Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 451 records · Page 25Linked to original sources

PubMed1998

2(1H)-quinolinone derivatives as novel anti-arteriostenotic agents showing anti-thrombotic and anti-hyperplastic activities.

In order to search for anti-arteriostenotic agents, a series of 2(1H)-quinolinone derivatives was synthesized and evaluated for anti-thrombotic activity and for anti-hyperplastic activity. From this series, (-)-6-[3-[3-cyclopropyl-3-[(1R,2R)-2-hydroxycyclohexyl]ureido]propoxy]-2 (1H)-quinolinone (1p, OPC-33509) was selected as the best candidate by balancing the efficacy on anti-thrombosis and anti-hyperplasia.

Animals↗

PubMed1998

Role of endogenous endothelin in the development of graft arteriosclerosis in rat cardiac allografts: antiproliferative effects of bosentan, a nonselective endothelin receptor antagonist.

BACKGROUND: The purpose of this study was to determine whether endothelin-1 (ET-1) contributes to the development of graft arteriosclerosis and whether the orally active nonpeptide endothelin receptor antagonist bosentan, which blocks both ETA and ETB receptors, can protect against this pathologic damage. METHODS AND RESULTS: Recipient male Lewis rats were divided into three groups; group 1 received heterotopic heart transplantations from Lewis donors and groups 2 and 3 received transplantations from Brown-Norway donors; group 3 recipients also received bosentan orally at the dose of 20 mg/kg per day for 120 days. All recipients were given cyclosporine and were euthanized at examination 120 days after transplantation. Plasma ET-1 levels were significantly higher in group 2 than in group 1 (6.99+/-0.91 and 4.15+/-.83 pg/mL, respectively). Strong ET-1 immunoreactivity was seen in both the thickened neointima and the media of the coronary arteries in group 2 but not in group 1. The mean ratio of the coronary luminal area to the total vascular area in group 2 (19.0+/-11.7%) was significantly lower than that in group 1 (34.2+/-9.9%) and was significantly increased in group 3 (33.2+/-9.2%). CONCLUSIONS: These results show that local upregulation of ET-1, mainly in the thickened neointima and the media of the coronary arteries, may play an important role in the pathogenesis of graft arteriosclerosis by stimulating ETA receptors, ETB receptors, or both. Orally active bosentan might be a useful agent for the clinical prevention of graft arteriosclerosis.

Actins↗

PubMed1998

Asynergy of the noninfarcted left ventricular inferior wall in anterior wall acute myocardial infarction secondary to isolated occlusion of the left anterior descending artery.

There are patients in whom left ventricular (LV) wall motion decreases in the noninfarcted region and LV systolic function declines globally despite the presence of a localized myocardial infarct attributable to narrowing or occlusion of a single coronary artery. This study examines angiographic characteristics of patients with chronic hypokinesia of noninfarcted myocardium after anterior wall acute myocardial infarction (AMI) due to narrowing of a single coronary artery, namely, the left anterior descending (LAD) artery. The LV ejection fraction, abnormalities in the motion of the noninfarcted LV inferior wall (SD/chord value by Sheehan's technique), the angiographic characteristics of the infarct-related coronary artery, the effect of acute reperfusion therapy, and presence of coronary risk factors were examined in 85 consecutive patients. The SD/chord value in the noninfarcted region showed a positive correlation with the LV ejection fraction (r = 0.505, p <0.0001). By multivariate analysis, hypertension (odds ratio = 0.53, 95% confidence interval [CI] 0.36 to 0.80), an infarct-related narrowing proximal to the origin of the first diagonal branch (odds ratio = 0.56, 95% CI 0.38 to 0.84), and patency of the infarct-related lesion during AMI (odds ratio = 1.56, 95% CI 1.03 to 2.30) were independent predictors of wall motion in the noninfarct region. In some patients with single-vessel anterior wall AMI, the motion of the noninfarcted inferior LV wall decreases during the chronic stage and cardiac function declines severely. In most of these patients, the infarct-related narrowing or occlusion is proximal to the origin of the first diagonal branch of the LAD artery.

Aged↗

PubMed1998

Scavenging Effect of Water Soluble Proteins in Broad Beans on Free Radicals and Active Oxygen Species.

