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1.
Hepatol Res ; 54(2): 131-141, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37621201

RESUMO

AIM: Nucleos(t)ide analogs do not completely prevent hepatocellular carcinoma (HCC) in chronic hepatitis B virus infection. This study aimed to evaluate the dynamics of a non-invasive liver fibrosis marker, the Fibrosis-4 (FIB-4) index, for predicting HCC development. METHODS: Among a total of 882 chronically hepatitis B virus infection-infected patients who were treated with nucleos(t)ide analogs, 472 patients without HCC history whose FIB-4 at baseline and 1 year of treatment was obtained were evaluated for the incidence of HCC. RESULTS: The median FIB-4 was 2.00 at baseline and was significantly reduced to 1.58 at 1 year (P < 0.001), but the reduction was small at 2 years or later. When a receiver operating characteristic analysis of FIB-4 was performed to predict HCC within 5 years, the area under the curve of FIB-4 at 1 year was higher than that at baseline (0.676 vs. 0.599). The HCC incidence was significantly higher in patients with FIB-4 ≥1.58 than in those with FIB-4 <1.58 (14.8% vs. 3.6% at 10 years, P < 0.001). Additionally, an abnormal alanine aminotransferase (≥31 U/L) at 1 year was an independent risk for HCC. When a fibrosis and alanine aminotransferase-1 (FAL-1) score was evaluated as an applicable number of FIB-4 ≥1.58, and alanine aminotransferase ≥31 as 0, 1, and 2, the HCC risk in patients with score 2 was significantly higher than in those with score 1 or score 0 (24.1% vs. 9.8% vs. 0.7% at 10 years, P < 0.001). CONCLUSIONS: FIB-4 ≥1.58 and alanine aminotransferase ≥31 at 1 year of nucleos(t)ide analog was an independent risk factor for HCC development, and a score using these factors stratified the risk of HCC.

2.
J Arthroplasty ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38909854

RESUMO

BACKGROUND: With the decreasing age threshold for patients undergoing total hip arthroplasty (THA), there is an escalating demand for enhanced polyethylene durability. Although reports assessing wear in remelted highly cross-inked polyethylene (HXLPE) through radiographic imaging exist, a consensus regarding its oxidation level is lacking. This study investigated the wear, oxidation levels, and degradation of remelted HXLPE that was retrieved at least 10 years after THA. METHODS: Our analysis focused on seven cases of melted HXLPE liners retrieved ≥ 10 years after THA. All patients were women, who had an average age of 64 ± 6.5 years at the initial operation, and the mean postoperative period after THA was 12 years and 11 months ± 1 year and 5 months. The wear conditions were measured by matching the shape analysis data obtained from a coordinate-measuring machine with a spherical model. Fourier-transform infrared spectroscopy was used to study the oxidation of polyethylene, and the polyethylene structure was evaluated using scanning electron microscopy. RESULTS: Osteolysis was not observed in any case on X-rays, computed tomography, or intraoperative findings during revision surgery. The average oxidation index of the sliding surface under load was 0.31 ± 0.22 in the six cases calculated after hexane treatment, and 0.69 for one case without hexane treatment. In the six cases calculated after hexane treatment, the average oxidation index of the non-load-bearing sliding surface was 0.11 ± 0.20. Average wear values were 0.33 ± 0.11 mm at 45 degrees from the equatorial direction and 0.04 ± 0.07 mm in the opposite direction. The initial structure of the polyethylene was preserved at all sites with low oxidation levels; however, in one case with stem subsidence, morphological changes and a high oxidation index were observed. CONCLUSION: Long-term oxidation and wear of remelted HXLPE liners retrieved from THA patients were minimal.

3.
J Neuroradiol ; 51(2): 214-219, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37625629

RESUMO

Transradial access during neurointerventions has increased in popularity because of reduced complications and patient preference. Nevertheless, transradial cannulation into the left common carotid artery can be difficult technically because of the lack of catheter support in the aortic arch. Furthermore, the use of large sheaths can increase the risk of complications at the access site. Here, we developed a new very-small-bore transradial system using a 3F Simmons guiding sheath, to increase the procedural success rate and minimize access-site complications. This system can represent a valuable treatment option for neurointerventions and has the potential to expand the indications for transradial access.


