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Biomedical subjects

H Matsubara

Publications and source records attributed to H Matsubara.

At least 199 records · Page 11Linked to original sources

Logistic characterization of left ventricular isovolumic pressure-time curve.

Although some investigators have attempted to express the left ventricular pressure-time curve by mathematical functions such as exponential and sinusoidal functions, none of them reasonably fits the left ventricular pressure-time curve. In the present study, we hypothesized that a ventricular isovolumic pressure-time curve could be expressed as the difference between two S-shaped curves for pressure rising and falling, and proposed a new "hybrid logistic" function to express the left ventricular isovolumic pressure-time curve. We investigated how well this hybrid logistic function fits left ventricular isovolumic pressure curves experimentally observed under physiological preload and contractility in the excised cross-circulated left ventricles of 10 dogs. The new function precisely fitted the isovolumic pressure curves regardless of preload and contractility with correlation coefficients above 0.9996, much better than the previously proposed functions. The observed values characterizing the magnitude and time course of the isovolumic pressure curve such as peak +/- dP/dt also closely correlated with the corresponding theoretical values calculated by the present best-fit function. We conclude that our new hybrid logistic function reasonably characterizes the canine left ventricular isovolumic pressure-time curve within physiological ranges of preload and contractility. The present results indicate that this hybrid logistic function is useful to evaluate left ventricular contraction and relaxation comprehensively.

Animals↗

Sinusoidal and exponential decays of postextrasystolic transient alternans in excised blood-perfused canine hearts.

We have recently reported that the postextrasystolic contractile potentiation decays in alternans after a compensatory pause in canine left ventricles even under normal coronary and contractile conditions. The transient alternans appears to consist primarily of a small-magnitude exponential decay and a large-magnitude sinusoidal decay. We, therefore, hypothesized that the contractility (y) of the postextrasystolic alternans beats (beat number x) could be expressed as y = a x exp[-(x-1)/b] + c x exp[-(x-1)/d] x sin[pi(x-0.5)] + yo, where a and c are the normalized magnitudes (relative to the preceding regular beat) of the two exponential terms in the first postextrasystolic beat, b and d are their time constants, and yo is the normalized magnitude of the post-alternans regular beat (approximately 1). The first exponential term represents the monotonic decay. The sine term multiplied by the second exponential term represents the alternating decay. Mathematical curve-fitting indicated: 1) the above equation very closely fitted the alternans data with a squared correlation coefficient of 0.9996 on average, 2) c was 7 times on average greater than a, indicating dominance of the sine component, 3) b and d were 2.5 and 1.0 beats on average, indicating a faster decay of the sine component, and 4) this b was comparable to the time constant of the exponential decay of the postextrasystolic potentiation after no compensatory pause. This study suggests that myocardium has a mechanism to switch the postextrasystolic potentiation between the exponential and alternans decays depending on the first postextrasystolic interval.

Animals↗

Left ventricular mechanoenergetics under altered coronary perfusion in guinea pig hearts.

Coronary perfusion pressure (CPP) is well known to affect left ventricular (LV) mechanoenergetics (Gregg's phenomenon). The garden hose effect via the Frank-Starling mechanism caused by coronary distension has long been considered to be the underlying mechanism of this phenomenon. However, recent studies have revealed a close correlation between CPP and the excitation-contraction coupling in myocytes. The aim of this study was to investigate the mechanoenergetic aspects of Gregg's phenomenon by the ventricular contractility (Emax) dependency of the myocardial oxygen consumption (VO2)-total mechanical energy (PVA, systolic pressure-volume area) relationship. Experiments were performed in the excised, cross-circulated guinea pig heart preparation. The protocol consisted of LV volume loading (VOL run), changing coronary perfusion pressure at a fixed LV volume (CPP run) and intracoronary calcium (Ca) infusion also at the same LV volume (Ca run). In all seven hearts, we obtained a linear VO2-PVA relation in VOL run. The VO2-PVA relations in CPP and Ca runs, which equally enhanced Emax, were highly linear and had no significant difference in their slopes, both significantly steeper than in VOL run. These findings suggest no significant difference in the oxygen cost of Emax between CPP and Ca runs. The enhanced LV mechanoenergetics under increasing CPP is characterized by increases in the VO2 component primarily for the excitation-contraction coupling to a greater degree than expected from the mechanical (garden hose) effect.

Animals↗

Suppressive effect of anti-alpha 1-antichymotrypsin serum on pulmonary fibrosis induced by phorbol myristate acetate in vivo.

