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Biomedical subjects

T Iwasaka

Publications and source records attributed to T Iwasaka.

At least 145 records · Page 8Linked to original sources

Skeletal muscle hypoperfusion during recovery from maximal supine bicycle exercise in patients with heart failure.

Leg blood flow (LBF) and its relation to central hemodynamics were examined during recovery following maximal supine bicycle exercise in 11 patients with heart failure and 20 patients with normal exercise capacity after myocardial infarction. The results indicate that LBF was markedly reduced in patients with heart failure, and that decreased cardiac output response and enhanced peripheral vasoconstriction, which functioned to prevent hypoperfusion in the nonexercising vital regions and to maintain arterial blood pressure, were responsible for the reduced LBF during recovery in heart failure.

Adult↗

Sustained ventricular tachycardias associated with myotonic dystrophy.

Patients with myotonic dystrophy are reported to have a higher frequency of sudden death than the general population. Although causes of sudden death in myotonic dystrophy are suggested to be due to conduction of defects progressing, the HV interval cannot predict whether conduction system disease would develop or progress. We report two cases of myotonic dystrophy complicated with sustained monomorphic ventricular tachycardias (VT), which can cause sudden death. In Case No. 1, although the patient was treated successfully for sustained VT with verapamil in electrophysiologic studies, another sustained VT was confirmed 2 years later. In Case No. 2, the patient showed decreased left ventricular ejection fraction and late potentials, and induced sustained VT that was identical to clinically documented VT. Although VT is believed to be rare in patients with myotonic dystrophy, these cases suggest that VT is a possible cause of sudden death.

Adult↗

Growth suppression of a cervical cancer cell line (TMCC-1) by the human wild-type p53 gene.

To investigate the effects of human wild-type p53 expression on the proliferation of cervical carcinoma cells, a plasmid, pMO7-hp53, which contains a full-length cDNA of the human wild-type p53 (wt-p53) gene, was transfected into a cell line (TMCC-1) derived from an endocervical type, human papilloma virus-positive adenocarcinoma of the uterine cervix. The exogenous wt-p53 expression induced growth suppression, morphological changes, and loss of anchorage-independent growth of the tumor cells. As the wt-p53 gene apparently plays a negative role in growth regulation of cervical carcinoma cells, this gene may possibly be of some use for treating subjects with a cervical carcinoma.

Adenocarcinoma↗

Influence of intrinsic limb vasodilator capacity on exercise tolerance in patients with recent myocardial infarction.

To investigate the influence of intrinsic limb vasodilator capacity on exercise performance, limb reactive hyperemic flows and their relations to exercise capacity during upright bicycle exercise were examined in 52 patients with recent myocardial infarction. Reactive hyperemic flow was measured in the forearm and the calf by venous occlusive plethysmography after 5 min of arterial occlusion. Calf reactive hyperemic flow correlated significantly with cardiac output, systemic vascular resistance, and oxygen consumption at peak exercise, whereas flow in the forearm did not. In patients with preserved exercise capacity (group 1, n = 20) compared with those with exercise impairment (group 2, n = 32), calf reactive hyperemic flow was significantly augmented, but forearm flow was similar in the two groups. There were no significant differences in hemodynamic parameters at rest between the two groups. At peak exercise, however, cardiac output was lower and systemic vascular resistance was higher in group 2 than in group 1, whereas arterial blood pressure was maintained identically in the two groups. Thus, intrinsic calf but not forearm vasodilator capacity was linked to exercise hemodynamic responses and exercise capacity in patients with recent myocardial infarction. In addition, reduced calf vasodilation and concomitant enhanced vascular tone seemed to be useful for preserving arterial blood pressure in the setting of decreased cardiac output response to exercise in patients with exercise impairment.

Adult↗

Prevalence, resolution, and determinants of late potentials in patients with unstable angina and left ventricular wall motion abnormalities.

