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Biomedical subjects

Masahiro Asaka

Publications and source records attributed to Masahiro Asaka.

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

Polaprezinc protects human colon cells from oxidative injury induced by hydrogen peroxide: relevant to cytoprotective heat shock proteins.

AIM: To investigate the effect of polaprezinc on cellular damage induced by hydrogen peroxide (H(2)O(2)) in human colon CaCo2 cells. METHODS: CaCo2 cells were treated with polaprezinc (10-100 micromol/L) for 6 h. After polaprezinc treatment, the cells were incubated with H(2)O(2) (20 micromol/L) for 1 h. Cell viability was measured by MTT assay. Western blot analysis for heat shock protein (HSP) 27 and HSP72 in the cells was performed. Moreover, cells were pretreated with quercetin (200 micromol/L), an inhibitor of HSP synthesis, 2 h before polaprezinc treatment, and cell viability and the expression of HSP27 and 72 were assessed in these cells. RESULTS: Polaprezinc significantly protected CaCo2 cells from cell damage induced by H(2)O(2), and up-regulated the expressions of HSP27 and HSP72 in the cells (10, 30 and 100 micromol/L of polaprezinc; 35.0% +/- 7.7%, 58.3% +/- 14.6% and 64.2% +/- 8.2%, respectively. P < 0.01 versus polaprezinc-nontreated cells; 6.0% +/- 4.4%). Quercetin inhibited the up-regulation of HSP27 and HSP72 by polaprezinc and diminished the protective effect of polaprezinc against H(2)O(2)-caused injury in the cells. CONCLUSION: Polaprezinc is a useful therapeutic agent for treatment of colitis and its effects depend on the function of cytoprotective HSP in colon.

Anti-Ulcer Agents↗
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

High salt diets dose-dependently promote gastric chemical carcinogenesis in Helicobacter pylori-infected Mongolian gerbils associated with a shift in mucin production from glandular to surface mucous cells.

Intake of salt and salty food is known as a risk factor for gastric carcinogenesis. To examine the dose-dependence and the mechanisms underlying enhancing effects, Mongolian gerbils were treated with N-methyl-N-nitrosourea (MNU), Helicobacter pylori and food containing various concentrations of salt, and were sacrificed after 50 weeks. Among gerbils treated with MNU and H. pylori, the incidences of glandular stomach cancers were 15% in the normal diet group and 33%, 36% and 63% in the 2.5%, 5% and 10% NaCl diet groups, showing dose-dependent increase (p < 0.01). Intermittent intragastric injection of saturated NaCl solution, in contrast, did not promote gastric carcinogenesis. In gerbils infected with H. pylori, a high salt diet was associated with elevation of anti-H. pylori antibody titers, serum gastrin levels and inflammatory cell infiltration in a dose-dependent fashion. Ten percent NaCl diet upregulated the amount of surface mucous cell mucin (p < 0.05), suitable for H. pylori colonization, despite no increment of MUC5AC mRNA, while H. pylori infection itself had an opposing effect, stimulating transcription of MUC6 and increasing the amount of gland mucous cell mucin (GMCM). High salt diet, in turn, decreased the amount of GMCM, which acts against H. pylori infection. In conclusion, the present study demonstrated dose-dependent enhancing effects of salt in gastric chemical carcinogenesis in H. pylori-infected Mongolian gerbils associated with alteration of the mucous microenvironment. Reduction of salt intake could thus be one of the most important chemopreventive methods for human gastric carcinogenesis.

Adenocarcinoma↗
PubMed2006

Resistance to experimental colitis depends on cytoprotective heat shock proteins in macrophage migration inhibitory factor null mice.

Macrophage migration inhibitory factor plays an important role in inflammatory diseases. We investigated the role of macrophage migration inhibitory factor (MIF) in the development of dextran sulfate sodium (DSS)-induced colitis using MIF null ((-/-)) mice. MIF(-/-) mice given 3% DSS showed no clinical and histological feature of colitis in contrast to wild-type (WT) mice. Lack of MIF suppressed the up-regulation of TNF-alpha and IFN-gamma as Th1-derived cytokines, and increased the level of IL-4 as Th2-derived cytokine in the colon tissues. Moreover, we found that the expressions of heat shock protein (HSP)40 and HSP70 were markedly up-regulated in the colon of MIF(-/-) mice in response to DSS compared with WT mice. Additionally, quercetin, an inhibitor of HSP synthesis, inhibited the up-regulation of HSP40 and 70 expressions and developed DSS-induced colitis in MIF(-/-) mice. Our findings in this study provide more information in the role of MIF in colitis.

