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Biomedical subjects

Y Nakashima

Publications and source records attributed to Y Nakashima.

At least 289 records · Page 16Linked to original sources
PubMed1994

Effect of low dose aspirin on augmented plasminogen activator inhibitor type 1 activity in patients with permanent pacemakers.

To clarify the activity states of coagulation and fibrinolysis in patients with a permanent pacemaker, we studied 29 patients more than 4 months after operation. They were divided into a single pacemaker lead group (S, n = 14) and a double lead group (D, n = 15). Prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III, tissue-type plasminogen activator (tPA) activity, plasminogen activator inhibitor type-1 (PAI-1) activity, and platelet aggregation were measured and compared to those in an age-matched control group (C, n = 7). The effects of low dose aspirin (81 mg/day) in the patients (n = 21) were also studied 2 weeks after administration. PAI-1 activity in groups S and D was significantly higher than that in the group C (53.5 +/- 36.5, 86.8 +/- 59.2 ng/mL vs 19.4 +/- 7.2 ng/mL; P < 0.01 and P < 0.005). Platelet aggregation induced by collagen was slightly higher in groups S and D than group C. Other parameters were not significantly different. In the patients, low dose aspirin significantly suppressed collagen induced platelet aggregation (71.8 +/- 20.3% vs 41.7 +/- 28.3%; P < 0.005), but not PAI-1 activity. tPA activity was increased significantly by the low dose aspirin administration (3.94 +/- 1.85 ng/mL vs 2.48 +/- 1.19 ng/mL; P < 0.005). Thus, PAI-1 activity in patients with a permanent pacemaker is elevated, and the activity is not suppressed by low dose aspirin unlike the platelet aggregation.

Adult↗
PubMed1994

Rate-limiting steps in activation of cardiac Cl- current revealed by photolytic application of cAMP.

Single myocytes were obtained from guinea-pig ventricles, and the catecholamine-induced Cl- current (ICl) was recorded by the patch-clamp method combined with the use of caged adenosine 3',5'-cyclic monophosphate (cAMP) and the concentration jump technique. The rapid bath application of isoprenaline was followed by a marked latency of approximately 1.7 s before a sigmoidal onset of the ICl activation, while the photolysis of caged cAMP was followed by no measurable latency. The ICl conductance was increased by increasing the concentration of caged cAMP with a threshold of approximately 5 microM and a one-half effective concentration of 25 microM. On the other hand, the rate of the activation increased in proportion to the logarithm of the concentration of caged cAMP. When the ultraviolet flash was repeated or the myocytes were pretreated with either forskolin, 3-isobutyl-1-methylxanthine, or okadaic acid, the rate of the ICl activation accelerated, and the whole time course of the ICl activation became monoexponential. These findings suggest that both the production of cAMP and reactions on the multiple phosphorylation sites of the channel protein are major rate-limiting steps in the ICl activation.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Wavelength index: a predictor of the response to disopyramide in paroxysmal lone atrial fibrillation.

We investigated whether the new parameter wavelength index could predict the response to chronic disopyramide therapy in patients with paroxysmal atrial fibrillation (AF). Twenty-seven patients with AF underwent electrophysiologic studies and the wavelength index was determined before and after intravenous administration of disopyramide. Then all patients were treated with oral disopyramide for 6 months. In 17 patients, AF was eliminated (group A), while it persisted in another 10 patients (group B). The ratio of the wavelength index before and after intravenous disopyramide was higher in group A than in group B. Thus, the wavelength index proved useful for predicting the response of AF to disopyramide.

Adult↗
PubMed1994

Increase in intracellular calcium ion in smooth muscle cells induced by low-density lipoprotein.

It was investigated whether low-density lipoprotein (LDL) had effects on intracellular Ca2+ concentration in the smooth muscle cell (SMC). LDL promoted SMC proliferation and increased intracellular Ca2+ by a two-phase pattern, an initial peak and a following plateau. Each phase was suppressed by treatment with ryanodine or extracellular Ca(2+)-free buffer. This increase in intracellular Ca2+ was also suppressed by anti-LDL receptor antibody. Moreover, inositol triphosphate (IP3) was elevated with short-term LDL treatment. Since SMC proliferation is the most important event in atherosclerosis and LDL is one of the main risk factors, it was concluded that LDL might trigger SMC proliferation by increasing IP3 and intracellular Ca2+ through LDL receptor.

Animals↗
PubMed1994

ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree.