Assuntos
Estenose das Carótidas , Artéria Radial , Humanos , Artéria Radial/cirurgia , Estenose das Carótidas/terapia , Artéria Carótida Primitiva , Cateterismo , Catéteres , Resultado do Tratamento
4.
Br J Neurosurg ; 37(6): 1786-1791, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33851560

RESUMO

BACKGROUND: The prognosis for spinal artery aneurysms associated with spinal cord arteriovenous malformations (AVMs) is poor because of the high rupture rate of aneurysms. However, endovascular treatment remains technically difficult because the catheter system must be constructed via the small-caliber anterior spinal artery (ASA) or posterior spinal artery (PSA), which feeds functionally eloquent spinal cord. A 2.6F Carnelian HF-S microcatheter (Tokai Medical Products, Aichi, Japan) has been specifically designed to assist a 1.6F Carnelian MARVEL S microcatheter (Tokai Medical Products) as a small-profile 'platform catheter' close to the target lesion. Here we present a prenidal ASA aneurysm treated using a 2.6F Carnelian HF-S microcatheter as an intraspinal canal platform catheter and review related literature. CASE PRESENTATION: A 50-year-old man presented with a subarachnoid haemorrhage due to cervical spinal cord AVM. Diagnostic vertebral angiography revealed the AVM supplied by the PSA originated from the right C2 segmental artery and ASA arising from the right V4 segment. Superselective angiography for each feeder was achieved through a 2.6F Carnelian HF-S microcatheter, and a prenidal ASA aneurysm was diagnosed, which was clinically consistent with haemorrhagic origin. A 1.6F Carnelian MARVEL S microcatheter was cannulated into the aneurysm through the 2.6F Carnelian HF-S microcatheter positioned at the ASA. The aneurysm coiling was successfully performed without system instability or periprocedural complications. CONCLUSIONS: Only a few cases have described endovascular treatment for spinal artery aneurysms. To date, no reports have been published regarding the use of an intraspinal canal platform catheter to treat spinal artery aneurysms. A 2.6F Carnelian HF-S microcatheter served as a useful intraspinal canal platform catheter for coil embolization of the ASA aneurysm. This system can provide excellent accessibility and controllability for endovascular treatment of spinal artery lesions.


Assuntos
Aneurisma , Malformações Arteriovenosas , Embolização Terapêutica , Aneurisma Intracraniano , Hemorragia Subaracnóidea , Masculino , Humanos , Pessoa de Meia-Idade , Aneurisma/terapia , Malformações Arteriovenosas/complicações , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/cirurgia , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/etiologia , Hemorragia Subaracnóidea/cirurgia , Artéria Vertebral/diagnóstico por imagem , Artéria Vertebral/cirurgia , Medula Espinal/diagnóstico por imagem , Medula Espinal/cirurgia , Embolização Terapêutica/efeitos adversos , Aneurisma Intracraniano/complicações
5.
Tohoku J Exp Med ; 258(4): 277-285, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36244758

RESUMO

Nucleos(t)ide analogues (NAs) suppress hepatitis B virus (HBV) replication, but the risk of hepatocellular carcinoma still remains. The presence of detectable HBV DNA in the serum during NA therapies for chronic hepatitis B patients has been reported to be associated with the risk of hepatocellular carcinoma. In this study, we investigated the antiviral effect of switching from entecavir (ETV) to tenofovir alafenamide fumarate (TAF) in chronic hepatitis B patients who had detectable HBV DNA in the serum at least once within a year. Among a total of 77 cases in 7 hospitals that switched NAs from ETV to TAF, 23 patients with detectable HBV DNA in a year before switching were analyzed. When the detection frequencies of HBV DNA in the 1st and 2nd years after switching to TAF were analyzed, they were significantly lower than those in the year before switching (68.8% vs. 34.1% for the 1st year and 21.3% for the 2nd year, P < 0.001 for both). The HBsAg decline tended to be larger after switching than before (-2.5% vs. -3.0% for 1st year and -3.1% for 2nd year), but the difference was not significant. One patient died of a cardiovascular event 11 months after the treatment switch, but no adverse effects due to TAF including renal function were observed. In conclusion, it was suggested that switching from ETV to TAF might be effective to suppress the HBV DNA level further in patients whose HBV DNA is detectable, even if at a very low level.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , DNA Viral/uso terapêutico , Tenofovir/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Adenina/uso terapêutico , Antivirais/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Fumaratos/uso terapêutico , Resultado do Tratamento
6.
Nihon Shokakibyo Gakkai Zasshi ; 119(5): 452-458, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35545544

