Search PubMed⌕ Search

Biomedical subjects

K Kawamura

Publications and source records attributed to K Kawamura.

At least 145 records · Page 8Linked to original sources
PubMed1998

Cardioprotective effects of quinapril after myocardial infarction in hypertensive rats.

Although angiotensin-converting enzyme inhibitors are beneficial for patients with congestive heart failure, the appropriate timing and dosage in acute myocardial infarction are still controversial. We examined the hemodynamic effects of quinapril administered before acute myocardial infarction in spontaneously hypertensive rats (SHR). Quinapril (10 mg/kg per day in drinking water) was started 1 week before infarction and continued for 4 weeks after infarction (total duration 5 weeks). The hemodynamic parameters were evaluated by cardiac catheterization 4 weeks after coronary ligation. Sham-operated SHR served as controls. After infarction, left ventricular end-diastolic and right atrial pressures were increased (P < 0.01) and blood pressure and cardiac index were decreased (P < 0.01); the magnitude of blood pressure reduction was similar in the treated and untreated rats with infarction. Quinapril improved these hemodynamic parameters significantly and decreased left and right ventricular weight. These results suggest that a prior treatment with quinapril in SHR with acute myocardial infarction is hemodynamically beneficial.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Penetration and intracellular routing of nucleus-directed peptide-based shuttles (loligomers) in eukaryotic cells.

Loligomers are multitasking, peptide-based shuttles that are able to penetrate cells and self-localize into distinct cellular compartments. In particular, loligomer 4 incorporates internalization and nuclear import sequences as well as reporter groups. The intracellular routing of loligomer 4 was analyzed by microscopy and flow cytometry, to define and demonstrate localization events. Electron micrographs of CHO cells exposed to a biotinylated derivative of loligomer 4 as well as confocal images of CHO cells treated with rhodamine-labeled loligomer 4 indicate their presence in the cytosol, endocytic vesicles, and the nucleus of CHO cells. Loligomer 4 accumulates irreversibly inside cells. Uptake of loligomer 4 by six mammalian cell lines (Daudi, EL4, CHO, COS-7, VERO, and HeLa) was proven by flow cytometry, establishing the generality of the principle. Cells presented as monolayers typically were less able to endocytose the construct than cells grown in suspension. Cellular accumulation of loligomer 4 varied between cell lines with COS-7 and VERO cells showing the highest level of uptake. Plasmids harboring reporter genes could be transported efficiently inside CHO cells, suggesting that loligomer 4 either alone or noncovalently associated with large macromolecules can effectively reach the nucleus of cells. In summary, loligomer 4 constructs provide a simple synthetic platform for the design of guided intracellular agents.

Animals↗
PubMed1998

Influence of altered loading conditions on left atrial appendage function in vivo.

This study sought to examine the influence of heart failure treatment on left atrial (LA) appendage function in 10 patients with left ventricular dysfunction. After treatment of heart failure, LA appendage function markedly improved, less dependent on LA and left ventricular functions, which suggests that with altered loading conditions, LA appendage function changes chiefly through its intrinsic contractile property.

Aged↗
PubMed1998

Collagen subtypes and matrix metalloproteinase in idiopathic restrictive cardiomyopathy.

BACKGROUND: Idiopathic restrictive cardiomyopathy is a rare disease characterized by diastolic dysfunction, and the pathogenesis of the stiff heart remains unclear. The purpose of this study was to analyze the subpopulation of collagen fibers and determine the expression of matrix metalloproteinase in restrictive cardiomyopathy. METHODS AND RESULTS: In endomyocardial biopsy specimens obtained from seven patients with restrictive cardiomyopathy, collagen fiber types I, III, and IV, and matrix metalloproteinase- and two were observed by light and electron microscopy, using monoclonal antibodies. Type I collagen was less prominent in the interstitium, whereas the immunoreactivity for type III collagen was marked. The immunoreactivity against matrix metalloproteinase-1 was observed along with types I and III collagen fibers and in the cytoplasm of some fibrocytes/fibroblasts. The matrix metalloproteinase-1 tended to increase when the reactivity against types I and III collagen was prominent. Both type IV collagen and matrix metalloproteinase-2 were observed along arterial walls and the basement membrane of cardiocytes. CONCLUSIONS: Increased type III collagen may play an important role as the cause of left ventricular stiffness in restrictive cardiomyopathy. The matrix metalloproteinase appeared to be involved in a cascade of collagen synthesis and the remodeling of the heart in patients with restrictive cardiomyopathy.

