Search PubMed⌕ Search

Biomedical subjects

T Ashikaga

Publications and source records attributed to T Ashikaga.

At least 55 records · Page 3Linked to original sources
PubMed1996

Induction of polymorphic ventricular tachycardia by programmed ventricular stimulation in vasospastic angina pectoris.

This study was designed to examine the ventricular vulnerability of patients with vasospastic angina. Fourteen patients (mean age 57 +/- 9 years) with vasospastic angina underwent electrophysiologic testing during the asymptomatic phase (baseline) and after the relief of acetylcholine-induced spasm with isosorbide dinitrates. Twenty patients without structural heart disease served as a control group. By programmed ventricular stimulation, polymorphic ventricular tachycardia (VT) was induced at baseline in 6 of 14 patients, with 1 patient developing ventricular fibrillation and 7 of 14 patients developing repetitive ventricular responses. After isosorbide dinitrate, polymorphic VT was induced in only 1 patient who had ventricular fibrillation at baseline. Repetitive ventricular responses were induced in 3 of 5 patients who had VT at baseline and in 4 of the 7 patients with repetitive ventricular responses at baseline. There was a significant difference in the incidences and severity of induced ventricular arrhythmias between the 2 phases (p <0.01). Among 20 control subjects, repetitive ventricular responses were induced only in 6 patients, but no VT was induced. There was a significant difference in the incidence of induced ventricular arrhythmias and VT at baseline between the vasospastic angina and control groups (p <0.001 and <0.01, respectively). Thus, patients with vasospastic angina had increased ventricular vulnerability, even during the symptom-free period without ischemic events, which could predispose to the development of life-threatening arrhythmias aggravated by vasospastic attacks.

Adult↗
PubMed1996

Effects of exercise on left ventricular performance determined by echocardiography in chronic, severe mitral regurgitation secondary to mitral valve prolapse.

Data on the effects of exercise on left ventricular (LV) volumes and ejection performance in patients with severe mitral regurgitation (MR) are limited. With use of a matched-pairs design, 10 asymptomatic patients with chronic, severe MR and normal LV systolic function who were not receiving vasodilator therapy (group 1) and 10 matched normal control subjects with no structural heart disease (group 2) performed symptom-limited upright bicycle ergometry with quantitative echocardiographic analysis. An additional 8 patients with severe, chronic MR and normal LV systolic function who were receiving vasodilator therapy at the time of testing (group 3) were studied for comparison. The 3 cohorts exercised for similar periods of time. Group 1 and 3 patients had similar end-diastolic volumes at rest, both of which were significantly greater than those of normal controls. Although resting LV end-systolic volume was greater in groups 1 and 3 than in normal controls, the 3 groups had similar relative percent reductions in end-systolic volume during exercise (30 +/- 12%, 32 +/- 13%, and 30 +/- 24%; p = NS). A similar percent increase in LV ejection fraction was also observed in all 3 cohorts (18 +/- 9%, 15 +/- 9%, and 14 +/- 6%; p = NS). Forward stroke volume increased significantly in group 1 (59 +/- 21 and 71 +/- 18 ml; p <0.001) and in group 3 (59 +/- 17 and 68 +/- 13 ml; p < 0.05). Thus, in asymptomatic patients with chronic, severe MR and normal LV ejection fraction at rest, there is an improvement in LV ejection fraction and an increase in forward stroke volume during exercise. These effects are comparable to those observed in normal controls. Directional differences in the cohort receiving no activity therapy were indistinguishable from either patients receiving vasodilator therapy or normal control subjects.

Adult↗
PubMed1996

Impact of nausea/vomiting on quality of life as a visual analogue scale-derived utility score.

