these regimens on early endpoints, including the pathological responses, chemotherapy-related toxicities, and surgical results. METHODS: Patients with M0 and either T4 or T3 in case of junctional cancer or scirrhous type received two or four courses of cisplatin (60 mg/m2 at day 8)/S-1 (80 mg/m2 for 21 days with 1 week rest) or docetaxel (40 mg/m2 at day 1)/cisplatin (60 mg/m2 at day 1)/S-1 (80 mg/m2 for 14 days with 2 weeks rest) as NAC. Patients then underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was the 3-year overall survival. RESULTS: Between October 2011 and September 2014, 132 patients were assigned to receive CS (n = 66; 33 in 2 courses and 33 in 4 courses) or DCS (n = 66; 33 in 2 courses and 33 in 4 courses). The respective major grade 3 or 4 hematological toxicities (CS/DCS) were leukocytopenia (14.1%/26.2%), neutropenia (29.7%/47.7%), anemia (14.1%/12.3%), and platelet reduction (3.1%/1.5%). The rate of pathological response, defined as a complete response or < 10% residual cancer remaining, was 19.4% in the CS group and 15.4% in the DCS group, and 15.6% in the two-course group and 19.0% in the 4-course group. The R0 resection rate was 72.7% in the CS group and 81.8% in the DCS group and 80.3% in the two-course group and the 74.2% in the four-course group. No treatment-related deaths were observed. CONCLUSIONS: Our results do not support three-drug therapy with a taxane over two-drug therapy, or any further treatment beyond two cycles as an attractive candidate for the test arm of NAC.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Neoadyuvante , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Cisplatino/administración & dosificación , Docetaxel , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Ácido Oxónico/administración & dosificación , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Taxoides/administración & dosificación , Tegafur/administración & dosificación
10.
Br J Surg ; 104(7): 885-890, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28240355

RESUMEN

BACKGROUND: The outcome for pT1 N+ or pT2-3 N0 gastric cancer is favourable, but some patients suffer from recurrent disease. The aim of this study was to identify prognostic factors in patients with pT1 N+ or pT2-3 N0 gastric cancer. METHODS: This was a multicentre, retrospective cohort study. All patients with pT1 N+ or pT2-3 N0 gastric cancer who underwent curative gastrectomy at five high-volume, specialized cancer centres in Japan between 2000 and 2008 were included. Demographic, clinical, surgical and pathological data were collected. Independent prognostic factors were identified using a Cox proportional hazards regression model. RESULTS: Some 1442 patients were included. The 5-year overall survival rate for patients with pT1 N+ or pT2-3 N0 gastric cancer was 92·0 per cent. Multivariable analysis for overall survival identified age (hazard ratio (HR) 2·67, 95 per cent c.i. 2·09 to 3·43), sex (HR 0·57, 0·39 to 0·83) and clinical tumour depth (cT) (HR 1·45, 1·06 to 1·98) as independent prognostic factors. CONCLUSION: Survival of patients with pT1 N+ or pT2-3 N0 gastric cancer is good. Age 65 years or above, male sex and cT2-4 category are associated with worse overall survival.


Asunto(s)
Neoplasias Gástricas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Gastrectomía , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Tasa de Supervivencia
11.
Br J Surg ; 104(4): 377-383, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28072447

