[Effect of ethyl loflazepate on age-dependent epileptic encephalopathy].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A Azuma.
Explore the source record for details and available documents.
The interaction between LFA-1 and its natural ligand, ICAM-1, plays an important role in leukocyte adhesion and signal transduction. LFA-1-mediated T-cell adhesion is generally activated by CD3-mediated signal in association with T-cell receptor-mediated recognition of the antigen/major histocompatibility complex on antigen-presenting cells. In the present study, we compared spontaneous or bispecific antibody (BsAb)-directed LAK cell cytotoxicity against ICAM-1+ or ICAM-1- small cell lung cancer (SCLC) cell lines. gamma-Interferon (IFN-gamma)-induced ICAM-1 expression on ICAM-1- SCLC cell lines, and susceptibility to LAK cells was increased simultaneously. Increased cytolysis of the IFN-gamma-treated SCLC was inhibited by an anti-ICAM-1 monoclonal antibody (mAb). Furthermore, LAK cell cytotoxicity directed by BsAb, which was composed of OKT3 and anti-SCLC mAb, was also increased by the IFN-gamma treatment of SCLC, and this increase was inhibited by an anti-ICAM-1 mAb but not by anti-Class I or anti-CD2 mAb. These results suggest that a prior administration of IFN-gamma would enhance the efficacy of the following specific targeting therapy utilizing BsAb and LAK cells by up-regulating the ICAM-1 expression on tumor target cells. The combinational use of IFN-gamma and anti-CD3 x anti-tumor BsAb might be a promising way of enhancing LAK cell-mediated adoptive immunotherapy in small cell lung cancer patients.
In 20 of 198 patients with hypertrophic cardiomyopathy, Doppler color flow imaging revealed diastolic paradoxic jet flow across the obliterated left ventricular apex toward the base that suggested the presence of a discrete apical chamber. This prospective study characterized echocardiographic, ventriculographic and scintigraphic findings in these patients, as well as their clinical features. Although echocardiography did not directly show the apical chamber in 13 of the 20 patients, left ventriculography always revealed a small apical outpouching separated from the major basal cavity. Systolic bulging of the apex was always followed by early diastolic shrinkage together with persistent cavity narrowing between the two chambers. After the systolic jet flow, the paradoxic jet flow lasted for 366 +/- 160 ms after aortic valve closure and always extended into the diastolic filling period. The maximal velocity of the paradoxic jet flow occurred during isovolumetric relaxation and the mean velocity was 2 +/- 0.8 m/s, indicating a higher diastolic pressure in the apical chamber than in the main ventricle. Compared with patients who manifested cavity obliteration alone, patients with a paradoxic jet flow more often developed systemic embolism (p less than 0.01), ventricular tachycardia (p less than 0.05) and thallium perfusion abnormalities localized to the apical region (p less than 0.01). Thus, paradoxic jet flow could be an important marker of concealed apical asynergy and the risk of adverse clinical events. The higher diastolic apical pressure suggested by the flow may contribute to the development of an apical aneurysm, even in the absence of fixed coronary artery disease.
In the elderly cardiac size and function are determined by their level of physical activity. In this study, we assessed by echocardiography, the anatomic and physiologic changes of the heart in 28 elderly patients who had no cardiac disease and who were chronically bedridden. The data obtained were compared to those obtained from a control group of 38 age and sex matched elderly people whose activities had not been restricted. Chronically bedridden patients had markedly smaller left ventricular dimensions in both end-diastole and end-systole and smaller left atrial dimensions than did control subjects (3.7 +/- 0.7 vs 4.7 +/- 0.6 cm, p less than 0.001, 2.4 +/- 0.8 vs 2.9 +/- 0.7 cm, p less than 0.02 and 3.2 +/- 0.5 vs 3.8 +/- 0.9 cm, p less than 0.01, respectively). Though the wall thickness of the interventricular septum did not differ between the study groups, the left ventricular posterior walls of the bedridden group were significantly thinner than in the control group (0.8 +/- 0.2 vs 1.0 +/- 0.2 cm, p less than 0.01). The bedridden group had a significantly lower stroke index (26.9 +/- 6.2 vs 47.0 +/- 11.1 ml/m2, p less than 0.001) and cardiac index (1.84 +/- 0.52 vs 3.15 +/- 0.63 l/min/m2, p less than 0.001) than did the control group. Left ventricular mass index and left ventricular systolic stress were significantly lower in bedridden patients than in control subjects (88.0 +/- 18.1 vs 143.5 +/- 30.9 g/m2, p less than 0.001, and 135.9 +/- 4.9 vs 186.6 +/- 35.7 10(3) dynes/cm2, p less than 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
A 13-year-old boy with severe coronary stenosis due to Kawasaki disease underwent percutaneous transluminal coronary angioplasty (PTCA). The guide wire and the balloon catheter easily passed through the stenosis in the left anterior descending artery. However, effective dilatation could not be achieved even when the balloon size was increased to 2.5 mm in diameter. We discontinued further inflation of the balloon because serious resistance was encountered on withdrawal of the balloon catheter. In patients with Kawasaki disease, the value of PTCA as a treatment for coronary stenosis is questionable.
