Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 26
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Gan To Kagaku Ryoho ; 51(9): 951-953, 2024 Sep.
Artículo en Japonés | MEDLINE | ID: mdl-39462634

RESUMEN

A 57-year-old man visited our hospital due to abnormal chest X-ray findings. Chest computed tomography(CT)showed amalgamated beaded solid nodules in the right upper lobe of the lung. Lobectomy of the right upper lobe was performed and the nodule was histologically determined to be seminoma. Positron emission tomography(PET)-CT showed high 18F-fluorodeoxyglucose(FDG)uptake in the lung nodules and faint uptake in the left testicle. As ultrasound and palpation detected no tumor in the testes, consent to perform orchiectomy was not obtained. Considering the PET-CT findings, we diagnosed testicular seminoma with solitary pulmonary metastasis, which is extremely rare.


Asunto(s)
Neoplasias Pulmonares , Seminoma , Neoplasias Testiculares , Humanos , Masculino , Seminoma/cirugía , Seminoma/patología , Seminoma/diagnóstico , Seminoma/secundario , Neoplasias Testiculares/patología , Neoplasias Testiculares/cirugía , Persona de Mediana Edad , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
2.
Gan To Kagaku Ryoho ; 50(10): 1077-1079, 2023 Oct.
Artículo en Japonés | MEDLINE | ID: mdl-38035838

RESUMEN

CASE: A 69-year-old man reported globus sensations since November X and was diagnosed with bilateral pneumonia in December at a local clinic. The patient was subsequently admitted to our hospital for a diagnosis and treatment. His pneumonia improved with antibiotics, but pneumonia recurred. However, pneumonia recurred in February X+1, and antibiotic treatment once again provided relief. However, globus sensations persisted even after the remission of pneumonia. Endoscopic observations revealed a tumor in the hypopharynx, which caused saliva aspiration into the insufficiently closed vocal cords. The hypopharyngeal cancer was treated with chemoradiotherapy, and thereafter, the frequency of aspiration pneumonia decreased. CONCLUSION: The present case illustrated that sometimes aspiration pneumonia may be caused by laryngeal and hypopharyngeal cancer.


Asunto(s)
Neoplasias Hipofaríngeas , Laringe , Neumonía por Aspiración , Masculino , Humanos , Anciano , Neoplasias Hipofaríngeas/terapia , Neoplasias Hipofaríngeas/complicaciones , Recurrencia Local de Neoplasia , Hipofaringe , Neumonía por Aspiración/etiología
3.
Dig Dis Sci ; 67(10): 4770-4779, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35088188

RESUMEN

BACKGROUND: We previously reported that clumps of a few epithelial cells were scattered in ulcer regions in a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis (UC). AIMS: To determine the ectopically localized epithelial clumps might be derived from stem cells or their daughter progenitor cells. METHODS: Female BALB/c mice were administered DSS in drinking water for 6 days, followed by withdrawal of DSS for 6 days. Histological and immunohistochemical examinations were conducted in the distal region and proximal region of the colorectum to determine expression of stem cell markers in the epithelial clumps. RESULTS: Similar to the characteristics of UC, the ulcers were more severe in the distal region close to the anus than in the proximal region of the colorectum. Quantitative analyses revealed that the epithelial clumps appeared in relation to the severity of the ulcer, and they expressed the cell adhesion molecules E-cadherin and ß-catenin. Among stem cell markers, the epithelial clumps primarily expressed +5 cell marker Dll1 as reserved intestinal stem cells, followed by +4 cell marker Bmi1 and crypt stem cell marker Lgr5 in that order. Nuclear expression of Sox9, but not nuclear ß-catenin, was identified in the clumps. CONCLUSION: The present results suggest that most epithelial clumps comprised crypt-derived, reserved stem cells, which might have potential for mucosal healing.