BACKGROUND: PMA induces pulmonary fibrosis in the rabbit (1). Pulmonary fibrosis induced by PMA occurs in the alveolar wall and has the same pattern as idiopathic pulmonary fibrosis (IPF)(2), so this system can be used as an animal model for IPF. PMA also increases the content of alpha-1-antichymotrypsin (ACT) in cultured alveolar macrophages of bronchoalveolar lavages (BAL), and dexamethasone inhibits this PMA-induced increase (3). Here we investigated the role of ACT in pulmonary fibrosis induced by PMA. EXPERIMENTAL DESIGN: Rabbits were treated intratracheally for 6 days with saline, dimethyl sulphoxide (DMSO) used as a solvent of PMA, PMA dissolved in DMSO or PMA plus anti-ACT rabbit serum. BAL samples were obtained. ACT in cell pellet and cell-free fluid of BAL were assayed by radioimmunoassay. Sections of the lung were examined histologically by a point count method. The ratio of fibrosis to elastosis (fibrotic ratio) was evaluated for each rabbit by the ratio of total points of collagen stained by the Azan-Mallory method to those of elastic fiber stained by the Elastica van Gieson method. Hydroxyproline (HP) was assayed biochemically, and the amount of HP in the alveolar wall for each rabbit was calculated using the assayed values of HP and the ratio of histologic collagen points in the alveolar wall to those in the lung tissue by a point count method. RESULTS: The fibrotic ratio of the PMA group increased fourfold compared with that of the saline group. The ratio of the PMA plus anti-ACT group decreased and was similar to that of the saline group. The ratio of the DMSO group was about two times as much as that of the saline or the PMA plus anti-ACT groups. The calculated amount of hydroxyproline in the alveolar wall of the PMA group increased and was approximately 1.5-fold compared with that of the saline group. The amount of HP of the PMA plus anti-ACT group decreased and was similar to that of the saline group. In the BAL, the amount and the percentage of ACT in cell pellet per macrophage of the PMA group increased more than those of the saline and DMSO groups. The amount and percentage of the PMA plus anti-ACT group were significantly less than those of the PMA group. Those of the DMSO group were similar to those of the saline group. CONCLUSIONS: These findings suggest that anti-ACT has a suppressive effect on pulmonary fibrosis induced by PMA and that ACT is important in the PMA model of pulmonary fibrosis.

Animals↗

[Prediction of ineffective outcome of surgical treatment for constrictive pericarditis].

The preoperative factors predicting the outcome of surgical treatment for constrictive pericarditis were investigated in 22 patients with constrictive pericarditis who underwent pericardiectomy. The NYHA functional class was improved in nine patients after surgery (improved group), but not in the other 13 patients (unimproved group). Preoperative right and left heart catheterization data and echocardiograms were compared between these two groups. Right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) were significantly higher in the unimproved group. The left atrial diameter (LAD) measured by echocardiography was significantly greater in the unimproved group. These results indicate that pericardiectomy will cause a worsened immediate outcome in patients with severe pericardial constriction. LAD was the most useful parameter in predicting the ineffectiveness of the pericardiectomy. If the borderline value of LAD is taken as 40 mm, the sensitivity and specificity predicting ineffective surgery were 92% and 89%, respectively. RAP and PCWP could not separate the two groups satisfactorily. Pericardiectomy should be performed before the pericardial constriction progresses, and before LAD reaches 40 mm.

Adult↗

[Pathophysiology and Diagnosis of the acute respiratory distress syndrome].

We studied methods for diagnosing the acute respiratory distress syndrome (ARDS) based on its characteristic abnormalities. A gamma-ray external counting method with Tc-99m human serum albumin revealed that pulmonary microvascular permeability was abnormally high in patients with ARDS. With this method, ARDS could be distinguished from cardiogenic pulmonary edema. Levels of interleukin-8 in bronchoalveolar fluid from patients with septic ARDS, reexpansion pulmonary edema, and inhalation burn injury were abnormally high. In 21 patients with acute lung injury, 15 of whom had ARDS, plasma concentrations of three inflammatory markers were measured: thiobarbituric acid reactive material which reflects cell membrane lipid peroxidation; 7S collagen, a component of basement membrane; and the soluble form of P-selectin, an adhesion molecule. Levels of all three were abnormally high in patients with ARDS, and correlated with the degree of lung injury and with the outcome in these patients. We conclude that these measurements in plasma or bronchoalveolar lavage fluid may enable us to assess the severity of ARDS.

Biomarkers↗

New crystal forms and preliminary X-ray diffraction studies of mitochondrial cytochrome bc1 complex from bovine heart.