Although transient myocardial ischemia such as exercise-induced ischemia has not been reported to be associated with the occurrence of late potentials, the association of late potentials with more profound ischemic damage, which is represented by reversible but prolonged left ventricular wall motion abnormalities, has not been demonstrated. We prospectively evaluated 37 unstable angina patients who had reversible but prolonged wall motion abnormalities after resolution of chest pain and electrocardiogram (ECG) changes. Signal-averaged ECG (SAECG) and echocardiogram were recorded during the acute phase and before hospital discharge. Late potentials were present in 6 (16 percent) patients on the initial SAECG recording and resolved in all 6 patients on the second recording before hospital discharge. Normalization of inferior left ventricular wall motion abnormality and multivessel disease were observed more frequently in patients with late potentials on the initial recording than in patients without (p < 0.05 and p < 0.05, respectively). In conclusion, late potentials were observed in patients who had reversible but prolonged wall motion abnormalities; these late potentials were resolved with improvement of left ventricular wall motion abnormalities. These results suggest that myocardial ischemia with prolonged wall motion abnormalities is a possible mechanism of the occurrence of late potentials.

Action Potentials↗

Flow cytometric analysis of platelet activation markers CD62P and CD63 in patients with coronary artery disease.

We investigated whether platelet activation could be quantitatively detected in patients with coronary artery disease using flow cytometric analysis of the expression of CD62P and CD63, which are activation-specific antigens on the platelet surface. Platelet samples were obtained from 16 healthy control subjects and 65 patients, of whom 25 had angiographically normal coronary arteries and 40 had at least one major coronary artery stenosis (> or = 50% narrowing). In both patient groups, CD62P expression was significantly higher than in the control group, but the difference between the two patient groups was not significant. In contrast, CD63 expression did not differ among the three groups. We also compared expression of these antigens after stratifying the patients according to the number of significant coronary artery stenoses. Patients with three-vessel disease had significantly increased CD62P and CD63 expression compared with the other subgroups. Our findings indicate that platelet activation occurs in patients with severe coronary artery stenosis.

Adult↗

Human papilloma virus and P53 overexpression in carcinomas of the uterine cervix, lower uterine segment and endometrium.

Inactivation of the wild type p53 protein through complexing of protein synthesized by specific subtypes of human papilloma virus (HPV) or mutation in the p53 gene in considered to play an important role in cervical carcinogenesis. The association between p53 overexpression and the presence of HPV 16 and 18 DNA was assessed in 29 cervical carcinomas, 15 carcinomas of the lower uterine segment and 30 endometrial carcinomas. In 29 cervical carcinomas (21 adenocarcinomas and 8 adenosquamous carcinomas), 7 cases were positive for HPV 16 DNA while 5 were positive for HPV 18 DNA. Nine cases (31%) showed p53 overexpression. An inverse association was seen between the presence of HPV DNA and the p53 overexpression. In 15 carcinomas of the lower uterine segment, one case was positive for HPV 16 DNA while 2 were positive for HPV 18 DNA. Overexpression of p53 was seen in 8 (53%) carcinomas of the lower uterine segment. Two of 3 HPV DNA positive carcinomas of the lower uterine segment revealed p53 overexpression. HPV DNA was not detected in endometrial carcinomas and p53 overexpression was shown in 12 (40%) cases. The association between HPV DNA and p53 overexpression differs among the tumors arising in the cervix, lower uterine segment and endometrium.

Adult↗

Translational regulation of angiotensin II type 1A receptor. Role of upstream AUG triplets.

The cDNA sequence of rat angiotensin II type 1A receptor (AT1AR) shows that AT1AR transcripts have AUG triplets in the 5'-leader region that may begin a short open reading frame encoding an 11-amino acid peptide. In this study, the mutational inactivation of the start codon of the short open reading frame in AT1AR-chloramphenicol acetyltransferase (CAT) reporter gene constructs resulted in a 2.6-fold increase in CAT activity, whereas CAT transcript levels were not affected. Furthermore, experiments with rat AT1AR cDNA-transfected Cos-7 cells revealed that mutagenesis of the upstream AUG increased the AT1AR protein up to 2.5-fold, although AT1AR transcript levels showed no changes. The synthetic peptide corresponding to the sequence of the short open reading frame significantly suppressed the amount of AT1AR product in the in vitro translation system. The inhibiting effect of the short open reading frame appears to operate at least in part at the level of translation initiation, because polysome analysis with transfected Cos-7 cells showed that mutagenesis of the upstream AUG resulted in a shift of AT1AR mRNA distribution from a smaller to larger fraction of polysomes. Taken together, these results show that the upstream AUG inhibits translational regulation, suggesting that the short open reading frame in the 5'-leader region of AT1AR transcripts has a certain role in the translation of AT1AR protein.

Animals↗

Mechanical stretch induces enhanced expression of angiotensin II receptor subtypes in neonatal rat cardiac myocytes.

