Biomedical subjects

M Inada

Publications and source records attributed to M Inada.

At least 109 records · Page 6Linked to original sources

PubMed1996

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↗

PubMed1996

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↗

PubMed1996

Thyroid cell proliferation-inhibiting activity in serum of patients with chronic renal failure on hemodialysis.

To investigate the possible humoral factor(s) influencing thyroid cell activity in chronic renal failure, we measured serum activity which stimulates or inhibits the [3H]thymidine incorporation by using a cultured functioning rat thyroid cell line (FRTL-5 cells) in 17 patients on hemodialysis and 19 healthy controls. Polyethylene glycol-treated serum was centrifuged and FRTL-5 cells were cultured with the supernatant. Thyroid stimulating activity was determined by [3H]thymidine incorporation after incubation for 72 h. There was no significant difference in [3H]thymidine incorporation between cultures incubated with patient and normal serum, suggesting the absence of the stimulating activity. But when patient serum was added to cultures together with 20 or 50 microU/ml of TSH, the TSH-stimulated increase in [3H]thymidine incorporation was significantly decreased, indicating the presence of thyroid inhibiting activity, which possibly inhibits the thyroid cell growth. This activity was not significantly altered by hemodialysis. No significant correlation was observed between this activity and serum levels of thyroid hormones or the iodine concentration. Patients on hemodialysis therefore have serum thyroid inhibiting activity which is nondialysable, differs from iodine, and could influence the thyroid cell growth.

Adult↗

PubMed1996

Plasma free thyroxine (FT4) concentrations during hemodialysis in patients with chronic renal failure: effects of plasma non-esterified fatty acids on FT4 measurement.

Plasma free T4 (FT4) concentrations could be increased during hemodialysis in patients with chronic renal failure (CRF) because an increase in non-esterified fatty acids (NEFA) could interfere with the binding of T4 to thyroxine-binding globulin. To evaluate the effect of hemodialysis on the FT4 concentration in patients with CRF, we measured the FT4 in 39 patients with CRF by four assay methods including equilibrium dialysis, the 125I-T4 analog method and enzyme immunoassay. The addition of the fatty acid sodium oleate to normal pooled sera led to a marked increase in FT4 as measured by equilibrium dialysis (Model FT4). A moderate increase in the serum FT4 concentration also was observed with an IMX enzyme immunoassay kit, whereas the Coat-A-Count analog method demonstrated no interference by sodium oleate. The mean serum FT4 prior to hemodialysis measured by equilibrium dialysis did not differ significantly from that in the normal control, although those measured by analog methods (Coat-A-Count and Amerlex) and IMX were subnormal. The FT4 by IMX were albumin-dependent, and the values decreased as the samples were serially diluted, but Model FT4 was not affected by the albumin level or the serial dilution. FT4 by Model FT4 showed a marked increase beginning 10 min after the start of dialysis, and it correlated well with the plasma concentration of NEFA and the NEFA/albumin molar ratio. The other three assay methods, including one which is not affected by NEFA, did not show a change in FT4 at 10 min, but a significant increase of 11 to 17% was observed by the end of dialysis. The TSH concentration decreased significantly during hemodialysis. These data suggest that (1) the low serum FT4 in hemodialysis patients measured by some immunoassay methods may be an underestimation due to the low albumin level; (2) FT4 actually increases during hemodialysis due to the actual increase in NEFA, although the marked increase in FT4 during hemodialysis as measured by equilibrium dialysis is an overestimation due to the in vitro generation of NEFA; and (3) one should beware of aberrations in thyroid hormone parameters during hemodialysis and potential complications.

Dialysis↗

PubMed1996

Age associated changes in the distribution of lpr gene-induced B220-positive T cells in lymphoid organs of MRL/Mp-lpr/lpr mice using dual exposure microphotographs of double immunofluorescence staining.

