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Biomedical subjects

W Sato

Publications and source records attributed to W Sato.

At least 19 recordsLinked to original sources
PubMed1997

Structure-activity relationship of newly synthesized quinoline derivatives for reversal of multidrug resistance in cancer.

The effect of 24 newly synthesized quinoline derivatives on tumor cell multidrug resistance (MDR) was examined in vitro. At low concentrations, these compounds enhanced the accumulation of [3H]vincristine in K562/ADM cells and reversed tumor cell MDR. The results of the structure-activity relationship analysis indicate that in highly active compounds the two aryl rings in the hydrophobic moiety deviate from a common plane, so they are capable of interacting with hydrogen bond donors of P-170 glycoprotein (P-gp) via pi-hydrogen-pi interactions. Other major structural features which influence the MDR-reversing activities of these compounds are a quinoline nitrogen atom and a basic nitrogen atom in piperazine. Furthermore, in highly active compounds, the distance between the hydrophobic moiety and the basic nitrogen atom (an atom connected to 2-hydroxypropoxyquinoline) must be at least 5 A. Several compounds were found to reverse vincristine resistance in K562/ADM cells in vitro, and compound 16 (MS-209) was selected for clinical studies.

Animals↗
PubMed1997

Spirometry and airway reactivity in elite track and field athletes.

OBJECTIVES: To characterize spirometry and to document the incidence of exercise-induced bronchospasm (EIB) during competition in elite track and field athletes. DESIGN: Spirometry was performed in 120 men and 69 women athletes before competition and peak expiratory flows in 50 men and 23 women athletes before and after competition. SETTING: The 1991 (Randalls Island, NY, U.S.A.) and the 1993 (Eugene, OR, U.S.A.) National Track and Field Championships (World Championship team-qualifying meet). PARTICIPANTS: American track and field athletes who met World Championship qualifying standards. MEASUREMENTS: Spirometry (Cybermedic, Inc., Boulder, CO, U.S.A.) and peak expiratory flows (Personal Best, Healthscan Products, Cedar Grove, NJ, U.S.A.)--the best of three reproducible efforts. RESULTS: Male sprinters had lower vital capacities than other track athletes, whereas both male and female field (throwing) athletes had larger vital capacities than both runners and other field athletes. Decreases of 10% peak expiratory flows were found in 10% of men and 26% of women track athletes within 15 min after competition. The incidence was higher in longer-distance events. Most participants did not have a history of asthma. CONCLUSIONS: A higher-than-expected prevalence of EIB was found in high-level track athletes. The results suggest that spirometry and/or peak flows should be measured in track athletes because small decreases in airflow may impair training or performance, a condition that is easily treated.

Adult↗
PubMed1997

Role of Bordetella bronchiseptica sialic acid-binding hemagglutinin as a putative colonization factor.

The role of Bordetella bronchiseptica sialic acid-binding hemagglutinin (SBHA) in bacterial colonization was studied by testing the ability of a phase-I strain carrying SBHA and its spontaneous mutants deficient in SBHA to colonize mouse tracheae. The mutants exhibited a remarkable reduction in colonizing ability, approximately 1,000-fold, when compared with that of the parent strain, suggesting that the possession of SBHA and the effective colonization by B. bronchiseptica organisms are closely related.

Animals↗
PubMed1997

[A study on supporting methods for house-bound home care elderly to get independent life (1st report)--relation between ADL and daily hours out of bed].

It is important to prevent the House-Bound home care elderly from getting worse to the Bed-bound. We studied the relation between "daily hours out of bed" and the activity of daily living (ADL) estimated by FIM (Functional Independence Measure) in 50 house-bound home care elderly persons. Result are as follows; (1) The level of independence of "Toileting", one of the FIM self-care items, was most highly correlated with the "daily hours out of bed" in the house-bound home care elderly. (2) The level of independence of "Mobility to the Toilet" and "Bowel Control" were also highly correlated with the "daily hours out of bed" in the house-bound home care elderly. (3) The level of independence of "Toileting" had high correlation with a total score of FIM moter items in the house-bound home care elderly (r = 0.83, p < 0.001).

Activities of Daily Living↗
PubMed1997

Hypertrophic obstructive cardiomyopathy with abnormalities of the mitral valve complex.