RESUMO

Intraductal papillary mucinous carcinoma (IPMC) arising from the heterotopic pancreas is rare. A case of IPMC metastasis from the jejunal heterotopic pancreas was described. The heterotopic pancreas could be the source of the submucosal tumor-like lesion found in the small intestine with an elevated carbohydrate antigen (CA) 19-9 level. A 60-year-old woman was admitted to the hospital with pulmonary thromboembolism and anemia. The level of CA19-9, a tumor marker, was found to be 211.8U/ml. A tumor in the jejunum was discovered using contrast-enhanced computed tomography. There were also a number of hepatic tumors found. A submucosal tumor-like lesion in the jejunum was discovered during an enteroscopy, and a biopsy revealed it to be an adenocarcinoma. Partial resection of the jejunum was performed to control hemorrhage. Histopathology revealed an invasive IPMC arising from a heterotopic pancreas (Heinrich type II) and chemotherapy with gemcitabine and nab-paclitaxel was initiated. There have only been three cases of invasive IPMC from a heterotopic pancreas reported, and this is the first one to include chemotherapeutic treatment of distant metastasis.


Assuntos
Adenocarcinoma Mucinoso , Adenocarcinoma Papilar , Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/cirurgia , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/cirurgia , Adenocarcinoma Papilar/cirurgia , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Feminino , Humanos , Jejuno/patologia , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas
7.
Pituitary ; 24(5): 690-697, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33811621

RESUMO

PURPOSE: Acromegaly is an acquired disorder usually caused by growth hormone-secreting pituitary adenoma, resolution of which requires correction of the excess hormone production. Recently, intraoperative magnetic resonance imaging (iMRI) was reported to be useful during the endoscopic endonasal approach (EEA) for pituitary adenoma. The present study was performed to quantitatively assess the role of iMRI in improving surgical outcomes in EEA for acromegaly. METHODS: Twenty surgeries for acromegaly in EEA performed at Shinshu University Hospital between April 2016 and March 2020 were reviewed retrospectively. The inclusion criteria were cases without severe cavernous sinus tumor invasion (Knosp grade 0 - 3) or history of prior pituitary surgery. Fifteen consecutive patients were enrolled in this study. Clinical characteristics and postoperative clinical outcomes were compared between patients with and without use of iMRI during EEA for acromegaly. RESULTS: Conventional navigation-guided surgery was performed in nine patients, and six underwent iMRI-guided EEA for acromegaly. Gross total resection (GTR) was obtained in the six (100%) patients in the iMRI group, and in four (44.4%) patients in the conventional group without iMRI. Postoperative clinical outcomes, including hormonal remission rate and surgical complications, were comparable between the two groups. CONCLUSION: Although iMRI significantly increased the GTR rate, we found no direct evidence of increased hormonal remission rate by use of iMRI. It is important to confirm complete tumor resection carefully with not only iMRI findings, but also with intraoperative high-definition endoscopic direct visualization to increase the hormonal remission rate of acromegaly.


