[Relationship of calcium, and magnesium with blood pressure].
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Biomedical subjects
Publications and source records attributed to T Mikawa.
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A 51-year-old man who had a past history of gastric resection for medically uncontrollable gastric ulcer has loss of appetite that recurs periodically. And he has frequently presented spontaneous angina early in the morning since 1984. He was diagnosed as having variant angina by the documentation of typical ST elevation during anginal attack and also by showing coronary artery spasm (#2 and #12) during hyperventilation on coronary arteriography. A large quantity of calcium blocking agents and nitrates could not improve his symptoms. Lack of intracellular magnesium by loss of appetite was suspected from a daily excretion of urine magnesium (5.3 mEq) and magnesium tolerance test (56.7%). To confirm the effect of magnesium administration, the second coronary arteriography was performed. After magnesium sulphate (80 mEq, hourly) was injected, coronary artery spasm could not be induced by ergonovine. And orally magnesium oxide, calcium blocking agents and nitrates were started. Anginal attack disappeared with increasing urine magnesium.
Bidirectional organelle movements taking place in the cytoplasm of the rhizomes of Caulerpa, a coenocytic marine green alga, have been indicated to be dependent on microtubules (Kuroda, K. & Manabe, E. (1983) Proc. Jpn. Acad. 59B, 131-134; Manabe, E. & Kuroda, K. (1984) Proc. Jpn. Acad. 60B, 118-121). However, when a crude extract of Caulerpa rhizomes was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and subjected to immunoblotting with monoclonal anti-tubulin antibody, no reacting band could be detected. This apparent absence of tubulin in the extract was found to be a result of the complete degradation of tubulin by potent intrinsic proteolytic activity. All of the commercially available protease inhibitors so far tested (p-chloromercuriphenylsulfonic acid, phenyl methylsulfonyl fluoride, 1-chloro-4-phenyl-3-tosylamido-2-butanone, 7-amino-1-chloro-3-tosylamido-2-heptanone, p-tosyl-L-arginine methyl ester, soybean trypsin inhibitor, antipain, chymostatin, leupeptin, and pepstatin) failed to inhibit the activity completely. But addition of casein at the concentration of 1% (weight per volume) to the solutions used for preparation was effective in protecting tubulin from proteolytic degradation, thus making it possible to prepare tubulin from the crude extract of Caulerpa. On SDS-PAGE, the Caulerpa alpha-tubulin thus prepared was a little smaller in molecular weight than that of rabbit brain.
Ten Drosophila thorax proteins (six myosin light chains and four proteins called a, b, c, d) were found to have high affinities with Ca2+. This was proved after subjecting the total Drosophila thorax proteins to two-dimensional (2D) transblot, followed by 45Ca2+ autoradiography. Three proteins (a, c, d) showed Ca2+ dependent electrophoretic mobility changes. To know their tissue-specific localization, fibrillar and tubular type muscle fibers were individually dissected from freeze-dried flies and separately subjected to 2D gel electrophoresis. Fibrillar type muscle had protein b and a small amount of protein a. Tubular type muscle had proteins c, d and a very large amount of protein a. Protein d was characterized to be calmodulin.
Two new cytotoxic polycyclic xanthones, actinoplanones A (1) and B (2) were isolated from the culture broth of Actinoplanes sp. R-304 by monitoring their bioactivity against HeLa cells. Compound 1 was extremely cytotoxic (IC50 0.00004 micrograms/ml) against HeLa cells. The structures of 1 and 2 were established mainly by analyses of 2D heteronuclear correlation NMR experiments. The absolute configurations of the asymmetric carbons of the compounds have been assigned to be 9R, 24S, 25R and 27S by circular dichroism spectra and NMR analysis using chiral derivatives (esters of alpha-methoxy-alpha-(trifluoromethyl)acetic acid).
