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Biomedical subjects

M Masuda

Publications and source records attributed to M Masuda.

At least 163 records · Page 9Linked to original sources

[Clinical results of mitral valve surgery in children].

The clinical results of mitral valve surgery in children were evaluated. Fifty children (age ranged between 1 month and 12 years) with mitral valve regurgitation have undergone valve surgery with low operative mortality (2%). Valve plasty using several techniques including annuloplasty have been performed with quite high success rate (92%), while valve replacement was required in four patients who had the prolapse of the anterior mitral leaflet (8%). Reoperation was required in 5 patients (10%), and there were 4 late deaths. Introduction of the reconstructive technique of the chordae tendinae using artificial chordae resulted 100% success rate of mitral repair for the prolapse of the anterior mitral leaflet without death and reoperation. The reoperation free rate and the actuarial survival rate at 15 years of the patients with mitral regurgitation were 70 +/- 12% and 85 +/- 7%, respectively. In ten patients with mitral valve stenosis (age ranged between 1 month and 5 years), 5 patients required valve replacement (50%), and 2 patients died (20%). The clinical results of the surgery for the mitral stenosis were still unsatisfactory, and the reoperation free rate at 2 years was 42 +/- 30% and the actuarial survival rate at 13 years were 32 +/- 18%.

Blood Vessel Prosthesis↗

Disruption of cholecystokinin (CCK)-B receptor gene did not modify bile or pancreatic secretion or pancreatic growth: a study in CCK-B receptor gene knockout mice.

Pancreatic exocrine function and bile secretion were examined in cholecystokinin (CCK)-B receptor gene-targeted mice and compared among different genotypes [i.e., CCK-B receptor gene: (+/+), wild-type; (+/-), heterozygous; and (-/-), homozygous deficient]. The histology and protein concentrations in the pancreas also were examined. Amylase release from the dispersed acini was examined in vitro by using the various doses of CCK-8, carbachol, and secretin. In vivo, the bile and pancreatic juice were collected, and the concentrations of amylase and bile acid were measured in anesthetized mice. The responses to CCK (100 pmol/kg) or acetyl-beta-methylcholine (500 nmol/kg) were examined. In vitro studies showed that the maximal effective concentrations of CCK-8 (10(-l0) M), carbachol (10(-5) M), and secretin (5 x 10(-7) M) were comparable for all genotypes. Fluid, amylase, and bile acid outputs in vivo also were comparable for all genotypes. Pancreatic wet weight and protein concentrations were not significantly different, and no abnormal findings were observed on histologic examination in any genotype. These results indicated that the CCK-B receptor has no role in pancreatic growth, exocrine secretion, or bile secretion in adult mice.

Aging↗

[Efficacy of intravenous administration of atrial natriuretic peptide after cardiac surgery in neonates and infants].

Intravenous infusion of alpha-human atrial natriuretic polypeptide (hANP) and furosemide was performed in 12 patients (4: TGA, 3: univentricular heart, 3: HLHS, 2: VSD) after cardiopulmonary bypass. Their mean age at the operation was 68 days (6 patients in neonate), the mean body weight was 3.3 kg. All patients were treated with nitroglycerin in dose of 2 micrograms/kg/min and chlorpromazine in dose of 2.8 micrograms/kg/min and catecholamine in mean dose of 6.5 micrograms/kg/min. The criteria of indication for hANP was poor effect of furosemide alone. The hANP was given for 6-144 hours in dose of 0.1-0.2 microgram/kg/min. With the hANP and furosemide infusion, urine volume increased from 85.0 +/- 14.2 ml/kg/day to 107.9 +/- 25.3 ml/kg/day (p < 0.05), whereas the systemic arterial pressure, the central venous pressure and the renal function were unchanged. We conclude that the combination of the hANP and the furosemide is very effective in neonates and infants.