RESUMEN

BACKGROUND: Total gastrectomy for gastric cancer is associated with excessive weight loss and decreased calorie intake. Nutritional support using eicosapentaenoic acid modulates immune function and limits catabolism in patients with advanced cancer, but its impact in the perioperative period is unclear. METHODS: This was a randomized phase III clinical trial of addition of eicosapentaenoic acid-rich nutrition to a standard diet in patients having total gastrectomy for gastric cancer. Patients were randomized to either a standard diet or standard diet with oral supplementation of an eicosapentaenoic acid (ProSure®), comprising 600 kcal with 2·2 g eicosapentaenoic acid, for 7 days before and 21 days after surgery. The primary endpoint was percentage bodyweight loss at 1 and 3 months after surgery. RESULTS: Of 127 eligible patients, 126 were randomized; 124 patients (61 standard diet, 63 supplemented diet) were analysed for safety and 123 (60 standard diet, 63 supplemented diet) for efficacy. Across both groups, all but three patients underwent total gastrectomy with Roux-en-Y reconstruction. Background factors were well balanced between the groups. Median compliance with the supplement in the immunonutrition group was 100 per cent before and 54 per cent after surgery. The surgical morbidity rate was 13 per cent in patients who received a standard diet and 14 per cent among those with a supplemented diet. Median bodyweight loss at 1 month after gastrectomy was 8·7 per cent without dietary supplementation and 8·5 per cent with eicosapentaenoic acid enrichment (P = 0·818, adjusted P = 1·000). Similarly, there was no difference between groups in percentage bodyweight loss at 3 months (P = 0·529, adjusted P = 1·000). CONCLUSION: Immunonutrition based on an eicosapentaenoic acid-enriched oral diet did not reduce bodyweight loss after total gastrectomy for gastric cancer compared with a standard diet. Registration number: UMIN000006380 ( http://www.umin.ac.jp/).


Asunto(s)
Ácido Eicosapentaenoico/administración & dosificación , Gastrectomía/métodos , Neoplasias Gástricas/cirugía , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Peso Corporal , Suplementos Dietéticos , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Laparoscopía/métodos , Masculino , Persona de Mediana Edad , Apoyo Nutricional/métodos , Atención Perioperativa/métodos , Neoplasias Gástricas/dietoterapia , Adulto Joven
12.
Phys Rev Lett ; 119(7): 077202, 2017 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-28949686

RESUMEN

We demonstrate the generation of alternating spin current (SC) via spin-rotation coupling (SRC) using a surface acoustic wave (SAW) in a Cu film. Ferromagnetic resonance caused by injecting SAWs was observed in a Ni-Fe film attached to a Cu film, with the resonance further found to be suppressed through the insertion of a SiO_{2} film into the interface. The intensity of the resonance depended on the angle between the wave vector of the SAW and the magnetization of the Ni-Fe film. This angular dependence is explicable in terms of the presence of spin transfer torque from a SC generated via SRC.

13.
Mol Psychiatry ; 21(11): 1504-1510, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-26782057

RESUMEN

Although evidence for mitochondrial dysfunction in the pathogenesis of bipolar disorder (BD) has been reported, the precise biological basis remains unknown, hampering the search for novel biomarkers. In this study, we performed metabolomics of cerebrospinal fluid (CSF) from male BD patients (n=54) and age-matched male healthy controls (n=40). Subsequently, post-mortem brain analyses, genetic analyses, metabolomics of CSF samples from rats treated with lithium or valproic acid were also performed. After multivariate logistic regression, isocitric acid (isocitrate) levels were significantly higher in the CSF from BD patients than healthy controls. Furthermore, gene expression of two subtypes (IDH3A and IDH3B) of isocitrate dehydrogenase (IDH) in the dorsolateral prefrontal cortex from BD patients was significantly lower than that of controls, although the expression of other genes including, aconitase (ACO1, ACO2), IDH1, IDH2 and IDH3G, were not altered. Moreover, protein expression of IDH3A in the cerebellum from BD patients was higher than that of controls. Genetic analyses showed that IDH genes (IDH1, IDH2, IDH3A, IDH3B) and ACO genes (ACO1, ACO2) were not associated with BD. Chronic (4 weeks) treatment with lithium or valproic acid in rats did not alter CSF levels of isocitrate, and mRNA levels of Idh3a, Idh3b, Aco1 and Aco2 genes in the rat brain. These findings suggest that abnormality in the metabolism of isocitrate by IDH3A in the mitochondria plays a key role in the pathogenesis of BD, supporting the mitochondrial dysfunction hypothesis of BD. Therefore, IDH3 in the citric acid cycle could potentially be a novel therapeutic target for BD.


