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Biomedical subjects

M Masuda

Publications and source records attributed to M Masuda.

At least 19 recordsLinked to original sources
PubMed2006

FLT3 is fused to ETV6 in a myeloproliferative disorder with hypereosinophilia and a t(12;13)(p13;q12) translocation.

The FMS-like tyrosine kinase 3 (FLT3) gene, belonging to the receptor tyrosine kinase (TK) subclass III family, plays an important role in normal hematopoiesis and is one of the most frequently mutated genes in hematologic malignancies as well as an attractive target for directed inhibition. Activating mutations of this gene, including internal tandem duplication in the juxtamembrane (JM) domain and point mutations in the TK domain, are found in approximately one-third of patients with acute myeloid leukemia and in a smaller subset of patients with acute lymphoblastic leukemia. We report here that FLT3 may contribute to leukemogenesis in a patient with myeloproliferative disorder and a t(12;13)(p13;q12) translocation through generating a fusion gene with the ETS variant gene 6 (ETV6) gene. ETV6 has been reported to fuse to various partner genes, including TK and transcription factors. Both ETV6/FLT3 and reciprocal FLT3/ETV6 transcripts were detected in the patient mRNA by reverse transcriptase-polymerase chain reaction. At the protein level, however, only ETV6/FLT3 products were expressed. Among them, one retains the helix-loop-helix (HLH) oligomerization domain of ETV6 and the JM as well as TK domain of FLT3. FLT3 receptor in leukemic cells might be inappropriately activated through dimerization by HLH domain of ETV6, which consequently interfered with proliferation and differentiation of hematopoietic cells.

Aged↗
PubMed2006

Cell adhesion and prostate tumor-suppressor activity of TSLL2/IGSF4C, an immunoglobulin superfamily molecule homologous to TSLC1/IGSF4.

The TSLL2/IGSF4C encodes an immunoglobulin (Ig) superfamily molecule showing significant homology with a lung tumor suppressor, TSLC1. The TSLL2 protein of 55 kDa is mainly expressed in the kidney, bladder, and prostate in addition to the brain. Here, we report the biological significance of TSLL2 in the urinary tissues. An immunohistochemical study reveals that TSLL2 is expressed at the cell-cell attachment sites in the renal tubules, the transitional epithelia of the bladder, and the glandular epithelia of the prostate. Confocal microscopy analysis demonstrates that TSLL2 is localized in the lateral membranes in polarized Mardin-Darby canine kidney (MDCK) cells. TSLL2 forms homo-dimers and its overexpression induces aggregation of suspended MDCK cells in a Ca2+/Mg2+-independent manner, suggesting that it is involved in cell adhesion through homophilic trans-interaction. The TSLL2 gene is mapped on the chromosomal region 19q13.2, whose loss of heterozygosity has been frequently reported in prostate cancer. TSLL2 protein is lost in nine of nine primary prostate cancers and in a prostate cancer cell, PPC-1. Introduction of TSLL2 into PPC-1 strongly suppresses subcutaneous tumor formation in nude mice. These results suggest that TSLL2 is a new member of the Ig superfamily cell adhesion molecules and is a tumor-suppressor candidate in prostate cancer.

Animals↗
PubMed2006

CYP2D-related metabolism in animals of the Canoidea superfamily - species differences.

CYP2D-related drug metabolism in liver microsomes from animals of the Canoidea super family, i.e. mink (Mustela vison), bears (Ursus arctos), foxes (Vulpes vulpes) and dogs, were investigated. Propranolol, bunitrolol and imipramine, which are typically substrates of CYP2D subfamilies, were used in the experiment. All the animals of the Canoidea superfamily that were tested lacked the ability to catalyse 7-hydroxylation of propranolol, which is one of the major metabolic pathways in rats. Stereoselectivity of propranolol metabolism was towards (S)-propranolol in all the reactions of the animals tested with the exception of mink, which showed a selective tendency towards (R)-propranolol in N-dealkylation. As far as metabolic patterns of (R)- and (S)-propranolol are concerned, bears, foxes and dogs are alike, but minks are somewhat different. Liver microsomes from mink showed, among the animals of the Canoidea superfamily, the lowest propranolol hydroxylase activity at 4- and 5-positions and imipramine 2-hydroxylation and {N-}demethylation activities. We could not detect bunitrolol 4-hydroxylation in mink liver microsomes at the low substrate concentration used. We conclude that mink have the lowest activity of CYP2D-related xenobiotic metabolism among the Canoidea superfamily.