Atrial Natriuretic Factor↗

[A multicenter early phase II study of high-dose chemotherapy with autologous peripheral blood stem cell transplantation for treatment of intermediate-grade non-Hodgkin's lymphoma. Japan Blood Cell Transplantation Study Group].

We conducted a multicenter early phase II study to evaluate the feasibility and therapeutic efficacy of high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation (auto-PBSCT) for the treatment of intermediate grade non-Hodgkin's lymphoma (IG-NHL). High-dose etoposide or cyclophosphamide followed by G-CSF was used for PBSC mobilization, and a sufficient number of CD34+ cells (> 1 x 10(6)/kg) were collected. Out of 81 enrolled patients, 50 received high-dose chemotherapy with auto-PBSCT; Hematologic recovery after transplantation was rapid. The incidence of grade III/IV toxicity (Bearman) was about 6%; treatment-related mortality was 6% (3/50). The Disease-free survival rate for the patients in complete remission who received high-dose chemotherapy with auto-PBSCT was better than that for the patients who were treated with conventional chemotherapy (57% vs 35%). These preliminary results indicated that high-dose chemotherapy with auto-PBSCT is feasible and effective. A prospective randomized phase III clinical trial will be required to assess the efficacy of high-dose chemotherapy with auto-PBSCT as a post-remission therapy for IG-NHL.

Adolescent↗

In vitro decidualization activity assay of human endometrial stromal cells.

To address the need for a simple and reliable system for evaluating the effects of bioactive substances on decidualization of endometrial stromal cells, we designed and tested an assay for measuring decidualization activity. With our assay, it is easy to examine the effects of various bioactive substances on endometrial stromal decidualization. For example, as shown in this study, it is now clear that neither RANTES nor gonadotropin releasing hormone agonist has any effect on endometrial stromal decidualization. Our simple assay has also made it possible to evaluate individual stromal decidualization activities and the regulation of decidualization.

Biological Assay↗

Central somatostatin diminished inhibitory action of central CGRP on pancreatic basal secretion in conscious rats.

We examined whether central somatostatin prevents an inhibitory effect of central calcitonin-gene related peptide (CGRP) on pancreatic secretion in conscious male Wistar rats (330-330 g). Rats were prepared with separate cannulas for draining bile and pancreatic juice and with a duodenal cannula and an extrajugular vein cannula. In addition, another cannula was stereotactically implanted into the left lateral cerebral ventricle. Rats were placed in restraint cages and experiments were conducted 4 days after the operation without anesthesia. An injection of CGRP (0.1, 1.0 nmol/10 microl) into the left lateral cerebral ventricle (i.c.v.) inhibited pancreatic secretion dose-dependently. To confirm the inhibitory effect of CGRP (i.c.v.) was mediated via sympathetic nerves, phentolamine was injected intravenously (i.v.) bolus (0.5 mg kg(-1)) 0.5-h before CGRP (i.c.v.), followed by continuous infusion of 0.2 mg kg(-1) h(-1). Phentolamine (i.v.) reversed the inhibition produced by CGRP (i.c.v.). An injection of 4 nmol/10 microl somatostatin (i.c.v.) 5 min prior to CGRP injection diminished the inhibitory effect of CGRP (i.c.v.). It is concluded that centrally administered somatostatin diminished the inhibitory action of CGRP (i.c.v.) on pancreatic secretion, probably via inhibiting autonomic (sympathetic) nerve excitation at the central site.

Animals↗

High alkaline phosphatase activity in 3p-induced human renal cancer cells.

Recent studies have suggested that a tumor suppressor gene is located on the short arm of chromosome 3 (3p) for tumorigenesis of sporadic renal cell carcinoma. In this study, we introduced 3p from normal human fibroblasts into the renal cancer cell line YCR and this introduction clearly resulted in inhibited growth in vitro and in vivo. Furthermore, we investigated several enzyme activities of original YCR cells and 3p-induced clones (YCR-151 and YCR-152) and found that only alkaline phosphatase activity in 3p-induced clones was significantly increased compared to that of the original YCR cells.

