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Biomedical subjects

Masahiro Imamura

Publications and source records attributed to Masahiro Imamura.

At least 19 recordsLinked to original sources
PubMed2007

Efficacy and safety of micafungin in febrile neutropenic patients treated for hematological malignancies.

OBJECTIVE: The purpose of this study was to prospectively evaluate the efficacy and safety of micafungin (MCFG) in empirical therapy for febrile neutropenic patients for whom antibiotic therapy was not effective for hematological malignancies. PATIENTS AND METHODS: Twenty-three hematological patients aged 27-82 years with febrile neutropenia for whom antibiotic therapy was not effective were enrolled in this study and responses to treatment were evaluated. RESULTS: Treatment success rate was 73.9%. Treatment success rates by primary diagnosis were 77.8% in patients with AML, 50.0% in patients with NHL and 87.5% in patients with other diseases. Moreover, MCFG at a dose of 100 mg or more have a tendency to be effective. One or more adverse events occurred in five (27.7%) of the patients during the study. All of these adverse events were below grade 2 toxicity. CONCLUSIONS: Although the number of patients studied was limited, MCFG as a monotherapy seems to be effective and safe as an empirical therapy in patients with febrile neutropenia. However, further investigation using large-scale studies is needed. This study demonstrated the clinical efficacy and safety of MCFG in patients with febrile neutropenia and with hematological malignancies.

Adult↗
PubMed2006

Effects of low-dose irradiation on enhancement of immunity by dendritic cells.

Low-doses of irradiation have been reported to have beneficial effects, particularly anti-tumor effects. In this paper, we show the effects of the low-dose irradiation on T cell activation induced by dendritic cells (DCs). DCs, which had been pre-irradiated at 0.02-1.0 Gy from a (137)Cs source, were cultured with allogeneic T cells, and the proliferation of T cells was then examined. The 0.05Gy-pre-irradiated DCs showed the highest proliferation capacity of T cells. The 0.05Gy-irradiation does not augment the expression of major histocompatibility complexes (MHCs) or costimulatory molecules on DCs, as with non-irradiated DCs or 1Gy-irradiated DCs, but does augment the production of IL-2, IL-12 and IFN-gamma DCs. These results suggest that the low-dose irradiation augments T cell-activation capacity through cytokine production by DCs, which might shift naïve helper T cells to Th1 cells.

Animals↗
PubMed2006

Relationship between preexisting anti-varicella-zoster virus (VZV) antibody and clinical VZV reactivation in hematopoietic stem cell transplantation recipients.

Reactivation of latent varicella-zoster virus (VZV), presenting as localized zoster or as disseminated infection, is a common and potentially serious complication in hematopoietic stem cell transplantation (HSCT) recipients. We retrospectively studied anti-VZV immunoglobulin G titers by the immune adherence hemagglutination method after HSCT and also studied VZV DNA by real-time PCR during clinical VZV reactivation using cryopreserved serum samples. No significant difference was found between anti-VZV titers in 13 patients with VZV infection (localized zoster in 11 patients and disseminated zoster in 2 patients) and in 13 subjects without VZV infection at each time point after HSCT. Preexisting anti-VZV titers of disseminated zoster cases tended to be lower than those of localized zoster cases (P=0.10). Serum VZV DNA copy numbers at the onset of disseminated zoster cases tended to be higher than those of localized zoster cases (P=0.09). A strong inverse correlation was found between preexisting anti-VZV titer and serum VZV DNA at onset (r=-0.90, P=0.006). In HSCT recipients, preexisting antibody does not prevent the development of VZV reactivation but may contribute to decreased viral load at onset, resulting in a mild clinical course.

Adult↗
PubMed2006

Effect of granulocyte colony-stimulating factor on IL-12 p40 production during chemotherapy for B-cell lineage non-Hodgkin's lymphoma patients.

