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Biomedical subjects

M Kawana

Publications and source records attributed to M Kawana.

At least 19 recordsLinked to original sources

Congestive heart failure after peripheral blood stem cell transplantation: role of cytokines.

A 32-year-old woman was admitted with the diagnosis of congestive heart failure (CHF) without organic heart disease after peripheral blood stem cell transplantation (PBSCT) for malignant lymphoma. Various cytokines have been reported to be released from stem cells after PBSCT and some have a suppressive effect on myocardial contractility; elevated levels of cytokines have been reported in dilated cardiomyopathy (DCM) and/or CHF patients. In the present case, elevated levels of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha) were observed, and there was a parallel relationship between the recovery of cardiac function and the decrease of these cytokines, strongly suggesting that the release of IL-6 and TNF-alpha after PBSCT might have been important in the pathogenesis of the CHF.

Adult↗

[Risk factors and effect of reperfusion therapy on left ventricular free wall rupture following acute myocardial infarction].

Reperfusion therapy is one of the most effective treatments for acute myocardial infarction, but the effect on left ventricular free wall rupture remains to be determined. This study tried to clarify the risk factors and effect of reperfusion therapy on the risk of free wall rupture following acute myocardial infarction. 2,671 consecutive patients with acute myocardial infarction admitted to our hospital were examined. Incidence of free wall rupture showed no degenerative change(0 to 5.8%; mean 2.1%). The 1,269 consecutive patients from 1985 to 1995 were examined closely to evaluate risk factors and the effect of reperfusion therapy on the risk of free wall rupture. Fourteen patients who underwent emergent coronary artery bypass surgery were excluded. Free wall rupture was found in 25 patients (2.0%). Multivariate analysis confirmed that high age(> or = 70 years) and first acute myocardial infarction were independent risk factors of free wall rupture (odds ratio 3.62, p = 0.003; odds ratio 7.69, p = 0.046, respectively). The incidence of free wall rupture in the conservative therapy group(n = 799) was 2.1%, successful reperfusion group(n = 373) was 0.5%, and unsuccessful reperfusion group(n = 83) was 7.2% with significant statistical differences(p < 0.01). There was no statistical difference between the direct percutaneous transluminal coronary angioplasty group(n = 84, 3.6%) and the thrombolysis group(n = 372, 1.3%). Successful reperfusion was the only independent factor in the reperfusion therapy group that reduced the incidence of free wall rupture(odds ratio = 0.07, p = 0.001). We conclude that reperfusion of the infarct-related artery and more intensive management of unsuccessful reperfusion is important to prevent free wall rupture following acute myocardial infarction.

Age Factors↗

[Diagnostic algorithm of idiopathic cardiomyopathy].

In this review, diagnostic algorithm of idiopathic cardiomyopathy is discussed. In the primary care, most of the patients with cardiomyopathy are initially found by signs and symptoms of systolic/diastolic cardiac dysfunction and arrhythmia, and the myocardial involvement is recognized by chest roentgenogram and electrocardiogram. In the next step, echocardiography is extremely useful to confirm cardiac size, ventricular hypertrophy, systolic/diastolic function and structural abnormalities. After this examination, detailed diagnostic approaches including invasive strategy can be planned to each type of cardiomyopathy(DCM, HCM, RCM, ARVC). In each case, any etiology to develop myocardial disorder should be carefully examined to exclude secondary cardiomyopathy.

Algorithms↗

Clinical potential of intravascular ultrasound for physiological assessment of coronary stenosis: relationship between quantitative ultrasound tomography and pressure-derived fractional flow reserve.