Assuntos
Acromegalia , Adenoma , Neoplasias Hipofisárias , Acromegalia/diagnóstico por imagem , Acromegalia/cirurgia , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Humanos , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Resultado do Tratamento
8.
Heart Vessels ; 36(7): 955-964, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33502572

RESUMO

In Japan, a robotic-assisted PCI (R-PCI) system, the CorPath GRX System (Corindus Inc.), has been approved for clinical use in 2018, which is the first introduction of R-PCI into Japan. In this study, the clinical performance of the R-PCI system in the initial year at Kurume University Hospital was evaluated comparing with conventional manual PCI (M-PCI). A total of 30 R-PCI and 77 M-PCI procedures performed between April 2019 and March 2020, were retrospectively included. The primary outcome was the rate of clinical success defined as < 30% residual stenosis without in-hospital major adverse cardiovascular events (MACE). The secondary outcomes were fluoroscopy time, dose area product (DAP), amount of radiation exposure to operators and assistants, procedural time, and contrast volume. Propensity-matching technique was used to match each R-PCI lesion to the nearest M-PCI lesion without replacement. After propensity score matching, 30 R-PCI procedures in 28 patients and 37 M-PCI procedures in 35 patients were analyzed. Clinical success rate with R-PCI was favorable and comparable to M-PCI (93.3 vs. 94.6%, p = 0.97), without any in-hospital MACE. The operator radiation exposure was significantly lower in R-PCI (0 vs. 24.5 µSV, p < 0.0001). Radiation exposure to the patients was tended to be reduced by R-PCI (DAP: 77.6 vs. 100.2 Gycm2, p = 0.07). There were no statistically significant differences in radiation exposure to the assistant, fluoroscopy time, procedural time and contrast volume between the two groups (radiation exposure to the assistant: 10.5 vs. 10.0 µSV, p = 0.64, fluoroscopy time: 27.5 vs. 30.1 min, p = 0.55, procedural time: 72.4 vs. 61.6 min, p = 0.23, and contrast volume: 93.2 vs. 102.0 ml, p = 0.36). R-PCI in selected patients demonstrated favorable clinical outcomes with dramatical reduction of radiation exposure to operators.


Assuntos
Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea/métodos , Sistema de Registros , Procedimentos Cirúrgicos Robóticos/instrumentação , Idoso , Angiografia Coronária/efeitos adversos , Doença da Artéria Coronariana/diagnóstico , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Masculino , Pontuação de Propensão , Exposição à Radiação/efeitos adversos , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Lesões por Radiação/prevenção & controle , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento
9.
J Virol ; 93(15)2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31118260

RESUMO

Viruses are considered to use vesicular trafficking in infected cells, but the details of assembly/release pathways of hepatitis B virus (HBV) are still unknown. To identify key regulators of HBV production, we performed short interfering RNA (siRNA) screening for Rab proteins, which are considered to act as molecular switches in vesicular trafficking using HepG2.2.15 cells. Among 62 Rab proteins, the suppression of Rab5B most significantly increased HBV DNA in the culture supernatant. Surprisingly, 5 days after the transfection of Rab5B siRNA, HBV DNA in the supernatant was increased more than 30-fold, reflecting the increase of infectious HBV particles. Northern blotting showed that transcription of 2.4/2.1-kb mRNA coding envelope proteins containing large hepatitis B surface protein (LHBs) was increased. Analysis of hepatocyte nuclear factors (HNFs) showed that transcription of HNF4α, which is known to enhance 2.4-kb mRNA transcription, was regulated by Rab5B. Also, it was revealed that LHBs had accumulated in the endoplasmic reticulum (ER) after Rab5B depletion but not in the multivesicular body (MVB), which is thought to be an organelle utilized for HBV envelope formation. Therefore, it was considered that Rab5B is required for the transport of LHBs from the ER to MVB. Immunofluorescent microscopy showed that HBs proteins, including LHBs, colocalized with HBc in the ER of Rab5B-depleted cells, suggesting that HBV envelopment occurs not only in the MVB but also in the ER. In conclusion, Rab5B is a key regulator of HBV production and could be a target of antiviral therapy.IMPORTANCE HBV infection is a worldwide health problem, but the mechanisms of how HBV utilizes cellular machinery for its life cycle are poorly understood. In particular, it has been unclear how the viral components and virions are transported among the organelles. The HBV budding site has been reported to be the ER or MVB, but it has not been clearly determined. In this study, siRNA-based screening of Rab proteins using HBV-expressing cells showed that Rab5B, one of the Rab5 isoforms, has important roles in late steps of the HBV life cycle. Although Rab5 is known to work on early endosomes, this study showed that Rab5B plays a role in the transport of LHBs between the ER and MVB. Furthermore, it affects the transcription of LHBs. This is the first report on the mechanisms of HBV envelope protein transport among the organelles, and the results provide important insights into the therapeutic control of HBV infection.


