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H Miwa

Publications and source records attributed to H Miwa.

At least 73 records · Page 4Linked to original sources
PubMed2000

Induction of chromosomal aberrations and growth-transformation of lymphoblastoid cell lines by inhibition of reactive oxygen species-induced apoptosis with interleukin-6.

Etiological evidence, indicating the relationships between the onset of malignant lymphoma and pre-existing chronic inflammation, has been accumulated. For the autonomous growth of malignant tumor, genetic lesions, such as chromosomal aberrations, amplification of oncogenes, and mutations of genes involved in the cell cycle regulation, must be essential. However, how the inflammation promotes the accumulation of genetic lesions and induces the autonomous growth of lymphoid cells remains unclear. Reactive oxygen species released by polymorphonuclear leukocytes and macrophages are factors causing DNA damage in the foci of inflammation, and thus could play a role in lymphomagenesis. The xanthine/xanthine oxidase (X/XOD) system produces a mixture of hydrogen peroxide and superoxide anion extracellularly, and thus serves as an in vitro source of reactive oxygen species. Cell death of lymphoblastoid cell lines (LCLs) was induced with X/XOD treatment in a dose-dependent manner. DNA fragmentation, which is the characteristic feature of apoptosis, was observed in LCLs at 4-8 hours after X/XOD treatment. Among cytokines such as interleukin-6 (IL-6), IL-10, and interferon-gamma, only pretreatment with IL-6 gave LCLs the resistance to X/XOD-induced cell death in a dose-dependent manner. The proportion of apoptotic cells in X/XOD-treated LCL culture was decreased with IL-6 pretreatment by quantification with flow cytometric analysis. Treatment of LCLs with IL-6 for 48 hours up-regulated bcl-2 mRNA expression. Furthermore, the LCLs repeatedly treated with X/XOD and cultured with or without IL-6 showed many more structural abnormalities of chromosomes than those without X/XOD treatment. Colony forming efficiency of X/XOD-treated LCLs with IL-6 was significantly higher than those without IL-6, and even relatively higher than LCLs without X/XOD treatment. IL-6 could support the survival of non-neoplastic B cells and accelerate the malignant transformation of B lineage cells in inflammatory lesions.

Apoptosis↗
PubMed2000

Role of hypermethylation of DAP-kinase CpG island in the development of thyroid lymphoma.

Death-associated protein-kinase (DAP-Kinase) is a serine/threonine kinase with a death domain that is involved in apoptosis induced by interferon-gamma, TNF-alpha, and Fas ligand. Epigenetic down-regulation of DAP-Kinase gene expression by hypermethylation of its promoter region was reported in B-cell malignancies. Previous pathoepidemiologic studies indicated that thyroid lymphoma (TL) evolves among active lymphoid cells in chronic lymphocytic thyroiditis (CLTH). With use of methylation-specific polymerase chain reaction, the methylation status of DAP-Kinase CpG island was examined in thyroid lesions of 19 cases with TL and 9 with CLTH. The frequency of methylation was higher in TL cases (16 of 19, 84.2%) than in CLTH cases (2 of 9, 22.2%) (p < 0.01). DNA extracted from peripheral blood leukocytes from TL and CLTH cases never showed methylation, indicating that the methylation occurred somatically in the lesional lymphocytes in thyroid. These findings suggested that methylation of the DAP-Kinase promoter region might be involved in the development of TL from CLTH.

Adult↗
PubMed2000

Heterogenous fusion transcripts involving the NUP98 gene and HOXD13 gene activation in a case of acute myeloid leukemia with the t(2;11)(q31;p15) translocation.

