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1.
Hum Genet ; 136(4): 387-397, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28197769

RESUMO

Crohn's disease (CD) involves chronic inflammation in the gastrointestinal tract due to dysregulation of the host immune response to the gut microbiome. Even though the host-microbiome interactions are likely contributors to the development of CD, a few studies have detected genetic variants that change bacterial compositions and increase CD risk. We focus on one of the well-replicated susceptible genes, tumor necrosis factor superfamily member 15 (TNFSF15), and apply statistical analyses for personal profiles of genotypes and salivary microbiota collected from CD cases and controls in the Ryukyu Islands, southernmost islands of the Japanese archipelago. Our association test confirmed the susceptibility of TNFSF15 in the Ryukyu Islands. We found that the recessive model was supported to fit the observed genotype frequency of risk alleles slightly better than the additive model, defining the genetic effect on CD if a pair of the chromosomes in an individual consists of all risk alleles. The combined analysis of haplotypes and salivary microbiome from a small set of samples showed a significant association of the genetic effect with the increase of Prevotella, which led to a significant increase of CD risk. However, the genetic effect on CD disappeared if the abundance of Prevotella was low, suggesting the genetic contribution to CD is conditionally independent given a fixed amount of Prevotella. Although our statistical power is limited due to the small sample size, these results support an idea that the genetic susceptibility of TNFSF15 to CD may be confounded, in part, by the increase of Prevotella.


Assuntos
Doença de Crohn/genética , Predisposição Genética para Doença , Microbiota , Ligante Indutor de Apoptose Relacionado a TNF/genética , Estudos de Casos e Controles , Fatores de Confusão Epidemiológicos , Humanos , Japão , Modelos Logísticos , Polimorfismo de Nucleotídeo Único , Saliva/microbiologia
2.
Helicobacter ; 18(1): 66-72, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23067336

RESUMO

BACKGROUND: Helicobacter pylori dupA can be divided into two types according to the presence or absence of the mutation. In addition, full-sequenced data revealed that dupA has two types with different lengths depend on the presence of approximately 600 bp in the putative 5' region (presence; long-type and absence; short-type), which has not been taken into account in previous studies. METHODS: A total of 319 strains isolated from Okinawa, the south islands of Japan, were included. The status of dupA and cagA was determined by polymerase chain reaction. The presence of mutations in long-type dupA was determined by DNA sequencing. RESULTS: The prevalence of long-type dupA was 26.3% (84/319). Sequence analysis showed that there were only six cases (7.1%) with point mutations lead to stop codon among 84 long-type dupA strains studied. Interestingly, intact long-type dupA without frameshift mutation, but not short-type dupA, was significantly associated with gastric ulcer and gastric cancer than gastritis (p = .001 and p = .019, respectively). After adjustment by age, gender, and cagA, the presence of intact long-type dupA was significantly associated with gastric ulcer and gastric cancer compared with gastritis (odds ratio [OR] = 3.35, 95% confidence interval [CI] = 1.55-7.24 and OR = 4.14, 95% CI = 1.23-13.94, respectively). CONCLUSIONS: Intact long-type dupA is a real virulence marker for severe outcomes in Okinawa, Japan. The previous information gained from PCR-based methods without taking long-type dupA into account must be interpreted with caution.


Assuntos
Gastrite/epidemiologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Neoplasias Gástricas/epidemiologia , Úlcera Gástrica/epidemiologia , Fatores de Virulência/genética , Adulto , Idoso , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , DNA Bacteriano/química , DNA Bacteriano/genética , Feminino , Gastrite/microbiologia , Marcadores Genéticos , Infecções por Helicobacter/complicações , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Neoplasias Gástricas/microbiologia , Úlcera Gástrica/microbiologia
3.
J Gastroenterol Hepatol ; 28(2): 291-6, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23190390

