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Hajime Isomoto

Publications and source records attributed to Hajime Isomoto.

At least 55 records · Page 3Linked to original sources

Hepatic mucosa-associated lymphoid tissue lymphoma and hepatocellular carcinoma in a patient with hepatitis B virus infection.

Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is an extremely rare disease. A 65-year-old female patient with chronic hepatitis B presented with multiple solid masses in segment (S) 4, S5, and S6 of the liver. The nodule in S5 was diagnosed preoperatively as hepatocellular carcinoma by computed tomography, magnetic resonance imaging, and angiography. The nodule in S4 was initially interpreted as lymphoid follicles by needle biopsy. Segmentectomy of S5 and partial resection of S6 were performed. Microscopic examination of the S5 nodule revealed moderately differentiated hepatocellular carcinoma. The nodule from S6 showed nodular proliferation of atypical intermediate to medium-sized lymphoid cells in the portal area and lymph epithelial lesions of bile ducts. The atypical lymphoid cells were positive for LCA, L-26 and bcl-2 and negative for UCHL-1. These features were consistent with the diagnosis of MALT lymphoma. This is the first case report of synchronous hepatic MALT lymphoma and hepatocellular carcinoma associated with chronic hepatitis B.

Aged↗

Preliminary analysis of a newly proposed prognostic scoring system (SLiDe score) for hepatocellular carcinoma.

BACKGROUND: The long-term prognosis of hepatocellular carcinoma (HCC) remains poor and the prediction of survival is often difficult because of the limited liver function and frequent recurrence of HCC in most patients. Therefore, a prognostic classification of HCC should account for both tumor-related variables and liver function. METHODS: The value of reported prognostic factors for HCC was assessed and a new prognostic classification was established called the 'SLiDe' scoring system (S, stage; Li, liver damage; De, des-gamma-carboxy prothrombin) using 'stage' and 'liver damage' of the recently revised 4th edition of the Japanese staging system edited by the Liver Cancer Study Group of Japan, and the serum level of des-gamma-carboxy prothrombin (DCP) in 177 patients with HCC. RESULTS: Univariate analysis identified Child-Pugh stage, liver damage, tumor morphology, portal vein thrombosis, stage, serum level of alpha-fetoprotein (AFP), serum level of DCP, and initial treatment as significant prognostic factors. Of these, liver damage, stage, and serum level of DCP remained independent predictive factors of survival after multivariate prognostic analysis using the proportional hazards regression model. Therefore, a new prognostic scoring system (SLiDe scoring system) was derived that assigned a linear score (0/1/2/3) to these three covariates. This SLiDe scoring system was statistically a better model for predicting outcome in the present study population than the Cancer of the Liver Italian Program (CLIP) and the Japan Integrated Staging (JIS) scoring systems, as judged by the Akaike Information Criteria. CONCLUSION: The SLiDe scoring system is useful for the assessment of the prognosis of patients with HCC as long as the Japanese staging system is used, although this uses parameters such as the indocyanine green retention test and DCP, which are not examined routinely in every part of the world. Therefore, the proposed classification should be further validated in other large study populations.

Adolescent↗

Enhanced expression of interleukin-8 and activation of nuclear factor kappa-B in endoscopy-negative gastroesophageal reflux disease.

OBJECTIVE: Interleukin-8 (IL-8) mediates neutrophil trafficking via its receptors. Recent studies have shown that IL-8 is likely involved in the development and progression of erosive reflux esophagitis (RE), yet little is known about its implication in endoscopy-negative gastroesophageal reflux disease (GERD). The purpose of this study was to determine IL-8 messenger ribonucleic acid (mRNA) expression levels in endoscopy-negative GERD, along with assessment of nuclear factor kappaB (NF-kappaB) activation, which upregulates IL-8 expression. METHODS: We studied 31 patients with endoscopy-negative GERD, 15 patients with erosive RE, and 15 asymptomatic controls. Paired biopsy samples were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap-frozen for measurement of IL-8 mRNA levels by real-time quantitative polymerase chain reaction, and another was formalin-fixed for histopathological evaluation. In nine endoscopy-negative GERD patients, the IL-8 mRNA expression levels were measured before and 8 wk after treatment with lansoprazole. We also sampled additional specimens for NF-kappaB-DNA binding assay and immunohistochemical analyses of NF-kappaB p65 and p50 subunits, IL-8 and specific IL-8 receptor, CXCR-1. RESULTS: The relative IL-8 mRNA expression levels were significantly higher in esophageal mucosa of patients with endoscopy-negative GERD than those of the controls. The presence of basal zone hyperplasia and intraepithelial neutrophils, histopathological hallmarks of GERD, were associated with higher levels of IL-8 mRNA. Lansoprazole treatment significantly reduced the IL-8 mRNA expression levels. The esophageal epithelium of patients with GERD showed intense immunoreactivity for IL-8, and expressed CXCR-1 antigen. We found NF-kappaB activation in esophageal mucosa in GERD patients and the NF-kappaB subunits were localized predominantly in the nuclei of IL-8-expressing cells. CONCLUSIONS: Our results demonstrate enhanced mucosal expression of IL-8 in incipient GERD even without mucosal breaks. NF-kappaB activation may be implicated in the pathogenesis in GERD.