Our previous finding of strong cytotoxic polycyclic xanthones, actinoplanones A (1) and B (2), in the culture broth of Actinoplanes sp. R-304 stimulated us to isolate further five new cytotoxic polycyclic xanthones which were named actinoplanones C (3), D (4), E (5), F (6) and G (7) from the broth. Actinoplanones C (3) and G (7) showed very strong cytotoxicity against HeLa cells at less than 0.00004 microgram/ml dosage (IC50). The structures of 3-7 were varieties of 1 for the N-2 and C-4 substituents. All or several actinoplanones showed strong antimicrobial activities against bacteria and the rice blast fungus. Actinoplanone A (1) was tested for cytotoxicity against various tumor cells and for inhibitory effect on HeLa cell macromolecular synthesis, and 1 exhibited strong cytotoxicity against the cells and inhibitory action on DNA synthesis.
The 1979 amino acid sequence of embryonic chicken gizzard smooth muscle myosin heavy chain (MHC) have been determined by cloning and sequencing its cDNA. Genomic Southern analysis and Northern analysis with the cDNA sequence show that gizzard MHC is encoded by a single-copy gene, and this gene is expressed in the gizzard and aorta. The encoded protein has a calculated Mr of 229 X 10(3), and can be divided into a long alpha-helical rod and a globular head. Only 32 to 33% of the amino acid residues in the rod and 48 to 49% in the head are conserved when compared with nematode or vertebrate sarcomeric MHC sequences. However, the seven residue hydrophobic periodicity, together with the 28 and 196 residue repeat of charge distribution previously described in nematode myosin rod, are all present in the gizzard myosin rod. Two of the trypsin-sensitive sites in gizzard light meromyosin have been mapped by partial peptide sequencing to 99 nm and 60 nm from the tip of the myosin tail, where these sites coincide with the two "hinges" for the 6 S/10 S transition. In the head sequence, several polypeptide segments, including the regions around the putative ATP-binding site and the reactive thiol groups, are highly conserved. These areas presumably reflect conserved structural elements important for the function of myosin. A multi-domain folding model of myosin head is proposed on the basis of the conserved sequences, information on the topography of myosin in the literature, and the predicted secondary structures. In this model, Mg2+ ATP is bound to a pocket between two opposing alpha/beta domains, while actin undergoes electrostatic interactions with lysine-rich surface loops on two other domains. The actin-myosin interactions are thought to be modulated through relative movements of the domains induced by the binding of ATP.
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To evaluate the relationship between the motion pattern and degree of organic change of the anterior mitral leaflet (AML) and the features of the mitral component of the first heart sound (M1) or the opening snap (OS), 37 patients with mitral stenosis (MS) were studied by auscultation, phonocardiography and echocardiography. Based on the features of M1 and OS according to auscultation and phonocardiography, the patients were categorized as group I, 18 patients with loud and snappy M1 and OS; group II, 12 patients with snappy M1 but small and dull OS; and group III, seven patients with small and dull M1 and OS. Intensities of M1 and OS were calculated by the ratios of their amplitudes to the aortic component of the second heart sound on the high frequency phonocardiograms recorded at points of the maximum intensities, respectively. Echocardiographic parameters related to productions of M1 and OS were obtained from M-mode and two-dimensional echograms of the AML; they were amplitudes and velocities on closing and opening, M1 area defined as that between end-diastolic and systolic echoes, OS area between systolic and early diastolic echoes, the doming area between the trailing edge of an early diastolic echo and a line projected from the anterior annulus to the tip of the leaflet, and the degree of systolic ballooning. Results were as follows: 1. Significant differences in the area of the mitral valve orifice were found among three groups. The area was maximum in group II, minimum in group III and intermediate in group I. 2. In group I, the body of the AML was pliable, resulting in a ballooning into the left atrium in systole and a marked doming toward the left ventricle in early diastole. Various parameters related to the production of M1 and OS in group I were significantly increased as compared with those of the other two groups. 3. In group II, the body of the AML was not pliable in spite of mild organic changes in the valve. The degree of early diastolic doming was mild. Compared to group III, the intensity of M1 in group II was significantly larger, but no significant difference was observed in the parameters related to the production of M1 between the two groups.(ABSTRACT TRUNCATED AT 400 WORDS)
