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1.
Gene Ther ; 22(6): 449-57, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25789461

ABSTRACT

Mesenchymal stromal cells (MSCs) are cardioprotective in acute myocardial infarction (AMI). Besides, we have shown that intramyocardial injection of plasmid-VEGF(165) (pVEGF) in ovine AMI reduces infarct size and improves left ventricular (LV) function. We thus hypothesized that MSCs overexpressing VEGF(165) (MSCs-pVEGF) would afford greater cardioprotection than non-modified MSCs or pVEGF alone. Sheep underwent an anteroapical AMI and, 1 week later, received intramyocardial MSCs-pVEGF in the infarct border. One month post treatment, infarct size (magnetic resonance) decreased by 31% vs pre-treatment. Of note, myocardial salvage occurred predominantly at the subendocardium, the myocardial region displaying the largest contribution to systolic performance. Consistently, LV ejection fraction recovered to almost its baseline value because of marked decrease in end-systolic volume. None of these effects were observed in sheep receiving non-transfected MSCs or pVEGF. Although myocardial retention of MSCs decreased steeply over time, the treatment induced significant capillary and arteriolar proliferation, which reduced subendocardial fibrosis. We conclude that in ovine AMI, allogeneic VEGF-overexpressing MSCs induce subendocardial myocardium salvage through microvascular proliferation, reducing infarct size and improving LV function more than non-transfected MSCs or the naked plasmid. Importantly, the use of a plasmid rather than a virus allows for repeated treatments, likely needed in ischemic heart disease.


Subject(s)
Mesenchymal Stem Cells/metabolism , Myocardial Infarction/metabolism , Vascular Endothelial Growth Factor A/metabolism , Animals , Cell Line , Humans , Magnetic Resonance Spectroscopy/methods , Male , Myocardial Infarction/physiopathology , Myocardium/pathology , Plasmids/metabolism , Sheep , Ventricular Function, Left
2.
J Thromb Haemost ; 12(5): 761-72, 2014 May.
Article in English | MEDLINE | ID: mdl-24606315

ABSTRACT

BACKGROUND: Familial platelet disorder with a predisposition to acute myelogenous leukemia (FPD/AML) is an inherited platelet disorder caused by a germline RUNX1 mutation and characterized by thrombocytopenia, a platelet function defect, and leukemia predisposition. The mechanisms underlying FPD/AML platelet dysfunction remain incompletely clarified. We aimed to determine the contribution of platelet structural abnormalities and defective activation pathways to the platelet phenotype. In addition, by using a candidate gene approach, we sought to identify potential RUNX1-regulated genes involved in these defects. METHODS: Lumiaggregometry, α-granule and dense granule content and release, platelet ultrastructure, αIIb ß3 integrin activation and outside-in signaling were assessed in members of one FPD/AML pedigree. Expression levels of candidate genes were measured and luciferase reporter assays and chromatin immunoprecipitation were performed to study NF-E2 regulation by RUNX1. RESULTS: A severe decrease in platelet aggregation, defective αIIb ß3 integrin activation and combined αδ storage pool deficiency were found. However, whereas the number of dense granules was markedly reduced, α-granule content was heterogeneous. A trend towards decreased platelet spreading was found, and ß3 integrin phosphorylation was impaired, reflecting altered outside-in signaling. A decrease in the level of transcription factor p45 NF-E2 was shown in platelet RNA and lysates, and other deregulated genes included RAB27B and MYL9. RUNX1 was shown to bind to the NF-E2 promoter in primary megakaryocytes, and wild-type RUNX1, but not FPD/AML mutants, was able to activate NF-E2 expression. CONCLUSIONS: The FPD/AML platelet function defect represents a complex trait, and RUNX1 orchestrates platelet function by regulating diverse aspects of this process. This study highlights the RUNX1 target NF-E2 as part of the molecular network by which RUNX1 regulates platelet biogenesis and function.


