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Biomedical subjects

K Takeda

Publications and source records attributed to K Takeda.

At least 559 records · Page 31Linked to original sources

Expression of neural cell adhesion molecule L1 in human lung cancer cell lines.

To investigate neuron-specific antigens, hybridoma cells were produced between mouse spleen cells immunized with human neuroblastoma cells (IMR-32) and mouse myeloma cells. 247 hybridoma clones were harvested and one of them was further cultured for recloning. Eventually, one hybridoma clone was obtained and its antibody was designated N-A8. The characteristics of this antibody were determined by immunostaining and flow cytometry. First, the antibody recognized the surface antigens of IMR-32 cells. Second, unexpectedly, N-A8 was reactive not only with human neuroblastoma cell lines but also with human lung cancer cell lines. As analyzed by immunoprecipitation method and SDS-PAGE, the molecular size of the antigen recognized by N-A8 was 210 kDa. The antigen was then purified by affinity chromatography and identified as neural adhesion molecule L1 by amino acid sequence analysis. By the present investigation, it was clearly demonstrated that L1 is expressed in human lung cancer cells.

Animals↗

Chronic angiotensin blockade with candesartan cilexetil in DOCA/salt hypertensive rats reduces cardiac hypertrophy and coronary resistance without affecting blood pressure.

To determine whether angiotensin II participates in the pathogenesis of cardiac hypertrophy and impairs coronary circulation in DOCA/salt hypertension, DOCA hypertensive rats were treated with candesartan cilexetil for 8 wk. DOCA/salt hypertension was induced in Wistar rats by removing the right kidney and subcutaneously injecting deoxycorticosterone acetate once a week. Control rats were given subcutaneous injections of saline and maintained on a normal diet. After 4 wk of observation, the angiotensin II receptor antagonist candesartan cilexetil was administered by oral gavage for 8 wk to 14 rats. Systolic blood pressure was measured weekly with the tail-cuff method. After 12 wk, the rats were killed and prepared. The isolated hearts were perfused by a Langendorff apparatus at constant flow. Perfusion pressure was measured by a small-volume transducer, and perfusion flow was recorded by a drop counter. Development of hypertension was not prevented by candesartan cilexetil treatment, but development of cardiac hypertrophy was inhibited. Minimum coronary vascular resistance (MCVR) obtained upon infusing adenosine into the isolated hearts was significantly higher in DOCA/salt hypertensive rats than in sham-operated controls. The elevated MCVR in DOCA/salt hypertensive rats was decreased by the administration of candesartan cilexetil for 8 wk. Thus, candesartan cilexetil regressed cardiac hypertrophy and improved coronary vascular resistance without affecting high blood pressure. These findings suggest that angiotensin II plays an important role in the pathogenesis of cardiac hypertrophy in DOCA/salt hypertension and that cardiac hypertrophy increases coronary vascular resistance.

Angiotensin Receptor Antagonists↗

Mutations in exon 7 of the GTP-binding protein Gs alpha were not a common cause of pseudohypoparathyroidism with Albright's hereditary osteodystrophy in Japanese.

The identification of unique point mutations in patients with pseudohypoparathyroidism (PHP) with Albright's hereditary osteodystrophy (AHO) in different ethnic backgrounds has proved that defects within the Gs alpha gene account for Gs alpha deficiency in those patients. To search a mutation hot spot of the Gs alpha gene in Japanese patients, we have screened exons 2-13 of the Gs alpha gene for mutations in three unrelated Japanese PHP patients with AHO. We could find no abnormalities by denaturing gradient gel electrophoresis and no mutations of sequencing of exon 7 in these subjects. This suggests that mutations in exon 7 of the Gs alpha gene may not be a common cause of PHP with AHO in Japanese.

Adult↗

Quantification of coronary artery volume flow rate using fast velocity-encoded cine MR imaging.

OBJECTIVE: Breath-hold velocity-encoded cine (VENC) MR imaging has been proposed as a method for measuring coronary blood flow. However, most studies have measured velocity rather than volume flow rate in the coronary arteries. The purpose of this study was to measure volume flow rate in the coronary artery of dogs using high-speed gradients and to compare MR flow measurements with those obtained with a sonographic flowmeter. MATERIALS AND METHODS: Fast VENC MR images were obtained with a high-speed-gradient 1.5-T MR system in seven anesthetized dogs before and after administration of dipyridamole. Images were acquired on double oblique planes perpendicular to the left anterior descending arteries with a slice thickness of 5 mm, a field of view of 20 x 10 cm, a velocity window of +/- 1 m/sec, an average imaging time of 21 sec, a TR/TE of 11/5, and a temporal resolution of 44 msec. RESULTS: Coronary flow measured with VENC MR imaging correlated well with flow measured by the flowmeter (r = .95, slope = 0.97, n = 88). Interobserver variability in measuring coronary flow volume was 8%. CONCLUSION: Fast VENC MR imaging with high-speed gradients can provide accurate quantification of volume flow rate in coronary arteries.