Mechanical stress plays a pivotal role in the development of cardiac hypertrophy during hemodynamic overload, and angiotensin (Ang) II secreted from stretched myocytes plays an important role in mechanical stretch-induced hypertrophy. In the present study, we examined stretch-induced expression of Ang II receptors in an in vitro stretch model using 1-day-old rat myocytes. Both Ang II type 1 receptor (AT1-R) and type 2 receptor (AT2-R) mRNA levels were upregulated by myocyte stretching with similar time courses: significant increases were evident 6 hours after stretching, maximal levels (2.8- and 3.3-fold, respectively) were observed at 12 hours, and these were sustained for up to 18 hours. Ang II receptor expression in fibroblast-rich cultures was not affected by stretching. Conditioned medium in which myocytes were stretched for 12 hours significantly downregulated AT1-R and AT2-R mRNA levels in recipient myocytes, and this effect was almost completely blocked by AT1-R antagonists but not AT2-R antagonists. Stretch-induced expression of AT1-R and AT2-R mRNAs was further increased by 27% and 31%, respectively, after pretreatment with AT1-R antagonists, suggesting that Ang II secreted from stretched myocytes downregulates both AT1-R and AT2-R. Western blot and binding assays showed that the number of AT1-Rs and AT2-Rs increased by 2.4- and 2.6-fold, respectively, without affecting receptor affinities. Inositol phosphate response to 0.5 mumol/L Ang II was enhanced 2.1-fold in stretched myocytes. Nuclear runoff assays and treatment with actinomycin D revealed that stretch-induced upregulation of AT1-R was mainly due to increased transcription, whereas that of AT2-R resulted from a stabilizing effect on AT2-R mRNA metabolism. Stretch-induced changes in levels of Ang II receptors were inhibited by genistein but not by H-7, staurosporin, and protein kinase C depletion or by BAPTA-AM. Exposure to cycloheximide did not affect stretch-induced changes. These findings indicate that nonsecretory pathways activated by myocyte stretching upregulate the expression of Ang II receptor subtypes transcriptionally and posttranscriptionally through mechanisms involving stretch-activated tyrosine kinases independently of de novo protein synthesis and that the AT1-R-mediated action of Ang II is functionally enhanced in stretched cardiac myocytes.

Angiotensin II↗

Down-regulation by cAMP of angiotensin II type 2 receptor gene expression in PC12 cells.

The rat angiotensin II type 2 receptor (AT2-R) gene was isolated, and cis-regulatory regions in its 5'-flanking area were analyzed. Primer extension and RNase protection analyses revealed a single transcriptional initiation site at the position 24 bp downstream of the TATA box. The 5'-flanking region of AT2-R contained several cis-regulatory elements, such as AP-1, AP-2, C/EBP, NF-1, NF-IL6, NF-kappa B, and glucocorticoid- and cAMP-responsive elements (CRE). The treatment of PC12 cells with dibutyryl cAMP caused a marked decrease (90%) in the AT2-R mRNA level, which was blocked by the inhibitor of protein kinase A and did not require new protein synthesis. The protein level was also reduced 84% after a 24-h exposure to cAMP and the binding affinity was unchanged. The half-life of the AT2-R mRNA decreased -66% by cAMP as compared with control (18.4 +/- 0.4 h). Deletion and mutation analyses of the 5'-flanking region (1.2 Kb) revealed that there were one negative (-1,199 to -739) and two positive cis-regulatory regions (-739 to -436 and -59 to +45), and that the CRE motif located at -426 repressed (-23%) the promoter activity of the rat AT2-R gene. The region between -59 and +45 containing TATA box and AP-2 site accounted for 70% of the promoter activity. These findings indicate that the promoter activity of the rat AT2-R gene is modulated by several cis-regulatory regions and that cAMP markedly downregulates the expression of the AT2-R mainly by inducing AT2-R mRNA destabilization rather than CRE-mediated inhibition of the gene transcription. Thus, humoral factors that transduce cAMP as an intracellular signal may modulate AT2-R-mediated function of Ang II by reducing AT2-R expression.

Animals↗

Cytologic changes in two cervical carcinoma cell lines after transfection of the wild-type p53 gene.

