Biomedical subjects

R Laguens

Publications and source records attributed to R Laguens.

At least 19 recordsLinked to original sources

PubMed2006

Plasmid-mediated VEGF gene transfer induces cardiomyogenesis and reduces myocardial infarct size in sheep.

We have recently reported that in pigs with chronic myocardial ischemia heart transfection with a plasmid encoding the 165 isoform of human vascular endothelial growth factor (pVEGF165) induces an increase in the mitotic index of adult cardiomyocytes and cardiomyocyte hyperplasia. On these bases we hypothesized that VEGF gene transfer could also modify the evolution of experimental myocardial infarct. In adult sheep pVEGF165 (3.8 mg, n=7) or empty plasmid (n=7) was injected intramyocardially 1 h after coronary artery ligation. After 15 days infarct area was 11.3+/-1.3% of the left ventricle in the VEGF group and 18.2+/-2.1% in the empty plasmid group (P<0.02). The mechanisms involved in infarct size reduction (assessed in additional sheep at 7 and 10 days after infarction) included an increase in early angiogenesis and arteriogenesis, a decrease in peri-infarct fibrosis, a decrease in myofibroblast proliferation, enhanced cardiomyoblast proliferation and mitosis of adult cardiomyocytes with occasional cytokinesis. Resting myocardial perfusion (99mTc-sestamibi SPECT) was higher in VEGF-treated group than in empty plasmid group 15 days after myocardial infarction. We conclude that plasmid-mediated VEGF gene transfer reduces myocardial infarct size by a combination of effects including neovascular proliferation, modification of fibrosis and cardiomyocyte regeneration.

Animals↗

PubMed2002

Trypanosoma cruzi: identification of a galactose-binding protein that binds to cell surface of human erythrocytes and is involved in cell invasion by the parasite.

Trypanosoma cruzi must invade mammalian host cells to replicate and complete its life cycle. Almost all nucleated mammalian cells can be invaded by the parasite following a receptor-ligand recognition as an early prerequisite. In this work, we describe a 67-kDa lectin-like glycoprotein that binds to desialylated human erythrocyte membranes in a galactose-dependent way. This protein is present on the parasite surface in both infective and non-infective stages of T. cruzi. More interestingly, we demonstrate by lectin-immuno-histochemistry assays that the 67kDa protein is involved in the recognition of host-cell receptors in mouse cardiac tissue and human cardiac aortic endothelium and mammary artery tissue. Moreover, antibodies against the 67kDa glycoprotein inhibit in vitro host-cell invasion by 63%. These data suggest that the 67kDa glycoprotein in vivo is needed for host-cell invasion by T. cruzi.

Animals↗

PubMed2002

Entrance in mitosis of adult cardiomyocytes in ischemic pig hearts after plasmid-mediated rhVEGF165 gene transfer.

Replacement of the cell loss occurring after acute myocardial infarction has been proposed as a potential treatment to prevent heart remodeling and failure. On account that cardiomyocytes express VEGF receptors and that VEGF triggers mitogen-activated protein kinases, we investigated if VEGF gene transfer may induce cardiomyocyte replication. In a pig model of chronic myocardial ischemia achieved by Ameroid occlusion of the left circumflex coronary artery, we observed that direct intramyocardial injection of a plasmid encoding human VEGF(165) induced a several-fold increase in cardiomyocyte mitotic index and in the number of cardiomyocyte nuclei per unit volume as compared with pigs receiving plasmid devoid of gene. Despite images of conventional cytokinesis were not observed, the fact that caryokinesis is an obligatory step for cell division suggests that our finding may contribute to the issue of heart regeneration and may potentially widen the therapeutic spectrum of VEGF gene transfer.

Animals↗

PubMed2001

Radial artery graft vasospasm.

We report an unusual case of vasospasm of a grafted radial artery complicated with ventricular fibrillation during the postoperative course of coronary artery bypass graft surgery. To our knowledge this is the first documented case of a radial artery graft spasm leading to a severe arrhythmia. The arrhythmia resolved spontaneously. Radial artery graft spasm was demonstrated by angiography and was successfully resolved by intravenous nitroglycerin administration.

Coronary Angiography↗

PubMed2000

Early diagnosis of recurrence of Trypanosoma cruzi infection by polymerase chain reaction after heart transplantation of a chronic Chagas' heart disease patient.

Heart transplantation is contraindicated as an effective treatment for end-stage Chagas' heart disease because of post-operative recurrence of Trypanosoma cruzi infection and reactivation of disease after immunosupression. In a follow-up study of a heart transplanted patient with Chagas' disease, we prospectively evaluated the usefulness of the polymerase chain reaction (PCR) for early diagnosis of reactivation. We monitored post-operative recurrence of Trypanosoma cruzi infection with microscopic observation of the parasite in peripheral blood (Strout's method), endomyocardial biopsies (EMBs), skin lesions, and 2 PCR assays, based on the amplification of specific T cruzi kinetoplastid and nuclear DNA sequences. During follow-up, parasite DNA was amplified in blood samples and EMB sections 41 days before we observed patent parasitemia and cutaneous manifestations of reactivation, proving that PCR is much more sensitive than direct microscopic observation for early diagnosis of disease reactivation in heart-transplanted Chagas' disease patients.

