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2.
Clin J Gastroenterol ; 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31970662

RESUMO

Epstein-Barr virus-associated gastric carcinoma (EBVaGC) can develop in gastric mucosa affected by Helicobacter pylori (H. pylori)-induced atrophic gastritis. However, it is unclear whether EBVaGC can develop in gastric mucosa after successful eradication of H. pylori. We report 3 cases of EBVaGC discovered more than 5 years after successful eradication of H. pylori. All 3 cases are men with a history of smoking. The periods from successful eradication to development of EBVaGC were 18, 8, and 9 years, respectively. Their tumors were mainly depressed lesions located in the gastric corpus. Two patients had intramucosal cancer and the other had advanced gastric cancer. Mucosal atrophy was present in the background gastric mucosa of all of three, and the anti-H. pylori antibody titer in each patient had fallen to < 3 U/mL. These cases indicate that EBVaGC can occur after successful eradication of H. pylori.

3.
Intern Med ; 59(2): 153-161, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31243237

RESUMO

Helicobacter pylori can infect the gastric mucosa and cause chronic inflammation, resulting in various diseases, including gastric cancer. Eradication of H. pylori in all infected subjects is recommended; however, the number of H. pylori strains with antibiotic resistance has increased, and the eradication rate has decreased. Vonoprazan, a potassium-competitive acid blocker, produces a stronger acid-inhibitory effect than proton pump inhibitors (PPIs). The H. pylori eradication rate with vonoprazan was found to be higher than that with PPIs. The H. pylori eradication rate with vonoprazan-based triple therapy (vonoprazan, amoxicillin, and clarithromycin) was approximately 90% and had an incidence of adverse events similar to that of PPIs. We review the current situation of H. pylori eradication in Japan, the first country in which vonoprazan was made available.

5.
J Hazard Mater ; 385: 121526, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31732351

RESUMO

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), commonly referred to simply as "dioxin", is a persistent environmental pollutant. Because of its high environmental persistence and biological accumulation, humans and animals are often exposed to TCDD. Therefore, the harmful effects on humans and animals is a major concern. Although studies have elucidated the adverse estrogenic and anti-estrogenic effects of TCDD, it is unclear in which tissues TCDD exerts these effects in vivo. To investigate the estrogen-related effects of TCDD in various tissues, we generated an improved estrogen-responsive reporter transgenic mouse in which the luciferase gene luc2 is expressed in response to estrogenic signals. Using these mice, we clarified that TCDD inhibits estrogenic signaling in liver and kidney but enhances estrogenic signaling in the pituitary gland in the same individual. Expression of aryl hydrocarbon receptor, aryl hydrocarbon receptor nuclear translocator, and estrogen receptor alpha mRNA was detected in liver, kidney, and pituitary gland, suggesting that the effects of TCDD on estrogenic signaling in these organs is independent of the expression pattern of these receptors. Thus, our results indicate that TCDD exerts both estrogenic and anti-estrogenic tissue-specific effects within the same individual.

6.
Microorganisms ; 7(12)2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31795435

RESUMO

BACKGROUND: Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is classified as one of the molecular subtypes of gastric cancer. We used droplet digital polymerase chain reaction (ddPCR) to enable highly sensitive and quantitative detection of EBV. METHODS: EBV-DNA load was calculated based on the copy number of the BamH1-W fragment of EBV by ddPCR, and the cut-off value of EBV-DNA load was set. We conducted both ddPCR and EBER1 ISH to examine whether their results coincided in 158 gastric cancer specimens of unknown EBV status. We prepared 26 biopsy specimens and 49 serum samples including EBVaGC and assayed them by ddPCR. RESULTS: The median values of EBV-DNA load for EBVaGC and EBV-negative control were 17.0 and 0.00308, respectively. A cut-off value of 0.032 was determined for which the sensitivity was 1. Among the 158 gastric cancer specimens, 14 lesions were judged as EBV-positive by the 0.032 cut-off value determined by ddPCR. The results of ddPCR and EBER1 ISH were in complete agreement. Even when using a biopsy specimen as a sample for ddPCR, the EBV-DNA load of all EBVaGCs was larger than the cut-off value. CONCLUSIONS: We established a new method of diagnosing EBVaGC from tissue samples by ddPCR.