Assuntos
Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B/crescimento & desenvolvimento , Hepatócitos/virologia , Interações entre Hospedeiro e Microrganismos , Proteínas rab5 de Ligação ao GTP/metabolismo , Linhagem Celular , Meios de Cultura/química , DNA Viral/análise , Retículo Endoplasmático/metabolismo , Inativação Gênica , Testes Genéticos , Humanos , Corpos Multivesiculares/metabolismo , Transporte Proteico , RNA Interferente Pequeno , Proteínas rab5 de Ligação ao GTP/genética
10.
Virus Genes ; 56(4): 439-447, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32361814

RESUMO

The frequency of HBV genomic methylation in the liver was reported to vary among patients, but the detailed mechanism is still unknown. In this study, the effects of HBV genome methylation on HBV replication were investigated in vitro. A total of 6 plasmids containing 1.24-fold the HBV genome of different genotypes (subgenotypes A1, A2, B1, and C2) were purified after in vitro methylation with CpG methyltransferase (M.SssI) and transfected into HepG2 cells. In genotype B and C strains, methylation markedly decreased the amount of hepatitis B e antigen (HBeAg) in the culture supernatant. A reduction of hepatitis B surface antigen (HBsAg) was found in some HBV strains but the reduction was smaller than that of HBeAg. There was no significant difference in particle-associated HBV DNA in the culture supernatant. These findings suggest that HBV genomic methylation might be involved in the HBeAg decline in genotype B and C, in part, and that the reduction of HBsAg was less than that of HBeAg. In conclusion, this study showed that the effect of HBV genomic methylation differs among HBV genotypes, suggesting a potential explanation for the different clinical outcomes of genotypes A, B, and C.


Assuntos
Metilação de DNA/genética , Antígenos E da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , DNA Viral/genética , Genótipo , Células Hep G2 , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/genética , Humanos , Replicação Viral/genética
11.
Sensors (Basel) ; 20(23)2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33291332

RESUMO

Orthoses and insoles are among the primary treatments and prevention methods of refractory plantar ulcers in patients with Hansen's disease. While dynamic plantar pressure and tactile sensory disturbance are the critical pathological factors, few studies have investigated whether a relationship exists between these two factors. In this study, dynamic pressure measured using F-scan system and tactile sensory threshold evaluated with monofilament testing were determined for 12 areas of 20 feet in patients with chronic Hansen's disease. The correlation between these two factors was calculated for each foot, for each clinical category of the foot (0-IV) and across all feet. A significant correlation was found between dynamic pressure and tactile sensation in Category II feet (n = 8, p = 0.016, r2 = 0.246, Spearman's rank test). In contrast, no significant correlation was detected for the entire foot or within the subgroups for the remainder of the clinical categories. However, the clinical manifestation of lesion areas showed high variability: (1) pressure concentrated, sensation lost; (2) margin of pressure concentration, sensation lost; (3) pressure concentrated, sensation severely disturbed but not lost; and (4) tip of the toe. These results may indicate that, even though there was a weak relationship between dynamic pressure and tactile sensation, it is important to assess both, in addition to the basics of orthotic treatment in patients with Hansen's disease presenting with refractory plantar ulceration.


