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Biomedical subjects

J Zamorano

Publications and source records attributed to J Zamorano.

At least 55 records · Page 3Linked to original sources

IL-4 protects cells from apoptosis via the insulin receptor substrate pathway and a second independent signaling pathway.

Although it has been known for some time that IL-4 protects cells from death via apoptosis, very little is known about the mechanism by which IL-4 exerts this effect. In this report, we have studied the molecular mechanisms of the IL-4-induced prevention of apoptosis in the 32D and B cell systems. IL-3 withdrawal has been shown to induce G1-arrest in 32D cells and subsequent death by apoptosis. We found that overexpression of IRS-1 protected 32D cells from death induced by IL-3 deprivation. IL-4 was able to protect 32D cells from apoptosis in the presence or absence of IRS-1. However, the protection from apoptosis of cells cultured in IL-4 was greater in the presence of IRS-1 and it reached levels comparable to those of cells cultured in IL-3. The IRS-1-dependent prevention of apoptosis is linked to the activation of PI 3'-kinase since wortmannin and LY294002, two inhibitors of PI 3'-K, partially inhibited the prevention of apoptosis mediated by IL-4 in 32D-IRS-1 cells after IL-3 withdrawal but not in 32D cells lacking IRS-1 expression. In addition, we found that the IRS/PI 3'-K pathway is, at least in part, responsible for the prevention of apoptosis by IL-4 in normal splenic B cell cultures. In spite of the ability of murine IL-4 to partially protect 32D cells lacking IRS-1 from apoptosis, human IL-4 was not able to prevent cell death in 32D-IRS-1 cells transfected with the human IL-4 receptor mutated in the insulin-lL-4 receptor motif (14R-motif) at amino acid 497 (Y497F). This mutation has previously been shown to abrogate the tyrosine phosphorylation of IRS-1 by human IL-4. These results demonstrate that IL-4 protects 32D cells from apoptosis by two different pathways, one of them mediated by IRS-1. In addition, these results suggest that the 14R-motif of the IL-4R is linked to both pathways.

Animals↗

Percutaneous mitral valvuloplasty with the Inoue technique in a patient with heavily calcified interatrial septum.

A 75-year-old woman with severe rheumatic mitral stenosis was admitted for percutaneous mitral valvuloplasty. Two-dimensional echocardiography disclosed severe calcification of the posterolateral left atrial wall and interatrial septum. Percutaneous mitral valvuloplasty, using the inoue technique, was successfully performed after a transseptal puncture through the calcified interatrial septum, avoiding the need for surgical intervention.

Aged↗

The aorta. Aortic aneurysm, trauma, and dissection.

Because of the close relationship between the esophagus and the aorta, multiplane transesophageal echocardiography provides an excellent way to view the thoracic aorta. In this article, clinical features of aortic aneurysm, trauma, and aortic dissection are described, as is the potential use of transesophageal echocardiography in the assessment of these entities.

Aortic Dissection↗

Value of intracoronary ultrasound and Doppler in the differentiation of angiographically normal coronary arteries: a prospective study in patients with angina pectoris.

BACKGROUND: A substantial proportion of patients undergoing heart catheterization for suspected coronary artery disease have normal angiograms. Coronary morphology and blood flow velocity can be assessed very accurately with intracoronary ultrasound and Doppler. The purpose of this study was to use both methods to classify further patients with suspected coronary artery disease but with coronary angiograms adjudged normal at the time. METHODS AND RESULTS: In forty-four patients with suspected coronary artery disease and normal coronary angiograms, intracoronary ultrasound and intracoronary Doppler were performed in the left anterior descending and left main coronary arteries. Coronary flow reserve was obtained by calculating the ratio of the maximal coronary flow mean velocity after the intracoronary administration of 10 mg papaverine to the coronary flow mean velocity at rest. Of 44 patients, 16 (36%) (group I) were found to have normal coronary morphology by intracoronary ultrasound and normal (> 3.0) coronary flow reserve (5.3 +/- 1.8). In seven patients (16%) (group II) there were normal intracoronary ultrasonic findings but a reduced coronary flow reserve (2.1 +/- 0.4). Plaque formation was found in a total of 21 (48%) of the 44 patients; mean plaque sizes were 3.6 +/- 1.6 mm2 for those in group III (normal coronary flow reserve) and 5.0 +/- 2.3 mm2 for those in group IV (reduced coronary flow reserve). Vessel area in both of these groups (16.3 +/- 8.0 mm2 and 19.2 +/- 6.1 mm2) was significantly larger than that of group I (14.6 +/- 5.7 mm2, P < 0.01). Plaque calcification was found in 25% of those in group III and 44% of those in group IV. Thus, only 36% of the patients with normal angiograms were true normal, 48% exhibited early stage of coronary atherosclerosis, and the other 16% might be considered as syndrome X. CONCLUSION: Intracoronary ultrasound and Doppler can be used to differentiate further heart disease in patients with normal coronary angiograms. Only a minority were true normal. Early signs of atherosclerosis cannot be detected by coronary angiography. This may have important therapeutic and prognostic implications.