Asunto(s)
Colitis Ulcerosa , Colitis , Agua Potable , Animales , Cadherinas/metabolismo , Colitis/inducido químicamente , Colitis Ulcerosa/patología , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Agua Potable/efectos adversos , Agua Potable/metabolismo , Células Epiteliales/metabolismo , Femenino , Mucosa Intestinal/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Células Madre/patología , Úlcera/inducido químicamente , Úlcera/patología , beta Catenina/metabolismo
4.
Digestion ; 102(4): 590-598, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32866955

RESUMEN

BACKGROUND: Submucosal fibrosis observed during colorectal endoscopic submucosal dissection (ESD) is an important factor related to incomplete resection. Biopsy is generally accepted as having the potential to elicit submucosal fibrosis, but few reports have presented definitive proof. This study investigated the relation between submucosal fibrosis and colorectal ESD outcomes and assessed factors related to fibrosis, including pretreatment biopsy. METHODS: After reviewing 369 records of colorectal ESD performed between January 2011 and December 2016, we assessed the relation between fibrosis and ESD outcomes. Multiple logistic regression analysis revealed fibrosis risk factors. RESULTS: Severe fibrosis was related significantly to ESD outcomes such as the mean procedure time (p < 0.001), en bloc resection rate (p < 0.001), and R0 resection rate (p = 0.011). Multivariate analyses indicated residual lesions (ORs 175.4, p < 0.001), pretreatment biopsy (ORs 8.30, p = 0.002), nongranular-type laterally spreading tumors (LST-NG; ORs 5.86, p = 0.025), and invasive carcinoma (ORs 5.83, p = 0.03) as independent risk factors of severe fibrosis. In each macroscopic type, LST-NG was more strongly related to fibrosis induced by pretreatment than granular-type laterally spreading tumors with adjust ORs of 50.8 and 4.69. CONCLUSIONS: Pretreatment biopsy causes submucosal fibrosis resulting in prolonged procedure times and incomplete resection. These findings suggest important benefits of avoiding biopsy before ESD.


Asunto(s)
Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Fibrosis de la Submucosa Bucal , Biopsia , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Resección Endoscópica de la Mucosa/efectos adversos , Fibrosis , Humanos , Mucosa Intestinal/patología , Mucosa Intestinal/cirugía , Fibrosis de la Submucosa Bucal/patología , Estudios Retrospectivos , Resultado del Tratamiento
5.
Cancer Sci ; 110(9): 2806-2821, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31254429

RESUMEN

In human and dogs, bladder cancer (BC) is the most common neoplasm affecting the urinary tract. Dog BC resembles human muscle-invasive BC in histopathological characteristics and gene expression profiles, and could be an important research model for this disease. Cancer patient-derived organoid culture can recapitulate organ structures and maintains the gene expression profiles of original tumor tissues. In a previous study, we generated dog prostate cancer organoids using urine samples, however dog BC organoids had never been produced. Therefore we aimed to generate dog BC organoids using urine samples and check their histopathological characteristics, drug sensitivity, and gene expression profiles. Organoids from individual BC dogs were successfully generated, expressed urothelial cell markers (CK7, CK20, and UPK3A) and exhibited tumorigenesis in vivo. In a cell viability assay, the response to combined treatment with a range of anticancer drugs (cisplatin, vinblastine, gemcitabine or piroxicam) was markedly different in each BC organoid. In RNA-sequencing analysis, expression levels of basal cell markers (CK5 and DSG3) and several novel genes (MMP28, CTSE, CNN3, TFPI2, COL17A1, and AGPAT4) were upregulated in BC organoids compared with normal bladder tissues or two-dimensional (2D) BC cell lines. These established dog BC organoids might be a useful tool, not only to determine suitable chemotherapy for BC diseased dogs but also to identify novel biomarkers in human muscle-invasive BC. In the present study, for the 1st time, dog BC organoids were generated and several specifically upregulated organoid genes were identified. Our data suggest that dog BC organoids might become a new tool to provide fresh insights into both dog BC therapy and diagnostic biomarkers.