Assuntos
Hanseníase , Monitorização Fisiológica , , Humanos , Hanseníase/complicações , Aparelhos Ortopédicos , Sapatos , Tato
12.
J Pathol ; 244(3): 367-379, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29235674

RESUMO

Oral squamous cell carcinoma (OSCC) has a very poor prognosis because of its highly invasive nature, and the 5-year survival rate has not changed appreciably for the past 30 years. Although cylindromatosis (CYLD), a deubiquitinating enzyme, is thought to be a potent tumour suppressor, its biological and clinical significance in OSCC is largely unknown. This study aimed to clarify the roles of CYLD in OSCC progression. Our immunohistochemical analyses revealed significantly reduced CYLD expression in invasive areas in OSCC tissues, whereas CYLD expression was conserved in normal epithelium and carcinoma in situ. Furthermore, downregulation of CYLD by siRNA led to the acquisition of mesenchymal features and increased migratory and invasive properties in OSCC cells and HaCaT keratinocytes. It is interesting that CYLD knockdown promoted transforming growth factor-ß (TGF-ß) signalling by inducing stabilization of TGF-ß receptor I (ALK5) in a cell autonomous fashion. In addition, the response to exogenous TGF-ß stimulation was enhanced by CYLD downregulation. The invasive phenotypes induced by CYLD knockdown were completely blocked by an ALK5 inhibitor. In addition, lower expression of CYLD was significantly associated with the clinical features of deep invasion and poor overall survival, and also with increased phosphorylation of Smad3, which is an indicator of activation of TGF-ß signalling in invasive OSCC. These findings suggest that downregulation of CYLD promotes invasion with mesenchymal transition via ALK5 stabilization in OSCC cells. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Movimento Celular , Enzima Desubiquitinante CYLD/metabolismo , Neoplasias Bucais/enzimologia , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/enzimologia , Idoso , Linhagem Celular Tumoral , Enzima Desubiquitinante CYLD/genética , Regulação para Baixo , Estabilidade Enzimática , Transição Epitelial-Mesenquimal , Feminino , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Invasividade Neoplásica , Fosforilação , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Transdução de Sinais , Proteína Smad3/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Fator de Crescimento Transformador beta/metabolismo
13.
Hepatol Res ; 49(8): 860-871, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30972908

RESUMO

AIM: Macrovesicular steatosis around the central vein (zone 3) is one of the pathological features of non-alcoholic fatty liver disease or steatohepatitis (NAFLD/NASH). The aim of this study is to elucidate precisely the association between the area of lipid droplets (LDs) and the plasma metabolic parameters in patients with NAFLD/NASH. METHODS: Eighty patients with NAFLD/NASH diagnosed by needle biopsy were enrolled. The LDs around zone 3 were counted automatically by image processing software, the total area of LDs (TLDs), the maximum area of LDs (MAXLDs), the average area of LDs (AVELDs) and the heterogeneity by the coefficient of variation (CV [%]) were quantified. The correlations between these values and plasma metabolic parameters were analyzed. We evaluated the association between branched chain amino acids (BCAAs) and the heterogeneity of LDs in hepatocytes in vitro and in vivo. RESULTS: The MAXLDs was significantly correlated with more metabolic parameters than AVELDs and TLDs. The level of BCAAs was independently associated with the CV among the metabolic parameters. In early stage NAFLD, aspartate and alanine aminotransferase were significantly higher in the high CV group than in the low CV group. The high concentration of BCAAs increased the CV of LDs in hepatocytes accompanied by the expression of phosphor-p70 S6 kinase and sterol regulatory element-binding protein 1 in vitro. A high BCAA diet induced high heterogeneity of LDs around zone 3 in ob/ob mice. CONCLUSIONS: The levels of BCAAs were associated with the LD heterogeneity of hepatocytes around zone 3 in patients with NAFLD/NASH.