Adult↗

Mucosal concentrations of proinflammatory cytokines and chemokines at gastric cardia: implication of Helicobacter pylori infection and gastroesophageal reflux.

OBJECTIVES: The pathogenesis of carditis remains unclear, although gastroesophageal reflux disease (GERD) and Helicobacter pylori infection have been proposed. Little is known about the profile of proinflammatory cytokines and chemokines in the pathogenesis of carditis. METHODS: We studied 28 patients with GERD and 40 controls. Two biopsy specimens were taken endoscopically from the cardiac mucosa within 5 mm from the squamocolumnar junction; one was snap frozen for measurement of mucosal levels of interleukin 1beta (IL-1beta), tumor necrosis factor-alpha, IL-6, IL-8, monocyte chemoattractant protein 1 (MCP-1), regulated on activation normal T-cell expressed and presumably secreted (RANTES) by enzyme-linked immunosorbent assays, while another was processed for histopathology. H. pylori infection was assessed by serology, rapid urease test, and histology with Giemsa staining. Samples were taken from the cardia of 18 H. pylori-positive patients, before and after eradication treatment. RESULTS: Carditis was significantly associated with H. pylori infection, but not GERD. IL-8, MCP-1, and RANTES levels were significantly higher in cardiac mucosa of patients with carditis than in those without it and in patients with than without H. pylori infection. IL-8 concentrations were significantly associated with the degree of neutrophil infiltration within the cardiac mucosa and decreased after cure of the infection. Mucosal MCP-1 and RANTES levels correlated positively with the grades of mononuclear cell infiltration and IL-1beta concentrations. CONCLUSION: Our results indicate that chemokines produced locally in the cardiac mucosa may be involved in the development of H. pylori-associated carditis.

Adult↗

Elevated concentrations of alpha-defensins in gastric juice of patients with Helicobacter pylori infection.

OBJECTIVE: Defensins (alpha- and beta-defensins) are endogenous antimicrobial peptides. Little is known about alpha-defensins during Helicobacter pylori infection. METHODS: The concentrations of human neutrophil peptides (HNP-1, -2, and -3), the major components of neutrophils-derived alpha-defensins, were measured by radioimmunoassay (RIA) in plasma and gastric juice of 61 H. pylori-infected and 33 uninfected subjects, and before and after anti-H. pylori treatment in 12 patients with H. pylori-associated gastritis. Interleukin (IL)-8 concentrations in gastric juice were measured by enzyme-linked immunosorbent assay. Histological grades of gastritis and neutrophil counts (/mm(2)) infiltrating in the gastric mucosa were determined using two biopsy specimens taken from the antrum and corpus. Immunohistochemistry and reverse-phase high performance liquid chromatography (RP-HPLC) were used to identify HNPs 1-3. RESULTS: HNP 1-3 concentrations in gastric juice were significantly higher in H. pylori-positive than in H. pylori-negative patients and significantly decreased after cure. HNP 1-3 concentrations in gastric juice correlated with IL-8 levels and neutrophil densities in the gastric mucosa and were associated with histological degree of gastritis, especially the grades of activity. Intense immunoreactivity for anti-HNPs 1-3 antiserum was noted in infiltrating neutrophils in H. pylori-infected mucosa. In RP-HPLC analysis, all of the HNP 1-3 molecules were identified as their mature forms. Plasma HNP 1-3 concentrations were similar in H. pylori-infected and non-infected groups and showed no correlations with other parameters. CONCLUSIONS: We demonstrated significantly elevated levels of HNPs 1-3 in gastric juice during H. pylori infection. The elevation of HNPs is presumably secondary to H.pylori-associated gastric inflammation involving neutrophil infiltration.