Two new crystal forms of the cytochrome bc1 complex (ubiquinol:ferricytochrome c oxidoreductase, EC. 1.10.2.2) from bovine heart mitochondria were obtained by the batch method with polyethylene glycol 4000 as the precipitant, when buffer was exchanged from Tris-HCl to potassium phosphate. The first crystal form belongs to the hexagonal space group P61 or P6(5) with unit-cell constants of a = b = 131 A and c = 720 A. The reproducibility of crystallization and the quality of this crystal form were improved by an addition of ZnCl2 to the protein solution. The second crystal form, obtained from the enzyme preparation purified by crystallization, belongs to the tetragonal space group P4(1) or P4(3) with unit-cell constants of a = b = 190 A and c = 445 A. Both crystals diffracted X-rays to 6.5 A resolution and gave sharper diffraction spots than the previous monoclinic form. X-ray intensity data to 8.0 A resolution for the hexagonal crystal and to 7.0 A resolution for the tetragonal one were collected with synchrotron radiation.

Animals↗

Crystal structure of the fungal peroxidase from Arthromyces ramosus at 1.9 A resolution. Structural comparisons with the lignin and cytochrome c peroxidases.

The crystal structure of the peroxidase (donor: H2O2 oxidoreductase, EC 1.11.1.7) from the hyphomycete Arthromyces ramosus (ARP) has been determined by the multiple isomorphous replacement method and refined by the simulated annealing method to a crystallographic R-factor of 17.4% for the 19,191 reflections with F > 2 sigma F between 7.0 and 1.9 A resolution. The model includes residues 9 to 344, the heme group, two N-acetylglucosamine residues, two calcium ions and 246 water molecules. The root-mean-square deviation of bond lengths from the ideal values is 0.02 A. The mean coordinate error is estimated as 0.2 A. The electron density of the glycine-rich region of the amino-terminal eight residues was invisible. ARP has ten major and two short alpha-helices and a few short beta-strands. The overall tertiary structure of ARP is similar to that of yeast cytochrome c peroxidase (CCP) and is particularly similar to that of the lignin peroxidase (LiP) from Phanerochaete chrysosporium. Relative to CCP, ARP and LiP each have an extension of approximately 40 residues at the carboxy terminus. All eight cysteine residues in ARP form disulfide bonds (C12:C24, C23:C293, C43:C129 and C257:C322). Two calcium sites are inaccessible to solvent. The four disulfide bonds and two calcium sites, which are lacking in CCP, are conserved in ARP and LiP. The bond from Asn304C to Ala305N in ARP is the site sensitive to proteases. An Asx turn present in the Asn303 to Ala305 segment appears to orient the side-chain of Asn304 to outward from the molecule, rendering it easily trappable by pockets of proteases. The proximal heme ligand is His184 in helix F (distance of N epsilon 2 ... Fe, 2.10 A), and one of several water molecules in the distal pocket of the heme bridges the iron atom and the N epsilon 2 of His56. The orientation of the imidazole ring of the distal histidine residue relative to the heme group in ARP differs significantly from that in LiP. The access channel to the distal side of the heme of ARP is markedly wider along the heme plane than that of LiP. Many of the amino acid residues that comprise the entrance of this channel differ for ARP and LiP. This may account for the differences in substrate specificity.

Acetylglucosamine↗

Coronary spasm in patients with coronary ectasia.

The incidence of coronary ectasia (CE) and the relationship between CE and coronary spasm that was said not to be apt to occur in patients with CE were studied. The study consisted of 1,373 patients (including 1,008 patients with ischemic heart disease) who underwent cardiac catheterization. In 74 patients with CE, coronary spasm was tested in 33 patients subjected to acetylcholine (ACh) provocation and in 17 patients subjected to ergonovine (Ergo) provocation. CE was found in 74 patients (5.4%), and its incidence was significantly higher (6.7%) in patients with ischemic heart disease. In addition, ACh and Ergo provocation tests gave positive results in 12 (36%) and 4 patients (24%), respectively. Spasm was not provoked as frequently in the ectatic portion as elsewhere. In addition, spasm was often found at the borders of the ectatic portion in both provocation tests. The incidence of coronary ectasia was higher than that described in previous reports, and coronary spasm was more often observed at the borders between ectatic and normal portions than elsewhere.

Acetylcholine↗

Effects of capsaicin on mechanoenergetics of excised cross-circulated canine left ventricle and coronary artery.

