Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 124
Filtrar
1.
Am J Med Genet A ; 191(12): 2837-2842, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37554039

RESUMO

Left main coronary artery ostial atresia (LMCAOA) is an extremely rare condition. Here, we report the case of a 14-year-old boy with Noonan syndrome-like disorder in whom LMCAOA was detected following cardiopulmonary arrest. The patient had been diagnosed with Noonan syndrome-like disorder with a pathogenic splice site variant of CBL c.1228-2 A > G. He suddenly collapsed when he was running. After administering two electric shocks using an automated external defibrillator, the patient's heartbeat resumed. Cardiac catheterization confirmed the diagnosis of LMCAOA. Left main coronary artery angioplasty was performed. The patient was discharged without neurological sequelae. Brain magnetic resonance imaging revealed asymptomatic Moyamoya disease. In addition, RNF213 c.14429 G > A p.R4810K was identified. There are no reports on congenital coronary malformations of compound variations of RNF213 and CBL. In contrast, the RNF213 p.R4810K polymorphism has been established as a risk factor for angina pectoris and myocardial infarction in adults, and several congenital coronary malformations due to genetic abnormalities within the RAS/MAPK signaling pathway have been reported. This report aims to highlight the risk of sudden death in patients with RASopathy and RNF213 p.R4810K polymorphism and emphasize the significance of actively searching for coronary artery morphological abnormalities in these patients.


Assuntos
Anormalidades Múltiplas , Parada Cardíaca , Doença de Moyamoya , Síndrome de Noonan , Adulto , Masculino , Humanos , Criança , Adolescente , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/metabolismo , Síndrome de Noonan/complicações , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/genética , Predisposição Genética para Doença , Adenosina Trifosfatases/genética , Ubiquitina-Proteína Ligases/genética , Doença de Moyamoya/genética , Parada Cardíaca/genética
2.
Environ Sci Technol ; 57(28): 10242-10251, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37405980

RESUMO

Biomineralization inspired the development of simultaneous biological transformations and chemical precipitation for simultaneous nitrogen removal and phosphorus recovery from wastewater, which could compensate for the incapacity of phosphorus management in the new biological route of anaerobic ammonium oxidation (anammox). In this study, we strengthened anammox-mediated biomineralization by long-term feeding of concentrated N, P, and Ca substrates, and a self-assembled matrix of anammox bacteria and hydroxyapatite (HAP) was fabricated in a granular shape, defined as HAP-anammox granules. HAP was identified as the dominant mineral using elemental analysis, X-ray diffraction, and Raman spectroscopy. The intensive precipitation of HAP resulted in a higher inorganic fraction and substantially improved settleability of anammox biomass, which facilitated HAP precipitation by acting as nucleation and metabolically elevated pH. By using X-ray microcomputed tomography, we visually represented the hybrid texture of interwoven HAP pellets and biomass, the core-shell layered architecture of different-sized HAP-anammox granules, and their homogeneously regulated thickness of the outer biofilm (from 118 to 635 µm). This unique architecture endows HAP-anammox granules with outstanding settleability, active biofilm, and tightly bonded biofilm with the carrier, which may explain the excellent performance of these HAP-anammox granules under various challenging operational conditions in previous studies.


Assuntos
Compostos de Amônio , Esgotos , Esgotos/química , Oxidação Anaeróbia da Amônia , Durapatita , Microtomografia por Raio-X , Reatores Biológicos/microbiologia , Fósforo , Nitrogênio , Biofilmes , Oxirredução , Desnitrificação
3.
Support Care Cancer ; 32(1): 69, 2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38157081