Animals↗

Distribution of IgE and IgG antibody levels against house dust mites in schoolchildren, and their relation with asthma.

Although asthmatic patients are known to have increased levels of IgG antibody against house dust mite (HDM), it is not clear whether or not the presence of HDM-specific IgG antibody is associated with the etiological mechanism of asthma. To address this problem, we evaluated the relationship between HDM-specific IgG antibody levels and incidence of asthma in a general pediatric population. IgE and IgG antibody levels against Dermatophagoides farinae (Df) were examined by RAST and ELISA in a total of 722 randomly selected schoolchildren including 26 subjects with asthma, and the relative prevalence rates of asthma in this population were evaluated in relation to both Df-specific IgE and IgG levels. The incidence of asthma correlated not only with levels of Df-specific IgE, but also with those of Df-specific IgG. There was a significant correlation between Df-specific IgE and IgG levels both in the total population and in the asthmatic children. Because IgG and IgE responses occurred in parallel in this population, the clinical significance of HDM-specific IgG anti-body remains unclear. However, our findings have suggested that clinical expression of asthma in children is primarily dependent on their capacity to mount a immune response to HDM, which includes both IgE and IgG responses.

Adolescent↗

P2Y- and P2U-mediated increases in internal calcium in single bovine aortic endothelial cells in primary culture.

Increases in intracellular calcium ([Ca2+]i) to ATP, ADP, AMP, adenosine, UTP, 2-methylthio ATP (2-MeSATP), 2-methylthio ADP (2-MeSADP) and alpha,beta-methylene ATP (alpha,beta-meATP) were investigated in single bovine aortic endothelial cells (BAEC) in primary culture using Indo-1. Evidence was obtained for the presence of P2Y and P2U, but not P2X receptors. Normalized concentration-effect curves for ATP, UTP and 2-MeSATP were biphasic in shape. At 10 nM, the agonist rank order was UTP > ATP approximately 2-MeSATP, while above 1 microM, it was ATP > or = UTP > or = 2-MeSATP. No cross-desensitization between responses to P2U and P2Y receptors was observed in normal external solution. However, when internal Ca2+ stores were depleted by exposure to 2-MeSATP or UTP in Ca2+-free solution and agonists then re-applied in presence of external Ca2+, homologous but not heterologous desensitization was seen. In the same conditions, heterologous desensitization was observed for UTP after ATP but not for ATP after UTP. Taken together, the results are consistent with the coexistence of P2Y and P2U receptors in primary-cultured BAEC and suggest that upon activation, different intracellular signaling pathways could be involved in increasing [Ca2+]i.

Adenine Nucleotides↗

Identification of the anti-adhesive site buried within the heparin-binding domain of fibronectin.

We recently found that heparin-binding domain 2 (Hep 2) of fibronectin (FN) exhibits cryptic anti-adhesive activity. In order to locate the anti-adhesive site, a number of synthetic peptides which represents the primary structure of the Hep 2 domain were characterized as to their ability to decrease the adhesion of A375SM melanoma cells to FN substrate. Only one peptide (T-E-A-T-I-T-G-L-E-P-G-T-E-Y-T-I-Y-V-I-A-L, residues 1835-1855) (peptide III14-2), which is situated between the previously identified adhesive sites, FN-C/H-I and II, decreased the cell adhesion to FN. Assaying of the anti-adhesive activities of sub-peptides showed that the hydrophobic moiety of peptide III14-2 (underlined sequence) seems to be indispensable for the anti-adhesive activity. These results suggest that anti-adhesive activity is closely associated with the sequence, Y-T-I-V-I-A-L, that is usually buried within the Hep 2 domain structure because of its hydrophobic nature.

Amino Acid Sequence↗

Iodine-123-BMIPP myocardial washout and cardiac work during exercise in normal and ischemic hearts.

UNLABELLED: Iodine-123-BMIPP washout at rest and after exercise was investigated in relation to cardiac work in normal and ischemic myocardium. METHODS: Sixteen healthy volunteers and 10 patients with ischemic heart disease were examined. After injection of 111 MBq of 123I-BMIPP, successive SPECT imaging was performed to evaluate washout ratio (WR) at rest and after mild and maximal exercise. RESULTS: In the healthy volunteers, the mean WR was 3.3 +/- 3.5% after 1 hr of rest and increased during both mild and maximal exercise. The WR showed a better correlation with net pressure rate product (PRP) than with the peak PRP. After maximal exercise, the WR showed a distinct correlation with the net PRP in the range from 200-300 x 10(3) mmHg/min and then showed a plateau greater than 10%. In five ischemic heart disease patients with the net PRP > or = 300 x 10(3) mmHg/min, the exercise WR values were significantly elevated in normal segments relative to ischemic segments. CONCLUSION: BMIPP washout increased with the increase in cardiac work during exercise in normal myocardium but not in ischemic myocardium. A certain amount of exercise is necessary to evaluate fatty acid metabolism in normal and ischemic myocardium.