BACKGROUND: To examine morphological changes in cervical carcinoma cells after induction of overexpression of wild-type (wt) p53. METHOD: A dexamethazone-inducible wt-p53 cDNA was introduced into two cervical carcinoma cell lines (TMCC-1 and ME180) and morphological changes were examined under a phase contrast microscope and following Papanicolaou staining. RESULTS: TMCC-1 clones obtained by transfection with wt-p53 gene had an altered morphology especially after induction of p53 expression by treatment with dexamethazone. These changes were characterized by cell flattening, multinucleation, micronucleation, and huge giant cells, yet the parental TMCC-1 had none of these morphological changes even after treatment with dexamethazone. Similar cellular changes were observed in ME180 clones obtained by transfection of wt-p53 gene. CONCLUSION: On the basis of our observations, we propose that the growth inhibition induced by expression of wt-p53 in these cervical carcinoma cell lines carrying HPV DNA sequences is not the result of G1 arrest but rather relates to a blockade in the M phase of the cell cycle.

Adenocarcinoma↗

Do human papillomaviruses have a role in the pathogenesis of bladder carcinoma?

PURPOSE: Since little is known of the associations between bladder carcinoma and human papillomaviruses (HPVs), data on the role of HPV in bladder carcinogenesis are controversial. We attempted to clarify whether HPVs are present in bladder carcinomas. MATERIALS AND METHODS: We examined 36 specimens of bladder carcinoma for HPV positivity by the polymerase chain reaction method. RESULTS: HPV-16 deoxyribonucleic acid was detected in 1 specimen (3%) of a transitional cell carcinoma from a 37-year-old woman who had concomitant squamous cell carcinoma of the uterine cervix with positive para-aortic lymph node metastasis. The cervical tumor, bladder tumor and para-aortic lymph node metastasis were all positive for the same type of HPV. CONCLUSIONS: On the basis of this low rate of HPV detection (3%), HPVs are not likely to have a prominent role in carcinogenesis of the bladder.

Adult↗

[Gadolinium-diethylenetriamine pentaacetic acid enhanced magnetic resonance imaging of dilated cardiomyopathy: clinical significance of abnormally high signal intensity of left ventricular myocardium].

This study investigated the clinical significance of abnormally high signal intensity in the left ventricular myocardium on gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhanced magnetic resonance (MR) imaging in patients with dilated cardiomyopathy. Gd-DTPA enhanced MR imaging, Tl-201 myocardial single photon emission computed tomography (SPECT), Tc-99m radionuclide angiocardiography, M-mode echocardiography, electrocardiography and chest radiography were performed in 18 patients with dilated cardiomyopathy. The left ventricle was divided into five areas, the anteroseptal, anterolateral, inferoseptal, posterolateral and apical areas. Five patients (group A) had 0-2 and 13 patients (group B) had 3-5 high signal intensity areas. High signal intensity areas were demonstrated in 19 of 90 areas (21%) before Gd-DTPA enhancement and 50 of 90 areas (56%) after enhancement. Fifteen of 34 areas (44%) with abnormal Tl-201 uptake showed high signal intensity before Gd-DTPA enhancement and 31 (91%) showed high signal intensity after enhancement. Fifteen areas without abnormal Tl-201 uptake also showed high signal intensity after enhancement. Left ventricular ejection fraction (LVEF) and percent fractional shortening (%FS) in group B were lower than those in group A. LVEF(r = 0.78) and %FS (r = 0.82) were significantly correlated with the number of high signal intensity areas. Systolic left ventricular dimension was larger in group B than that in group A, and a significant correlation (r = 0.62) between systolic left ventricular dimension and the number of high signal intensity areas was found. There was no significant difference in right ventricular ejection fraction, left ventricular peak filling rate, diastolic left ventricular dimension, left ventricular thickness, cardiothoracic ratio or SV1+RV5 or 6 between group A and B. There was no correlation of peak filling rate, diastolic left ventricular dimension, cardiothoracic ratio or SV1+RV5 or 6 with the number of high signal intensity areas. These results suggest that abnormal high signal intensity on Gd-DTPA enhanced MR imaging may reflect myocardial degeneration, necrosis or fibrosis, and the high signal intensity predicts the severity of left ventricular dysfunction in dilated cardiomyopathy.

Adult↗

[Three-dimensional reconstructed magnetic resonance imaging for diagnosing persistent left superior vena cava: comparison with magnetic resonance angiography and plain chest radiography].

