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Masahiro Fujii

Publications and source records attributed to Masahiro Fujii.

36 records · Page 2Linked to original sources
PubMed2004

PDZ domain-binding motif of human T-cell leukemia virus type 1 Tax oncoprotein augments the transforming activity in a rat fibroblast cell line.

While human T-cell leukemia virus type 1 (HTLV-1) is associated with the development of adult T-cell leukemia (ATL), HTLV-2 has not been reported to be associated with such malignant leukemias. HTLV-1 Tax1 oncoprotein transforms a rat fibroblast cell line (Rat-1) to form multiple large colonies in soft agar, and this activity is much greater than that of HTLV-2 Tax2. We have demonstrated here that the increased number of transformed colonies induced by Tax1 relative to Tax2 was mediated by a PDZ domain-binding motif (PBM) in Tax1, which is absent in Tax2. Tax1 PBM mediated the interaction of Tax1 with the discs large (Dlg) tumor suppressor containing PDZ domains, and the interaction correlated well with the transforming activities of Tax1 and the mutants. Through this interaction, Tax1 altered the subcellular localization of Dlg from the detergent-soluble to the detergent-insoluble fraction in a fibroblast cell line as well as in HTLV-1-infected T-cell lines. These results suggest that the interaction of Tax1 with PDZ domain protein(s) is critically involved in the transforming activity of Tax1, the activity of which may be a crucial factor in malignant transformation of HTLV-1-infected cells in vivo.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Atrial septal defect with borderline pulmonary vascular disease: surgery and long-term oral prostacyclin therapy for recalcitrant pulmonary hypertension.

The hemodynamic determination of operability in atrial septal defect (ASD) with severe pulmonary hypertension is problematic. Therefore, we perform an open lung biopsy prior to the corrective surgery in cases with pulmonary vascular resistance greater than 8 units x m2 and/or pulmonary arterial peak pressure greater than 70 mmHg. We present 4 cases showing occlusion of more than 70% of the small pulmonary arteries and arterioles by musculoelastosis, thromboembolism and mixed-type (musculoelastosis and plexogenic arteriopathy) which was considered borderline in terms of operability. After complete closure of the ASD and postoperative long-term oral prostacyclin (PGI2) therapy, pulmonary artery peak pressure decreased from 110-72 (mean 84) to 105-45 (mean 74) mmHg immediately after operation and 65-40 (mean 57) mmHg after PGI2 therapy. The New York Heart Association functional status of the patients improved from class II-III to class I with oral PGI2 only. Our cases demonstrate that despite more than 70% occlusion of the small pulmonary arteries and arterioles, surgery and long-term PGI2 therapy can reduce pulmonary artery pressure and improve the quality of life.

Adolescent↗
PubMed2004

Experimental studies on myocardial protection with intermittent cross-clamp fibrillation: additive effect of the sodium-hydrogen exchanger inhibitor, cariporide.