Animals↗

PubMed1997

Densitometric quantitative analysis of intracoronary ultrasound images: anatomopathological correlation.

To establish if the videodensitometric analysis (VDA) of the intracoronary ultrasound images (IVUS) can predict the qualitative and quantitative composition of the atherosclerotic coronary plaques, thirty-one patients who had undergone anatomopathological study of directional coronary atherectomy (DCA) samples and pre- and post-intervention IVUS image were analyzed. The video IVUS images were digitized in a 512 x 512 matrix and analyzed for densitometric differences with an Automatic Image Analysis System (AIAS) (Vidas 2000, Zeiss Kontron). The components of the plaque were arbitrarily divided into three densitometric categories using a 256 gray scale: high density (HD) 121-255, medium (MD) 81-120 and low (LD) 30-80. The relative percentage of each component was automatically recorded. The DCA samples were microscopically examined and put into the AIAS. The components were divided into: collagenous tissue (CT); lipid-necrotic debris (LND); proliferative tissue (PT). The area of each component was expressed as a percentage of the total. Linear correlation analysis was applied. Comparison between the IVUS and the histological composition of the plaque showed that: HD corresponded to CT; MD to PT; LD to LND. The correlation between the percentage distribution of the densitometric categories and the anatomopathological components showed a correlation coefficient r = 0.91 between HD and CT; r = 0.87 between MD and PT; r = 0.88 between LD and LND. The VDA of the IVUS can distinguish three basic components of the atherosclerotic plaque: fibrous, lipid-necrotic and proliferative tissue, allowing absolute and relative quantitative analysis. This capability may be of interest for device selection and histopathological correlation.

Adult↗

PubMed1997

Immunization with recombinant Trypanosoma cruzi ribosomal P2beta protein induces changes in the electrocardiogram of immunized mice.

Molecular expression cloning techniques revealed that patients with severe chronic Chagas heart disease showed a strong humoral response against the cloned C-terminal portion of the Trypanosoma cruzi ribosomal P2beta protein, previously named JL5. The main linear epitope of this polypeptide was mapped to the 13 C-terminal amino acid sequence EEEDDDMGFGLFD (named R13), which is almost identical to the mammalian ribosomal P consensus sequence EESDDDMGFGLFD (named H13). Enzyme-linked immunosorbent assay measurements demonstrated that sera from patients with chronic Chagas heart disease presented a very specific anti-P humoral response with high anti-R13, but low H13 antibody levels. We attempted to develop an animal model that would reproduce, at least partially, two features of the human infection: (1) the serological pattern of the anti-P response, and (2) specific cardiac symptoms. To this effect, mice were immunized with T. cruzi P2beta recombinant protein. Immunization reproduced the typical anti-P antibody profile defined for chronic infections, but did not induce cardiac inflammatory lesions. However, it altered significantly the electrocardiograms of immunized mice. It is suggested that this assay represents a functional test for assessing the biological activity of antibodies against T. cruzi ribosomal P protein on cardiac muscle.

Animals↗

PubMed1990

Demonstration and characterization of HLA-DR positive cells in the stroma of human endometrium.

The proportion of stromal cells expressing DR antigens of the HLA system or reacting with an anti-macrophage antibody was studied by immunohistochemical methods in human proliferative, secretory and post-menopausal endometria. DR+ cells showed a rounded morphology with short expansions and represented 13-25% of the stromal cells in the proliferative and 16-43% in the secretory endometrium. The cells reacting with the anti-macrophage antibody were similar to DR+ cells, but their number was between 1/2 and 1/10 of DR+ cells. In the post-menopausal endometria no DR+ cells or elements reacting with anti-macrophage antibody were observed. These results suggest that a significant proportion of endometrial stromal cells expressing type II histocompatibility antigens do not belong to the monocyte-phagocyte system and that their number is under hormonal regulation.

Antibodies, Monoclonal↗

PubMed1975

Ultrastructural and immunohistochemical study of the human kidney in Argentine haemorrhagic fever.

In six lethal cases of Argentine Haemorrhagic Fever (AHF) a disease caused by Junin virus, kidney samples were studied by means of immunofluorescent and electron microscopic techniques.--The ultrastructural studies showed that the distal and collecting tubes presented a large number of virus like intracytoplasmic particles. Those particles were present in the lumen of the endoplasmic reticulum cisternae and showed two distinct morphological aspects. Some of them were of high electron density and contained a few granules. The others were larger in size, electron lucid, and contained a variable number of ribosome like granules. Both types of particles originated from the endoplasmic reticulum wall by a process of budding. The presence of these particles was coincident with a severe cell damage which lead to necrosis and desquamation; and with large quantities of Junin virus antigen as demonstrated by immunofluorescence.--On the basis of these observations it is assumed that in AHF the cell damage is due to direct viral replication within the affected cells.

Antigens, Viral↗

PubMed1974