The mechanism of obstruction of the left ventricular outflow tract (LVOT) in hypertrophic obstructive cardiomyopathy (HOCM) is mainly due to dynamic systolic anterior motion (SAM) of the mitral valve. We report a case of HOCM with mitral regurgitation (MR) associated with complicated abnormalities of the mitral apparatus which contributed to a high pressure gradient through the LVOT. A small, 53-year-old woman was admitted for chest pain and palpitation. Examinations revealed asymmetric septal hypertrophy of the left ventricle, MR, SAM of the mitral valve and a high pressure gradient (108 mmHg) through the LVOT. Operative findings revealed an abnormally hypertrophied interventricular septum, an extensively thickened and enlarged anterior mitral leaflet (AML), malposition of the origin of the anterior papillary muscle arising closer to the aortic annulus than normal, and its direct insertion into the AML without any distinguishable chordae tendineae. The hypertrophied septum and the large and protruding AML appeared to obstruct the LVOT, resulting in a loss of subaortic clearance that was recovered after mitral valve replacement and myectomy. Pathology of the papillary muscle was characteristic of HOCM, showing disorganization and disarray of myocardial fibers, bizarre-shaped nuclei, and intercellular fibrosis, while those of the mitral leaflets negated both rheumatic changes and endocarditis.

Cardiomyopathy, Hypertrophic↗
PubMed1997

Potentiation of the antitumor activity by a novel quinoline compound, MS-209, in multidrug-resistant solid tumor cell lines.

A novel quinoline compound, MS-209, was examined for its ability to reverse multidrug resistance (MDR) in several murine and human MDR solid tumor cell lines both in vitro and in vivo. MS-209 strongly reversed drug resistance to adriamycin (ADM) and vincristine (VCR) in acquired MDR tumor cell lines, 2780AD and KB-C1. In addition, MS-209 enhanced the cytotoxic effect of ADM and VCR on various human and murine cell lines. Particularly in 4-1St cells, which are extremely resistant to ADM and VCR, MS-209 at a concentration of 3 microM enhanced the cytotoxicity of ADM and VCR, 88- and 350-fold, respectively. MS-209 administered orally, together with ADM, enhanced the antitumor activity of ADM on Colon 26 and 4-1St tumors implanted subcutaneously (SC) in mice; the antitumor effect of ADM plus MS-209 was higher than that of ADM alone at the maximum tolerated dose (MTD). Furthermore, the coadministration schedules of MS-209 to attain the highest potentiation of ADM activity were examined using Colon 26 tumors. The maximum antitumor activity was obtained when MS-209 was administered on the same day as ADM. MS-209 administered a day before the ADM injection exhibited no potentiation effect, whereas MS-209 administered a day after the ADM injection showed a moderate effect. The effect of MS-209 was weaker when administered in a fractionated manner than when administered as a single dose. The results presented in this article suggest that MS-209 is an effective agent to overcome MDR in cancer chemotherapy.

Adenocarcinoma↗
PubMed1996

Double balloon catheter for concomitant augmentation of abdominal organ perfusion during intraaortic balloon counterpulsation.

A newly devised double balloon catheter to augment abdominal organ perfusion concomitant with original cardiac assist during intraaortic balloon counterpulsation provided satisfactory hemodynamics and urinary output around cardiac surgical procedures in 2 patients with coronary artery disease. Some optional advantages in clinical application and problems arising in the catheter design which need to be investigated are discussed.

Acetylglucosaminidase↗
PubMed1996

[Surgical treatment for ischemic cardiomyopathy].

From June 1970 to Aug. 1995. We were experienced 2,235 coronary surgical patients at the Heart Institute of Japan. Among them, the ischemic cardiomyopathy (ICM) was defined as the elective, isolated CABG with the EF of less than 20%. Among the 1,640 cases of elective, isolated CABG, the cases with the EF of less than 20% were 29, 1.8% of the total. The hospital mortality was 2 cases (6.9%). The late mortality was 2 cases. The graft patency rate was 96.6%. An actuarial survival rates at 1 year, 3 years and 5 years were 93%, 93 and 87%. Operative mortality and 5-year survival rate of CABG for ICM are acceptable, and appear comparable to that achieved in similar patients after transplantation.

Adult↗
PubMed1996

[Effect of sevoflurane on release of TNF-alpha and IL-1 beta from human monocytes].