BACKGROUND: We previously showed that intermittent cross clamping with fibrillation affords myocardial protection equivalent to cardioplegic arrest. In this study, we examined whether cariporide (Aventis Pharma, Frankfurt, Germany), a specific sodium-hydrogen exchanger inhibitor, enhanced the protective effect of intermittent cross-clamp fibrillation (ICCF). METHODS: Isolated rat hearts were Langendorff-perfused (20 mins) with bicarbonate buffer and function (left ventricular developed pressure) measured. In each of three separate protocols that incorporated progressively longer ischemic durations, hearts were randomly allocated to one of three groups: group 1 was the control group with 40, 60, or 80 minutes of continuous global ischemia. Group 2 was the ICCF group with 4, 6, or 8 cycles of 10 minutes ICCF and 10 minutes of reperfusion in sinus rhythm. Group 3 was the ICCF plus cariporide group, which was the same as group 2, but also with 3 micromoles/L cariporide present in perfusate from 10 minutes before the ICCF cycles. Hearts were reperfused for 60 minutes with drug-free buffer and recovery (percentage of initial function) was measured. Hearts were maintained at 37 degrees C throughout the protocols. In protocol 3 (80 minutes ischemia per 8 cycles of ICCF), creatine kinase leakage (myocardial injury) and triphenyl tetrazolium chloride staining (myocardial viability) were also measured. Protocols 1, 2, and 3 had n = 8 hearts, n = 6 hearts, and n = 6 hearts in each group, respectively. RESULTS: In the three protocols, the recoveries of left ventricular developed pressure in the control group, the ICCF group, and the ICCF plus cariporide group, respectively, for protocol 1 were: 26% +/- 3%, 70% +/- 2% (p < 0.05 vs the control group) and 74% +/- 2% (p < 0.05 vs the control group), respectively. For protocol 2 these were: 16% +/- 2%, 55% +/- 1% (p < 0.05 vs the control group), and 70% +/- 3% (p < 0.05 vs the control and ICCF groups), respectively. For protocol 3 these were: 8% +/- 2%, 41% +/- 3% (p < 0.05 vs the control group), and 63% +/- 2% (p < 0.05 vs the control and ICCF groups), respectively. Recovery of left ventricular end-diastolic pressure mirrored that of left ventricular developed pressure in all protocols. In protocol 3, total creatine kinase leakage (international units per gram wet weight) was 88 +/- 12, 47 +/- 4 (p < 0.05 vs the control group), and 17 +/- 1 (p < 0.05 vs the control and ICCF groups), respectively, and triphenyl tetrazolium chloride staining (arbitrary units per gram wet weight) was 0.17 +/- 0.04 in the control group, 0.39 +/- 0.04 (p < 0.05 vs the control group) in the ICCF group, and 0.47 +/- 0.08 (p < 0.05 vs the control group) in the ICCF plus cariporide group, respectively. CONCLUSIONS: Sodium-hydrogen exchanger inhibition with cariporide enhances the myocardial protection afforded by ICCF, with the additive benefit becoming more apparent with increasing severity of the ischemic insult. Sodium-hydrogen exchanger inhibition may provide a significant protective reserve during ICCF, particularly when longer procedures are required.

Animals↗
PubMed2004

Visualization of a functional KSHV episome-maintenance protein LANA in living cells.

The latency-associated nuclear antigen (LANA) of Kaposi's saroma-associated herpesvirus (KSHV) can maintain a plasmid containing the KSHV origin of DNA replication (oriP) as episomes in dividing human cells. Hence, LANA is considered to play crucial roles in persistent KSHV infection in human cells. In this study, we characterized a LANA fusion protein of green fluorescent protein (GFP-LANA). Like the wild-type LANA, GFP-LANA interacted tightly with mitotic chromosomes, and maintained the plasmid selectively with the KSHV oriP for more than three weeks in a human B cell line. Moreover, equivalent amount of GFP-LANA protein was segregated into two daughter cells in living metaphase cells. Our results suggested that the activity of LANA serves the segregation of equivalent amounts of viral genomes tethered with LANA into two daughter progeny cells during cell division. Thus, GFP-LANA is a useful tool for the analyses of the functions and dynamics of LANA in living cells.

Antigens, Viral↗
PubMed2004

Measurement of end-tidal carbon dioxide in patients with cardiogenic shock treated using a percutaneous cardiopulmonary assist system.