Adult↗
PubMed1998

Intracellular distribution of adenylate cyclase in human cardiocytes determined by electron microscopic cytochemistry.

Subcellular localization of adenylate cyclase (AC) in human cardiocytes was studied by electron microscopic cytochemistry using ventricular biopsies from various diseased hearts. In addition to the weak enzyme activity on the sarcolemma, the intense reaction products of AC were demonstrated within distinctive morphologic components of sarcoplasmic reticulum, nuclear envelope, and other internal membranes such as parallel lamellar structures and interlaced tubular structures in the perinuclear regions and stacked membranous structures beneath sarcolemma in cardiocytes. The distribution and intensity of cytochemical activity within different organelles was variable among biopsy cases. The reaction products of AC cytochemistry within the sarcoplasmic reticulum could be related to signal transduction targeting Ca2+ handling by the organella. Cytochemical activity within the nuclear envelope and perinuclear internal membranes possibly reflects AC participation in a signal function to regulate nuclear activity, such as gene expression. Cytochemical distribution of the enzyme in membranous structures beneath the sarcolemma is most likely related to hormone receptors and the linked activity of AC. The subcellular distribution of AC on various internal membrane structures in cardiocytes may reflect compartmentalization of the enzyme at individual intracellular sites to regulate a preferential specific signal function among multiple potential signal transductions by a cascade of AC, cyclic AMP, and cyclic AMP-dependent protein kinase. Alternatively, subcellular localization of the reaction products may reflect local enzyme synthesis or represent sites of enzyme transport, e.g., to terminal localization beneath the sarcolemma.

Adenylyl Cyclases↗
PubMed1998

Deficiency in protein L-isoaspartyl methyltransferase results in a fatal progressive epilepsy.

Protein L-isoaspartyl methyltransferase (PIMT) is suggested to play a role in the repair of aged protein spontaneously incorporated with isoaspartyl residues. We generated PIMT-deficient mice by targeted disruption of the PIMT gene to elucidate the biological role of the gene in vivo. PIMT-deficient mice died from progressive epileptic seizures with grand mal and myoclonus between 4 and 12 weeks of age. An anticonvulsive drug, dipropylacetic acid (DPA), improved their survival but failed to cure the fatal outcome. L-Isoaspartatate, the putative substrate for PIMT, was increased ninefold in the brains of PIMT-deficient mice. The brains of PIMT-deficient mice started to enlarge after 4 weeks of age when the apical dendrites of pyramidal neurons in cerebral cortices showed aberrant arborizations with disorganized microtubules. We conclude that methylation of modified proteins with isoaspartyl residues is essential for the maintenance of a mature CNS and that a deficiency in PIMT results in fatal progressive epilepsy in mice.

Animals↗
PubMed1998

Circadian variation of myocardial ischemia in patients with unstable angina pectoris secondary to fixed and/or spastic coronary narrowing.

We investigated the circadian variation of myocardial ischemia in patients with unstable angina using a 24-hour 12-lead electrocardiographic monitoring system with computer analysis. The circadian variation of ischemic attacks in patients who had ST elevation showed a similarity to that of the onset of acute myocardial infarction and most of these patients had vasospasm without organic stenosis; no similarity was seen in patients with organic stenosis.

Aged↗
PubMed1998

[A successful valve repair case of isolated tricuspid regurgitation due to traumatic lacerated papillary muscle of the tricuspid valve].

A case of tricuspid valve regurgitation due to a non-penetrating chest trauma was presented. This case involves a 20-year-old man, who was admitted to a nearby hospital because of rib fracture, mandibular fracture, and hemorrhage of the left hemopneumothorax, caused by a traffic accident. Palpitation and chest discomfort were observed at admission time, but there was no follow-up. Tricuspid regurgitation was pointed out during surgery for the mandibular fracture, and he continued follow up treatment at an outpatient clinic. However his palpitation and chest discomfort worsened, and he was admitted to our department 8 month after injury. During surgery to repair the tricuspid valve, a papillary muscle rupture, valve cusp laceration, and anulus dilatation were found. We performed a papillary muscle repair (chorda tendineae reconstruction), valve cusp suture, and annuloplasty. Absence of the left pericardium was observed during the operation. We reported valve repair of traumatic tricuspid regurgitation which with papillary muscle rupture. Due to its rarity and the fact that there has been no reported cases of papillary muscle repair for traumatic tricuspid regurgitation in Japan, we used researched information on the subject.