Interleukin (IL)-12 is a 70-kDa cytokine comprised of two disulfide-linked proteins (p35 and p40) and is essential for the initiation of effective immune response. Granulocyte-colony stimulating factor (G-CSF) affects the balance in the production of anti-inflammatory cytokines. We investigated the serum IL-12 p40 and IL-12 Mix (p40 and p70) production in 28 patients with B-cell lineage non-Hodgkin's lymphoma (NHL) treated with chemotherapy (e.g., CHOP regimen) with or without G-CSF administration and eight healthy volunteers. We found that serum levels of IL-12 p40 (191.2 +/- 150.0 pg/mL) and IL-12 Mix (277.4 +/- 274.5 pg/mL) in the patients before chemotherapy were higher than those in the healthy volunteers (IL-12 p40: 76.4 +/- 25.3 pg/mL, IL-12 Mix: 48.5 +/- 33.4 pg/mL) (P = 0.04 and 0.02, respectively). Next, we examined the serum IL-12 p40 and IL-12 Mix levels in nine patients receiving chemotherapy with administration of G-CSF (CG group, n = 9) and without G-CSF (C group, n = 9). Serum IL-12 p40 and IL-12 Mix levels were decreased on 10 d after chemotherapy in both groups, and those in CG groups were significantly lower than those in C group. These results indicated that administration of G-CSF decreased serum IL-12 p40 and IL-12 Mix levels. Overall survival (OS) at 24 months was not significantly different in the two groups (58.3% in group C vs. 80.0% in group CG, P = 0.67). However, the survival rate of patients at clinical stages III and IV in CG group (n = 6, 66.0%) was significantly better than that of patients in C group (n = 4, 25.0%) (P = 0.02). Long-term administration of G-CSF appears to influence the survival rate by reducing immunosuppressive IL-12 p40 production.

Adult↗
PubMed2006

Effect of macrophage migration inhibitory factor (MIF) on acute graft-versus-host disease in a murine model of allogeneic stem cell transplantation.

Macrophage migration inhibitory factor (MIF) may play an important role in the pathogenesis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). We examined whether MIF has an influence on the development of aGVHD and survival using BALB/c-based MIF knock-out (MIF KO) mice. Although MIF expression was observed in lymphocytes that had infiltrated the liver during aGVHD in both wild-type (WT) and MIF KO mice that received bone marrow cells (BM) and spleen cells (SP) from C57BL/6N mice, no significant difference was found in severity of aGVHD or survival rate between the two groups of mice. However, MIF level had decreased at 1 week after HSCT when MIF KO mice were used as the recipients. In the experiment using MIF KO mice as the donors, the recipient mice transplanted with BM and SP from MIF KO mice had significantly lower aGVHD scores on days 14, 21, and 35 than those in the recipient mice transplanted with BM and SP from WT-BALB/c mice. Histopathological findings supported these observations, showing that the bile ducts and lobules in the liver were destroyed by infiltrating MIF-expressing lymphocytes in the recipients of BM and SP from WT-BALB/c mice, while the bile ducts were not destroyed even by infiltrating MIF-deficient lymphocytes in the recipients of BM and SP from MIF KO mice. Therefore, these findings suggest that MIF has an effect on the development of aGVHD in a murine model of allogeneic stem cell transplantation.

Acute Disease↗
PubMed2006

Overexpression of the oncoprotein prothymosin alpha triggers a p53 response that involves p53 acetylation.

Activation of the tumor suppressor protein p53 is a critical cellular response to various stress stimuli and to inappropriate activity of growth-promoting proteins, such as Myc, Ras, E2F, and beta-catenin. Protein stability and transcriptional activity of p53 are modulated by protein-protein interactions and post-translational modifications, including acetylation. Here, we show that inappropriate activity of prothymosin alpha (PTMA), an oncoprotein overexpressed in human cancers, triggers a p53 response. Overexpression of PTMA enhanced p53 transcriptional activity in reporter gene assays for p53 target gene promoters hdm2, p21, and cyclin G. Overexpressed PTMA resulted in increased mRNA and protein levels for endogenous p53 target genes, hdm2 and p21, and in growth suppression. In contrast, reduction of endogenous PTMA through RNA interference decreased p53 transcriptional activity. Histone acetyltransferases (HATs) act as p53 coactivators and acetylate p53. PTMA, known to interact with HATs, led to increased levels of acetylated p53. PTMA did not increase the transcriptional activity of an acetylation-deficient p53 mutant, suggesting that p53 acetylation is an indispensable part of the p53 response to PTMA. Chromatin immunoprecipitation assays showed that excess PTMA associates with the p21 promoter and results in increased levels of acetylated p53 at the p21 promoter. Our findings indicate that overexpressed PTMA elicits a p53 response that involves p53 acetylation.