Asunto(s)
Técnicas de Cultivo de Célula/métodos , Enfermedades de los Perros/patología , Organoides/patología , Neoplasias de la Vejiga Urinaria/veterinaria , Vejiga Urinaria/patología , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/genética , Enfermedades de los Perros/orina , Perros , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Masculino , Organoides/efectos de los fármacos , Organoides/metabolismo , Análisis de Secuencia de ARN , Regulación hacia Arriba , Vejiga Urinaria/citología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/orina , Orina/citología , Urotelio/citología
6.
Nihon Shokakibyo Gakkai Zasshi ; 114(2): 274-282, 2017.
Artículo en Japonés | MEDLINE | ID: mdl-28163293

RESUMEN

A 65-year-old female presented with an elevated lesion that was identified in the gallbladder fundus via abdominal ultrasound during a medical checkup. The tumor was a pedunculated lesion, measuring 30mm in diameter, that exhibited a blood flow pattern with gradual dense staining throughout the equilibrium phase on the abdominal contrast computed tomography and a high signal intensity on T2-weighted magnetic resonance imaging. Histopathological findings revealed the proliferation of poorly differentiated adenocarcinoma, including signet ring cells, throughout the tumor along with the formation of a mucous lake. The patient was consequently diagnosed with poorly differentiated mucinous carcinoma of the gallbladder.


Asunto(s)
Adenocarcinoma Mucinoso/diagnóstico por imagen , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Adenocarcinoma Mucinoso/cirugía , Anciano , Femenino , Neoplasias de la Vesícula Biliar/patología , Humanos , Imagen por Resonancia Magnética , Imagen Multimodal , Tomografía Computarizada por Rayos X
7.
Nihon Shokakibyo Gakkai Zasshi ; 114(9): 1639-1648, 2017.
Artículo en Japonés | MEDLINE | ID: mdl-28883293

RESUMEN

BACKGROUNDS AND AIMS: Peripherally inserted central catheters (PICC) have been widely used as a blood access route for total parenteral nutrition (TPN) in recent years. However, there have been few reports that evaluated the usefulness of PICC for patients with inflammatory bowel disease (IBD). In this study, we compared the clinical courses in patients with IBD who received TPN during their hospitalization by conventional central venous catheters (CVC) and PICC. PATIENTS AND METHODS: A total of 137 IBD patients were enrolled. The CVC group and the PICC group included 56 and 81 patients, respectively. The clinical courses in both groups were compared retrospectively. RESULTS: As a complication of the puncture, pneumothorax occurred in two patients (3.6%) in the CVC group, but in none (0%) in the PICC group. The PICC group had significantly higher rates of achieving the scheduled TPN without removing the catheter, lower rates of catheter-related blood stream infection (CRBSI) and longer periods without CRBSI than the CVC group. CONCLUSION: PICC might be more useful than CVC in terms of safety and the ability to deliver scheduled TPN for IBD patients.


Asunto(s)
Enfermedades Inflamatorias del Intestino/terapia , Nutrición Parenteral Total , Adulto , Cateterismo Periférico , Femenino , Humanos , Masculino , Estudios Retrospectivos
8.
Micromachines (Basel) ; 14(2)2023 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-36838100

RESUMEN

To expand the applications of the electroencephalogram (EEG), long-term measurement, a short installation time, and little stress on the participants are needed. In this study, we designed, fabricated, and evaluated an EEG headset with three candle-like microneedle electrodes (CMEs). The user is able to detach and reattach the electrodes, enabling long-term measurement with little stress. The design of the CMEs was experimentally determined by considering the skin-to-electrode impedance and user comfort. An EEG was successfully measured from areas with a high hair density without any preparation. The installation time was shorter than 60 s and the electrodes could be detached and reattached. The headset was designed such that the discomfort caused by its ear pads was higher than that caused by the electrodes. In 1 h experiments, the participants did not feel pain and the detachment of the CMEs was found to improve the comfort level of the participants in most cases. A successful demonstration of the long-term measurement of EEGs while watching a whole movie verified that the developed EEG headset with CMEs is applicable for EEG measurement in a variety of applications.