Pharmacoeconomic analysis is often based upon incremental cost per increase in survival (cost-effectiveness). Using this definition supportive care measures, which increase quality but not quantity of life, generate a zero denominator and cannot be directly compared with other components of health care cost. Cost-utility analysis, which measures incremental cost per increase in quality-adjusted life-years (QALY), where QALY = utility score x time at risk, addresses this problem, since successful supportive intervention increases the utility score and thus provides a finite denominator in QALY even when absolute survival is unchanged. However, utility scores for various supportive care modalities have not been well defined. As a pilot study to generate a first approximation of a utility score for nausea/vomiting, we used a rating scale technique and administered two visual analogue scale questions to 30 patients completing a cycle of chemotherapy. Patients rated their global quality of life during their previous cycle of chemotherapy with hypothetical absence or presence of nausea/vomiting as the only variable. The study population included 8 male and 22 female patients, with a median age of 56 years. The most common malignancies were breast cancer (8 patients), lung cancer (7 patients), and hematologic malignancies (7 patients). On a 100 mm visual analogue scale, the mean score for overall quality of life during chemotherapy was 79 mm without nausea/vomiting and 27 mm with nausea/vomiting (P < 0.001, paired t-test). The implied marked increase in utility with relief of nausea/vomiting suggests a significant impact on cost-utility analysis. Similar methodology could be used to estimate utility scores in other areas of supportive care.

Adult↗
PubMed1996

Comparison of effects of vasoactive agents on adenylate cyclase activity in endothelial and smooth muscle cells from the same specimen of fetal bovine aorta.

1. Adenylate cyclase activity in vascular endothelial cells (EC) has not been adequately defined. We compared adenylate cyclase activities in EC and smooth muscle cells (SMC) from the same specimen of fetal bovine aorta. 2. The basal adenylate cyclase activities of EC and SMC did not differ significantly (18.9 +/- 0.8 and 21.4 +/- 1.7 pmol/mg protein per min, n = 10, respectively). 3. The adenylate cyclase of EC responded dramatically to catecholamines, with the ED50 value for isoproterenol being 0.036 mu mol/L, and was also more sensitive to calcitonin gene-related peptide than that of SMC. 4. The adenylate cyclase of SMC was more sensitive to prostaglandins (with the ED50 for PGI2 being 0.024 mu mol/L) and glucagon than that of EC, and responded modestly to catecholamines and was almost selectively sensitive to beta1-adrenoceptor agonists. 5. Maximum responses of adenylate cyclase to F-, guanosine 5'-o-(3-thiotriphosphate) and forskolin were greater in SMC than in EC. 6. Based on these findings, it was concluded that EC and SMC differed significantly in adenylate cyclase responsiveness to agonists including hormones, prostaglandins, peptides and substances which may modify the effects of G proteins, although they shared a common developmental origin. Presumably, beta-adrenoceptor agonists in EC and prostaglandins in SMC may appear to play an important role in cellular functions which are mediated by increases in cAMP.

Adenine↗
PubMed1995

Relation between left ventricular shape and Doppler filling parameters in patients with left ventricular dysfunction secondary to coronary artery disease.

Left ventricular (LV) shape is an independent predictor of exercise capacity in patients with systolic LV dysfunction. Recent studies suggest that end-systolic LV shape is related to the generation of restoring forces during contraction that facilitate filling at lower LV pressure during subsequent diastole. To test the hypothesis that preservation of a more elliptical LV shape would be associated with a distribution of diastolic inflow characterized by increased early relative-to-late filling, 32 outpatients with coronary artery disease and ejection fraction < 40% underwent quantitative 2-dimensional and Doppler echocardiography. LV volumes, ejection fraction, and eccentricity index were measured as were standard Doppler indexes of LV filling. Simple and multiple linear regression models were used to examine relations between LV shape and Doppler measurements. LV eccentricity at end-systole correlated strongly with the Doppler atrial filling fraction (r = -0.670; p < 0.001) and the ratio of early-to-late flow velocity integrals (r = 0.648; p < 0.001). No other 2-dimensional echocardiographic variable was significantly correlated with any other Doppler index of LV filling. Thus, LV shape at end-systole appears to be an important determinant of diastolic filling patterns. In patients with systolic LV dysfunction, preservation of a more elliptical chamber is associated with a diastolic inflow pattern characterized by increased early relative-to-late diastolic filling.

Aged↗
PubMed1995

Estimation of EDRF and nitric oxide release using [3H]GTP-labeled human platelets.