Water soluble proteins (WSP) in broad beans, Vicia faba, were purified, and their scavenging effects on free radicals and active oxygen species were investigated. The purification steps included ammonium sulfate precipitation followed by sequential chromatography on Sephadex G-75. The final gel filtration step yielded two peaks of scavenging activity, each containing M(r) values of 70 kDa (peak I) and 28 kDa (peak II). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of peak II fraction gave a single band with M(r) of 14 kDa, indicating that peak II protein is dimeric. WSP exhibited a marked scavenging effect on superoxide, and also an effect on hydrogen peroxide, but not so much on 1,1-diphenyl-2-picrylhydrazyl radical. WSP had only a small amount of sulfhydryl groups. Thus, the sulfhydryl groups are not responsible for the scavenging activity of WSP.

Journal Article↗

PubMed1998

Glutathione concentration may be a useful predictor of response to second-line chemotherapy in patients with ovarian cancer.

BACKGROUND: No useful predictor of resistance or sensitivity to second-line chemotherapy is known for ovarian cancer. The objective of this prospective study was to determine the utility of tumor glutathione S-transferase-pi (GST-pi) expression or glutathione (GSH) concentration in predicting ovarian cancer patients' responses to second-line chemotherapy. METHODS: Tumor samples were obtained from 26 patients with relapsed epithelial ovarian cancer 3-4 weeks before the initiation of second-line chemotherapy with etoposide (daily on Days 1-5) and cisplatin (on Day 5). The expression of GST-pi in tumor samples was determined by immunohistochemical staining and Western blot analysis. GSH concentration was measured by an enzymatic assay. RESULTS: The response rate was 38.4%. The estimated 3-year survival rate for the responders (66.7%) significantly exceeded that for the nonresponders (9.1%). Expression of GST-pi by immunohistochemical staining was more frequently observed in nonresponders (2 of 10 responders vs. 11 of 16 nonresponders). Western blot analysis detected GST-pi in all cases. There was no significant difference in the relative density values of the GST-pi Western blot analysis between the two groups. The mean value of GSH concentration in nonresponders was significantly higher than in responders (18.4 +/- 9.7 vs. 7.5 +/- 8.2 microg/mg protein). GSH concentration was below the cutoff point (10.3 microg/mg protein) in all responders except one. CONCLUSIONS: Second-line chemotherapy consisting of etoposide and cisplatin is effective in the treatment of relapsed epithelial ovarian cancer. In addition, tumor concentration of GSH may be a useful predictor of the response to this therapy.

Adult↗

PubMed1998

The gain of the hepatorenal reflex in anesthetized dogs.

To determine the overall gain of the hepatorenal reflex, hypertonic NaCl solutions were infused into the portal vein or inferior vena cava of anesthetized dogs at a rate of 0.01 ml/kg/min for 30 min and the urinary Na excretion measured. Infusion of 2.25% NaCl into either the portal vein or inferior vena cava had no effect. Portal infusion of 4.5% or 9% NaCl produced an increase of 36 +/- 16 or 40 +/- 17 microeq/kg/30 min, respectively, while inferior vena caval infusion had no effect. With 13.5% NaCl infusion, a significant increase in the natriuretic response was seen with portal venous infusion, with no significant difference between portal venous and inferior vena caval infusion. Thus, the difference in the natriuretic response between portal venous and inferior vena caval infusion was dependent on the degree of input; when an appropriate input was given, natriuresis was induced only by portal venous infusion, probably mediated by the hepatorenal reflex. The gain of the hepatorenal reflex was calculated from the output divided by the input. When 4.5% or 9% NaCl was infused into the portal vein, the 2-h gain of the hepatorenal reflex was 0.38 +/- 0.15 or 0.34 +/- 0.14, respectively.

Animals↗

PubMed1998

Video-assisted thoracic surgery through a single skin incision.

OBJECTIVE: To develop a minimally invasive video-assisted thoracic surgery technique. DESIGN: Case series. SETTING: University referral center. PATIENTS: Six consecutive patients with a pneumothorax who underwent video-assisted thoracic surgery through a single skin incision. INTERVENTIONS: A flexible digital bronchoscope was placed in a scope guide. A single 2.0-cm skin incision was made in the midaxillary line. The entire lung was carefully explored. An endoscopic stapling device was then inserted, and the lung resection was performed through a single skin incision. PRIMARY OUTCOME MEASURES: Operative time, estimated amount of blood loss, operative complications, and postoperative air leakage were recorded. RESULTS: The video-assisted thoracic surgery procedure through a single incision was successful in all 6 patients. There were no associated complications at 1-year follow-up. CONCLUSIONS: We were able to perform the video-assisted thoracic surgery procedure through a single skin incision using a scope guide and a flexible scope that enables visualization of the entire pleural cavity, providing even laser ablation. This new technique can be used to treat patients with pneumothoraces without the need for additional skin incisions.