Adult↗

Expression of heat shock protein (Hsp) 70 and Hsp 40 in gastric cancer.

Heat shock proteins (Hsp) 70 and Hsp 40 are stress proteins that cooperate as chaperones in mammalian cells. We determined the expression of Hsp 70 and Hsp 40 in 81 gastric cancers. Immunoreactivities to Hsp 70 and Hsp 40 were detected in 67.9 and 22.2% of tumors, respectively. Immunohistochemical analysis showed enhanced Hsp 70 and Hsp 40 expression in gastric tumor tissue, relative to the surrounding normal tissue. Overexpression of Hsp 70 and Hsp 40 was also confirmed by immunoblotting. Among various clinicopathological parameters, low histopathological differentiation was associated with reduced expression of both proteins.

Adult↗

Immune thrombocytopenic purpura in patients with ulcerative colitis.

Extraintestinal manifestations of ulcerative colitis (UC) are well known, but immunologically mediated hematological diseases are relatively rare. We describe two cases of immune thrombocytopenic purpura (ITP) associated with preexisting UC. Our patients had typical symptoms of UC, and endoscopy showed pancolitis. During treatment with 5-aminosalicylic acid and steroids, severe thrombocytopenia was noted. ITP was diagnosed based on a normal to high number of megakaryocytes in the bone marrow, positive autoantibody to platelet membrane antigen, and absence of splenomegaly. Medical treatment, including increased dosage of steroids, failed to control UC and ITP in both patients. In the first patient, the platelet count recovered after colectomy, while the second patient died of a cerebral hemorrhage. We stress that a diagnosis of ITP should be considered for thrombocytopenia in patients with UC, especially those showing extensive and significant colonic inflammation, and that colectomy of UC might resolve resistant ITP.

Adult↗

Evaluation of newly developed ELISA using "MESACUP-2 test mitochondrial M2" kit for the diagnosis of primary biliary cirrhosis.

OBJECTIVES: An enzyme-linked immunosorbent assay (ELISA) using MESACUP-2 Test Mitochondria M2 kit (new-M2 ELISA) has recently become commercially available. The aim of this study was to evaluate the clinical utility of this newly developed ELISA for the diagnosis of primary biliary cirrhosis (PBC). DESIGN AND METHODS: We tested the immunoreactivity of sera from 82 Japanese PBC patients to the 2-oxo-acid dehydrogenase complex (2-OADC) enzymes by indirect immunofluorescence, enzyme inhibition assay using commercially available TRACE Enzymatic Mitochondrial Antibody (M2) Assay (EMA) kit, commercial ELISAs using MESACUP Mitochondria M2 kit (old-M2 ELISA) and new-M2 ELISA, and immunoblotting on bovine heart mitochondria. RESULTS: Each test gave the following positive results; antimitochondrial antibodies (AMA) by immunofluorescence in 71 (87%) out of the 82 sera, enzymatic inhibitory antibody to pyruvate dehydrogenase complex (PDC) by EMA in 61 (74%), immunoglobulin (Ig) G class anti-PDC antibody by old-M2 ELISA in 55 (67%), IgG/M/A class anti-E2 subunit of PDC (PDC-E2)/anti-E2 subunit of branched chain oxo-acid dehydrogenase complex (BCOADC-E2)/anti-E2 subunit of 2-oxoglutarate dehydrogenase complex (OGDC-E2) antibodies by new-M2 ELISA in 73 (89%), and IgG, IgM, or IgA class antibodies against at least one of the 2-OADC enzymes by immunoblotting in 82 (100%). Fifty-three of the 82 sera (65%) were all positive by these five assays. Of the 18 sera that were positive by new-M2 ELISA but negative by old-M2 ELISA, 12 were theoretically interpretable. Of the 11 sera that were negative for AMA by immunofluorescence but positive for at least one of anti-2-OADC enzymes by immunoblotting, four (36%) were positive by new-M2 ELISA, whereas only two and one sera were positive by EMA and old-M2 ELISA, respectively. CONCLUSIONS: Our results indicated that the sensitivity of the newly developed new-M2 ELISA was higher than that of EMA and old-M2 ELISA, and comparable with that of immunofluorescence. However, it is still unclear whether the new-M2 ELISA could replace the conventional immunofluorescence testing for routine assay requests because six (7%) sera showed discrepant results between these two assays.

Adult↗

Detection of nuclear factor-kappaB in IgA nephropathy using Southwestern histochemistry.