We have developed a new bioassay for endothelium-derived relaxing factor (EDRF) or nitric oxide (NO) using human [3H]guanosine triphosphate (GTP)-labeled platelets. The labeled platelets were preincubated with isobutyl-methylxanthine and co-cultured with endothelial cells and the [3H]cyclic guanosine monophosphate (cGMP) formed was isolated by ion-exchange chromatography. Endothelial cells, either in monolayer cells or in suspension, increased platelet cGMP accumulation dose-dependently, a significant increase being detected with 5000 endothelial cells or more/assay when suspended cells were used. Co-culturing with the same number of skin fibroblasts failed to elevate platelet cGMP. Preincubation of endothelial cells with bradykinin and superoxide dismutase (SOD) synergistically potentiated the increase in platelet cGMP, but was attenuated by Nomega-nitro-L-arginine, with partial restoration by L-arginine but not by D-arginine. These compounds, however, did not affect cGMP accumulation by sodium nitroprusside. Moreover, preincubation of the labeled platelets with the NO synthase inhibitor prior to EDRF assay had no effect. We conclude that [3H]GTP-labeled platelets could provide a simple, sensitive and specific bioassay for estimating EDRF or NO release.

Animals↗
PubMed1995

What effect does controlling platelets have on atherosclerosis?

Platelets play important roles for hemostasis with activated platelets adhering to the injured vessel wall to initiate platelet aggregation. At the same time, our study revealed the cytotoxic effect on endothelial cells characterized by an increase of intracellular Ca++ and a decrease of EDRF production, which may cause plasmal infiltration including blood cells and lipids. Our clinical survey using a small dose of aspirin as an antiplatelet therapy clearly demonstrated its suppressive effect on platelet aggregation and its favorable effect on fibrinolysis. These data suggest that the therapeutic effect of aspirin in vascular disease could be applied to the prevention of thrombus formation and the protection of endothelial cells from the cytotoxic effect of activated platelets.

Adenylyl Cyclases↗
PubMed1995

Effect of nifedipine on cyclic GMP turnover in cultured coronary smooth muscle cells.

We investigated the effects of nifedipine on cyclic GMP turnover and the pertinent enzyme activities in cultured coronary smooth muscle cells (SMC). Nifedipine at high concentrations slightly decreased basal soluble guanylate cyclase activity and inhibited the action of sodium nitroprusside (SNP) but had no effect on the particulate form of the enzyme. In contrast, nifedipine inhibited cyclic GMP hydrolysis by directly inhibiting the partially purified calmodulin-stimulated isoform of phosphodiesterase (type I PDE) with IC50 of 4.2 microM. Nifedipine > or = 1.0 microM enhanced cyclic GMP accumulation in response to 1.0 microM SNP, although nifedipine alone exerted no influence on cyclic GMP levels. Enhancement of cyclic GMP accumulation by nifedipine in response to SNP was not affected by BAY K 8644, a calcium channel agonist. These properties may be shared by other dihydropyridines since nicardipine and nisoldipine also inhibited type I PDE with similar IC50. However, some other structurally unrelated calcium channel blockers, diltiazem and verapamil, had little effect on cyclic nucleotide hydrolysis or on cyclic GMP accumulation in response to SNP. Nifedipine may synergistically enhance cyclic GMP accumulation in response to nitric oxide (NO)-releasing agents by directly inhibiting type I PDE in coronary SMC. Such effects of nifedipine may partly contribute to coronary vasodilation and prevention of coronary spasm in patients with ischemic heart disease.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

TNF modulates endothelial properties by decreasing cAMP.

Tumor necrosis factor-alpha (TNF-alpha), a monokine that contributes to vascular dysfunction accompanying the host response to gram-negative sepsis, has been shown to increase vascular permeability in vivo and to diminish the barrier function of cultured endothelial cell (EC) monolayers. The studies reported here indicate that a mechanism through which TNF alters EC barrier function involves a reduction in intracellular adenosine 3',5'-cyclic monophosphate (cAMP) content, due in part to increased cyclic nucleotide phosphodiesterase (CNPDE) activities. TNF increased the diffusional transit of [3H]sorbitol, [3H]inulin, and 125I-labeled albumin across confluent bovine aortic EC monolayers. This effect of TNF was both time and dose dependent and occurred in parallel with a fall in EC cAMP. cAMP analogues, such as dibutyryl cAMP (DBcAMP), prevented TNF-induced perturbation of EC barrier function. TNF also mediated another important alteration in the EC phenotype, in that both mRNA and activity of the anticoagulant cofactor thrombomodulin were reduced after exposure of EC to TNF and were normalized by the addition of DBcAMP. EC monolayers exposed to TNF-alpha showed increased cAMP levels when exposed to 3-isobutyl-1-methylxanthine, a nonspecific CNPDE inhibitor. Ion exchange chromatography of cytosol derived from TNF-treated EC consistently showed an approximately 245% increase in phosphodiesterase (PDE) IV (high-affinity, cAMP-specific PDE) activity as identified by rolipram inhibition. PDE II activity was increased by 150% after TNF-alpha treatment of early passage EC, which was identified by cGMP-activated hydrolysis of cAMP. Western and Northern analyses, as well as activity studies, revealed that TNF treatment did not change the amount of PDE IV protein or mRNA but rather increased the specific activity of the isozyme, suggesting that a posttranslational modification had occurred. These data indicate that activation of EC CNPDE activity and decreased intracellular cAMP may represent a mechanism by which TNF increases EC permeability and promotes a procoagulant EC phenotype.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

The Maine and Vermont three-decade studies of serious mental illness. I. Matched comparison of cross-sectional outcome.

BACKGROUND: This study compared long-term outcome of serious mental illness in two states using a matched design to assess psychiatric rehabilitation programmes; Vermont subjects participated in a model psychiatric rehabilitation programme, while the Maine group received more traditional care. METHOD: Maine and Vermont subjects (n = 269) were matched by age, sex, diagnosis, and chronicity. Demographic, illness, and life history information were abstracted from hospital records by clinicians blind to outcome. DSM-III criteria were applied retrospectively. Outcome was assessed by clinicians blind to history. RESULTS: Vermont subjects alive at follow-up (n = 180) were more productive (P < 0.0009), had fewer symptoms (P < 0.002), better community adjustment (P < 0.001) and global functioning (P < 0.001) than Maine subjects (n = 119). CONCLUSIONS: Outcome differences may be due to Vermont's model programme and a policy of allowing an earlier opportunity for community life.

Activities of Daily Living↗
PubMed1995

The Maine and Vermont three-decade studies of serious mental illness. II. Longitudinal course comparisons.

BACKGROUND: This paper supplements the cross-sectional outcome comparisons of the companion paper by providing a brief account of the longitudinal courses of the Maine and Vermont samples across several outcome domains. METHOD: A Life Chart method was used to document changes in individual lives over the domains of residence, work, income source, and use of community resources over a 20-year period. Reliability studies between states were conducted. RESULTS: Throughout much of the period, more Vermont subjects lived independently, were working, and were less likely to use community resources compared to Maine subjects. CONCLUSIONS: Differences in both policies and programmes contributed to course differences between the groups. System characteristics that may lead to better outcomes are discussed.

Activities of Daily Living↗
PubMed1994

Measurement of user performance and attitudes assists the initial design of a computer user display and orientation method.

OBJECTIVE: The objective of our study was to assess the acceptability of a proposed user interface to visually interfaced computer-assisted anesthesia record (VISI-CAARE), before the application was begun. The user interface was defined as the user display and its user orientation methods. METHODS: We designed methods to measure user performance and attitude toward two different anesthesia record procedures: (1) the traditional pen and paper anesthetic record procedure of our hospital, and (2) VISI-CAARE. Performance measurements included the reaction speed (identifying the type and time of an event) and completion speed (describing the event). Performance also included accuracy of the recorded time of the event and accuracy of the description. User attitude was measured by (1) the physician's rating on a scale of 0 to 9 of the potential usefulness of computers in anesthesia care; (2) willingness to use the future application in the clinical environment; and (3) user suggestions for change. These measurements were used in a randomized trial of 21 physicians, of which data from 20 were available. RESULTS: After exposure to VISI-CAARE, the experimental subjects' ranking of computer usefulness in anesthesia care improved significantly (4.2 +/- 1.1 to 7.6 +/- 1.5, p = 0.0001), as did controls' (5.2 +/- 2.6 to 8 +/- 1.5, p = 0.0019). All the volunteers were willing to try the proposed prototype clinically, when it was ready. VISI-CAARE exposure was associated with faster and more accurate reaction to events over the traditional pen and paper machine, and slower and more accurate description of events in an artificial mock setting. VISI-CAARE 1.1 demonstrated significant improvements in both reaction speed and completion speed over VISI-CAARE 1.0, after changes were made to the user display and orientation methods. CONCLUSION: With graphic user interface prototyping environments, one can obtain preliminary user attitude and performance data, even before application programming is begun. This may be helpful in revising initial display and orientation methods, while obtaining user interest and commitment before actual programming and clinical testing.

Anesthesia↗
PubMed1994

Atrial natriuretic peptide reduces cyclic AMP by activating cyclic GMP-stimulated phosphodiesterase in vascular endothelial cells.

Bovine aortic endothelial cells contain cyclic GMP-stimulated phosphodiesterase (PDE) regulating intracellular cyclic AMP and cyclic GMP levels. To investigate the roles of this PDE isoform for cyclic AMP hydrolysis in intact endothelial cells (EC), we used an adenine prelabeling method to determine cyclic AMP accumulation in response to agents that might produce effects that increase cyclic GMP levels. Atrial natriuretic peptide (ANP), which dramatically increased cyclic GMP accumulation, reduced cyclic AMP in cultured EC from bovine aorta with or without addition of L-isoproterenol (L-ISO), whereas sodium nitroprusside (SNP) and 8-bromo cyclic GMP had no effect. The reduction in cyclic AMP by ANP was dose dependent (> or = 1.0 nM) and rapid (significant reduction was induced in < or = 15 s) and was abolished when EC were preincubated with 3-isobutyl-1-methylxanthine (IBMX) and HL-725, both nonselective PDE inhibitors. ANP had no effects on adenylate cyclase activity, nor any direct effects on the activities of partially purified cyclic GMP-stimulated PDE isoform or cyclic AMP-specific isoform. However, cyclic AMP hydrolyzing activities of EC were enhanced when EC were pretreated with 0.1 microM ANP. ANP activates cyclic GMP-stimulated PDE and induces reduction of cyclic AMP accumulation in intact EC, which may modify cyclic GMP-dependent endothelial function involved in ANP.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Development and characterization of macrophage hybridomas derived from murine peritoneal exudate cells.

Mouse macrophage (Mphi) hybridoma clones were generated by somatic cell hybridization of myeloma X63 cells (H-2d) with C57BL/6 (H-2b) peritoneal exudate cells elicited with a streptococcal preparation, OK432, or thioglycollate medium. Although they hardly adhered to plastic dishes and could not be morphologically distinguished from parental X63 tumor cells, the clones retained Mphi characteristics. These included phagocytosis and production of lysozyme and nonspecific esterase, suggesting that they were hybridomas derived from Mphi. Some of them expressed various levels of Ia antigen and Fc receptor. Because they induced proliferation of T cells from Balb/c mice but not those from C57BL/6 mice, the Ia antigen of Mphi hybridoma was assumed to be derived from peritoneal Mphi. The level of proliferation induction was correlated to the level of Ia antigen expression. Several clones produced a factor that cytostatically inhibited growth of murine mammary carcinoma and was serologically identified with arginine deiminase.

Animals↗
PubMed1994

Longitudinal pulmonary function losses in Vermont granite workers. A reevaluation.

Previous studies have suggested that excessive losses of FVC and FEV1 were occurring in Vermont granite workers despite the fact that mean quartz levels existing in the industry were below the current OSHA standard of 100 micrograms/m3. We reexamined these losses in granite workers over an 8-year period, testing the workforce biennially from 1979 to 1987. All workers, including stone shed, quarry, and office, were offered forced spirometry using a 10-L water-sealed spirometer (Collins). In the peak year of participation (1983), 887 workers out of a total of approximately 1,400 were tested. Estimates of longitudinal loss were based on 711 workers who participated in at least three of the surveys. The mean age of this group was 42.9 years, and the mean years employed was 19.3 years; 21.4 percent were non-smokers (NS), 34.2 percent were ex-smokers (ES), and 44.4 percent were current smokers (CS). Average annual losses of FVC were 0.018 (SD = 0.056) L (CS, 0.025 L; NS, 0.006 L: and ES, 0.016 L). Average annual losses of FEV1 were 0.030 (SD = 0.041) L (CS, 0.038 L; NS, 0.020 L; and ES, 0.027 L). Analysis of covariance indicated that losses were related to the initial values for FVC or FEV1, height, age, and smoking status. After adjusting for these variables, the losses of both FVC and FEV1 were not correlated with years employed in the granite industry. No significant differences existed in the loss of FVC or FEV1 in categories of workers exposed to different levels of granite dust, eg, office, quarry, and stone shed workers. The annual losses of pulmonary function were significantly smaller than those estimated previously, which were 0.070 to .080 L in FVC, and 0.050-0.070 L in FEV1. We conclude that dust levels in the Vermont granite industry, which have been in conformance with OSHA permissible exposure limits, do not accelerate pulmonary function loss.

Adult↗
PubMed1993

Ethanol modulates cyclic GMP metabolism in cultured coronary smooth muscle cells.

The authors tested the hypothesis that ethanol or its metabolite acetaldehyde might interfere in cyclic guanosine monophosphate (GMP) metabolism in coronary smooth muscle cells. Ethanol at the physiologically relevant concentration of 4.0 mg/mL or more significantly decreased basal guanylate cyclase activity and inhibited activation of the enzyme by sodium nitroprusside (SNP) in cultured porcine coronary smooth muscle cells. Two isoforms of phosphodiesterase (PDE), cyclic GMP-specific form and calmodulin-stimulated form, were both inhibited by 12.0 mg/mL or more ethanol. Intact cell study revealed that although 12.0 mg/mL or more ethanol was needed to significantly decrease cyclic GMP accumulation in control cells, 4.0 mg/mL or more ethanol significantly inhibited the increase of cyclic GMP accumulation induced by 1 microns SNP. Acetaldehyde showed similar effects, but the concentrations involved were more than physiological. Thus, ethanol may decrease cellular cyclic GMP levels and attenuate cyclic GMP accumulation in response to SNP in coronary smooth muscle cells by inhibiting soluble guanylate cyclase activity at physiologically relevant concentrations.

Acetaldehyde↗
PubMed1992

Alteration of adenine nucleotide metabolism in coronary smooth muscle cells by activated platelets.

Cultured porcine coronary smooth muscle cells were preloaded with [3H]adenine and the inside and outside radioactive metabolites of the cells were analyzed following exposure to activated platelets. Incubation of the cells with human platelets activated by collagen enhanced intracellular conversion of ATP to ADP and caused dose- and time-dependent increase in radioisotopic release, mainly adenosine. Isolation of cyclic AMP revealed decreased cyclic AMP levels in the treated cells, both intra- and extracellularly. Of the substances released by the activated platelets, thromboxane A2 and serotonin enhanced radioisotopic release. The modulation of adenine metabolism by the activated platelets was preceded by increase in accumulation of inositol phosphates in the cells and was prevented by Iloprost (1 microM), a prostacyclin analog, cilostamide (10 microM), a cyclic AMP-specific phosphodiesterase inhibitor, or dibutyryl cyclic AMP (1 mM). Nifedipine showed only minor preventive effect. The agents which elevate cyclic AMP accumulation also attenuated phosphoinositide hydrolysis, whereas nifedipine had no effect. These results suggest that activated platelets may stimulate adenine metabolism in coronary smooth muscle cells, presumably due to activation of phosphoinositide turnover resulting in increased intracellular calcium. Enhanced adenosine release from the cells exposed to activated platelets may be a compensatory mechanism to prevent further platelet aggregation and contraction of coronary smooth muscle.

Adenine↗