BACKGROUND: Little is known regarding intravascular ultrasound (IVUS) criteria to determine the functional severity of coronary stenosis. Recently, fractional flow reserve (FFR) has emerged as a lesion-specific index of the functional severity of a coronary stenosis that is independent of systemic hemodynamic variability. The present study was undertaken to determine the IVUS parameters for the physiological severity of coronary stenosis. METHODS AND RESULTS: Fifty-one lesions in 42 patients were evaluated by means of quantitative coronary angiogram, IVUS, and intracoronary pressure measurements. The FFR was calculated as the ratio of the distal coronary pressure divided by the proximal coronary pressure under hyperemia. We considered a value of the FFR <0.75 as significant in determining inducible ischemia, according to the previous studies. The minimal luminal area (MLA) and the area stenosis were measured by IVUS. By regression analysis, the MLA showed a positive correlation with the FFR value (r(2)=0.62, P<0.0001). The area stenosis had a significant inverse correlation with the value of FFR (r(2)=0.60, P<0.0001). The IVUS thresholds that maximized the sensitivity and specificity were MLA <3.0 mm(2) (sensitivity, 83.0%; specificity, 92.3%) and area stenosis >0.6 (sensitivity, 92.0%; specificity, 88.5%). The combination of both criteria (MLA <3.0 mm(2) and area stenosis <0.6) without exception met a value of the FFR <0.75. CONCLUSIONS: Anatomic parameters obtained by IVUS showed a significant correlation to the FFR values. The present study demonstrated that the combination of the MLA and area stenosis measured by IVUS can be an anatomic predictor for the physiological impact of coronary epicardial stenosis.

Coronary Angiography↗

Course of IL-1beta, IL-6, IL-8, and TNF-alpha in the middle ear fluid of the guinea pig otitis media model induced by nonviable Haemophilus influenzae.

To characterize the local response in acute otitis media, courses of interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor (TNF)alpha in middle ear fluid (MEF) of the guinea pig otitis media model induced by nonviable Haemophilus influenzae were investigated with enzyme-linked immunosorbent assay (ELISA) kits. The IL-1beta concentration in H. influenzae-inoculated ears peaked 24 hours after inoculation. The IL-8 concentration was significantly higher in H. influenzae-inoculated ears than in controls 48 and 96 hours after inoculation. The TNF-alpha concentration in H. influenzae-inoculated ears had an initial peak 6 hours after inoculation and had significant late increases 48 and 96 hours after inoculation. The results suggest that IL-1beta and TNF-alpha were produced by middle ear mucosa in the early stage of the experiment by stimulation of bacterial inoculation, which caused subsequent inflammatory cell accumulation, and that IL-8 and TNF-alpha were produced in the late stage by accumulating inflammatory cells.

Acute Disease↗

Cloning and characterization of developmental endothelial locus-1: an embryonic endothelial cell protein that binds the alphavbeta3 integrin receptor.

We have taken advantage of an enhancer trap event in a line of transgenic mice to identify a unique developmentally regulated endothelial cell locus (Del1). The protein encoded in this locus contains three EGF-like repeats homologous to those in Notch and related proteins, including an EGF-like repeat that contains an RGD motif, and two discoidin I-like domains. Del1 is shown to be a matrix protein and to promote adhesion of endothelial cells through interaction with the alphavbeta3 integrin receptor. Embryonic endothelial-like yolk sac cells expressing recombinant Del1 protein, or grown on an extracellular matrix containing Del1 protein, are inhibited from forming vascular-like structures. Expression of Del1 protein in the chick chorioallantoic membrane leads to loss of vascular integrity and promotes vessel remodeling. Del1 is thus a new ligand for the alphavbeta3 integrin receptor and may function to regulate vascular morphogenesis or remodeling in embryonic development.

Amino Acid Sequence↗

Hepatitis C virus infection and heart diseases: a multicenter study in Japan.

As a collaborative research project of the Committees for the Study of Idiopathic Cardiomyopathy, a questionnaire was sent out to 19 medical institutions in Japan in order to examine the possible association between hepatitis C virus (HCV) infection and cardiomyopathies. Hepatitis C virus antibody was found in 74 of 697 patients (10.6%) with hypertrophic cardiomyopathy (mean age, 57.7 years) and in 42 of 663 patients (6.3%) with dilated cardiomyopathy (mean age, 56.5 years); these prevalences were significantly higher than that found in volunteer blood donors in Japan (2.4%, 50-59 years of age, each p<0.0001). The prevalence was significantly higher in patients suffering from hypertrophic cardiomyopathy as opposed to those with dilated cardiomyopathy (p<0.01). The presence of HCV antibody was detected in 650 of 11,967 patients (5.4%) patients seeking care in 5 academic hospitals. Various cardiac abnormalities were found among these patients, arrhythmias being the most frequent. These observations suggest that HCV infection is an important cause of a variety of otherwise unexplained heart diseases.