RESUMO

PURPOSE: We investigated whether twice-daily administration of a bilayer tablet formulation of tramadol (35% immediate-release [IR] and 65% sustained-release) is as effective as four-times-daily IR tramadol capsules for managing cancer pain. METHODS: This randomized, double-blind, double-dummy, active-comparator, non-inferiority study enrolled opioid-naïve patients using non-steroidal anti-inflammatory drugs or acetaminophen (paracetamol) to manage cancer pain and self-reported pain (mean value over 3 days ≥ 25 mm on a 100-mm visual analog scale [VAS]). Patients were randomized to either bilayer tablets or IR capsules for 14 days. The starting dose was 100 mg/day and could be escalated to 300 mg/day. The primary endpoint was the change in VAS (averaged over 3 days) for pain at rest from baseline to end of treatment/discontinuation. RESULTS: Overall, 251 patients were randomized. The baseline mean VAS at rest was 47.67 mm (range: 25.6-82.7 mm). In the full analysis set, the adjusted mean change in VAS was - 22.07 and - 19.08 mm in the bilayer tablet (n = 124) and IR capsule (n = 120) groups, respectively. The adjusted mean difference was - 2.99 mm (95% confidence interval [CI] - 7.96 to 1.99 mm). The upper 95% CI was less than the predefined non-inferiority margin of 7.5 mm. Other efficacy outcomes were similar in both groups. Adverse events were reported for 97/126 (77.0%) and 101/125 (80.8%) patients in the bilayer tablet and IR capsule groups, respectively. CONCLUSION: Twice-daily administration of bilayer tramadol tablets was as effective as four-times-daily administration of IR capsules regarding the improvement in pain VAS, with comparable safety outcomes. CLINICAL TRIAL REGISTRATION: JapicCTI-184143/jRCT2080224082 (October 5, 2018).


Assuntos
Dor do Câncer , Neoplasias , Tramadol , Humanos , Acetaminofen/uso terapêutico , Analgésicos Opioides/uso terapêutico , Dor do Câncer/tratamento farmacológico , Preparações de Ação Retardada/uso terapêutico , Método Duplo-Cego , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Dor/tratamento farmacológico , Comprimidos/uso terapêutico , Tramadol/uso terapêutico , Resultado do Tratamento
4.
Cancer Sci ; 113(8): 2778-2787, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35579212

RESUMO

This multicenter, prospective phase IIb trial evaluating the efficacy and safety of tucidinostat (HBI-8000) in patients with relapsed or refractory (R/R) adult T-cell leukemia/lymphoma (ATLL) was undertaken in Japan. Eligible patients had R/R ATLL and had failed standard of care treatment with chemotherapy and with mogamulizumab. Twenty-three patients received tucidinostat 40 mg orally twice per week and were included in efficacy and safety analyses. The primary end-point was objective response rate (ORR) assessed by an independent committee. The ORR was 30.4% (95% confidence interval [CI], 13.2, 52.9]. Median progression-free survival was 1.7 months (95% CI, 0.8, 7.4), median duration of response was 9.2 months (95% CI, 2.6, not reached), and median overall survival was 7.9 months (95% CI, 2.3, 18.0). All patients experienced adverse events (AEs), which were predominantly hematologic and gastrointestinal. Incidence of grade 3 or higher AEs was 78.3%; most were laboratory abnormalities (decreases in platelets, neutrophils, white blood cells, and hemoglobin). Tucidinostat was well tolerated with AEs that could be mostly managed with supportive care and dose modifications. Tucidinostat is a meaningful treatment option for R/R ATLL patients; further investigation is warranted.


Assuntos
Leucemia-Linfoma de Células T do Adulto , Linfoma Folicular , Adulto , Benzamidas , Inibidores de Histona Desacetilases/efeitos adversos , Humanos , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Linfoma Folicular/tratamento farmacológico , Estudos Prospectivos , Piridinas , Recidiva , Resultado do Tratamento
5.
BMC Cardiovasc Disord ; 21(1): 389, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380423

RESUMO

BACKGROUND: We report a rare case of left ventricular inflow obstruction from a branch of the left circumflex coronary artery to the right atrium caused by a coronary arteriovenous fistula (CAVF) in a young Japanese male child. CASE PRESENTATION: The patient was diagnosed with CAVF following a heart murmur shortly after birth. The left-to-right shunt caused right ventricular volume overload and pulmonary congestion. An emergency surgical intervention was performed for the CAVF on day 6 after birth. However, by 5 years of age, his left ventricular inflow obstruction worsened. We found an abnormal blood vessel originating from the proximal part of a branch of the left circumflex coronary artery, circling the outside of the mitral valve annulus along the medial side of the coronary sinus. As the child gets older, the blood inflow into the left ventricle might get restricted further, resulting in left-sided heart failure. CONCLUSION: Our findings suggest that even after CAVF closure surgery, it is essential to monitor for complications caused by progressive dilatation of a persistent CAVF.