Capsaicin selectively acts on sensory nerve endings in cardiac muscles and coronary arterial smooth muscles. Capsaicin at high doses has cell-nonselective effects including both inhibition of cardiac muscle exciteability and enhancement of vascular smooth muscle tone. We studied whether and how intracoronary infusion of capsaicin affects mechanoenergetics of the excised blood-perfused canine heart and coronary vascular resistance. We found that capsaicin at low concentrations increased Emax (a contracility index) and oxygen consumption (VO2) possibly due to a specific action on capsaicin-sensitive sensory nerves in left ventricular muscles, though in a small number of hearts (3/10). This result coincides with the reported histochemical observations that the distribution of capsaicin-sensitive sensory nerves in the canine left ventricle is not dense. Capsaicin at high doses dose-dependently decreased Emax and proportionally decreased coronary flow. It also lowered the linear VO2-PVA (pressure-volume area; total mechanical energy) relationship without a change in the slope, decreasing unloaded VO2 (VO2 intercept of the VO2-PVA relation). These effects of high-dose capsaicin seem to be direct negative inotropic action on cardiac muscles associated with enhancement of coronary arterial smooth muscle tone, since these effects were not desensitized. No morphological changes of myocardial cells or mitochondria were detected. Therefore, the negative inotropic action is not due to the toxic effect of capsaicin.

Animals↗

Postextrasystolic transient contractile alternans in canine hearts.

We found that postextrasystolic potentiated contractility after a spontaneous extrasystole most frequently decayed as a transient alternans over several beats in excised, cross-circulated, atrially paced canine hearts. This type of heart preparation; which we have been using consistently in mechanoenergetic studies, had normal coronary blood perfusion pressure as well as flow and mechanoenergetic performance. Spontaneous atrial and ventricular extrasystoles occurred occasionally in every heart. Arrhythmic changes in left ventricular (LV) pressure at a fixed volume reflected corresponding changes in contractility. We analyzed nearly 3,600 cases of postextrasystolic potentiation in 68 hearts; 84% decayed as transient alternans, 6% decayed exponentially, and 10% belonged to neither type. We found that a postextrasystolic compensatory pause always preceded the transient alternans after either an atrial or ventricular extrasystole at any constant atrial pacing rate (85-188 beats/min). The decay was either exponential or nonalternating when the pause did not exist after an atrial extrasystole during occasional pacing failure. Therefore, the compensatory pause after either an atrial or ventricular extrasystole seems essential for the postextrasystolic transient alternans of LV contractility in the type of canine heart preparation we have been using.

Animals↗

An amino acid from Solorina crocea.

A new amino acid, named solorinine, isolated from the lichen, Solorina crocea was determined by a single-crystal X-ray diffraction analysis. NMR data are also reported.

Amino Acids↗

Molecular cloning and nucleotide sequences of cDNAs encoding subunits I, II, and IX of Euglena gracilis mitochondrial complex III.

cDNA clones encoding subunits I, II, and IX of Euglena gracilis mitochondrial complex III have been isolated from a lambda gt11 cDNA expression library by immunoscreening with an antiserum against the complex of the organism. Determination of the nucleotide sequences and amino-terminal amino acid sequences of purified subunits revealed that subunits II and IX, respectively, consist of 432 and 70 amino acids as their mature forms and possess potential presequences of 42 and 30 amino acids. The amino-terminal parts of the presequences had typical structural features of the mitochondrial targeting signal. Such features were also found at the amino-terminal region of the predicted subunit I protein, which comprises 494 residues. However, the amino terminus of the purified subunit I could not be detected, possibly because of a post-translational modification. Euglena subunits I and II both showed similarities to the members of the protein family which comprises complex III core proteins, mitochondrial processing peptidases (MPP) and processing enhancing proteins (PEP). Namely, the Euglena subunit I could be assigned to core 1 protein and the subunit II to core 2 protein in the family. In contrast, the subunit IX seemed to be peculiar to Euglena complex III. At 5'-untranslated regions, the three cloned cDNAs for subunits I, II, and IX had a common poly(T)CG structure which has also been reported for other Euglena cDNAs of nuclear genes.

Amino Acid Sequence↗

Crystallization and preliminary X-ray diffraction studies of the alpha-amylase inhibitor coded 0.19 from wheat kernel.

The alpha-amylase inhibitor coded 0.19 (0.19AI) from wheat kernel is a dimeric protein which inactivates exogenous alpha-amylases. Crystals of 0.19AI were grown at room temperature and pH 7.0 from a protein solution with a low salt concentration. They were trigonal, belonged to space group P3(1) or P3(2), and had unit cell dimensions of a = b = 79.3 A and c = 60.8 A. The crystals diffract X-rays to at least 2.0 A resolution and are stable to X-ray beams. The asymmetric unit appears to contain two 0.19AI dimers. A potential heavy-atom derivative was prepared by soaking the crystal in a HgCl2 solution.