Homozygous MRL/Mp-lpr/lpr [MRL/lpr] mice, which have an autosomal recessive mutant lpr gene and exhibit defects in Fas antigen, spontaneously develop autoimmune disease with progressive expansion and accumulation of characteristic abnormal CD4-CD8-double negative T cells that express B220 surface antigen, a B cell-specific surface marker in normal mice. We analyzed the distribution and age related changes of lpr gene-induced abnormal T cells (B220-positive lpr T cells) in the lymphoid organs of MRL/lpr mice. We studied cryostat sections of the spleen, peripheral lymph nodes, mesenteric lymph nodes, and Peyer's patches at different stages using FITC [fluorescein isothiocyanate)-conjugated monoclonal antibodies directed against B220 (RA3-6B2) and PE (phycoerythrin)-conjugated anti-mouse CD3 (2C11) monoclonal antibody, examining dual-exposure microphotographs of double-immunofluorescence stained preparations. We observed that in aged MRL/lpr mice, B220-positive abnormal lpr T cells were not present in the thymus-dependent area, and the majority of the follicular area cells were displaced by lpr T cells. These findings suggest that the cellular trafficking of B220-positive lpr T cells differs from that of conventional T cells and that these lpr-derived T cells play a role in the follicle.

Aging↗

PubMed1996

[Modulation of evoked potentials following electrical tooth stimulation by pre-auditory stimulus].

Modulation of evoked potentials following electrical tooth stimulation (Dental EPs) and visual analogue scale (VAS) were studied in 11 healthy adult volunteers to investigate the possibility of controlling reaction of pain sensation by using pre-auditory stimulus. They were recorded by these two paradigms. 1) Only electrical tooth stimulation delivered in random interval. 2) A preceding tone beep, to enable subjects to anticipate the coming tooth stimulus. Preceding time, inter stimulation intervals (ISI) were 0.5, 1.0, 3.0, 5.0, and 7.0sec. The results were as follows: 1) The Dental EPs were recorded in every volunteer, and the N2-P2 amplitude was the largest at vertex areas (Cz). 2) The P2 latency and N2-P2 amplitude were modulated by the preceding tone beep, reduced in ISI = 0.5 and 1.0sec, and increased in ISI = 5.0 and 7.0sec., and a linear correlation was found between their variations. 3) There were no significant differences in the VAS score between each paradigm. These findings suggested that: 1) The late component of Dental EPs reflects not only the physiological process of the pain sensation but also psychological process of expectation and anxiety. 2) Pre-auditory stimulus and time lag between pre-auditory stimulus and electrical tooth stimulation influence the psychological process and modulate the Dental EP result.

Acoustic Stimulation↗

PubMed1996

[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↗

PubMed1996

[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↗

PubMed1996

[Effects of nicorandil on coronary collateral circulation depend on the donor arteries].

The effects of nicorandil on coronary collateral circulation during exercise-induced ischemia were compared between the different donor arteries in 13 patients with effort angina, 7 with complete obstruction of the left anterior descending artery (LAD) with well-developed collateral vessels from the right coronary artery (RCA) (LAD group), and 6 with complete occlusion of the RCA (segment 2-3) with well-developed collateral vessels from the LAD (RCA group). Initial percentage thallium (%TI) uptake (thallium-201 single photon emission computed tomography) and washout rate were measured in the anterior, septal and posterior regions during ergometer exercise. The submaximal treadmill exercise test was also performed using a cardiopulmonary monitoring system to measure Vo2 at anaerobic threshold (AT). After the controls were obtained, nicorandil (15 mg/day) was administered for 4 weeks, during which ergometer exercise and treadmill exercise tests were carried out repeatedly. A significant improvement of initial %TI uptake on exercise was observed in the LAD group with nicorandil therapy, but no improvement was shown in the RCA group. The AT significantly increased after nicorandil treatment in the LAD group (13.9 +/- 0.38-->16.8 +/- 1.18 ml/min/kg), reflecting the improvement of cardiac function through the increased collateral flow. However, in the RCA group, it remained unchanged, suggesting no improvement of cardiac function. Nicorandil was effective to increase collateral flow from the RCA, but ineffective on that from the LAD. Nicorandil is an effective coronary dilator and is reported to affect both large and small coronary arteries. The effect on the collateral circulation is dependent on the donor artery supplying different areas. The vasodilator effect of nicorandil is mainly on the LAD, which is large enough to supply blood to a wider area of the heart, rather than the RCA.

Adult↗

PubMed1995

Gene transcription of angiotensin II type 2 receptor is repressed by growth factors and glucocorticoids in PC12 cells.

The rat angiotensin II type 2 receptor (AT2-R) expression was markedly downregulated by the mitogenic action of serum, growth factors and dexamethasone. The regulation by serum or growth factors did not affect the AT2-R mRNA half-life (18 h), whereas the AT2-R half-lives of dexamethasone-treated cells and proliferating cells decreased to 10 h and 15 h, respectively. Nuclear run-off assays indicated the mechanism of repression of AT2-R expression by serum, growth factors and dexamethasone or in proliferating cells to be, in large part, transcriptional. These findings indicate that transcription of the AT2-R gene is regulated in a growth state-dependent manner and suggest that this regulation provides a means by which cells can modulate their responsiveness to the actions of angiotensin II mediated through AT2-R.