Assuntos
Fístula Arteriovenosa/complicações , Anomalias dos Vasos Coronários/complicações , Ventrículos do Coração , Hiperemia/etiologia , Fatores Etários , Fístula Arteriovenosa/cirurgia , Pré-Escolar , Seio Coronário , Anomalias dos Vasos Coronários/cirurgia , Dilatação Patológica/complicações , Humanos , Hipocinesia/diagnóstico por imagem , Recém-Nascido , Masculino , Valva Mitral , Veias Pulmonares , Disfunção Ventricular Esquerda/diagnóstico por imagem
6.
Ann Hematol ; 99(10): 2351-2356, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32865607

RESUMO

Lenalidomide (Len) and dexamethasone (dex) therapy is a standard therapy in patients with multiple myeloma. Elderly or unfit patients may reduce Len or dex doses to prevent toxicities that lead to treatment discontinuation. However, there have been few studies evaluating the efficacy and safety of lower doses of Len and dex. We conducted a phase II study of 1.5-year low-dose Len and dex therapy following melphalan and prednisolone (MP), the number of which cycles was determined by a response within 9 cycles. The Len dose was 10 mg daily and the dex dose was 20 mg weekly, which were continued for 1.5 years. Twenty-one patients were enrolled. The median number of cycles of MP was 3 (range, 2-9). The overall response rate was 81% and a very good partial response or better was achieved in 33.3% of patients. The median follow-up time for survivors was 70.5 months (range, 42-83 months), the median progression-free survival (PFS) was 27 months (95% CI, 21-33 months), and the median overall survival was not reached. Grade 3 or 4 adverse events were observed in 28.6% of patients. In conclusion, the low-dose Len and dex therapy safely achieved comparable efficacies to the standard-dose regimen in elderly patients with newly diagnosed multiple myeloma. UMIN000007889.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anemia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Neutropenia Febril/induzido quimicamente , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Lenalidomida/administração & dosagem , Lenalidomida/efeitos adversos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Intervalo Livre de Progressão , Indução de Remissão , Resultado do Tratamento , Adulto Jovem
7.
Heart Vessels ; 35(4): 586-592, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31562553

RESUMO

Recent reports suggested that cardiopulmonary bypass (CPB) time is one of the risk factors for postoperative complications after Fontan conversion. Although Fontan conversion may be performed for the patients with hepatic fibrosis after initial Fontan procedure, there is no predictive indicator regarding the liver function associated with hemostasis which can affects CPB time. Thirty-one patients who underwent Fontan conversion using the same surgical procedure (extracardiac conduit conversion with right atrium exclusion) were enrolled. In multivariate analyses including age at Fontan conversion, interval from initial Fontan to conversion, hemodynamic data such as right atrial pressure, ventricular end-diastolic pressure, and cardiac index, hepatic data such as platelet count, prothrombin time international normalized ratios, serum total bilirubin, hyaluronic acid levels, five known indices for hepatic fibrosis (Forns Index, APRI, FIB4, FibroIndex, and MELD-XI), and liver stiffness measured by ultrasound elastography, only the Forns Index remained independently associated with the CPB time (P < 0.01) and blood transfusions (plasma transfusions and platelet concentrations: P < 0.01 for both). The cutoff level for Forns Index to predict the prolonged CPB time (exceeding 240 min) was 4.85 by receiver-operating characteristic curve (area under the curve 0.823, sensitivity 76.9%, and specificity 72.2%). Three patients with Forns Index > 7.0 had poor outcomes with long CPB time and massive blood transfusions in contrast with the other 28 patients. In conclusion, Forns Index could serve as a practical predictor of CPB time and is associated with blood transfusion volume in Fontan conversion.