Adult↗

Improvement of coronary morphology and blood flow after stenting. Assessment by intravascular ultrasound and intracoronary Doppler.

Intravascular ultrasound (IVUS) and intracoronary Doppler (ICD) were performed in eight patients (54.3 +/- 6.5 years, 6 male) immediately after PTCA and after stenting. ICD was also performed before PTCA. After PTCA, IVUS has demonstrated intimal rupture in all patients. After stenting, IVUS revealed wall wrapping of the intimal flap with a free lumen in all patients. The lumen diameter was 2.42 +/- 0.55 mm after PTCA and was 2.74 +/- 0.49 mm after stenting (p < 0.001). The cross-sectional area increased from 4.70 +/- 1.99 mm2 post-PTCA to 6.40 +/- 2.15 mm2 post-stent (p < 0.005). Coronary flow velocity reserve, calculated by the ratio of mean flow velocity at rest and after intracoronary papaverine administration, increased from 2.05 +/- 1.01 to 2.99 +/- 1.14 after PTCA (p = 0.015); and increased to 4.51 +/- 1.33 after stenting (p < 0.001). The morphological data derived from IVUS correlated with the functional information obtained with ICD. In addition to its established role in bail out situations, stent implantation may be considered when a suboptimal morphological and functional result has been demonstrated.

Angioplasty, Balloon, Coronary↗

Upregulated expression of IL-4 receptors and increased levels of IL-4 in rheumatoid arthritis patients.

The level of IL-4R expression on peripheral lymphocyte subsets from rheumatoid arthritis (RA) patients and controls was studied by flow cytometric analysis of the binding of phycoerythrin-labelled IL-4 (PE-IL-4). In normal lymphocytes, IL-4R is mainly expressed on CD19+ cells, although it was also seen, at lower levels, on CD3+, CD4+ and CD8+ cells. In RA patients, a significantly increased spontaneous expression of IL-4R was observed, compared with controls, in the CD3+, CD4+ and CD19+ cell subsets. No significant differences in IL-4R expression were found between patients receiving steroids and those who were not, suggesting that steroids are not involved in upregulating IL-4R levels in vivo. Because IL-4 is a potent upregulator of IL-4R, we considered the possibility that incremented levels of circulating IL-4 in RA accounted for the high surface expression of IL-4R. By ELISA, we found abnormally high levels of immunoreactive IL-4 in 35.13% of patient serum samples, while it was undetectable in control sera. In addition, we examined IL-4 mRNA expression by polymerase chain reaction (PCR) in the PBMC of patients and controls. IL-4 PCR products were observed in four out of 10 patients studied but in none of the controls. No correlation was observed between the seric concentrations of IL-4 and IL-4R, indicating that activator factors other than IL-4 contribute to the upregulation of IL-4R expression in RA. Since the patients' sedimentation rate and CRP values did not correlate with the concentration of circulating IL-4, we conclude that this lymphokine does not contribute to the deleterious effect of the disease. Rather, due to its antiinflammatory properties, the overproduction of IL-4 in RA may be a compensatory mechanism neutralizing the harmful effect of activated macrophages.

Aged↗

Soluble, but not immobilized, anti-IgM antibody inhibits post-activation events leading to T-cell-dependent B-cell differentiation.

The potential for surface immunoglobulin-binding ligands to modify B-cell differentiation responses induced by activated T cells has been investigated. Activated T cells in human splenic mononuclear cells cultured on anti-CD3-coated plates induced B cells to produce large amounts of IgM and IgG. In this experimental system, cross-linking of B-cell antigen receptors by soluble, bivalent monoclonal or polyclonal anti-IgM antibodies completely inhibited IgM production, and greatly diminished IgG production, in a dose-dependent manner. Similar results were obtained using a F(ab')2 fragment of a goat anti-IgM antibody. Inhibition of B-cell differentiation by bivalent cross-linking reagents did not require the presence of antigen-presenting cells (APC), as comparable results were obtained in co-cultures of purified T and B cells. In contrast, enhanced immunoglobulin secretion was seen when surface IgM was cross-linked using anti-IgM antibody immobilized on the culture plate. Interestingly, activated T cells induced similar levels of expression on B cells of the activation antigens CD23, CD25 and CD71, and of class II molecules, irrespective of any treatment with soluble or immobilized anti-IgM antibody. This indicates that soluble anti-IgM specifically inhibits B-cell differentiation without altering initial events of T-cell-dependent B-cell activation.