Adult↗
PubMed1998

Expression and function of a retinoic acid receptor in budding ascidians.

Retinoic acid is thought to induce transdifferentiation of multipotent epithelial stem cells in the developing buds of the ascidian Polyandrocarpa misakiensis. We isolated a cDNA clone from this species, named PmRAR, encoding a retinoic acid receptor (RAR) homologue. PmRAR clusters with other RARs on phylogenetic trees constructed by three different methods. Within the cluster, PmRAR is on a separate branch from all the subtypes of RARs, suggesting that RAR subtypes arose in the ancestral vertebrates after divergence of vertebrates and urochordates. The embryos of another ascidian species Ciona intestinalis were co-electroporated with a mixture of a PmRAR expression vector and a lacZ reporter plasmid containing vertebrate-type retinoic acid response elements. The expression of lacZ depended on the presence of both retinoic acid and PmRAR, suggesting that PmRAR is a functional receptor. PmRAR mRNA is expressed in the epidermis and mesenchyme cells of the Polyandrocarpa developing bud. The mRNA is not detectable in the mesenchyme cells in the adult body wall, but its expression can be induced by retinoic acid in vitro. These results suggest that the PmRAR is a mediator of retinoic acid signalling in transdifferentiation during asexual reproduction of protochordates.

Amino Acid Sequence↗
PubMed1998

Spontaneous myocarditis in DBA/2 mice. Light microscopic study with transmission and X-ray analytical electron microscopic studies.

DBA/2 inbred mice spontaneously develop myocarditis and a unique form of subepicardial inflammation of the right ventricle characterized by a prominent eosinophilic infiltrate with calcinosis. We studied this myocarditis using light microscopy and both transmission and analytical X-ray electron microscopy, paying particular attention to eosinophil-associated cardiocyte injury. At 5 weeks of age, many eosinophils and mononuclear cells (MNCs) were seen in the subepicardium of the right ventricle. Electron microscopy showed that cardiocytes underwent degenerative changes, including myofibrillar lysis, accumulation of Z-band material and mitochondrial inclusions, and rupture of plasma membranes. The infiltrating eosinophils appeared to be activated, and cells with cytoplasmic vacuoles, suggestive of degranulation, were noted. The myocardial injury was most severe in the 7th week and healed with myocardial fibrosis and calcinosis by the 8th week. Analytical X-ray electron microscopy showed that the calcinosis was initiated in mitochondrial inclusions of injured cardiocytes. The peripheral eosinophil count did not increase during the course of the disease, but there was a positive correlation between the ratio of eosinophils to infiltrated white blood cells (Eo/WBCs) in the right ventricle and the severity of myocardial damage. Eosinophils may play a significant part in subepicardial cardiocyte injury seen in DBA/2 mice.

Animals↗
PubMed1998

Renin-producing adrenal tumor: report of a case.

A 19-year-old man with an adrenal tumor associated with hypertension is herein described. The plasma renin activity (PRA) was markedly elevated and the plasma aldosterone level was also increased. The catecholamine level was within the normal range and the glucagone-regitine test was negative. An angiogram revealed the left renal artery to have no stenotic segments, but instead was curved caudally. Magnetic resonance imaging showed a tumor measuring about 8 cm in diameter to be clearly recognized from the left kidney. The blood pressure did not drop when a calcium-channel blocker was used, but was gradually stabilized with the angiotensin converting enzyme (ACE) antagonist. The adrenal tumor was then removed surgically. Normal adrenal tissue was scarcely recognized to the left of the tumor. After surgery, the PRA decreased and blood pressure stabilized rapidly without the ACE antagonist. The possibility of massive renal renin secretion due to suppression by the adrenal tumor was excluded by a method using an antibody to purified human renin.

