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1.
Blood Adv ; 4(6): 1062-1071, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32196559

RESUMO

Adult T-cell leukemia/lymphoma (ATL) is a human T-cell leukemia virus type 1 (HTLV-1)-associated T-cell malignancy with generally poor prognosis. Although only ∼5% of HTLV-1 carriers progress to ATL, early diagnosis is challenging because of the lack of ATL biomarkers. In this study, we analyzed blood plasma profiles of asymptomatic HTLV-1 carriers (ACs); untreated ATL patients, including acute, lymphoma, smoldering, and chronic types; and ATL patients in remission. Through SOMAscan, expression levels of 1305 plasma proteins were analyzed in 85 samples (AC, n = 40; ATL, n = 40; remission, n = 5). Using gene set enrichment analysis and gene ontology, overrepresented pathways in ATL vs AC included angiogenesis, inflammation by cytokines and chemokines, interleukin-6 (IL-6)/JAK/STAT3, and notch signaling. In selecting candidate biomarkers, we focused on soluble tumor necrosis factor 2 (sTNFR2) because of its active role in enriched pathways, extreme significance (Welch's t test P < .00001), high discrimination capacity (area under the curve >0.90), and novelty in ATL research. Quantification of sTNFR2 in 102 plasma samples (AC, n = 30; ATL, n = 68; remission, n = 4) using enzyme-linked immunosorbent assay showed remarkable elevations in acute ATL, at least 10 times those of AC samples, and return of sTNFR2 to AC state levels after achieving remission. Flow cytometry and immunostaining validated the expression of TNFR2 in ATL cells. No correlation between sIL-2 and sTNFR2 levels in acute ATL was found, suggesting the possibility of sTNFR2 as an independent biomarker. Our findings represent the first extensive blood-based proteomic analysis of ATL, suggesting the potential clinical utility of sTNFR2 in diagnosing acute ATL.

2.
Circ J ; 84(2): 203-216, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31956209

RESUMO

BACKGROUND: Although full-volume quantification of epicardial adipose tissue (EAT) is a predictor of LV diastolic dysfunction (LVDD), how localized EAT depots are linked to LVDD remains unclear. We evaluated the effect of local EAT depots on LV diastolic function parameters in patients with preserved LV ejection fraction (LVEF).Methods and Results:From 423 consecutive patients who underwent cardiac CT angiography, we recruited 252 with sinus rhythm and normal LVEF. The EAT volume index (EATV/body surface area) and the localized EAT thickness around the right coronary artery (EATRCA), left anterior descending artery (EATLAD), left circumflex artery (EATLCX), right ventricle (EATRV), left ventricle (EATLV), right atrium (EATRA), and left atrium (EATLA) were measured using cardiac CT. In the LVDD group (n=71), the EATV index (75±30 vs. 64±28 mL/m2, P=0.010), EATLCX(10.7±3.8 vs. 9.4±3.4 mm, P=0.008), and EATLV(2.6±1.6 vs. 2.1±1.4 mm, P=0.024) were greater than in the non-LVDD group (n=181). In contrast, EATLCXand EATLVwere markedly associated with decreased lateral e' and increased lateral E/e'. Multiple regression analysis indicated that EATLCXand EATLVwere strongly associated with LV diastolic function parameters. CONCLUSIONS: Localized EAT depots are linked to altered mitral annular motion. Further study is warranted to clarify whether localized EAT depots are functionally linked to the clinical manifestations of LVDD.

3.
Intern Med ; 59(2): 247-252, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31941871

RESUMO

Studies reporting chest images of respiratory syncytial virus (RSV)-induced lower respiratory tract infection (LRTI) in an outbreak setting and their relationship to the clinical manifestation are limited. During a genetically confirmed RSV outbreak, eight patients underwent both chest X-ray and computed tomography (CT). Among these, 5 cases had newly appearing abnormalities on CT, although chest X-ray was able to detect abnormalities in only 2 cases (40%). Although bronchial wall thickening was common, other findings and their distribution were variable, even in an outbreak setting. All patients with both a history of anticancer chemotherapy against hematological cancer and lower respiratory symptoms, such as wheezing, sputum, and hypoxemia, had abnormalities on CT, suggesting that these two factors might be important for predicting the existence of LRTI in RSV-infected patients.


Assuntos
Infecções por Vírus Respiratório Sincicial/diagnóstico por imagem , Infecções Respiratórias/diagnóstico por imagem , Idoso , Surtos de Doenças , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Sons Respiratórios , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções Respiratórias/epidemiologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Adulto Jovem
4.
Bone Marrow Transplant ; 55(1): 233-241, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31534195

RESUMO

Outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with adult T cell leukemia/lymphoma (ATL) are not satisfactory, particularly in patients in non-complete remission at transplantation (Pt-non-CR). We conducted a regional retrospective study in the ATL endemic area of Okinawa, Japan. Of 62 ATL patients, 21 received allo-HSCT in CR and 41 in non-CR. The 3-year overall survival (3yOS) rate and median survival time for the whole cohort was 25.6% and 7.7 months, respectively. The 3yOS of Pt-non-CR was significantly lower than that of patients in CR (Pt-CR) (16.8% vs. 43.6%, P = 0.005). Transplant-related mortality (TRM) was significantly higher in Pt-non-CR than in Pt-CR (46.3% vs. 15.7%, P = 0.025), while there was no significant difference in disease-associated mortality (DAM) between Pt-non-CR and Pt-CR. Multivariable analysis for Pt-non-CR revealed that poor performance status (poor-PS) and higher sIL-2R level (high sIL-2R) adversely affected OS. Poor-PS was associated with higher TRM, but not with higher DAM in Pt-non-CR. High sIL-2R did not affect TRM or DAM in Pt-non-CR. Overall, high TRM rates rather than DAM contribute to the poor outcomes of Pt-non-CR, suggesting that not only disease control but also management of transplant-related complications is required for allo-HSCT in ATL patients.

5.
Neurosci Lett ; 714: 134550, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31634502

RESUMO

BACKGROUND: Cannabinoid receptor 1 (CB1R) is a GPCR expressed widely in the brain as well as in peripheral metabolic organs. Although pharmacological blockade of CB1R has been effective for the treatment of obesity and tobacco addiction, precise distribution of CB1R within the brain and potential changes by obesity or nicotine exposure have not been thoroughly addressed. METHODS: To examine CB1R distribution within the central energy center, we performed immunostaining and qPCR analysis of micro-dissected hypothalamic nuclei from male C57BL/6 mice. To address the effect of nicotine on food intake and body weight, and on potential changes of CB1R levels in the hypothalamus, mice kept on a high fat diet (HFD) for four weeks were challenged with nicotine intraperitoneally. RESULTS: Validity of the micro-dissected samples was confirmed by the expression of established nucleus-enriched genes. The expression levels of CB1R in the arcuate and lateral nuclei of the hypothalamus were higher than paraventricular and ventral-dorsal medial nuclei. Nicotine administration led to a significant suppression of food intake and body weight either under standard or high fat diet. Neither HFD nor nicotine alone altered CB1R levels in any nucleus tested. By contrast, treatment of HFD-fed mice with nicotine led to a significant increase in CB1R levels in the arcuate, paraventricular and lateral nuclei. CONCLUSIONS: CB1R was widely distributed in multiple hypothalamic nuclei. The expression of CB1R was augmented only when mice were treated with HFD and nicotine in combination. These data suggest that the exposure to nicotine may provoke an enhanced endocannabinoid response in diet-induced obesity.

6.
Eur J Nutr ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506767

RESUMO

PURPOSE: Extra virgin olive oil (EVOO) and flaxseed oil (FO) contain a variety of constituents beneficial for chronic inflammation and cardio-metabolic derangement. However, little is known about the impact of EVOO and FO on dysbiosis of gut microbiota, intestinal immunity, and barrier. We, therefore, aimed to assess the impact of EVOO and FO on gut microbiota, mucosal immunity, barrier integrity, and metabolic health in mice. METHODS: C57BL/6 J mice were exposed to a low-fat (LF), lard (HF), high fat-extra virgin olive oil (HF-EVOO), or high fat-flaxseed oil (HF-FO) diet for 10 weeks. Gut microbiota assessment was undertaken using 16S rRNA sequencing. Levels of mRNA for genes involved in intestinal inflammation and barrier maintenance in the intestine and bacterial infiltration in the liver were measured by qPCR. RESULTS: HF-EVOO or HF-FO mice showed greater diversity in gut microbiota as well as a lower abundance of the Firmicutes phylum in comparison with HF mice (P < 0.05). The qPCR analyses revealed that mRNA level of FoxP3, a transcription factor, and IL-10, an inducer of regulatory T cells, was significantly elevated in the intestines of mice-fed HF-EVOO in comparison with mice-fed HF (P < 0.05). The mRNA level of the antimicrobial peptide, RegӀӀӀγ, was markedly elevated in the intestines of HF-EVOO and HF-FO compared with HF group (P < 0.05). CONCLUSIONS: Our data suggest that the consumption of EVOO or FO can beneficially impact gut microbiota, enhance gut immunity, and assist in the preservation of metabolic health in mice.

8.
Cancer Sci ; 110(9): 2982-2991, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31237072

RESUMO

Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell neoplasm, and is divided into 2 indolent (smoldering and chronic) and 2 aggressive (acute and lymphoma) clinical subtypes. Based on previous integrated molecular analyses suggesting the importance of the JAK-STAT pathway in ATLL, we attempted to clarify the clinicopathological significance of this pathway. Clinical and morphological findings were reviewed in 116 cases with ATLL. The nuclear localizations of phosphorylated STAT3 (pSTAT3), pSTAT5, and pSTAT6 were analyzed by immunohistochemistry. Targeted sequencing was undertaken on the portion of STAT3 encoding the Src homology 2 domain. Expression of pSTAT3 was observed in 43% (50/116) of ATLL cases, whereas pSTAT5 and pSTAT6 were largely undetected. Cases with the lymphoma type showed significantly less frequent pSTAT3 expression (8/45, 18%) than those with the other subtypes (41/66, 62%; P < .001). STAT3 mutations were detected in 36% (10/28) and 19% (12/64) of cases with the smoldering and aggressive types of ATLL, respectively. The correlation between STAT3 mutation and pSTAT3 expression was not significant (P = .07). Both univariate and multivariate analysis revealed that pSTAT3 expression was significantly associated with better overall survival and progression-free survival in the smoldering type of ATLL, whereas STAT3 mutation was not related to a line of clinical outcome. Collectively, our data show that only the lymphoma type showed a low prevalence of tumor cells positive for pSTAT3 expression, and raises the possibility that pSTAT3 expression is a novel biomarker to predict better prognosis in the smoldering type of ATLL.


Assuntos
Leucemia-Linfoma de Células T do Adulto/patologia , Fator de Transcrição STAT3/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Núcleo Celular/patologia , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Fosforilação , Prognóstico , Intervalo Livre de Progressão , Fator de Transcrição STAT3/genética
9.
Transpl Immunol ; 55: 101205, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30946889

RESUMO

Graft-versus-host disease (GVHD) constitutes the most frequent complications after the allogeneic hematopoietic stem cell transplantation for a variety of hematological malignancies. In the present study, we explored the prophylactic potential of adipose tissue-derived mesenchymal stem cells (AD-MSCs) in controlling GVHD in murine models with a special focus on bone marrow aplasia related with acute GVHD. The CB6F1 mice were induced GVHD by the injection intravenously of C57BL/6 (B6-Ly-5.1) splenocytes without conditioning irradiation or chemotherapy. AD-MSCs from C3H mice were injected intravenously via tail veins. GVHD was assessed using flowcytometry analysis of peripheral blood cells and histopathologic analysis of target organs. Histopathological analyses revealed that AD-MSCs markedly suppressed the infiltration of lymphocytes into liver as well as the aplasia in bone marrow. This study is the first to clarify the effectiveness of AD-MSCs against bone marrow aplasia in GVHD, supporting a rationale of AD-MSCs for ameliorating bone marrow suppression and infectivity after allo-HSCT in human clinics.


Assuntos
Doenças da Medula Óssea , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Tecido Adiposo , Aloenxertos , Animais , Doenças da Medula Óssea/etiologia , Doenças da Medula Óssea/imunologia , Doenças da Medula Óssea/patologia , Doenças da Medula Óssea/terapia , Modelos Animais de Doenças , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/terapia , Células-Tronco Mesenquimais/patologia , Camundongos
10.
Neurourol Urodyn ; 38(4): 1106-1110, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30848839

RESUMO

AIM: To validate a novel digital health monitoring system to measure the volume of voided urine. METHODS: Micturition volume was calculated using our novel digital self-health monitoring system of urine excretion (s-HMSU) in 18 participants (16 women and 2 men; average age, 40.8 years), without a history of voiding symptoms. Participants completed a self-reported questionnaire regarding their medical history and water intake during the period of observation, as well as the Core Lower Urinary Tract Symptom Score (CLSS) questionnaire. To assess the reliability of the voided volumes measured using the s-HMSU, the intraclass correlation coefficient (ICC) was calculated between the volume and the change in body weight before and after micturition. RESULTS: The CLSS questionnaire confirmed the absence of urinary system diseases in all participants. The medical history was also negative with the exception of hypertension in one participant. The ICC (1,1) between the measured volume of urine excretion using the s-HMSU and the change in body weight was 0.972 (95% confidence interval, 0.957-0.982). CONCLUSIONS: The s-HMSU system provides a reliable measure of voiding volume and is appropriate for home use. It has the potential to facilitate large-scale clinical research to examine the relationship between medical diseases and voiding dysfunction.


Assuntos
Sintomas do Trato Urinário Inferior/diagnóstico , Bexiga Urinária/fisiologia , Micção/fisiologia , Adulto , Testes Diagnósticos de Rotina , Feminino , Humanos , Sintomas do Trato Urinário Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Inquéritos e Questionários , Urina
11.
J Diabetes Investig ; 10(1): 94-103, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29862667

RESUMO

AIMS/INTRODUCTION: There is controversy as to whether hyperuricemia is an independent risk factor for cardiometabolic diseases. The serum level of uric acid is affected by a wide variety of factors involved in its production and excretion. In contrast, evidence has accumulated that locally- and systemically-activated xanthine oxidase (XO), a rate-limiting enzyme for production of uric acid, is linked to metabolic derangement in humans and rodents. We therefore explored the clinical implication of plasma XO activity in patients with type 2 diabetes mellitus and metabolic syndrome (MetS). MATERIALS AND METHODS: We enrolled 60 patients with type 2 diabetes mellitus and MetS. MetS was defined according to the 2005 International Diabetes Federation guidelines. Plasma XO activity was measured by highly-sensitive fluorometric assay measuring the conversion of pterin to isoxanthopterin, and explored associations between the value of plasma XO activity and metabolic parameters. RESULTS: The value of plasma XO activity was correlated with indices of insulin resistance and the level of circulating liver transaminases. In contrast, the level of serum uric acid was not correlated with indices of insulin resistance. The value of plasma XO activity was not correlated with the serum uric acid level. CONCLUSIONS: Plasma XO activity correlates with indices of insulin resistance and liver dysfunction in Japanese patients with type 2 diabetes mellitus and MetS. Through assessing the plasma XO activity, patients showing normal levels of serum uric acid with higher activity of XO can be screened, thereby possibly providing a clue to uncovering metabolic risks in type 2 diabetes mellitus and MetS patients.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Resistência à Insulina , Hepatopatias/sangue , Síndrome Metabólica/sangue , Xantina Oxidase/sangue , Adulto , Idoso , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Hepatopatias/complicações , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Risco , Adulto Jovem
12.
Jpn J Clin Oncol ; 49(2): 153-159, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30452692

RESUMO

Background: Cutaneous adverse reactions are frequently induced by mogamulizumab. Cases of Stevens-Johnson syndrome, toxic epidermal necrolysis and severe photosensitivity related to mogamulizumab have been reported. This study investigated whether severe radiation-induced dermatitis occurred in patients undergoing radiotherapy after the administration of mogamulizumab for adult T-cell leukaemia/lymphoma. Methods: We retrospectively reviewed 46 courses of radiotherapy administered to 15 consecutive patients with adult T-cell leukaemia/lymphoma (acute, n = 7; lymphoma, n = 7; smouldering, n = 1) who received mogamulizumab before or during radiotherapy at three institutions between 2012 and 2017. Results: During 43 of the 46 radiotherapy courses, patients developed Grade ≤1 radiation-induced dermatitis. No patient developed Grade ≥3 radiation-induced dermatitis. No patient was prescribed ointments as prophylactic treatment for radiation-induced dermatitis. Development of radiation-induced dermatitis was not significantly associated with the number of days since the administration of mogamulizumab prior to radiotherapy (P = 0.85), frequency of administration of mogamulizumab before/during radiotherapy (P = 0.33), administration of mogamulizumab during radiotherapy (P = 0.41) or types of lesions in adult T-cell leukaemia/lymphoma cases (cutaneous vs. non-cutaneous, P = 0.74). Development of radiation-induced dermatitis was significantly related to the total cutaneous dose (mean, 31.9 Gy [95% confidence interval: 26.6-37.1 Gy] vs. 19.7 Gy [95% confidence interval: 16.2-23.2 Gy], P = 0.0004) and total prescribed dose (mean, 31.5 Gy [95% confidence interval: 26.2-36.8 Gy] vs. 18.5 Gy [95% confidence interval: 15.0-22.0 Gy], P = 0.0002). Conclusion: None of the 15 patients who received moderate-dose radiotherapy developed severe radiation-induced dermatitis during the 46 courses of radiotherapy after mogamulizumab administration.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Radiodermatite/induzido quimicamente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/radioterapia , Masculino , Pessoa de Meia-Idade , Radiodermatite/diagnóstico por imagem , Estudos Retrospectivos , Pele/patologia , Pele/efeitos da radiação , Análise de Sobrevida
13.
J Diabetes Investig ; 10(1): 18-25, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29978570

RESUMO

Chronic overconsumption of animal fats causes a variety of health problems, including diabetes mellitus and obesity. Underlying molecular mechanisms encompass leptin resistance, a decrease in rewarding effects of physical activities, xanthine oxidase-induced oxidative stress in vasculature and peripheral tissue, impaired activation of incretin signaling, deviation in food preference, and dysbiosis of gut microbiota. Based on our clinical observation that daily intake of brown rice effectively ameliorates bodyweight gain, impaired glucose tolerance/insulin resistance and dependence on fatty foods in obese, prediabetes men, a line of research on brown rice (rice bran)-derived γ-oryzanol in mice experiments, cultured cells and human clinical trials is underway in our laboratory. Our works in mice showed that γ-oryzanol, an ester mixture of ferulic acid and several kinds of phytosterols, acts as a molecular chaperone, thereby attenuating the strong preference for animal fats through suppression of endoplasmic reticulum stress in the hypothalamus. In pancreatic islets from both high-fat diet-induced and streptozotocin-induced diabetic mice, γ-oryzanol ameliorates endoplasmic reticulum stress and protects ß-cells against apoptosis. Noticeably, γ-oryzanol also acts as a potent inhibitor against deoxyribonucleic acid methyltransferases in the brain reward system (striatum) in mice, thereby attenuating, at least partly, the preference for a high-fat diet through the epigenetic modulation of striatal dopamine D2 receptor. Because dopamine D2 receptor signaling in the brain reward system is considerably attenuated in obese humans and rodents, γ-oryzanol might represent a unique property to ameliorate both hedonic and metabolic dysregulation of feeding behavior, highlighting a promising prophylactic avenue to protect against metabolic derangement.


Assuntos
Diabetes Mellitus/metabolismo , Obesidade/metabolismo , Fenilpropionatos/metabolismo , Animais , Dieta Hiperlipídica , Estresse do Retículo Endoplasmático , Humanos , Hipotálamo/metabolismo , Ilhotas Pancreáticas/metabolismo , Oryza , Fenilpropionatos/administração & dosagem , Recompensa
14.
J Radiat Res ; 60(1): 98-108, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30124892

RESUMO

Adult T-cell leukemia/lymphoma (ATL) is an aggressive peripheral T-cell neoplasm that occurs only in patients with human T-cell leukemia virus type 1. No large study or randomized trial investigating radiotherapy (RT) for ATL has been performed. We retrospectively reviewed 55 courses of RT for 41 consecutive patients with ATL who underwent RT between 2000 and 2016 at our institutions. The results showed that RT for local ATL lesions can achieve symptomatic improvement in 92% of cases. Local remission, either complete remission (CR) or partial response (PR), was achieved in 100% of the patients (CR: 89%, PR: 11%) with ≥40 Gy irradiation. CR or PR was achieved in 71% (CR: 29%, PR: 43%) with 30-39 Gy and in 73% (CR: 6.7%, PR: 67%) with ≤29 Gy irradiation. The mean total radiation dose in the CR and PR groups differed significantly (38 vs 25 Gy, P = 0.0002). The maximum acute toxicity was Grade 0-2 in all patients, except for one patient experienced Grade 3 radiation dermatitis. In-field relapses occurred in 36% of patients, and the frequency of in-field relapses was 11%, 30% and 71% among those who achieved CR, PR and SD, respectively. All 9 patients who received total skin irradiation experienced cutaneous relapses, with a median of 63 days (range, 7-210 days). Almost all (39 of 41) patients with ATL experienced out-of-field progression after RT. In conclusion, RT was confirmed to be effective and safe for palliative treatment of local ATL lesions.


Assuntos
Leucemia-Linfoma de Células T do Adulto/radioterapia , Dosagem Radioterapêutica , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta à Radiação , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Resultado do Tratamento
15.
Am J Cardiol ; 122(10): 1694-1700, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30244845

RESUMO

Although increasing evidence suggests that epicardial adipose tissue volume (EATV) is associated with post-ablation atrial fibrillation (AF), ranges of EATV predictive of post-ablation recurrence of AF remain unclear. In this study, we evaluated: (1) relationships between EATV and characteristics of AF, (2) impact of EATV on recurrent AF after radiofrequency ablation; , and (3) cut-off point for recurrent AF using a receiver operating characteristic curve. In 218 consecutive symptomatic patients undergoing who underwent ablation for AF (143 paroxysmal AF; 78 persistent AF), the EATV index (EATVI: EATV/body surface area, mL/m2) was measured using 320-row multidetector computed tomography. The high EATV group showed specific cardiometabolic derangements as well as left atrial dilatation and left ventricular dysfunction. Multivariate regression analysis showed that the EATVI was an independent predictor of recurrent AF after catheter ablation. High EATV (EATVI ≥ 85 mL/m2) or EATVI cutoff ≥116 mL/m2 can predict recurrent AF after catheter ablation, independent of other risk factors. In conclusion, EATVI was an independent predictor of recurrent AF after catheter ablation; a high EATV tertile or EATVI cutoff may be useful for prediction of recurrent AF after catheter ablation. Future studies should determine the utility of the EATVI in the clinical setting of AF ablation.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Fibrilação Atrial/diagnóstico , Ablação por Cateter/métodos , Tomografia Computadorizada Multidetectores/métodos , Pericárdio/diagnóstico por imagem , Idoso , Fibrilação Atrial/cirurgia , Ecocardiografia/métodos , Feminino , Seguimentos , Átrios do Coração/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Recidiva , Estudos Retrospectivos , Fatores de Risco , Função Ventricular Esquerda/fisiologia
16.
Circ J ; 82(7): 1778-1787, 2018 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-29806623

RESUMO

BACKGROUND: Although increasing evidence suggests that epicardial adipose tissue volume (EATV) is associated with atrial fibrillation (AF), it is controversial whether there is a dose-response relationship of increasing EATV along the continuum of AF. We evaluated the effect of the EATV on the prevalence of paroxysmal AF (PAF) and persistent AF (PeAF) and the relationships with cardiac structure and functional remodeling.Methods and Results:Subjects who underwent multidetector computed tomography (MDCT) coronary angiography because of symptoms suggestive of coronary artery disease were divided into sinus rhythm (SR) (n=112), PAF (n=133), and PeAF (n=71) groups. The EATV index (EATV/body surface area, mL/m2) was strongly associated with the prevalence of PAF and PeAF on the model adjusted for known AF risk factors. The effect of the EATV index on the prevalence of PeAF, but not on that of PAF, was modified by the left atrial (LA) dimension, suggesting that extension of the LA dimension is related to EATV expansion in PeAF. The cutoff value of the EATV index for the prevalence was higher in PeAF than in PAF (64 vs. 55 mL/m2, P<0.01). CONCLUSIONS: The EATV index is associated with the prevalence of PAF and PeAF, and its cutoff values are predictive for PAF and PeAF development independently of other AF risk factors.


Assuntos
Tecido Adiposo/patologia , Fibrilação Atrial/etiologia , Pericárdio/citologia , Idoso , Angiografia Coronária/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores/métodos , Obesidade , Prevalência , Estudos Retrospectivos , Fatores de Risco
17.
Cancer Sci ; 109(7): 2286-2293, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29772611

RESUMO

Aggressive adult T-cell leukemia/lymphoma (ATL) has an extremely poor prognosis and is hyperendemic in Okinawa, Japan. This study evaluated two prognostic indices (PIs) for aggressive ATL, the ATL-PI and Japan Clinical Oncology Group (JCOG)-PI, in a cohort from Okinawa. The PIs were originally developed using two different Japanese cohorts that included few patients from Okinawa. The endpoint was overall survival (OS). Multivariable Cox regression analyses in the cohort of 433 patients revealed that all seven factors for calculating each PI were statistically significant prognostic predictors. Three-year OS rates for ATL-PI were 35.9% (low-risk, n = 66), 10.4% (intermediate-risk, n = 256), and 1.6% (high-risk, n = 111), and those for JCOG-PI were 22.4% (moderate-risk, n = 176) and 5.3% (high-risk, n = 257). The JCOG-PI moderate-risk group included both the ATL-PI low- and intermediate-risk groups. ATL-PI more clearly identified the low-risk patient subgroup than JCOG-PI. To evaluate the external validity of the two PIs, we also assessed prognostic discriminability among 159 patients who loosely met the eligibility criteria of a previous clinical trial. Three-year OS rates for ATL-PI were 34.5% (low-risk, n = 42), 9.2% (intermediate-risk, n = 109), and 12.5% (high-risk, n = 8). Those for JCOG-PI were 22.4% (moderate-risk, n = 95) and 7.6% (high-risk, n = 64). The low-risk ATL-PI group had a better prognosis than the JCOG-PI moderate-risk group, suggesting that ATL-PI would be more useful than JCOG-PI for establishing and examining novel treatment strategies for ATL patients with a better prognosis. In addition, strongyloidiasis, previously suggested to be associated with ATL-related deaths in Okinawa, was not a prognostic factor in this study.


Assuntos
Doenças Endêmicas , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Taxa de Sobrevida
18.
J Gerontol A Biol Sci Med Sci ; 73(11): 1448-1452, 2018 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-29688278

RESUMO

FOXO3 is one of the most prominent genes demonstrating a consistently reproducible genetic association with human longevity. The mechanisms by which these individual gene variants confer greater organismal lifespan are not well understood. We assessed the effect of longevity-associated FOXO3 alleles on age-related leukocyte telomere dynamics in a cross-sectional study comprised of samples from 121 healthy Okinawan-Japanese donors aged 21-95 years. We found that telomere length for carriers of the longevity associated allele of FOXO3 single nucleotide polymorphism rs2802292 displayed no significant correlation with age, an effect that was most pronounced in older (>50 years of age) participants. This is the first validated longevity gene variant identified to date showing an association with negligible loss of telomere length with age in humans in a cross-sectional study. Reduced telomere attrition may be a key mechanism for the longevity-promoting effect of the FOXO3 genotype studied.


Assuntos
Proteína Forkhead Box O3/genética , Leucócitos/metabolismo , Longevidade/genética , Polimorfismo de Nucleotídeo Único , Encurtamento do Telômero/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos Transversais , Feminino , Genótipo , Heterozigoto , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Am J Respir Crit Care Med ; 198(2): 232-244, 2018 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-29480750

RESUMO

RATIONALE: Nitric oxide (NO), synthesized by NOSs (NO synthases), plays a role in the development of pulmonary hypertension (PH). However, the role of NO/NOSs in bone marrow (BM) cells in PH remains elusive. OBJECTIVES: To determine the role of NOSs in BM cells in PH. METHODS: Experiments were performed on 36 patients with idiopathic pulmonary fibrosis and on wild-type (WT), nNOS (neuronal NOS)-/-, iNOS (inducible NOS)-/-, eNOS (endothelial NOS)-/-, and n/i/eNOSs-/- mice. MEASUREMENTS AND MAIN RESULTS: In the patients, there was a significant correlation between higher pulmonary artery systolic pressure and lower nitrite plus nitrate levels in the BAL fluid. In the mice, hypoxia-induced PH deteriorated significantly in the n/i/eNOSs-/- genotype and, to a lesser extent, in the eNOS-/- genotype as compared with the WT genotype. In the n/i/eNOSs-/- genotype exposed to hypoxia, the number of circulating BM-derived vascular smooth muscle progenitor cells was significantly larger, and transplantation of green fluorescent protein-transgenic BM cells revealed the contribution of BM cells to pulmonary vascular remodeling. Importantly, n/i/eNOSs-/--BM transplantation significantly aggravated hypoxia-induced PH in the WT genotype, and WT-BM transplantation significantly ameliorated hypoxia-induced PH in the n/i/eNOSs-/- genotype. A total of 69 and 49 mRNAs related to immunity and inflammation, respectively, were significantly upregulated in the lungs of WT genotype mice transplanted with n/i/eNOSs-/--BM compared with those with WT-BM, suggesting the involvement of immune and inflammatory mechanisms in the exacerbation of hypoxia-induced PH caused by n/i/eNOSs-/--BM transplantation. CONCLUSIONS: These results demonstrate that myelocytic n/i/eNOSs play an important protective role in the pathogenesis of PH.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Células Precursoras de Granulócitos/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/fisiopatologia , Hipóxia/tratamento farmacológico , Hipóxia/fisiopatologia , Óxido Nítrico Sintase/uso terapêutico , Animais , Humanos , Masculino , Camundongos , Modelos Animais , Substâncias Protetoras/uso terapêutico
20.
Cell Rep ; 22(3): 706-721, 2018 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-29346768

RESUMO

Food selection is essential for metabolic homeostasis and is influenced by nutritional state, food palatability, and social factors such as stress. However, the mechanism responsible for selection between a high-carbohydrate diet (HCD) and a high-fat diet (HFD) remains unknown. Here, we show that activation of a subset of corticotropin-releasing hormone (CRH)-positive neurons in the rostral region of the paraventricular hypothalamus (PVH) induces selection of an HCD over an HFD in mice during refeeding after fasting, resulting in a rapid recovery from the change in ketone metabolism. These neurons manifest activation of AMP-activated protein kinase (AMPK) during food deprivation, and this activation is necessary and sufficient for selection of an HCD over an HFD. Furthermore, this effect is mediated by carnitine palmitoyltransferase 1c (CPT1c). Thus, our results identify the specific neurons and intracellular signaling pathway responsible for regulation of the complex behavior of selection between an HCD and an HFD. VIDEO ABSTRACT.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Neurônios/fisiologia , Animais , Carboidratos , Dieta , Masculino , Camundongos
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