Cardiomyopathies↗

[Catheter intervention for adult congenital heart diseases].

The efficacy of catheter intervention for adult congenital heart diseases was evaluated in 27 patients aged 20 to 52 years (mean age at catheterization 25 +/- 7 years) from 1986 to 1996. Four patients had pulmonary valve stenosis, four had aortic valve stenosis, three had coarctation of the aorta, 10 had pulmonary artery stenosis, four had cyanotic heart diseases and aorto-pulmonary collateral arteries, one had patent ductus arteriosus, and one had cyanotic heart disease and stenotic Blalock-Taussig shunt. Balloon dilation was successful in all patients with pulmonary valve stenosis, and follow-up evaluation (1-8 years) showed no restenosis in any patients. Balloon dilation was successful in all patients with aortic valve stenosis, and follow-up evaluation (0.5-5 years) showed transvalvular pressure gradient < 50 mmHg. Stenosis was relieved successfully in all patients with coarctation of the aorta, and follow-up evaluation showed no restenosis. Balloon dilation was successful in eight of 13 locations (62%) in patients with pulmonary artery stenosis. Coil embolization was successful in all patients with cyanotic heart diseases and aortopulmonary collateral arteries. In a patient with patent ductus arteriosus, two coils were placed in the ductus arteriosus but were retrieved because hemolysis was observed after the embolization. These data indicate that catheter intervention in young adults with congenital heart diseases is as effective as in children.

Adult↗

Functional activity of the CFTR Cl- channel in human myocardium.

The cyclic AMP (cAMP)-dependent chloride channel in the heart has been identified in various species as the cystic fibrosis transmembrane conductance regulator (CFTR). Although functional expression of the channel in the human atrium has been reported, we could not induce any cAMP-dependent chloride conductance in the atrial cells even with maximal cAMP stimulation, whereas the conductance could be induced in rabbit ventricular cells. To clarify the discrepancy between the results, we examined the level of CFTR mRNA expression in both conductance-positive (human colonic epithelium and rabbit ventricle) and -negative (human atrium) tissues. Total RNA samples prepared from these tissues were subjected to the reverse transcription-polymerase chain reaction (RT-PCR). While CFTR transcripts were amplified from the conductance-positive samples, no amplified products could be detected from the conductance-negative sample. A nested PCR performed on the RT-PCR products of the conductance-negative sample resulted in successful amplification of the transcripts, indicating that the level of the CFTR mRNA expression in human atrium is extremely low compared with that in colonic epithelium and rabbit ventricle. The same molecular results were observed in human ventricular tissues. A nucleotide sequencing of the amplified transcripts showed that exon 5 of the CFTR gene was not alternatively spliced in human atrium and ventricle, and both the exon 5 spliced and unspliced isoforms were expressed in rabbit ventricle, unlike the findings of previous reports. Our data suggest that the amount of CFTR expressed in human myocardium might be physiologically insufficient to activate detectable cAMP-dependent chloride conductance.

Adolescent↗

Evaluation of mastoid air cell system by three-dimensional reconstruction using sagittal tomography of the temporal bone.