Asunto(s)
Trastorno Bipolar/metabolismo , Isocitrato Deshidrogenasa/metabolismo , Adulto , Animales , Trastorno Bipolar/líquido cefalorraquídeo , Encéfalo/metabolismo , Expresión Génica/genética , Humanos , Isocitrato Deshidrogenasa/líquido cefalorraquídeo , Isocitratos/metabolismo , Masculino , Metabolómica/métodos , Mitocondrias/metabolismo , Ratas
14.
Cell Mol Biol (Noisy-le-grand) ; 62(6): 27-32, 2016 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-27262798

RESUMEN

The purpose of this study was to clarify the precise effect of argatroban on the inhibition of cytokine secretion induced by thrombin on synovial cells. The efficiency of thrombin inactivation by thrombin inhibitors was evaluated in human synovial fluids (SFs). In SFs from 13 osteoarthritis (OA) and 11 rheumatoid arthritis (RA) patients, thrombin, Factor Xa (FXa), plasmin activity, IL-6, MMP-3, VEGF, and D-dimer concentrations were measured. Tissue factor (TF) activity or IL-6, MMP-3, and VEGF secretion of human synovial cells with or without thrombin and argatroban were measured. The efficiency of thrombin inactivation in SFs was compared for thrombin inhibitors: argatroban, antithrombin III (ATIII), or heparin cofactor II (HCII). In SFs, thrombin, FXa, plasmin, D-dimer, IL-6, and MMP-3 were significantly higher in RA than in OA. In synovial cell experiments, TNF-alpha and thrombin enhanced TF activity on the cell surface, and IL-6, MMP-3, and VEGF secretion were enhanced by thrombin. Increased TF activity, and IL-6, MMP-3, and VEGF secretion induced by thrombin were inhibited by argatroban. In SFs, argatroban inactivated thrombin more effectively than ATIII or HCII. Since thrombin plays an important role in the disease activity of OA and RA, it is a potential therapeutic molecular target. Argatroban was the most effective anticoagulant to inhibit thrombin activity in SF. Intra-articular injection is ideal administration because it can deliver high dose of argatroban without high risk of systematic complication.


Asunto(s)
Antitrombinas/farmacología , Ácidos Pipecólicos/farmacología , Líquido Sinovial/metabolismo , Trombina/farmacología , Anciano , Anciano de 80 o más Años , Arginina/análogos & derivados , Coagulación Sanguínea/efectos de los fármacos , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Sulfonamidas , Líquido Sinovial/efectos de los fármacos , Tromboplastina/metabolismo
15.
Ann Surg Oncol ; 22(7): 2317-22, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25752893

RESUMEN

BACKGROUND: Clinical T1 gastric cancer has low metastatic potential to lymph nodes and is generally curable by local treatment. Endoscopic resection can preserve the whole stomach and does not impair the patient's quality of life; however, its indication is strictly limited to the subset of patients without nodal metastasis. The study was designed to predict reliably the patients without nodal metastasis based only on the clinical information. METHODS: We examined patients with clinical T1 disease who were treated with surgery. The clinically available information was evaluated for its ability to predict nodal metastasis by logistic regression model. Then, the predictive ability of the logistic regression model using the risk factors for nodal metastasis was evaluated by a receiver operating characteristic curve. RESULTS: A total of 511 patients were entered into this study. The clinical depth (cT1a or cT1b), maximal tumor diameter, and pathological type were confirmed to be significantly different between patients with and without nodal metastasis. The cutoff value of the tumor diameter differed depending on the histology and clinical depth: 79 mm for differentiated type and 48 mm for undifferentiated type in cT1a tumors, and 43 mm for differentiated type and 11 mm for undifferentiated type in cT1b tumors. According to these criteria, 348 of the 511 patients (68.1 %) were classified to have predictive N0 status. The negative predictive value was 95.7 % (95 % confidence interval 94.0-97.5 %). CONCLUSIONS: The predictive criteria based on the multivariate logistic model identified that almost two-thirds of the patients with clinical T1 gastric cancer were possible candidates for endoscopic treatment.