Although isoflurane inhibits TNF-alpha and IL-1 beta release from human monocytes stimulated by LPS in dose dependent fashion, it is unclear whether sevoflurane has the same effects. Therefore, we investigated whether sevoflurane could inhibit TNF-alpha and IL-1 beta secretions from human monocytes stimulated by LPS in dose dependent fashion in vitro. Human monocytes stimulated by LPS were cultured for 3 h in the presence of sevoflurane 1% or 5%. Another group of human monocytes were cultured in the absence of sevoflurane. TNF-alpha and IL-1 beta increased after stimulation of LPS and these increases were not inhibited by sevoflurane in a dose dependent fashion. We conclude that sevoflurane does not inhibit TNF-alpha and IL-1 beta release from monocytes stimulated by LPS.

Anesthetics, Inhalation↗
PubMed1996

[Emergency coronary artery bypass in an 84-year-old patient with severe left main disease and cardiogenic shock].

An 84-year-old male was admitted to pur hospital because of unstable angina. The patient presented in cardiogenic shock with a cardiac index of 1.3 l/min/m2 associated with hypotension (systolic blood pressure < 80 mmHg) and oliguria, and in ventricular fibrillation after an acute broad anterolateral infarction due to severe left main coronary disease. The patient received an intra-aortic balloon pumping (IABP) and underwent emergency CABG. After completion of CABG, left ventricular contractility was markedly diminished to maintain systemic circulation. Because the patient could not be weaned from cardio-pulmonary bypass (CPB) in spite of IABP and high-dose of catecholamines, we decided to continue CPB. It was continued for 163 minutes and the patient was successfully weaned from CPB. In spite of the high risk of operative mortality with CABG for left main shock syndrome in elderly patients, CABG could be performed safely. The patient ran an uneventful postoperative course and is now doing well.

Aged↗
PubMed1995

Relationship between multidrug resistant gene expression and multidrug resistant-reversing effect of MS-209 in various tumor cells.

MS-209 is a novel quinoline compound which can overcome multidrug resistance (MDR) both in vitro and in vivo, while having a low level of side effects, and is now being evaluated in a clinical phase II study. Reverse transcription-polymerase chain reaction (RT-PCR) was used to quantitate the expression levels of MDR genes in various mouse and human tumor cell lines. The MDR gene and the beta actin gene, as the internal reference standard, were coamplified separately, and the relative expression of the MDR gene was represented by the MDR/beta actin ratio. The in vitro MDR-reversing effect of MS-209 was then compared with the MDR gene expression (MDR/beta actin ratio). We found a significant correlation between these two parameters. Moreover, a significant correlation was also observed between the level of expression of the MDR1 gene and that of P-glycoprotein in human cell lines. Therefore, the efficacy of MS-209 seems to specifically depend on the level of MDR gene expression (P-glycoprotein). From these observations, it is suggested that RT-PCR assays of MDR1 gene in tumor biopsy specimens might be an effective means to predict the response of tumor cells to combination therapy with MS-209.

Animals↗
PubMed1995

Reversal of multidrug resistance by a novel quinoline derivative, MS-209.

MS-209, a novel quinoline derivative, was examined for its reversing effect on multidrug-resistant tumor cells. MS-209 at 1-10 microM completely reversed resistance against vincristine (VCR) in vitro in multidrug-resistant variants of mouse leukemia P388 cells (VCR-resistant P388/VCR and Adriamycin (ADM)-resistant P388/ADM) and human leukemia K562 cells (VCR-resistant K562/VCR and ADM-resistant K562/ADM). MS-209 at 1-10 microM also completely reversed resistance against ADM in vitro in P388/VCR cells, K562/VCR cells, and K562/ADM cells. In ADM-resistant P388 (P388/ADM) cells, however, ADM resistance was only partially reversed at the MS-209 concentrations tested. MS-209 enhanced the chemotherapeutic effect of VCR in P388/VCR-bearing mice. When MS-209 was given p.o. at 80 mg/kg twice a day (total dose, 160 mg/kg per day) with 100 micrograms/kg VCR, a treated/control (T/C) value of 155% was obtained. MS-209 also enhanced the chemotherapeutic effect of ADM in P388/ADM-bearing mice. The most prominent effects were obtained when MS-209 was given with 2 mg/kg ADM, yielding T/C values of 150%-194% for the combined treatment at an MS-209 dose of 200-450 mg/kg. MS-209 inhibited [3H]-azidopine photolabeling of P-glycoprotein efficiently. Furthermore, the accumulation of ADM in K562/ADM cells was increased more efficiently by MS-209 than by verapamil. These results indicate that MS-209, like verapamil, directly interacts with P-glycoprotein and inhibits the active efflux of antitumor agents, thus overcoming multidrug resistance in vitro and in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Detection of neoplastic clone in the hypoplastic and recovery phases preceding acute lymphoblastic leukemia by in vitro amplification of rearranged T-cell receptor delta chain gene.