Adult↗

PubMed1998

Clinical and cytogenetic remission induced by interferon-alpha in a patient with chronic eosinophilic leukemia associated with a unique t(3;9;5) translocation.

A patient with chronic eosinophilic leukemia and a unique complex chromosomal translocation 46,XY,t(3;9;5)(q25;q34;q33) who had elevated blood interleukin-5 is reported. Complete cytogenetic remission was induced by interferon-alpha after treatment failure with corticosteroids and cytotoxic drugs. Severe cardiopulmonary symptoms due to hypereosinophilia and thromboembolic complication improved dramatically in the first 6 months of interferon therapy. Since it is known that the gene encoding for interleukin-5 resides on the long arm of chromosome 5, it may be possible that the chromosomal translocation in our patient resulted in overproduction of this cytokine, and our findings may be helpful for understanding the pathogenesis of this disorder.

Adult↗

PubMed1998

Clonal analysis of hematopoietic cells using a novel polymorphic site of the X chromosome.

Clonality of hematopoietic cells on a smale scale (nanogram amounts of DNA) can be detected by X-chromosome inactivation using the polymerase chain reaction (PCR). The human androgen-receptor gene (HUMARA) has a polymorphic short tandem repeat (STR), and has generally been used for clonality analysis since heterozygosity for the gene occurs in 90% of caucasian females. We examined heterozygosity of the STR on HUMARA in 110 Japanese females and found heterozygosity in 74 of 110 (67%). To examine for hematologic clonality in females with HUMARA homozygosity, we used a primer specific for a novel polymorphic STR site between DXS15 and DXS134 (DXS15-134) on Xq28. Heterozygosity for this site was found in 50 of 110 females (46%). Clonality of the hematopoietic cells was detected in 91 of 110 females (83%) using PCR of either the STR sites on HUMARA or DXS15-134. The X-inactivation patterns using PCR of DXS15-134 corresponded exactly with those obtained using PCR of HUMARA in 18 females who were heterozygous for both DXS15-134 and HUMARA. Using PCR of DXS15-134, we examined the clonality of bone marrow cells separated by flow cytometry in a patient with erythroleukemia (M6). Clonality was found not only in myeloid lineage cells but also in B lymphocytes. The clonality assay for DXS15-134 may be useful to assess for clonality of hematopoietic cells in the Japanese population, when combined with the HUMARA assay.

Base Sequence↗

PubMed1998

pp60c-src activation in hepatocellular carcinoma of humans and LEC rats.

For the related Src kinases, a close correlation exists between elevated tyrosine kinase activity and cell transformation. However, the involvement of pp60c-src in hepatocellular carcinoma (HCC) remains obscure. The aim of this study was to evaluate whether pp60c-src tyrosine kinase activity is elevated in HCC. We analyzed the kinase activity of pp60c-src in normal liver tissue, chronic hepatitis liver tissue, and tumorous and adjacent nontumorous portions of HCC tissue from patients and Long-Evans cinnamon (LEC) rats that are known to develop liver cancer spontaneously. The kinase activity of pp60c-src was rarely detected in the normal human liver tissue and chronic hepatitis liver tissue, but it was elevated in tumorous and nontumorous portions of HCC tissue. Furthermore, the kinase activity of pp60c-src was significantly elevated in tumorous tissues compared with nontumorous tissues. The kinase activity of pp60c-src was also higher in poorly differentiated HCC. In addition, the kinase activity of pp60c-src increased proportionately with the development of HCC of LEC rats. Our results suggest that activation of the protooncogene product pp60c-src may play an important role in the malignant transformation of hepatocytes in human and LEC rats, and that it may be closely related to the histopathological grading of human HCC.

Animals↗

PubMed1998

Influence of aging or left ventricular hypertrophy on the human heart: contents of phosphorus metabolites measured by 31P MRS.