We have reported that percutaneous cardiopulmonary assist systems (PCPS) are effective in treating life-threatening cardiogenic shock that is intractable to treatment with intraaortic balloon pumping (IABP). However, there are few clinical indices that can be used to evaluate the effectiveness of PCPS. End-tidal carbon dioxide (ET-CO(2)) content reflects pulmonary blood flow. We monitored ET-CO(2) continuously and determined whether we could use it as a new index to evaluate the effectiveness of PCPS. Seventeen patients with cardiogenic shock were intubated and evaluated by ET-CO(2) monitoring during PCPS. The etiology of shock included acute myocardial infarction (n=10), acute myocarditis (n=2), recent coronary artery bypass graft (n=1), cardiac rupture (n=1), hypertrophic obstructive cardiomyopathy complicated by ventricular fibrillation (n=1), left atrial myxoma (n=1) and artificial valve malfunction (n=1). PCPS was extremely effective in 10 of 17 patients (58.8%), and they recovered from the cardiogenic shock. The remaining 7 patients did not recover from shock, and died during PCPS. Six of ten patients who recovered from shock were successfully weaned from PCPS and 4 patients had good long-term survival. In the cases where PCPS was effective, the ET-CO(2) measured soon after the beginning of PCPS was significantly higher than in the cases in which PCPS was ineffective. Furthermore, the ET-CO(2) content increased gradually with the improvement in hemodynamics. In contrast, ET-CO(2) content remained low if PCPS was not effective. The ET-CO(2) represents a useful predictor of survival or death and is also a good index for weaning in patients treated with PCPS.

Adult↗
PubMed2004

Optimal time of surgical treatment for Kawasaki coronary artery disease.

BACKGROUND: The major complication of Kawasaki coronary disease is myocardial infarction caused by thrombus formation inside the aneurysm or by organic obstructive lesion following the regression of aneurysm, while the indications for surgical therapy remain controversial. We have adopted coronary artery bypass grafting (CABG) even in young children for giant coronary aneurysms (more than 8 mm diameter) with or without a stenotic region when myocardial ischemia is detected. We hypothesized that a shorter time-period from diagnosis of acute Kawasaki disease (KD) to CABG would lead to better postoperative results. To elucidate the validity of our strategy, we evaluated preoperative patient characteristics and long-term outcome. METHODS: Twenty-one patients (mean age: 12.0 years old) with Kawasaki coronary disease had undergone CABG during the last 12 years. The mean age at the time of acute KD was 2.7 years and the mean time range from diagnosis of acute KD to CABG was 8.1 years. The incidence of preoperative reduced ventricular function was 10 per 21 patients (47.6%). A multivariate logistic regression analysis using patient characteristics showed that the time range from acute KD to CABG was the only predictor for ventricular functional deterioration (p=0.03, odds ratio 1.55. 95%CI: 1.033 approximately 2.325). Based on these results, we divided the patients into two groups of short time range (mean: 3.7 years; group S) and long time range (mean: 13.9 years; group L). RESULTS: Preoperative left ventricular functional deterioration was recognized more frequently in group L (9/9, 100%) than in group S (1/12, 8.3%)(p<0.01). Myocardial infarction was documented significantly higher in the group L (6/9, 66.7%) than group S (1/12, 8.3%)(p=0.04). There was no surgical mortality in either group. The arterial grafts demonstrated good potential for growth and graft patency was 96.9%. Moreover, seven of the giant aneurysms proximal to the graft anastomosis showed complete thrombotic occlusion after CABG without development of myocardial infarction. The cardiac events free rate of group L and group S was 66.7% and 100%, respectively, during the postoperative follow up periods of 5.5+/-1.1 years (group L) and 4.7+/-1.1 years (group S). CONCLUSIONS: We successfully applied CABG for Kawasaki coronary disease. Based on our experience, a short interval after acute KD appears to be ideal for surgical treatment of Kawasaki coronary disease.

Child↗
PubMed2003

Latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus interacts with human myeloid cell nuclear differentiation antigen induced by interferon alpha.

Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpes virus type 8 (HHV-8) is tightly linked to the development of Kaposi's sarcoma, primary effusion lymphoma (PEL) and some cases of multicentric Castleman's disease. Latency-associated nuclear antigen (LANA) is one of a limited number of KSHV genes consistently expressed in these diseases as well as in KSHV-infected cell lines derived from PEL, and has been shown to play crucial role in persistence of KSHV genomes in the infected cells. In this study, we explored the cellular factors that interact with LANA using yeast two-hybrid screening, and isolated a part of gene encoding human myeloid cell nuclear differentiation antigen (MNDA). MNDA is a hematopoietic interferon-inducible nuclear proteins with a HIN-200 family member with conserved 200-amino acid repeats. Immunoprecipitation assay revealed that LANA interacted with MNDA in a mammalian embryonic kidney cell line. MNDA transcript was undetectable in three PEL cell lines by reverse-transcription polymerase chain reaction, but it was induced by interferon alpha (IFNalpha). Moreover, LANA and MNDA were co-localized in the nuclei of MNDA-expressing PEL cells. Our results suggest that LANA interacts with MNDA in KSHV-infected cells exposed to IFNalpha. Such interaction may modulate IFN-mediated host defense activities.

Antigens, Differentiation, Myelomonocytic↗
PubMed2003

Rapid tumor formation of human T-cell leukemia virus type 1-infected cell lines in novel NOD-SCID/gammac(null) mice: suppression by an inhibitor against NF-kappaB.

We established a novel experimental model for human T-cell leukemia virus type 1 (HTLV-1)-induced tumor using NOD-SCID/gammac(null) (NOG) mice. This model is very useful for investigating the mechanism of tumorigenesis and malignant cell growth of adult T-cell leukemia (ATL)/lymphoma, which still remains unclear. Nine HTLV-1-infected cell lines were inoculated subcutaneously in the postauricular region of NOG mice. As early as 2 to 3 weeks after inoculation, seven cell lines produced a visible tumor while two transformed cell lines failed to do so. Five of seven lines produced a progressively growing large tumor with leukemic infiltration of the cells in various organs that eventually killed the animals. Leukemic cell lines formed soft tumors, whereas some transformed cell lines developed into hemorrhagic hard tumors in NOG mice. One of the leukemic cell lines, ED-40515(-), was unable to produce visible tumors in NOD-SCID mice with a common gamma-chain after 2 weeks. In vivo NF-kappaB DNA binding activity of the ED-40515(-) cell line was higher and the NF-kappaB components were changed compared to cells in vitro. Bay 11-7082, a specific and effective NF-kappaB inhibitor, prevented tumor growth at the sites of the primary region and leukemic infiltration in various organs of NOG mice. This in vivo model of ATL could provide a novel system for use in clarifying the mechanism of growth of HTLV-1-infected cells as well as for the development of new drugs against ATL.

Animals↗
PubMed2003

[HTLV-1, 2].

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Animals↗
PubMed2002

Homotypic cell-cell adhesion induced by human T cell leukemia virus type 1 tax protein in T cell lines.

Cell-cell adhesion is involved in the processes of cell growth, activation and migration, and inflammation. T cells infected with human T cell leukemia virus type 1 (HTLV-1) exhibit a high degree of homotypic cell-cell adhesion in vitro. In this study, we investigated the involvement of the viral protein Tax in such process. Expression of Tax in an interleukin (IL)-2-dependent mouse T cell line (CTLL-2) increased homotypic cell-cell adhesion; however, less cell adhesion was induced by Tax than that observed in HTLV-1-infected T cell lines. Moreover, Tax induced cell-cell adhesion in a human T cell line, in which the expression of Tax is inducible. Microscopic examination also revealed Tax-induced morphologic changes, including rounding of CTLL-2 cells, increased cell volume, and increased nucleus size. Taken together, our results suggest that Tax induces cell-cell adhesion and morphologic changes in HTLV-1-infected cells. Tax may thus play a role in persistent HTLV-1 infection and the pathogenesis of associated disease.

Animals↗
PubMed2002

Bay 11-7082 inhibits transcription factor NF-kappaB and induces apoptosis of HTLV-I-infected T-cell lines and primary adult T-cell leukemia cells.

