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Biomedical subjects

K Kodama

Publications and source records attributed to K Kodama.

At least 505 records · Page 28Linked to original sources

[Discrepancies between wall motion abnormalities and regional myocardial perfusion in patients with myocardial infarction: evaluation by myocardial contrast echocardiography].

Regional myocardial perfusions obtained by myocardial contrast echocardiography were compared with wall motion abnormalities evaluated by two-dimensional echocardiography in 26 patients with old myocardial infarction (12 with a QS pattern and 14 with a non-QS pattern on electrocardiograms). Myocardial contrast echocardiography was performed by the intracoronary injection of 2 ml of hand-agitated Urografin-76, and short-axis views of the left ventricle were recorded on VTR. Regional myocardial perfusion was categorized using a three-point scale based on the gray levels, and was compared with wall motion abnormalities of the corresponding region as assessed by two-dimensional echocardiography.

Adult↗

[Serial myocardial lactate metabolic changes after intracoronary thrombolysis in evolving myocardial infarction].

To ascertain whether early intracoronary reperfusion (less than 3 hours) preserves aerobic myocardial metabolism in acute myocardial infarction, serial changes in trans-cardiac lactate extraction after intracoronary thrombolysis were examined in 35 patients with acute anteroseptal myocardial infarction. Eight patients without intracoronary reperfusion served as controls. In the chronic phase, we also observed abnormally contracting myocardial segments as an index of infarct size and the regional ejection fraction as an index of chronic regional cardiac function. In the early reperfusion group (less than 3 hours; 15 cases), positive lactate extraction was restored; there were small abnormally-contracting segments and a high regional ejection fraction. However, the intermediate reperfusion group (3-5 hours; 10 cases) had sustained anaerobic lactate extraction, large abnormally-contracting segments and a low regional ejection fraction. The late reperfusion (greater than 5 hours; 10 cases) group showed apparent aerobic lactate extraction, but had large abnormally-contracting segments and a low regional ejection fraction. Thus, early reperfusion preserves aerobic lactate metabolism and good ventricular function in the chronic phase.

Heart Ventricles↗

[A double-blind comparative study of intracoronary administration of GE-0943 and urokinase: multicenter study].

Coronary thrombolysis with plasminogen proactivator, GE-0943, was undertaken in patients with acute myocardial infarction and compared with urokinase. Fifty patients were given 6000 units of GE-0943 intracoronary and the totally occluded infarct-related arteries were recanalized in 92.0%. Fifty-four patients who were given 3000 units of GE-0943 intracoronary demonstrated a recanalization rate of 68.2%, while intracoronary administration of urokinase in 54 patients showed a recanalization rate of 70.4%. There was only one patient with hemorrhagic complication among GE-0943 3000-units group, none among GE-0943 6000-units group, and 5 among urokinase group. Thus, intracoronary administration of GE-0943 is very effective and safe with a dose up to 6000 units.

Adult↗

Regression of MOPC 104E plasmacytoma with monoclonal anti-idiotype antibodies.

We investigated the therapeutic effectiveness of monoclonal anti-idiotype (anti-M104E5) antibodies. Our in vitro studies show monoclonal anti-idiotype-specific antibody SJL18-1 showed a selective inhibitory property for MOPC 104E cells over two cross-reactive idiotype antibodies N-20-2 (IgM, IdX-M104E, and J558) and CD3-2 (IgG1, IdX-M104E, and J558). Based on these observations, we further examined their biological activities in vivo. Mice given 2 x 10(4) MOPC cells s.c. were treated with various doses of the antibodies i.v. on days 0, 7, 14, 21, and 28 after tumor transplantation. In the group treated with 100 micrograms of N-20-2 antibody, the antibody treatment prevented the growth of MOPC 104E in some of the mice. Treatment of tumor-bearing mice with SJL18-1 antibody (10 to 1,000 micrograms/mouse) did not provide any survival benefit. On the other hand, in mice treated with 50 micrograms of CD3-2 antibody, four of ten mice had regression of their palpable tumors. It is important to note that the least effective antibody (CD3-2) in vitro was the most effective in vivo, and the most effective antibody (SJL18-1) in vitro did not show any survival benefit. Preliminary data indicate that the most likely mechanism of in vivo regulation of MOPC 104E myeloma is by cytostatic lymphocytes.