Subject(s)
Blood Platelet Disorders/blood , Blood Platelet Disorders/complications , Blood Platelets/cytology , Core Binding Factor Alpha 2 Subunit/metabolism , Leukemia, Myeloid, Acute/blood , Leukemia, Myeloid, Acute/complications , Adenosine Triphosphate/metabolism , Adult , Family Health , Female , Gene Expression Profiling , Humans , Integrin beta3/metabolism , Male , NF-E2 Transcription Factor, p45 Subunit/metabolism , Pedigree , Phenotype , Phosphorylation , Platelet Aggregation , Platelet Function Tests , Platelet Membrane Glycoprotein IIb/metabolism , Signal Transduction , Tyrosine/metabolism , Young Adult
3.
Platelets ; 22(1): 28-38, 2011.
Article in English | MEDLINE | ID: mdl-21143024

ABSTRACT

The aim of this study was to evaluate cell maturation and the platelet production capacity of the megakaryoblastic DAMI cell line, to characterize platelet-like particles produced and to investigate the mechanisms involved in their production. DAMI cell maturation was induced by phorbol myristate acetate (PMA) and thrombopoietin (TPO). Expression levels of GATA-1, Fli-1 and NF-E2 were evaluated using real-time PCR and western blot. Platelet-like particles were characterized by the presence of GPIb and GPIIb by flow cytometry, while the soluble fragment of GPIb, glycocalicin, was detected by enzyme immunoassay. Dense and alpha granules were evaluated by mepacrine staining and thrombospondin-1 detection, respectively, and by electron microscopy. Functional capacity of platelet-like particles was studied by measuring P-selectin membrane after thrombin stimulation by flow cytometry and actin polymerization using phalloidin-FITC by immunofluorescence. We found that stimulation of DAMI cells with high concentration of PMA and TPO induced the expression of transcription factors GATA-1 and Fli-1 followed by an increase in the isoform a of NF-E2. Mature DAMI cells give rise to extensions resembling proplatelets and later, produce platelet-like particles expressing GPIIb and GPIb on their surface and containing dense and alpha granules, which were confirmed by electron microscopy. Platelet functionality was demonstrated by the increase in P-selectin membrane expression after thrombin stimulation and by their ability to spread on fibrinogen matrices. DAMI cell line induced to differentiate into mature megakaryocytes is able to produce functional platelets providing a suitable model to study the mechanisms involved in platelet generation.


Subject(s)
Blood Platelets/cytology , Megakaryocytes/cytology , Models, Biological , Actins/analysis , Blood Platelets/drug effects , Cell Differentiation/drug effects , Cell Line , Cytoplasmic Granules/ultrastructure , Flow Cytometry , GATA1 Transcription Factor/genetics , GATA1 Transcription Factor/metabolism , Gene Expression/drug effects , Humans , Megakaryocytes/metabolism , Microfilament Proteins/genetics , Microfilament Proteins/metabolism , NF-E2 Transcription Factor, p45 Subunit/genetics , NF-E2 Transcription Factor, p45 Subunit/metabolism , P-Selectin/genetics , P-Selectin/metabolism , Platelet Count , Platelet Membrane Glycoproteins/genetics , Platelet Membrane Glycoproteins/metabolism , Polymerization/drug effects , Receptors, Cytoplasmic and Nuclear/genetics , Receptors, Cytoplasmic and Nuclear/metabolism , Tetradecanoylphorbol Acetate/pharmacology , Thrombin/pharmacology , Thrombopoietin/pharmacology , Thrombospondins/genetics , Thrombospondins/metabolism , Trans-Activators
4.
Gene Ther ; 16(6): 716-23, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19340019

ABSTRACT

Vascular endothelial growth factor (VEGF) gene transfer-mediated angiogenesis has been proposed for peripheral artery disease. However, protocols using single administration have shown little benefit. Given that the transient nature of VEGF gene expression provokes instability of neovasculature, we hypothesized that repeated administration would provide efficient tissue protection. We thus compared single vs repeated transfection in a rabbit model of hindlimb ischemia by injecting a plasmid encoding human VEGF165 (pVEGF165) at 7 (GI, n=10) or 7 and 21 (GII, n=10) days after surgery. Placebo animals (GIII, n=10) received empty plasmid. Fifty days after surgery, single and repeated administration similarly increased saphenous peak flow velocity and quantity of angiographically visible collaterals. However, microvasculature increased only with repeated transfection: capillary density was 49.4+/-15.4 capillaries per 100 myocytes in GI, 84.6+/-14.7 in GII (P<0.01 vs GI and GIII) and 49.3+/-13.6 in GIII, and arteriolar density was 1.9+/-0.6 arterioles per mm2 in GI, 3.0+/-0.9 in GII (P<0.01 vs GI and GIII) and 1.5+/-0.6 in GIII. Muscle lesions were reduced only within repeated transfection. With single administration, gene expression peaked at 7 days and declined rapidly, but with repeated administration, it remained positive at 50 days. At 90 days of repeated transfection (additional animals), gene expression decreased significantly, but neovessel densities did not. Thus, repeated, but not single, VEGF gene transfection resulted in increased microvasculature, which, in turn, afforded effective protection against ischemic muscle damage.