Initial description of apolipoprotein (apo) E-deficient transgenic mice demonstrated the development of severe hypercholesterolemia due to probable delayed clearance of large atherogenic particles from the circulation. Examination of these mice demonstrated foam cell accumulation in the aortic root and pulmonary arteries by 10 weeks of age. In the present study, the animals were fed either chow or a high-fat, Western-type diet and examined at ages ranging from 6 to 40 weeks. Gross examination by dissection microscopy revealed a predilection for development of lesions in the aortic root, at the lesser curvature of the aortic arch, the principal branches of the aorta, and in the pulmonary and carotid arteries. Monocyte attachment to endothelial cells was observed by light and electron microscopic examination at 6 weeks, the earliest time point examined. Foam cell lesions developed as early as 8 weeks, and after 15 weeks advanced lesions (fibrous plaques) were observed. The latter consisted of a fibrous cap containing smooth muscle cells surrounded by connective tissue matrix that covered a necrotic core with numerous foamy macrophages. Mice fed the Western-type diet generally had more advanced lesions than those fed a chow diet. The apoE-deficient mouse contains the entire spectrum of lesions observed during atherogenesis and is the first mouse model to develop lesions similar to those in humans. This model should provide numerous opportunities to study the pathogenesis and therapy of atherosclerosis in a small, genetically defined animal.

Animals↗
PubMed1994

Atrioventricular (AV) nodal reentry associated with 2:1 infra-His conduction block during tachycardia in a patient with AV nodal triple pathways.

We report a patient with atrioventricular (AV) nodal reentry in which a 2:1 infra-His conduction block was demonstrated during tachycardia. The electrocardiogram (ECG) at the time of attack showed two types of supraventricular tachycardias. The first type was a narrow QRS tachycardia associated with 1:1 AV conduction at a rate of 170 beats/minute. The second type was a narrow QRS associated with 2:1 AV block at a rate of 85 beats/minute. Electrophysiological study revealed AV nodal reentry based on AV nodal triple pathways. The AV conduction curve obtained by atrial premature stimulation showed two discontinuous points at two different basic cycle lengths (500 msec, 400 msec) and from two different pacing sites (high right atrium, distal coronary sinus). These two types of tachycardias were induced by both atrial premature and overdrive stimulation. In the first type, the impulse conducted in the slow pathway antegradely with 1:1 AV conduction and in the fast pathway retrogradely. In the second type, the impulse was conducted beat-to-beat by either a slow pathway or a very slow pathway antegradely with the retrograde limb being the fast pathway and 2:1 infra-His conduction block. Only when the impulse was conducted in the slow pathway antegradely was the infra-His conduction block observed during the tachycardia. The tachycardia in this patient was drug refractory and controlled by an anti-tachycardia pacemaker.

Aged↗
PubMed1994

The design of oral sustained-release theophylline dosing after conversion from intravenous to oral therapy.

We studied the design of oral sustained-release theophylline dosing after conversion from constant aminophylline infusion. Twelve children with bronchial asthma (9 boys and 3 girls) were evaluated in this study. Each patient received a constant intravenous administration of aminophylline for 4-10 days. Three hours after conversion from constant aminophylline infusion, they received oral sustained-release theophylline twice daily at 12-hour intervals. Blood samples were obtained at least once during the aminophylline infusion, just before conversion from the aminophylline infusion, and 0, 3 and 6 hours, and 4-5 days after administering oral theophylline. Pharmacokinetic parameters were estimated using the serum theophylline concentrations that were obtained during constant aminophylline infusion. These estimates of pharmacokinetic parameters were used to predict the serum theophylline concentrations during oral theophylline therapy. Predicted serum theophylline concentrations using individual pharmacokinetic parameters were fitted with actual measured values in this study. When switching a patient from intravenous aminophylline to sustained-release oral theophylline, the use of Bayesian analysis of serum theophylline concentration values obtained during intravenous therapy works well in predicting serum theophylline concentrations and in determining oral dosages that maximize the drug's effectiveness.

Administration, Oral↗
PubMed1994

C-type natriuretic peptide stimulates catecholamine synthesis through the accumulation of cyclic GMP in cultured bovine adrenal medullary cells.