RESUMO

BACKGROUND AND AIM: Helicobacter pylori cagA can be classified into mainly two types (East-Asian-type and Western-type cagA) according to the repeat regions located in the 3' region. Recent studies showed that the Western-type cagA in strains from Okinawa, Japan formed a different cluster (J-Western-type cagA subtype). It has also been reported that J-Western-type cagA possesses a 12-bp insertion located in the 5' region of cagA sequence. METHODS: The prevalence of 12-bp insertion in cagA in Okinawa and the United States (U.S.) was examined by DNA sequencing. The primer pair that can detect the 12-bp insertion only by polymerase chain reaction was then designed. The prevalence of strains with 12-bp insertion was examined in 336 strains isolated from Okinawa by polymerase chain reaction. RESULTS: In case of Western-type cagA/vacA s1m2 strains, the prevalence of 12-bp insertion was significantly higher in strains isolated from Okinawa than that from the U.S. (P = 0.002). Phylogenetic tree showed that strains with 12-bp insertion formed two individual clusters within J-Western-type cagA subtype; one is from Okinawa and another is from the U.S. The designed primer set showed high sensitivity (100%) and specificity (90.8%) in Okinawa. The 12-bp insertion was found in 23.7%, 14.3%, 4.2%, and 4.0% of strains with duodenal ulcer (DU), gastritis, gastric cancer, and gastric ulcer (GU), respectively (P < 0.001 for DU vs GU) in Okinawa. CONCLUSIONS: Although the mechanisms are unknown, the presence of 12-bp insertion was associated with the presence of DU and might have a suppressive action on GU and gastric cancer.


Assuntos
Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , DNA Bacteriano/análise , Úlcera Duodenal/diagnóstico , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/genética , Mutagênese Insercional , Biópsia , Distribuição de Qui-Quadrado , Análise Mutacional de DNA , Primers do DNA , Úlcera Duodenal/epidemiologia , Úlcera Duodenal/microbiologia , Feminino , Gastrite/diagnóstico , Gastrite/microbiologia , Marcadores Genéticos , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/classificação , Humanos , Japão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Filogenia , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/microbiologia , Úlcera Gástrica/diagnóstico , Úlcera Gástrica/microbiologia , Estados Unidos/epidemiologia
4.
Nihon Shokakibyo Gakkai Zasshi ; 110(6): 998-1006, 2013 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-23739732

RESUMO

A 36-year-old woman presented with fever, diarrhea, and weight loss in April 2011. Upper GI endoscopy and colonoscopy showed a diffuse yellow-white shaggy mucosa in the second part of the duodenum and the ileum end, respectively. These lesions in these 2 locations were biopsied, and both specimens showed distended epithelial villi and massive infiltration of foamy macrophages in the lamina propria. PCR was performed to identify causative bacilli. DNA extracted from the duodenal mucosa showed a specific PCR product, confirming the diagnosis of Whipple's disease. The patient was treated with a 2-week course of ceftriaxone, followed by sulfamethoxazole/trimethoprim. After we started the treatment, the patient developed complications of infective endocarditis and meningitis. The patient was relieved of her symptoms using a combination of gentamicin, penicillin G, ampicillin, meropenem, and vancomycin.


Assuntos
Doença de Whipple/diagnóstico , Adulto , Endocardite/etiologia , Feminino , Humanos , Meningites Bacterianas/etiologia , Doença de Whipple/complicações
5.
J Gastroenterol ; 58(3): 205-216, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36607399

RESUMO

BACKGROUND: Given the increasing health concerns for patients with inflammatory bowel disease (IBD), amidst the COVID-19 pandemic, we investigated the impact of the pandemic on the anxiety and behavioral changes in Japanese patients with IBD. METHODS: We analyzed 3032 questionnaires from patients with IBD, aged 16 years or older visiting 30 hospitals and 1 clinic between March 2020 and June 2021. The primary outcome was the score of the anxiety experienced by patients with IBD during the pandemic. RESULTS: Participants reported a median age of 44 years; 43.3% of the patients were women. Moreover, 60.6% and 39.4% were diagnosed with ulcerative colitis and Crohn's disease, respectively, with a median disease duration of 10 years. Participants indicated an average of disease-related anxiety score of 5.1 ± 2.5 on a ten-point scale, with a tendency to increase, 1 month after the number of infected persons per population increased. The top three causes for anxiety were the risk of contracting COVID-19 during hospital visits, SARS-CoV-2 infection due to IBD, and infection by IBD medication. Factors associated with anxiety were gender (women), being a homemaker, hospital visit timings, mode of transportation (train), use of immunosuppressive drugs, and nutritional therapy. Most patients continued attending their scheduled hospital visits, taking their medications, experienced the need for a family doctor, and sought guidance and information regarding COVID-19 from primary doctors, television, and Internet news. CONCLUSIONS: Patients with IBD experienced moderate disease-related anxiety due to the pandemic and should be proactively informed about infectious diseases to relieve their anxiety.