Subject(s)
Genetic Therapy/methods , Ischemia/therapy , Muscle, Skeletal/blood supply , Neovascularization, Physiologic , Peripheral Vascular Diseases/therapy , Vascular Endothelial Growth Factor A/genetics , Animals , Disease Models, Animal , Gene Expression/physiology , Gene Transfer Techniques , Hindlimb/blood supply , Humans , Injections, Intramuscular , Ischemia/etiology , Microvessels/diagnostic imaging , Peripheral Vascular Diseases/complications , Plasmids , Polymerase Chain Reaction , RNA, Messenger/analysis , Rabbits , Radiography , Regional Blood Flow/physiology , Time Factors , Transfection , Transgenes , Vascular Endothelial Growth Factor A/analysis , Vascular Endothelial Growth Factor A/metabolism
5.
Transplant Proc ; 39(2): 355-7, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17362729

ABSTRACT

BACKGROUND: Low-potassium-dextran preservation solution Perfadex (PER) may provide better outcome of transplanted lungs than high-potassium Euro-Collins (EC) solution. However, there are no comparative studies of the recipient inflammatory response to the graft. PURPOSE: The purpose of this study was to compare EC versus PER as preservation solutions with respect to the functional performance and inflammatory response in single-lung transplantation from heart-beating donors in pigs. MATERIALS AND METHODS: The donor left lung flushed with the corresponding cold preservation solution was stored at 3 degrees C for 3 hours. We assessed hemodynamic values and pulmonary function in the recipient over a 2-hour reperfusion period calculated as percent of basal values, and expressed as mean of the reperfusion period. Interleukin-8 (IL-8) concentration in the donor was estimated in bronchoalveolar lavage fluid 2 hours after recipient reperfusion. Biopsies of the donor right lung and the transplanted lung were obtained to measure myeloperoxidase (MPO) activity. IL-8 and MPO values were expressed as percent of the donor value. We evaluated the wet/dry pulmonary weight ratio (W/D), polymorphonuclear neutrophil count (PMN), and a score of histological damage in the transplanted graft. RESULTS: Pulmonary function evaluated by % static: 66.6 +/- 6.8 (EC), 82.3 +/- 10.2 (PER), and dynamic: 74.0 +/- 7.3 (EC), 89.3 +/- 7.7 (PER) compliances, as well as % IL-8: 562.5 +/- 168.6 (EC), 232.3 +/- 148.7 (PER), % MPO: 485.9 +/- 194.9 (EC), 140.8 +/- 21.1 (PER), W/D: 9.9 +/- 3.1 (EC), 6.8 +/- 1.4 (PER), PMN 13.5 +/- 6.8 (EC), 5.5 +/- 3.3 (PER) and the histological damage score: 3.0 +/- 1.5 (EC), 0.7 +/- 0.4 (PER) showed significant differences between the EC and the PER (P < .01). CONCLUSIONS: PER affords good lung preservation with early graft function and modest evidences of inflammation, lung injury, and edema compared with the EC perfused lung.


Subject(s)
Graft Survival/physiology , Lung Transplantation/physiology , Organ Preservation Solutions , Animals , Citrates , Hypertonic Solutions , Lung Compliance , Models, Animal , Swine , Tissue Donors/statistics & numerical data , Vascular Resistance
6.
Gene Ther ; 13(15): 1133-42, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16572192

ABSTRACT

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.