Adrenergic Uptake Inhibitors↗
PubMed2006

[Nephrotic syndrome after extended thymectomy for thymoma with myasthenia gravis; report of a case].

A 35-year-old man visited our hospital complaining of blepharoptosis and fatigability of the left arm. Under a diagnosis of myasthenia gravis (Osserman Ila), ambenonium was administered and improvements were noted. At 40-year-old, the patient underwent extended thymectomy due to the development of thymoma, which invaded the lung and pericardium (Masaoka stage Ill). Then ADOC therapy (doxorubicin hydrochloride+cisplatin+vincristine sulfate+cyclophosphamide) was initiated. At 47-year-old, we found recurrence of disseminated thymoma in thoracic cavity. Because of multiple metastatic lesions, radiotherapy in combination with chemotherapy was chosen and these lesions were reduced in size. Facial and foot edema developed at 50-year-old. Chest X-ray revealed bilateral pleural effusion. He was diagnosed as minimal change nephrotic syndrome and steroid therapy was started. The changes in cellular immunity due to thymoma is considered to be causative in the development of nephrotic syndrome. We report the clinical course of our case and discuss with reference to the literature.

Adult↗
PubMed2005

Campylobacter gene polymorphism as a determinant of clinical features of Guillain-Barré syndrome.

BACKGROUND: Ganglioside epitopes on Campylobacter jejuni are hypothesized as the key to the development and characterization of Guillain-Barré syndrome (GBS), but a comprehensive theory has yet to be established. A C jejuni gene, cst-II, involved in the biosynthesis of ganglioside-like lipo-oligosaccharide, shows a polymorphism (Asn/Thr51) that affects ganglioside epitopes. OBJECTIVE: To examine the hypothesis that this polymorphism determines autoantibody reactivity, and thereby neurologic presentations in GBS. METHODS: C jejuni isolates were collected from 105 GBS (including its variants) and 65 uncomplicated enteritis patients. The authors examined the frequency of cst-II and polymorphism (Asn/Thr51) in connection with the bacterial ganglioside epitopes, autoantibody reactivities against GM1, GD1a, and GQ1b, and patients' neurologic findings. RESULTS: Neuropathic strains more frequently had cst-II, in particular cst-II (Thr51), than did enteritic ones (85% vs 52%; p < 0.001). Strains with cst-II (Asn51) regularly expressed the GQ1b epitope (83%), whereas those with cst-II (Thr51) had the GM1 (92%) and GD1a (91%) epitopes. The presence of these bacterial epitopes in neuropathy patients corresponded to autoantibody reactivity. Patients infected with C jejuni (Asn51) more often were positive for anti-GQ1b IgG (56% vs 8%; p < 0.001) and had ophthalmoparesis (64% vs 13%; p < 0.001) and ataxia (42% vs 11%; p = 0.001). Patients who had C jejuni (Thr51) more frequently were positive for anti-GM1 (88% vs 35%; p < 0.001) and anti-GD1a IgG (52% vs 24%; p = 0.006) and had limb weakness (98% vs 71%; p < 0.001). CONCLUSIONS: The genetic polymorphism of C jejuni determines autoantibody reactivity as well as the clinical presentation of Guillain-Barré syndrome (GBS), possibly through modification of the host-mimicking molecule. The GBS paradigm is the first to explain the detailed pathogenesis of a postinfectious, autoimmune-mediated, molecular mimicry-triggering disorder.