BACKGROUND: The transcription factor nuclear factor-kappaB (NF-kappaB) is involved in inflammatory and immune responses through induction of various cytokines and growth factors. The aim of this study is to examine the correlation between NF-kappaB expression and severity of tissue injury in immunoglobulin A (IgA) nephropathy and the mechanism of such correlation. METHODS: The study included 43 renal tissue samples from 28 patients, including 28 samples of IgA nephropathy, 5 samples of non-IgA mesangial proliferative glomerulonephritis (non-IgA nephropathy), and 10 samples with nonproliferative glomerulonephritis (membranous nephropathy [MN] n = 5; minimal change nephrotic syndrome [MCNS]; n = 5). Tissue sections were examined by Southwestern histochemistry and immunohistochemistry for monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and intercellular cell adhesion molecule-1 (ICAM-1), which are regulated by NF-kappaB. Normal portions of surgically resected kidney with adenocarcinoma served as controls. RESULTS: In normal kidney, MCNS, and MN sections, NF-kappaB expression was detected in a few mesangial cells and tubular epithelial cells. In IgA nephropathy and non-IgA nephropathy samples, NF-kappaB was expressed in mesangial, glomerular endothelial and epithelial cells, tubular epithelial cells, and infiltrating cells. Expression in both glomeruli and interstitium correlated with progression of tissue injury. In IgA nephropathy samples, MCP-1 and GM-CSF expression was increased in both glomeruli and interstitium and correlated with progression of tissue injury. Glomerular ICAM-1 expression was weaker in severe lesions, whereas interstitial expression correlated with progression of tissue injury. CONCLUSION: Our results indicate that NF-kappaB is involved in the progression of tissue injury in IgA nephropathy through the induction of transcriptionally regulated genes.

Adenocarcinoma↗

Pure red cell aplasia associated with parvovirus B19 infection in a patient with ulcerative colitis.

Anemia is a common problem that results from various causes in patients with ulcerative colitis (UC), but there is little information on the association of UC with pure red cell aplasia (PRCA). We describe the first case of parvovirus-induced PRCA in UC. A 28-year-old woman with chronic UC was admitted to the hospital for treatment of active pancolitis. Three courses of pulse therapy with methylprednisolone provided complete remission. However, the patient developed reticulocytopenia and a subsequent fall in hemoglobin to 6.2 g/dl. Bone marrow examination revealed selective aplasia of red cell precursors and giant pronoromoblasts. Enzyme immunoassay identified specific immunoglobulin M antibody against parvovirus B19 in the serum. Based on these findings, the diagnosis of PRCA caused by the virus was made. The patient was treated with a 3-day course of intravenous immunoglobulin (5 g/day), resulting in brisk reticulocytosis, folowed by normalization of hemoglobin level. In conclusion, Chronic or acute blood loss in UC associated with enhanced red cell turnover might be a risk factor for PRCA when affected patients contract parvovirus B19 infection.

Adult↗

Lafutidine, a novel histamine H2-receptor antagonist, vs lansoprazole in combination with amoxicillin and clarithromycin for eradication of Helicobacter pylori.

BACKGROUND: In contrast to the growing amount of data concerning proton pump inhibitor-based triple therapy for Helicobacter pylori infection, it is still controversial whether proton pump inhibitor can be replaced by H2 receptor antagonist without compromising efficacy. Lafutidine is a novel potent H2 receptor antagonist with gastroprotective activities such as enhancement of gastric mucosal blood flow. METHODS: 122 outpatients with positive cultures and subsequent successful cultivation of H. pylori for antimicrobial susceptibility tests were randomized to receive a 7-day course of either lafutidine (20 mg twice daily) or lansoprazole (30 mg twice daily), plus clarithromycin (200 mg twice daily) and amoxicillin (750 mg twice daily). Eradication was considered successful if the rapid urease test, culture, histology and [13]C-urea breath test were all negative at least 4 weeks after cessation of therapy. Cytochrome p450 2C19 genotype status using polymerase chain reaction-restriction fragment length polymorphism was also studied. RESULTS: On intention-to-treat basis, H. pylori cure was achieved in 52 of 61 (85.2%) patients and 49 of 61 (80.3%) patients for the lafutidine- and lansoprazole-based therapies, respectively. The predicted 95% confidential intervals for the 4.9% of the difference were -1.8-11.6%. Using per protocol analysis, the eradication rates were 88.2% (52/59) and 84.5% (49/58), respectively. The predicted 95% confidential intervals for the 3.7% of the difference were -2.6-10.0%. Adverse events were observed in five and six patients, from the lafutidine and lansoprazole groups, respectively, but they were generally mild. Genetic predisposition of cytochrome p450 2C19 had no significant influence on treatment outcome in both regimens. CONCLUSIONS: The lafutidine-clarithromycin-amoxicillin therapy yielded satisfactory results for eradicating H. pylori, which was comparable with those of the lansoprazole-based regimen with the same drug combination.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Anti-extractable nuclear antigens (ENA) antibodies in patients with chronic hepatitis C before and after treatment with interferon.