Adrenal Gland Neoplasms↗
PubMed1998

Assessment of left atrial appendage function after cardioversion of atrial fibrillation: relation to left atrial mechanical function.

Although several flow patterns in the left atrial appendage have been described, mechanical determinants of its function have not been elucidated in human beings. We attempted to investigate changes in left atrial appendage function after cardioversion of atrial fibrillation and examine the potential relation between appendage function and left atrial mechanical function. Twenty patients without mitral valvular disease underwent transesophageal and transthoracic echocardiography at 24 hours and 1 week after cardioversion of atrial fibrillation. Left atrial appendage function was assessed by the pulsed Doppler measurements of left atrial appendage emptying and filling velocities corresponding to early and late ventricular diastole, respectively. Left atrial mechanical function was evaluated by the transmitral A-wave velocity, percent atrial contribution of the total left ventricular filling (percent atrial filling), and the pulmonary venous A-wave velocity. Left ventricular function was also estimated with conventional M-mode echocardiography. The late appendage emptying and filling velocities markedly increased during 1 week after cardioversion (p < 0.0001, respectively). This finding was associated with an increase in left atrial mechanical function. Changes in the late emptying and filling velocities significantly correlated with changes in the transmitral A-wave velocity (r = 0.59, p < 0.01), percent atrial filling (r = 0.61, p < 0.005), and the pulmonary venous A-wave velocity (r = 0.56, p < 0.05). In contrast, little change was observed in the early emptying and filling velocities. There was no relation between the indexes of left ventricular function and those of appendage function. In conclusion, unless there was an alteration of the loading conditions, left atrial appendage function improved over several days after cardioversion, and its function was related to left atrial mechanical function.

Adult↗
PubMed1998

Preventive effects of an antiallergic drug, pemirolast potassium, on restenosis after percutaneous transluminal coronary angioplasty.

BACKGROUND: We recently confirmed that pemirolast potassium, an antiallergic agent, markedly inhibits migration and proliferation of vascular smooth muscle cells. It has also been reported that pemirolast inhibits intimal hyperplasia in animal experiments. METHODS AND RESULTS: To elucidate the preventive effects of pemirolast on restenosis after percutaneous transluminal coronary angioplasty (PTCA), 227 patients were enrolled in this prospective, randomized trial. A total of 205 patients who were compatible with the protocol were analyzed (pemirolast group, 104 patients with 140 lesions; control group, 101 patients with 133 lesions). Patients in the pemirolast group received 20 mg/d of pemirolast from 1 week before PTCA until the time of follow-up angiography (4 months after PTCA). Angiographic restenosis was defined as diameter stenosis >/=50% at follow-up. Restenosis rates were significantly lower in the pemirolast group than in the control group (24.0% vs 46.5% of patients, 18.6% vs 35.3% of lesions, P <.01, respectively). During 8 months of follow-up, there were no coronary events (death, myocardial infarction, coronary artery bypass surgery, or repeated PTCA) in 81.7% of the pemirolast group and in 63.4% of the control group (P =.013). CONCLUSIONS: This study suggested that pemirolast would be useful in the clinical setting to prevent restenosis after PTCA.

Aged↗
PubMed1998

Reversible left atrial dysfunction possibly due to afterload mismatch in patients with left ventricular dysfunction.

Limited data are available concerning the influence of altered loading conditions on left atrial (LA) function. In addition, the underlying mechanism of the augmentation of atrial filling (A) velocity (assessed by transmitral Doppler measurement) after treatment of heart failure has been less studied. Therefore, we examined various indexes of LA function during the depression of left ventricular (LV) filling pressure resulting from treatment of heart failure. Twelve patients with LV dysfunction (ejection fraction < 50%) underwent right heart catheterization and transthoracic echocardiography before and after optimal treatment of heart failure. LV/LA volume and ejection fraction and mitral and pulmonary venous flow velocities were measured. LV stiffness (substitute for LA afterload) was assessed by the ratio of LV filling pressure to LV end-diastolic volume. After treatment of heart failure, the mitral A velocity significantly increased (38 +/- 9 to 58 +/- 16 cm/sec, p < 0.005) and there was a distinct attenuation of the difference of the pulmonary venous and mitral A-wave duration (43 +/- 29 to -8 +/- 31 msec, p < 0.005). These findings were associated with a marked decrease in LV stiffness (0.12 +/- 0.04 to 0.05 +/- 0.02 mm Hg/ml, p = 0.0001) and an increase in LA ejection fraction (27% +/- 7% to 38% +/- 8%, p < 0.005). There was a significant curvilinear relation between LA ejection fraction and LV stiffness (r = 0.63, p < 0.01). The mitral A velocity correlated positively with LA ejection fraction (r = 0.77, p < 0.0001) and inversely with LV stiffness (r = -0.52, p < 0.01). The reversible LA dysfunction suggests that the initial LA dysfunction is due to LA afterload mismatch rather than intrinsic LA disease, which also contributes to the augmentation of the mitral A velocity after heart failure treatment.