Autoantibodies↗
PubMed2005

Allogeneic hematopoietic stem cell transplantation provides sustained long-term survival for patients with adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a distinct peripheral T-cell neoplasm that is highly resistant to chemotherapy. Several groups, including ours, have reported encouraging results of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with ATLL. To confirm our previous report and to establish the basis for a phase II clinical study, we analyzed 40 allo-HSCT for acute and lymphoma types of ATLL in seven institutions in Japan between 1997 and 2002. All evaluable cases entered complete remission (CR) after allo-HSCT and the median survival time was 9.6 months for all patients. The estimated 3-year overall and relapse-free survival, and disease relapse were 45.3, 33.8 and 39.3%, respectively. Among 10 cases with ATLL relapse, five cases achieved CR again: three by the reduction or cessation of immunosuppressive agents, which suggested a graft-versus-ATLL (GvATLL) effect. However, univariate or multivariate analysis did not show any benefit of graft-versus-host disease (GVHD) on the prevention of relapse. These results suggested that allo-HSCT was effective for some patients with aggressive ATLL, and that the GvATLL effect could be achieved even without GVHD. A new phase II trial to test the efficacy of allo-HSCT for ATLL is warranted.

Adult↗
PubMed2005

Sensitivity of adult T-cell leukaemia lymphoma cells to tumour necrosis factor-related apoptosis-inducing ligand.

Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in many transformed cells, but not in normal cells, and hence TRAIL has recently emerged as a novel anti-cancer agent. Adult T-cell leukaemia lymphoma (ATLL) is a neoplasm of T-lymphocyte origin aetiologically associated with human T-lymphotropic virus type 1 (HTLV-I), and is resistant to standard anti-cancer therapy. We thus characterized the sensitivity of ATLL cells to TRAIL in this study. Although most primary ATLL cells and cell lines expressed TRAIL death receptors on their surface, they showed only restricted sensitivity to TRAIL. Among the 10 ATLL cell lines examined, one was sensitive, but two had insufficient death-receptor expression, two had an unknown resistant mechanism with abrogation of the death signal upstream of caspase-8, and the remaining five showed attenuation of the signal in both extrinsic and intrinsic pathways by X-linked inhibitor of apoptosis and Bcl-2/Bcl-xL respectively. Furthermore, the level of HTLV-I tax expression was significantly correlated to TRAIL resistance. Interestingly, ATLL cells themselves expressed TRAIL on the cell surface. Constitutive production of TRAIL may offer resistance, thus allowing the development of TRAIL-resistant ATLL cells. Consequently, the resistant mechanism in ATLL cells against TRAIL was assigned to multiple factors and was not explained by a definitive single agent.

Antineoplastic Agents↗
PubMed2005

Effect of the adenovirus E1A gene on nitric oxide production in alveolar epithelial cells.

This study determined the effect of the adenovirus E1A gene on nitric oxide (NO) production in alveolar epithelial (A549) cells. E1A-positive A549 cells (E1A transfectants), E1A-negative A549 cells (control transfectants) and untransfected A549 cells were placed in 96-well tissue culture plates. After stimulation with lipopolysaccharide (LPS) or cytokine mixture (CM), the biochemical reaction products of NO (nitrite and nitrate) in the culture medium were measured by chemiluminescence. The inducible (iNOS) and the endothelial (eNOS) isoforms of nitric oxide synthase (NOS) protein expression were examined by Western blotting. iNOS mRNA expression was examined by Northern blotting and RT-PCR. CM-induced NO production by E1A-positive A549 cells was significantly lower than that of E1A-negative cells (p < 0.0001). LPS stimulation failed to enhance NO production in both cell types. CM induced iNOS protein expression in E1A-negative A549 cells, but not in E1A-positive cells. eNOS protein expression was constitutive and was not affected by CM stimulation, LPS stimulation or E1A. CM induced iNOS mRNA expression in E1A-negative A549 cells, but not in E1A-positive cells. In conclusion, the adenovirus E1A gene suppressed NO production through transcriptional control of the iNOS gene in A549 cells. This inhibition of NO production may enable the virus to persist in human tissue, since NO is an antiviral effector of the innate immune system.