Alkaline Phosphatase↗

Expression of functional tissue factor on small vesicles of lipopolysaccharide-stimulated human vascular endothelial cells.

We examined tissue factor expression on lipopolysaccharide-stimulated endothelial cells and their small vesicles by using specific antibodies and flow cytometry. Tissue factor functional activity was also assessed by activation of factor X. Endothelial cells were stimulated with 10 microg/ml of lipopolysaccharide in M-199/bovine serum albumin. Flow cytometry showed that expression of tissue factor on endothelial cells reached a maximum at 6 hours after stimulation, whereas that on small vesicles reached a maximum after 12 hours. Factor X activation mediated by factor VIIa and tissue factor was observed over a similar time course and was inhibited by the addition of antitissue factor antibody. Immunoelectron microscopy suggested that small vesicles with expression of some tissue factor were produced from the surface of endothelial cells. Our findings thus showed that tissue factor on endothelial cells produced by lipopolysaccharide stimulation was partly released to small vesicles. This may cause disseminated intravascular coagulation and related coagulation disorders.

Cells, Cultured↗

Cre-loxP-mediated DNA flip-flop in mammalian cells leading to alternate expression of retrovirally transduced genes.

While DNA excision by Cre-loxP homologous recombination has been exploited for mammalian genetic engineering, it has not been reported whether DNA inversion is achievable by the same mechanism in mammalian cells. To investigate whether Cre-loxP-mediated DNA inversion takes place in mammalian cells, a novel retroviral vector, NT(FF), was constructed. The vector carries a marker gene cassette consisting of the neo and tk genes linked tail-to-tail to each other and flanked by an inverted repeat of loxP sequences. In NT(FF)-transduced Rat2 cells, the marker gene cassette was inverted reversibly in a Cre-dependent manner, leading to DNA "flip-flop" associated with alternate expression of the neo and tk genes. This study provides the first example of Cre-loxP-mediated DNA inversion in mammalian cells facilitating regulation of retrovirally transduced genes, suggesting the usefulness of the system for genetic engineering.

Animals↗

Strain differences in CYP3A-mediated C-8 hydroxylation (1,3,7-trimethyluric acid formation) of caffeine in Wistar and Dark Agouti rats. Rapid metabolism of caffeine in debrisoquine poor metabolizer model rats.

We observed significant strain differences [Dark Agouti (DA) > Wistar] in 1,3,7-trimethyluric acid formation (C-8 hydroxylation) during caffeine metabolism, though not in N-demethylations, in adult male DA and Wistar rats. In contrast, adult female and immature male rats of both DA and Wistar strains did not show significant differences in activity levels of C-8 hydroxylation. Kinetic studies using liver microsomes revealed that adult male DA rats have a larger Vmax for C-8 hydroxylation than do Wistar rats. Troleandomycin (TAO), known as a cytochrome P450 (CYP) 3A inhibitor, and an anti-rat CYP3A2 polyclonal antibody effectively reduced C-8 hydroxylation by rat liver microsomes in a concentration-dependent manner, suggesting that C-8 hydroxylation in rats is mediated largely by an isoform(s) of the CYP3A subfamily. Troleandomycin and the antibody did not inhibit the N-demethylations of caffeine by rat liver microsomes. Treatment of rats with CYP3A inducers caused a marked increase in C-8 hydroxylase activity. These results indicate that the rat CYP3A subfamily is capable of catalyzing C-8 hydroxylation of caffeine as is the case for human CYP3A4. The results of western blotting analysis using anti CYP3A antiserum showed that the staining intensity of the protein band in DA rat liver microsomes was higher than that in Wistar rat liver microsomes. We concluded that marked sex-dependent strain differences in C-8 hydroxylation of caffeine between Wistar and DA rats are due to the differences in the levels of expression of CYP3A in these strains of rats.

Aging↗

Tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 induced by lysophosphatidylcholine in cultured endothelial cells.