The mastoid air cell system has been recognized as an important contributor to the pathophysiology of middle ear inflammatory diseases. Various methods of temporal bone imaging have been designed to investigate the correlation between middle ear disease and mastoid pneumatization. In this study, the mastoid air cell system was reconstructed three-dimensionally from sagittal tomographic images of the temporal bone on X-ray films, using a personal computer to evaluate the mastoid pneumatization in a total of 29 patients with chronic otitis media, adhesive otitis media, adhesive-type cholesteatoma, attic cholesteatoma and cholesterol granuloma, and in five normal subjects as controls. Reconstructed three-dimensional images of the mastoid air cell system and its volume were analyzed. The reconstructed images were helpful in recognizing the three-dimensional solid appearance of the mastoid air cell system. The volume of the reconstructed mastoid air cell system was significantly reduced compared with that in the controls in each of the patient groups. Mastoid pneumatization in the patients with adhesive-type cholesteatoma was significantly suppressed compared with that in the adhesive otitis media patients. Interestingly, the adhesive otitis media group showed cell development at the tip of mastoid process, whereas the group of adhesive-type cholesteatoma did not, suggesting a difference in the pathophysiology in the two diseases. We found that three-dimensional reconstruction of the temporal bone using sagittal tomographic images was useful in evaluating the state of mastoid air cell system development in individual cases and in investigating the pathophysiology in middle ear disease.

Adolescent↗

Radiological findings of adenolymphoma (Warthin's tumor).

The radiological findings of adenolymphomas (Warthin's tumor) treated in six hospitals between 1985 and 1994 were compared with the operative and histological findings and the usefulness of the radiological examinations was evaluated. The total number of patients was 72. The mean age was 61.8 years; 61 were males and 11 were females. All tumors developed in the parotid gland. Tc-99m-pertechnetate salivary gland scanning was performed in 13 patients and an increased uptake of the isotope was observed in only six patients. Even if Tc-99m-pertechnetate salivary gland scanning does not reveal intense accumulation, this tumor should not be ruled out. By computed tomography (CT), ultrasonography (US), and magnetic resonance imaging (MRI), the margin of all tumors was evident; however, the contents of the tumor varied. The contents and multiplicity of the tumors were well demonstrated by MRI, which was found to be the most accurate imaging modality.

Adenolymphoma↗

The role of cadherin-catenin-cytoskeleton complex in angiogenesis: antisense oligonucleotide of plakoglobin promotes angiogenesis in vitro, and protein kinase C (PKC) enhances angiogenesis through the plakoglobin signaling pathway.

Angiogenesis plays an important role in various diseases and conditions such as malignant tumor, wound healing, and atherosclerosis. Since cell-to-cell adhesion may play a key role in angiogenesis, we investigated the effect of the cadherin-catenin-cytoskeleton complex on angiogenesis in human umbilical vein endothelial cells (HUVECs). Immunofluorescence staining revealed that alpha-catenin, beta-catenin, and plakoglobin were concentrated at cell-cell contacts in HUVECs. Antisense oligonucleotide (AS-oligo), complementary to the region of human plakoglobin was dissolved in saline and applied to the media at 1 mM every 12 h for 4 days, and sense oligonucleotide (S-oligo) was used as control. HUVEC migration from an injury line was enhanced by AS-oligo. Interestingly, HUVECs migrated in line with S-oligo, and in a scattered fashion with AS-oligo. Tube formation on Matrigel occurred earlier with AS-oligo than with S-oligo. These findings indicate that plakoglobin inhibited HUVEC migration and tube formation (angiogenesis) by regulating cell-cell adhesion.

Cadherins↗

Endogenous endothelin-1 mediates cardiac hypertrophy and switching of myosin heavy chain gene expression in rat ventricular myocardium.

OBJECTIVES: We investigated the role of endogenous endothelin-1 in the development of cardiac hypertrophy in vivo under pressure overload conditions. BACKGROUND: Endothelin-1, a potent vasoconstrictor peptide, has recently been shown to act as a growth factor of myocardial cells in culture. METHODS: We examined the effect of an endothelin-A receptor antagonist (FR139317) on the development of right ventricular hypertrophy in rats with monocrotaline-induced pulmonary hypertension. Three groups of rats were studied: those given monocrotaline alone or monocrotaline plus FR139317 and those given vehicle alone (control group). RESULTS: The ratio of right ventricular systolic pressure to aortic systolic pressure was similarly elevated in rats treated with monocrotaline and monocrotaline plus FR139317. The right ventricular/left ventricular weight ratio was increased in monocrotaline-treated rats but lower in rats treated with monocrotaline plus FR139317 than in those treated with monocrotaline alone (p < 0.01). As a biochemical marker of hypertrophy, the isoform ratio of beta-myosin heavy chain protein was determined for the right ventricular tissue samples. This ratio was increased in all monocrotaline-treated rats but was lower (p < 0.01) in rats given monocrotaline plus FR139317 than in those given monocrotaline alone. The isoform ratio of beta-myosin heavy chain messenger ribonucleic acid quantitated by S1 nuclease mapping also was lower (p < 0.025) in rats receiving monocrotaline plus FR139317 than in those receiving monocrotaline alone. CONCLUSIONS: These data suggest that blocking the action of endothelin-1 with a receptor antagonist ameliorates cardiac hypertrophy in this model system, and that this action is not mediated by ameliorating hemodynamic changes.