Adult↗

Correlation between HLA-DR expression and level of poly(ADP-ribose) synthetase in human thyroid carcinoma cells.

The expression of MHC class II molecules is normally restricted to antigen presenting cells. Aberrant expression of class II molecules, however, was detected in the thyrocytes of autoimmune thyroid diseases. We attempted to regulate the expression of HLA-DR molecules in thyroid carcinoma cells by expressing the exogenous poly(ADP-ribose) synthetase gene. We transfected a metal inducible expression plasmid capable of expressing poly(ADP-ribose) synthetase gene into thyroid carcinoma 8505C cells and the transformants, treated with metal and IFN-gamma, were separated by Magnetic Cell Separation. The activity of the synthetase was increased in the HLA-DR-enriched transformants as compared with that in control or the HLA-DR+ transformants. RNA blot analysis and flow cytometric analysis revealed that the IFN-gamma-inducible expression of HLA-DR molecules was depressed by the induction of exogenous poly(ADP-ribose) synthetase gene. This result indicates that HLA-DR expression was correlated with the level of poly(ADP-ribose) synthetase in human thyroid carcinoma cells. Furthermore we examined the level of poly(ADP-ribose) synthetase in patients with autoimmune thyroid diseases. We observed a significant decrease in poly(ADP-ribose) synthetase in the patients. Taken together with the previous observation, the decrease in poly(ADP-ribose) synthetase is closely linked to the aberrant expression of HLA-DR molecules in some autoimmune thyroid diseases.

Autoimmune Diseases↗

[Postoperative epidural fentanyl administration in patients for hysterectomy with para-aortic lymph node resection].

In our experience, continuous epidural administration of fentanyl in doses of 12.5 micrograms.h-1, has not been sufficient to relieve postoperative pain in patients after hysterectomy with para-aortic lymph node resection. Thus, a prospective, randomized, single-blind study was performed to compare the analgesic efficacy of fentanyl 25 micrograms.h-1 with 12.5 micrograms.h-1 in these patients for 48 hours after surgery. Twenty-one women undergoing hysterectomy with para-aortic lymph node resection were allocated into three groups; Group C (control, n = 7): fentanyl 12.5 micrograms.h-1, infusion rate 2 ml.h-1, Group S2 (double speed, n = 7): fentanyl 25 micrograms.h-1, infusion rate 4 ml.h-1, and Group C2 (double concentration, n = 7): fentanyl 25 micrograms.h-1, infusion rate 2 ml.h-1. At postoperative 0, 2, 6, 12, 24, and 48 hours, the degree of analgesia was evaluated by visual analogue scale (VAS) and verbal pain scores at both rest and movement. Groups S2 and C2 showed significantly lower VAS scores than group C at the postoperative 6- and 24-hour points. At movement, the analgesic efficacy was not sufficient in any groups, but, at rest, groups S2 and C2 experienced significantly less pain than the group C. The degree of pain relief was not different between groups S2 and C2. In conclusion, epidural fentanyl 25 micrograms.h-1 provided significantly superior analgesia compared with epidural fentanyl 12.5 micrograms.h-1.

Analgesia, Epidural↗

Myocardial contractility of the canine left ventricle during unsynchronized dual chamber pacing.