Human T-cell leukemia virus type I (HTLV-I) is the causative agent of an aggressive form of leukemia designated adult T-cell leukemia (ATL). We have previously demonstrated that all T-cell lines infected with HTLV-I and primary leukemic cells from ATL patients display constitutively high activity of transcription factor NF-kappaB. In this study we showed that Bay 11-7082, an inhibitor of NF-kappaB, induced apoptosis of HTLV-I-infected T-cell lines but only negligible apoptosis of HTLV-I-negative T cells. Bay 11-7082 rapidly and efficiently reduced the DNA binding of NF-kappaB in HTLV-I-infected T-cell lines and down-regulated the expression of the antiapoptotic gene, Bcl-x(L), regulated by NF-kappaB, whereas it had little effect on the DNA binding of another transcription factor, AP-1. Although the viral protein Tax is an activator of NF-kappaB, Bay 11-7082-induced apoptosis of HTLV-I-infected cells was not associated with reduced expression of Tax. Furthermore, Bay 11-7082- induced apoptosis of primary ATL cells was more prominent than that of normal peripheral blood mononuclear cells, and apoptosis of these cells was also associated with down-regulation of NF-kappaB activity. Our results indicate that NF-kappaB plays a crucial role in the pathogenesis and survival of HTLV-I-infected leukemic cells and that it is a suitable target for the prevention and treatment of ATL.

Adult↗
PubMed2002

Activation of cyclin D1 and D2 promoters by human T-cell leukemia virus type I tax protein is associated with IL-2-independent growth of T cells.

Our aim was to examine the involvement of G(1) cell-cycle regulators in cell growth dysregulation induced by HTLV-I. Compared to uninfected cells, higher expression levels of cyclin D1 and D2 mRNA were detected in HTLV-I-infected T-cell lines, which were at least in part mediated by the viral transforming protein Tax since Tax activated both cyclin D1 and D2 promoters in the human T-cell line Jurkat. A Tax mutant that did not activate NF-kappaB failed to activate cyclin D1 and D2 promoters. Inhibitors of NF-kappaB (dominant negative IkappaBs mutants) suppressed Tax-dependent activation of cyclin D1 and D2 promoters, indicating that Tax-induced activation was mediated by NF-kappaB. Wild-type and mutant Tax capable of activating NF-kappaB, but not Tax mutant incapable of activating NF-kappaB, converted cell growth of a T-cell line from being IL-2-dependent to being IL-2-independent; and this conversion was associated with IL-2-independent induction of cyclins D1 and D2. Our data suggest that induction of cyclins D1 and D2 by Tax is involved in IL-2-independent cell-cycle progression as well as IL-2-independent transformation of primary human T cells by HTLV-I. High expression levels of cyclin D1 and D2 mRNAs were also detected in some patients with ATL. Our findings link HTLV-I infection to changes in cellular D-type cyclin gene expression, transformation of T cells and subsequent development of T-cell leukemia.

Animals↗
PubMed2002

Efficacy of intraoperative mapping to optimize the surgical ablation of atrial fibrillation in cardiac surgery.

BACKGROUND: Observation during open heart surgery in patients with chronic atrial fibrillation (AF) showed that the activation sequence of the left atrium was regular and that of the right atrium chaotic in most patients. We speculate that the left atrium plays a role as an important electrical driving chamber for AF and by mapping pre-operatively, optimal sites for the cryoablation can be determined to minimize the extensiveness of the cryolesions. METHODS: Forty patients who underwent cardiac surgery and cryoablation guided by epicardial mapping data to eliminate AF originating from the left atrium were included in this study. RESULTS: Sustained reentrant movement or repetitive firing from foci located in the right atrium was never observed. Foci or reentry circuits located in the left atrium were clearly identified in 11 cases. Nine of the 11 cases resumed sinus rhythm by placing cryolesions at these sites. Two cases needed a pacemaker implantation. The exact site had not been identified in the 29 remaining cases. In these 29 cases a left atrial posterior longitudinal linear cryoablation was placed. Sinus rhythm resumed in 22 cases. Six cases still remained in AF and a pacemaker was implanted in 1 case. Ultimately, in this series of operations sinus rhythm was resumed in 31 of 40 cases; AF remained in 6 of them and pacemaker implantation was required in 3 cases. CONCLUSIONS: Mapping was useful to distinguish the two etiologies of the AF to facilitate optimal placement of the cryolesions. Sustained reentrant movement or repetitive firing from foci located in the right atrium was never observed and the left atrium played an important role as the electrical driving chamber for AF.

