Biomedical subjects

M Yokota

Publications and source records attributed to M Yokota.

At least 145 records · Page 8Linked to original sources

PubMed1997

Dynamic exercise-induced changes in diastolic properties of the regional myocardium in hypertensive left ventricular hypertrophy.

We investigated the effect of mild exercise on global and regional diastolic function in patients with hypertensive left ventricular hypertrophy (LVH), using simultaneous measurement of micromanometric left ventricular pressure and echocardiographic indexes. Although left ventricular end-diastolic pressure (LVEDP) at rest in the hypertensive LVH group was similar to that in the control normotensive group, who had no abnormality on echocardiography or cardiac catheterization, LVEDP showed a marked increase during exercise only in the hypertensive LVH group. The pressure-dimension relation was shifted upward during exercise in all patients with hypertensive LVH. We utilized a new index of regional diastolic myocardial stiffness, KDM, which is derived from the diastolic relation between the mean wall stress and the natural logarithm of the reciprocal of wall thickness. Although KDM at rest was similar in the two groups, KDM increased significantly during exercise, both in the septum and posterior wall in patients with hypertensive LVH. The present results imply that even low-grade exercise may have deleterious effects on regional myocardial performance in patients with hypertensive LVH.

Diastole↗

PubMed1997

Detection of thalassemia genes using smeared blood film or leukocytes adhering to polysthylene fibers.

Presently genetic analyses for thalassemia types require relatively large amounts of heparinized blood (5 to 10 ml), and transport as well as degeneration of these sample is a problem in the developing world. We have developed a new method to simplify this procedure and obtain DNAs from small specimens. As experimental materials, thinly smeared blood on a glass slide or blood filtered with and adhered on polysthylene telephtalate (PST) fibers were used. These materials could be safely stored without interfering with DNA extraction for up to 3 months. The slide materials were digested with proteinase K, and DNA was extracted with Tris-EDTA-phenol:chloroform and precipitated with absolute ethanol. The PST specimens were washed with physiologic saline and treated in the same manner as described above. Products were easily amplified by PCR and digested with restriction endonucleases for beta thalassemia typing as well as for HLA-DQA1 gene typing. Results obtained by this method correlated well with previously reported incidences for thalassemia and HLA-DQA1 types in Thailand. This method can be used in the routine laboratory because it allows for stable and biosafe genetic analyses.

DNA↗

PubMed1996

Oxygen uptake efficiency slope: a new index of cardiorespiratory functional reserve derived from the relation between oxygen uptake and minute ventilation during incremental exercise.

OBJECTIVES: We investigated the usefulness of a new variable, oxygen uptake efficiency slope (OUES), as a submaximal measure of cardiorespiratory functional reserve. The OUES is derived from the relation between oxygen uptake (Vo2 [ml/min]) and minute ventilation (VE [liters/min]) during incremental exercise and is determined by VO2 = a log VE + b, where a = OUES, which shows the effectiveness of Vo2. BACKGROUND: Maximal oxygen uptake (VO2max) is effort dependent. There is no standard submaximal measurement of cardiorespiratory reserve that provides generally acceptable results. METHODS: Exercise tests, following a standard Bruce protocol, were performed on a treadmill by 108 patients with heart disease and 36 normal volunteers. Expired gas was continuously analyzed. The OUES was calculated from data of the first 75%, 90% and 100% of exercise duration. We also determined the following submaximal variables: the ventilatory anaerobic threshold (VAT), the slope of the regression line of the minute ventilation-carbon dioxide production relation (VE-VCO2 slope) and the extrapolated maximal oxygen consumption (EMOC). We analyzed the relation of OUES and other submaximal variables against VO2max and examined the effects of submaximal exercise on OUES. RESULTS: The correlation coefficient of the logarithmic curve-fitting model was 0.978 +/- 0.016 (mean +/- SD). The OUES and VO2max had a significant correlation (r = 0.941, p < 0.0001). The correlation between VO2max and OUES was stronger than that between VO2max and VAT, the VE-VCO2 slope or EMOC. The OUES values for 100% and 90% of exercise were not different from each other (at an alpha value of 0.05 and treatment effect of 170, the power of the test [1-beta] was 0.90); OUES for 75% of exercise was slightly lower (3.5%). CONCLUSIONS: Our results suggest that OUES may provide an objective, effort-independent estimation of cardiorespiratory functional reserve that is related both to pulmonary dead space and to metabolic acidosis.