Using digital subtraction coronary angiography (DSA), we evaluated the regional myocardial coronary blood flow reserve (rMFR) in 18 patients with hypertrophic cardiomyopathy (HCM). There were 13 patients with asymmetrical septal hypertrophy (ASH), and 5 with asymmetrical apical hypertrophy (AAH). Eight subjects without apparent cardiac abnormality served as controls. Relations between the rMFR and regional wall thickness as determined by echocardiography were also investigated. Peak contrast density (Cm) and time to Cm (Tm) were measured from digital angiograms at the middle and distal ventricular septum (VS) and at the apical and left ventricular posterior wall (PW). The rMFR of each region of interest was expressed as the ratio of Cm/Tm at the baseline and at peak hyperemic response induced by intracoronary administration of papaverine. The rMFR was significantly lower at the VS and apex in HCM than in controls: middle VS, 1.9 +/- 0.5 vs 3.9 +/- 0.5, p < 0.001; distal VS, 2.0 +/- 0.5 vs 4.4 +/- 0.9, p < 0.001; and the apex, 2.0 +/- 0.7 vs 4.5 +/- 1.6, p < 0.01. However, it did not differ at the PW; 2.6 +/- 0.9 vs 3.0 +/- 0.9 between the 3 groups. The middle VS and apex, where the wall was the thickest, had the lowest rMFR in ASH and AAH. Furthermore, at the VS and apex, a curvilinear relationship was observed between the rMFR and wall thickness (rMFR = -0.88 in WT + 2.39, r = -0.57, p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
The anaerobic threshold (AT) is regarded an objective parameter for evaluating exercise tolerance, but its relationship to the improvement of myocardial ischemia remains uncertain. To investigate this relationship, submaximal treadmill exercise tests were performed for 15 consecutive patients with angina pectoris who had undergone successful percutaneous transluminal coronary angioplasty (PTCA). Before and after PTCA, the AT was determined using cardiorespiratory monitoring, while the patients were receiving their usual vasodilator medications. 1) Before PTCA, the minute oxygen uptake (VO2) at the AT correlated well with the peak VO2 (r = 0.92, p < 0.002). The VO2 at the AT, however, showed less correlation (r = 0.71, p < 0.002) with the VO2 at ST segment depression, while the latter parameter correlated closely with the peak VO2 (r = 0.91, p < 0.002). 2) After PTCA, exercise time, peak VO2, and the double product at peak exercise increased significantly (from 640.1 +/- 212.2 to 772.9 +/- 230.0 sec, p < 0.001, from 19.1 +/- 5.2 to 22.4 +/- 4.9 ml/min/kg, p < 0.05, and from 19.7 +/- 5.0 x 10(3) to 23.7 +/- 4.5 x 10(3), p < 0.001, respectively). However, the VO2 at the AT did not increase significantly (from 15.8 +/- 4.1 to 16.6 +/- 3.5 ml/min/kg, p = NS). The heart rate, systolic blood pressure, and double product at the AT did not change significantly. In conclusion, in patients with angina pectoris, the AT is apparently related to the onset of myocardial ischemia. However, the AT does not necessarily reflect acute improvement of myocardial ischemia immediately after PTCA.
In normal hearts, two-dimensional echocardiography from the apical window displays the left ventricular wall as a three-layered appearance (TLA): central bright layer and bilateral sonolucent zones. The TLA is considered to reflect the normal myocardial architecture: the predominant latitudinal fiber bundles of the midwall layer, and longitudinal or oblique ones on both sides. We analysed the TLA of the ventricular septum in 20 normal subjects, 20 patients with left ventricular hypertrophy due to pressure load (LVH), and 81 patients with hypertrophic cardiomyopathy (HCM). Of the 81 HCM patients, the layering was often obscure or absent in 53 (65%), whereas LVH patients showed clear TLA as well as normal hearts. In patients with severe layering disorder (n = 30), the age at diagnosis was lower (40 +/- 15 vs 50 +/- 12, p less than 0.05), and familial occurrence (53 vs 11%, p less than 0.01) and severe functional limitation (NYHA greater than or equal to III) were more common (27 vs 4%) than in those with clear TLA (n = 28). The disturbed layering detectable by echocardiography may reflect the disorder of basic myocardial fiber architecture in the ventricular septum, and is likely to become a useful marker of the pathologic severity of the disease.