Animals↗

[Surgical treatment and indication for metastatic lung tumor].

Prognostic factors of patients with metastatic lung tumors were evaluated on 72 patients who were treated with pulmonary resection (49 via lateral thoracotomy and 23 via median sternotomy). The 5-year survival rate of these patients was 41.3%. Two factors, i.e., tumor free interval (TFI) and tumor size, significantly affected the survival after surgery. Patients with a longer TFI and smaller tumor(s) were associated with a favorable prognosis. The prognosis, however, was neither affected by the number of metastatic lung tumors nor whether they were unilateral or bilateral. The prognosis of lung metastases from colorectal cancer was the most favorable (61.4% at 5-year). On the other hand, patients with lung metastases from renal cell carcinoma and breast carcinoma showed poor prognosis respectively. As for testicular tumors and bone or soft tissue sarcomas, chemo-sensitivity is the most important prognostic factor. Good responders to prior chemotherapy showed a better prognosis than poor responders. These results urge the reappraisal of the role of surgery in the treatment of metastatic lung tumors and demonstrate that aggressive surgery can be indicated even for multiple or bilateral lung metastases. Nature of metastatic tumors, i.e., their origin and chemo-sensitivity, must be taken into consideration when the indication for surgery is decided.

Bone Neoplasms↗

[Clinical usefulness of three-dimensional brain imaging with N-isopropyl-p-[123I]iodoamphetamine (IMP)].

Three-dimensional reconstruction from N-isopropyl-p-[123I]iodoamphetamine (IMP) tomography has been applied clinically to the detection of perfusion defects in 22 cases (15 cerebrovascular diseases and 7 normal controls confirmed by CT and MRI), with data being analyzed in terms of receiver operating characteristic curves (ROC). The results showed that three-dimensional (3-D) image could make better diagnostic capability especially in inexperienced examiner and that it was useful decreasing of difference of diagnostic capability. 3-D image could be taken within 1 minute and 15 seconds. We concluded that the three-dimensional brain imaging with IMP using this system was clinically useful because examiner could easily diagnose perfusion defects.

Aged↗

Free and bound forms of atrial natriuretic peptide (ANP) in rat plasma: preferential increase of free ANP in spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP).

Free and bound forms of atrial natriuretic peptide (ANP) in rat plasma were analysed by gel permeation chromatography combined with a radioimmunoassay (RIA) for rat ANP (rANP). Gel permeation chromatography showed two immunoreactive peaks in rat plasma, one corresponding to alpha-rANP, rANP(99-126), and the other eluted at a high molecular weight, clearly different from gamma-rANP, rANP(1-126). The chromatographic profile of rat plasma after incubation with synthetic alpha-rANP demonstrated that the high molecular immunoreactivity had ANP-binding capacity. This bound form of ANP was almost totally excluded following extraction procedure, therefore, the immunoreactive ANP (ir-ANP) measured with the extraction assay was mainly free ANP. On the other hand, direct RIA may detect not only the free but also the bound form of ANP. Using both direct RIA and the extraction method, bound forms of plasma ANP in spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) were compared to normotensive Wistar Kyoto rats (WKY). Bound forms of plasma ANP in 20-week-old SHR and SHRSP were significantly higher than that in age-matched WKY. The ratio of free/bound form of plasma ANP in SHR and SHRSP also significantly increased compared to WKY, indicating a preferential increase in free ANP in the plasma of these hypertensive rats. These findings suggest that a bound form of ANP may be present in rat plasma and that it may play some pathophysiological role in the hypertension of SHR and SHRSP. Increased free ANP in plasma may indicate a compensatory increase in ANP release in these hypertensive rats.