14.
Hepatol Res ; 49(11): 1263-1274, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31254482

RESUMO

AIM: Hepatitis B virus genotype B (HBV/B) has been reported to have less risk of liver cirrhosis and hepatocellular carcinoma (HCC), but long-term observation has rarely been reported. We aimed to clarify the characteristics of HBV/B in nucleos(t)ide analog-treated patients in an area where HBV/B is more prevalent than in other areas of Japan. METHODS: A total of 498 chronically HBV-infected patients treated with nucleos(t)ide analog (lamivudine, entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate) for >6 months (mean 70.6 months) were included from nine hospitals in northeast Japan. The frequencies of hepatitis B surface antigen loss and HCC occurrence were analyzed. RESULTS: Among 427 patients whose genotype could be determined, 34.0% and 64.4% were infected with HBV/B and genotype C (HBV/C), respectively. The age of patients with HBV/B was significantly older than those with HBV/C (57.7 vs. 48.1). The cumulative rate of hepatitis B surface antigen loss was significantly higher in HBV/B than in HBV/C (3.6% vs. 0.7% at 10 years). Among 480 patients without HCC history, HCC occurrence was found in 40 patients (13.4% at 10 years). There was no cumulative rate difference of HCC occurrence among the genotypes, but after propensity score matching for age/sex, it was significantly lower in HBV/B than in HBV/C (5.3% vs. 18.5% at 10 years). CONCLUSIONS: Although a lower rate of HCC occurrence in HBV/B was shown by an age/sex-matched analysis than that in HBV/C, patients with HBV/B were significantly older and had a comparative risk of HCC occurrence in nucleos(t)ide analog-treated patients.

15.
Int J Mol Sci ; 20(10)2019 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-31109142

RESUMO

The highly malignant phenotype of oral squamous cell carcinoma (OSCC), including the presence of nodal and distant metastasis, reduces patient survival. High-mobility group A protein 2 (HMGA2) is a non-histone chromatin factor that is involved in advanced malignant phenotypes and poor prognosis in several human cancers. However, its biological role in OSCC remains to be elucidated. The purpose of this study was to determine the clinical significance and role of HMGA2 in the malignant potential of OSCC. We first investigated the expression pattern of HMGA2 and its clinical relevance in 110 OSCC specimens using immunohistochemical staining. In addition, we examined the effects HMGA2 on the regulation of vascular endothelial growth factor (VEGF)-A, VEGF-C, and fibroblast growth factor (FGF)-2, which are related to angiogenesis, in vitro. High expression of HMGA2 was significantly correlated with distant metastasis and poor prognosis. Further, HMGA2 depletion in OSCC cells reduced the expression of angiogenesis genes. In OSCC tissues with high HMGA2 expression, angiogenesis genes were increased and a high proportion of blood vessels was observed. These findings suggest that HMGA2 plays a significant role in the regulation of angiogenesis and might be a potential biomarker to predict distant metastasis and prognosis in OSCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Proteína HMGA2/metabolismo , Neoplasias Bucais/metabolismo , Neovascularização Patológica/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/irrigação sanguínea , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Feminino , Proteína HMGA2/análise , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/irrigação sanguínea , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/patologia , Invasividade Neoplásica/patologia , Neovascularização Patológica/diagnóstico , Neovascularização Patológica/patologia , Prognóstico
16.
Tohoku J Exp Med ; 241(1): 21-28, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28049871

RESUMO

It is important to determine the genotypes or serotypes of hepatitis C virus (HCV) in patients before treatment with direct-acting antiviral agents (DAAs), because the effects of DAAs differ among genotypes. In Japan, two tests for HCV typing are available clinically, but only serotyping, not genotyping, is approved by the public health insurance. Although most serotype-1 Japanese patients are infected with genotype 1b HCV, it is known that a small proportion of patients show different results from two typing methods. This study focused on such patients and the effectiveness of treatment with daclatasvir plus asunaprevir (DCV/ASV) was evaluated. We analyzed 644 DCV/ASV-treated patients with serotype 1 or genotype 1b, and among them, 166 serotype-1 patients received a commercial-based direct sequencing (DS) test for resistant-associated variants of genotype 1b HCV. We found four patients (2.4%) with DS test failure, suggesting that the PCR primers targeting genotype 1b may not match. Importantly, none of the four patients achieved a sustained virological response. Our in-house DS test analyzing the 5'-untranslated region and coding regions for NS4 and NS5B of HCV showed that three of the four patients were infected with genotype 2 HCV, and one patient was infected with genotype 1a HCV. No recombinant virus of different genotypes was found. This study indicates that a subset of serotype-1 hepatitis C patients is infected with HCV of genotype 2 or 1a in Japan and that DCV/ASV is not effective for such patients. Thus, attention should be paid to DAA treatment without HCV genotyping.