Adolescent↗

PubMed1996

Purification and some properties of hemagglutinin from the Myxomycete, Physarum polycephalum.

A new hemagglutinin was isolated from the plasmodium of Physarum polycephalum by salting out with ammonium sulphate followed by chromatography on DE-32, DEAE-Toyopearl and hydroxyapatite. This hemagglutinin, named physarumin, was purified 1000-fold over crude extracts. The molecular weight of physarumin was determined to be 22,000 by size exclusion chromatography on Bio-Gel P-60 and 8,700 by SDS-polyacrylamide gel electrophoresis. Physarumin agglutinated rabbit, guinea pig, horse and human erythrocytes. Physarumin-induced hemagglutination was inhibited by fetuin and alpha 1-acid glycoprotein, but not by commercially available mono- and disaccharides. Hemagglutinating activity was blocked by EDTA, and was restored by adding Ca2+ but not by Mg2+.

Amino Acids↗

PubMed1996

Correlation between left ventricular contractility and relaxation in patients with idiopathic dilated cardiomyopathy.

BACKGROUND AND HYPOTHESIS: It is not fully understood whether alterations in left ventricular (LV) relaxation in patients with idiopathic dilated cardiomyopathy (DCM) precede or follow alterations in LV systolic function. Accordingly, we investigated the relationship between LV systole and diastolic relaxation in patients with DCM using LV pressure-volume analysis. METHODS: Hemodynamic data were collected for 38 consecutive patients with DCM in normal sinus rhythm and in the resting steady state (New York Heart Association functional class II to III). Continuous simultaneous pressure-volume relationships were obtained by conductance catheter. Left ventricular end-systolic elastance (Ees) was determined during transient occlusion of the inferior vena cava. RESULTS: Left ventricular ejection fraction, peak negative dP/dt, and peak positive dP/dt were depressed (31 +/- 11%, -1242 +/- 351 mmHg/s, and 1118 +/- 253 mmHg/s, respectively). The LV end-diastolic volume index, the time constants of isovolumic LV pressure decay TL and TD were increased (141 +/- 38 ml/m2, 54 +/- 14 ms, and 69 +/- 17 ms, respectively). Ees was markedly depressed (0.9 +/- 0.5 mmHg/ml) and was not correlated with established systolic or diastolic indices except for peak positive dP/dt. Our results showed that abnormalities of relaxation were not correlated with contractile dysfunction in patients with DCM in the resting steady state; however, most patients (79%) had both prolonged relaxation and extremely depressed contractility. Abnormal relaxation may have been transient or compensated in some patients (21%) with DCM who had preserved relaxation despite severely depressed contractility.

Adolescent↗

PubMed1996

Simultaneous expression of keratan sulphate epitope (a sulphated poly-N-acetyllactosamine) and blood group ABH antigens in papillary carcinomas of the human thyroid gland.