Assuntos
Ponte Cardiopulmonar , Técnica de Fontan/efeitos adversos , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/etiologia , Complicações Pós-Operatórias/etiologia , Adolescente , Adulto , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Biomarcadores/metabolismo , Técnicas de Imagem por Elasticidade , Feminino , Cardiopatias Congênitas/cirurgia , Hemodinâmica , Humanos , Cirrose Hepática/metabolismo , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
8.
Heart Vessels ; 35(9): 1307-1315, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32285188

RESUMO

Congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) is one of the major complications in patients with CHD. A timely closure of the left-to-right shunt will generally result in the normalization of the pulmonary hemodynamics, but a few patients have severe prognosis in their early childhood. We hypothesized that wide-ranging pathological mechanism in PAH could elucidate the clinical state of severe CHD-PAH. Using electronic medical records, we retrospectively analyzed six infants with severe CHD-PAH who had treatment-resistant PH. All patients were born with congenital malformation syndrome. After starting on a pulmonary vasodilator, five of the six patients developed complications including pulmonary edema and interstitial lung disease (ILD), and four patients had alveolar hemorrhage. After steroid therapy, the clinical condition improved in four patients, but two patients died. The autopsy findings in one of the deceased patients indicated the presence of recurrent alveolar hemorrhage, pulmonary venous hypertension, ILD, and PAH. Based on the clinical course of these CHD-PAH in patients and the literature, CHD-PAH can occur with pulmonary vascular obstructive disease (PVOD)/pulmonary capillary hemangiomatosis (PCH), ILD, and/or alveolar hemorrhage. The severity of CHD-PAH may depend on a genetic disorder, respiratory infection, and upper airway stenosis. Additionally, pulmonary vasodilators may be involved in the development of PVOD/PCH and ILD. When patients with CHD-PAH show unexpected deterioration, clinicians should consider complications associated with PVOD/PCH and/or pulmonary disease. In addition, the choice of upfront combination therapy for pediatric patients with CHD-PAH should be selected carefully.


Assuntos
Anti-Hipertensivos/efeitos adversos , Pressão Arterial/efeitos dos fármacos , Cardiopatias Congênitas/complicações , Hipertensão Arterial Pulmonar/tratamento farmacológico , Artéria Pulmonar/efeitos dos fármacos , Vasodilatadores/efeitos adversos , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/cirurgia , Hemangioma Capilar/complicações , Hemangioma Capilar/fisiopatologia , Hemorragia/etiologia , Hemorragia/fisiopatologia , Humanos , Lactente , Recém-Nascido , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/fisiopatologia , Masculino , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/fisiopatologia , Artéria Pulmonar/fisiopatologia , Edema Pulmonar/etiologia , Edema Pulmonar/fisiopatologia , Pneumopatia Veno-Oclusiva/etiologia , Pneumopatia Veno-Oclusiva/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
9.
J Card Surg ; 35(9): 2382-2384, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32557698

RESUMO

A 72-year-old man was referred to our institution because of an arch aneurysm and acute aortic dissection (thrombosed Stanford type A). Anti-impulse therapy was initiated. He developed a high fever after admission. Blood culture was negative. Five days after admission, he developed back pain. Thoracoabdominal computed tomography revealed a new low-density area from the distal arch to the descending aorta. We performed emergent total arch replacement. Although we discontinued all sedative drugs after surgery, coma continued. Brain magnetic resonance imaging with diffusion-weighted imaging revealed ventriculitis with brain infarction. After antimicrobial therapy was started, his consciousness level improved. Ventriculitis should be suspected when disturbance of consciousness continues longer than we predict after emergent arch aneurysm surgery. Delay in diagnosis can lead to a life-threatening condition.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Ventriculite Cerebral , Idoso , Dissecção Aórtica/cirurgia , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino
10.
Acta Haematol ; 139(1): 35-44, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29339642