We examined the effects of C-type natriuretic peptide (CNP) on cyclic GMP production and catecholamine synthesis in cultured bovine adrenal medullary cells. 1) CNP increased intracellular cyclic GMP content in a concentration-dependent manner (10-1000 nM). 2) The cyclic GMP production induced by 1 microM CNP reached a 200-fold increase, and the effect of CNP was most potent among the natriuretic peptide family. 3) The CNP-induced cyclic GMP production was attenuated by endothelin (1 microM) and angiotensin II (0.1-1 microM). 4) When the cells were cultured with hypertonic NaCl medium, the CNP-induced cyclic GMP production was potentiated in a time (1-4 days)- and concentration (25-100 mM)-dependent manner. 5) CNP stimulated the synthesis of 14C-labeled catecholamines from [14C] tyrosine but not from [14C] dopa. The stimulatory effect of CNP on the 14C-labeled catecholamine synthesis was observed at the concentrations of 100 to 100 nM. 6) 8-Bromo cyclic GMP, a membrane-permeable cyclic GMP analog, and sodium nitroprusside, an activator of soluble guanylate cyclase, also stimulated the synthesis of 14C-labeled catecholamines from [14C]tyrosine, whereas C-ANF, a specific ligand for the ANP-C (clearance) receptor that does not increase cyclic GMP content, failed to stimulate the synthesis of 14C-labeled catecholamines. 7) CNP (1 microM) as well as 8-bromo cyclic GMP and sodium nitroprusside increased the activity of tyrosine hydroxylase in the cells. These results suggest that in the adrenal medulla, CNP is a potent agonist for cyclic GMP production, which is modulated by endothelin, angiotensin II and the hypertonic NaCl condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1994

[Expression of PDGF-A and -B in human coronary atherosclerotic lesion: immunohistochemical and in situ hybridization study].

We studied the role of platelet-derived growth factor (PDGF) on the development of atherosclerosis of human coronary arteries of 63 autopsied cases. Smooth muscle cells in fibrocellular intimal thickening lesion showed no significant immunohistochemical reaction of antibodies for PDGF-A or PDGF-B or PDGF-receptor. In atherosclerotic lesions, foam cells derived from macrophages and smooth muscle cells showed intense immunohistochemical reaction with antibodies of PDGF-B and PDGF-receptor, but not with that of PDGF-A. By in situ hybridization, no significant signals of PDGF-A or PDGF-B or PDGF-receptor were demonstrated in proliferating intimal smooth muscle cells in fibrocellular intimal thickening lesions. Uncomplicated atherosclerotic lesions expressed significant amount of m-RNA of c-sis protooncogene and PDGF-B receptor in foam cells. However, no significant signals of PDGF-A were observed in uncomplicated atherosclerotic lesions. These results suggest that foam cells-producing PDGF-B play an important role for the progression of atherosclerotic lesions in human coronary arteries.

Coronary Artery Disease↗
PubMed1994

[Left atrial isolation for chronic atrial fibrillation caused by mitral valvular stenosis and regurgitation].

Surgical isolation of the left atrium was performed for the treatment of chronic atrial fibrillation secondary to mitral valvular disease in a 65-year-old woman who underwent mitral valvular replacement. Left atrial isolation was simple procedure, prolonging the usual paraseptal atriotomy toward the both mitral valvular commissures anteriorly and posteriorly. The incision was conducted two centimeters apart from the mitral valve annulus, and cryoablation was added at the edges to ensure isolation of the residual left atrium. We suggest performing this simple procedure in patients with chronic atrial fibrillation undergoing mitral valvular replacement, in whom correction of irregular beat and compromised hemodynamics can be obtained.

Aged↗
PubMed1994

Effect of sustained release diltiazem (Diltiazem-R) in patients with stable effort angina.

Ca++-antagonist is effective not only for variant angina but also for effort angina. The effects of sustained release diltiazem (diltiazem-R) and beta 1-blocker (atenolol) on exercise tolerance were studied in seven patients with stable effort angina in a cross over trial. Diltiazem-R (100mg) or atenolol (50mg) was given once a day, each treatment period lasting for two weeks after a two-week control period. The treadmill exercise test was performed on the last day of each protocol. Both diltiazem-R and atenolol decreased heart rate at rest and the decrease with atenolol was greater than that with diltiazem-R. The systolic blood pressure was unchanged at rest by both drugs. At maximal work levels, atenolol decreased the heart rate and pressure rate product significantly but diltiazem-R did not. Both diltiazem-R and atenolol significantly prolonged the exercise time (average 137 and 165 seconds respectively), time to onset of 1mm ST depression (240 and 288 seconds respectively). There was no significant difference in exercise tolerance between diltiazem-R and atenolol. These findings suggest that diltiazem-R, a sustained release Ca++-antagonist, provides beneficial effects in patients with stable effort angina.