Assuntos
Hepacivirus/classificação , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Imidazóis/uso terapêutico , Isoquinolinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Carbamatos , Progressão da Doença , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Hepacivirus/isolamento & purificação , Humanos , Imidazóis/farmacologia , Isoquinolinas/farmacologia , Masculino , Pessoa de Meia-Idade , Filogenia , Pirrolidinas , Sorotipagem , Sulfonamidas/farmacologia , Fatores de Tempo , Resultado do Tratamento , Valina/análogos & derivados , Proteínas não Estruturais Virais/genética
17.
J Orthop Sci ; 22(5): 905-908, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28551281

RESUMO

BACKGROUND: A few reports have shown that the reliability of the Japanese Orthopaedic Association stage classification of hip osteoarthritis was not high. The objective of this study was to assess the reliability of the stage classification of coxarthrosis, and to evaluate whether a modification of the classification improves reliability. MATERIALS AND METHODS: We retrospectively investigated 200 hips in 100 patients with hip pain. We collected radiographs of their hip joints with the patients in both a supine and a standing position. Four orthopaedic surgeons evaluated the stage of coxarthrosis employing the JOA classification. The percentage of agreement of examiners and the value of the kappa statistic were calculated. Furthermore, to improve the reliability of classification, we modified the classification based on previous reports. Partial narrowing of the joint space and disappearance of the joint space were defined as maintained if it was 2 mm or more, and as the width of the loss of joint space that was 10 mm or more respectively. Using this classification, the same examiners assessed the stage on the same radiographs again three months after the previous evaluation. RESULTS: The percentages of agreement were 28.5% and 27% and the interobserver value of the kappa statistic was 0.45 and 0.44 in supine and standing position respectively. After modification of the classification, the percentages of agreement were 36.5% and 44% and the interobserver value of the kappa statistic was 0.48 and 0.56 in supine and standing positions respectively, and the intraobserver value of the kappa statistic was 0.55. The modification significantly improved the reliability only in the percentage of the agreement for the standing position. CONCLUSION: This study showed that the reliability of the JOA stage classification of coxarthrosis was not as high as previous reports have showed. Modification of the classification improved interobserver reliability.


Assuntos
Artrografia , Osteoartrite do Quadril/classificação , Osteoartrite do Quadril/diagnóstico por imagem , Idoso , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença
18.
Langmuir ; 32(37): 9557-65, 2016 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-27556745

RESUMO

Anion conductivity at the surfaces of two anion-exchange membranes (AEMs), quaternized ammonium poly(arylene ether) multiblock copolymer (QPE-bl-3) and quaternized ammonium poly(arylene perfluoro-alkylene) copolymer (QPAF-1), synthesized by our group was investigated using current-sensing atomic force microscopy under purified air at various relative humidities. The anion-conducting spots were distributed inhomogeneously on the surface of QPE-bl-3, and the total areas of the anion-conducting spots and the current at each spot increased with humidity. The anion-conductive areas on QPAF-1 were found on the entire surface even at a low humidity. Distribution of the anion-conducting spots on the membrane was found to directly affect the performance of an AEM fuel cell.

20.
J Phys Ther Sci ; 28(10): 2904-2908, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27821959

RESUMO

[Purpose] The aims of the present study were to investigate the most suitable location for vibroarthrography measurements of the knee joint to distinguish a healthy knee from knee osteoarthritis using Wavelet transform analysis. [Subjects and Methods] Participants were 16 healthy females and 17 females with severe knee osteoarthritis. Vibroarthrography signals were measured on the medial and lateral epicondyles, mid-patella, and tibia using stethoscopes with a microphone while subjects stood up from a seated position. Frequency and knee flexion angles at the peak wavelet coefficient were obtained. [Results] Peak wavelet coefficients at the lateral condyle and tibia were significantly higher in patients with knee osteoarthritis than in the control group. Knee joint angles at the peak wavelet coefficient were smaller (more extension) in the osteoarthritis group compared to the control group. The area under the receiver operating characteristic curve on tibia assessment with the frequency and knee flexion angles was higher than at the other measurement locations (both area under the curve: 0.86). [Conclusion] The tibia is the most suitable location for classifying knee osteoarthritis based on vibroarthrography signals.

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