We report the characterization of a rare chromosomal translocation, a t(2;11)(q31;p15), which occurred in a patient with de novo acute myeloid leukemia (AML-M4). By 3'-RACE and RT-PCR analyses, two kinds of NUP98-HOXD13 fusion transcript were detected. In addition, we identified a novel fusion transcript, NUP98-FN1, in the same patient. Ectopic expression of the wild-type HOXD13 gene was also observed in the patient, suggesting that HOXD13 contributes to the development of this type of leukemia. The NUP98-HOXD13 fusion transcript was predicted to encode a 552 or 569-amino acid protein containing the Phe-Gly (FG) repeat region of NUP98 and the homeodomain of HOXD13. The NUP98-FN1 fusion transcript was predicted to encode a 482 or 499-amino acid protein consisting of the same N-terminal region of NUP98 and a C-terminal region of 12 amino acids derived from a previously unidentified sequence. We isolated and characterized the chromosomal breakpoints. The breakpoint at 11p15 is mapped within a LINE repetitive element in a 9 kb intron of NUP98, and more than 60% of the sequenced 3 kb region surrounding the breakpoint junction consists of repetitive elements. The other breakpoint at 2q31 is in an intron of FN1, which is located 7 kb upstream of HOXD13, and the repetitive sequence content of the breakpoint junction is low. Local sequence duplications at genomic breakpoints suggest that the t(2;11) translocation is mediated through staggered double-strand DNA breaks. These results throw light on the mechanisms responsible for the generation of t(2;11) translocation and on the processes leading to t(2;11) leukemia.

Acute Disease↗
PubMed2000

Do mucosal defensive agents improve the cure rate when used with dual or triple therapy regimens for eradicating Helicobacter pylori infection?

BACKGROUND: Some of mucosal defensive agents have anti-Helicobacter pylori activities. However, their effectiveness in eradicating H. pylori infection has not been evaluated. AIM: To assess the additive effect of mucosal defensive agents in eradication regimens using statistical analysis. METHODS: Pertinent studies were retrieved using the Medline and the Igaku-chuo-zasshi databases in Japan, reference and congress abstract lists. Studies in which regimens consisted of dual or triple therapy with mucosal defensive agents and without them, were selected from the retrieved studies. Eradication rates were extracted from studies according to intention-to-treat analysis. We evaluated the efficacies of mucosal defensive agents by pooled relative risk of eradication rates and its 95% confidence intervals (95% CI), which were calculated by Mantel-Haenszel method. Heterogeneity among the studies in treatment effect was evaluated by a chi2-test. RESULTS: In dual therapy regimens, mucosal defensive agents demonstrated significant additive effects (pooled relative risk 1.41; 95% CI: 1.24-1.61). In triple therapy regimens, these agents did not provide significant additive effect. The clinical usefulness of specific agents could not be established, when each agent was analysed independently. CONCLUSIONS: Mucosal defensive agents improve the cure rate when used with existing dual therapy regimens for eradicating H. pylori infection.

Anti-Ulcer Agents↗
PubMed2000

Cure of Helicobacter pylori infection does not improve symptoms in non-ulcer dyspepsia patients-a double-blind placebo-controlled study.

BACKGROUND: It remains controversial whether the cure of H. pylori infection improves NUD symptoms. AIM: To conduct a double-blind placebo-controlled single centre study with concealed allocation to investigate this question. PATIENTS AND METHODS: Ninety NUD patients with H. pylori infection were randomly assigned to either the treatment group (50 patients) or placebo group (40 patients). The treatment group received omeprazole, amoxycillin, clarithromycin and the placebo group received omeprazole and placebos for 7 days. Symptoms were assessed every week for up to 12 weeks after completion of medication by a symptom questionnaire. Alteration of histological parameters for gastritis was also evaluated. RESULTS: The infection was cured in 41 out of 48 patients in the treatment group and none in the placebo group. There was no significant difference in the mean symptom scores at any assessment point up to 12 weeks between the treatment and placebo groups. Regarding histological parameters, activity and inflammation, not atrophy or intestinal metaplasia, were significantly improved in the treatment group. CONCLUSION: Although histological parameters were significantly improved in the treatment group, there was no significant improvement in symptoms of NUD in the treatment group compared to placebo.

Adult↗
PubMed2000

The incidence of reflux oesophagitis after cure of Helicobacter pylori in a Japanese population.