8.
Intern Med ; 58(22): 3247-3250, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31735737

RESUMO

A 73-year-old man visited our hospital for the treatment of an early gastric cancer (GC) lesion. We performed en bloc resection using endoscopic submucosal dissection (ESD) for his GC lesion. The present GC lesion was Epstein-Barr virus (EBV)-associated poorly differentiated-type adenocarcinoma invading into the submucosal layer. Recently, accumulating data has shown that the risk of lymph node metastasis from early EBV GC without local lymphovascular infiltration is low. The present patient has been in good health for over three years since ESD. Some cases of early EBV GC with invasion into the submucosal layer may be candidates for further extension of the ESD criteria.


Assuntos
Adenocarcinoma/cirurgia , Adenocarcinoma/virologia , Detecção Precoce de Câncer/métodos , Ressecção Endoscópica de Mucosa/métodos , Herpesvirus Humano 4/isolamento & purificação , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/virologia , Adenocarcinoma/fisiopatologia , Idoso , Humanos , Masculino , Neoplasias Gástricas/fisiopatologia , Resultado do Tratamento
9.
Microorganisms ; 7(9)2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31480554

RESUMO

: Epstein-Barr virus (EBV) is a ubiquitous human herpes virus, but related with several types of malignancies. Among EBV-related malignancies, EBV-associated gastric carcinoma (EBVaGC) has the largest patient's number. We screened for EBV infection in 1067 GC lesions of 1132 patients who underwent surgical resection from 2007 to 2017 in Japan and examined clinicopathological features of EBVaGC. EBV infection was detected by in situ hybridization with EBV-encoded small RNA 1(EBER-1 ISH). EBV was infected in 80 GC lesions (7.1%). Mean age was significantly lower in patients with EBVaGC than with EBV-negative GC. EBVaGC was more frequent in men than in women. EBVaGC was found twice as frequent in the upper or middle stomach as in the lower stomach. Early EBVaGC was more frequent, and submucosally invaded cases were dominant. The presence of lymphatic vessel invasion was less in EBVaGC, but frequency of lymph node metastasis was similar. Carcinoma with lymphoid stroma (CLS) was found in 3.8% (43/1132) of all lesions with 60.5% of EBV positivity. The synchronous or metachronous multiple GC was frequent in EBVaGC. We clarified clinicopathologic characteristics of EBVaGC over the past decade in Japan. EBV infection should be examined in gastric cancer cases showing these characteristics.

10.
Endosc Int Open ; 7(7): E871-E882, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31286056

RESUMO

Background and study aims We developed an e-learning program for endoscopic diagnosis of invasion depth of early gastric cancer (EGC) using a simple diagnostic criterion called non-extension sign, and the contribution of self-study quizzes to improvement of diagnostic accuracy was evaluated. Methods We conducted a prospective randomized controlled study that recruited endoscopists throughout Japan. After completing a pretest, the participants watched video lectures and undertook post-test 1. The participants were then randomly allocated to either the self-study or non-self-study group, and participants in the first group completed the self-study program that comprised 100-case quizzes. Finally, participants in both groups undertook post-test 2. The primary endpoint was the difference in post-test 2 scores between the groups. The perfect score for the tests was set as 100 points. Results A total of 423 endoscopists completed the pretest and were enrolled. Post-test 1 was completed by 415 endoscopists and 208 were allocated to the self-study group and 207 to the non-self-study group. Two hundred and four in the self-study group and 205 in the non-self-study group were included in the analysis. Video lectures improved the mean score of post-test 1 from 72 to 77 points. Participants who completed the self-study quizzes showed significantly better post-test 2 scores compared with the non-self-study group (80 vs. 76 points, respectively, P  < 0.0001). Conclusions Our e-learning program showed that self-study quizzes consolidated knowledge of the non-extension sign and improved diagnostic ability of endoscopists for invasion depth of EGC.