Angina Pectoris↗
PubMed1993

Increased expression of membrane-associated phospholipase A2 shows malignant potential of human breast cancer cells.

BACKGROUND: Recently, the authors reported that membrane-associated phospholipase A2 (M-PLA2) was one of the acute phase reactants and increased in serum of patients with various malignant tumors. METHODS: M-PLA2 concentrations in tissue specimens from 78 breast cancers, 16 benign breast tumors, and 10 normal breast tissues were determined by a specific radioimmunoassay recently developed. Immunohistochemical staining was performed on all specimens by the avidin-biotin-peroxidase method. RESULTS: Tissue levels of M-PLA2 concentration were significantly higher in breast cancer than in benign breast tumor or normal breast tissue (P < 0.01). Correlation analyses between the tissue concentration of M-PLA2 and clinicopathologic factors showed that tissue M-PLA2 levels were significantly higher in patients with skin or muscle invasion, vessel involvement, and distant metastasis than in those without. In addition, this enzyme concentration was significantly greater in scirrhous carcinoma than in papillotubular or solid-tubular carcinoma. No association was found between M-PLA2 concentration and steroid hormone receptor status. Immunohistochemically, M-PLA2 was preferentially stained in the invading zone of breast cancer tissues, especially in scirrhous carcinoma. Patients with breast cancer with low levels of M-PLA2 showed significantly longer overall survival and disease-free survival compared with those with high levels of this enzyme at the cutoff point of 50 ng/100 mg protein. The combination of estrogen receptor status with M-PLA2 concentration could be a powerful prognostic factor in predicting such survival rates. CONCLUSIONS: M-PLA2 is closely related to the malignant potential of breast cancers, and the M-PLA2 contents in breast cancer tissues could be a new valuable prognostic factor, other than the hormone receptor, in delineating the status of human breast cancer.

Breast↗
PubMed1993

Tumor necrosis factor alpha-induced alteration of glycosaminoglycans in cultured vascular smooth-muscle cells.

We studied alteration of glycosaminoglycans (GAGs) induced by recombinant human tumor necrosis factor alpha (rhTNF alpha) in vascular smooth-muscle cells from bovine aorta in a culture system. It was found that rhTNF alpha at 10 ng/ml and below significantly increased the incorporation of [35S]sulfate (35S) but conversely decreased that of [3H]glucosamine (3H) into GAGs in the trypsinate fraction of the cell layer after a 24-h incubation. These results suggested that rhTNF alpha reduced the formation and/or the anchorage of sugar chains in the cell layer but enhanced their sulfation in whole GAG synthesis by the cells. In results, the ratio of 35S to 3H in the GAGs was markedly increased. This increase occurred after 24 h and longer when the cells were treated with 1.0 ng/ml rhTNF alpha. The TNF alpha-induced alteration of the incorporation of both 35S and 3H was completely blocked by anti-rhTNF alpha antibody. Other cytokines including recombinant human interleukin-1 beta and -6, and platelet-derived growth factor failed to alter the ratio of 35S to 3H in the GAGs of the trypsinate fraction of the cell layer. In cultured vascular endothelial cells from bovine aorta, however, rhTNF alpha at 1.0 ng/ml significantly decreased the incorporation of both 35S and 3H into GAGs of both the trypsinate fraction and the medium; the ratio of 35S to 3H was not changed. Characterization of GAGs in vascular smooth muscle cell trypsinate fraction revealed that rhTNF alpha at 10 ng/ml induced (i) no change of the incorporation of 3H in the hyaluronate fraction, (ii) a marked increase in the incorporation of 35S and no change of that of 3H in chondroitin sulfates (A plus C) fraction, (iii) a significant decrease in the incorporation of both 35S and 3H in the heparan sulfate fraction, and (iv) no change of the incorporation of 35S and a marked decrease in that of 3H in the dermatan sulfate fraction. In the medium, rhTNF alpha also induced various changes of GAGs. It was therefore concluded that TNF alpha may have a capacity of inducing a qualitative change of vascular smooth-muscle cell GAGs, which may be involved in the vascular pathology such as atherosclerosis.

Animals↗
PubMed1993

[Comparison of the casual serum triglyceride levels at health check-up with the values during fasting].