Lysophosphatidylcholine (lyso-PC), a biologically active phospholipid, appears to modulate various endothelial cell functions through tyrosine kinase-dependent signaling pathways. In cultured bovine aortic endothelial cells (BAEC), we have found that a 130 kDa protein (p130) was rapidly tyrosine phosphorylated within 2 min and sustained for, at least, 1 hr in response to 10 mumol/L of lyso-PC but not to phorbol myristate acetate (PMA). Prolonged preexposure to PMA did not affect lyso-PC-induced p130 tyrosine phosphorylation, suggesting that mechanisms independent of protein kinase C may be involved. Fractionation of the cell lysates revealed that p130 was detectable in the membrane fraction but not in the cytosolic fraction. Immunoprecipitation followed by immunoblotting of lyso-PC-treated BAEC identified p130 as bovine PECAM-1. Tyrosine phosphorylation of PECAM-1 appears to be one of the earliest events elicited by lyso-PC, and may play a role in lyso-PC-induced modulation of endothelial functions.

Animals↗

Association of nucleoside diphosphate kinase nm23-H2 with human telomeres.

Telomeres, the ends of eukaryotic chromosomes, are essential structures formed by specific protein-DNA complexes that protect chromosomes from degradation and end-to-end fusion. TRF1, a double-stranded telomeric TTAGGG-repeat binding protein, is associated with mammalian telomeres and controls telomere length by inhibiting the action of telomerase. We identified human nucleoside diphosphate kinase nm23-H2 as a human TRF1-interacting protein by yeast two-hybrid screening. In vitro-binding assays using different recombinant nucleoside diphosphate kinases showed that TRF1 predominantly binds the nm23-H2 isoform rather than nm23-H1. Electrophoretic mobility shift analysis revealed that the recombinant nm23-H2 protein can bind the single-stranded telomeric TTAGGG-repeat while it cannot bind the double-stranded telomeric repeat. The synthetic 20 base oligoribonucleotide, which consists of the template sequence CUAACCCUAAC and the adjacent region of the RNA component of human telomerase, was also found to form the complex with the recombinant nm23-H2 protein. Furthermore, the affinity of telomerase for its substrate was increased in vitro by presence of the plentiful nm23-H2 protein. These findings indicate a close relationship between nm23-H2 and human telomeres and suggest a new biological role for nucleoside diphosphate kinase.

Cloning, Molecular↗

Large granular lymphocyte leukemia with pure red cell aplasia in a renal transplant recipient.

Neoplastic disorders sometimes accompany a renal transplant. Herein, we report a large granular lymphocyte (LGL) leukemia patient with pure red cell aplasia (PRCA) after renal transplantation. A 36-year-old female was presented to our department with anemia in February 1996. She had undergone hemodialysis because of pregnancy in December 1981. She received a renal transplantation from her mother in April 1986. After the transplantation, she received cyclosporin A (CyA) at 2 mg/kg/day, mizoribine at 1 mg/kg/day, and methylprednisolone at 0.1 mg/kg/day for 8 years. In July 1995, her hemoglobin level dropped to 9.3 g/dl, and anemia developed gradually. In January 1996, her hemoglobin was 5.8 g/dl, and she was given a red blood cell transfusion. Laboratory findings were as follows: RBC 1.46 x 10(12)/L; hemoglobin 5.8 g/dl; hematocrit 17.8%; leucocytes 5.2 x 10(9)/L with 62.4% neutrophils, 34.1% lymphocytes, 2.6% monocytes; platelets 50.8 x 10(10)/L; reticulocytes 0.4%. Bone marrow aspirate smears and biopsy sections revealed normal myeloid and megakaryocyte differentiation with few erythroid precursors. The lymphocytes were of medium size with granules in the cytoplasm. More than 90% of lymphocytes were of the LGL type. Surface markers of peripheral blood mononuclear cells demonstrated increases in the CD2+, CD3+, CD4-, and CD8+ populations. A monoclonal rearrangement of T-cell receptor (TCR)-beta chain gene was found by Southern blot analysis of the mononuclear cells in peripheral blood. A diagnosis of LGL leukemia with PRCA was made. During the next 4 months, she received six red blood cell transfusions, a total of 12 U. In March 1996, the patient was treated with cyclophosphamide (1 mg/kg/day). After 1 month of treatment, serum GPT levels increased to 60 IU/l. The dose of cyclophosphamide was reduced to 0.5 mg/kg/day. Two months after initiation of the therapy, the patient developed reticulocytosis and blood transfusion was not needed thereafter. During remission, the number of CD2+, CD3+, CD4-, and CD8+ lymphocytes decreased. Large granular lymphocytes decreased to less than 10% of peripheral blood. The monoclonal rearrangement of the TCR-beta chain gene in peripheral blood disappeared.