11.
J Cardiol ; 74(6): 494-500, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31255462

RESUMO

BACKGROUND: Second-generation cryoballoon (2G-CB) ablation is highly effective for achieving pulmonary vein isolation (PVI) with a promising clinical outcome. However, the ideal freezing strategy for preventing gastroesophageal excessive transmural injury (ETI) remains under debate. This study aimed to clarify the correlation between gastroesophageal ETI and a bonus-freeze protocol after PVI using 2G-CBs. METHOD: This study included 100 patients who underwent PVI using 2G-CB followed by an endoscopic examination. The freeze-cycle duration was set at 180s. In the first 33 patients a 120s bonus-freeze was applied after successful PVI (bonus group), while in the following 67 the bonus freeze was omitted (non-bonus group). Early freezing interruption was performed when the esophageal temperature reached 25°C. Gastroesophageal ETI was defined as any injury that resulted from the PVI, including esophageal damage or periesophageal nerve injury. RESULTS: Gastroesophageal ETIs were observed in 9 (27.3%) and 6 (9.0%) patients and were all asymptomatic, esophageal damage in 3 and 0, and periesophageal nerve injury in the remaining 6 and 6 in the bonus group and non-bonus group, respectively (p=0.033). In the multivariate analysis, the bonus freeze protocol (odds ratio 3.527; 95% confidence interval 1.110-11.208; p=0.033) was the sole independent predictor of gastroesophageal ETI. During a one-year follow-up 26 of 33 bonus group patients (78.8%) and 52 of 67 (77.6%) non-bonus group patients remained in stable sinus rhythm without any differences between the groups. CONCLUSIONS: In the patients with a bonus-freeze protocol using the 2G-CB, gastroesophageal ETIs were detected more often than in those with the non-bonus freeze protocol. In contrast, freedom from atrial fibrillation after the 2G-CB based PVI was comparable when applying either a bonus or non-bonus freeze protocol.

12.
Brain Res ; 1721: 146312, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31323198

RESUMO

The local application of electrical currents to the cortex is one of the most commonly used techniques to activate neurons, and this intracortical stimulation (ICS) could potentially lead to new types of neuroprosthetic devices that can be directly applied to the cortex. To identify whether ICS-activated circuits are physiological vs. profoundly artificial, it is necessary to record in vivo the responses of the same neuronal population to both natural sensory stimuli and artificial electric stimuli. However, few studies have extensively reported simultaneous electrophysiological recordings combined with ICS. Here, we evaluated the similarity between sound- and ICS-driven cortical response patterns in different cortical layers. In the mouse auditory cortex, we performed laminar recordings using 16-channel silicon electrodes and ICS using sharp glass-pipette electrodes containing biocytin for layer identification. In different cortical depths, short current pulses were delivered in vivo to mice under urethane anesthesia. For the recorded data, we mainly analyzed properties of local field potentials and current source densities (CSDs). We demonstrated that electrical stimulation evoked different excitation patterns according to the stimulated cortical layer; responses to electric stimuli in layer 4 were most likely to mimic acoustic responses. Next, we proposed a CSD-based stimulation method to artificially synthesize sound-driven responses, using an approximation method associated with a linear combination of CSD patterns electrically stimulated in the different cortical layers. The result indicates that synthesized responses were consistent with the canonical model of sound processing. Using these approaches, we provide a new technique in which natural sound-driven responses can be mimicked by well-designed computational stimulation pattern sequences in a layer-dependent manner. These findings may aid in the future development of an electrical stimulation methodology for a cortical prosthesis.