AIM: To investigate the incidence of reflux oesophagitis after antibacterial therapy for Helicobacter pylori infection in our patient population. METHODS: Subjects were 451 H. pylori-infected patients (primary symptom: peptic ulcer disease in 347, nonulcer dyspepsia in 100, and reflux oesophagitis in four): 11 of these patients had reflux oesophagitis on study entry. H. pylori infection was treated by a proton pump inhibitor/amoxycillin-clarithromycin regimen for either 7 or 14 days. Each patient was examined by endoscopy before treatment and more than 6 months after treatment to compare oesophageal findings. In addition, 227 patients were interviewed regarding reflux symptoms, using symptom questionnaires, before and more than 6 months after treatment. RESULTS: Among 440 patients who did not have reflux oesophagitis prior to antibacterial treatment (340 peptic ulcer patients and 100 nonulcer dyspepsia patients), 23 patients whose infection was eradicated developed reflux oesophagitis (5.4%). The 11 patients who had reflux oesophagitis prior to treatment were all successfully cured of infection. Six of these patients showed no change in their oesophagitis, while the condition improved in three and worsened in two. Symptom scores improved in 34 of the 36 patients who reported reflux symptoms. Among 19 patients who showed persistent infection, only one developed reflux oesophagitis (5.2%), while none complained of newly developed symptoms following treatment. CONCLUSIONS: Development of reflux oesophagitis after treatment of H. pylori infection was observed in a Japanese population. However, the incidence of this condition was comparable between those with persistent H. pylori infection and those in whom the infection was eradicated.

Adult↗
PubMed2000

Effects of growth factors on aspirin-induced inhibition of wound repair in a rabbit gastric epithelial cell model.

BACKGROUND: Aspirin is known to cause adverse effects, including gastric mucosal injury, and to retard gastric wound healing. Growth factors including hepatocyte growth factor (HGF), epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) have been shown to play an important role in the repair of gastric mucosal injury. AIM: To employ the cultured gastric epithelial cell model to elucidate the effects of aspirin, as well as several growth factors (HGF, EGF and IGF-I), on gastric wound repair. METHODS: Isolated rabbit gastric epithelial cells (92% mucous cells) were cultured in F-12 medium and formed a complete monolayer cell sheet in 48 h. A wound with a cell-free area of constant size (2 mm2) was then created and the wound repair process was monitored by measuring wound size every 12 h. Proliferating cells were detected by BrdU staining. Effects of aspirin (8 mM), HGF (10 ng/mL), EGF (10 ng/mL) and IGF-I (30 ng/mL) were assessed. RESULTS: Aspirin significantly retarded wound healing, but simultaneous addition of growth factors significantly accelerated wound repair compared with aspirin alone. Growth factors reversed the aspirin-induced inhibition of cell proliferation. CONCLUSION: Growth factors, including HGF, EGF and IGF-I, reversed the aspirin-induced inhibition of wound repair through their cytoprotective effects on gastric epithelial cells.

Animals↗
PubMed2000

Functional dyspepsia and Helicobacter pylori infection: a recent consensus up to 1999.

With accumulated evidence for a close relationship between Helicobacter pylori infection and many gastric disorders, the idea that this infection may invoke dyspeptic symptoms appears realistic. If curative therapy for H. pylori can bring about relief of symptoms in these patients, we would possess a new therapeutic tool for functional dyspepsia. Although there have been many clinical trials on this issue, the benefits of H. pylori treatment have been controversial. However, several large-scale clinical studies have been very recently published, and suggest a specific direction on this clinical question. From these results, the current consensus is that H. pylori infection does not directly affect symptoms in patients with functional dyspepsia. However, most clinical trials have been performed on Western populations, and there are few reports from Asian countries. Our recent study on the Japanese population also supported the consensus, that is, a negative relationship between H. pylori infection and symptoms in functional dyspepsia patients.

Asia↗
PubMed2000

Addition of metronidazole to rabeprazole-amoxicillin-clarithromycin regimen for Helicobacter pylori infection provides an excellent cure rate with five-day therapy.