Antibodies, Anti-Idiotypic↗

[Cardiac tamponade with the absence of a paradoxical pulse. The practical utility of echocardiography].

A patient with cardiac tamponade but without hypotension and pulsus paradoxus is reported. In this patient, echocardiography confirmed the diagnosis of cardiac tamponade, showing diastolic collapse of the right ventricle and also the presence of an atrial septal defect (ostium secundum) that explains the absence of pulsus paradoxus. The role of echocardiography in those rare clinical situations that in the presence of cardiac tamponade showed no pulsus paradoxus are discussed.

Cardiac Tamponade↗

Determinants of coronary compliance in patients with coronary artery disease: an intravascular ultrasound study.

OBJECTIVES: The aim of this study was to elucidate determinants of coronary compliance in patients with coronary artery disease. BACKGROUND: Intravascular ultrasound potentially enables in vivo evaluation of coronary artery compliance. METHODS: Twenty-seven patients (mean age [+/- SD] 57 +/- 11 years, three women) undergoing coronary angioplasty were studied with intravascular ultrasound imaging. A mechanical intravascular ultrasound system (4.8F, 20 MHz) was used. A total of 58 different coronary segments (proximal to the target angiographic lesion) were studied. Of these, 35 were located in the left anterior descending, 9 in the left main, 8 in the left circumflex and 6 in the right coronary arteries. During intravascular ultrasound imaging, 22 segments (38%) appeared normal, but 36 (62%) had plaque (24 fibrotic, 3 lipidic and 9 calcified). Systolic-diastolic changes in area (delta A) and pressure (delta P) with respect to vessel area (A) were used to study normalized compliance (Normalized compliance = [delta A/A]/delta P [mm Hg-1 x 10(3)]). RESULTS: Lumen area and plaque area were 12.6 +/- 5.7 and 3 +/- 3 min2, respectively. Plaque was concentric (more than two quadrants) at 10 sites, but the remaining 26 plaques were eccentric. Compliance was inversely related to age (r = -0.34, p < 0.05) but was not related to other clinical variables. Compliance was greater in the left main coronary artery (3.9 +/- 2.1 vs. 1.8 +/- 1.2 mm Hg-1, p < 0.05) and in coronary segments with normal findings on ultrasound imaging (2.9 +/- 1.9 vs. 1.6 +/- 1.1 mm Hg-1, p < 0.01). Moreover, at diseased coronary segments compliance was lower in calcified plaques than in other types of plaques (1.2 +/- 0.7 vs. 2.3 +/- 1.6 mm Hg-1, p < 0.01) but was similar in concentric and eccentric plaques (1.6 +/- 1.5 vs. 1.6 +/- 0.9 mm Hg-1). Plaque area (r = -0.38, p < 0.01) was inversely correlated with compliance. On multivariate analysis, only age and plaque area were independently related to compliance. CONCLUSIONS: Intravascular ultrasound may be used to evaluate compliance in patients with coronary artery disease. Compliance is reduced with increasing age and is mainly determined by the arterial site and by the presence, size and characteristics of plaque on intravascular ultrasound imaging.

Age Factors↗

Assessment of spontaneous coronary artery dissection by intravascular ultrasound in a patient with unstable angina.

We describe a case of spontaneous coronary artery dissection that gave rise to post infarction unstable angina. An ambiguous angiographic appearance was shown by intracoronary ultrasound to arise from an extensive coronary dissection. The dissection membrane separating true and false lumina and features to suggest sluggish flow and early thrombosis in the false lumen were observed. No increase in lumen calibre was evident on ultrasound after PTCA (probably a consequence of the relatively large ultrasound catheter blank), but coronary flow reserve measured with intracoronary Doppler did improve and the patient remained stable and free of angina following the procedure.

Angina, Unstable↗

Angiographic changes (Dotter effect) produced by intravascular ultrasound imaging before coronary angioplasty.

Intravascular ultrasound (IVUS) imaging of the coronary arteries has recently been introduced for the study of coronary lesions, but the angiographic effects produced by an IVUS examination before coronary angioplasty are unknown. Accordingly, the feasibility of and the potential angiographic changes caused by IVUS study (4.8F catheter) of severe coronary lesions was prospectively studied. Thirty consecutive coronary lesions were analyzed before intervention (29 patients, mean age 61 +/- 9 years, 5 women and 24 men). Before and after IVUS examination, intracoronary nitroglycerin 0.2 mg, was administered and two orthogonal angiographic views obtained. In 17 (57%) lesions the transducer of the IVUS catheter (radiopaque) could be gently advanced for precise location at the lesion site, and in every case the ultrasonic images revealed that the catheter was wedged into the plaque. In the remaining 13 lesions only the catheter tip but not the transducer could be located at the lesion site. Baseline minimal luminal diameter was similar in the crossed lesions and in lesions that prevented complete advancement of the IVUS catheter (0.86 +/- 0.2 vs 0.82 +/- 0.2 mm, difference not significant). Lesion characteristics could not predict the feasibility of the IVUS study. No complications resulted from the IVUS study. Quantitative angiography (automatic edge-detection system) revealed a significant increment in minimal luminal diameter (0.84 +/- 0.2 vs 1.16 +/- 0.3 mm, p < 0.001) and minimal luminal cross-sectional area (0.67 +/- 0.4 vs 1.09 +/- 0.5 mm2, p < 0.01) after passage of the IVUS catheter.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Intravascular ultrasound imaging of angiographically normal coronary segments in patients with coronary artery disease.