The monoclonal antibody 5-D-4 recognizes heavily sulphated forms of keratan sulphate epitope. It reacted strongly with the cell surfaces of most thyroid papillary carcinomas from all the individuals examined, independently of the blood group of the patients. Cells of follicular variants of papillary carcinomas were also labelled by 5-D-4. In contrast, no labelling with this antibody was observed in other types of thyroid neoplasms, or in normal tissues. The reactivity of 5-D-4 with papillary carcinomas was markedly reduced or abolished by prior digestion with endo-beta-galactosidase, keratanase II, or N-glycosidase F. Although keratanase digestion had no effect on 5-D-4 labelling, it revealed the binding sites of Griffonia simplicifolia agglutinin II (GSA-II), which recognizes terminal N-acetylglucosamine in a limited number of carcinoma cells from some individuals. Blood group ABH antigens, which are simultaneously expressed together with keratan sulphate epitope in cancer cells, were eliminated by digestion with endo-beta-galactosidase and N-glycosidase F, but were resistant to keratanase and keratanase II treatment. These results indicate that keratan sulphate oligosaccharides are cancer-associated and are probably oncofoetal antigens, as are the blood group antigens in human thyroid glands. The results suggests that poly-N-acetyllactosamine, which is ubiquitously and consistently produced in papillary carcinomas, is modified in two different ways: sulphation on the 6-position of at least some units of either galactose or N-acetylglucosamine or both, and decoration of non-reducing termini with the blood group antigens. Along with the endo-beta-galactosidase-GSA-II labelling procedure, labelling with 5-D-4 may be a useful diagnostic means for distinguishing papillary carcinoma from other types of thyroid neoplasms.

ABO Blood-Group System↗

PubMed1996

Azulene derivatives as TXA2/PGH2 receptor antagonists--II. Synthesis and biological activity of 6-mono- and 6-dihydroxylated-isopropylazulenes.

In order to examine the correlation between activity and hydrophilicity of the side chain of sodium 3-[4-(4-chlorobenzenesulfonylamino)butyl]-6-isopropylazulene -1-sulfonate (KT2-962), a non-prostanoid TXA2/PGH2 receptor antagonist, one or two hydroxyl groups were introduced into the isopropyl moiety. A series of 6-hydroxylated-isopropylazulenes were synthesized by regioselective oxidation of 6-isopropylazulenes and their in vitro and in vivo antagonistic activities were studied. Both the primary and tertiary alcohols, monohydroxylated derivatives, exhibited potent biological activities comparable to unmodified 6-isopropylazulenes both in vitro and in vivo. In contrast, the activities of 1,2- and 1,3-diols of 6-substituted derivatives, markedly decreased, but recovered by O-isopropylidenation of the dihydroxyl moiety. These findings indicate that the moderate hydrophobicity of substituent at the 6-position of the azulene ring might be required for the activity and the size of the substituent at this position, not so rigid for keeping potent biological activity.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1996

A novel inotropic vasodilator, OPC-18790, reduces myocardial oxygen consumption and improves mechanical efficiency with congestive heart failure.

We analyzed the left ventricular (LV) pressure-volume relation and obtained direct measurements of myocardial oxygen consumption (MVO2) before and after drug administration in 21 patients with New York Heart Association functional class II to III congestive heart failure to compare the mechanoenergetic effects of OPC-18790, a novel inotropic agent, and dobutamine. Pressure-volume data were obtained by the conductance method, and MVO2 measurements were obtained with a double-thermistor coronary sinus catheter before and after administration of OPC-18790 and dobutamine. The LV end-diastolic volume index decreased significantly without an increase in the heart rate after administration of OPC-18790, unlike that after administration of dobutamine. Both drugs significantly increased the LV contractility index (Emax) and caused similar improvements in ventricular-arterial coupling. OPC-18790 significantly reduced MVo2, whereas dobutamine increased MVo2. The ratio of the pressure-volume area to myocardial oxygen consumption (PVA/MVo2) remained unchanged after administration of OPC-18790 and decreased after administration of dobutamine. The ratio of external work to the pressure-volume area (EW/PVA) was similarly increased by both drugs, resulting in an improvement in mechanical efficiency (EW/MVo2) with OPC-18790 (p < 0.05) and in a deterioration with dobutamine (p < 0.05). OPC-18790 had an energetic advantage over dobutamine in spite of its positive inotropic effect. Our findings suggest that OPC-18790 may be useful for the treatment of patients with congestive heart failure.