Angiotensin II↗

PubMed1995

Identification of a negative cis-regulatory element and trans-acting protein that inhibit transcription of the angiotensin II type 1a receptor gene.

The rat angiotensin II type 1a receptor (AT1a-R) gene is expressed in a cell-specific manner. We demonstrated that the negative regulatory element (NRE) between -489 and -331 is active in PC12 cells (Murasawa, S., Matsubara, H., Urakami, M., and Inada, M. (1993) J. Biol. Chem. 268, 26996-27003). Gel retardation assays confirmed that PC12 cells have a trans-acting factor bound to the NRE. By means of a DNase I footprint assay we identified the core of the NRE as an (A+T)-rich sequence (TAATCTTTTATTTTA) located at nucleotides -456 to -442. Oligonucleotides corresponding to the NRE core sequence bound to nuclear protein. Site-directed mutagenesis at nucleotides -451 to -448 eliminated the specific protein/DNA binding and restored expression of the AT1a-R in transient transfection assays (2.7-fold increase). The NRE did not negatively affect the thymidine kinase promoter. No homology was found with known NREs, suggesting that this is a novel NRE. Southwestern blotting revealed a 53-kDa, specific binding protein in PC12 cells and the rat brain, but not in the liver, spleen, adrenal gland, and kidney. These findings demonstrate that the NRE of the rat AT1a-R is an (A+T)-rich sequence located at nucleotides -456 to -442 and the 53-kDa protein is a specific binding protein, and suggest that this protein may be a trans-acting factor which determines the neuron-specific down-regulation of the AT1a-R gene.

Angiotensin II↗

PubMed1995

Structure of the rat V1a vasopressin receptor gene and characterization of its promoter region and complete cDNA sequence of the 3'-end.

The gene encoding the rat V1a arginine vasopressin (AVP) receptor was isolated, and its structural organization and 5'-flanking region were characterized. In addition, the complete cDNA sequence of the major transcript of the rat V1a receptor gene was determined. Southern blots demonstrated a single copy of the V1a receptor gene in the rat genome, spanning a region of 3.8 kilobases (kb) and consisting of two exons and one intron (1.8 kb). The location of the intron was unique among G protein-coupled receptor genes in that the first exon encodes six of the seven transmembrane regions, the seventh region being encoded by the second exon. Primer extension, RNase protection, and rapid amplification of the 5'-end of the cDNA identified three transcriptional initiation sites (-405, -243, and -237), the major transcription initiation sites being mapped to positions -243 and -237 base pairs (bp) upstream of the ATG initiation codon (+1 bp). This portion of the 5'-flanking region has neither a TATA nor a CCAAT box, is GC-rich but has no GC box motif, and has features of promoters seen in housekeeping genes. Chimeras containing 2.2 kb of the 5'-flanking region and deletion analyses using the chloramphenicol acetyltransferase gene indicated that a "minimal" region, exhibiting promoter activity and tissue specificity, is located between nucleotides -296 and -221, when transfected into vascular smooth muscle cells. Gel mobility shift assay and Southwestern blotting suggested that approximately 30- and approximately 28-kDa nuclear proteins specifically bind to this region. Rapid amplification of the 3'-end of the cDNA showed that the major transcript terminates 442 bp downstream of the stop codon, in agreement with the mRNA size (2.1 kb). This study demonstrated a distinctive feature in the structural organization of the AVP-oxytocin receptor family genes, and characterization of the 5'-flanking region reported here will lead to a better understanding of the mechanism of transcriptional regulation of the rat V1a AVP receptor gene.

3T3 Cells↗

PubMed1995

Two vasopressin type 2 receptor gene mutations R143P and delta V278 in patients with nephrogenic diabetes insipidus impair ligand binding of the receptor.