Animals↗

Role of endothelin in a rabbit model of acute myocardial infarction: effects of receptor antagonists.

The role of endothelin (ET) in acute myocardial infarction and proarrhythmic potential was investigated in a rabbit model. One group of rabbits underwent 30 min of circumflex occlusion and 3 h of reperfusion with measurements of myocardial blood flow and myocardial levels of ET-1 messenger RNA (mRNA). In a second group, the systemic and coronary effects of exogenous ET were studied in animals pretreated with either saline, FR139317, an ETA-receptor antagonist, or PD145065, an ETA-and ETB-receptor antagonist. In a third study, animals undergoing 30 min of circumflex occlusion followed by 48 h of reperfusion were treated with exogenous ET-1, FR139317, PD145065, or saline. Arrhythmias were recorded and infarct size measured at 48 h. These studies revealed that ischemia and reperfusion was followed by a progressive microcirculatory failure ("no-reflow phenomenon") in rabbits. This was associated with a 2.6-fold elevation in levels of myocardial ET-1 mRNA in the ischemic zone in comparison to the nonischemic zone (p = 0.04). Exogenous ET-1 caused elevation in coronary and systemic vascular resistance that was significantly blocked by antagonism of the ETA receptor. In rabbits subjected to myocardial ischemia and reperfusion, ET-1 infusion led to a higher incidence of ventricular arrhythmias, whereas ET-receptor antagonism with PD145065 significantly reduced ventricular arrhythmias. Exogenous ET-1 and FR139317 failed to alter infarct size (AN) of the area at risk (AR) compared with control [AN/AR(%) was 46 +/- 8, 55 +/- 9, and 47 +/- 7, respectively]. However, PD145065 significantly decreased AN/AR (22 +/- 7; p < or = 0.02). The increased production of ET-1, resulting from increased levels of mRNA after reperfusion, may contribute to the no-reflow phenomenon. Although the vasoconstrictor effects of ET-1 can be blocked by ETA-receptor antagonism alone, only blockade of both the ETA and ETB receptors significantly reduced infarct size. These data suggest that production of ET increases in the heart during ischemia and is deleterious to the reperfused myocardium.

Animals↗

[Twenty-one cases of malignant tumor of the external auditory canal or middle ear].

Between 1982 and 1994, 21 patients with malignant tumors of the external auditory canal and middle ear were treated at the Department of Otolaryngology, Niigata University. Eleven patients with tumors of the external auditory canal and 10 tumors of the middle ear were registered. There were 9 males and 12 females, and their ages ranged from 10 to 80 years (median: 61). Otalgia, otorrhea or bloody otorrhea were the chief complaints of most patients with external auditory canal of middle ear tumors. Pathological examination revealed squamous cell carcinoma in 16 patients, adenoid cystic carcinoma in 3 patients, and basal cell carcinoma and rhabdomyosarcoma in 1 patient each. External auditory canal tumors were surgically excised, while radical mastoidectomy and subsequent irradiation were performed for the middle ear tumors. The five-year survival rate determined by the Kaplan-Meier method, was 77.8% for patients with external auditory canal tumors and 40% for those with middle ear tumors.

Adolescent↗

Early inflammatory changes of the Haemophilus influenzae-induced experimental otitis media.