9.
DEN Open ; 3(1): e126, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36247312

RESUMEN

We report two cases of the rare complication of a colonoscope incarcerated in an inguinal hernia. The first patient was a 73-year-old man in whom a colonoscope was incarcerated in a left inguinal hernia on attempted withdrawal. The incarcerated colonoscope was successfully reduced manually under fluoroscopic guidance. The hernia was subsequently repaired using an extraperitoneal approach followed by a successful colonoscopy. The second patient was a 74-year-old man in whom the colonoscope became incarcerated in a left inguinal hernia on insertion. Similar to the first case, the colonoscope was manually reduced under fluoroscopy and the entire colonoscopy was then uneventfully performed. An advanced sigmoid cancer was identified and treated with sigmoidectomy. The hernia resolved after this operation. When a colonoscope becomes incarcerated in an inguinal hernia, the manual reduction should be attempted. Subsequent colonoscopy can be safely performed under certain circumstances.

10.
J Toxicol Sci ; 47(7): 289-300, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35786680

RESUMEN

To study the effects of autophagy inducer carbamazepine (CBZ) in a high-fat diet (HFD)/streptozotocin (STZ)-related early hepatocarcinogenesis model, we determined autophagic flux by immunohistochemical analysis of autophagy marker expression in preneoplastic liver foci and compared that with the expression of the NADPH oxidase subunit. Male F344 rats were fed a basal diet or HFD and subjected to two-stage hepatocarcinogenesis; diabetes mellitus was induced via STZ administration. Several STZ-treated, HFD-fed rats were administered CBZ (a total of five doses every one or two days) at week 7 and 8. STZ-treated, HFD-fed rats decreased ß cells in the islet of Langerhans and increased adipophilin-positive lipid droplets in the liver; moreover, they had a larger area of glutathione S-transferase placental form-immunopositive preneoplastic liver foci, which was associated with inhibition of autophagy and induction of the NADPH oxidase subunit, as demonstrated by increased immunohistochemical expression of an autophagosome receptor marker microtubule-associated protein light chain 3 (LC3)-binding protein p62, and of an NADPH oxidase subunit p22phox in the preneoplastic foci. An increased trend of an autophagy phagophore marker LC3 in preneoplastic foci was also detected. CBZ administration could induce autophagy and impair p22phox expression, as shown by altered expression of autophagy regulators (Atg5, Atg6, Lamp1, Lamp2, and Lc3), NADPH oxidase subunits (P22phox and P67phox), and antioxidant enzymes Gpx1 and Gpx2. These results suggest that inhibition of autophagy and induction of p22phox might contribute to HFD/STZ-related early hepatocarcinogenesis in rats; however, the effects of CBZ administration on the STZ/HFD-increased preneoplastic foci were marginal in this study.


Asunto(s)
Dieta Alta en Grasa , NADPH Oxidasas , Animales , Autofagia , Carcinogénesis , Dieta Alta en Grasa/efectos adversos , Femenino , Masculino , Proteínas Asociadas a Microtúbulos , NADPH Oxidasas/metabolismo , Placenta/metabolismo , Embarazo , Ratas , Ratas Endogámicas F344 , Estreptozocina
11.
Nutr Res ; 85: 99-118, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33460863

RESUMEN

An amorphous formula of curcumin (CUR) has shown to enable an improved bioavailability after ingestion. The aim of this study was to investigate the hypothesis that exogenously administered CUR has an advantage in ameliorating post-traumatic stress disorder at low doses. To this end, Long-Evans rats were dietary exposed to CUR at 0.1% or 0.5% from gestational day 6 to postnatal day (PND) 74 or 77. Offspring exposed to 0.1% CUR revealed facilitation of anti-anxiety-like behavior in the open field test and fear-extinction learning tested during PND 62 to 74, increases in hippocampal granule cells expressing immediate-early gene proteins and a decrease in prelimbic cortical neurons expressing phosphorylated extracellular signal-regulated kinase 1/2 after the last trial of the fear-extinction learning test on PND 74. The constitutive gene expression levels of Gria1, Gria2, Grin2d, Slc17a6, and Slc17a7 were altered in the hippocampal dentate gyrus and amygdala on PND 77. These results suggest alterations in synaptic plasticity to strengthen neural circuits in promoting the behavioral effects by 0.1%-CUR. In contrast, 0.5% CUR revealed a lack of any of the changes in behavioral tests that were observed at 0.1%; however, this dose upregulated oxidative stress and neuroinflammation-related genes in the hippocampal dentate gyrus, and increased neural stem cells and proliferation activity of the subgranular zone in the dentate gyrus. These results suggest a possible preventive use of CUR at low doses in mitigating some stress disorders; however, excessively absorbed doses may prevent behavioral changes by inducing neuroinflammation that affects hippocampal neurogenesis involving neural stem cells.