Acetylation↗
PubMed2006

Delayed reduction in left ventricular function following treatment of non-Hodgkin's lymphoma with chemotherapy and rituximab, unrelated to acute infusion reaction.

We report 3 cases of reduced cardiac function with complications in non-Hodgkin's lymphoma patients who were treated with rituximab. Patients experienced reduced cardiac functions after the administration of rituximab; there was no evidence of any preceding infusion reactions. Reticulin fiber was observed diffusely in cardiac muscles. Transforming growth factor-beta levels were elevated after the administration of rituximab. We believe that continuous elevation of transforming growth factor-beta may promote the growth of reticulin fiber in cardiac muscles. Reduction in cardiac functions is a severe complication that must be considered when rituximab is administered.

Aged↗
PubMed2006

Effect of imatinib mesylate combined with granulocyte colony-stimulating factor on leukaemic blast cells derived from advanced-stage chronic myelogenous leukaemia patients.

Neutropenia is a severe adverse effect that can occur when treating patients with imatinib mesylate for advanced-stage chronic myelogenous leukaemia (CML). Therefore, we evaluated in vitro the combined effect of imatinib and granulocyte colony-stimulating factor (G-CSF) on proliferation and apoptosis of Bcr-Abl-expressing leukaemic cells to infer the safety of G-CSF administration. In KU812 and K562 cell lines, G-CSF neither stimulated their proliferation nor abolished the suppressive effect of imatinib. However, it stimulated the proliferation of blast cells in 2 out of the 5 cases with advanced-stage CML. These in vitro studies appear to provide data for the decision of G-CSF administration in combination with imatinib in the treatment of neutropenic patients with advanced-stage CML.

Antineoplastic Agents↗
PubMed2006

Current status of hematopoietic cell transplantation for adult patients with hematologic diseases and solid tumors in Japan.

A nationwide survey of hematopoietic cell transplantation (HCT) was started in Japan in 1991, and the analyzed survey data have been presented as the annual report of the Japan Society for Hematopoietic Cell Transplantation. The 10-year overall survival (OS) rates after HCT for each disease are as follows: acute myelogenous leukemia, 44.2%; acute lymphocytic leukemia, 33.7%; adult T-cell leukemia, 24.6%; chronic myelogenous leukemia, 53.3%; myelodysplastic syndrome, 37.3%; non-Hodgkin's lymphoma, 41.5%; Hodgkin's lymphoma, 50.8%; aplastic anemia, 72.5%; breast cancer, 37.1%; germ cell tumor, 52.6%; and ovarian cancer, 44.2%. The 5-year OS rates for multiple myeloma and lung cancer were 40.6% and 23.6%, respectively. Except in cord blood transplantation, engraftment was accomplished in more than 90% of patients. The respective frequencies of acute graft-versus-host disease (GVHD) and chronic GVHD were 41.1% and 34.9% for related bone marrow transplantation (BMT), 66.8% and 34.5% for unrelated BMT, 52.9% and 36.0% for allogeneic peripheral blood stem cell transplantation, and 53.3% and 32.1% for allogeneic cord blood transplantation. OS for each disease was analyzed by patient age, stem cell source, donor type, disease status, and disease type. These data provide objective and valuable information for hematologists as well as for patients who need HCT.

Adolescent↗
PubMed2006

Donor-type myelodysplastic syndrome with t(2;3) and monosomy 7 after allogeneic peripheral blood stem cell transplantation and liver transplantation in a patient with severe-type aplastic anemia.