There has been no report that Accelerated Idioventricular rhythm (AIVR) causes a syncope attack. The patient described in this report is very rare because AIVR chronic without any heart diseases has been observed for 13 years, and because it is considered that AIVR is closely associated with his repeated blackouts. A 62-year-old male was admitted to our hospital because of repeated syncopal attacks. He reported that he occasionally felt lightheaded after strenuous lifting and pushing or pulling against resistance. We found that AIVR could produce a remarkable arterial pressure drop partly because of ventricular asynergy and loss of timed atrial contribution. Furthermore, we observed syncopal attacks during Valsalva maneuver and found abnormalities of baroreceptor reflex (Lack of reflex tachycardia and weakened evershoot phenomenon). It is concluded that AIVR is not a benign arrhythmia in this patient because it has been a possible cause of syncope attack due to systemic arterial pressure drop and baroreceptor abnormalities.
Explore the source record for details and available documents.
123I-BMIPP myocardial scintigraphy was performed in 13 patients with hypertrophic cardiomyopathy and compared with 201Tl myocardial scintigraphy performed within 3 months for evaluating the clinical significance of 123I-BMIPP myocardial scintigraphy. SPECT images were divided into 13 segments and segmental images were visually scored on a 4 (increased tracer uptake) to 0 (severely decreased tracer uptake) scale according to the tracer uptake. In comparison of 123I-BMIPP early images and 201Tl perfusion images, mismatches were seen in about 70% of all segments. The number of segments demonstrating lower myocardial uptake of 123I-BMIPP was larger than that of 201Tl. In hypertrophic regions, the tracer uptake of 123I-BMIPP early images was significantly lower than that of 201Tl images and the lower uptake of 123I-BMIPP delayed images was more marked. In non-hypertrophic regions, no significant difference was seen between the tracer uptakes of 123I-BMIPP early images and 201Tl images but the tracer uptake of 123I-BMIPP delayed images was significantly lower than that of 201Tl images. The mismatch between the tracer uptakes of 123I-BMIPP images and 201Tl images was thought to be a reflection of disordered myocardial fatty acid metabolism. "Washout", the difference between the tracer uptakes of 123I-BMIPP early images and delayed images was also thought to be a reflection of disordered myocardial fatty acid metabolism. These results suggest that 123I-BMIPP is a promising radiopharmaceutical for evaluating disordered myocardial fatty acid metabolism in patients with HCM.
A case of aortic valve stenosis without coronary artery disease was confirmed to have diffuse subendocardial ischemia by exercise Thallium-201 myocardial single photon emission computed tomography. A 72-year-old woman, who had been diagnosed as aortic valve stenosis, was admitted because of chest pain during exercise. In cardiac catheterization findings, the patient angiographically had normal coronary arteries and no asynergy of left ventricular wall motion. The peak flow velocity in continuous wave Doppler echocardiography was about 5.0 m/sec at aortic valve level, providing a pressure drop of 100 mmHg across a stenotic valve with calculating on a modified Bernoulli equation (PG = 4V2). Thallium-201 myocardial SPECT images during exercise showed a transient "dilation and a widespread wall thinning" of left ventricle with apical perfusion defect. Simultaneous electrocardiogram showed further ST depression and the patient had chest pain. In 6 months after aortic valve replacement the patient no longer demonstrated both apical perfusion defect and "wall thinning" in postoperative thallium-201 myocardial SPECT images and also had neither ST depression nor chest pain. Thus; a transient "dilation and wall thinning" of left ventricle in this patient is suspected to be a sign of diffuse subendocardial ischemia.
Explore the source record for details and available documents.
To assess the integrity of an adrenergic nervous function in acute myocardial ischemia, the contractile response of the ischemic region to cardiac sympathetic nervous stimulation (CSNS) was measured in comparison that with to exogenous noradrenaline (NA) infusion. In 13 anesthetized open chest mongrel dogs, haemodynamic changes, segmental wall motion, and the concentration of NA in the efferent coronary vein were measured. CSNS was performed by electrically stimulating the left ansa subclavia. Data concerning baseline values, values during CSNS, and those obtained during NA infusion both before and up to 5 h after coronary occlusion were compared. Regional myocardial blood flow of the ischemic region was also measured using the H+ clearance method. Systolic expansion with coronary occlusion was not changed or augmented by CSNS. However, improvement was observed in all experiments when NA infusion was used. The percent change of systolic shortening, indicating the response of segmental wall motion to CSNS, decreased soon after occlusion, recovered temporarily within 30 min after occlusion, but did not improve throughout the period after 60 min. The decrease of NA overflow into the efferent vein by CSNS showed a biphasic pattern; reduction occurring immediately after occlusion and again 3-5h after occlusion. Throughout these experimental studies it was considered that the preserved responses to the exogenous injected NA represented the contribution of presynaptic factor.