Asunto(s)
Ansiedad , Conducta Animal , Encéfalo/fisiología , Curcumina/administración & dosificación , Miedo , Animales , Animales Recién Nacidos , Condicionamiento Psicológico , Curcumina/análisis , Curcumina/farmacología , Giro Dentado/fisiología , Extinción Psicológica , Femenino , Expresión Génica , Hipocampo/fisiología , Masculino , Neurogénesis , Neuroglía/citología , Plasticidad Neuronal , Neuronas/metabolismo , Corteza Prefrontal/fisiología , Embarazo , Efectos Tardíos de la Exposición Prenatal , Ratas , Ratas Long-Evans , Sinapsis/fisiología
12.
JGH Open ; 4(4): 624-631, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32782948

RESUMEN

BACKGROUND AND AIM: The T-cell receptor (TCR) repertoire was assessed in response to various antigens and was considered to be associated with the pathogenesis of inflammatory bowel disease (IBD). Thus, we performed TCR repertoire analysis to examine the pathology of IBD from changes in the TCR repertoire of memory T cells in the intestinal lamina propria mononuclear cells (LPMCs) and peripheral blood mononuclear cells (PBMCs) of patients with IBD. METHODS: LPMCs in the surgical specimens and PBMCs were isolated from 12 patients with IBD (5 patients with ulcerative colitis [UC] and 7 patients with Crohn's disease [CD]). PBMCs were collected from 10 healthy individuals as controls. Comprehensive TCR sequence analyses of adaptor-ligation polymerase chain reaction (PCR) products were performed using MiSeq. RESULTS: The diversity of TCR-α and TCR-ß in PBMCs was significantly lower in patients with IBD than that in controls (P = 0.00084 and 0.0013, respectively). Comparisons of TCR diversity in LPMCs and PBMCs between CD and UC showed that the diversity in LPMC was not affected by diseases, whereas that in PBMCs was significantly lower in CD than in UC (P = 0.045 and 0.049, respectively). Some TCR clones may have shown a specific increase or decrease in CD and UC, and many clones were common to both LPMCs and PBMCs in the same patients. CONCLUSION: The diversity of TCR clones in LPMCs and PBMCs in patients with IBD was significantly lower than that of PBMCs in controls. TCR diversity in PBMCs was particularly low in patients with CD.

13.
J Gastroenterol ; 55(1): 67-77, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31641873

RESUMEN

BACKGROUND: The genetic variants of NUDT15 have been verified to induce adverse events (AEs) of thiopurines. Codon 139 variants are frequently observed in Asians, while multiple variants are seen in codon 18 which also cause AEs including the European ancestry. The purpose of this study is to establish a technique capable of the simple genotyping of NUDT15 codon 18 and to evaluate its efficacy. METHODS: A high-resolution melt (HRM) technique is performed to simply determine genotypes. The accuracy of HRM analysis was evaluated with DNAs from 1245 Japanese patients with inflammatory bowel diseases. Subsequently, another group of 572 patients was analyzed to verify the method. The diplotypes and the frequency of their AEs were estimated on the basis of codon 18 and 139 genotypes. RESULTS: The HRM analysis enabled the correct identification of the three main genotypes, ref/ref, ref/ins, and ref/V18I, in 1236 of 1241 cases. All rare genotypes including ref/del were identified as the impossible-to-determine group, the proper diagnosis rate was 99.6%. In the verification test using other samples, the diagnosis rate was 99.7%. By estimating diplotypes using both codon 18 and 139 genotypes, 2.74% and 2.13% of Japanese patients with Arg/Arg and Arg/Cys of codon 139 have a lower enzymatic activity of NUDT15 and a higher risk for adverse responses than those estimated by codon 139 genotypes alone. CONCLUSIONS: Our study showed that HRM method enables simple genotyping of complicated codon 18 variants essential to haplotype estimation of the NUDT15.