Adenovirus E1A Proteins↗
PubMed2005

Experiments of high-amplitude and shock-free oscillations of air column in a tube with array of Helmholtz resonators.

This experimental study is made to verify the weakly nonlinear theory for high-amplitude and shock-free oscillations of an air column developed in the previous paper [Sugimoto et al., J. Acoust. Soc. Am., 114, 1772-1784 (2003)]. The experiments use a new tube and resonators designed so as to not only avoid higher harmonic resonances and evanescences but also reduce the values of the coefficient of Q in the amplitude equation, and a rubber diaphragm sandwiched by circular plates to drive the air column. The steady-state pressure field in the tube and in the cavities of the resonators is measured, from which Fourier coefficients are obtained. In spite of nonlinearity, higher harmonics are suppressed significantly as designed, and the frequency response measured shows quantitatively good agreement with the one predicted up to about 170 dB (SPL). The first harmonics and the nonoscillatory component in the pressure field are well predicted, though the second harmonics show a quantitative discrepancy with the theory. In view of the good agreement of the frequency response, it is concluded that the theory is valid and useful enough to provide guidelines in designing the tube with the array of resonators.

Journal Article↗
PubMed2005

Increased serum concentrations of tissue inhibitor of metalloproteinase-1 in COPD patients.

Matrix metalloproteinase (MMP)-9 and tissue inhibitors of metalloproteinase (TIMP)-1 concentrations are increased in the sputum of asthma and chronic bronchitis patients, and are thought to be related to airflow obstruction. However, serum concentrations of these enzymes have not been clearly evaluated in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to examine the serum concentrations of these enzymes in COPD and asthmatic patients in order to determine their relationship with airway obstruction. Serum samples were obtained from 72 patients with COPD: 66 control subjects and 26 patients with asthma. Smoking histories of control subjects were matched with those of COPD patients. Serum concentrations of TIMP-1 and MMP-9 were determined by ELISA. The circulating TIMP-1 concentration was significantly higher in stable COPD patients than in control and asthmatic subjects, and was significantly negatively correlated with forced expiratory volume in one second/forced vital capacity in COPD patients. The molar ratio between MMP-9 and TIMP-1 was significantly lower in COPD patients than in control subjects. In patients with COPD, the serum TIMP-1 concentration was significantly increased during disease exacerbation. In conclusion, the current findings suggest that serum tissue inhibitors of metalloproteinase-1 concentration can be used as a serum marker of airway obstruction and exacerbation in chronic obstructive pulmonary disease patients.

Adrenal Cortex Hormones↗
PubMed2005

[Renal cell carcinoma extending into the right atrium; report of a case].

A 62-year-old male was diagnosed through abdominal ultrasonography, with right renal cell carcinoma extending into the inferior vena cava. Surgery was performed because echocardiography revealed the tumor to have reached the right atrium. The portion of the tumor situated in the right atrium was resected under the extracorporeal circulation. Distal part of inferior vena cava was resected with the tumor included. The tumor remaining in the confluence of hepatic veins was removed from the incised end of the inferior vena cava and was detached from the venous wall. Postoperative abdominal echography revealed a small additional tumor mass in hepatic veins. Although this mass was considered to be a remnant of the intravenous tumor, an additional surgical procedure was judged to be impossible. In retrospect, an additional long-axis incision on the inferior vena cava might have enabled us to catch the remnant of the tumor thrombus in the hepatic vein.

Carcinoma, Renal Cell↗
PubMed2004

A nationwide survey of deep fungal infections and fungal prophylaxis after hematopoietic stem cell transplantation in Japan.