The influence of changes of left ventricular (LV) myocardial contractility on the decrease of cardiac output during atrial fibrillation was investigated in dogs using the slope (Ec) and the length intercept (Lo) of the LV end-systolic force-length relationship. The hearts of nine healthy adult mongrel dogs were instrumented with ultrasonic crystals and a micromanometer, after which pharmacologic autonomic blockade was instituted. The LV diameter and pressure data were recorded during inferior vena caval occlusion. Hemodynamic parameters were measured during pacing from the right atrial appendage at a pacing rate 30 beat/min greater than the natural heart rate using a cardiac stimulator (atrial pacing), and during simultaneous pacing from the right atrial appendage and right ventricular apex at the same rate (unsynchronized dual chamber pacing). Cardiac hemodynamics in the absence of synchronized left atrial contraction were simulated by unsynchronized pacing. During atrial pacing, the cardiac output (1.68 +/- 0.25 vs 1.57 +/- 0.21 l/min, p < 0.005) and Ec (110.1 +/- 58.5 vs 81.8 +/- 30.8 g/cm, p < 0.05) were significantly greater than during normal sinus rhythm, whereas the stroke volume (12.4 +/- 2.4 vs 15.1 +/- 3.1 ml, p < 0.005) and LV end-diastolic volume (16.6 +/- 2.7 vs 19.5 +/- 3.4 ml, p < 0.005) were significantly smaller. Lo did not change during pacing. During unsynchronized dual chamber pacing, cardiac output (1.46 +/- 0.17 vs 1.68 +/- 0.25 l/min, p < 0.005), stroke volume (10.8 +/- 1.7 vs 12.4 +/- 2.4 ml, p < 0.005), and LV end-diastolic volume (15.0 +/- 2.0 vs 16.6 +/- 2.7 ml, p < 0.05) were significantly smaller than during atrial pacing. However, Ec and Lo were similar during both types of pacing. These findings suggest that the decrease of cardiac output and stroke volume during atrial fibrillation is chiefly due to the decrease of LV end-diastolic volume through loss of left atrial contraction, and is not due to a change of LV myocardial contractility.

Animals↗

[Long-term beneficial effect of dual chamber pacing in a patient with hypertrophic obstructive cardiomyopathy].

Dual chamber (DDD) pacing therapy was effective to reduce the left ventricular outflow tract pressure gradient for a long time in a patient with pharmacotherapy-resistant hypertrophic obstructive cardiomyopathy. A 52-year-old man with pharmacotherapy-resistant pressure gradient was treated by a DDD pacemaker implantation, because the pressure gradient was proved to be reduced (94-->16 mmHg) by transient DDD pacing with an atrioventricular delay of 50 msec. Hemodynamics and ventricular wall thickness were serially observed after the implantation for 2 years. The pressure gradient progressively decreased during the pacing period, at 4 months and 2 years follow-up, (10-->2 mmHg) and during the sinus rhythm period (60-->25 mmHg), and left ventricular ejection fraction and end-diastolic volume index were increased. Although the ventricular wall thickness remained constant, the systolic anterior motion of the mitral valve and A/E were reduced during the pacing period in the echocardiography. During the acute effect of DDD pacing, the pressure gradient reduction seemed to be related to dilatation of the left ventricular outflow tract induced by a change of contraction modality of the intraventricular septum. Improved left ventricular diastolic function may contribute to the pressure gradient reduction during extended periods of pacing therapy.

Cardiac Pacing, Artificial↗

[Echocardiographic prediction of risk for embolism in patients with infective endocarditis].

The relationship between two-dimensional echocardiographic findings of vegetation and embolic events was investigated in 26 patients with infective endocarditis (17 males and 9 females, mean [+/-SD] age 51 +/- 17 years). The size and the other morphologic characteristics of vegetation (mobility, extent and consistency) were analyzed retrospectively according to the criteria by Sanfilippo, et al., and parameters were assigned scores from 1 to 4 to provide a total score. Patients with a maximum vegetation diameter > 10 min had a significantly higher incidence of embolic events than those with < or = 10 mm (p < 0.05). Each parameter of vegetation showed no significant difference between patients with and without embolic events; but the total score was significantly higher in patients with embolic events (p < 0.05). Particularly, all patients with a total score > or = 10 had embolic events, whereas those without embolic events had a total score < or = 9. There were no significant differences in the frequency of emergent valve replacement between patients with aortic value and mitral valve endocarditis. However, the incidence of heart failure was higher, but not significantly, in patients with aortic valve (67%) and combined valve endocarditis (67%) than in those with mitral valve endocarditis (36%). The maximum size and total score reflecting mobility, extent and consistency of vegetation using two-dimensional echocardiography provide useful information to predict the occurrence of embolic events in patients with infective endocarditis.

Adult↗

[Assessment of coronary flow reserve using fast phase contrast cine MR imaging].

Physiological significance of coronary artery stenosis can be evaluated by measuring coronary flow reserve(CFR). Segmented k-space cine phase-contrast(PC) MR method has been used for measuring coronary blood flow and CFR. MR measurement of the CFR ratio(1.62 +/- 0.50, n = 10) in patients with coronary arterial stenosis was significantly lower than that measured in healthy subjects(3.14 +/- 0.59, n = 10, p < .01). The CFR measured by MRI demonstrated a good linear correlation with the CFR directly measured by Doppler flow wire during X-ray angiography(r = 0.91, n = 19). MR measurement of flow volume in the coronary sinus and myocardial mass can provide evaluation of blood flow rate per myocardial mass for the entire left ventricle, which was substantially decreased in patients with hypertrophic cardiomyopathy.

Cardiomyopathy, Hypertrophic↗