We recently identified vasopressin type 2 receptor gene mutations in two unrelated Japanese families with X-linked nephrogenic diabetes insipidus, which were a missense mutation from Arg143 to Pro (R143P) and a single amino acid deletion of Val278 or 279 (delta V278). To investigate the mechanism by which the mutations cause arginine vasopressin (AVP) resistance in this disorder, we expressed them in mammalian cells and analyzed their functional properties. Stable expression study with Chinese hamster ovary (CHO) cells demonstrated that the R143P mutation reduced receptor binding capacity to 10% of normal. However, the R143P mutant itself had a normal affinity for AVP and stimulated adenylyl cyclase production at up to 50% of the wild-type level, suggesting that the mutant receptors could function normally despite their reduced surface expression. In contrast, the delta V278 mutation totally abolished receptor-ligand binding and subsequent adenylyl cyclase stimulation, indicating that delta V278 mutant is virtually nonfunctional receptor. Northern blotting revealed that mutant CHO cell lines produced levels of receptor mRNA similar to the wild-type cell line. Our results suggest that the two mutations impair binding activity of the receptor without affecting mRNA accumulation, thereby causing AVP resistance through a posttranscriptional mechanism.

Amino Acid Sequence↗

PubMed1995

Characterization of glucocorticoid response element of rat angiotensin II type 1A receptor gene.

The responsiveness of the rat angiotensin II type 1a and type 1b receptor (AT1a-R and AT1b-R) genes to glucocorticoid was examined in rat vascular smooth muscle cells (VSMCs) and the glucocorticoid response element (GRE) of the AT1a-R gene was characterized. Glucocorticoid induced an increase in AT1a-R mRNA levels, whereas AT1b-R mRNA levels were unaffected. The nuclear run-off assay indicated that the transcription of the AT1a-R gene, but not that of the AT1b-R gene, was increased by glucocorticoid. The mRNA stability of AT1a-R was unchanged by glucocorticoid. Promoter/chrolamphenicol acetyltransferase reporter analysis demonstrated that the 5'-flanking region of the AT1a-R gene was functional in rat VSMCs and established that the GRE motif between -770 to -756 could confer glucocorticoid responsiveness on the AT1a-R gene.

Angiotensin II↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

Regulation by basic fibroblast growth factor of glycosaminoglycan biosynthesis in cultured vascular endothelial cells.

The alteration of glycosaminoglycans (GAGs) in cultured bovine aortic endothelial cells after exposure to basic fibroblast growth factor (bFGF) was investigated. It was found that the incorporation of [3H]glucosamine into GAGs was markedly increased by bFGF in both the cell layer and the conditioned medium; however, that of [35S]sulfate was not changed by the growth factor. These results indicated that bFGF enhanced the sugar-chain formation but did not affect their sulfation in endothelial GAG production. Similar changes were observed in either bovine aortic smooth-muscle cells and human fibroblastic IMR-90 cells to greater and lesser degrees, respectively. Characterization of GAGs in the endothelial cell layer and the conditioned medium revealed that bFGF enhanced both heparan sulfate and the other GAGs to a similar degree. The present data suggest that bFGF may be involved in the regulation of the blood coagulation system via altering GAGs of the vascular tissue when the endothelium was damaged.

Animals↗

PubMed1995

No detectable cytomegalovirus and Epstein-Barr virus genomes in the pancreas of recent-onset IDDM patients.

Viral infection is assumed to trigger or exacerbate autoimmune responses against pancreatic beta cells leading to the development of insulin-dependent diabetes mellitus (IDDM). We therefore examined by polymerase chain reaction the presence of two candidate viruses, cytomegalovirus and Epstein-Barr virus, in IDDM pancreases. Pancreas tissues were obtained by biopsy under laparoscopy from 16 recent-onset IDDM patients: age 17-53 years; disease duration 0-7 months; six had flu-like symptoms before onset. Frozen sections were made and subjected to DNA amplification. DNA samples were prepared from the frozen sections and polymerase chain reaction was performed using primers specific to cytomegalovirus, Epstein-Barr virus and control gene for HLA-DP. Cytomegalovirus- and Epstein-Barr virus-infected cells were used for positive control. Southern blot analysis could detect cytomegalovirus DNA from as few as 2 x 10(-1) cytomegalovirus-infected cells and Epstein-Barr virus DNA from two Epstein-Barr virus-infected cells. This highly sensitive analysis, however, could not detect cytomegalovirus or Epstein-Barr virus genomes in pancreases of recent-onset IDDM. A single copy human gene (HLA-DP) was amplified from all IDDM pancreases indicating that DNA amplification was performed without inhibition. We conclude that cytomegalovirus or Epstein-Barr virus genomes are unlikely to exist in pancreas biopsy specimens of recent-onset IDDM patients.

Adolescent↗