Adult↗

Expression of bcl-2-, p53, and Ki-67 and outcome of patients with primary nasopharyngeal carcinomas following DNA-damaging treatment.

BACKGROUND: Recent studies suggest that apoptosis is important in the cell death induced by treatment that damages deoxyribonucleic acid (DNA). We assessed the correlation between the expression of the apoptosis-related proteins, p53 and bcl-2, and the clinical outcome of patients with nasopharyngeal carcinomas (NPCs) who were treated with both DNA-damaging treatments. We also assessed the level of Ki-67, a marker of cell proliferation, in these tumors. METHODS: We evaluated statistically the relationships among the expression of p53, bcl-2, and Ki-67 and clinicopathologic factors, the sensitivity to radiation, the incidence of distant metastases, and survival. RESULTS: The group that was positive for p53 tended to be resistant to radiotherapy and to have a significantly poorer prognosis (p = .05). CONCLUSIONS: The enhanced expression of p53 may be a prognostic factor in patients with NPCs whose tumor is resistant to therapy that damages DNA.

Adult↗

Hearing in the MRL/lpr mouse as a possible model of immune-mediated sensorineural hearing loss.

In order to clarify the possible mechanism of hearing loss in immune-mediated sensorineural hearing loss, basic research needed includes animal model studies. In the present investigation, we examined hearing thresholds and cochlear histologies of the MRL/lpr mouse which is now well-known as a model for pathology consistent with systemic lupus erythematosis (SLE). Present findings demonstrated that there were no statistically significant differences in auditory brainstem response (ABR) thresholds between 4- to 6-week-old "young" and 20- to 25-week-old "old" MRL mice. These differences were not sex-dependent. Under light microscopy, there were no abnormal morphological findings in the cochleas of either young or old MRL mice. With immunohistochemistry, mouse IgG was detected around the capillary walls in the stria vascularis in both young and old MRL mice. Serum IgG level of the MRL mice significantly decreased after predonisolone (PSL) administration. However, expression of mouse IgG in the stria vascularis was not observed in the MRL mice after PSL administration. From these results, we speculate that the hearing of the MRL mouse does not always deteriorate, and the deposition of mouse IgG on the capillary wall in the stria vascularis is not a sufficient factor to induce hearing loss. At this point, we conclude that the MRL mouse should not be considered a useful model for immune-mediated sensorineural hearing loss.

Aging↗

Clinical results of the staged Fontan procedure in high-risk patients.