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To clarify the mechanism of the reduced intensity of the mitral component of the first heart sound (IM) in complete left bundle branch block (LBBB), electrocardiograms, phonocardiograms, apexcardiograms and mitral valve echograms of 12 patients with LBBB (LBBB group) and 13 normal subjects (normal group) were simultaneously recorded. The first derivative of the apexcardiogram was also studied. One of the 12 patients had an intermittent LBBB. There was no significant difference in the P-Q interval between the two groups. The following results were obtained: 1. In the LBBB group; 1) The intensity of the IM, expressed as a ratio of the amplitude of the IM to that of the aortic component of the second heart sound (IIA) on the apical phonocardiograms, was significantly reduced except in one patient who had a relatively short P-Q interval. 2) The timings of the onset of the upstroke of the apexcardiogram and mitral valve closure were significantly and equally delayed. 3) The amplitude of the mitral valve echogram at the onset of the upstroke of the apexcardiogram (end-diastolic amplitude of the mitral valve) was significantly decreased. The closing velocity of the mitral valve was also decreased. 4) The amplitude ratio (H2/H1) and the rate of rise (A) of the apexcardiogram at the onset of the IM were significantly decreased. 2. The intensity of the IM, H2/H1 and A of the apexcardiogram at the onset of the IM were compared for three cases with nearly equal end-diastolic mitral valve amplitudes in each group. The intensity of the IM was apparently reduced in the LBBB group, compared with that of the normal group, and its intensity correlated inversely with H2/H1 and A. These results indicate that the reduced intensity of the IM in LBBB is caused mainly by the decreased amplitude of the mitral valve excursion at the onset of left ventricular contraction. An additional cause is the decreased tension on the closed mitral valve resulting from the slow rate of left ventricular pressure rise at the onset of the IM.
The clinical significance of the mode of left ventricular (LV) diastolic filling in hypertrophic cardiomyopathy was studied by the LV inflow velocity patterns (LVIF) of pulsed Doppler echocardiography and LV early diastolic filling rates (V2) of radionuclide (RI) angiography. The relationship between the deceleration time (DT) obtained from LVIF and the V2 was evaluated in 34 patients with nonobstructive hypertrophic cardiomyopathy (HCM) and in nine with obstructive hypertrophic cardiomyopathy (HOCM), and the results were compared with those of 10 patients with dilated cardiomyopathy (DCM), of two with restrictive cardiomyopathy (RCM), and of 19 normal subjects. HCM was subdivided into the following groups according to V1-DT relationships: Group 1 with prolonged DT and decreased V1, Group 2 with normal or short DT and normal V1, and Group 3 with normal or short DT and decreased V1. There were significant negative correlations between V2 and DT in Groups 1 and 2 of HCM, normal and HOCM. However, there were significant positive correlations in Group 3 of HCM, DCM and RCM. Nearly all patients in Group 3 had decreased LV ejection fraction and % fractional shortening, distinct B-B' step formation of the mitral valve echogram, and huge A wave of the apexcardiogram. These findings suggested that the LV rapid filling interval gradually became shorter because the LV contraction is decreased as myocardial fibrosis develops in HCM, and that we must pay attention to the diagnosis of such abnormalities, similar to those of DCM or RCM.
To clarify the genesis of a protodiastolic extra heart sound (S3') which was occasionally recorded at about the beginning of a diastolic rumble in mitral stenosis (MS), phono-, apex- and echocardiography were performed for 33 patients with MS, and left ventricular (LV) cineangiography was performed for eight of them. The patients were classified as S3'(+) and S3'(-) groups, according to whether they had S3'. Results were as follows: The S3' was synchronous with the rapid filling (RF) wave of the apexcardiogram (ACG). Its amplitude was proportional to the size of the RF wave. The RF wave was significantly sharper in the S3'(+) group as compared with that of the S3'(-) group. The S3' always appeared after onset of dispersion of dots in the velocity pattern of blood flow at the mitral valve orifice according to pulsed Doppler echocardiography. There was no significant difference between the S3'(+) and S3'(-) groups in the region of the mitral valve orifice according to two-dimensional echocardiography, and at the peak rate of change of the LV dimension during diastole as determined by M-mode echocardiography. The peak rate of change of the long-axis dimension of the LV during diastole as determined by cineangiography was significantly greater in the S3'(+) group than in the S3'(-) group. However, there was no significant difference between the two groups regarding the peak rate of change in the short-axis dimension of the LV during diastole as determined by cineangiography. The amplitude of the early diastolic dip of the interventricular septum (IVS) was significantly greater in the S3'(+) group as compared with that of the S3'(-) group. The amplitude of the S3' and the size of the RF wave correlated positively with the amplitude of the early diastolic dip of the IVS in pts with atrial fibrillation. Fractional shortening of the LV ascertained by M-mode echocardiography was significantly greater in the S3'(+) group than in the S3'(-) group. The end-systolic dimension of the LV tended to be less in the former than in the latter group. In conclusion, the S3' in MS was considered to be a third heart sound. Expansion along the long-axis of the LV and its sudden change in early diastole may account for the genesis of the S3', and this expansion may be accentuated by restoring force and active diastolic suction of the LV, and by velocity, direction and spread toward the cardiac apex of the stenotic mitral jet flow.
