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Biomedical subjects

T Ashikaga

Publications and source records attributed to T Ashikaga.

At least 19 recordsLinked to original sources
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

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

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↗
PubMed1992

Inhibition of platelet aggregation by prostacyclin is attenuated after exercise in patients with angina pectoris.

We tested whether alteration of platelet sensitivity to prostacyclin (PGI2) is involved in the activation of platelets induced by exercise in patients with stable angina. Twenty patients and 20 control subjects underwent treadmill testing. Blood samples were obtained before and immediately after exercise for plasma thromboxane B2 (TXB2) and 6-keto-PGF1 alpha (6kP) assays and platelet aggregation studies. Dose-response curves for platelet aggregation to collagen were obtained in the presence and absence of 1 nmol/L PGI2 to quantify the antiaggregation effects of PGI2. At rest, platelet aggregation by collagen was enhanced in the patients. However, platelets were more sensitive to exogenous PGI2, apparently associated with lower plasma 6kP levels in the patients. After exercise, plasma TXB2 levels increased in the patients but not in the control subjects. Plasma 6kP levels remained unchanged and platelet sensitivity to PGI2 decreased in the patients whereas these values increased in the control subjects. The exercise-induced changes in platelet sensitivity to PGI2 correlated with those of platelet adenylate cyclase activity in response to 1 nmol/L PGI2 (r = 0.787, p less than 0.01). Thus impaired sensitivity of platelets to PGI2, in addition to the reduced response of prostanoid secretion, might be relevant to the platelet activation associated with exercise in patients with stable angina.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Radiographic abnormalities in Vermont granite workers exposed to low levels of granite dust.

The issue of whether low levels of granite dust exposure lead to radiographic abnormalities after a lifetime of exposure has not been settled. In 1983, we carried out a radiographic survey of the Vermont granite industry, consisting of quarry and stone shed workers who had been exposed to the low dust levels prevailing in the industry since 1938 to 1940. Films were read by three "B" readers, using the ILO classification system, which requires the identification of both rounded and irregular opacities, as well as combinations of both. X-ray films were taken of 972 workers, out of a total work force of approximately 1,400. Of these films, 28 (3 percent) were interpreted by either two or three of the three readers as showing abnormalities consistent with pneumoconiosis. Only seven films (or 0.7 percent of the entire cohort) showed nodular or rounded opacities of the type typically seen in uncomplicated silicosis. The remainder of the abnormal x-ray films showed irregular opacities, largely in the lower lung zones, which are of uncertain significance, but may be related to heavy cigarette smoking and aging, and possibly dust inhalation. In addition, total gravimetric dust concentrations in the workplace were measured; 417 respirable-size mass samples showed concentrations of 601 micrograms/cu m +/- 368 micrograms/cu m. Using previously published estimates of 10 percent quartz in granite dust, the average quartz concentration was 60 micrograms/cu m. Twelve percent of the samples exceeded 100 micrograms/cu m, the current OSHA standard for quartz. We conclude that control of quartz exposure in the Vermont granite industry to levels which are on average less than the current OSHA standard has essentially eliminated definite radiographic changes of silicosis. The significance of the irregular opacities in the lower lung zones seen on a majority of the 28 x-ray films judged to be abnormal is not clear.

Adult↗
PubMed1990

Antiplatelet therapy for atherosclerotic disorders.

Recent studies have revealed the important roles of platelets in atherogenesis via vascular injury. Our in vivo and in vitro studies clearly demonstrate that activated platelets directly inflict injury to vascular endothelial cells, which is associated with a decrease in intracellular cyclic AMP levels in vascular tissues. Antiplatelet therapy is clinically important not only for the prevention of thrombotic episodes but also for the prevention of vascular injury and atherosclerosis. A small dose of aspirin (80 mg) induces clinically hypoaggregativeness of platelets with concomitantly decreased levels of thromboxane A2 in plasma. Our clinical study involving more than 3 years of treatment with small doses of aspirin demonstrated favorable therapeutic effects characterized by hypoaggregation of platelets and increased levels of cAMP and 6-keto PGF1 alpha in plasma which will aid in the prevention of atherosclerosis.

Animals↗
PubMed1989

Utilization of a murine model to optimize volume and dwell time of intraperitoneal cisplatin.

The pharmacokinetics of intraperitoneal (ip) cisplatin were investigated in a murine model. Groups of six animals were studied at initial cisplatin concentrations (Ci) of 50, 100, 200, and 400 micrograms/ml, and at injection volumes (V) of 0.5, 1, 2, and 4 ml. For each Ci and V, four dwell times (Dt) between 1.5 and 120 min were studied. At 180 min mice were killed and five tissues (heart, kidney, liver, bowel, and peritoneum) were obtained for platinum measurement. Platinum recovered from the peritoneal cavity at the end of the dwell time and platinum tissue levels were determined by a radioactive tracer assay using Pt 195m-labeled cisplatin. A total of 384 mice were studied. The permeability times the effective surface area product (pS) was found to be independent of Ci, V, and Dt. Platinum tissue levels were proportional to absorbed dose. As the ratio of platinum tissue level to absorbed dose is constant, it is not possible to change Ci, V, nor Dt to minimize toxicity from a given absorbed dose. This study suggests that the therapeutic index of an individual intraperitoneal cisplatin treatment will not be changed by modifying Ci, V, nor Dt.

Absorption↗