Although both aging and hypertrophy are extremely important factors for cardiac performance, their influence on cardiac metabolism, especially that of high-energy phosphates, has not been fully elucidated as yet. Quantitative measurements of high-energy phosphates were attempted by comparing myocardial 31P NMR spectra with an external reference using depth-resolved surface-coil spectroscopy. The voxel size of the region of interest (ROI) was disk-shaped with 15-cm diameter and 25-mm thickness, but the left ventricular weight actually involved in the ROI was estimated to be between 22 and 66 g using MRI. Myocardial phosphocreatine (PCr) content and adenosine triphosphate (ATP) content for the 30 normal volunteers showed significant age dependence since both decreased in relation to increasing age. Myocardial PCr content and ATP content in patients with hypertension did not differ significantly from the age-matched control group. PCr content (6.1 +/- 2.2 micromol/g wet tissue, n = 10) and ATP content (4.1 +/- 1.3 micromol/g wet tissue) in patients with hypertrophic cardiomyopathy were less than the age-matched control group (n = 15; PCr: 9.7 +/- 2.5 micromol/g wet tissue, P < 0.01; ATP: 6.4 +/- 1.8 micromol/g wet tissue, P < 0.05), respectively. These results indicate that quantitative 31P MRS may be valuable in the assessment of changes in high-energy phosphate metabolism caused by aging or hypertrophy.

Adenosine Triphosphate↗

PubMed1998

Formal representation of summary tables for health care statistical database management.

There is an ever-increasing demand for statistical information in health-care societies, and voluminous statistics are collected every year. When one needs information on survey results, it is generally not allowed to access the original data, and the summary tables are the most important source of information which can be shared. In order to store summary tables as a well-organized database and to perform flexible retrieval, a formal study has been made on the structure of summary tables. We introduce the notion of summary table scheme and define the operations called table transformation. A statistical database management system has been implemented based on the study. In our study, a statistical database is a collection of summary tables obtained from a survey. If a survey is conducted periodically, a database consists of all the tables obtained in the past. System utilities have been implemented for handling time-oriented information.

Algorithms↗

PubMed1998

Indication and efficacy of radiation therapy following radical surgery in patients with stage IB to IIB cervical cancer.

OBJECTIVE: To determine the role of radiation therapy following radical surgery in patients with cervical cancer. METHOD: A total of 104 patients with International Federation of Gynecology and Obstetrics stage IB to IIB cervical cancer who underwent radical hysterectomy and pelvic lymph node dissection at Tottori University Hospital between 1988 and 1994 were entered in this study. The criteria for postoperative radiotherapy included positive lymph node involvement, compromised surgical margin, parametrial extension, or deep stromal invasion of cervix with less than 3 mm of distance from serosa. Postoperative radiotherapy consisted of 10-20 Gy whole pelvis and an additional parametrial dose with a midline block to deliver a total of 44-50 Gy to the pelvic side wall. RESULTS: Sixty-two patients (59.6%) who met the criteria received postoperative radiotherapy. Lymph node metastasis was most frequent in stage IIB followed by stage IIA and then stage IB (36.7, 22.2, and 10.7%, respectively). Parametrial extension was observed 8.7% of patients with stage IB and 27.7% of those with stage IIA. The estimated 5-year survival rate for patients undergoing surgery alone was 97.6% and that for patients receiving postoperative radiotherapy was 82.7% (P = 0.038). Multivariate analysis showed that lymph node metastasis and parametrial extension were major prognostic factor, but the survival rate did not relate to depth of stromal invasion. CONCLUSION: Postoperative radiotherapy may improve the survival of patients with cervical cancer exhibiting lymph node metastasis or parametrial extension.

Adult↗

PubMed1998

Immediate increase in circulating hepatocyte growth factor/scatter factor by heparin.

Circulating levels of hepatocyte growth factor (HGF)/scatter factor have been recently found to be increased in the early phase of myocardial infarction, and it has been hypothesized that HGF plays a role in angiogenesis and collateral vessel growth. Heparin has also been shown to enhance angiogenesis and to improve collateral blood flow. This study was designed to study the effect of heparin on the release of HGF. In an experimental study, heparin was given to rats intravenously and plasma was collected for measurements of HGF by enzyme-linked immunosorbent assay. A dose-dependent increase in circulating HGF was measured with peak levels occurring 10 min after injection of 300 units/kg of heparin (15.4+/-2.0 ng/ml after v 0. 17+/-0.14 ng/ml before injection,P<0.0001). In a subsequent clinical study, 12 patients received 3000 units of heparin during cardiac catheterization. Circulating HGF increased steeply within 3 min of the injection. Comparable changes in plasma concentrations were measured in samples obtained from femoral vein (8.7+/-3.5 after v 0. 33+/-0.07 before injection P<0.05) or artery (10.5+/-3.2 ng/mlv 0. 27+/-0.05 P<0.01), pulmonary artery (9.1+/-2.0 ng/mlv 0.36+/-0.06 ng/ml,P=0.07 ) or right atrium (8.5+/-1.6 ng/mlv 0.42+/-0.11,P<0.01). This study suggests that heparin-induced effects such as the promotion of angiogenesis may be at least partly due to the release of HGF.