A high prevalence of serological markers classically associated with autoimmune hepatitis or other autoimmune diseases has been reported in patients with chronic hepatitis C. However, the prevalence of antibodies to extractable nuclear antigens (anti-ENA) are rarely reported in such patients and the effect of treatment with interferon (IFN) on their prevalence is not known. In the present study, serum samples collected from 44 patients with chronic hepatitis C and 44 patients with non-hepatitis C virus (HCV) infected liver diseases were tested for anti-ENAs (U1 RNP, Sm, Ro/SS-A, La/SS-B and Scl-70) antibodies by enzyme-linked immunosorbent assay (ELISA). In 26 patients with chronic hepatitis C who received IFN treatment, serum samples were also collected just after completion of IFN treatment, and/or at 6-40 months after completion of the treatment, and tested for these antibodies. Sixteen (36%) of 44 sera from patients with chronic hepatitis C were positive for at least one of the above anti-ENA antibodies, whereas only 7 (16%) of 44 sera from patients with non-HCV infected liver diseases were positive for such antibodies (p = 0.0290). There was no significant difference in the prevalence of each of anti-ENA antibody between men and women. Results of anti-ENA antibodies in most IFN-treated patients with chronic hepatitis C did not change after treatment. However, in some cases serum anti-U1 RNP, anti-La/SS-B and anti-Scl-70 became negative or converted to the gray zone after completion of IFN treatment regardless of HCV elimination. Our results showed that the overall prevalence of anti-ENA antibodies was significantly higher in patients with chronic hepatitis C than in those with non-HCV-infected liver diseases. However, the disappearance of anti-ENA antibodies after IFN treatment in patients with chronic hepatitis C may be due to the immunomodulating effects of IFN rather than HCV elimination.

Adult↗

Two cases of adult T-cell leukemia/lymphoma involving the terminal ileum.

We describe two cases of adult T-cell leukemia/lymphoma (ATLL) with terminal ileal involvement. The first case, a 71-year-old man with lymphoma subtype of ATLL, had a polypoid lesion in the terminal ileum, in addition to a duodenal mass. The second case, a 58-year-old woman with lymphoma subtype of ATLL, had an irregular ulcerative lesion in the terminal ileum and multiple ulcers throughout the stomach. Biopsies from these lesions revealed mucosal invasion of ATLL cells in each case. In the second case, combination chemotherapy was transiently effective, resulting in the disappearance of gastric and terminal ileal lesions. Prospective and careful examination of additional cases should further characterize the clinicopathological features of terminal ileal involvement in ATLL.

Aged↗

Successful treatment with cyclosporin in adult-onset Still disease manifesting as acute hepatitis with marked hyperferritinemia.

A 48-year-old woman was admitted because of spiking high fever, sore throat, and jaundice. A diagnosis was made of adult-onset Still disease (AOSD) presenting with acute hepatitis and very high serum ferritin levels (32,240 ng/mL), and she was treated with 2 courses of pulse therapy of methylprednisolone (2 g/day for 3 days) followed by 40 mg/day prednisolone. Subsequently, the serum level of ferritin decreased, but serum total bilirubin increased to 17.3 mg/dL. Therefore, cyclosporin was administered orally. Within the next 3 months, results of liver function tests, as well as serum levels of ferritin, soluble interleukin-2 receptor, interferon-gamma, interleukin-6, and tumor necrosis factor-alpha gradually returned to within normal limits, and cyclosporin administration was subsequently reduced gradually. The clinical presentation suggests that AOSD should be considered when liver dysfunction is accompanied with high fever and extreme hyperferritinemia, and that treatment with cyclosporin or other immunosuppressive drugs that selectively suppress cytokine production by helper T cells is a valuable option in the treatment of AOSD with very high serum ferritin levels.

Administration, Oral↗