To investigate the mechanism of an apical mid-diastolic rumble in hypertrophic cardiomyopathy (HCM), we recorded left ventricular (LV) inflow velocity patterns using pulsed Doppler echocardiography and apexcardiography for 10 HCM patients with rumble and 20 HCM patients without rumble. Controls consist of 17 normal subjects, three patients with complete atrioventricular block and two patients with artificial right ventricular pacemakers. The LV inflow velocity profiles were analyzed in terms of acceleration time (AT) and deceleration time (DT) of the rapid filling wave, and the ratio of peak velocity of the atrial contraction wave to that of the rapid filling wave (A/D ratio). The results were as follows: The apical mid-diastolic murmur in HCM had a crescendo-decrescendo character mainly of medium frequency, and increased in intensity after the inhalation of amyl nitrite. All patients with rumble had asymmetric septal hypertrophy and the five of these had LV outflow obstruction. In six of the 10 patients with rumble, mild mitral regurgitation was detected. In HCM with rumble, the AT tended to be shorter than that of HCM without rumble, but it was significantly longer than the AT of normal subjects. In HCM with rumble, the DT was significantly shorter than that of HCM without rumble, but it was significantly longer than the DT of normal subjects. There was no significant difference in the A/D ratio between the HCM with rumble and the normal subjects, but the A/H ratio of the apexcardiogram was significantly increased in HCM with rumble as compared with those of HCM without rumble and of the normal subjects. The LV dimension was significantly decreased in HCM with rumble as compared with those of HCM without rumble and the normal subjects. Peak negative VCF was significantly decreased in HCM with rumble as compared with that of HCM without rumble. But there was no significant difference in this parameter between HCM with rumble and the normal subjects. In simultaneous recordings of apical mid-diastolic rumble and LV inflow velocity patterns, the rumble appeared to start after the beginning of the diastolic rapid filling wave and to stop before or at the end of the diastolic rapid filling wave. In patients with complete atrioventricular block and with artificial right ventricular pacemakers, the apical mid-diastolic rumble appeared when the P wave was during the rapid filling phase of the left ventricle.(ABSTRACT TRUNCATED AT 400 WORDS)
A new simple method of detecting calcium binding proteins in a protein mixture is described. A sample which might include calcium binding proteins was subjected to SDS-polyacrylamide gel electrophoresis and then electrophoretically transferred to a nitrocellulose membrane. The membrane was then incubated with 45Ca to detect calcium binding proteins as radioactive bands by autoradiography. Purified troponin-C, calmodulin, myosin DTNB light chain, and parvalbumin were clearly identified by this method. In the whole homogenate of chicken skeletal muscle, myosin DTNB light chain, troponin-C, and 55K calcium binding protein were found to be radioactive. In the frog skeletal muscle, small molecular weight proteins of approximately 13-15K and 70K protein appeared to be the calcium binding proteins. In the case of the carp skeletal muscle, small molecular weight proteins including parvalbumin and two proteins of about 80K seemed to bind calcium ion. Two high molecular weight calcium binding proteins were present in the scallop striated muscle. The procedure described can be completed within 24 h and can detect as little as 2 micrograms of calcium binding protein in the starting sample. Under appropriate conditions it was possible to detect only high affinity calcium binding proteins.