The usefulness of low-cost, three-dimensional (3D) images reconstructed from magnetic resonance (MR) imaging for investigating persistent left superior vena cava was assessed and compared to the diagnostic accuracy of chest radiography. MR imaging by the spin-echo technique and MR angiography were performed in 10 patients with this anomaly diagnosed previously by contrast echocardiography and radionuclide angiocardiography. Four patients had complicating cardiac anomalies, one with postoperative atrial septal defect, one with postoperative ventricular septal defect, one with atrial septal defect and partial anomalous pulmonary venous return, and one with aortic coarctation and patent ductus arteriosus. Multisectional and multiphasic MR images were used for the 3D-reconstruction of the cardiovascular and mediastinal structures with a NeXT workstation and a 3D-kit. The 3D-reconstructed MR imaging clearly showed the persistent left superior vena cava and the anatomical relationship with the other cardiovascular and mediastinal structures in all 10 patients. Vascular shadows were observed outside the upper left border of the aortic arch on the chest radiographs in seven patients, and the 3D-reconstructed MR images revealed these shadows to be compatible with superior caval vein. The ratios of the diameter between the left and right superior venae cavae with and without the left innominate vein were 0.63 +/- 0.14 (mean +/- SD) and 0.94 +/- 0.08, respectively. Three-dimensional reconstructed MR imaging is a useful method for recognizing persistent left superior vena cava and precise examination of the chest radiographs often allowed detection of the vascular shadows caused by this anomaly.

Adolescent↗

PQ segment depression in acute Q wave inferior wall myocardial infarction.

BACKGROUND: PQ segment deviation is almost as characteristic as the classic ST segment deviation and is detected in most patients with pericarditis. However, as infarction-associated pericarditis remains over the infarct zone, PQ segment depression is observed much less often in patients with acute myocardial infarction. METHODS AND RESULTS: We designed this study to examine the clinical significance of PQ segment depression in acute Q wave inferior myocardial infarction. We examined 171 consecutive patients with acute Q wave inferior myocardial infarction by means of auscultation, ECG, and two-dimensional echocardiography. The diagnosis of pericarditis was made on the basis of pericardial rub detected by more than two observers during the first 3 days after admission. At least 0.5 mm of PQ segment depression from the TP segment lasting more than 24 hours in both limb and precordial leads was considered diagnostic of PQ segment depression. CONCLUSIONS: PQ segment depression was present in 14 patients and absent in 157 patients. Eleven patients with and 55 patients without PQ segment depression had advanced asynergy (akinesis or dyskinesis) in the posterior segments, whereas 9 patients with and 20 patients without PQ segment depression had pericardial rub. When multivariate analysis was performed to determine the important variables related to the occurrence of PQ segment depression, pericardial rub was selected with advanced asynergy of the posterior segment as significant factors related to PQ segment depression. Major complications (ventricular fibrillation, sustained ventricular tachycardia, cardiogenic shock, need for pacing) were present in 63 patients; 9 with (64%) and 54 without (34%) PQ segment depression. PQ segment depression was one of the clinical signs of more extensive damage extending to the posterior segments and increased incidence of major complications.

Aged↗

Effects of left ventricular diastolic dysfunction on exercise capacity three to six weeks after acute myocardial infarction in men.

To examine the effects of left ventricular (LV) diastolic dysfunction on exercise capacity, hemodynamic and radionuclide responses were measured at rest and during exercise in 50 patients with recent myocardial infarction. The ratio of an increase in pulmonary arterial wedge pressure (PAWP) to an increase in LV end-diastolic volume (EDV) from rest to peak exercise (delta PAWP/delta EDV) was used as an index of LV diastolic function, delta PAWP/delta EDV had modest and negative correlations with peak oxygen consumption (VO2), cardiac output, and stroke volume in all patients. Among patients with peak VO2 > or = 20 ml/min/kg (group I, n = 24) and those with peak VO2 < 20 ml/min/kg (group II, n = 26), there were no differences between the 2 groups with regard to resting LV ejection fraction, EDV, PAWP, cardiac output, and stroke volume. Although there was no significant difference in LV ejection fraction at peak exercise, group II had significantly reduced EDV, increased PAWP, and decreased cardiac output and stroke volume than those in group I. As a result, delta PAWP/delta EDV was significantly higher in group II. These results suggest that LV diastolic dysfunction has a key role in determining exercise capacity in patients with reduced exercise capacity after recent myocardial infarction.

Adolescent↗