Angina Pectoris↗

PubMed1998

Long pedunculated colonic polyp composed of mucosa and submucosa: proposal of a new entity, colonic muco-submucosal elongated polyp.

We encountered 15 patients with colonic polyps showing histologic features that did not belong to any of the known categories. All polyps were elongated and drumstick-shaped, with lengths of 12 to 160 (mean, 29 mm) mm. Histologically, the polyps were covered with normal mucosa and consisted of edematous, loose, fibrous, connective tissues and dense, fibrous submucosal layers, often showing dilation of blood vessels and lymphatics. Although the mechanism of generation of such polyps remains unknown, their elongation may be caused by intestinal motion. Because this kind of polyp has not been described previously outside Japan, we here introduce a new type of polyp, which we have proposed calling the colonic muco-submucosal elongated polyp.

Adult↗

PubMed1998

Radical surgery following neoadjuvant chemotherapy for patients with stage IIIB cervical cancer.

BACKGROUND: We conducted a phase II trial of radical surgery following neoadjuvant chemotherapy in patients with stage IIIB cervical cancer. METHODS: A total of 26 patients with stage IIIB cervical cancer were entered in this study. Patients were treated with a chemotherapeutic regimen consisting of intraarterial infusion of cisplatin and intravenous infusion of other anticancer agents, to a maximum of 3 courses. If the results of the evaluation indicated that surgery was feasible, radical surgery, including complete removal of pelvic vessels, partial resection of adjacent organs, and pelvic and paraaortic lymphadenectomy, was performed. Patients whose tumors showed no response received radiotherapy. We evaluated operability, survival rate, toxicities, and complications. Additionally, we examined prognostic variables by multivariate analysis in the patients treated by radical surgery. RESULTS: Eighteen patients (69.2%) underwent radical surgery. The remaining eight patients received radiation therapy. The 3-year disease-free survival rate was 72.2% in patients who received surgery and 25.0% in those who received radiotherapy. Multivariate analysis did not show any independent prognostic factors in the patients who underwent surgery. CONCLUSION: Radical surgery following neoadjuvant chemotherapy may be feasible in two thirds of patients with stage IIIB cervical cancer; therefore, phase III trials can be recommended.

Adult↗

PubMed1998

Ligation of medically refracted patent ductus arteriosus (PDA) in an extremely low body weight premature infant.

Medically refracted patent ductus arteriosus (PDA) in an extremely low birth weight (ELBW) preterm (gestation 24 weeks 2 days) infant was successfully ligated under general anesthesia in the neonatal intensive care unit (NICU). Pharmacological agents are more effective to close PDA in preterm infants than in full-term infants, although within 48 h three doses of indomethacin were not sufficient to close PDA in this case. At the age of 69 h the infant developed severe symptoms including bradycardia, systemic hypotension, pulmonary hypertension, diastolic steal (reverse distal aorta flow velocity), and anuria. A PDA ligation was thus performed surgically at 72 h of age. General anesthesia and surgical stress were tolerated by this 531 g infant. Postoperatively all symptoms improved dramatically and the general conditions were stable. On the 38th day the endotracheal tube was extubated and on the 50th day nasogastric milk feeding was started. The oxygen supply was weaned on the 78th day. Growth and development until 6 months were within the normal range of very low birth weight infants. A surgical ligation as early as possible in medically refracted PDA in an ELBW infant is thus considered to be a safe and effective treatment. It prevents the development of further complications of cardiopulmonary vascular problems. Color Doppler echocardiography can reliably measure the PDA size, flow velocity, and hemodynamic changes of persistent PDA, even in tiny infants.

Ductus Arteriosus, Patent↗

PubMed1998

Two cases of synchronous multiple thymoma.

We report two cases of synchronous double primary thymoma without myasthenia gravis. These cases suggest the possibility of multicentric thymoma and confirm the validity of a complete thymectomy.

Adult↗