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Biomedical subjects

K Kawamura

Publications and source records attributed to K Kawamura.

At least 19 recordsLinked to original sources
PubMed1998

Neuronal src and trk a protooncogene expression in neuroblastomas and patient prognosis.

Neuroblastomas present a wide variety of clinical and biological behaviors, which are reflected by the heterogeneous expressions of protooncogenes related to the neuronal differentiation and amplification of the N-myc gene. High expression of trk A and Ha-ras in neuroblastomas has been shown to be associated with an excellent patient outcome. We have previously reported that neuron-specific src mRNA was increased in chemically differentiated neuroblastoma cell lines and in clinically observed neuroblastomas without N-myc amplification. In the present study, to clarify both the value of neuronal c-srcN2 expression as a prognostic indicator and the significance of the coexpression of these protooncogenes, we examined the expression of 3 alternatively spliced src, trk A and Ha-ras in neuroblastoma tissues from 60 patients by competitive RNA-polymerase chain reaction (PCR). The results indicate that protooncogene expression in neuroblastomas correlated with a favorable outcome for c-srcN2 and trk A. N-myc gene was amplified exclusively in tumors with low levels of trk A. Low expression of c-srcN2 and trk A might thus characterize different aggressive phenotypes due to different signal transduction pathways of neural differentiation in neuroblastoma. The combined analyses for c-srcN2 and trk A expression by RNA-PCR should provide information about the biological phenotype of a neuroblastoma within a short period of time after obtaining tumor material.

Genes, myc↗
PubMed1998

Coordinate expression of L1 and 6B4 proteoglycan/phosphacan is correlated with the migration of mesencephalic dopaminergic neurons in mice.

Mesencephalic dopaminergic (DA) neurons of mice are generated from embryonic day 10 to 12 (E10-12) in the ventricular zone of the mesencephalon. They first migrate toward the ventral mesencephalon, and then turn laterally, or tangentially, in the basal part of the mesencephalon. With immunohistochemical analysis of E10-E15 ICR mice, we found that cell adhesion molecule L1 was transiently expressed on the median part of tangential fibers coincident with the lateral migration of DA neurons from E11 to E13, when neurons move along the tangential fibers toward their final destinations: the reticular formation, the substantia nigra pars compact, and the ventral tegmental area. While L1 expression was not observed in DA neurons, they expressed a chondroitin sulfate proteoglycan, 6B4 proteoglycan/phosphacan, which has been shown to bind to L1/Ng-CAM in vitro. These results suggest that the heterophilic interaction between 6B4 proteoglycan on the neurons and L1 on the fibers is involved in the lateral migration of mesencephalic DA neurons in mice.

Animals↗
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

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

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↗