Haemophilus influenzae is one of the most frequent pathogens of acute otitis media. To determine the middle ear response during the early stage of acute inflammation, a small amount of H. influenzae was inoculated into the bullae of guinea pigs through the tympanic membrane. The bullae were harvested at 6, 12, 24, 36, and 48 hours after H. influenzae inoculation and washed with phosphate-buffered saline (PBS). The number of viable H. influenzae and inflammatory cells, the concentrations of myeloperoxidase (MPO) and lysozyme in the washing suspensions were measured, and compared with those in PBS-inoculated control ears. The number of viable H. influenzae increased very rapidly from 6 to 12 hours after inoculation and remained stationary up to 48 hours. The number of inflammatory cells and the MPO concentration were significantly higher in the H. influenzae-inoculated ears than in the control ears from 12 to 48 hours after inoculation. The lysozyme concentration was already significantly higher at 6 hours in the H. influenzae-inoculated ears; the lysozyme was released in the middle ear before the accumulation of inflammatory cells and degranulation of MPO from inflammatory cells. The results indicated that inflammatory reactions were present already at 6 hours after bacterial inoculation, and were rapidly accelerated during the subsequent hours. Consequently, acute middle ear inflammatory responses were seen immediately following inoculation of viable bacteria, and these responses originated in direct responses of middle ear mucosa, and oxidative and non-oxidative neutrophil metabolic products, which may cause tissue injury.

Acute Disease↗

Cooperative interaction of GATA-2 and AP1 regulates transcription of the endothelin-1 gene.

Endothelin-1 (ET-1) is a 21-amino-acid vasoactive peptide initially characterized as a product of endothelial cells. Reporter gene transfection experiments have indicated that a GATA site and an AP1 site are essential for ET-1 promoter function in endothelial cells, and GATA-2 appears to be the active GATA factor which regulates ET-1 expression. To look for interactions between AP1 and GATA-2, transactivation experiments were performed with expression vectors encoding c-Jun, c-Fos, and GATA-2. Cooperativity between the AP1 complex and GATA-2 was observed as a synergistic increase in transcriptional activity of the ET-1 reporter plasmid. In addition, AP1 was able to potentiate the action of GATA-2 on reporter constructs lacking a functional AP1 site. In a similar fashion, GATA-2 was able to potentiate the action of AP1 despite deletion of the GATA site. Experiments with GATA-1 and GATA-3 expression vectors provided evidence that this capacity to interact with AP1 may be a characteristic of all GATA family members. Biochemical evidence for AP1-GATA interaction was provided by immunoprecipitation experiments. A GATA-2-specific antiserum was shown to immunoprecipitate in vitro-synthesized Jun and Fos protein from reticulocyte lysate. Also, antisera directed against Jun and Fos were able to immunoprecipitate from nuclear extracts a GATA-binding protein, indicating the association of AP1 and GATA proteins in vivo.

Base Sequence↗

Long-term prognosis of medically treated patients with acute myocardial infarction and one-vessel coronary artery disease.

Long-term prognosis was studied in 156 patients with acute myocardial infarction (AMI) with 1-vessel coronary artery disease (CAD). During a mean follow-up period of 110 months, 19 patients (14%) had reinfarction, 15 (9.6%) died (including 7 deaths of cardiac origin) and 15 (9.6%) were hospitalized for worsening of angina. A coronary arteriogram was obtained twice in 54 patients. The coronary arteriogram revealed multivessel CAD in all cases with reinfarction (n = 14). Ten percent of the patients with multivessel disease experienced a reinfarction during the initial 3 years after the onset of the first AMI. The recurrence rate of AMI in patients with 1-vessel disease increased gradually from the third year after the onset of their first AMI, reaching 10% in 6.7 years. The recurrence of AMI at the same region as the original infarction was detected in only 1 patient. Six of 19 patients (32%) with recurrence of AMI died and 13 survived after the reinfarction. It was difficult to predict future progression from the outcome of the comparison between the first and second coronary arteriograms. Thus, in patients with uncomplicated AMI with 1-vessel CAD, the prognosis is relatively good and the frequency of reinfarction is very low with conservative treatment.

Adult↗