Assuntos
COVID-19 , Doenças Inflamatórias Intestinais , Adulto , Feminino , Humanos , Masculino , Ansiedade/epidemiologia , Ansiedade/etiologia , COVID-19/epidemiologia , População do Leste Asiático , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Pandemias
6.
J Clin Microbiol ; 50(3): 876-83, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22189111

RESUMO

The incidence of gastric cancer in Okinawa is lowest in Japan. Some previous reports using small number of strains suggested that the high prevalence of Helicobacter pylori with Western-type cagA in Okinawa compared to other areas in Japan might contribute to the low incidence of gastric cancer. It has still not been confirmed why the prevalence of Western-type cagA strains is high in Okinawa. We examined the association between the virulence factors of H. pylori and gastroduodenal diseases in Okinawa. The genotypes of cagA and vacA of 337 H. pylori strains were determined by PCR and gene sequencing. The genealogy of these Western-type cagA strains in Okinawa was analyzed by multilocus sequence typing (MLST). Overall, 86.4% of the strains possessed cagA: 70.3% were East-Asian type and 16.0% were Western type. After adjustment by age and sex, the presence of East-Asian-type cagA/vacA s1m1 genotypes was significantly associated with gastric cancer compared to gastritis (odds ratio = 6.68, 95% confidence interval = 1.73 to 25.8). The structure of Western-type CagA in Okinawa was different from that of typical Western-type CagA found in Western countries. Intriguingly, MLST analysis revealed that the majority of Western-type cagA strains formed individual clusters but not hpEurope. Overall, low prevalence of gastric cancer in Okinawa may result from the high prevalence of non-East-Asian-type cagA strains. The origin of Western-type cagA strains in Okinawa may be different from those of Western countries.


Assuntos
Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Variação Genética , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Fatores de Virulência/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA Bacteriano/química , DNA Bacteriano/genética , Feminino , Gastrite/microbiologia , Gastrite/patologia , Genótipo , Infecções por Helicobacter/complicações , Helicobacter pylori/classificação , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Tipagem de Sequências Multilocus , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Adulto Jovem
7.
Dig Endosc ; 24(6): 407-11, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23078431

RESUMO

AIM: The main aim of this study was to determine whether questionnaire evaluations of clinical symptoms in gastroesophageal reflux disease were useful to assess proton pump inhibitor therapy. METHODS: A total of 185 Japanese patients (men, 88; women, 97; age: 55.7 ± 16.1 years) with gastroesophageal reflux disease were enrolled. The patients were divided based on the frequency scale for symptoms of gastroesophageal reflux disease: severe symptoms with scores ≥8 and mild symptoms with scores ≤7. Quality of life was evaluated with the Medical Outcomes Study 8-Item Short-Form Health Survey. All patients were treated with a proton pump inhibitor, rabeprazole (10 mg/day), for 8 weeks. RESULTS: Patients were classified into four groups: reflux esophagitis with severe symptoms (n = 92, 49.7%); reflux esophagitis with mild symptoms (n = 17, 9.2%); non-erosive reflux disease with severe symptoms (n = 66, 35.7%); and non-erosive reflux disease with mild symptoms (n = 10, 5.4%). The dysmotility score was high in non-erosive reflux disease with severe symptoms compared with reflux esophagitis with severe symptoms (9.1 ± 0.5 vs 6.8 ± 0.5, P < 0.05). The symptom score and quality of life in the severe symptoms groups for both reflux esophagitis and non-erosive reflux disease were significantly improved by rabeprazole treatment. Only the reflux score was improved by rabeprazole in the reflux esophagitis with mild symptoms group; no therapeutic effect was observed for the non-erosive reflux disease with mild symptoms group. CONCLUSIONS: Low scores on the frequency scale for the symptoms of gastroesophageal reflux disease indicate poor responsiveness to proton pump inhibitor treatment, and high scores indicate good responsiveness.


Assuntos
2-Piridinilmetilsulfinilbenzimidazóis/uso terapêutico , Refluxo Gastroesofágico/diagnóstico , Inibidores da Bomba de Prótons/uso terapêutico , Qualidade de Vida , Idoso , Antiulcerosos/uso terapêutico , Feminino , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/epidemiologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , ATPases Translocadoras de Prótons/antagonistas & inibidores , Rabeprazol , Estudos Retrospectivos , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do Tratamento
9.
iScience ; 25(7): 104477, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35720267

RESUMO

A virulence bacterium, Helicobacter pylori, evolved parallel to its host human, therefore, can work as a marker for tracing the human migration. We found H. pylori strains indigenous in the southernmost islands of Japanese Archipelago, Okinawa, and defined them as hspOkinawa and hpRyukyu. Genome data of the strains revealed that hspOkinawa diverged from other East Asian strains about 20,000 years ago, and that hpRyukyu diverged about 45,000 years ago. The closest strains of hpRyukyu were found from Afghanistan, Punjab, and Nepal, which suggest this strain originated in the central Asia and traveled across the Eurasian continent during Paleolithic era. The divergence date of hpRyukyu corresponds with human fossil records in Okinawa. Although it is controversial from human DNA analyses whether descendants of the Paleolithic migrants remain in the modern Japanese population, this study reveals that the bacterium of Paleolithic origin remains in the stomachs of current Japanese.

10.
J Clin Med ; 11(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36079125

RESUMO

Epinephrine local injection is a hemostatic procedure used in active diverticular bleeding that elicits vasoconstriction and tamponade effects. We compared the additional benefit of combination therapy with HSE-C (hypertonic saline epinephrine injection with clipping) to clipping monotherapy. Retrospective data on diverticular bleeding between 2011 and 2016 was reviewed. Those with an active bleeding source confirmed by colonoscopy (excluding non-bleeding vessels and adherent clots) who received either HSE-C or clipping were evaluated. Endpoints were rates of successful primary hemostasis, recurrent bleeding, and surgical intervention during hospitalization. A total of 320 patients with diverticular bleeding were evaluated, on which either HSE-C (n = 35) or clipping monotherapy (n = 18) was performed. Rates of successful primary hemostasis (91.4% vs. 66.7%, p = 0.048) and direct placement of endoclips (60.0% vs. 16.7%, p = 0.004) were significantly higher in the HSE-C group. Although not statistically significant, the HSE-C group had a higher rate of early rebleeding (18.8% vs. 8.3%, p = 0.653), while no difference was seen in the number of patients requiring surgery (11.4% vs. 5.5%, p = 0.651). HSE-C is associated with a higher rate of successful primary hemostasis for severe active diverticular bleeding but has no significant difference in reducing early recurrent bleeding or the number of patients requiring surgery, suggesting that hemostatic effects may be temporary.

11.
Digestion ; 83(3): 210-4, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21266818

RESUMO

BACKGROUND/AIMS: Strongyloidiasis, which is caused by Strongyloides stercoralis, is one of the prevalent infections in the tropical and subtropical regions worldwide. The larvae mainly infect the small intestine and cause serious disseminated strongyloidiasis. Although upper gastrointestinal features in strongyloidiasis are well known, colonoscopic evaluation has not been established yet. The aim of this study is to clarify the characteristic findings on colonic lesions in strongyloidiasis. METHOD: From January 2005 to December 2009, 10 cases with strongyloidiasis underwent colonoscopy at a single center on an endemic island of Japan. The clinical and colonoscopic findings were analyzed retrospectively. RESULTS: Six (60%) cases had an immunocompromised condition, including human T lymphotropic virus type 1 infection, corticosteroids, and chemotherapy. Hyperinfection or disseminated strongyloidiasis was not presented. Endoscopic features included yellowish-white nodules, erythema, and loss of vascular pattern, which were mainly observed in the right colon. Pathological examination revealed the filariform Strongyloides larvae and the eosinophilic infiltration of the lamina propria. CONCLUSION: This study demonstrates that colonoscopic observation and biopsies are very useful to diagnose strongyloidiasis. Asymptomatic cases with strongyloidiasis can have colonic involvement. Yellowish-white nodules may be a characteristic finding of colonic lesions in strongyloidiasis and can be a cautious marker to prevent fatal disseminated strongyloidiasis in endemic regions.


Assuntos
Colite/patologia , Strongyloides stercoralis , Estrongiloidíase/patologia , Idoso , Idoso de 80 Anos ou mais , Animais , Biópsia , Colite/diagnóstico , Colite/parasitologia , Colo/patologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Estrongiloidíase/diagnóstico
12.
Infect Immun ; 77(4): 1337-48, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19179414

RESUMO

Interleukin-12 (IL-12) is a heterodimeric cytokine produced by antigen-presenting cells that promotes the development of T-helper lymphocyte 1 (Th1). Chronic gastritis induced by Helicobacter pylori is considered a Th1-mediated process. IL-12 levels in gastric biopsy samples of H. pylori-infected patients are higher than in those of uninfected individuals, but the cellular source of IL-12 remains elusive. IL-12 staining was detected in mucosal epithelial cells, lymphocytes, and macrophages in specimens of patients with H. pylori-positive gastritis. Therefore, we investigated IL-12 p40 mRNA induction by H. pylori in gastric epithelial cells and T cells. Although cag pathogenicity island (PAI)-positive H. pylori induced IL-12 p40 mRNA expression, an isogenic mutant of the cag PAI failed to induce it in both cell types. Supernatants from H. pylori cultures and H. pylori VacA induced IL-12 p40 mRNA expression in T cells but not in epithelial cells. The activation of the IL-12 p40 promoter by H. pylori was mediated through NF-kappaB. The transfection of IkappaB kinase and NF-kappaB-inducing kinase dominant-negative mutants inhibited H. pylori-induced IL-12 p40 activation. Inhibitors of NF-kappaB, phosphatidylinositol 3-kinase, p38 mitogen-activated protein kinase, and Hsp90 suppressed H. pylori- and VacA-induced IL-12 p40 mRNA expression. The results indicate that H. pylori induces IL-12 p40 expression by the activation of NF-kappaB, phosphatidylinositol 3-kinase, and p38 mitogen-activated protein kinase. Hsp90 is also a crucial regulator of H. pylori-induced IL-12 p40 expression. In addition to the cag PAI, VacA might be relevant in the induction of IL-12 expression and a Th1-polarized response only in T cells.


Assuntos
Gastrite/imunologia , Regulação da Expressão Gênica , Infecções por Helicobacter/imunologia , Helicobacter pylori/patogenicidade , Subunidade p40 da Interleucina-12/metabolismo , Animais , Biópsia , Linhagem Celular , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Mucosa Gástrica/citologia , Mucosa Gástrica/imunologia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite/microbiologia , Gastrite/patologia , Ilhas Genômicas , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/imunologia , Humanos , Subunidade p40 da Interleucina-12/genética , Células Jurkat/citologia , Células Jurkat/imunologia , Células Jurkat/microbiologia , Macrófagos/citologia , Macrófagos/imunologia , Macrófagos/microbiologia , Camundongos , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
BMC Microbiol ; 9: 36, 2009 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-19216748

RESUMO

BACKGROUND: The inflammatory response in Helicobacter pylori-infected gastric tissue is mediated by cag pathogenicity island (PAI)-dependent activation of nuclear factor-kappaB (NF-kappaB). Phosphatidylinositol 3-kinase (PI3K)/Akt signaling is known to play a role in NF-kappaB activation, but little information is available on the relationship between H. pylori and PI3K/Akt signaling in gastric epithelial cells. We examined whether H. pylori activates Akt in gastric epithelial cells, the role of cag PAI in this process and the role of Akt in regulating H. pylori-induced NF-kappaB activation. RESULTS: Phosphorylated Akt was detected in epithelial cells of H. pylori-positive gastric tissues. Although Akt was activated in MKN45 and AGS cells by coculture with cag PAI-positive H. pylori strains, a cag PAI-negative mutant showed no activation of Akt. H. pylori also induced p65 phosphorylation. PI3K inhibitor suppressed H. pylori-induced p65 phosphorylation and NF-kappaB transactivation, as well as interleukin-8 expression. Furthermore, transfection with a dominant-negative Akt inhibited H. pylori-induced NF-kappaB transactivation. Transfection with small interference RNAs for p65 and Akt also inhibited H. pylori-induced interleukin-8 expression. CONCLUSION: The results suggest that cag PAI-positive H. pylori activates Akt in gastric epithelial cells and this may contribute to H. pylori-mediated NF-kappaB activation associated with mucosal inflammation and carcinogenesis.


Assuntos
Helicobacter pylori/metabolismo , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição RelA/metabolismo , Linhagem Celular , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Regulação da Expressão Gênica , Ilhas Genômicas , Infecções por Helicobacter/metabolismo , Helicobacter pylori/genética , Humanos , Interleucina-8/biossíntese , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Interferência de RNA
15.
Helicobacter ; 14(4): 271-9, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19674131

RESUMO

BACKGROUND: Helicobacter pylori secretes vacuolating cytotoxin (VacA) that damages the gastric epithelium by erosion and loosening of tight junctions. VacA has also immunosuppressive effects, inhibiting interleukin (IL)-2 secretion by interference with the T cell receptor/IL-2 signaling pathway. This study investigated the effect of VacA on gene expression of T cells. MATERIALS AND METHODS: Gene expression profile of a T cell line, Jurkat, was analyzed by the cDNA microarray technique after VacA challenge. The expression of specific mRNAs was assessed by reverse transcription-polymerase chain reaction. Interleukin (IL)-8 concentrations in culture supernatants and cell surface expression of CD69 were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively. We evaluated nuclear factor-kappaB (NF-kappaB) activation in Jurkat cells challenged with VacA by luciferase assay, electrophoretic mobility shift assay, and Western blot analysis. RESULTS: VacA produced two or greater fold up-regulation of expression of 60 genes. Most of these genes were associated with signal transduction, regulation of gene expression, apoptosis, and inflammation. Up-regulation of four genes (IL8, IL2RA, ICAM1, and CD69) was confirmed. The supernatants of cells incubated with VacA showed significantly higher secretion levels of IL-8 than those incubated without VacA. VacA also induced the cell surface expression of CD69. Since microarray analysis indicated NF-kappaB was involved in the transcriptional activation of the above genes, we examined NF-kappaB signaling pathway. VacA activated NF-kappaB via classical but not alternative pathway. CONCLUSIONS: VacA has two paradoxical effects on T cells, immunosuppression, and proinflammatory effects. The latter is mediated by NF-kappaB activation.


Assuntos
Proteínas de Bactérias/imunologia , Infecções por Helicobacter/genética , Helicobacter pylori/imunologia , NF-kappa B/genética , Transdução de Sinais , Linfócitos T/imunologia , Proteínas de Bactérias/genética , Linhagem Celular , Perfilação da Expressão Gênica , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Humanos , NF-kappa B/imunologia , Linfócitos T/metabolismo
16.
J Gastroenterol Hepatol ; 24(4): 633-8, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19220681

RESUMO

BACKGROUND AND AIM: We compared endoscopic findings of the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), a written questionnaire developed in Japan, to that for the questionnaire for the diagnosis of reflux esophagitis (QUEST) for the diagnosis of reflux esophagitis. METHODS: We registered 475 patients with untreated symptoms of upper abdominal pain (male/female: 252/223, average age 52.4 +/- 17.8 years). Subjects were assessed first with the FSSG and QUEST questionnaires, then by endoscopy, before allocation to a gastric ulcer (GU), duodenal ulcer (DU), gastroesophageal reflux disease (GERD) or functional dyspepsia (FD) group. RESULTS: On the basis of the endoscopic findings the diagnoses for the 475 subjects were as follows: FD 52.2%, DU 7.6%, GU 7.8%, and GERD 32.4% (Grade M 10.1%, Grade A + B 20.2%, Grade C + D 2.3%). There was no difference between the FSSG and QUEST in sensitivity, specificity or accuracy for any condition. The FSSG score rose with increasing endoscopic severity of GERD, but there was no correlation between the QUEST score and endoscopic severity. The FSSG total score was inferior to QUEST in terms of distinguishing GERD from other conditions, but when only the questions relating to reflux symptoms were used, the FSSG was able to distinguish GERD from other conditions as well as QUEST. CONCLUSIONS: The FSSG score reflects the severity of the endoscopic findings of GERD.


Assuntos
Úlcera Duodenal/diagnóstico , Dispepsia/diagnóstico , Endoscopia do Sistema Digestório , Esofagite Péptica/diagnóstico , Refluxo Gastroesofágico/diagnóstico , Úlcera Gástrica/diagnóstico , Dor Abdominal/etiologia , Dor Abdominal/patologia , Adulto , Idoso , Úlcera Duodenal/complicações , Úlcera Duodenal/patologia , Dispepsia/complicações , Dispepsia/patologia , Esofagite Péptica/complicações , Esofagite Péptica/patologia , Feminino , Refluxo Gastroesofágico/patologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Úlcera Gástrica/complicações , Úlcera Gástrica/patologia , Inquéritos e Questionários
17.
J Gastroenterol ; 54(3): 249-260, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30219994

RESUMO

BACKGROUND: Capsule endoscopy can be used to identify the early stage of small bowel Crohn's disease (CD). We evaluated significant small bowel capsule endoscopy (SBCE) findings that can lead to early diagnosis of CD. METHODS: We retrospectively accumulated clinical and SBCE data of 108 patients (63 with and 45 without CD). Types of small bowel mucosal injuries, including erosion, ulceration, and cobblestone appearance, and the alignment of diminutive lesions were compared between patients with and without CD. Inter- and intra-observer agreement in the determination of lesions was assessed in 25 pairs of SBCE from the two groups. RESULTS: Under SBCE, cobblestone appearance (33% vs. 2%, p < 0.0001), longitudinal ulcers (78% vs. 20%, p < 0.0001), and irregular ulcers (84% vs. 60%, p < 0.01) were more frequently found in patients with CD. Linear erosion (90% vs. 38%, p < 0.0001) and irregular erosion (89% vs. 64%, p < 0.005) were also more frequent in patients with CD. Furthermore, circumferential (75% vs. 9%, p < 0.0001) and longitudinal (56% vs. 7%, p < 0.0001) alignment of diminutive lesions, mainly observed in the 1st tertile of the small bowel, was more frequent in patients with CD. Good intra-observer agreement was found for ulcers, cobblestone appearance, and lesion alignment. However, inter-observer agreement of SBCE findings differed among observers. CONCLUSIONS: Circumferential or longitudinal alignment of diminutive lesions, especially in the upper small bowel, may be a diagnostic clue for CD under SBCE, while inter-observer variations should be cautiously considered when using SBCE.


Assuntos
Doença de Crohn/diagnóstico , Adulto , Idoso , Endoscopia por Cápsula , Estudos de Casos e Controles , Doença de Crohn/classificação , Doença de Crohn/patologia , Feminino , Humanos , Mucosa Intestinal/patologia , Japão , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Retrospectivos , Sensibilidade e Especificidade , Gravação em Vídeo
18.
Am J Gastroenterol ; 103(7): 1721-9, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18616656

RESUMO

OBJECTIVES: Anal fistulas are common in individuals with Crohn's disease (CD). We sought to evaluate the efficacy of oral spherical adsorptive carbon (AST-120) (Kremezin; Kureha Corporation, Tokyo, Japan) for the treatment of intractable anal fistulas in patients with CD. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, patients with CD and at least one active anal fistula under treatment were assigned to receive either AST-120 or placebo for 8 wk. Improvement was defined as a reduction of 50% or more from baseline in the number of draining fistulas observed at both 4 and 8 wk. Remission was defined by closure of all draining fistulas at both 4 and 8 wk. The Perianal Disease Activity Index (PDAI) and Crohn's Disease Activity Index (CDAI) were also assessed. RESULTS: In total, 62 patients were randomized, of whom 57 received AST-120 (N = 27) or placebo (N = 30). The improvement rate in the AST-120 group (37.0%) was significantly greater than that in the placebo group (10.0%) (P= 0.025). The corresponding remission rates were 29.6% and 6.7%, respectively (P= 0.035). PDAI significantly improved at both 4 and 8 wk with AST-120, compared to placebo (P= 0.004 and P= 0.005, respectively). CDAI was also significantly improved at both 4 and 8 wk in the AST-120 group, compared to the placebo group (P= 0.007 and P= 0.001, respectively). AST-120 treatment was well tolerated and no life-threatening adverse events were observed. CONCLUSION: AST-120 is useful for the control of intractable anal fistulas in CD patients.


Assuntos
Carbono/uso terapêutico , Doença de Crohn/complicações , Óxidos/uso terapêutico , Fístula Retal/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fístula Retal/etiologia , Resultado do Tratamento
19.
World J Gastroenterol ; 14(11): 1768-73, 2008 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-18350608

RESUMO

AIM: To investigate endoscopic and histopathological findings in the duodenum of patients with Strongyloides stercoralis (S. stercoralis) hyperinfection. METHODS: Over a period of 23 years (1984-2006), we investigated 25 patients with S. stercoralis hyperinfection who had had an esophagogastroduodenoscopy before undergoing treatment for strongyloidiasis. The clinical and endoscopic findings were analyzed retrospectively. RESULTS: Twenty-four (96%) of the patients investigated were under immunocompromised condition which was mainly due to a human T lymphotropic virus type 1 (HTLV-1) infection. The abnormal endoscopic findings, mainly edematous mucosa, white villi and erythematous mucosa, were observed in 23 (92%) patients. The degree of duodenitis including villous atrophy/destruction and inflammatory cell infiltration corresponded to the severity of the endoscopic findings. The histopathologic yield for identifying larvae was 71.4% by duodenal biopsy. The endoscopic findings of duodenitis were more severe in patients whose biopsies were positive for larvae than those whose biopsies were negative (Endoscopic severity score: 4.86 +/- 2.47 vs 2.71 +/- 1.38, P < 0.05). CONCLUSION: Our study clearly demonstrates that, in addition to stool analysis, endoscopic observation and biopsies are very important. We also emphasize that S. stercoralis and HTLV-1 infections should be ruled out before immunosuppressive therapy is administered in endemic regions.


Assuntos
Duodenite/patologia , Duodeno/patologia , Endoscopia do Sistema Digestório , Strongyloides stercoralis/isolamento & purificação , Estrongiloidíase/patologia , Idoso , Animais , Biópsia , Duodenite/parasitologia , Duodeno/parasitologia , Fezes/parasitologia , Feminino , Infecções por HTLV-I/complicações , Humanos , Mucosa Intestinal/parasitologia , Mucosa Intestinal/patologia , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Escarro/parasitologia , Estrongiloidíase/complicações , Estrongiloidíase/parasitologia
20.
World J Gastroenterol ; 14(29): 4701-4, 2008 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-18698688

RESUMO

A primary aortoenteric fistula (PAEF), defined as a communication between the native aorta and the gastrointestinal tract, is a rare cause of gastrointestinal bleeding. The preoperative diagnosis of PAEF is extremely difficult. Consequently, PAEF may cause sudden and unexpected death. We present an autopsy case of a 68-year-old man who died of massive gastrointestinal bleeding due to a PAEF. Autopsy revealed a pinhole rupture located on the third part of the duodenal mucosa and fistulized into the adjacent abdominal aortic aneurysm (AAA). Our case indicates that the aortoenteric fistula can result in fatal gastrointestinal bleeding. Consequently, a PAEF should be included in the differential diagnosis of gastrointestinal bleeding.


Assuntos
Doenças da Aorta/diagnóstico , Duodenopatias/diagnóstico , Endoscopia Gastrointestinal , Fístula Intestinal/diagnóstico , Idoso , Aorta Abdominal/patologia , Doenças da Aorta/complicações , Diagnóstico Diferencial , Duodenopatias/complicações , Duodeno/patologia , Evolução Fatal , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Humanos , Fístula Intestinal/complicações , Masculino
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