[A quantitative analysis of left ventricular behavior in cineangiogram].
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Biomedical subjects
Publications and source records attributed to Y Yabe.
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Two atrial natriuretic peptides, containing 25 amino acid residues, ANF IV, and 21 amino acid residues, ANF V, were synthesized by a solid phase method and oxidized with K3Fe(CN)6 to form a disulfide bridge. Synthetic ANF IV exhibited a natriuretic activity with an ED50 70 times higher than that of synthetic ANF V, whereas the longer peptide was only 2.5 times more potent in chick rectal smooth muscle relaxant activity. Both peptides inhibited norepinephrine-induced contraction of rabbit aorta. The shorter peptide, ANF V, was 300 times less efficient than the longer peptide, ANF IV. It is proposed that the carboxy-terminal of ANF IV seems to have a modulating effect on receptor affinity in kidney and vascular tissue.
We designed aldehyde derivatives of small peptides representing the C-terminal portion of angiotensin I sequence as an inhibitor of human renin. Among compounds that we synthesized, benzyloxycarbonyl (Z)-Phe-His-Leucinal (compound V), Z-Pro-Phe-His-Leucinal (Compound IV) and Z-[3-(1'-naphthyl)Ala]-His-Leucinal (compound VII) markedly inhibited human renin (IC50, 7.5 X 10(-7), 3.2 X 10(-7) and 8.0 X 10(-8) mol/l, respectively). Compound VII was shown to be noncompetitive (Ki = 2.4 X 10(-7) mol/l). It did not inhibit either cathepsin D or pepsin. Compound V had slight or no inhibitory effect at the concentration of 10(-5) mol/l on six animal renins except for monkey and rabbit renins. Results obtained show that these aldehyde compounds are highly selective and species specific inhibitors for human and monkey renins.
Four peptides possessing both natriuretic and smooth muscle relaxant activities were purified from rat heart atrium and their amino acid sequences were determined. All contained a common sequence which contains a macro-ring structure formed by 17 amino acid residues and a disulphide bridge. The major atrial peptide in the atrium was identified as that containing 31 amino acid residues. The cDNA of the atrial peptide precursor was cloned and its nucleotide sequence determined. The amino acid sequence of the precursor deduced from the nucleotide sequence contained 152 residues and a potential signal peptide sequence characteristic of secretory polypeptides.
This investigation was designed to evaluate the difference in DNA activity between biopsy specimens obtained from right and left ventricles. Nucleic DNA in the myocardial cells of hypertrophied and congestive forms of cardiomyopathy was analyzed to investigate the relationship between cell function and clinical manifestations. Endomyocardial biopsy specimens were obtained simultaneously from right ventricular septal wall and left ventricular inferolateral wall by a transcatheter biotome. Measurement of DNA was based on the Feulgen reaction and dual wavelength cytophotometry. In this series, 12 patients with hypertrophic cardiomyopathy and four patients with congestive cardiomyopathy were studied. In the normal heart, the DNA value (arbitrary units) of the right ventricle was 138.6, whereas that of the left ventricle was 144.4. In the hypertrophic group, the mean DNA value in the right ventricle was 279.9, whereas that of the left ventricle was 317.5. In the congestive group, the DNA mean value in the right ventricle was 108.8, whereas that of left ventricle was 144.8. The linear relationship (r = 0.67) between right and left ventricular DNA values suggests that cellular function of one ventricle is affected by that of the other side. Higher DNA values of the left ventricle may indicate the difference in work load between the ventricles. The relationships among DNA values, LV wall thickness, LV mass, and parameters of contractility were statistically high.
A key enzyme of glycolysis (pyruvate kinase) and main enzymes of the electron transport system (NADH cytochrome c reductase, succinic cytochrome c reductase, and cytochrome c oxidase) were measured in left ventricular biopsy specimens from six hypertrophic (HCM) and six congestive (CCM) cardiomyopathy. Pyruvate kinase was 104.0 and 45.0 mU/mg protein in HCM and CCM, respectively. NADH cytochrome c reductase, succinic cytochrome c reductase, and cytochrome c oxidase were 146.0, 9.9, and 775.0 mU/mg protein in HCM and 87.4, 5.2, and 502.0 mU/mg protein in CCM, respectively. From these data, it is evident that glycolysis and enzyme activities of the electron transport system are increased in HCM and decreased in CCM. Cardiac function reflects the state of these energy metabolism pathways in the myocardium. The changing energy metabolism in the right ventricle of the emphysema hamster seems to support this concept.