Animals↗
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

Multiple myeloma associated with sialyl salivary-type amylase.

BACKGROUND: There have been several reports describing a notable hyperamylasaemia in patients with multiple myeloma. Such amylase-producing myelomas have been mainly described in the context of concomitant salivary-type hyperamylasaemia, with sialyl salivary-type amylase identified in a portion of those cases. We investigated the incidence of the production of sialyl salivary-type amylase in serum of multiple myeloma patients. METHODS: Eleven patients (6 male and 5 female) who had been diagnosed as having multiple myeloma were enrolled in this study. Sialyl salivary-type amylase was detected by isoamylase electrophoresis and HPLC analysis, and identified by detecting either abnormal neuraminidase-sensitive band through isoamylase electrophoresis or abnormal extra-elution peak of amylase by means of HPLC analysis. RESULTS: Sialyl salivary-type amylase was detected in 7 out of 11 (63.6%) patients. Median total amylase activity was 154 U/l (range 109-43020). Isoamylase electrophoretic patterns of patients' serum were normal in 5 patients (71.4%) out of 7 patients and salivary-dominant in 2 (50.0%) out of 4 patients. CONCLUSIONS: We consider that there is no significant relationship between total serum amylase level and amylase isoenzyme pattern in the incidence of production of sialyl salivary-type amylase with multiple myeloma.

Aged↗
PubMed2006

Modulation of acute graft-versus-host disease and chimerism after adoptive transfer of in vitro-expanded invariant Valpha14 natural killer T cells.

Mouse natural killer T cells with an invariant Valpha14-Jalpha18 TCR rearrangement (Valpha14i NKT cells) are able to regulate immune responses through rapid and large amounts of Th1 and Th2 cytokine production. It has been reported that in vivo administration of the Valpha14i NKT cell ligand, alpha-galactosylceramide (alpha-GalCer) significantly reduced morbidity and mortality of acute graft-versus-host disease (GVHD) in mice. In this study, we examined whether adoptive transfer of in vitro-expanded Valpha14i NKT cells using alpha-GalCer and IL-2 could modulate acute GVHD in the transplantation of spleen cells of C57BL/6 mice into (B6xDBA/2) F(1) mice. We found that the adoptive transfer of cultured spleen cells with a combination of alpha-GalCer and IL-2, which contained many Valpha14i NKT cells, modulated acute GVHD by exhibiting long-term mixed chimerism and reducing liver damage. Subsequently, the transfer of Valpha14i NKT cells purified from spleen cells cultured with alpha-GalCer and IL-2 also inhibited acute GVHD. This inhibition of acute GVHD by Valpha14i NKT cells was blocked by anti-IL-4 but not by anti-IFN-gamma monoclonal antibody. Therefore, the inhibition was dependent on IL-4 production by Valpha14i NKT cells. Our findings highlight the therapeutic potential of in vitro-expanded Valpha14i NKT cells for the prevention of acute GVHD after allogeneic hematopoietic stem cell transplantation.

Acute Disease↗
PubMed2006

Identification of novel mutations in ACT1 and SLA2 that suppress the actin-cable-overproducing phenotype caused by overexpression of a dominant active form of Bni1p in Saccharomyces cerevisiae.

A formin Bni1p nucleates actin to assemble actin cables, which guide the polarized transport of secretory vesicles in budding yeast. We identified mutations that suppressed both the lethality and the excessive actin cable formation caused by overexpression of a truncated Bni1p (BNI1DeltaN). Two recessive mutations, act1-301 in the actin gene and sla2-82 in a gene involved in cortical actin patch assembly, were identified. The isolation of sla2-82 was unexpected, because cortical actin patches are required for the internalization step of endocytosis. Both act1-301 and sla2-82 exhibited synthetic growth defects with bni1Delta. act1-301, which resulted in an E117K substitution, interacted genetically with mutations in profilin (PFY1) and BUD6, suggesting that Act1-301p was not fully functional in formin-mediated polymerization. sla2-82 also interacted genetically with genes involved in actin cable assembly. Some experiments, however, suggested that the effects of sla2-82 were caused by depletion of actin monomers, because the temperature-sensitive growth phenotype of the bni1Delta sla2-82 mutant was suppressed by increased expression of ACT1. The isolation of suppressors of the BNI1DeltaN phenotype may provide a useful system for identification of actin amino-acid residues that are important for formin-mediated actin polymerization and mutations that affect the availability of actin monomers.