Intravascular ultrasound imaging (IVUS) constitutes a new diagnostic technique that provides unique information concerning arterial wall structure and luminal dimensions. To assess the anatomic features of angiographically normal coronary arteries in patients with coronary artery disease, 25 patients (aged 61 +/- 9 years) underwent an IVUS examination before coronary angioplasty. A mechanical (20 MHz) IVUS system was used. Atherosclerotic plaques were identified by IVUS as well-defined structures of variable echodensity protruding into the coronary lumen or disrupting normal coronary wall architecture. Five (20%) patients had minor angiographic irregularities proximal to the target lesion, and all 5 had plaque on IVUS. In the remaining 20 patients the coronary segments proximal to the target lesion were angiographically normal. Of these, IVUS demonstrated the presence of plaque in 16 (80%) patients at 19 different angiographic sites (3 lipidic, 13 fibrotic, 3 calcified). Fifteen plaques had a semilunar appearance and did not disrupt luminal contour, but four clearly protruded into the coronary lumen. Six plaques were located in the left main artery, 4 in the left anterior descending artery, 4 in the left circumflex artery, 4 in the right coronary artery, and 1 in a vein graft. On quantitative angiography, luminal diameter, at sites angiographically normal but with plaque on IVUS, was 3.6 +/- 1 mm. At these sites, both minimal luminal diameter (3.5 +/- 1 mm) and maximal luminal diameter (4.3 +/- 1 mm) on IVUS correlated (r = 0.59 and r = 0.61, respectively) with angiographic measurements (p < 0.05). No complications resulted from the IVUS study.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Angiography↗

Spontaneous plaque rupture visualized by intravascular ultrasound.

An intravascular ultrasound examination was performed in order to evaluate an angiographically complicated lesion. Intravascular ultrasound was able to demonstrate spontaneous plaque rupture in a patient with recent acute subendocardial infarction. The inconclusive angiographic appearance was clarified by the intravascular examination and led us to conclude that the myocardial infarction was due to plaque rupture with subsequent thrombotic occlusion, which had spontaneously resolved by the time of the study.

Aged↗

Vessel wall changes in the proximal non-treated segment after PTCA. An in vivo intracoronary ultrasound study.

Intimal disruption is known to induce prolonged intimal functional disturbance and is thought to be one of the mechanisms contributing to restenosis after PTCA. Although such damage can be induced by minimal trauma, the inevitable far greater disruption caused by passage of the PTCA apparatus through the stenosis does not appear to induce significant angiographically documented intimal proliferation. Pathological studies, however, have suggested that such a process might occur. Intravascular ultrasound allows in vivo study of vessel wall shape and constitution and is a far more sensitive detector of coronary atheroma than angiography. In this study we sought to determine the frequency of such functional disturbances and to assess their significance with respect to restenosis. The study group comprised 18 patients who underwent IVUS examination immediately after PTCA and at 6-months follow-up. They were analysed for luminal dimensions and vessel wall changes at the site of PTCA and at the level of the proximal non-treated segment. Seven patients (38%) had restenosed at follow-up IVUS examination; two patients had angiographically demonstrated luminal narrowing proximal to the PTCA site whereas seven had new intimal thickening in the proximal non-treated segment demonstrated by IVUS. Six patients had no intimal changes in either PTCA treated or untreated segments. Proximal intimal thickening was seen more frequently in those in whom increased intimal thickening at the PTCA site was noted. A trend (P < 0.1) was found towards an increased rate of new proximal vessel disease in those patients who had angiographically restenosed. IVUS demonstrates new intimal thickening in proximal non-treated segments in a considerable number of or patients undergoing PTCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Acute coronary closure complicating intravascular ultrasound examination.

A patient with an excellent angiographic result after directional atherectomy suffered an acute coronary closure during an intravascular ultrasound study performed after the intervention. Intravascular ultrasound revealed a large medial dissection which could be successfully managed only with intracoronary stenting. The pathogenesis and implications of this rare major complication are discussed.

Aged↗