Asunto(s)
Técnicas de Genotipaje/métodos , Inmunosupresores/efectos adversos , Enfermedades Inflamatorias del Intestino/genética , Mercaptopurina/efectos adversos , Variantes Farmacogenómicas , Pirofosfatasas/genética , Femenino , Marcadores Genéticos , Humanos , Inmunosupresores/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/metabolismo , Masculino , Mercaptopurina/uso terapéutico , Pirofosfatasas/metabolismo
15.
Biomaterials ; 237: 119823, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32044522

RESUMEN

Non-alcoholic steatohepatitis (NASH) is associated with liver fibrosis and cirrhosis, which eventually leads to hepatocellular carcinoma. Although several animal models were developed to understand the mechanisms of NASH pathogenesis and progression, it remains obscure. A 3D organoid culture system can recapitulate organ structures and maintain gene expression profiles of original tissues. We therefore tried to generate liver organoids from different degrees [defined as mild (NASH A), moderate (NASH B) and severe (NASH C)] of methionine- and choline-deficient diet-induced NASH model mice and analyzed the difference of their architecture, cell components, organoid-forming efficacy, and gene expression profiles. Organoids from each stage of NASH model mice were successfully generated. Interestingly, epithelial-mesenchymal transition was observed in NASH C organoids. Expression of Collagen I and an activated hepatic stellite cell marker, α-sma was upregulated in the liver organoids from NASH B and C mice. The analysis of RNA sequencing revealed that several novel genes were upregulated in all NASH liver organoids. These results suggest that our generated liver organoids from different stages of NASH diseased mice might become a useful tool for in vitro studies of the molecular mechanism of NASH development and also for identifying novel biomarkers for early diagnosis of NASH disease.


Asunto(s)
Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Animales , Modelos Animales de Enfermedad , Hígado/patología , Cirrosis Hepática/patología , Neoplasias Hepáticas/patología , Ratones , Ratones Endogámicos C57BL , Organoides
16.
Sci Rep ; 10(1): 10236, 2020 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-32581322

RESUMEN

Expression quantitative trait locus (eQTL) analyses have enabled us to predict the function of disease susceptibility SNPs. However, eQTL for the effector memory T cells (TEM) located in the lamina propria mononuclear cells (LPMCs), which play an important role in Crohn's disease (CD), are not yet available. Thus, we conducted RNA sequencing and eQTL analyses of TEM cells located in the LPMCs from IBD patients (n = 20). Genome-wide association study (GWAS) was performed using genotyping data of 713 Japanese CD patients and 2,063 controls. We compared the results of GWAS and eQTL of TEM, and also performed a transcriptome-wide association study using eQTL from Genotype Tissue Expression project. By eQTL analyses of TEM, correlations of possible candidates were confirmed in 22,632 pairs and 2,463 genes. Among these candidates, 19 SNPs which showed significant correlation with tenascin-XA (TNXA) expression were significantly associated with CD in GWAS. By TWAS, TNFSF15 (FDR = 1.35e-13) in whole blood, ERV3-1 (FDR = 2.18e-2) in lymphocytes, and ZNF713 (FDR = 3.04e-2) in the sigmoid colon was significantly associated with CD. By conducting integration analyses using GWAS and eQTL data, we confirmed multiple gene transcripts are involved in the development of CD.


Asunto(s)
Enfermedad de Crohn/genética , Perfilación de la Expresión Génica/métodos , Estudio de Asociación del Genoma Completo/métodos , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Adulto , Anciano , Estudios de Casos y Controles , Proteínas de Unión al ADN/genética , Femenino , Regulación de la Expresión Génica , Predisposición Genética a la Enfermedad , Humanos , Japón , Masculino , Persona de Mediana Edad , Análisis de Secuencia de ARN , Subgrupos de Linfocitos T/metabolismo , Tenascina/genética , Factores de Transcripción/genética , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/genética , Adulto Joven
17.
Inflamm Bowel Dis ; 26(8): 1177-1187, 2020 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-32072174