Subject(s)
Genetic Therapy/methods , Myocardial Infarction/therapy , Myocardium/metabolism , Plasmids/administration & dosage , Vascular Endothelial Growth Factor A/genetics , Animals , Fibrosis , Injections , Male , Mitosis , Models, Animal , Myocardial Infarction/metabolism , Myocardial Infarction/pathology , Myocardium/pathology , Myocytes, Cardiac/pathology , Neovascularization, Physiologic , Regeneration , Sheep , Tomography, Emission-Computed, Single-Photon , Transfection/methods
7.
Colorectal Dis ; 7(5): 492-5, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16108887

ABSTRACT

OBJECTIVE: The aim of the present work was to evaluate the presence of human papillomavirus genotypes in malignant and normal mucosa of the colon and rectum in order to determine if a relationship exists between HPV infection and colon neoplasms. MATERIALS AND METHODS: Thirty normal colon tissues and 54 sporadic adenocarcinomas were screened for HPV positivity using nested-PCR. Detection of viral types 6, 11, 16, 18, 33, 34 and 51 was performed by the LIS-SSCP (Low Ionic Strength-Single Strand Conformational Polymorphism) procedure. RESULTS: Significant differences in high risk HPV infection were found between normal samples and adenocarcinomas (P < 0.001). Among the cases, an inverse association between HPV infection and Dukes staging was also found (P = 0.020). Finally, there was no significant association between HPV and some classical clinicopathological features, although a gradient of infection form rectum to cecum was evident. CONCLUSION: The present study demonstrates that HPV may infect the glandular mucosa of the colon and suggests a possible association between HPV and colorectal cancer.


Subject(s)
Adenocarcinoma/virology , Colonic Neoplasms/virology , Papillomaviridae/isolation & purification , Papillomavirus Infections/diagnosis , Rectal Neoplasms/virology , Adenocarcinoma/genetics , Aged , Aged, 80 and over , Chi-Square Distribution , Colonic Neoplasms/genetics , DNA, Viral/analysis , Female , Genotype , Humans , Male , Middle Aged , Papillomaviridae/genetics , Papillomavirus Infections/genetics , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational , Rectal Neoplasms/genetics
8.
Acta Gastroenterol Latinoam ; 33(4): 193-8, 2003.
Article in Spanish | MEDLINE | ID: mdl-14708471

ABSTRACT

BACKGROUND: Helicobacter pylori infection is presumed to be the major causal agent of chronic active gastritis in humans. The persistent infection with this pathogen would be an important factor in the pathogenesis of peptic ulcer and also gastric cancer. METHODS: We investigated relationship between H. pylori characteristics in 42 patients with normal mucosa or gastritis with minor changes and 40 patients with mild and severe gastritis. Detection and typing of vacA and cagA genes were performed using a polymerase chain reaction method. RESULTS: The analysis of vacA prevalence and the type (S1 or S2) showed non-significant differences between the two groups studied (p > 0.05). However, cagA analysis showed highly significant differences between the groups classified as normal tissue-weak gastritis and mild-severe gastritis (p < 0.0001; OR = 8.4; CI = 3.1-22.8). CONCLUSIONS: cagA status is associated to the grade of gastritis, finding higher frequencies of H. pylori cagA+ in the moderate-severe gastritis group. These highly significant differences could make cagA status a genetic marker for disease progress.


Subject(s)
Antigens, Bacterial/genetics , Bacterial Proteins/genetics , Gastritis/microbiology , Helicobacter Infections/microbiology , Helicobacter pylori/genetics , Polymerase Chain Reaction , Adolescent , Adult , Aged , Antigens, Bacterial/analysis , Bacterial Proteins/analysis , Bacterial Proteins/isolation & purification , Dyspepsia/microbiology , Dyspepsia/pathology , Female , Gastritis/pathology , Genetic Markers , Genotype , Humans , Intestinal Mucosa/microbiology , Male , Middle Aged , Retrospective Studies
9.
Acta gastroenterol. latinoam ; 33(4): 193-8, 2003.
Article in Spanish | BINACIS | ID: bin-38810

ABSTRACT

BACKGROUND: Helicobacter pylori infection is presumed to be the major causal agent of chronic active gastritis in humans. The persistent infection with this pathogen would be an important factor in the pathogenesis of peptic ulcer and also gastric cancer. METHODS: We investigated relationship between H. pylori characteristics in 42 patients with normal mucosa or gastritis with minor changes and 40 patients with mild and severe gastritis. Detection and typing of vacA and cagA genes were performed using a polymerase chain reaction method. RESULTS: The analysis of vacA prevalence and the type (S1 or S2) showed non-significant differences between the two groups studied (p > 0.05). However, cagA analysis showed highly significant differences between the groups classified as normal tissue-weak gastritis and mild-severe gastritis (p < 0.0001; OR = 8.4; CI = 3.1-22.8). CONCLUSIONS: cagA status is associated to the grade of gastritis, finding higher frequencies of H. pylori cagA+ in the moderate-severe gastritis group. These highly significant differences could make cagA status a genetic marker for disease progress.