Asunto(s)
Adenocarcinoma/cirugía , Endoscopía , Gastrectomía , Modelos Estadísticos , Calidad de Vida , Neoplasias Gástricas/cirugía , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Curva ROC , Factores de Riesgo , Neoplasias Gástricas/patología
16.
Br J Surg ; 102(4): 341-8, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25605628

RESUMEN

BACKGROUND: The optimal surgical approach for treatment of oesophagogastric junction (OGJ) cancer is controversial. A randomized clinical trial (JCOG9502) comparing transhiatal (TH) and left thoracoabdominal (LTA) approaches was stopped after the first interim analysis owing to limited efficacy for LTA resections. Complete 10-year follow-up data are now available. METHODS: Patients with histologically proven adenocarcinoma of the OGJ or gastric cardia with oesophageal invasion of 3 cm or less were randomized to a TH or LTA approach. Both groups underwent total gastrectomy and splenectomy with D2 nodal dissection plus para-aortic lymphadenectomy above the left renal vein. For LTA, a thorough mediastinal lymphadenectomy below the left inferior pulmonary vein was also mandatory. The primary endpoint was overall survival. RESULTS: A total of 167 patients (82 TH, 85 LTA) were enrolled. The 10-year overall survival rate was 37 (95 per cent c.i. 26 to 47) per cent for the TH approach and 24 (15 to 34) per cent for the LTA technique (P = 0·060). The hazard ratio for death was 1·42 (0·98 to 2·05) for the LTA technique. Subgroup analysis based on the Siewert classification indicated non-significant survival advantages in favour of the TH approach. CONCLUSION: LTA resections should be avoided in the treatment of adenocarcinoma of the OGJ or gastric cardia. REGISTRATION NUMBER: NCT00149266 (https://www.clinicaltrials.gov).


Asunto(s)
Adenocarcinoma/cirugía , Cardias/cirugía , Neoplasias Esofágicas/cirugía , Unión Esofagogástrica/cirugía , Gastrectomía/métodos , Neoplasias Gástricas/cirugía , Adenocarcinoma/mortalidad , Adulto , Anciano , Terminación Anticipada de los Ensayos Clínicos , Neoplasias Esofágicas/mortalidad , Femenino , Estudios de Seguimiento , Gastrectomía/mortalidad , Humanos , Estimación de Kaplan-Meier , Escisión del Ganglio Linfático/métodos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/etiología , Estudios Prospectivos , Neoplasias Gástricas/mortalidad , Resultado del Tratamiento
17.
Vox Sang ; 109(4): 417-9, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26031768

RESUMEN

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tickborne virus in the Bunyaviridae family. This virus has recently been found in China, Japan and Korea. The risk of transfusion-transmitted SFTSV infection (TTI-SFTSV) is a concern because person-to-person transmission resulting from contact with SFTSV-contaminated blood has been reported. Therefore, we investigated the efficacy of the Mirasol pathogen reduction technology (PRT) system for inactivating SFTSV in vitro. The Mirasol PRT system achieved a > 4.11 log10 reduction value (LRV) for SFTSV. In conclusion, we showed that the Mirasol PRT system could potentially be used to reduce the risk of TTI-SFTSV.


Asunto(s)
Seguridad de la Sangre/métodos , Phlebovirus/efectos de los fármacos , Antivirales/farmacología , Seguridad de la Sangre/instrumentación , Humanos , Phlebovirus/efectos de la radiación , Rayos Ultravioleta
18.
Transpl Infect Dis ; 17(5): 728-31, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26176562

RESUMEN

We analyzed 3 hematopoietic stem cell transplant (HSCT) recipients with inherited chromosomally integrated human herpesvirus-6 (inherited CIHHV-6). Cases 1 (inherited CIHHV-6A) and 2 (inherited CIHHV-6B) were inherited CIHHV-6 recipients. Case 3 received bone marrow from a donor with inherited CIHHV-6B. Following HSCT, HHV-6B was isolated from Case 1. HHV-6A and -6B messenger RNAs were detected in Cases 1 and 3.


Asunto(s)
ADN Viral/aislamiento & purificación , Trasplante de Células Madre Hematopoyéticas , Herpesvirus Humano 6/genética , Integración Viral , Niño , Preescolar , Femenino , Herpesvirus Humano 6/aislamiento & purificación , Humanos , Masculino , Adulto Joven
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