Animals↗

Structure-activity relationships of 4'-O-substituted 1-benzylisoquinolines with respect to their actions on the cell membrane of blood platelets and erythrocytes.

4'-O-Substituted 1-benzyl-2-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines inhibited the collagen-induced activation (aggregation and ATP secretion) of rabbit platelets and transformed the shape of human erythrocytes in a dose-dependent manner. Both effects increased with increasing number of carbon atoms of the 4'-substituted hydrocarbon moiety. The incorporation of these compounds into the erythrocyte membrane was also dependent on the number of carbon atoms of the 4'-substituted radical. The most potent phenoxy derivative suppressed arachidonic acid release from membrane phospholipids but had no effect on arachidonic acid metabolism in platelets. This indicated that the effects are comparable to those of a natural bisbenzylisoquinoline, cepharanthine. These effects appear to be due to a perturbing action on the membrane lipid bilayer.

Adenosine Triphosphate↗

The effect of CV-4151, a selective inhibitor of thromboxane synthetase, on prostanoid formation and platelet aggregation in humans.

The pharmacokinetics and pharmacologic effects of a potent, selective inhibitor of thromboxane synthetase, CV-4151 [(E)-7-phenyl-7-(3-pyridyl)-6-heptenoic acid] on prostanoid formation and platelet aggregation were studied in 42 healthy male volunteers. The drug was well tolerated. After oral administration of 10 to 100 mg of CV-4151, peak plasma levels of 1-6 micrograms/mL were reached in a dose-dependent manner within 1 hour. Elimination followed first-order fashion with elimination half-life of about 1 hour. Serum levels of thromboxane B2 reduced to 4% to 15% of control at 2 hours after drug ingestion dose-dependently. Serum levels of 6-keto-prostaglandin F1 alpha increased to about four to six times basal levels. Platelet aggregation induced by collagen and arachidonate was inhibited in most cases. Such pharmacologic effects outlasted serum drug levels. In repeated administration, stable inhibition of serum thromboxane B2 production and platelet aggregation in proportion to the enhancement of serum 6-keto-prostaglandin F1 alpha production was observed although no drug accumulation was found. These results indicate that CV-4151 may be suitable for clinical trials in cardiovascular diseases in which imbalance between thromboxane and prostacyclin may be involved in the pathogenesis.

Adult↗

Cyanide distribution in five fatal cyanide poisonings and the effect of storage conditions on cyanide concentration in tissue.

The cyanide distribution in five fatal cyanide poisonings was analyzed by the pyridine-pyrazolone method using a Conway diffusion cell. In order to study the effect of storage conditions on cyanide concentration in tissue samples, the cyanide concentrations were first measured immediately after collection of the samples at autopsy, then measured again after storage in a refrigerator (4 degrees C) or in a freezer (-20 degrees C) for periods ranging from 1 day to 3 weeks. Concentrations in all but three of the blood samples stored at 4 degrees C or -20 degrees C increased, with concentration ratios based on measurement made before and after storage ranging from 0.71 to 1.46. The concentrations in the liver, kidney, and brain samples either increased or decreased, with ratios of from 0.2 to 8.8. The concentrations in the stomach contents samples decreased rapidly at 4 degrees C, but hardly changed at all at -20 degrees C.

Adult↗

Effects of changes in coronary stenosis on left ventricular diastolic filling assessed with pulsed Doppler echocardiography.