Since higher levels of serum triglycerides were frequently found during the UOEH physical check-up for employees and students in 1989, we analysed subjects with higher triglyceride levels and discussed ways of handling them. Blood sampling to determine serum lipids was done between 13:00-15:00. Of the total (males 1257, females 1267), 272 had higher serum triglyceride levels (over 200 mg/dl) (males 246, females 26) (1st TG). One hundred and twenty-one of the group with higher TG levels in the 1st examination were reevaluated by blood sampling the morning after overnight fasting (2nd TG). There was a significant positive correlationship between the TG levels from the 1st examination and those from the 2nd examination (r = 0.62, n = 121, P < 0.0001). The predictive value calculated from the equation between the TG in the first and second measurements was 341.7 mg/dl. There was a 14.9% rate of false negatives in subjects under 341.7 mg/dl on the first TG measurement. However, there were only 6.3% false negatives in the subjects under 250 mg/dl on the first TG measurement. Age, body mass index and serum cholesterol level were significantly higher in the group with the higher TG level on reevaluation (more than 160 mg/dl) than those in the group with the lower TG level on reevaluation (less than 160 mg/dl). We concluded from these results that the casual serum TG levels above 250 mg/dl might be a suitable cut off level in physical check-ups.

Adolescent↗
PubMed1993

Interleukin 6 stimulates the production of immunoreactive endothelin 1 in human breast cancer cells.

To investigate the potential regulation of endothelin 1 production in human breast cancer cells, we measured the release of immunoreactive endothelin 1 (ir-ET-1) from the MCF-7 and ZR-75-1 breast cancer cell lines in response to various agents including estrogen and tamoxifen as well as several cytokines. ir-ET-1 was detected in conditioned medium of MCF-7 cells and ZR-75-1 cells by specific radioimmunoassay. Among the agents tested, estrogen, tamoxifen, tumor necrosis factor, gamma-interferon, interleukin (IL) 1, and transforming growth factor beta had no effect on ir-ET-1 secretion by these breast cancer cells. However, IL-6 (20 ng/ml) treatment of MCF-7 cells and ZR-75-1 cells caused maximal increases in the amount of ir-ET-1 secreted into the culture medium to 206 and 314% of basal values after 6 h, respectively. This effect of IL-6 on ir-ET-1 secretion was inhibited by actinomycin D and cycloheximide, indicating that IL-6 stimulates de novo synthesis of ir-ET-1 at a transcriptional level. Reverse-phase high performance liquid chromatography coupled with radioimmunoassay in the conditioned medium from IL-6-treated cells revealed one major ir-ET-1 component corresponding to human standard ET-1. The present study demonstrates the potential for IL-6 to stimulate ir-ET-1 production in human breast cancer cells, which may participate in the process of acute phase reactant-like expression of this peptide and/or in the process of IL-6 enhanced breast cancer cell motility, the latter being recently clarified.

Breast Neoplasms↗
PubMed1993

Developmental change of distribution of beta-galactoside alpha 2,6-sialyltransferase mRNA in rat retina.

A substantial change in the glycoconjugates of the rat interphotoreceptor matrix (IPM) has recently been shown to occur between post-natal day (P) 14 and P16 in rat retinas using lectin histochemistry. This suggests that the sialic acid content on the terminus of N-glycoside linked carbohydrate chains of the IPM increases between P14 and P16. In the present study, to test this hypothesis, we examined the developmental change of distribution of beta-galactoside alpha 2,6-sialyltransferase mRNA in rat retina using in situ hybridization histochemistry. C-DNA of rat alpha 2,6-sialyltransferase was isolated by PCR and cloned into the polylinker site of Bluescript KS (+). Antisense and sense RNA probes were labelled with digoxigenin-UTP by in vitro transcription with T3 and T7 RNA polymerases, respectively. Paraffin sections of rat retinas between P12 and P42 were incubated with the antisense or sense RNA probes. Specific labelling with the antisense probe was observed strongly in the cytoplasm of all ganglion cells and weakly in partial cells of the inner nuclear layers throughout the examined postnatal days. A remarkable change was observed in the photoreceptor cells between P14 and P16. Hybridization signals of the outer nuclear layer was observed from P14, while those of the inner segments were detected on P16 and thereafter. The alpha 2,6-sialyltransferase newly expressed in the inner segments on P16 appears to sialylate the Gal beta 1, 4GlcNAc residue of N-glycosidically linked glycoconjugates of the IPM, resulting in the change of lectin staining profiles.

Animals↗