We conducted a nationwide survey to define incidence of deep fungal infections and fungal prophylaxis practices after HSCT. In all, 63 institutions responded. Total number of in-patient transplantations was 935: 367 autologous, 414 allogeneic myeloablative, and 154 allogeneic reduced-intensity (RIST) (n=154). Number of patients who were cared for in a clean room at transplant was 261 (71%) in autologous, 409 (99%) in conventional and 93 (66%) in RIST, respectively. All patients received prophylactic antifungal agents; 89% fluconazole. Number of patients who received the dosage recommended in the CDC guidelines (400 mg/day) was 135 (42%) in conventional transplant and 34 (30%) in RIST (P=0.037). Number of patients who received fluconazole until engraftment and beyond day 75 in conventional transplant vs RIST was, respectively, 324 (100%) vs 109 (97%), and 39 (12%) vs 18 (16%), with no significant difference between the two groups. A total of 37 patients (4.0%) were diagnosed with deep fungal infections; autologous transplantation (0.03%), conventional transplantation (6.0%) and RIST (7.1%). Wide variations in antifungal prophylaxis practice according to the type of transplant and the institutions, and deep fungal infection remain significant problems in RIST.

Antifungal Agents↗
PubMed2004

Effects of p27Kip1 on cell cycle status and viability in A549 lung adenocarcinoma cells.

p27Kip1 is a cyclin-dependent kinase inhibitor, it negatively regulates G1 progression and is reported to modulate apoptosis. Phosphorylation of this protein is thought to regulate its intracellular localisation and affect its stability. The aim of this study was to regulate p27Kip1 expression levels, and to examine how this protein affects cell cycle status and modulates viability in A549 lung adenocarcinoma cells. In addition, the association between phosphorylation status of p27Kip1 and its intracellular localisation was investigated, using expression vectors with cDNA of p27Kip1 or mutants in which the phosphorylation sites had been mutated. Although overexpression of p27Kip1 reduced cell cycle progression, its removal did not change cell cycle status. Modest induction of p27Kip1 rescued adenovector-induced apoptosis and its removal with short interfering RNA increased spontaneous cell death. It was also observed that p27Kip1 localised mainly in the cytoplasm, and forced expression of p27Kip1 cDNA with the substitution of serine (S) 10, threonine (T) 157 and T198 to glutamate (phosphor-mimetic) induced its cytoplasmic localisation. In conclusion, p27Kip1, when expressed physiologically, exists mainly in the cytoplasm, has little effect on cell cycle status and contributes viability in A549 lung adenocarcinoma cells. It was also surmised that intracellular localisation of p27Kip1 dominates its function and that its localisation was partly determined by its phosphorylation.

Adenocarcinoma↗
PubMed2003

Functional posterior rhizotomy for severely disabled children with mixed type cerebral palsy.

The authors evaluated the impact of functional posterior rhizotomy (FPR) for children with severely disabled mixed type cerebral palsy (CP). Three quadriplegic children at the age of 3, 4, and 10 years underwent FPR. They were classified as mixed type CP based on the clinical presentation of marked spasticity with dystonic posture. Preoperative Ashworth score of the lower extremity was 3.5, 4.5, 4.8 respectively. Two children showed prominent opisthotonus and all showed severe subluxation of the hip joint. Advanced scoliosis was associated in two children. FPR was performed from L2 to S1 in one child, L2 to S2 in one and L2 to S1/S2 in one based on the result of pudendal mapping. Rootlet cutting rate ranged from 66 to 75%. Postoperatively, Ashworth score dropped to 1.4, 1.2, 1.3, respectively. Functional improvement of the upper extremity and urination were confirmed in two children. Hip subluxation was reduced in one child and remained stable in two. A one-year follow-up review confirmed no relapse of spasticity among them. FPR achieved highly satisfactory surgical effects in children with severe mixed type CP. Although long-term follow-up is mandatory since there was a report of relapsed spasticity after FPR in this particular population of CP, FPR could be a choice of surgery in severely disabled children with mixed type CP.