RESUMEN

BACKGROUND: To clarify the genetic background of ulcerative colitis (UC) in the Japanese population, we conducted a genome-wide association study (GWAS) using a population-specific single nucleotide polymorphism (SNP) array. METHODS: We performed a GWAS and replication study including 1676 UC patients and 2381 healthy controls. The probability of colectomy was compared between genotypes of rs117506082, the top hit SNP at HLA loci, by the Kaplan-Meier method. We studied serum expression of miR-622, a newly identified candidate gene, from 32 UC patients and 8 healthy controls by quantitative reverse-transcription polymerase chain reaction. RESULTS: In the GWAS, only the HLA loci showed genome-wide significant associations with UC (rs117506082, P = 6.69E-28). Seven nominally significant regions included 2 known loci, IL23R (rs76418789, P = 6.29E-7) and IRF8 (rs16940202, P = 1.03E-6), and 5 novel loci: MIR622 (rs9560575, P = 8.23E-7), 14q31 (rs117618617, P = 1.53E-6), KAT6B (rs12260609, P = 1.81E-6), PAX3-CCDC140-SGPP2 (rs7589797, P = 2.87E-6), and KCNA2 (rs118020656, P = 4.01E-6). Combined analysis revealed that IL23R p.G149R (rs76418789, P = 9.03E-11; odds ratio [OR], 0.51) had genome-wide significant association with UC. Patients with GG genotype of rs117506082 had a significantly lower probability of total colectomy than those with the GA+AA genotype (P = 1.72E-2). Serum expression of miR-622 in patients with inactive UC tended to be higher than in healthy controls and patients with active UC (inactive UC vs healthy controls, P = 3.03E-02; inactive UC vs active UC, P = 6.44E-02). CONCLUSIONS: IL23R p.G149R is a susceptibility locus for UC in Japanese individuals. The GG genotype of rs117506082 at HLA loci may predict a better clinical course.


Asunto(s)
Pueblo Asiatico/genética , Colitis Ulcerosa/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple/genética , Estudios de Casos y Controles , Colitis Ulcerosa/etnología , Sitios Genéticos/genética , Estudio de Asociación del Genoma Completo , Genotipo , Antígenos HLA/genética , Humanos , Japón , Estimación de Kaplan-Meier , MicroARNs/sangre , Análisis de Componente Principal , Receptores de Interleucina/genética
18.
J Toxicol Sci ; 44(8): 565-574, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31378768

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive deposition of droplets in hepatocytes. Patients with NAFLD can be at risk for nonalcoholic steatohepatitis, which can lead to hepatocellular carcinoma. Autophagy is a cellular pathway that is crucial for survival and homeostasis, and which protects against pathophysiological changes like obesity and cancer. We determined the expression of autophagy markers in preneoplastic hepatic lesions and the effects of an autophagy repressor chloroquine (CQ) or inducer amiodarone (AM) in a steatosis-related hepatocarcinogenesis model. Male F344 rats were fed a control diet or high fat diet (HFD), and subjected to initiation and promotion steps with N-nitrosodiethylamine injection at week 0 and a partial hepatectomy at week 3. Several HFD-fed rats were administered 0.1% CQ and 0.5% AM in their drinking water during week 2 and 8. CQ and AM did not improve HFD-induced obesity. AM, but not CQ, significantly decreased the number of glutathione S-transferase placental form-positive preneoplastic liver foci in the liver. Autophagosome markers LC3 and the LC3-binding protein p62 were heterogeneously expressed in the preneoplastic foci. CQ might inhibit autophagy by significantly increased p62/LC3 ratio, while AM might have a potential of inducing autophagy by showing an increased gene expression of the autophagy regulator, Atg5. These results suggest that preneoplastic lesions express autophagosome markers and that AM might decrease steatosis-related early hepatocarcinogenesis by potentially inducing autophagy in HFD-fed rats, while inhibition of autophagy by CQ did not alter the hepatocarcinogenesis. However, an immunohistochemical trial revealed a technical limitation in detecting autophagosome markers because there were variations in each preneoplastic lesion.