Secondary clonal hemaloiogical disease in donor cells has rarely been reported as a complication of allogeneic stem cell transplantation in hematological disease. We report a case of myelodysplastic syndrome that showed cytogenetic abnormalities of t(2;3) and monosomy 7, which developed 2 years after peripheral blood stem cell transplantation for aplastic anemia and 1 year after liver transplantation for drug-induced hepatic failure. This secondary malignancy of donor origin is most frequently seen in patients with leukemia. We suspect that the chromosomal abnormalities are related to hepatitis-associated aplastic anemia, administration of granulocyte colony-stimulating factor and erythropoietin for posttransplantion pancytopenia, and repeated infections after liver transplantation.

Adult↗
PubMed2005

The immunosuppressive agent FK506 enhances the cytolytic activity of inhibitory natural killer cell receptor (CD94/NKG2A)-expressing CD8 T cells.

Tacrolimus (FK506) is a potent immunosuppressive agent that inhibit transcription of cytokines such as IL-2 in T cells. The C-type lectin superfamily inhibitory NKR CD94/NKG2A-expressing cells can monitor the global status of HLA class I on tumor and leukemic cells through the recognition of HLA-E and induce cytolytic attack without an inhibitory signal against HLA class I-decreased target cells. We found that there was no effect of FK506 on the expansion of inhibitory NKR CD94/NKG2A-expressing T cells from granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (G-PBMCs). However, cytolytic activity levels of purified CD94-expressing cells from 7-day cultures with FK506 were much higher than those from 7-day cultures without FK506. These data suggested that FK506 did not inhibit cytolytic activities of inhibitory NKR-expressing T cells and that there was a possibility of cytolytic activities being enhanced through the induction of cytotoxic molecules such as NKG2D and granzyme during a seven-day culture with FK506.

CD8-Positive T-Lymphocytes↗
PubMed2005

Regulation of Toll-like receptor 4 expression in mouse colon by macrophage migration inhibitory factor.

Recent studies have indicated that macrophage migration inhibitory factor (MIF) and Toll-like receptor (TLR) play an important role in the regulation of innate immune responses. In this study, we investigated the effect of MIF on the expression of TLR4, a receptor that recognizes lipopolysaccharide, in colon using MIF-deficient mice. TLR4 mRNA expression in the colon tissues was determined by northern blot analysis. Western blot analysis and immunohistochemistry in the colon tissues were performed to evaluate the expression of TLR4 protein. The expressions of TLR4 mRNA and protein were remarkably down-regulated in colon tissues of MIF-deficient mice compared with wild-type mice and up-regulated by treatment with recombinant MIF. Immunohistochemical study revealed the presence of TLR4-positive staining in mononuclear cells in the lamina propria and intraepithelial mononuclear cells as well as weak staining in epithelial cells and crypts in colon tissues of wild-type mice. In contrast, MIF-deficient mice did not show TLR4-positive staining in the colonic mucosa. In MIF-deficient mice injected with recombinant mouse MIF (rMIF), TLR4-positive staining cells were observed in colon tissues similar to the findings in wild-type mice. Administration of dextran sulfate sodium (DSS) up-regulated the expression of TLR4 in the colons of WT mice but not in those of MIF-deficient mice. Furthermore, pretreatment with rMIF up-regulated the expression of TLR4 in response to DSS in MIF-deficient mice. Our results suggest that MIF affects the expression of TLR4 in mouse colon under both normal and colitic conditions.

Animals↗
PubMed2005

Randomized study of Helicobacter pylori eradication therapy and proton pump inhibitor monotherapy for idiopathic thrombocytopenic purpura.

Helicobacter pylori (HP) eradication therapy is a useful treatment for idiopathic thrombocytopenic purpura (ITP). Some investigators have also reported the effects of proton pump inhibitor (PPI) monotherapy on ITP. We performed a randomized study of HP eradication therapy and PPI monotherapy on ITP. Four of nine patients achieved complete remission (CR), two of nine achieved partial remission (PR) in HP eradication therapy, three of eight achieved CR, and two of eight achieved PR in PPI monotherapy. No significant differences were observed in the CR + PR of these patients between HP eradication therapy and PPI monotherapy. As for cost comparisons, HP eradication therapy is cheaper than PPI monotherapy, but it is less effective.

2-Pyridinylmethylsulfinylbenzimidazoles↗