BACKGROUND: New triple therapy for eradication of Helicobacter pylori based on a proton pump inhibitor (PPI) provides a cure rate of approximately 90% with few adverse effects. Recently, a PPI-based quadruple therapy, which consists of a PPI plus bismuth-based triple therapy for 7 days, has been studied, and a sufficient eradication rate has been achieved. However, a shorter duration results in improved compliance. In this study, newly developed short-term, simple twice-daily quadruple therapy consisting of rabeprazole, amoxicillin, clarithromycin, and metronidazole (RACM) was compared with a PPI-based triple-therapy regimen for eradication of H. pylori. PATIENTS AND METHODS: This study was designed as a randomized open, prospective single-center study. Of a total of 105 H. pylori-positive patients, 55 received the RACM regimen for 5 days (rabeprazole, 10 mg bid; amoxicillin, 750 mg bid; clarithromycin, 200 mg bid; and metronidazole, 250 mg bid), and 50 received the RAC regimen for 5 days (rabeprazole, 10 mg bid; amoxicillin, 750 mg bid; and clarithromycin, 200 mg bid). Cure of the infection was assessed by HpSA (H. pylori stool antigen immunoassay) 1 month after completion of therapy. RESULTS: The rates of eradication of H. pylori by RACM versus RAC were 94.5% (95% CI, 85-99) versus 80.0% (95% CI, 66-90) by intention-to-treat analysis; 98.1% (95% CI, 90-100) versus 87.0% (95% CI, 74-95) by all-patients-treated analysis; and 98.1% (95% CI, 90-100) versus 86.7% (95% CI, 73-95) by per-protocol analysis. No major adverse effects were reported, and 98.0% of patients reported complete compliance. CONCLUSIONS: The simple twice-daily and short-term quadruple regimen for only 5 days provided an excellent eradication rate. Compliance with the regimen was high, and serious adverse effects were few. Therefore, the RACM regimen can be considered as safe and effective.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Expressions of Fas ligand and other apoptosis-related genes and their prognostic significance in epithelial ovarian neoplasms.

Expression of apoptosis-related proteins, bcl-2, Bax, Fas and Fas ligand (L), in ovarian epithelial neoplasms together with its clinical relevance was examined by immunohistochemistry. They included 36 cases with adenoma, 33 with low potential malignancy (LPM) and 63 with carcinomas. bcl-2 expression was observed in 14 of 36 cases (39%) with adenoma, five of 33 (15%) with LPM (P< 0.05) and 12 of 63 (19%) with carcinoma (P < 0.05). Cases with bcl-2 expression showed more favourable prognosis than those without, but the difference was not statistically significant. There was no difference in frequency of Bax and Fas expression between each histologic category. Fas L expression was observed in one of 36 cases (3%) with adenoma, but in 12 of 33 (36%) with LPM (P < 0.001) and 42 of 63 (67%) with carcinoma (P < 0.0001). In carcinomas, cases expressing Fas L showed a less favourable prognosis than those without (P = 0.02). Density of CD8+ lymphocytes, possibly cytotoxic T-cells, was higher in serous carcinoma with negative Fas L expression than those with positive Fas L expression. These findings suggest that Fas L expressing carcinomas induce apoptosis in infiltrating CTL with Fas expression, and escape from immune surveillance.

Adenoma↗
PubMed2000

Usefulness of a novel enzyme immunoassay for the detection of Helicobacter pylori in feces.

BACKGROUND: In this study we assessed the reliability of a newly developed enzyme immunoassay (HpSA) kit for detecting Helicobacter pylori antigen in stool. METHODS: This study included 309 patients, 147 of whom were defined as positive and 162 as negative by the 13C-urea breath test, rapid urease test, and pathologic findings. From these patients fresh stool specimens were collected for HpSA. RESULTS: When 0.100 was adopted as the cut-off value, in accordance with the manufacturer's recommendations, the sensitivity, specificity, and accuracy of the HpSA were 98.0%, 87.0%, and 92.2%, respectively. However, these values were much improved when a cut-off value of 0.300 was adopted, which was obtained with our receiver-operator characteristics curve; with this value the sensitivity, specificity, and accuracy of HpSA were 93.9%, 95.7%, and 94.8%, respectively. CONCLUSION: These results indicate that HpSA is a highly reliable diagnostic method for H. pylori infection and is useful in confirming eradication.

Antigens, Bacterial↗
PubMed2000

Pyruvate secreted by human lymphoid cell lines protects cells from hydrogen peroxide mediated cell death.