Adult↗
PubMed2002

Castleman's disease of the buccal mucosa: report of a case and review of the literature of head and neck cases.

A case of Castleman's disease occurring in the buccal mucosa is described. An 84-year-old woman noticed that a mass in the left buccal mucosa that had been present for half a year. Computed tomography revealed a well-demarcated submucosal tumor, measuring 4.0 x 3.0 x 2.0 cm. The patient received no treatment at this time, and continued growth of the mass was observed. After incisional biopsy, the lesion was surgically removed. Histologically, the tumor consisted of an enlarged lymph node with conspicuous lymph follicles, in which vascular channels and deposits of eosinophilic material were noted. Laboratory examination showed an increase of serum antibody level of cytomegalovirus but of no other viruses. The patient was followed up for 1(1/2) years, with no clinical evidence of recurrence. This is the first report of Castleman's disease presenting in an oral site.

Aged↗
PubMed2002

Chromosome binding site of latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus is essential for persistent episome maintenance and is functionally replaced by histone H1.

Latency-associated nuclear antigen 1 (LANA1) of Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus 8) persistently maintains a plasmid containing the KSHV latent origin of replication (oriP) as a closed circular episome in dividing cells. In this study, we investigated the involvement of chromosome binding activity of LANA1 in persistent episome maintenance. Deletion of the N-terminal 22 amino acids of LANA1 (DeltaN-LANA) inhibited the interaction with mitotic chromosomes in a human cell line, and the mutant concomitantly lost activity for the long-term episome maintenance of a plasmid containing viral oriP in a human B-cell line. However, a chimera of DeltaN-LANA with histone H1, a cellular chromosome component protein, rescued the association with mitotic chromosomes as well as the long-term episome maintenance of the oriP-containing plasmid. Our results suggest that tethering of KSHV episomes to mitotic chromosomes by LANA1 is crucial in mediating the long-term maintenance of viral episomes in dividing cells.

Antigens, Viral↗
PubMed2002

Human T-cell leukemia virus type 2 (HTLV-2) Tax protein transforms a rat fibroblast cell line but less efficiently than HTLV-1 Tax.

Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 are retroviruses with similar biological properties. Whereas HTLV-1 is the causative agent of an aggressive T-cell leukemia, HTLV-2 has been associated with only a few cases of lymphoproliferative disorders. Tax1 and Tax2 are the transcriptional activators of HTLV-1 and HTLV-2, respectively. Here we show that Tax2 transformed a Rat-1 fibroblast cell line to form colonies in soft agar, but the size and number of the colonies were lower than those of Tax1. Use of a chimeric Tax protein showed that the C-terminal amino acids 300 to 353 were responsible for the high transforming activity of Tax1. Activation of cellular genes by Tax1 through transcription factor NF-kappa B is reportedly essential for the transformation of Rat-1 cells. Tax2 also activated the transcription through NF-kappa B in Rat-1 cells, and such activity was equivalent to that induced by Tax1. Thus, the high transforming activity of Tax1 is mediated by mechanisms other than NF-kappa B activation. Our results showed that Tax2 has a lower transforming activity than Tax1 and suggest that the high transforming activity of Tax1 is involved in the leukemogenic property of HTLV-1.

Amino Acid Sequence↗