13.
Hypertension ; 73(6): 1283-1290, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31006333

RESUMO

Peripheral 18-oxocortisol (18oxoF) level could contribute to the detection of aldosterone-producing adenoma (APA) in patients with primary aldosteronism. However, peripheral 18oxoF varies among such patients, which is a big drawback concerning its clinical application. We studied 48 cases of APA, 35 harboring KCNJ5 mutation, to clarify the significance of clinical and pathological parameters about peripheral 18oxoF. Peripheral 18oxoF concentration ranged widely from 0.50 to 183.13 ng/dL and correlated positively with intratumoral areas stained positively for steroidogenic enzymes ( P<0.0001). The peripheral 18oxoF level also correlated significantly with that of circulating aldosterone ( P<0.0001) but not with that of cortisol, a precursor of 18oxoF. However, a significant correlation was detected between peripheral 18oxoF and intratumoral glucocorticoids ( P<0.05). In addition, peripheral 18oxoF correlated positively with the number of hybrid cells double positive for 11ß-hydroxylase and aldosterone synthase ( P<0.0001). Comparing between the cases with and those without KCNJ5 mutation, the KCNJ5-mutated group demonstrated a significantly higher concentration of peripheral 18oxoF (28.4±5.6 versus 3.0±0.9 ng/dL, P<0.0001) and a larger intratumoral environment including the hybrid cells ( P<0.001), possibly representing a deviation from normal aldosterone biosynthesis. After multivariate analysis, KCNJ5 mutation status turned out to be the most associated factor involved in 18oxoF synthesis in APA ( P<0.0001). Results of our present study first revealed that enhanced 18oxoF synthesis in APA could come from a functional deviation of aldosterone biosynthesis from the normal zona glomerulosa and the utility of peripheral 18oxoF measurement could be influenced by the prevalence of KCNJ5 mutation in an APA.


Assuntos
Neoplasias do Córtex Suprarrenal/genética , Adenoma Adrenocortical/genética , Aldosterona/metabolismo , DNA de Neoplasias/genética , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genética , Hidrocortisona/análogos & derivados , Mutação/genética , Neoplasias do Córtex Suprarrenal/metabolismo , Adenoma Adrenocortical/metabolismo , Análise Mutacional de DNA , Feminino , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/metabolismo , Humanos , Hidrocortisona/biossíntese , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
J Gastrointest Cancer ; 50(3): 386-391, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29504086

RESUMO

PURPOSE: The utility of chromoendoscopy for early gastric cancer (GC) was determined by machine learning using data of color differences. METHODS: Eighteen histopathologically confirmed early GC lesions were examined. We prepared images from white light endoscopy (WL), indigo carmine (Indigo), and acetic acid-indigo carmine chromoendoscopy (AIM). A border between cancerous and non-cancerous areas on endoscopic images was established from post-treatment pathological findings, and 2000 pixels with equivalent luminance values were randomly extracted from each image of cancerous and non-cancerous areas. Each pixel was represented as a three-dimensional vector with RGB values and defined as a sample. We evaluated the Mahalanobis distance using RGB values, indicative of color differences between cancerous and non-cancerous areas. We then conducted diagnosis test using a support vector machine (SVM) for each image. SVM was trained using the 100 training samples per class and determined which area each of 1900 test samples per class came from. RESULTS: The means of the Mahalanobis distances for WL, Indigo, and AIM were 1.52, 1.32, and 2.53, respectively and there were no significant differences in the three modalities. Diagnosability per endoscopy technique was assessed using the F1 measure. The means of F1 measures for WL, Indigo, and AIM were 0.636, 0.618, and 0.687, respectively. AIM images were better than WL and Indigo images for the diagnosis of GC. CONCLUSION: Objective assessment by SVM found AIM to be suitable for diagnosis of early GC based on color differences.