Reactive oxygen species (ROS) released from polymorphonuclear leukocytes and macrophages could cause DNA damage, but also induce cell death. Therefore inhibition of cell death must be an important issue for accumulation of genetic changes in lymphoid cells in inflammatory foci. Scavengers in the post culture medium of four lymphoid cell lines, lymphoblastoid cell lines (LCL), Raji, BJAB and Jurkat cells, were examined. Over 80% of cultured cells showed cell death 24 h after xanthine (X)/xanthine oxidase (XOD) treatment, which was suppressed by addition of post culture medium from four cell lines in a dose-dependent manner. H2O2 but not O2*- produced by the X/XOD reaction was responsible for the cytotoxity, thus we used H2O2 as ROS stress thereafter. The H2O2-scavenging activity of post culture media from four cell lines increased rapidly at the first day and continued to increase in the following 2-3 days for LCL, Raji and BJAB cells. The scavenging substance was shown to be pyruvate, with various concentrations in the cultured medium among cell lines. Over 99% of total pyruvate was present in the extracellular media and less than 1% in cells. alpha-Cyano-4-hydroxycinnamate, a specific inhibitor of the H+-monocarbohydrate transporter, increased the H2O2-scavenging activity in the media from all four cell lines via inhibition of pyruvate re-uptake by cultured cells from the media. These findings suggest that lymphoid cells in inflammatory foci could survive even under ROS by producing pyruvate, so that accumulation of lymphoid cells with DNA damage is possible.

Cell Death↗
PubMed2000

Characteristics of cutaneous lymphomas in Osaka, Japan (1988-1999) based on the European Organization for Research and Treatment of Cancer classification.

Based on accumulating information, European investigators proposed a new classification for primary cutaneous lymphomas known as the European Organization for Research and Treatment of Cancer (EORTC) classification. The clinical utility of this classification in Japanese cases has not been evaluated. Material from 65 patients with cutaneous lymphomas (48 with primary disease and 17 with secondary disease) who were admitted to Osaka University Hospital during the period 1988 through 1999 was reviewed. Immunohistochemical analysis was performed in all cases. Cutaneous T-cell lymphoma (CTCL) comprised mycosis fungoides (15 cases), Sézary syndrome (1 case), lymphomatoid papulosis (5 cases), large cell CTCL (13 cases), pleomorphic small- or medium-sized CTCL (2 cases), and cutaneous natural killer /T-cell lymphoma (4 cases). B-cell lymphomas comprised 7 cases of follicle center cell lymphoma and 1 case of diffuse large B-cell lymphoma of the leg. Each category of disease in the EORTC scheme showed its characteristic features in our series. Five of 13 large cell CTCL cases were positive for CD30, and 5 were negative. The 5-year survival rate of patients with large cell CTCL CD30+ disease was 100% and that of patients with CD30- disease was 0%. (p > 0.1). Only 1 of 7 CTCL cases expressing CD30 was ALK-1+, and all 7 cases showed a favorable clinical course. The EORTC classification is effective in dealing with Japanese cases of cutaneous lymphomas.

Adolescent↗
PubMed2000

Analysis of T-cell antigen receptor gamma chain gene rearrangement by polymerase chain reaction in combination with denaturing gradient gel electrophoresis in the differential diagnosis of cutaneous T-lymphoproliferative diseases.

A polymerase chain reaction (PCR)-based strategy has been developed for analysis of clonal rearrangement of the T-cell receptor gamma gene (TCR gamma) and was shown to be useful for detection of clonal T-cell populations. In this study, we performed PCR combined with denaturing gradient gel electrophoresis (DGGE) on fresh frozen biopsy samples from 16 patients with cutaneous T-lymphoproliferative diseases in whom a definite diagnosis was difficult to make on morphological and immunohistochemical grounds alone. Ages of the patients at biopsy ranged from 28 to 81 (median 62) years, and the subjects consisted of 8 men and 8 women. They presented with erythema on the extremities in 5 cases, trunk in 7, buttock in 2, and papules on the trunk and face in one case each. Clonal rearrangement of TCR gamma was observed in 3 of 16 cases. Clinical diagnoses of these three cases were mycosis fungoides, cutaneous invasion of adult T-cell leukemia (ATL), and large granular lymphocytic leukemia (LGL) of T-cell type, respectively, but they were histologically difficult to differentiate from reactive cutaneous T-cell proliferation. The skin lesions of the LGL case worsened, and this patient died two years after biopsy. Another patient with suspected mycosis fungoides in the plaque stage died due to dissemination of tumors 22 months after biopsy. The remaining one patient with ATL survived with cutaneous lesions for over four years. Clonality was not demonstrated in the remaining 13 cases, and their clinical courses were favorable. These findings showed that demonstration of clonal TCR gamma gene rearrangement using the PCR-DGGE method is very helpful for diagnosis of cutaneous T-cell neoplasms.