RESUMO

Autologous stem cell transplantation (ASCT) has been employed for patients with relapsed multiple myeloma (MM) after up-front ASCT. The present retrospective study aimed to examine the survival benefit from salvage ASCT. Among 446 patients with relapsed MM after up-front single ASCT, 70 patients received salvage ASCT, the employment of which reduced the risk of mortality after relapse (p = 0.041). Using the parameters before initial ASCT, the advantage of salvage ASCT compared to standard therapy was confirmed in the subgroup with an international staging system stage of I or II (p = 0.040), good performance status (PS; p = 0.043), or no/mild renal comorbidity (p = 0.029). The advantage of salvage ASCT was also confirmed in the subgroup excluding those with early relapse within 7 months after initial ASCT (p = 0.026). Among patients who received salvage ASCT, a favorable prognosis is apparent for those with a time to relapse after initial ASCT of longer than 24 months. The overall survival after salvage ASCT was favorable excluding patients with the following factors: early relapse, poor PS, moderate/severe renal comorbidity, and progressive disease (p < 0.001). In conclusion, our results reinforced the evidence for encouraging salvage ASCT for eligible patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Adulto , Idoso , Biomarcadores Tumorais , Progressão da Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Estadiamento de Neoplasias , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores de Risco , Terapia de Salvação , Transplante Autólogo , Adulto Jovem
11.
Asian-Australas J Anim Sci ; 31(10): 1542-1549, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29531186

RESUMO

OBJECTIVE: Because lactation periods in dairy cows lengthen with increasing total milk production, it is important to predict individual productivities after 305 days in milk (DIM) to determine the optimal lactation period. We therefore examined whether the random regression (RR) coefficient from 306 to 450 DIM (M2) can be predicted from those during the first 305 DIM (M1) by using a RR model. METHODS: We analyzed test-day milk records from 85,690 Holstein cows in their first lactations and 131,727 cows in their later (second to fifth) lactations. Data in M1 and M2 were analyzed separately by using different single-trait RR animal models. We then performed a multiple regression analysis of the RR coefficients of M2 on those of M1 during the first and later lactations. RESULTS: The first-order Legendre polynomials were practical covariates of RR for the milk yields of M2. All RR coefficients for the additive genetic (AG) effect and the intercept for the permanent environmental (PE) effect of M2 had moderate to strong correlations with the intercept for the AG effect of M1. The coefficients of determination for multiple regression of the combined intercepts for the AG and PE effects of M2 on the coefficients for the AG effect of M1 were moderate to high. The daily milk yields of M2 predicted by using the RR coefficients for the AG effect of M1 were highly correlated with those obtained by using the coefficients of M2. CONCLUSION: Milk production after 305 DIM can be predicted by using the RR coefficient estimates of the AG effect during the first 305 DIM.

12.
Nihon Ronen Igakkai Zasshi ; 55(1): 90-97, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-29503373

RESUMO

OBJECTIVE: The hemodialysis (HD) diet, which is a high-calorie and high-fat regimen, may inadvertently lead to an inadequate dietary intake, resulting in undernutrition among elderly HD patients. Therefore, an attempt was made to improve the dietary intake by implementing a modified diet regimen in eligible elderly HD patients. SUBJECTS: Elderly HD patients who had ingested < 50% of the meals provided and were diagnosed with undernutrition among all elderly patients institutionalized at the special elderly nursing home annexed to Nagasaki Kidney Hospital between June and November 2012. RESULTS: Of the elderly HD patients in the nursing home (n = 27), the study included a total of 7 consecutive patients (male/female, 1/6; mean age, 84.1±6.4 years old; duration of HD, 4.3±3.8 years; geriatric nutritional index [GNRI], 83.5±8.3; normalized protein catabolic ratio [nPCR], 0.78±0.14). The modified diet regimen, which involved reducing food portion sizes and incorporating a liquid diet, led to a significant increase in their dietary intake from 48.1% at baseline to 97.1% of the meals provided 3 months after the start of the modified HD diet regimen. Their GNRI also significantly increased from 83.5±8.3 to 86.1±10.2, and their serum albumin levels significantly increased from 3.2±0.2 g/dL to 3.4±0.4 g/dL, suggesting improvements in their nutritional status. CONCLUSIONS: The attempted dietary approach for elderly HD patients was shown to potentially increase their dietary intake and improve their nutritional status without affecting the efficiency of HD being implemented.