Assuntos
Corantes/química , Endoscopia do Sistema Digestório/métodos , Mucosa Gástrica/patologia , Gastroscopia/métodos , Neoplasias Gástricas/classificação , Neoplasias Gástricas/diagnóstico , Máquina de Vetores de Suporte , Idoso , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Prognóstico
17.
Intern Med ; 58(5): 757-758, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30333416
18.
Gastric Cancer ; 22(3): 486-496, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30264329

RESUMO

BACKGROUND: Epstein-Barr virus (EBV) is an oncogenic human herpesvirus involved in the development of around 10% of gastric cancers. The overexpression of PD-L1 is one of the features of EBV-associated gastric cancer (EBVaGC); however, the function of PD-L1 has not been studied in EBVaGC. METHODS: We used three EBVaGC cell lines, SNU719 cells, NCC24 cells, and YCCEL1 cells, to evaluate the PD-L1 expression and function in EBVaGC. Jurkat T-lymphocytes expressing PD-1 were co-cultured with NCC24 and YCCEL1 cells and the cell cycles were analyzed. To study the regulatory mechanism for PD-L1 expression, the 3'UTR of PD-L1 was sequenced, and the effect of inhibitors of the IFN-γ signaling pathway was evaluated. RESULTS: All of the EBVaGC cell lines expressed PD-L1, and its expression was further enhanced by stimulation with IFN-γ. In Jurkat T-cells co-cultured with IFN-γ-stimulated NCC24 and YCCEL1 cells, the number of cells in the G0/G1 phase was significantly increased. This G0/G1 arrest was partially released by administration of anti-PD-L1 antibody. We found SNPs in PD-L1 3'UTR nucleotide sequences that were located at seed regions for microRNAs. Treatment of EBVaGC cell lines with JAK2-inhibitor, PI3K-inhibitor, and mTOR inhibitor reduced the level of PD-L1 expression to the same level as cells without IFN-γ stimulation. CONCLUSIONS: EBVaGC cells expressing high levels of PD-L1 suppress T-cell proliferation, and the IFN-γ signaling pathway is involved in the expression of PD-L1.


Assuntos
Antígeno B7-H1/metabolismo , Infecções por Vírus Epstein-Barr/complicações , Regulação Neoplásica da Expressão Gênica , Herpesvirus Humano 4/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias Gástricas/imunologia , Linfócitos T/imunologia , Apoptose , Antígeno B7-H1/genética , Ciclo Celular , Proliferação de Células , Inibidores Enzimáticos/farmacologia , Infecções por Vírus Epstein-Barr/virologia , Humanos , Polimorfismo de Nucleotídeo Único , Receptor de Morte Celular Programada 1/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/virologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Células Tumorais Cultivadas
19.
Parasite ; 25: 58, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30474599

RESUMO

Peniculus hokutoae n. sp. is described on the basis of an ovigerous adult female parasitizing the caudal fin of the myctophid fish Symbolophorus evermanni (Gilbert, 1905), collected from Suruga Bay, Japan. This is the first record of parasitism by this genus on mesopelagic myctophid fish. The new species is easily distinguished from other congeners in: (1) the presence of a conical process anterior to the rostrum; (2) the secondary elongation of the first pedigerous somite; (3) the incorporation of the third and fourth pedigerous somites into the trunk; (4) the unilobate maxillule bearing two unequal apical setae; (5) the lack of any processes on the first segment of the maxilla. Four morphological patterns of the cephalothorax, neck and anterior parts of the trunk can be found in the genus. We infer that initial colonization of a mesopelagic myctophid fish as host is likely to have occurred when the diurnally-migrating myctophid host was feeding in near-surface waters at night and was exposed to infective stages of Peniculus.


Assuntos
Copépodes/fisiologia , Ectoparasitoses/veterinária , Doenças dos Peixes/parasitologia , Nadadeiras de Animais/parasitologia , Animais , Copépodes/anatomia & histologia , Copépodes/genética , Ectoparasitoses/epidemiologia , Ectoparasitoses/parasitologia , Feminino , Doenças dos Peixes/epidemiologia , Peixes , Japão/epidemiologia , Alimentos Marinhos/parasitologia , Fatores Socioeconômicos , Especificidade da Espécie , Simbiose
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