BACKGROUND: For high-risk Fontan candidates, the introduction of a bidirectional Glenn shunt before total cavopulmonary connection (a two-staged strategy) may extend the indications for the Fontan procedure. The clinical results of the two-staged and one-staged Fontan procedure were thus reviewed and compared. METHODS: Between November 1991 and July 1996, the two-staged strategy was performed in 40 high-risk Fontan candidates with a mean interval of 17.2 months after introducing the bidirectional Glenn shunt (staged group). We considered a young age (<2 years), high mean pulmonary arterial pressure (> or =20 mm Hg), high pulmonary vascular resistance (> or =3 Wood units), small pulmonary artery (Nakata index <200 mm2/m2), atrioventricular valve incompetence (> or = moderate), distortion of pulmonary artery, anomalous pulmonary venous return, and poor ventricular function as risk factors for the successful completion of Fontan circulation. During the same period, 68 patients underwent the modified Fontan procedure in a one-step fashion (primary group). RESULTS: In the staged group after the bidirectional Glenn shunt, the mean pulmonary arterial pressure and ventricular end-diastolic pressure were both found to have decreased significantly to the same level as those in the primary group, whereas the pulmonary artery demonstrated a significantly smaller size than that in the primary group. Operative morbidity was similar in both groups. Operative mortality was also similar and low in both groups (1.5% in the primary group and 0% in the staged group). CONCLUSIONS: A bidirectional Glenn shunt was found to be a useful interim palliation in high-risk Fontan candidates. This two-staged strategy may extend the operative indications for the Fontan procedure.

Adolescent↗

Lazaroid U74500A is superior to U74006F in preserving rabbit heart for 24 hours.

BACKGROUND: Lazaroid, a series of 21-aminosteroids, has been shown to reduce free-radical-mediated injury after ischemia and reperfusion. Recent in vitro studies have demonstrated that, among the various compounds studied, the most efficient agent was U74500A. The question is whether these findings apply to the whole heart experiencing ischemia-reperfusion injury. In this study we compared the myocardial protective effects of U74006F, the only clinical candidate, and U74500A. METHODS: An isolated rabbit heart preparation perfused with the blood from a support rabbit was used. All hearts were divided into three groups according to the administration of U74500A (4 mg/kg, group A; n = 7), U74006F (4 mg/kg, group F; n = 7), or solvent (group S; n = 7) to the donor rabbit before preservation. After 24 hours of preservation with University of Wisconsin solution at 0 degrees C, all hearts were perfused with cross-circulated blood for 60 minutes with the Langendorff mode followed by 40 minutes in the working mode. RESULTS: After 10 minutes of reperfusion the serum lipid peroxide levels were significantly (p < 0.05) lower in group A (0.62+/-0.31 nmol/mL) than those in group S (2.1+/-1.3 nmol/mL) and group F (1.0+/-0.6 nmol/mL). The aortic flow rate at 10 mm Hg of left atrial pressure was significantly higher in group A (164+/-37 mL/min) than that of other groups (71+/-28 mL/min in group S and 97+/-28 mL/min in group F). There were no significant differences in high-energy phosphate levels after reperfusion among the three groups. CONCLUSION: These data imply that U74500A inhibits lipid peroxidation and prevents ischemia-reperfusion injury more efficiently than U74006F.

Animals↗

Cyclin D1 protein overexpression is related to tumor differentiation, but not to tumor progression or proliferative activity, in transitional cell carcinoma of the bladder.

PURPOSE: We attempted to clarify the significance of cyclin D1 in the development and progression of transitional cell carcinoma of the bladder in humans. MATERIALS AND METHODS: Immunohistochemical staining of archival tissue specimens of transitional cell bladder carcinoma obtained from 163 patients was performed by the labeled streptavidin-biotin-peroxidase method. RESULTS: Cyclin D1 protein overexpression was observed in 51 of the 163 specimens (31.3%). Cyclin D1 protein overexpression was showed a highly significant inverse correlation with the histological grade of malignancy (p < 0.01). Grade 3 tumors showed a highly significant low incidence of cyclin D1 protein overexpression as compared with grade 2 tumors (p < 0.01). There was no significant correlation between the overexpression of cyclin D1 protein and tumor stage or the Ki-67 labeling index. CONCLUSION: Cyclin D1 in transitional cell bladder carcinoma was closely related to tumor differentiation but not to tumor progression. Transitional cell carcinoma of the bladder may utilize another pathway for proliferation that is independent of cyclin D1.

Carcinoma, Transitional Cell↗