10.
Acta gastroenterol. latinoam ; 33(4): 193-198, 2003. tab
Article in Spanish | BINACIS | ID: bin-4799

ABSTRACT

BACKGROUND: Helicobacter pylori infection is presumed to be the major causal agent of chronic active gastritis in humans. The persistent infection with this pathogen would be an important factor in the pathogenesis of peptic ulcer and also gastric cancer. METHODS: We investigated relationship between H. pylori characteristics in 42 patients with normal mucosa or gastritis with minor changes and 40 patients with mild and severe gastritis. Detection and typing of vacA and cagA genes were performed using a polymerase chain reaction method. RESULTS: The analysis of vacA prevalence and the type (S1 or S2) showed non-significant differences between the two groups studied (p > 0.05). However, cagA analysis showed highly significant differences between the groups classified as normal tissue-weak gastritis and mild-severe gastritis (p < 0.0001; OR = 8.4; CI = 3.1-22.8). CONCLUSIONS: cagA status is associated to the grade of gastritis, finding higher frequencies of H. pylori cagA+ in the moderate-severe gastritis group. These highly significant differences could make cagA status a genetic marker for disease progress.(AU)


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Polymerase Chain Reaction , Helicobacter Infections/microbiology , Helicobacter pylori/genetics , Gastritis/microbiology , Antigens, Bacterial/genetics , Helicobacter pylori/classification , Helicobacter pylori/pathogenicity , Bacterial Typing Techniques/methods , DNA, Bacterial/analysis , Genetic Markers , Virulence , Gastritis/pathology , Dyspepsia/microbiology , Dyspepsia/pathology , Genotype , Retrospective Studies , Antigens, Bacterial/analysis , Gastric Mucosa/microbiology , Nucleic Acid Amplification Techniques , Bacterial Proteins/genetics , Bacterial Proteins/isolation & purification
11.
Acta gastroenterol. latinoam ; 33(4): 193-198, 2003. tab
Article in Spanish | LILACS | ID: lil-359983

ABSTRACT

BACKGROUND: Helicobacter pylori infection is presumed to be the major causal agent of chronic active gastritis in humans. The persistent infection with this pathogen would be an important factor in the pathogenesis of peptic ulcer and also gastric cancer. METHODS: We investigated relationship between H. pylori characteristics in 42 patients with normal mucosa or gastritis with minor changes and 40 patients with mild and severe gastritis. Detection and typing of vacA and cagA genes were performed using a polymerase chain reaction method. RESULTS: The analysis of vacA prevalence and the type (S1 or S2) showed non-significant differences between the two groups studied (p > 0.05). However, cagA analysis showed highly significant differences between the groups classified as normal tissue-weak gastritis and mild-severe gastritis (p < 0.0001; OR = 8.4; CI = 3.1-22.8). CONCLUSIONS: cagA status is associated to the grade of gastritis, finding higher frequencies of H. pylori cagA+ in the moderate-severe gastritis group. These highly significant differences could make cagA status a genetic marker for disease progress.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Antigens, Bacterial/genetics , Gastritis/microbiology , Helicobacter Infections/microbiology , Helicobacter pylori/genetics , Polymerase Chain Reaction , Antigens, Bacterial/analysis , Bacterial Proteins/genetics , Bacterial Proteins/isolation & purification , Bacterial Typing Techniques/methods , DNA, Bacterial/analysis , Dyspepsia/microbiology , Dyspepsia/pathology , Gastric Mucosa/microbiology , Gastritis/pathology , Genetic Markers , Genotype , Helicobacter pylori/classification , Helicobacter pylori/pathogenicity , Nucleic Acid Amplification Techniques , Retrospective Studies , Virulence
12.
Gene Ther ; 9(24): 1676-81, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12457281

ABSTRACT

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.