Actins↗
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

Histologic results of EMR for esophageal lesions diagnosed as high-grade intraepithelial squamous neoplasia by endoscopic biopsy.

BACKGROUND: Biopsy specimens obtained from esophageal lesions detected in endoscopic screening with iodine staining have often been diagnosed as high-grade intraepithelial squamous neoplasia (WHO 2000). However, a management strategy for such lesions has not been established. The purpose of this study was to perform EMR for such lesions and to determine the actual tumor stage in patients with complete resection and the outcomes after EMR. PATIENTS: During the study period, 51 patients were found to have esophageal lesions diagnosed as high-grade intraepithelial squamous neoplasia by using endoscopic iodine staining in biopsy specimens. All of the patients underwent EMR, and resected specimens were reviewed microscopically. RESULTS: Histologic examination of totally resected specimens revealed that 12 (23.5%) of the 51 patients had tumor invasion of the lamina propria mucosae and that 4 (7.8%) had tumor invasion of the muscularis mucosae. The remaining 35 patients (68.6%) were confirmed to have high-grade intraepithelial squamous neoplasia. The invasive focus in all of the 16 lesions of invasive squamous-cell carcinoma was surrounded by high-grade intraepithelial squamous neoplasia. After a median of 23 months of follow-up, there were two recurrences, and those patients required second EMR. CONCLUSIONS: Histologic results suggested that high-grade intraepithelial squamous neoplasia of the esophagus has characteristics of carcinoma in the preinvasive stage. EMR should be performed for esophageal lesions diagnosed by endoscopic biopsy as high-grade intraepithelial squamous neoplasia, not only because of its probable malignant potential but also because more than 30% of such lesions are actually invasive carcinoma.

Aged↗
PubMed2006

Endoscopic submucosal dissection for treatment of early stage hypopharyngeal carcinoma.

BACKGROUND: Early detection of hypopharyngeal carcinoma is increasingly possible and patients with such early lesions can be treated with endoscopic resection. OBJECTIVE: To identify the optimal relationship between the mucosal defect of the hypopharynx and malfunction of the hypopharynx after endoscopic resection of early hypopharyngeal carcinoma. DESIGN: Case series. SETTING: Referral center in Japan. PATIENTS: Four patients with early-stage squamous cell carcinoma of the hypopharynx underwent endoscopic submucosal dissection (ESD). By using ESD, an accurate incision line close to the tumor margin could be confirmed while performing treatment. ESD was performed with a small-caliber-tip transparent hood (ST-hood) to open the incision line for better visualization of the submucosa. MAIN OUTCOME MEASUREMENTS: Feasibility of en bloc resection, complications, and recurrence after ESD. RESULTS: No early or late complications due to treatment occurred in the patients. Histological examination of resected specimens revealed that 2 patients had carcinoma in situ and 2 patients had tumor invasion of the subepithelium. There was no local recurrence or distant metastasis in any of the patients during the follow-up period (3-14 months). CONCLUSIONS: We consider that ESD is the optimal method for endoscopic resection not only because it enables an en bloc resected specimen to be obtained but also because it can prevent removal of excess mucosa of the hypopharynx, which is a very narrow and important organ related to swallowing and speech.

Aged↗
PubMed2006

Protective effects of heat shock protein 70 induced by geranylgeranylacetone on oxidative injury in rat intestinal epithelial cells.

OBJECTIVE: Geranylgeranylacetone (GGA), an anti-ulcer agent, has recently been demonstrated to protect a variety of cells and tissues via induction of heat shock protein (HSP)70 against numerous stresses. We investigated whether GGA induces HSP70 and protects against an oxidative stressor, monocrolamine (NH(2)Cl), in a rat intestinal epithelial cell line (IEC-18). MATERIAL AND METHODS: IEC-18 cells pretreated with GGA (0.1-10 microM) were subjected to injury induced by NH(2)Cl. Cell viability was assessed, and endogenous HSP70 levels were determined by enzyme-linked immunosorbent assay in IEC-18 cells. RESULTS: Treatment with GGA (0.1-10 microM) was found rapidly to elevate HSP70 levels and to protect against NH(2)Cl-induced injury in IEC-18 cells. Furthermore, quercetin, an inhibitor of HSP70 synthesis, diminished the protective effects of GGA in IEC-18 cells upon NH(2)Cl-caused injury. CONCLUSIONS: The results of this study suggest that GGA plays an important role in defense mechanisms against oxidative injury in the intestine, primarily via induction of HSP70.

Animals↗