Atrial Function, Left↗
PubMed1998

Ratio of pulmonary venous to mitral A velocity is a useful marker for predicting mean pulmonary capillary wedge pressure in patients with left ventricular systolic dysfunction.

In patients with an elevated left ventricular filling pressure, the mitral A wave is diminished while the pulmonary venous A wave is augmented because of decreased left ventricular compliance. We examined whether an increase in the ratio of pulmonary venous to mitral A velocity might be a marker for an elevated mean pulmonary capillary wedge pressure. Forty-one patients who had left ventricular systolic dysfunction underwent transthoracic Doppler echocardiography simultaneously or within 24 hours of right heart catheterization. There were 29 men and 12 women 61 +/- 12 (mean +/- SD) years of age. Underlying heart disease was ischemic cardiomyopathy in 27 and nonischemic cardiomyopathy in 14 patients. The same Doppler-hemodynamic study was performed on 8 patients after optimal management of heart failure. The ratio of pulmonary venous to mitral A velocity correlated strongly with mean pulmonary wedge pressure (r = 0.72, P < .0001). When the cutoff value of the ratio was set at 0.5 or higher, the sensitivity for predicting a pulmonary capillary wedge pressure of 15 mm Hg or more was 88%, and the specificity was 80%. The serial Doppler-hemodynamic study showed that the ratio decreased markedly after treatment of heart failure. The value was 0.84 +/- 0.29 before treatment and 0.36 +/- 0.17 after treatment (P = .001). An increased ratio of pulmonary venous to mitral A velocity is a useful marker for elevated pulmonary capillary wedge pressure among patients with left ventricular systolic dysfunction.

Aged↗
PubMed1998

Developmental studies for identification of the inhibitory center of melanotropes in the toad, Bufo japonicus.

Two series of experiments were performed to identify the inhibitory center of the melanotropes in the intermediate lobe of hypophysis of the toad, Bufo japonicus. First, developmental changes in the distribution of dopaminergic neurons were examined from hatching stage to postmetamorphosis using an antiserum against dopamine synthase (tyrosine hydroxylase, TH). In the postmetamorphic toads, TH-positive cell bodies were localized in three clusters. One was the preoptic recess organ (PRO) in the prechiasmatic area, the other two were the paraventricular organ (PVO) and infundibular nucleus (IN) in the postchiasmatic area. Each of them exhibited different ontogenetic changes. During larval development, TH-positive cell bodies were first detected in the PVO and IN at a premetamorphic stage. The number of immunoreactive cells increased rapidly in both loci as metamorphosis proceeded, although the two nuclei showed different growth profiles. By contrast, in the PRO, a very small number of immunoreactive cells were observed before the onset of the prometamorphic period. Although the number of immunoreactive neurons increased as metamorphosis progressed, early neurons were confined to the caudal area of the PRO (cPRO), the rostral area of the PRO (rPRO) being devoid of TH-positive cells. Immunoreactive TH neurons appeared in the rPRO for the first time at the end of metamorphic climax. This timing coincided well with the development of TH-positive nerve endings in the pars intermedia (PI) and median eminence. In the second series of experiments, the embryonic primordium of the PRO was surgically extirpated from open neurulae to examine the effects of PRO-ectomy. In 75% of the operated animals, background adaptation was not observed, their dermal melanophores remained permanently dispersed even on the white background. Dopaminergic neurons in the rPRO and the immunoreactive nerve endings in the PI and median eminence were scarcely observed in these animals. It was concluded that the present data strongly support the hypothesis that rPRO is the center of white-background adaptation.

Animals↗