Cardiotonic Agents↗

PubMed1996

Impaired response of left ventricular relaxation to exercise-induced adrenergic stimulation in patients with hypertrophic cardiomyopathy.

OBJECTIVES: We investigated the effect of adrenergic stimulation on left ventricular relaxation in patients with hypertrophic cardiomyopathy. BACKGROUND: Exercise-induced decreases in acceleration of left ventricular relaxation have been observed in patients with hypertrophic cardiomyopathy. However, data on sequential changes in left ventricular relaxation during exercise are limited. METHODS: We measured right (fluid filled) and left (high fidelity micromanometer) ventricular pressures during moderate supine ergometer exercise and during rapid right atrial pacing in four groups of patients: 9 with severe hypertrophic cardiomyopathy, 9 with moderate hypertrophic cardiomyopathy, 10 with hypertension and moderate hypertrophy and 5 control subjects. RESULTS: There was a curvilinear relation between the time constant of relaxation (tau) and heart rate in all groups during exercise. There was no difference in the slope of this relation between the two hypertrophic cardiomyopathy subgroups. Although the slope of this relation between tau and heart rate was steeper in the hypertensive than the moderate hypertrophic cardiomyopathy group (p < 0.001, analysis of covariance), the decrease in tau during right atrial pacing was similar in both groups. There were no significant differences in plasma levels of catecholamines at rest or at peak exercise among groups or in maximal heart rate during pacing. CONCLUSIONS: Pacing-induced changes in tau in hypertrophic cardiomyopathy were similar to those in hypertensive hypertrophy, but remarkable decrease in exercise-induced acceleration of tau were observed only in hypertrophic cardiomyopathy. Our results may indicate a depressed left ventricular relaxation response to exercise-induced adrenergic stimulation in hypertrophic cardiomyopathy.

Adult↗

PubMed1996

Production of C-type natriuretic peptide in human aortic endothelial cells induced by activation of protein kinase C.

The effects of activators and inhibitors of protein kinase C (PKC) on the production of C-type natriuretic peptide (CNP) by cultured human aortic endothelial cells were examined. The PKC activators phorbol 12-myristate 13-acetate (PMA) and 1-oleoyl 2-acetyl glycerol (OAG) stimulated CNP release; the maximal effects were apparent at 4 h, at which time release was 934 and 205% of the control value, respectively. The PKC inhibitors staurosporine and H-7 did not affect basal CNP release, but each abolished the increase in CNP release induced by PMA or OAG. PKC was activated and translocated from cytosolic to membrane fractions in endothelial cells exposed to PMA or OAG; the maximal effect was apparent at 1 h. PMA and OAG each increased the abundance of CNP mRNA, with the maximal effect at 2 h. These data suggest that activation of PKC by PMA or OAG results in an increase in the abundance of CNP mRNA and subsequent enhancement of CNP production and release in human aortic endothelial cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1996

Insufficient calcium and iron intakes among general female population in Japan, with special reference to inter-regional differences.

Dietary intakes of calcium (Ca) and iron (Fe) were investigated in 227 women (mostly housewives) in 12 regions in Japan in 1991-1993 by the 24-hour food duplicate method. Nine regions out of 12 had been previously studied in 1977-1982. Utilizing Standard Food Composition database, mean Ca and Fe-intakes in 1991-1993 were estimated to be 602 and 10.4 mg/day, respectively; the former was barely sufficient and the latter was below sufficiency when compared with the Recommended Daily Allowance in Japan for pre-menopausal women. Ca- and Fe-intake did not increase in the 10-year period. Further analysis after classification of the women into three groups of farmers in Okinawa, farmers in Mainland Japan and urban residents showed that Ca and Fe insufficiency was most evident among Okinawa farmers. The leading Ca sources were milk, pulse, vegetables and fish-shellfish, but consumption of milk was generally low, especially among Okinawa farmers. Pulse, vegetables and fish-shellfish were 3 major Fe sources; Okinawa farmers depended more on vegetables and less on fish-shellfish.