The problems involved in the treatment, the criterion for selective initial treatment, and the relationship between the treatment and the prognosis were studied in 48 patients with unstable angina pectoris, based on coronary arteriographic findings, left ventricular performance, coronary circulation and myocardial energetics with various interventional observations. Among these patients 43.7% initially responded to medication and 56.3% did not. In newly developed angina at rest, the effectiveness of an isolated sustained administration of isosorbide dinitrate (ISDN) or Ca2+ antagonist (nifedipine) was 100%, while in the changing pattern type of effort angina, the effectiveness of nifedipine was 71.4%, being higher than that of other drugs. As for coronary circulation, nifedipine, having different effects from ISDN, acted directly on resistance vessels and increased the endocardium/epicardium blood flow ratio by its powerful preload-unloading effect. Percutaneous transluminal coronary angioplasty (PTCA) was performed on 5 patients with unstable angina pectoris (USP). A completely asymptomatic condition, significant dilatation and improvement of coronary circulation were obtained after PTCA. The prognosis of UAP was not good with a mortality rate of 21%. Therefore, initial intensive medical therapies and the earliest stabilization of the patients' conditions are also important. The mechanism of the resistance to medical treatment is an important problem to be solved in the near future. In addition to the validity of the definitions of this disease, the appropriate long-term management must also be considered.
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Left ventricular performance, survival rate and subjective symptoms were analyzed in 243 cases of angina pectoris (147 cases of A-C bypass and 96 cases of medical treatment) and 58 cases of left ventricular aneurysm (21 cases of surgical treatment and 37 cases of medical treatment). Left ventricular performance of angina pectoris were improved in surgical group 6 months after A-C bypass with the significance of p less than 0.02-0.05. However, in the medical group, it showed unchanged or aggravated tendency during average 18 months. Similar results were obtained in the patients with left ventricular aneurysm and furthermore, aggravation of EF and Max dp/dt/p in some medically treated cases was observed. Operative death by A-C bypass was seen in 4 cases (2.7%) and 5 years cumulative survival rate was 92.6% including late death cases died during average 30.1 months in the medical group and its 5 years survival rate was 77.3%. For left ventricular aneurysm, no operative death was recognized and the 5 years cumulative survival rate was 95%. Whereas during average 32.7 months in the medical group, 8 cases died and 5 years cumulative survival rate was 78.6%. Improvement of subjective symptoms after treatment for both ischemic heart diseases was also conspicuous in the surgical group.
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Inosine at the dose of 200 mg was administered via central vein to 16 cases of various cardiac diseases, including effort angina pectoris, myocardial infarction, valvular disease, idiopathic cardiomyopathy, and congenital heart disease. Left ventricular performance was assessed by the time-course of various hemodynamic parameters (pulmonary wedge pressure, heart rate, LVP, LVEDP, max dp/dt, dp/dt/P, and cardiac output) including ejection fraction in some cases. Inosine caused significant decrease in pulmonary wedge pressure ranged from-7% to -47% during 5 min period following injection. Significant decrease in LVEDP ranged from -4% to -67% was also observed. Meanwhile significant decrease in systolic left ventricular pressure (LVP) was observed. In patients with relatively low value of max dp/dt (less than 1,500 mmHg/sec), the increase ranged from 100 to 300 mmHg/sec (6% to 38%) except 1 case with hypertrophic obstructive cardiomyopathy. In all cases, increase in dp/dt/P ranged from 4% to 44% during 5 min period following injection. In addition, the ejection fraction increased slightly in 2 out of the 3 cases studied. Cardiac output increased in all cases except a normal case by 1% to 31% during the period of 5 to 10 min following injection. Change in the heart rate was not significant. Quantitative evaluation disclosed the beneficial effects of inosine on the left ventricular function through the remarkable load-reducing effect and the unequivocal positive inotropic effect, particularly in the cases of disturbed functions. In addition, mild coronary vasodilation action was also noted.
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Mason-Pfizer monkey virus (MPMV), baboon endogenous virus (BaEV) and simian sarcoma virus associated virus (SSAV) induced fusion in cultured human cells derived from tumors or transformed in vitro. Not only virus-transformed cells, but also cells transformed spontaneously by 4-nitroquinoline 1-oxide (4-NQO) treatment or by 60Co-gamma ray irradiation were fused by these simian retroviruses. Non-transformed cells derived from normal human embryos were not fused by any of these viruses. Of these tumor or transformed cells, cells carrying Rous sarcoma virus (RSV) genome were most extensively fused by these simian retroviruses. Anti-MPMV, anti-BaEV and anti-SSAV sera blocked the cell fusion mediated by MPMV, BaEV and SSAV, respectively, and not that by other viruses, indicating that the cell fusion was virus-specific.
To observe changes in nucleic acid synthesis, which represent the major role in cell function, DNA volume was measured for each myocardial cell biopsied from 28 patients that were cineangiographically recognized as hypertrophic cardiomyopathy or congestive cardiomyopathy with the use of Feulgen cytophtometry. Normal heart muscle cell are diploid to tetraploid. In hypertrophic cardiomyopathy (HCM), nucleic DNA are hyperploid compared to normal hearts. In HCM with obstruction, cell nuclei are tetraploid to octoploid. In HCM without obstruction, cell nuclei can be recognized as both tetraploid to octoploid and hexaploid to decaploid, having two kinetic patterns. In congestive cardiomyopathy DNA values are lower compared to control, and nucleic DNA has a tendency to hypodiploidy. Correlation between DNA values and wall thickness are highest. Correlation between DNA and other left ventricular functions (ejection fraction, mean VCF, and Vmax) is also high.
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