Cerebral Palsy↗
PubMed2003

Measurement of soluble Fcgamma receptor type IIIa derived from macrophages in plasma: increase in patients with rheumatoid arthritis.

FcgammaRIII (CD16) is found in two alternative forms, a transmembrane FcgammaRIIIa expressed on NK cells and macrophages, and a glycosylphosphatidylinositol-linked FcgammaRIIIb present on neutrophils. Previously, we measured soluble FcgammaRIIIa (sFcgammaRIIIa) in plasma of NA(1 +, 2-) phenotyped donors with the anti-FcgammaRIII monoclonal antibody (MoAb) GRM1, which recognizes NA2-FcgammaRIIIb and FcgammaRIIIa. The level of sFcgammaRIIIa, as well as the total sFcgammaRIII (sFcgammaRIIIa plus sFcgammaRIIIb) in patients with rheumatoid arthritis (RA) was significantly higher than that in healthy controls. In this study, we measured sFcgammaRIIIa(M)(phi) in plasma with a newly developed anti-FcgammaRIII MoAb, MKGR14 (mIgM), which recognizes FcgammaRIIIa(M)(phi) specifically. From the recovery of purified sFcgammaRIIIa(M)(phi), the amount of sFcgammaRIIIa(M)(phi) present was about half that of sFcgammaRIIIa(NK), and that of sFcgammaRIIIa was about 50 times lower than that of sFcgammaRIIIb in pooled plasma from healthy NA(1 +, 2-) phenotyped donors. The level of sFcgammaRIIIa(M)(phi) in RA patients was about four times higher than that in healthy controls. In RA patients, both the sFcgammaRIIIa(M)(phi) and sFcgammaRIIIa levels were increased as proportionally as the Lansbury Index. The sFcgammaRIIIa, but not sFcgammaRIIIa(M)(phi) levels, were increased directly proportional to C-reactive protein. sFcgammaRIIIa(M)(phi) may be a novel marker of disease activity in RA.

Adult↗
PubMed2003

Frequency response of nonlinear oscillations of air column in a tube with an array of Helmholtz resonators.

Nonlinear cubic theory is developed to obtain a frequency response of shock-free, forced oscillations of an air column in a closed tube with an array of Helmholtz resonators connected axially. The column is assumed to be driven by a plane piston sinusoidally at a frequency close or equal to the lowest resonance frequency with its maximum displacement fixed. By applying the method of multiple scales, the equation for temporal modulation of a complex pressure amplitude of the lowest mode is derived in a case that a typical acoustic Mach number is comparable with the one-third power of the piston Mach number, while the relative detuning of a frequency is comparable with the quadratic order of the acoustic Mach number. The steady-state solution gives the asymmetric frequency response curve with bending (skew) due to nonlinear frequency upshift in addition to the linear downshift. Validity of the theory is checked against the frequency response obtained experimentally. For high amplitude of oscillations, an effect of jet loss at the throat of the resonator is taken into account, which introduces the quadratic loss to suppress the peak amplitude. It is revealed that as far as the present check is concerned, the weakly nonlinear theory can give quantitatively adequate description up to the pressure amplitude of about 3% to the equilibrium pressure.

Journal Article↗
PubMed2003

[Is the quality of off-pump coronary artery bypass grafting equivalent to that of conventional coronary artery bypass grafting].

We analyzed 44 patients undergoing coronary artery bypass grafting (CABG) from November 2001 to March 2003. Of 44 patients, 40 patients (29 men and 11 women; mean age 68.1 +/- 9.2 years) underwent off-pump CABG (OPCAB) [90.9%]. The mean number of bypass grafts was 2.53 +/- 0.78. In-hospital mortality was none and major complications except for one case of reexploration for bleeding were not seen. The early patency rate of over-all grafts was 94.6%. The quality of OPCAB was considered to be equivalent to conventional CABG.

Aged↗