In order to evaluate the clinical significance of the markedly protruding interventricular septum into the left ventricular (LV) cavity (sigmoid septum), we performed non-invasive studies including amyl nitrite (AN) inhalation in 21 patients (pts) with two-dimensional echocardiographic (2DE) documentations. LV outflow tract (LVOT) obstruction was determined by the presence at least three of the following findings at rest or during AN inhalation: 1) a loud apical ejection systolic murmur (ESM), 2) a midsystolic dip in the carotid pulse, 3) systolic anterior motion (SAM) of the mitral valve (MV) or chordae tendineae, and 4) systolic semiclosure of the aortic valve (AV). The 21 pts were subdivided into six pts (group I) with resting (two pts) or provocative (four) obstruction, and 15 pts (group II) without obstruction. Their ages ranged from 40 to 85 years with an average of 65. No pt had evidence of hypertrophic cardiomyopathy. Results were as follows: In five pts of group I a long ESM with a mid-systolic peak was recorded near the apex. After AN inhalation, this murmur was markedly intensified. On the contrary, all pts of group II had a short and early systolic murmur, which was not markedly intensified by AN. In contrast to group II, group I pts had a significantly smaller LV end-diastolic dimension, a smaller LVOT dimension, higher percent thickening of the LV posterior wall, higher fractional shortening and decreased aorto septal angle (the angle between the anterior aortic wall and the interventricular septum by 2DE). On 2DE, each pt of group I showed significant narrowing between the protruded septum and the hypercontractile LV posterior wall with the papillary muscle. Anteriorly shifted chordae tendineae noted as the SAM on the M-mode echocardiogram might also play an important role on the genesis of obstruction. The signs of LVOT obstruction at rest disappeared following oral administration of propranolol in two pts of group I. These observations suggested that LVOT obstruction might occur in some pts with sigmoid septum and the hypercontractile state, and that a systolic murmur observed in this condition should be differentiated from a functional murmur in the aged or a systolic murmur in hypertrophic obstructive cardiomyopathy.
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Two-dimensional echocardiograms (2-DE) and phonocardiograms (PCG) were used to clarify the genesis of mitral valve prolapse (MVP) and mitral regurgitation (MR) in 44 patients with funnel chest. These patients were categorized in three groups on the basis of the fronto-sagittal index (FSI) as determined from chest radiographs; 17 as mild, 15 as moderate and 12 as severe funnel chest. Their ages ranged from 5 to 65 years and averaged 24 years. MVP was diagnosed using the long-axis view of the 2-DE, and MR was diagnosed phonocardiographically including provocative test using angiotensin II. The results were as follows: In 44 patients with funnel chest, 20 (45%) had MVP and 15 (34%) had MR, respectively. The incidence of MVP increased directly in proportion to the severity of index, but the incidence of MR did not. In the short-axis view of the left ventricle at the level of the papillary muscles, there was more marked flattening of the interventricular septum than of the left ventricular posterior wall, resulting in deformity of the left ventricular geometry. A distortion index (DI) was used to quantify the degree of distortion of left ventricular shape, calculated as follows: DI = (R-r)/r, where R and r were radii of the curvatures of the interventricular septum and the left ventricular posterior wall, respectively. The DI in end-diastole (DId) and end-systole (DIs) increased in proportion to the severity of funnel chest. Patients were subdivided into four groups on the basis of DId. Incidence of MVP increased in proportion to the degree of distortion of the left ventricular shape. There was, however, no significant difference in the incidence of MR among the four groups. Patients were subdivided; one group of 13 under 14 years of age; another, 31 over 15 years old. The incidence was much higher in the latter than the former, but the incidence of MVP increased in proportion to the severity of funnel chest in both groups. MR was complicated by MR in nearly all cases in the latter group, but none had MR in the former. The DI of patients, whose FSI improved with surgery, apparently improved in addition to the disappearance and/or improvement of their MVP and MR. However, patients whose FSI did not improve with surgery showed little change in DI and persistence of MVP and/or MR.(ABSTRACT TRUNCATED AT 400 WORDS)