Subject(s)
Endothelial Growth Factors/genetics , Genetic Therapy/methods , Genetic Vectors/administration & dosage , Intercellular Signaling Peptides and Proteins/genetics , Lymphokines/genetics , Myocardial Ischemia/therapy , Myocytes, Cardiac/pathology , Animals , Cells, Cultured , Endothelial Growth Factors/analysis , Immunohistochemistry , Intercellular Signaling Peptides and Proteins/analysis , Lymphokines/analysis , Microscopy, Fluorescence , Mitosis , Models, Animal , Myocytes, Cardiac/metabolism , Random Allocation , Reverse Transcriptase Polymerase Chain Reaction , Sus scrofa , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
13.
Exp Parasitol ; 100(4): 217-25, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12128048

ABSTRACT

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.


Subject(s)
Calcium-Binding Proteins , Erythrocyte Membrane/metabolism , Helminth Proteins/isolation & purification , Monosaccharide Transport Proteins/isolation & purification , Periplasmic Binding Proteins , Trypanosoma cruzi/physiology , Animals , Blotting, Western , Chromatography, Affinity , Electrophoresis, Polyacrylamide Gel , Endothelium, Vascular/metabolism , Endothelium, Vascular/parasitology , Erythrocyte Membrane/parasitology , Fluorescent Antibody Technique , Galactose/metabolism , Heart/parasitology , Helminth Proteins/immunology , Helminth Proteins/physiology , Humans , Immune Sera/immunology , Immunohistochemistry , Lectins , Mice , Mice, Inbred BALB C , Monosaccharide Transport Proteins/immunology , Monosaccharide Transport Proteins/physiology , Rabbits , Trypanosoma cruzi/chemistry
14.
Cardiovasc Pathol ; 10(2): 53-7, 2001.
Article in English | MEDLINE | ID: mdl-11425598

ABSTRACT

Two patients with end-stage dilated cardiomyopathy of ischemic and idiopathic origin were treated with a left ventricular assist device (LVAD) as a bridge for heart transplantation. Myocardial tissue was collected during LVAD insertion and from the left ventricular apex of the explanted hearts. The myocyte diameter, nuclear area and DNA content of myocyte nuclei were measured by static cytomorphometry in tissue sections and in isolated myocytes with a digital analysis system. The presence of apoptotic nuclei was investigated by the TdT mediated X-dUTP nick end labeling technique (TUNEL). The prolonged use of a LVAD was associated with a reduction in myocyte diameter, indicating that the LVAD may induce a reversion of myocyte hypertrophy, a process described as "reverse remodeling." In addition, unloading of the heart induced a reduction in the size and DNA content of myocyte nuclei. These results suggest that the cardiomyocyte nuclei are in a dynamic state and, as it occurs with cell hypertrophy, nuclear hypertrophy and polyploidization may be a reversible phenomenon.


Subject(s)
Cardiomyopathy, Dilated/therapy , Cell Nucleus/pathology , Heart-Assist Devices , Myocardium/pathology , Ploidies , Adult , Apoptosis , Cardiomyopathy, Dilated/genetics , DNA/analysis , Humans , Image Cytometry , Image Processing, Computer-Assisted , In Situ Nick-End Labeling , Male , Middle Aged , Ventricular Remodeling/physiology
15.
Am Heart J ; 141(5): 780-3, 2001 May.
Article in English | MEDLINE | ID: mdl-11320366

ABSTRACT

BACKGROUND: We studied whether the level of anti-skeletal muscle glycolipid antibodies (AGA), a marker of acute rejection in heart transplantation, may be associated with an adverse prognosis in unstable angina. METHODS AND RESULTS: The in-hospital evolution of 50 patients with unstable angina (Braunwald class III B) was assessed. We determined the incidence of death, myocardial infarction, and refractory angina. Blood was collected at admission and 24 hours later for determination of AGA levels by enzyme-linked immunosorbent assay. Twenty-three patients showed a decrease in the AGA level at 24 hours after admission. Ten in-hospital cardiac events occurred in these patients (43.4%) as compared with 4 (14.8%) in the 27 patients who did not show a decrease (P =.025). In patients with previous myocardial infarction (n = 26), the AGA assay was a powerful predictor of outcome. In this subgroup, 66.6% of patients who had decreased AGA levels (8 of 12) had cardiac events as compared with 14.2% (2 of 14) of those who did not have that decrease (P =.001). CONCLUSIONS: We conclude that a decrease of AGA levels 24 hours after admission is associated with a complicated in-hospital course. This finding may provide new insights in the phenomenon of plaque instability involved in the development of acute coronary syndromes.