To determine the effects of changes in coronary stenosis on left ventricular diastolic filling, diastolic filling was serially examined before and after percutaneous transluminal coronary angioplasty using pulsed Doppler echocardiography in 50 patients with stable exertional angina pectoris. Peak rapid filling velocity and the ratio of peak atrial filling to peak rapid filling velocities were measured from the transmitral flow velocity pattern before and 2 and 9 days after coronary angioplasty. Peak rapid filling velocity increased and the ratio of peak atrial filling to peak rapid filling velocities decreased gradually after coronary angioplasty. The improvement in left ventricular diastolic filling was greater in patients with severe (greater than 90%) coronary stenosis than in patients with mild (less than or equal to 90%) coronary stenosis. In the long-term follow-up period, the improved left ventricular diastolic filling worsened in only 11 patients with marked progression to greater than 90% coronary stenosis. Thus, left ventricular diastolic filling improved gradually after coronary angioplasty, possibly reflecting post-ischemic "stunned" myocardium. Serial examinations of left ventricular diastolic filling with pulsed Doppler echocardiography may be a means of noninvasively assessing the temporal changes in the coronary stenosis and predicting the occurrence of coronary restenosis after coronary angioplasty.

Adult↗

A comparison of the 12-year mortality and predictive factors of coronary heart disease among Japanese men in Japan and Hawaii.

The mortality and predictive factors of coronary heart disease among men of Japanese ancestry in Japan and Hawaii were compared on the basis of 12 years follow-up data using comparable methods of case ascertainment and risk factor measurements. Among 1,687 men (Japan) and 7,536 men (Hawaii) who were free of coronary heart disease and aged 45-69 at baseline examination in 1965-1968, 20 (Japan) and 123 (Hawaii) cases of fatal coronary heart disease were identified. The age-adjusted mortality rate was 40% higher in Hawaii than in Japan. The difference was not statistically significant, but consistent with earlier studies. More than half of this difference in mortality rate was attributed to different levels of known risk factors in the two cohorts. In multivariate analysis using the combined population, age, blood pressure, serum cholesterol, serum glucose, cigarette smoking, and alcohol intake (inversely) remained as significant predictors of coronary heart disease mortality. Although the associations of risk factors with coronary heart disease tended to be stronger in Hawaii than in Japan, there was no statistically significant difference in regression coefficient for any of the risk factors studied. These findings cannot be claimed to be definitive because of the small number of cases, especially in Japan.

Actuarial Analysis↗

Molecular cloning of a gene affecting the autolysin level and flagellation in Bacillus subtilis.

A 2.8 kb PstI fragment of Bacillus subtilis 168W DNA has been cloned into Escherichia coli HB101 and B. subtilis AG5 using pAC3 as a shuttle plasmid. The new plasmid (pBRG1), of 10.2 kb, complemented flaD mutations which show reduced production of autolysin(s), filamentation and non-motility (deficiency of flagella). Deletion experiments showed that the suppressive gene is located between the HindIII and XbaI sites (1.0 kb apart) in pBRG1. The integration of a plasmid having chloramphenicol resistance closely linked to the flaD gene into the B. subtilis AC703 chromosome and its genetic analysis indicated that the cloned fragment contained the flaD gene itself. A high-copy-number plasmid carrying the cloned gene did not lead to an increase in autolysin production above the wild-type level, but it changed the colony morphology from smooth to rough. Among several autolysin-deficient mutations, lyt-151 was suppressed only by the high-copy-number plasmid carrying the cloned gene.

Bacillus subtilis↗

Value and limitations of Doppler echocardiography in the quantification of stenotic mitral valve area: comparison of the pressure half-time and the continuity equation methods.

Two Doppler methods, the pressure half-time method proposed by Hatle and the method based on the equation of continuity, were used to estimate stenotic mitral valve area noninvasively, and the accuracy of these methods was examined in patients with and without associated aortic regurgitation. Mitral valve area determined at catheterization by the Gorlin formula was used as a standard of reference. The study population consisted of 41 patients with mitral stenosis, and 20 of the 41 patients had associated aortic regurgitation. According to the equation of continuity, mitral valve area was determined as a product of aortic or pulmonic annular cross-sectional area and the ratio of time velocity integral of aortic or pulmonic flow to that of the mitral stenotic jet. Mitral valve area was determined by the pressure half-time method as 220/pressure half-time, the time from the peak transmitral velocity to one-half the square root of the peak velocity on the continuous-wave Doppler-determined transmitral flow velocity pattern. The pressure half-time method tended to overestimate catheterization measurements, and the correlation coefficient for this relation was .69 (SEE = 0.44 cm2). The correlation coefficient improved to .90 when the patients with associated aortic regurgitation were excluded. Mitral valve areas determined by the continuity equation method correlated well with catheterization measurements at a correlation coefficient of .91 (SEE = 0.24 cm2), irrespective of the presence of aortic regurgitation. The ratio of the time-velocity integral or aortic or pulmonic flow to the time-velocity integral of mitral stenotic jet also correlated well with mitral valve area determined by catheterization at a correlation coefficient of .84 (SEE = 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Randomized, double-blinded multicenter study. Comparison of intracoronary single-chain urokinase-type plasminogen activator, pro-urokinase (GE-0943), and intracoronary urokinase in patients with acute myocardial infarction.