This study assessed the clonality of hypoplastic and subsequent recovery phases before the development of overt leukemia by molecular genetic analysis. We describe a boy who had transient granulocytopenia and anemia before the development of acute lymphoblastic leukemia (ALL). Initially, his bone marrow was hypocellular with 23.6% of lymphoblastic cells, whereas subsequent marrow after the administration of granulocyte colony-stimulating factor (G-CSF) appeared almost normal without any lymphoblasts. At diagnosis, we found the rearrangement of T cell receptor (TCR) delta gene in the leukemic cell DNA by Southern blot hybridization. The junctional sequence of the V delta 2-D delta 3 recombination of leukemic cells obtained by polymerase chain reaction (PCR) was used for a clonospecific probe. Using the probe, the presence of leukemic clone in the materials before and after diagnosis was examined. We found that the clonospecific probe could detect one leukemic cell in 10,000 normal cells, and we demonstrated the presence of the leukemic clone at the initial hypoplastic and the subsequent recovery phase. The PCR method is very useful to confirm the presence of leukemic clone even in a retrospective analysis using low-quality materials and may be helpful to understand the pathogenesis of a smoldering preleukemic phase.

Bone Marrow↗
PubMed1995

Identification and expression of a missense mutation (Y446C) in the acid sphingomyelinase gene from a Japanese patient with type A Niemann-Pick disease.

Types A and B Niemann-Pick disease (NPD), an autosomal recessive lysosomal storage disorder, are caused by deficiency of acid sphingomyelinase (ASM). The recent identification of mutations in ASM gene causing types A and B NPD has led to the investigation of the phenotypic heterogeneity and the ethnic distribution of this disease, especially in Ashkenazi Jewish population. To characterize the mutations causing NPD in Japanese population, we analyzed the genomic sequence of ASM from a Japanese patient with type A NPD by PCR amplification and sequencing. A new mutation, Y446C, was identified. The authenticity of this lesion was demonstrated by the expression of the Y446C allele in COS-1 cells. No residual ASM activity was detected from the expression of the Y446C.

Amino Acid Sequence↗
PubMed1995

Isolation of cDNA encoding the human liver phosphorylase kinase alpha subunit (PHKA2) and identification of a missense mutation of the PHKA2 gene in a family with liver phosphorylase kinase deficiency.

X-linked liver glycogenosis (XLG) due to liver phosphorylase kinase (PHK) deficiency is the most frequent liver glycogen storage disease. The affected patients present in early childhood with hepatomegaly and growth retardation. We isolated and determined the structure of human liver alpha subunit of PHK (PHKA2) cDNA. The 3705 base pair open reading frame encodes a polypeptide of 1235 amino acid residues, and the deduced amino acid sequence shows 93 and 68% homology to that of rabbit liver alpha subunit of PHK and human muscle alpha subunit of PHK, respectively. We identified a missense mutation, a valine substitution for glycine at amino acid 193, in the PHKA2 gene of a family with XLG.

Amino Acid Sequence↗
PubMed1995

[Milrinone suppresses TNF-alpha and IL-1 beta release in mouse peritoneal macrophages].

Tumor necrosis factor-alpha (TNF-alpha) exerts a wide spectrum of biological activities and contributes to the pathophysiology of septic shock. We studied whether milrinone suppresses TNF-alpha and IL-1 beta releases from mouse peritoneal macrophages. Mouse peritoneal macrophages were stimulated for 18 hr with lipopolysaccharide and different doses of milrinone. TNF-alpha release was suppressed in a dose-dependent fashion with milrinone, reaching half-maximal inhibition at 30 microM. Release of IL-1 beta was not suppressed with 25 microM of milrinone, but it was suppressed with 250 microM of milrinone. We conclude that TNF-alpha release is suppressed by therapeutically administered milrinone.

Animals↗