Subject(s)
Angina, Unstable/immunology , Autoantibodies/blood , Glycolipids/immunology , Muscle, Skeletal/immunology , Adult , Aged , Aged, 80 and over , Angina, Unstable/blood , Biomarkers/blood , Disease Progression , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Prognosis
16.
Eur J Cardiothorac Surg ; 19(1): 102-4, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11163573

ABSTRACT

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.


Subject(s)
Coronary Artery Bypass , Coronary Vasospasm/diagnostic imaging , Graft Occlusion, Vascular/diagnostic imaging , Postoperative Complications/diagnostic imaging , Radial Artery/transplantation , Coronary Angiography , Coronary Vasospasm/drug therapy , Graft Occlusion, Vascular/drug therapy , Humans , Infusions, Intravenous , Male , Middle Aged , Nitroglycerin/administration & dosage , Postoperative Complications/drug therapy
17.
Breast ; 10(2): 179-81, 2001 Apr.
Article in English | MEDLINE | ID: mdl-14965582

ABSTRACT

The expression of heat shock protein 27 (Hsp 27) in breast cancers correlates with stage of disease, the lower the stage the higher the expression, and with the presence or absence of lymph node metastases; lymph node negative patients being more likely to express Hsp 27 (P<0.04).

18.
J Heart Lung Transplant ; 19(11): 1114-7, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11077230

ABSTRACT

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.


Subject(s)
Chagas Cardiomyopathy/surgery , Heart Transplantation , Polymerase Chain Reaction , Postoperative Complications/diagnosis , Trypanosoma cruzi/isolation & purification , Animals , Biopsy , Chagas Cardiomyopathy/blood , Chagas Cardiomyopathy/diagnosis , Endocardium/pathology , Female , Follow-Up Studies , Graft Rejection/blood , Graft Rejection/diagnosis , Humans , Middle Aged , Myocardium/pathology , Postoperative Complications/blood , Predictive Value of Tests , Prospective Studies , Recurrence
19.
J Exp Clin Cancer Res ; 19(2): 155-9, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10965811

ABSTRACT

Lymphocyte functional activity from lymph nodes draining human malignancies reflects the host immune response against tumour. Breast cancer is the neoplasia with the greatest amount of identified antigens but a weak inducer of a host efficient immune response. In our study we compared the mitogen stimulated-proliferative response of cells isolated from metastases-free lymph nodes draining breast cancer (Group 1), other malignant tumours (Group 2), and those obtained from patients without malignancies (Control group). A significant decrease of the proliferative response in cells isolated from lymph nodes draining breast cancer was observed comparing it to the other groups. Quantitative analysis of B and T cells showed a higher number of B cells than T cells in Groups 1 and 2. Moreover, Group 1 presented a two fold increase of T cells compared with Group 2. Our results suggest that the immunosuppression observed in lymph nodes draining breast cancer is higher than the inmunosuppression presented in other malignant tumours and that impaired function is not correlated with the increased number of T cells.


Subject(s)
Breast Neoplasms/immunology , Lymph Nodes/immunology , Lymphocyte Activation/physiology , T-Lymphocytes/immunology , Adult , Aged , Aged, 80 and over , Axilla , B-Lymphocytes/immunology , Female , Humans , Immunohistochemistry , Immunosuppression Therapy , Lymphocyte Count , Middle Aged , Neoplasms/immunology
20.
Can J Cardiol ; 15(3): 341-2, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10202198

ABSTRACT

A rare development of acute inferior myocardial infarction is reported in a 23-year-old man with no previous history of cardiovascular disease. In an echocardiographic study a left intraventricular tumour was diagnosed. Cineangiographic study showed normal coronary arteries. The tumour, a myxoma, originating in the ventricular septum, was resected through the left atrium after the anterior leaflet of the mitral valve was detached. Postoperative course was uneventful and the patient remained healthy 48 months after surgery.


Subject(s)
Heart Neoplasms/complications , Myocardial Infarction/etiology , Myxoma/complications , Adult , Cardiac Surgical Procedures , Cineangiography , Coronary Angiography , Echocardiography , Follow-Up Studies , Heart Neoplasms/diagnosis , Heart Neoplasms/surgery , Humans , Male , Myocardial Infarction/diagnosis , Myxoma/diagnosis , Myxoma/surgery
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