Assuntos
Ingestão de Energia , Idoso , Idoso de 80 Anos ou mais , Dieta , Feminino , Humanos , Masculino , Estado Nutricional , Projetos Piloto , Diálise Renal
13.
Cancer Sci ; 108(3): 435-443, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28075522

RESUMO

Carbonic anhydrase IX (CA9) is a membrane-associated carbonic anhydrase that regulates cellular pH, is upregulated in various solid tumors, and is considered to be a therapeutic target. Here, we describe the essential role of CA9 in the tumorigenicity of cells derived from human adult T-cell leukemia/lymphoma (ATL). We previously established the highly tumorigenic ST1-N6 subline from the ATL-derived ST1 cell line by serial xenotransplantation in NOG mice. In the present study, we first show that CA9 expression is strongly enhanced in ST1-N6 cells. We then sorted ST1 cells by high or low CA9 expression and established ST1-CA9high and ST1-CA9low sublines. ST1-CA9high cells, like ST1-N6 cells, were more strongly tumorigenic than ST1-CA9low or parental ST1 cells when injected into NOG mice. Knockdown of CA9 with shRNAs suppressed the ability of ST1-CA9high cells to initiate tumors, and the tumorigenicity of ST1 cells was significantly enhanced by introducing wild-type CA9 or a CA9 mutant with deletion of an intracytoplasmic domain. However, a CA9 with point mutations in the catalytic site did not increase the tumorigenicity of ST1 cells. Furthermore, we detected a small population of CA9+ CD25+ cells in lymph nodes of ATL patients. These findings suggest that CA9, and particularly its carbonic anhydrase activity, promotes the tumorigenicity of ATL-derived cells and may be involved in malignant development of lymphoma-type ATL.


Assuntos
Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Anidrase Carbônica IX/genética , Anidrase Carbônica IX/metabolismo , Transformação Celular Neoplásica/patologia , Leucemia-Linfoma de Células T do Adulto/patologia , Animais , Domínio Catalítico/genética , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Humanos , Linfonodos/citologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Transplante de Neoplasias , Interferência de RNA , RNA Interferente Pequeno/genética , Transplante Heterólogo
14.
Cancer Sci ; 107(5): 638-43, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26928911

RESUMO

The transplantation of human cancer cells into immunodeficient NOD/SCID/IL-2Rγc(null) (NOG) mice often causes highly malignant cell populations like cancer stem cells to emerge. Here, by serial transplantation in NOG mice, we established two highly tumorigenic adult T-cell leukemia-derived cell lines, ST1-N6 and TL-Om1-N8. When transplanted s.c., these cells formed tumors significantly earlier and from fewer initial cells than their parental lines ST1 and TL-Om1. We found that protein kinase B (AKT) signaling was upregulated in ST1-N6 and TL-Om1-N8 cells, and that this upregulation was due to the decreased expression of a negative regulator, INPP5D. Furthermore, the introduction of a constitutively active AKT mutant expression vector into ST1 cells augmented the tumorigenicity of the cells, whereas treatment with the AKT inhibitor MK-2206 attenuated the progression of tumors induced by ST1-N6 cells. Collectively, our results reveal that the AKT signaling pathway plays a critical role in the malignancy of adult T-cell leukemia-derived cells.