Coronary recanalization rates and changes in the coagulation and fibrinolysis system were evaluated in a randomized fashion in patients with acute myocardial infarction after intracoronary administration of single-chain urokinase-type plasminogen activator (pro-urokinase: GE-0943) or urokinase. Three groups of patients were studied: group H (n = 50), 6,000 units pro-urokinase i.c.; group L (n = 44), 3,000 units pro-urokinase i.c.; and group U (n = 54), 960,000 IU urokinase i.c. Coronary recanalization rates determined angiographically after 45 minutes of intracoronary infusion averaged 90% in group H, 59% in group L, and 61% in group U. The differences were statistically significant between group H and the latter two groups. Pro-urokinase affected plasma proteins of the fibrinolytic system to a lesser degree than urokinase. Bleeding complications were present in one patient in group L, in none in group H, and in five in group U. Thus, intracoronary administration of 6,000 units pro-urokinase is more effective in coronary thrombolysis and causes less systemic fibrinogenolysis than intracoronary administration of urokinase.

Adult↗

Effect of OPC-8212 (2(1H)-quinolinone), a new inotropic agent, on myocardial energy metabolism in patients with coronary heart disease.

We examined the effects of a new inotrope, OPC-8212 (OPC: 2(1H)-quinolinone), on coronary sinus flow (CSF), myocardial oxygen consumption, myocardial lactate extraction ratio (LER), cardiac index (CI) and pulmonary arterial diastolic pressure (PADP) in eleven patients with prior myocardial infarction. Measurements were taken before (control) and 8 hours after administration of OPC (480 mg, p.o.). A cardiac function curve was obtained in each stage with rapid intravenous administration of 500 ml of saline (loaded state) after baseline measurements. There was a significant increase in the cardiac index and decrease in the pulmonary arterial diastolic pressure in the loaded state after OPC. Thus the ventricular function curve was shifted to the left and showed a steep incline, indicating an increased inotropic state. On the other hand, myocardial oxygen consumption and myocardial lactate extraction ratio were unchanged. Thus we concluded that OPC improved cardiac performance without increasing myocardial oxygen consumption.

Adult↗

Serial myocardial lactate metabolic changes after intracoronary thrombolysis in evolving myocardial infarction.

To investigate whether early reperfusion (less than or equal to 3 hours) preserves aerobic myocardial metabolism in acute myocardial infarction, we examined serial changes in trans-cardiac lactate extraction after thrombolysis in 43 patients with acute antero-septal myocardial infarction. In the chronic phase, we also determined abnormally contracting segments as an index of infarct size and regional ejection fraction as an index of chronic regional cardiac function. In the early reperfusion group (less than or equal to 3 hours), positive lactate extraction was restored and there were small abnormally contracting segments and a high regional ejection fraction. The intermediate reperfusion group (3-5 hours), however, had sustained anaerobic lactate extraction, large abnormally contracting segments and a low regional ejection fraction. The late reperfusion (greater than 5 hours) group showed apparently aerobic lactate extraction, but had large abnormally contracting segments and a low regional ejection fraction. Thus, early reperfusion preserves aerobic lactate metabolism and good chronic ventricular function.

Adult↗