Adult↗
PubMed2000

Elevation of antibody against Epstein-Barr virus genes BRLF1 and BZLF1 in nasopharyngeal carcinoma.

PURPOSE: Epstein-Barr virus immediate early genes BZLF1 and BRLF1 encode the Z and R proteins respectively. Elevation of the anti-Z immunoglobulin (Ig) antibody titer is a common feature of nasopharyngeal carcinoma (NPC) in areas where the disease endemic, whereas R levels have not been examined. This study was performed to analyze antibody titers against Z and R in Japan. METHODS: Sera from 14 patients with newly diagnosed NPC, 7 with NPC in complete remission, 15 with head and neck squamous cell carcinoma (HNSCC), and 31 controls were evaluated by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: Both anti-Z and anti-R Ig were significantly increased in sera from patients with NPC compared with those in remission, those with HNSCC, and controls (Z, P = 0.0016, = 0.0344, = 0.0002; R, P = 0.0015, = 0.0004, <0.0001 respectively). By immunoblot analysis, anti-Z and anti-R Ig were detected in 9 of 9 cases of NPC, 1 of 3 cases NPC in remission, and 2 of 13 cases of HNSCC. Anti-Z and anti-R antibody titers were nine times higher in NPC than in other groups. None of 15 control cases showed positive reactivity against either Z or R. CONCLUSION: Coupled evaluation of anti-Z and anti-R Ig by ELISA might be a useful system for screening NPC.

Carcinoma, Squamous Cell↗
PubMed2000

[Transient improvement in motor function and hemineglect by vestibular stimulation in a patient with right middle cerebral artery embolism].

A 62-year-old Japanese man presented left hemiparesis and left visuospatial hemineglect following a right hemispheric stroke. His CTs and MRIs of the brain revealed a large embolic infarction of the middle cerebral artery territory. A month after the cerebrovascular event, his weakness of the left lower limb almost recovered fully. However, his upper limb motor function was still disabled; in particular, his ability of finger flexion in the left hand was almost lost. Then, vestibular stimulation using either a cold caloric stimulation to the left ear or a warm caloric stimulation to the right ear was performed, and the effect on the hemineglect symptoms were assessed by a line bisection task. After vestibular stimulation, not only his hemineglect symptoms but also his motor functions of left upper limb transiently improved; he became able to make a fist. The improvement of his hemineglect symptoms was obtained by vestibular stimulation using either a cold or a warm caloric stimulation. However, the effect on the motor function was obtained only by the cold caloric stimulation applied to the left ear. Based on the effect of the vestibular stimulation, we postulates that the impairment of the motor function in the present patient is not only a paresis caused by the pyramidal tract lesion but also symptoms related to the hemineglect syndrome.

Hemiplegia↗
PubMed2000

Effects of cyclosporin A on refractory B-cell chronic lymphocytic leukemia.

This report details the effects of cyclosporin A (Cs-A) on the clinical course of B-cell chronic lymphocytic leukemia (B-CLL) with an increase in circulating T cells that express CD3, CD8, CD25, CD45RO, and T-cell receptor alpha beta chain. Cs-A was used for treatment of a female patient with refractory B-CLL and was shown to increase dramatically the number of leukemic B cells in association with a simultaneous increase in T cells in vivo. To study this effect more precisely, CD19+ (B cells) and CD3+ (T cells) cells were isolated from the patient and cultured in the presence or absence of Cs-A. When Cs-A was added to the culture, no cell stimulation was seen. However, CD3+ cells from the patient underwent cell death, relative to those from healthy donors. On the other hand, CD19+ cells from the patient were more resistant to Cs-A than those from healthy donors. Because in vitro experiments cannot explain this phenomenon of Cs-A increasing leukemic cells (not only B-CLL cells but also T cells), care should be exercised in the clinical use of Cs-A in B-CLL patients.

Antigens, CD19↗