Assuntos
Transformação Celular Neoplásica/patologia , Leucemia-Linfoma de Células T do Adulto/patologia , Transplante de Neoplasias , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transplante Heterólogo , Animais , Linhagem Celular Tumoral , Transformação Celular Neoplásica/metabolismo , Regulação para Baixo , Ativação Enzimática , Humanos , Leucemia-Linfoma de Células T do Adulto/enzimologia , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/metabolismo , Proto-Oncogene Mas , Transdução de Sinais , Regulação para Cima
15.
J Med Virol ; 88(12): 2206-2210, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27219865

RESUMO

Occult hepatitis B virus (HBV) infection is a clinical challenge, but its relationship to clinicopathologic features and the risk of progression to malignant lymphoma (ML) are poorly defined. We estimated the prevalence of HBV infection of 1,358 patients with newly diagnosed ML. HBV infection was more prevalent in ML than in control patients. The occult HBV infection group had a higher median onset age, no liver or spleen involvement, and higher prevalence of diffuse large B-cell lymphoma than the other groups, indicating that occult HBV infection is a distinct clinicopathologic entity. J. Med. Virol. 88:2206-2210, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Infecções Assintomáticas , Hepatite B/complicações , Linfoma Difuso de Grandes Células B/complicações , Linfoma/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Assintomáticas/epidemiologia , DNA Viral/genética , Feminino , Hepatite B/epidemiologia , Anticorpos Anti-Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Humanos , Japão/epidemiologia , Linfoma/epidemiologia , Linfoma Difuso de Grandes Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Adulto Jovem
16.
No Shinkei Geka ; 44(7): 583-90, 2016 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-27384119

RESUMO

We report a case of subarachnoid hemorrhage(SAH)from an intracranial vertebral artery(VA)dissection in a patient with fibromuscular dysplasia(FMD)who presented with headache. A 54-year-old woman complained of spontaneous occipital headache. The dilatation of the left VA was detected on magnetic resonance angiography(MRA). She was diagnosed with left VA dissection(headache onset type). After sudden onset of headache on the second day of hospitalization, her consciousness level, as defined by the Japan Coma Scale, was 300. Computed tomography(CT)revealed SAH. Cerebral angiography showed the dilatation of the left intracranial VA and contrast material pooling, which was suspected to be a sign of dissection. We performed VA intravascular ligation by coil embolization. The postoperative course was good but postoperative MRA revealed arterial wall irregularities in both the extra cranial internal carotid artery and the right VA. Cerebral angiography showed the presence of the string-of-beads sign at these arteries. She was diagnosed with FMD. SAH might develop during the follow-up period in patients with VA dissection, even those in whom the initial symptom is headache. In addition, cases of FMD might also be complicated by various lesions of the main trunk of the cerebral artery.


Assuntos
Displasia Fibromuscular/diagnóstico por imagem , Cabeça/diagnóstico por imagem , Pescoço/diagnóstico por imagem , Artéria Vertebral/diagnóstico por imagem , Angiografia Cerebral , Feminino , Displasia Fibromuscular/cirurgia , Humanos , Angiografia por Ressonância Magnética , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
18.
No Shinkei Geka ; 43(10): 901-6, 2015 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-26435369

RESUMO

We report 9 cases of cerebellar contusion from April 2011 to September 2014 at our department. Frequency, clinicoradiological findings, mechanism of injury, treatments, and outcomes were retrospectively analyzed. Of 239 head injury cases admitted to our department during the same period, 9(3.8%)were diagnosed as cerebellar contusion. Among these 9 cases, 7 were men, and 2 were women. The patient age ranged from 12 to 83 years with a mean age of 64.7 years. The mechanism of injury was traffic accident in one patient, and fall in 8. All cases were associated with direct head trauma to the occiput, and radiographic studies showed occipital bone fracture in 8 cases. Six cases were managed conservatively. Three cases underwent suboccipital craniectomies and clot evacuations. Glasgow Outcome Scale(GOS)score at discharge were Good Recovery(GR)in 2, Moderate Disability(MD)in 2, Severe Disability(SD)in 3, Vegetative State(VS)in 1, and Dead(D)in 1. GOS scores in surgically treated cases were GR in 1, SD in 1, and VS in 1. Supratentorial severe traumatic lesions were concomitant with poor prognosis. Coup injury was a significant cause of cerebellar contusion. External decompression and clot evacuation were useful in patients who suffered severe cerebellar contusion;however, concomitant supratentorial lesions influenced the prognosis.