Crystallization↗

Differential gene expression and regulation of angiotensin II receptor subtypes in rat cardiac fibroblasts and cardiomyocytes in culture.

Although both rat cardiac nonmyocytes (mostly fibroblasts) and cardiomyocytes have a functional angiotensin II (AngII) receptor, the regulation mechanism of its subtype expression in the rat heart remains unknown. In this study, by using a binding assay and a competitive reverse-transcriptase polymerase chain reaction, we examined the regulation of AngII types 1a and 1b (AT1a-R and AT1b-R) and type 2 receptor (AT2-R) expression in embryonal day 19 (E19) and neonatal (1-d) rat cardiac fibroblasts and cardiomyocytes. The number of AT2-R in E19 fibroblasts was dramatically decreased (from 305 to 41 fmol/mg protein) in 1-d fibroblasts, whereas that of AT1-R and the mRNA levels remained unchanged. The ratio of AT1a-R to AT1b-R mRNA in both E19 and 1-d fibroblasts was 9:1. The number of AT2-R in E19 cardiomyocytes was also significantly decreased (from 178 to 87 fmol/mg protein) in 1-d cardiomyocytes, whereas the magnitude was less prominent compared with that in fibroblasts. AT1-R expression remained unaltered in E19 and 1-d cardiomyocytes. In E19 and 1-d cardiomyocytes, the AT1b-R mRNA level was 1.5-fold higher than that of AT1a-R mRNA. Dexamethasone induced significant increases in AT1a-R mRNA (2.1-fold) and numbers (1.8-fold) without changing the affinity, whereas neither AT1b-R mRNA nor the number of AT2-R was affected by dexamethasone. The AT1a-R gene transcription rate, determined by means of a nuclear run-off assay, was increased (2-fold) by dexamethasone. The half-life of AT1a-R mRNA (18 h) was unchanged by dexamethasone. These data indicate that AngII receptor subtype expression in the rat heart is regulated in a cell- and subtype-specific manner.

Angiotensin II↗

cAMP responsive element-mediated regulation of the gene transcription of the alpha 1B adrenergic receptor by thyrotropin.

To elucidate the molecular mechanism of the stimulatory effect of thyrotropin on the gene regulation of alpha 1B adrenergic receptor in functioning rat thyroid (FRTL-5) cells, we established a competitive reverse-transcriptase (RT) polymerase chain reaction (PCR) and nuclear run-off assay to quantify changes in mRNA levels and transcription rates. A binding assay showed that FRTL-5 cells predominantly expressed alpha 1B adrenergic receptor and that thyrotropin increased its expression sevenfold. By means of RT-PCR, we found that thyrotropin induced an 11-fold increase in alpha 1B receptor mRNA abundance. The nuclear run-off assay demonstrated that thyrotropin caused a ninefold increase at the gene transcriptional level, which occurred in the presence of the protein synthesis inhibitor cycloheximide. The half-life of the alpha 1B receptor mRNA in cells incubated with thyrotropin for 1 h increased 1.5-fold but returned to the original value after 12 h. Dibutyryl cAMP and forskolin mimicked the stimulatory effects of thyrotropin on the gene transcriptional level. The 5'-flanking region of the rat alpha 1B receptor gene contained a putative cAMP responsive element (CRE) at nucleotide -438 relative to the translation start site. The promoter analysis using the reporter gene indicated that the CRE motif confers the cAMP sensitivity to the transcription of the rat alpha 1B receptor gene. These results demonstrated that a CRE-mediated mechanism is involved in the transcriptional regulation of the alpha 1B receptor gene by thyrotropin without requiring new protein synthesis.

Animals↗

Estimation of total carbon dioxide contents in canine coronary arterial and venous whole blood samples.

We examined whether total carbon dioxide content (CCO2) estimation equations for human whole blood in the literature are applicable to canine coronary arterial and venous blood samples. PCO2 of the tested blood samples covered 19-52 mmHg; PO2 19-398 mmHg. Three CCO2 estimation equations developed by Kelman, Godfrey, and Douglas et al yielded CCO2 values over a range of 26.7-54.9 vol%, where plasma CCO2 values calculated by the Henderson-Hasselbalch equation ranged over 27.7-62.2 vol%. The estimated blood CCO2 values were almost identical among the three equations. They also closely correlated with plasma CCO2 values measured after hemolysis with saponin. We conclude that the human whole blood CCO2 estimation equations are applicable to canine coronary arterial and venous blood samples. These CCO2 equations may be used for canine cardiac metabolic studies.

Animals↗