Calcium↗

PubMed1996

Atrial natriuretic peptide accelerates proliferation of chick embryonic cardiomyocytes in vitro.

The developing embryonic heart has been reported to contain significant levels of atrial natriuretic peptide (ANP). In this study, the role of ANP in cardiac development was evaluated using cultured cardiomyocytes isolated from chick embryos. We analyzed the effect of ANP on cell number, DNA synthesis, total RNA level, the expression of cell-cycle-specific and sarcomeric proteins, and levels of lactate dehydrogenase and creatine phosphokinase. ANP increased overall DNA synthesis (measured by BrdU incorporation, P < 0.01) and enhanced cell proliferation. Morphologically, the development of the cardiomyocyte network was distinctly enhanced in the ANP-treated cells. Cellular RNA content was elevated; likewise, myosin and tropomyosin biosynthesis was significantly greater in ANP-treated cells. In addition, expression of G1/S-specific protein increased, whereas G2/M-specific protein remained unchanged by ANP treatment. An antibody against ANP and a specific ANP receptor antagonist, HS-142-1, antagonized and/or attenuated the action of ANP on both cell proliferation and protein biosynthesis. These results indicate that ANP accelerates myocardial cell proliferation by enhancing entry into S phase and by increasing DNA synthesis during S phase specifically through receptor mediated pathway. The in vitro effects of ANP on myocardial cell proliferation, together with the elevated levels of ANP seen in vivo during normal heart formation, suggest a possible autocrine function of ANP in embryonic cardiac development.

Animals↗

PubMed1996

Enhancement of barrier function of human aortic endothelial cells by activators of protein kinase C.

We investigated the role of protein kinase C (PKC) in regulating the permeability of human and bovine aortic endothelial cells (AECs) cultured on micropore filters. AECs cultured in the upper chamber were incubated with medium containing a PKC agonist, phorbol 12-myristate 13-acetate (PMA) or 1-oleoyl-2-acetyl-glycerol (OAG) for 15 min to 8 h, after which the cells were incubated with albumin for 1 h. The amount of albumin that had transferred through AECs was determined. Activation of PKC by exposure to PMA or OAG inhibited albumin permeability in human AECs, but increased it in bovine AECs. While the PKC inhibitor, staurosporine, did not itself influence endothelial permeability, it reduced the decrease or increase in permeability induced by exposure to PMA or OAG in human and bovine AECs, respectively. Activation of PKC thus enhanced the barrier function of human AECs, but reduced it in bovine AECs.

Albumins↗

PubMed1996

Squamous cell carcinoma associated with verruciform xanthoma of the penis.

We report a case of squamous cell carcinoma of the penis that seemed to arise within a verruciform xanthoma of this organ. A lesion in the prepuce was initially diagnosed as a verruciform xanthoma histopathologically and was removed in part. Six years later, the patient exhibited a well-differentiated squamous cell carcinoma of the penis that contained many clusters of xanthoma cells in the stroma. Although the retrospective examination of biopsy specimens of the initial lesion in this patient showed the features mainly of verruciform xanthoma, significant architectural and cytological atypia was also present in the overlying epidermis. Thus, we must be careful not to overlook the presence of a squamous cell carcinoma arising within a benign reactive lesion such as a verruciform xanthoma.

Carcinoma, Squamous Cell↗

PubMed1996

Cytotoxic fragment of amyloid precursor protein accumulates in hippocampus after global forebrain ischemia.

We developed an antibody specific to beta-amyloid precursor protein (beta APP) fragments possessing the exact amino terminus of the beta-amyloid peptide and examined its induction in postischemic hippocampus. In control hippocampus, this APP fragment was lightly observed in pyramidal neurons of CA sectors and dentate granule cells. Transient forebrain ischemia enhanced accumulation of the APP fragment in CA1 pyramidal neurons. Seven days after the ischemia, while the APP fragment was still observed in dentate granule cells and CA3 neurons, it disappeared in dead CA1 neurons. While astrocytes did not show in any immunoreactivity throughout the experiment, those in the CA1 sector showed moderate immunoreactivity 7 days after the ischemia. The APP fragment has a cytotoxic effect on cultured neurons. These results suggest that the accumulation of the cytotoxic APP fragment in CA1 neurons may play a role in the development of delayed neuronal death after the ischemic insult.

Amyloid beta-Protein Precursor↗

PubMed1996

Direct interactions of plasminogen activators with human aortic and pulmonary artery endothelial cells in vitro: implications for thrombolytic therapy.

Direct interactions of plasminogen activators with arterial endothelial cells are important in the pathogenesis of vascular complications associated with thrombolytic therapy. We investigated the direct effects of various plasminogen activators on human aortic and pulmonary artery endothelial cell functions in vitro. The effects of plasminogen activators on endothelial cells were not caused by generation of plasmin, as shown by the absence of plasminogen and alpha(2)-plasmin inhibitor-plasmin complex both before and after addition of plasminogen activators to endothelial cells. High concentrations of plasminogen activators increased the permeability of aortic endothelial cells to albumin. Alteplase (50 x 10(3) IU/ml), a recombinant tissue-type plasminogen activator (t-PA), increased prostaglandin I(2) (PGI(2)) production by aortic endothelial cells from 175.5 +/- 13.8 to 870.8 +/- 131.0 pg/mg cellular protein during a 2-h incubation; other plasminogen activators increased PGI(2) production to a lesser extent. Alteplase (100 x 10(3) IU/ml) also increased PGI(2) production from 152.0 +/- 16.2 to 1,080 +/- 95.1 pg/mg cellular protein in human pulmonary artery endothelial cells. High concentrations of urokinases decreased the amount of endothelin-1 in the medium of aortic or pulmonary artery endothelial cells by as much as 93%; part of this decrease was attributable to degradation of endothelin-l by urokinases. Other plasminogen activators either had no effect on or slightly increased the production of endothelin-1. These changes in the function of human arterial endothelial cells induced by plasminogen activators may affect regional vascular tone, endothelial permeability, and platelet aggregability, all of which are important in the efficacy of thrombolysis and in the pathogenesis of such vascular complications as rethrombosis and hemorrhage.

Aorta↗

PubMed1996

Serological characterization of Trichosporon cutaneum and related species.

Recent molecular biological, chemical, physiological and morphological studies indicate that Tri-chosporon cutaneum and related species should be reclassified. In this study, antigenic characteristics of the species were determined. The results of adsorption experiments revealed that there were at least three serological types: I, II and III. Specific factor sera I, II and III were prepared on the basis of adsorption experiments and isolates were serotyped by cell slide agglutination (CSA). Since the CSA test was difficult to read in some strains, the results of the CSA test were compared with the findings from an enzyme-linked immunosorbent assay (ELISA). For the ELISA, crude polysaccharide antigens prepared from the culture supernatant were used as the antigen. The types determined by ELISA correlated well with those determined by the CSA test. These data suggest that T. cutaneum and related species have at least three serological types, and that the typing can be done by either CSA or ELISA.

Agglutination Tests↗

PubMed1996

4-(3,4-Dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline derivatives. II. Their renal vasodilation activity and structure-activity relationship.

A series of 4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline derivatives showed potent DA1 agonistic activities. We investigated the structure-activity relationship of the racemic compounds of this series. 4-(3,4-Dihydroxyphenyl)-7-methanesulfonamido-1,2,3,4-tetrahydroiso quinoline (43) was identified as a potent renal vasodilator with activity almost equal to that of YM435 (1).

Animals↗