Assuntos
Lesões Encefálicas/diagnóstico , Lesões Encefálicas/terapia , Contusões/etiologia , Idoso , Idoso de 80 Anos ou mais , Lesões Encefálicas/patologia , Criança , Contusões/diagnóstico , Contusões/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
19.
No Shinkei Geka ; 43(5): 419-27, 2015 May.
Artigo em Japonês | MEDLINE | ID: mdl-25926538

RESUMO

PURPOSE: The long-term results of decompressive surgery for degenerative spondylolisthesis (DS) were evaluated with reference to instability. MATERIALS AND METHODS: Patients (n=48) undergoing decompressive surgery without fusion were studied. The diagnosis of spondylolisthesis was made based on the presence of sagittal vertebral slippage greater than 3mm. Instability was defined as translation more than 2mm on lateral functional radiography. Surgical interventions were divided into two groups: bilateral laminotomy (n=25)and laminectomy (n=23). Clinical results were evaluated according to the McCulloch's classification and Japanese Orthopedic Association(JOA)score. RESULTS: Of 48 patients, 25 showed preoperative instability. Eleven patients showed both pre-and postoperative instability. The mean pre-and postoperative slippages were 7.5 and 7.6mm, respectively. Of 23 patients without preoperative instability, nine developed postoperative instability. In this group, slippage changed from 6.2 to 6.1mm. Instability was not related to slippage progression. Surgical results of patients undergoing laminotomy were superior to those undergoing laminectomy. The mean pre-and postoperative JOA scores and recovery rate were 14.5, 20.9, and 63.1 in instability group patients with laminotomy and 15.6, 23.2, and 59.0 in the non-instability group, respectively. Surgical results were similar and not related to preoperative instability. Low back pain (LBP) showed no correlation to the degree of slippage, instability, and surgery type. LBP improved in each group. CONCLUSIONS: Instability, defined by vertebral translation on lateral functional radiography, did not affect the surgical results of patients with DS treated with laminotomy.


Assuntos
Descompressão Cirúrgica , Espondilolistese/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Laminectomia , Dor Lombar/etiologia , Masculino , Pessoa de Meia-Idade , Radiografia , Espondilolistese/diagnóstico por imagem , Fatores de Tempo , Resultado do Tratamento
20.
Biochim Biophys Acta ; 1833(5): 1017-27, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23337771

RESUMO

In most eukaryotic cells, mitochondria have various essential roles for proper cell function, such as energy production, and in mammals mitochondria also act as a platform for antiviral innate immunity. Mitochondrial-mediated antiviral immunity depends on the activation of the cytoplasmic retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) signaling pathway, and on the participation of mitochondrial antiviral signaling (MAVS), which is localized on the mitochondrial outer membrane. After RNA virus infection, RLRs translocate to the mitochondrial surface to interact with MAVS, and the adaptor protein undergoes a conformational change that is essential for downstream signaling, although its structural features are poorly understood. Here we examined the MAVS-regulatory mechanism on the mitochondrial outer membrane using bioluminescence resonance energy transfer (BRET) in live cells. Using a combination of BRET and functional analysis, we found that the activated MAVS conformation is a highly ordered oligomer, at least more than three molecules per complex unit on the membrane. Hepatitis C virus NS3/4A protease and mitofusin 2, which are known MAVS inhibitors, interfere with MAVS homotypic oligomerization in a distinct manner, each differentially altering the active conformation of MAVS. Our results reveal structural features underlying the precise regulation of MAVS signaling on the mitochondrial outer membrane, and may provide insight into other signaling systems involving organelles.


Assuntos
RNA Helicases DEAD-box , Imunidade Inata , Mitocôndrias , Membranas Mitocondriais/metabolismo , Animais , Técnicas de Transferência de Energia por Ressonância de Bioluminescência , Proteína DEAD-box 58 , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Metabolismo Energético , Células HEK293 , Humanos , Imunidade Inata/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Infecções por Vírus de RNA/genética , Infecções por Vírus de RNA/metabolismo , Receptores Imunológicos , Transdução de Sinais , Proteínas não Estruturais Virais/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA