RESUMEN
A 19-year-old man was admitted to our hospital because of persistent fever of >38°C for 6 days and diarrhea for 4 days. Initially, he was treated for infectious enteritis, but on his second day in the hospital, the two sets of blood cultures came back positive. Cultures from the blood and stool yielded Salmonella sp. (Group O4). The patient's symptoms improved after treatment with fluoroquinolone-based antimicrobial agents for 14 days. Cases of nontyphoidal Salmonella bacteremia are rare;therefore, we reported this case with bibliographic consideration of the risk factors for Salmonella bacteremia.
Asunto(s)
Bacteriemia , Infecciones por Salmonella/tratamiento farmacológico , Adulto , Antibacterianos/uso terapéutico , Diarrea , Humanos , Masculino , Salmonella , Adulto JovenRESUMEN
A previous genome-wide association study (GWAS) performed in 963 Japanese individuals (487 primary biliary cholangitis [PBC] cases and 476 healthy controls) identified TNFSF15 (rs4979462) and POU2AF1 (rs4938534) as strong susceptibility loci for PBC. In this study, we performed GWAS in additional 1,923 Japanese individuals (894 PBC cases and 1,029 healthy controls), and combined the results with the previous data. This GWAS, together with a subsequent replication study in an independent set of 7,024 Japanese individuals (512 PBC cases and 6,512 healthy controls), identified PRKCB (rs7404928) as a novel susceptibility locus for PBC (odds ratio [OR] = 1.26, P = 4.13 × 10-9). Furthermore, a primary functional variant of PRKCB (rs35015313) was identified by genotype imputation using a phased panel of 1,070 Japanese individuals from a prospective, general population cohort study and subsequent in vitro functional analyses. These results may lead to improved understanding of the disease pathways involved in PBC, forming a basis for prevention of PBC and development of novel therapeutics.
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Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Cirrosis Hepática Biliar/genética , Proteína Quinasa C beta/genética , Pueblo Asiatico , Femenino , Genotipo , Humanos , Japón , Cirrosis Hepática Biliar/patología , Masculino , Polimorfismo de Nucleótido SimpleRESUMEN
A 66-year-old man was referred to our hospital after being diagnosed with a pelvic tumor. A subsequent transperineal biopsy revealed spindle cells with CD34·c-kit(+). An enhanced computed tomography scan showed a giant rectal-derived tumor in the pelvis. The tumor was pressing on the urinary bladder and the prostate, and appeared to invade the posterior wall ofthese organs. The patient was diagnosed with rectal GIST, and neoadjuvant therapy with 400mg/day imatinib was initiated. Three months later, the tumor reduction rate was at 33.6%, and surgery was performed. The operative method applied was pelvic exenteration and ileal conduit, for local R0 resection. The patient has remained recurrence free for 2.5 years since the surgery.
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Antineoplásicos/uso terapéutico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Mesilato de Imatinib/uso terapéutico , Terapia Neoadyuvante , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Anciano , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Masculino , Neoplasias del Recto/cirugía , Resultado del TratamientoRESUMEN
The evaluation of the transport rates of hydrophilic substances is important in agricultural and pharmaceutical chemistry and in the cosmetics and food-processing industries. Although there are some estimation methods focusing on the diffusion of the substances through the oil phase of the W/O/W core-shell double emulsions (oil microcapsules), all of them take several hours or days. This long-time measurement has a risk of rupture of the oil microcapsules, which causes significant errors. If it were possible to measure the transport rate of substances in the oil phase of the oil microcapsules in real time, the risk of rupture could be reduced. Here, we propose a new estimation method for the transport rates of hydrogen peroxide (H2O2) in the oil phase of an oil microcapsule for real-time estimation by means of chemiluminescence (CL) emission of the luminol reaction. We theoretically give the relationship among the CL emission intensity, diffusion coefficient, microcapsule size, and experimental time and successfully estimate the diffusion coefficient of H2O2 in the oil phase of the oil microcapsule from the experimental data. Moreover, we discuss the dependence of the permeation of H2O2 through the oil phase on the concentration of the oil-soluble surfactant; the difference in the permeation rate is likely to be attributed not to the diffusion coefficient but to the partition coefficient of H2O2 in the oil microcapsule.
RESUMEN
In cases of gastrointestinal stromal tumor (GIST) with intraluminal growth, determining the minimal resection line is difficult; however, the combined use of endoscopy can overcome this limitation. We performed robot-assisted partial gastrectomy with endoscopy for two cases of internally developed GISTs located on the posterior wall near the esophagogastric junction (EGJ). We confirmed the tumor location and determined minimal surgical margins using endoscopy. The double bipolar method (DBM), which is performed with Maryland bipolar forceps in the right hand and fenestrated bipolar forceps in the left hand, was used to reduce residual gastric damage and prevent tumor damage. The characteristics of robot-assisted surgery made it easier to precisely perform anastomosis of the upper part of the stomach, as compared with laparoscopic surgery, thus minimizing gastric deformity. Both patients were discharged without postoperative complications. In conclusion, robot-assisted partial gastrectomy using the DBM may represent a viable treatment option for gastric submucosal tumors close to the EGJ.
RESUMEN
Genome-wide association studies (GWASs) in European and East Asian populations have identified more than 40 disease-susceptibility genes in primary biliary cholangitis (PBC). The aim of this study is to computationally identify disease pathways, upstream regulators, and therapeutic targets in PBC through integrated GWAS and messenger RNA (mRNA) microarray analysis. Disease pathways and upstream regulators were analyzed with ingenuity pathway analysis in data set 1 for GWASs (1,920 patients with PBC and 1,770 controls), which included 261 annotated genes derived from 6,760 single-nucleotide polymorphisms (P < 0.00001), and data set 2 for mRNA microarray analysis of liver biopsy specimens (36 patients with PBC and 5 normal controls), which included 1,574 genes with fold change >2 versus controls (P < 0.05). Hierarchical cluster analysis and categorization of cell type-specific genes were performed for data set 2. There were 27 genes, 10 pathways, and 149 upstream regulators that overlapped between data sets 1 and 2. All 10 pathways were immune-related. The most significant common upstream regulators associated with PBC disease susceptibility identified were interferon-gamma (IFNG) and CD40 ligand (CD40L). Hierarchical cluster analysis of data set 2 revealed two distinct groups of patients with PBC by disease activity. The most significant upstream regulators associated with disease activity were IFNG and CD40L. Several molecules expressed in B cells, T cells, Kupffer cells, and natural killer-like cells were identified as potential therapeutic targets in PBC with reference to a recently reported list of cell type-specific gene expression in the liver. Conclusion: Our integrated analysis using GWAS and mRNA microarray data sets predicted that IFNG and CD40L are the central upstream regulators in both disease susceptibility and activity of PBC and identified potential downstream therapeutic targets.
RESUMEN
Autoimmune hepatitis (AIH) is an autoimmune liver disease and cirrhosis is sometimes complicated with AIH at diagnosis, influencing its prognosis. TNFAIP3 gene encodes A20, an inhibitor of nuclear factor-κB pathway, and is a susceptibility gene for autoimmune diseases. We investigated deleterious variants in the coding regions of TNFAIP3 gene of Japanese AIH patients or those with cirrhosis. The deleterious variants in the coding regions of TNFAIP3 gene were analyzed by the cycle sequencing method and the frequencies of deleterious TNFAIP3 alleles of AIH or AIH with cirrhosis were compared with those of Japanese controls. The deleterious alleles in TNFAIP3 were not associated with AIH. A significant association was shown for the deleterious alleles in TNFAIP3 (P = 0.0180, odds ratio (OR) 4.28, 95% confidence interval (CI) 1.53-11.95) with AIH with cirrhosis at presentation. The serum IgM levels in AIH patients with deleterious alleles in TNFAIP3 were tended to be lower than those without (P = 0.0152, Q = 0.1216). The frequency of deleterious alleles in TNFAIP3 was higher in the AIH subset without the DRB1 risk alleles than that with (P = 0.0052, OR 5.10, 95%CI 1.55-16.74). The deleterious alleles in TNFAIP3were associated with AIH with cirrhosis.
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Hepatitis Autoinmune/genética , Cirrosis Hepática/genética , Polimorfismo de Nucleótido Simple , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/genética , Adulto , Anciano , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Hepatitis Autoinmune/complicaciones , Hepatitis Autoinmune/epidemiología , Humanos , Japón/epidemiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/epidemiología , Masculino , Persona de Mediana EdadRESUMEN
Primary biliary cholangitis (PBC) is a chronic and cholestatic autoimmune liver disease caused by the destruction of intrahepatic small bile ducts. Our previous genome-wide association study (GWAS) identified six susceptibility loci for PBC. Here, in order to further elucidate the genetic architecture of PBC, a GWAS was performed on an additional independent sample set, then a genome-wide meta-analysis with our previous GWAS was performed based on a whole-genome single nucleotide polymorphism (SNP) imputation analysis of a total of 4,045 Japanese individuals (2,060 cases and 1,985 healthy controls). A susceptibility locus on chromosome 3q13.33 (including ARHGAP31, TMEM39A, POGLUT1, TIMMDC1, and CD80) was previously identified both in the European and Chinese populations and was replicated in the Japanese population (OR = 0.7241, P = 3.5 × 10-9). Subsequent in silico and in vitro functional analyses identified rs2293370, previously reported as the top-hit SNP in this locus in the European population, as the primary functional SNP. Moreover, e-QTL analysis indicated that the effector gene of rs2293370 was Protein O-Glucosyltransferase 1 (POGLUT1) (P = 3.4 × 10-8). This is the first study to demonstrate that POGLUT1 and not CD80 is the effector gene regulated by the primary functional SNP rs2293370, and that increased expression of POGLUT1 might be involved in the pathogenesis of PBC.
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Glucosiltransferasas/genética , Cirrosis Hepática Biliar/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Japón , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Recent studies have demonstrated that micro (mi)RNA molecules can be detected in the circulation and can serve as potential biomarkers of various diseases. This study used microarray analysis to identify aberrantly expressed circulating miRNAs in patients with type 1 autoimmune hepatitis (AIH) compared with healthy controls. Patients with well-documented and untreated AIH were selected from the National Hospital Organization (NHO)-AIH-liver-network database. They underwent blood sampling and liver biopsy with inflammation grading and fibrosis staging before receiving treatment. To further confirm the microarray data, circulating expression levels of miR-21 and miR-122 were quantified by real-time quantitative polymerase chain reaction in 46 AIH patients, 40 patients with chronic hepatitis C (CHC), and 13 healthy controls. Consistent with the microarray data, serum levels of miR-21 were significantly elevated in AIH patients compared with CHC patients and healthy controls. miR-21 and miR-122 serum levels correlated with alanine aminotransferase levels. Circulating levels of miR-21 and miR-122 were significantly reduced in AIH patients with liver cirrhosis, and were inversely correlated with increased stages of fibrosis. By contrast, levels of circulating miR-21 showed a significant correlation with the histological grades of inflammation in AIH. We postulate that aberrantly expressed serum miRNAs are potential biomarkers of AIH and could be implicated in AIH pathogenesis. Alternations of miR-21 and miR-122 serum levels could reflect their putative roles in the mediation of inflammatory processes in AIH.
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Hepatitis Autoinmune/sangre , MicroARNs/sangre , Corticoesteroides/uso terapéutico , Adulto , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Hepatitis C Crónica/sangre , Hepatitis Autoinmune/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Previous genome-wide association studies have evaluated the impact of common genetic variants and identified several non-HLA risk loci associated with autoimmune liver diseases. More recent genome-wide association studies and replication analyses reported an association between variants of the CARD10 polymorphism rs6000782 and risk of type 1 autoimmune hepatitis (AIH). In this case-control study, we genotyped 326 Japanese AIH patients and 214 control subjects. RESULTS: Genomic DNA from 540 individuals of Japanese origin, including 326 patients with type-1 AIH and 214 healthy controls, was analyzed for two single nucleotide polymorphisms (SNPs) in the CARD10 gene. We selected CARD10 rs6000782 SNPs and genotyped these using PCR-RFLP method and direct sequencing. The Chi square test revealed that the rs6000782 variant alle (c) was not associated with the susceptibility for AIH in a Japanese population [p = 0.376, odds ratio (OR) 1.271, 95 % confidence interval (CI) 0.747-2.161] in an allele model. Our data also showed that CARD10 rs6000782 variants were not associated with AIH or with the clinical parameters of AIH. CONCLUSIONS: In this study we examined an association between rs6000782 SNPs in the CARD10 gene and type-1 AIH. Results showed no significant association of rs62000782 with type-1 AIH in a Japanese population. This study demonstrated no association between CARD10 rs6000782 variants and AIH in a Japanese population.
Asunto(s)
Proteínas Adaptadoras de Señalización CARD/genética , Predisposición Genética a la Enfermedad/genética , Hepatitis Autoinmune/genética , Polimorfismo de Nucleótido Simple , Anciano , Pueblo Asiatico/genética , Secuencia de Bases , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/etnología , Genotipo , Hepatitis Autoinmune/clasificación , Hepatitis Autoinmune/etnología , Humanos , Japón , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Factores de Riesgo , Análisis de Secuencia de ADNRESUMEN
BACKGROUND/AIMS: Recent studies demonstrated an association of STAT4 polymorphisms with autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, indicating multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 polymorphisms on the susceptibility and phenotype of type-1 autoimmune hepatitis in a Japanese National Hospital Organization (NHO) AIH multicenter cohort study. METHODOLOGY/PRINCIPAL FINDINGS: Genomic DNA from 460 individuals of Japanese origin including 230 patients with type-1 autoimmune hepatitis and 230 healthy controls was analyzed for two single nucleotide polymorphisms in the STAT4 gene (rs7574865, rs7582694). The STAT4 rs7574865T allele conferred risk for type-1 autoimmune hepatitis (ORâ=â1.61, 95% CIâ=â1.23-2.11; Pâ=â0.001), and patients without accompanying autoimmune diseases exhibited an association with the rs7574865T allele (ORâ=â1.50, 95%CIâ=â1.13-1.99; Pâ=â0.005). Detailed genotype-phenotype analysis of type-1 autoimmune hepatitis patients with (nâ=â44) or without liver cirrhosis (nâ=â186) demonstrated that rs7574865 was not associated with the development of liver cirrhosis and phenotype (biochemical data and the presence of auto-antibodies). CONCLUSIONS/SIGNIFICANCE: This is the first study to show a positive association between a STAT4 polymorphism and type-1 autoimmune hepatitis, suggesting that autoimmune hepatitis shares a gene commonly associated with risk for other autoimmune diseases.
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Predisposición Genética a la Enfermedad , Hepatitis Autoinmune/genética , Polimorfismo Genético , Factor de Transcripción STAT4/genética , Adulto , Anciano , Alelos , Pueblo Asiatico/genética , Estudios de Cohortes , Femenino , Variación Genética , Genotipo , Humanos , Japón , Masculino , Persona de Mediana Edad , Fenotipo , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis (PBC). In order to dissect the genetic basis for the production of these autoantibodies, as well as the development and progression of PBC in Japanese patients, we examined single nucleotide polymorphisms (SNPs) in cytotoxic T-lymphocyte antigen 4 (CTLA4) and solute carrier family 4 anion exchanger, member 2 (SLC4A2), which have been associated with the pathogenesis of PBC in Caucasian patients. METHODS: Four SNPs for both CTLA4 and SLC4A2 were genotyped, using the polymerase chain reaction-restriction fragment length polymorphism method and TaqMan assay, in 450 Japanese PBC patients and 371 sex-matched healthy controls. RESULTS: The CTLA4 rs231775, rs3087243, and rs231725 SNPs were significantly associated with PBC susceptibility. The CTLA4 rs231725 SNP was significantly associated with progression to late-stage disease. The CTLA-4 haplotype 1 (rs231775 G, rs231777 C, rs3087243 G, rs231725 A; GCGA) was a risk factor for PBC susceptibility but a protective factor for PBC progression. Conversely, the CTLA-4 haplotype 2 (ACAG) was a protective and risk factor, respectively, for PBC susceptibility and progression. In addition, the CTLA4 rs231777 SNP and haplotype 3 (ATGG) was significantly associated with anti-gp210 antibody production, while SLC4A2 haplotype 4 (rs2069443 A, rs2303933 G, rs2303937 A, rs2303941 T; AGAT) and haplotype 3 (AAGC) were significantly associated with PBC susceptibility and anti-centromere antibody production, respectively. CONCLUSIONS: CTLA4 and SLC4A2 genetic polymorphisms are differentially associated with PBC development and progression, as well as anti-gp210 or anti-centromere antibody production, in Japanese PBC patients.