In this study, we show that bispecific hetero-F(ab')2 enhances cytolytic activity in human lymphokine activated killer (LAK) cells derived from peripheral blood mononuclear cells against human small cell lung cancer (SCLC) cell lines. We used two types of bispecific F(ab')2 (anti-CD3-LU246mAb, anti-CD16-LU246mAb) which play different roles in the enhancement of cytolytic activity in LAK cells against the human SCLC cell lines N231, H69 and Lu135. Anti-CD3 Fab' or anti-CD16 Fab' were coupled with LU246 Fab' that recognized the antigen on human SCLC cells for reproducing bispecific F(ab')2. Anti-CD16 (3G8) Fab' conjugated with LU246 Fab' targeted NK-LAK cells to SCLC cells to mediate cytolysis, but NK-LAK cells induced by LGL-enriched fraction did not display enhanced cytotoxicity even when bispecific antibody was used in 51Cr release assay. Anti-CD3 (OKT3) Fab' conjugated with LU246 Fab' cross-linked T-LAK cells to SCLC cells activated T-LAK cells through the CD3 complex, and enhanced the cytolytic activity of T-LAK cells against SCLC lines. Although OKT3-LU246 F(ab')2 was not so potent in enhancing cytolytic activity in 51Cr release assay, it played a greater role in enhancing the inhibitory effect on tumor growth than 3G8-LU246 F(ab')2 in human tumor clonogenic assay and in vivo tumor neutralization assay. In addition, the enhancement of target cell lysis by bispecific antibodies was generally more potent than antibody dependent cellular cytotoxicity (ADCC) using LU246 monoclonal antibody.
A high-frequency transducer was used to determine the optimal parameters for visualizing the heart in 40 normal Wistar, 15 SHR, and 10 aorta-banded rats. The rats were 5 to 30 weeks old and weighed between 105 and 705 grams. Two-dimensional and M-mode views of the ventricles, atria, valves, and great arteries were obtained by placing the transducer beneath the rats through the left or right parasternal window in either the prone or the right decubitus positions, respectively. Left ventricular (LV) mass was determined on the basis of a spheroid model; these values correlated well with the LV weight for both the Wistar rats (r = 0.94, p less than 0.001) and the rats with cardiac hypertrophy due to pressure load (r = 0.87, p less than 0.001). These results were highly reproducible. This indicates that echocardiography is useful for obtaining quantitative measurements in rats.
In order to enhance cytolytic activity of lymphokine activated killer (LAK) cells against human small cell lung cancer (SCLC), bispecific F(ab')2 was used with human LAK cells and human SCLC cell lines (i.e. N231 and H69) as targets. For the construction of bispecific F(ab')2, LU246 monoclonal antibody (mAb) recognizing the antigen expressed on the surface of both SCLC cell lines, was employed. OKT3 or 3G8 mAbs recognizing CD3 on T cell and CD16 on NK cell functional molecules respectively, were chemically cross-linked to LU246 mAb using 5,5'-dithio-bis 2-nitrobenzoic acid (DTNB). Bispecific F(ab')2 adding to LAK cells increased the conjugation with target cells. The phenotypes of LAK cells change at their various culture times. Although cytolytic activity of LAK cells gradually decreases after one week of culture time, the enhanced cytotoxicity of LAK cell using bispecific F(ab')2 has been kept even after long culture. Furthermore, target cell lysis enhanced by bispecific F(ab')2 has been greater than that by classical ADCC using LU246 mAb. These bispecific antibodies should be effective reagents for adoptive immunotherapy in human SCLC patients.
We examined whether recurrent transient ischemia may effect left ventricular systolic and diastolic function or not. Left ventricular systolic and diastolic function during the asymptomatic period was studied by gated radionuclide ventriculography (RNV) in 25 patients with vasospastic angina (VA) who had no significant coronary stenosis, in 25 patients with effort angina (EA), and in 20 controls (C). There was no significant difference among patients in all three groups in regards to systolic indices (Ejection Fraction, Peak Ejection Rate). But diastolic indices (Peak Filling Rate, Time to Peak Filling Rate, 1/3 Mean Filling Rate, 1/3 Filling Fraction) were impaired not only in patients with EA but also in patients with VA. The treatment with nitrates and/or Ca antagonist for 6-24 months did not bring about any changes in these data concerning systolic and diastolic function in patients with VA. Thus, it is suggested that the diastolic function is impaired in patients with VA even during the asymptomatic period, though systolic function remains normal. Recurrent transient ischemia may cause irreversible myocardial injury.