Asunto(s)
Autofagosomas , Autofagia/genética , Dieta Alta en Grasa/efectos adversos , Expresión Génica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Hígado/metabolismo , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Lesiones Precancerosas/genética , Lesiones Precancerosas/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Amiodarona/farmacología , Animales , Autofagia/efectos de los fármacos , Proteína 5 Relacionada con la Autofagia/genética , Proteína 5 Relacionada con la Autofagia/metabolismo , Cloroquina/farmacología , Modelos Animales de Enfermedad , Humanos , Inmunohistoquímica , Masculino , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Ratas Endogámicas F344
19.
J Vet Med Sci ; 81(12): 1749-1752, 2019 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-31645509

RESUMEN

A 25-month-old female crossbred cow presented with astasia, emaciation, and stunted growth. Macroscopic examination revealed a large mass in the abdominal cavity, approximately 100 × 30 × 30 cm. Microscopic examination revealed that the mass consisted of multilobular mature and immature cartilaginous matrices with chondrocytic cells, surrounded by spindle to pleomorphic mesenchymal tumor cells. The cartilaginous matrices consisted of hyaline and elastic cartilages, as confirmed with Azan stain, and Victoria Blue and Van Gieson stain. Immunohistochemistry revealed that the chondrocytic and mesenchymal cells both expressed S-100. The tumor was diagnosed as an extraskeletal chondrosarcoma in the abdominal cavity of this cow.


Asunto(s)
Cavidad Abdominal/patología , Neoplasias Abdominales/veterinaria , Enfermedades de los Bovinos/patología , Condrosarcoma/veterinaria , Neoplasias Abdominales/patología , Animales , Bovinos , Condrocitos/metabolismo , Condrosarcoma/patología , Femenino , Células Madre Mesenquimatosas/metabolismo , Proteínas S100/metabolismo
20.
J Crohns Colitis ; 13(5): 648-658, 2019 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-30500874

RESUMEN

BACKGROUND AND AIMS: Genome-wide association studies [GWASs] of European populations have identified numerous susceptibility loci for Crohn's disease [CD]. Susceptibility genes differ by ethnicity, however, so GWASs specific for Asian populations are required. This study aimed to clarify the Japanese-specific genetic background for CD by a GWAS using the Japonica array [JPA] and subsequent imputation with the 1KJPN reference panel. METHODS: Two independent Japanese case/control sets (Tohoku region [379 CD patients, 1621 controls] and Kyushu region [334 CD patients, 462 controls]) were included. GWASs were performed separately for each population, followed by a meta-analysis. Two additional replication sets [254 + 516 CD patients and 287 + 565 controls] were analysed for top hit single nucleotide polymorphisms [SNPs] from novel genomic regions. RESULTS: Genotype data of 4 335 144 SNPs from 713 Japanese CD patients and 2083 controls were analysed. SNPs located in TNFSF15 (rs78898421, Pmeta = 2.59 × 10-26, odds ratio [OR] = 2.10), HLA-DQB1 [rs184950714, pmeta = 3.56 × 10-19, OR = 2.05], ZNF365, and 4p14 loci were significantly associated with CD in Japanese individuals. Replication analyses were performed for four novel candidate loci [p <1 × 10-6], and rs488200 located upstream of RAP1A was significantly associated with CD [pcombined = 4.36 × 10-8, OR = 1.31]. Transcriptome analysis of CD4+ effector memory T cells from lamina propria mononuclear cells of CD patients revealed a significant association of rs488200 with RAP1A expression. CONCLUSIONS: RAP1A is a novel susceptibility locus for CD in the Japanese population.


Asunto(s)
Enfermedad de Crohn/genética , Predisposición Genética a la Enfermedad/genética , Proteínas de Unión al GTP rap1/fisiología , Adulto , Estudios de Casos y Controles , Enfermedad de Crohn/epidemiología , Femenino , Perfilación de la Expresión Génica , Estudio de Asociación del Genoma Completo , Humanos , Japón/epidemiología , Masculino , Polimorfismo de Nucleótido Simple/genética , Adulto Joven , Proteínas de Unión al GTP rap1/genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA