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Patrick Bruneval

Publications and source records attributed to Patrick Bruneval.

At least 37 records · Page 2Linked to original sources
PubMed2005

Noncultured cell transplantation in an ovine model of right ventricular preparation.

OBJECTIVE: Beyond the first 2 months of life, pulmonary artery banding is warranted before two-stage arterial switch operation. The aim of this study was to explore whether myogenic cell transplantation could contribute to right ventricular function during pulmonary artery constriction in an ovine model. METHODS: Sixteen rams were assigned to one of the following groups: group 1, simple pulmonary artery banding (n = 5); group 2, pulmonary artery banding and cell implantation in the right ventricle (n = 7); and group 3, pulmonary artery banding and placebo injection in the right ventricle (n = 4). Hemodynamic assessment with pressure-volume loops was performed on days 0 and 60. The pulmonary artery banding and the injections were achieved through a left fourth intercostal thoracotomy. Autologous myogenic cell implantation was carried out with a noncultured cell preparation, as previously described by our group. Implanted sites were processed with monoclonal antibodies to a fast skeletal-specific isoform of myosin heavy chain (MY32). RESULTS: Skeletal myosin heavy chain expression was detected at 2 months after noncultured cell implantation in all grafted animals. Right ventricular training resulted in statistically significant increased signs of contractility in all three groups. There was no observed difference, however, between the cell therapy group and the other two groups with respect to signs of cardiac function. CONCLUSION: Successful engraftment of noncultured cells into right ventricular myocardium did not translate into a functional benefit that we could demonstrate in our ovine model. Cellular therapy thus is probably not useful to strengthen a left ventricle being retrained through pulmonary artery banding before arterial switch operation. However, cell transplantation may affect the outcome of right ventricular failure long term after atrial switch operation. Although preliminary, this investigation paves the way for further research into cellular cardiomyoplasty, right ventricular failure, and congenital heart disease.

Age Factors↗
PubMed2005

Enhancement of the functional benefits of skeletal myoblast transplantation by means of coadministration of hypoxia-inducible factor 1alpha.

OBJECTIVE: Early cell death remains a major limitation of skeletal myoblast transplantation. Because the poor vascularization of the target scars contributes to cell loss, we assessed the effects of combining skeletal myoblast transplantation with administration of hypoxia-inducible factor 1alpha, a master gene that controls the expression of a wide array of angiogenic factors. METHODS: A myocardial infarction was created in 56 rats by means of coronary artery ligation. Eight days later, rats were randomly allocated to receive in-scar injections of culture medium (control animals, n = 11), skeletal myoblasts (5 x 10(6) , n = 13), adenovirus-encoded hypoxia-inducible factor 1alpha (1.0 x 10(10) pfu/mL, n = 7), or skeletal myoblasts (5 x 10(6)) in combination with an empty vector (n = 3) or active hypoxia-inducible factor 1alpha (1.0 x 10(10) pfu/mL, n = 13). A fifth group (n = 9) underwent a staged approach in which hypoxia-inducible factor 1alpha (1.0 x 10(10) pfu/mL) was injected at the time of infarction, followed 8 days later by skeletal myoblasts (5 x 10(6)). Left ventricular function was assessed echocardiographically before transplantation and 1 month thereafter. Explanted hearts were then processed for the immunohistochemical detection of myotubes, quantification of angiogenesis, myoblast engraftment, and cell survival. RESULTS: Baseline ejection fractions were not significantly different among groups (35%-40%). One month later, ejection fraction had decreased from baseline in control hearts and in those injected with hypoxia-inducible factor 1alpha. In contrast, it did not deteriorate after injections of skeletal myoblasts alone or combined with either the empty vector or active hypoxia-inducible factor 1alpha administered sequentially. The most striking change occurred in the skeletal myoblast plus hypoxia-inducible factor 1alpha combined group in which ejection fraction increased dramatically (by 27%) above baseline levels and was thus markedly higher than in all other groups ( P = .0001 and P = .001 vs control animals and animals receiving hypoxia-inducible factor 1alpha, respectively). Compared with skeletal myoblasts alone, the coadministration of hypoxia-inducible factor 1alpha resulted in a significantly greater degree of angiogenesis, cell engraftment, and cell survival. CONCLUSION: Induction of angiogenesis is an effective means of potentiating the functional benefits of myoblast transplantation, and hypoxia-inducible factor 1alpha can successfully achieve this goal.

Adenoviridae↗
PubMed2005

[Phenotypic and functional analysis of T lymphocytes in cancer patients].

In preclinical tumor model and in human cancer, tumor antigen specific T lymphocytes play a key role in the control of tumor development. Nevertheless in numerous cases, the infiltrating tumor T cells do not seem to influence the clinical progression of the tumor. A better phenotypic and functional characterization of T cells in close contact with tumor associated with a comprehensive analysis of tumor evasion mechanism to the host response should lead to an optimization of cancer immunotherapy protocols.

Antigens, CD↗
PubMed2005

[Mitochondrial hepatic toxicity associated with antiretroviral treatment].

Highly active antiretroviral therapy (HAART) has become the gold standard treatment of HIV/AIDS infection. NRTI-related mitochondrial toxicity has been recognized as a serious adverse effect of HAART. The mechanisms underlying NRTI-induced mitochondriopathy involve the inhibition of the human DNA polymerase gamma mtDNA mutations and oxidative stress. The clinical spectrum of NRTI-related toxicity ranges from a subclinical disease e.g. mild hepatic abnormalities, to a rare life-threatening condition with lactic acidosis and hepatic insufficiency. In the latter, liver histology shows massive steatosis. Ultrastructural assessment of mitochondrial abnormalities may be of help to address the NRTI toxicity in poorly symptomatic patients. Efforts have been recently made to assess the clinical relevance of non-invasive tests including the evaluation of mtDNA or mitochondrial functions in peripheral blood mononuclear cells for the diagnosis of NRTI-associated toxicity.

Acquired Immunodeficiency Syndrome↗
PubMed2005

[Mycoses of the head and neck].

In recent years, mycoses have emerged as important infections in clinical practice. This phenomenon is explained by the ever growing number of immunocompromised patients and the increasing number of people travelling in areas where fungal diseases are endemic. Head and neck infections are common in disseminated mycoses and may simulate carcinoma or cause upper airway obstruction. The most frequent causative yeasts or yeast-like organisms include Candida albicans, Cryptococcus neoformans, Histoplasma capsulatum var capsulatum, Blastomyces dermatitidis, Paracoccidioides brasiliensis and Coccidioides immitis. Other causative fungal pathogens include Aspergillus fumigatus and less frequently, Rhizopus oryzae and Rhinosporidium seeberi. Since in most cases their pathophysiology is similar, those microorganisms share a common clinical pathological presentation. Symptoms such as dysphonia or dysphagia associated with hyperplastic and ulcerative lesions on endoscopic examination should prompt biopsies. A purulent or granulomatous inflammatory tissue reaction with pseudoepitheliomatous hyperplasia warrants caution since it may lead to a mistaken diagnosis of carcinoma. The pathologist must look carefully for microorganisms with Grocott and PAS stains. The causative agent can be identified if the pathologist is aware of the risk. Positive culture is needed to institute adequate treatment.

Aspergillosis↗
PubMed2005

Podocyte involvement in human immune crescentic glomerulonephritis.

BACKGROUND: The role of podocytes in human crescentic glomerulonephritis (GN) has been underestimated. This may be due to the confounding fact that "dysregulated" podocytes are able to proliferate, lose their markers, and acquire new epitopes. Moreover, in experimental anti-glomerular basement membrane (GBM) crescentic GN, podocytes participate in the crescent formation. The aim of this study was to investigate the involvement of podocytes in human immune crescentic GN. METHODS: Renal biopsies from 12 patients with anti-GBM disease and 14 with class IV lupus GN were studied by immunohistochemistry for the following markers: (1) synaptopodin, GLEPP1, podocalyxin, podocin, alpha-actinin-4, and vimentin for podocyte identification; (2) PCNA, Ki-67, and p57 for cell cycle assessment; (3) cytokeratins for identifying epithelial cells but not normal podocytes; (4) CD68 for tagging a macrophagic epitope; (5) alpha-smooth-muscle actin (alpha-SMA), a phenotypic marker of myofibroblasts. RESULTS: "True" (capsular) crescents lining Bowman's capsule and (tuft) "pseudocrescents" covering the glomerular tuft with a persistent patent urinary space were present in the 2 types of crescentic GN in similar percentages. Several features indicated that podocytes were involved in the formation of the both crescent types. Identifiable podocytes expressed proliferation markers. Podocyte cytoplasmic expansions and racket-like podocytes bridged between the tuft and Bowman's capsule. True and pseudocrescents contained labeled podocytes. In addition, podocytes located outside of the crescents had often lost their markers (dedifferentiation) and acquired new epitopes (cytokeratins and CD68). CONCLUSION: In human immune crescentic GN, podocytes undergo proliferation and dysregulation that are indicative of a podocytopathy. Podocytes contribute to crescent formation.

Actins↗
PubMed2005

[Podocytopathie and transdifferentiation of the podocytes in human glomerulonephritis. An immunomorphological study].

Transdifferentiation is characterized by a loss of normal epitopes by differentiated cells, accompanied by the acquisition of new epitopes and new functions. Podocytes are differentiated epithelial cells that cover and adhere to the outer surface of the glomerular basement membrane (GBM). The podocyte/GBM complex contributes to the selective filter function of the glomerular tuft. We have shown that, in various human glomerulonephritides, "dysregulated" podocytes acquire the potential to proliferate and multiply, undergo profound morphologic changes, detach from the GBM, and show phenotypic changes indicative of transdifferentiation. In the course of these events they lose their original epitopes and acquire macrophagic markers.

Basement Membrane↗
PubMed2004

Does the functional efficacy of skeletal myoblast transplantation extend to nonischemic cardiomyopathy?

BACKGROUND: The benefits of skeletal myoblast (SM) transplantation on infarcted myocardium have been investigated extensively; however, little is known about its effects in nonischemic cardiomyopathy models. To address this issue, we tested SM transplantation in CHF147 Syrian hamsters, a strain characterized by a delta-sarcoglycan deficiency that phenotypically features the human setting of primary dilated cardiomyopathy. METHODS AND RESULTS: Cell culture techniques were used to prepare approximately 5x10(6) muscle cells from autologous tibialis anterior muscle, of which 50% were SMs (desmin staining). The cells were injected in 6 sites across the left ventricular wall (n=14). Control animals (n=12) received equivalent volumes of culture medium. Left ventricular systolic function was assessed in a blinded fashion from 2D echocardiographic left ventricular fractional area change, before transplantation, and 4 weeks later. Explanted hearts were processed for the detection of myotubes and quantification of fibrosis. Baseline functional data did not differ between the 2 groups. Four weeks after transplantation, 6 of the 10 surviving grafted hamsters were improved compared with 0 of the 8 survivors of the control group. This translated into a 6% decrease in fractional area change in controls compared with a 24% increase in cell-transplanted hamsters (P=0.001). Engrafted myotubes were consistently detected in all SM transplanted hearts by immunohistochemistry, whereas fibrosis was not worsened by cell injections. CONCLUSIONS: These data suggest that the functional benefits of SM transplantation might extend to nonischemic cardiomyopathy.

Animals↗
PubMed2004

Comparison of human skeletal myoblasts and bone marrow-derived CD133+ progenitors for the repair of infarcted myocardium.

OBJECTIVES: The present study was designed as a face-to-face functional comparison of human skeletal myoblasts (SMs) and CD133(+) bone marrow-derived hematopoietic progenitors in an animal model of semichronic myocardial infarction. BACKGROUND: Compared with SMs, bone marrow-derived cells have the advantage of plasticity and might more effectively regenerate ischemic cardiac tissue. However, few data exist on the comparative efficacy of these two cell types in semichronic infarcts. METHODS: A myocardial infarction was created by coronary ligation in 32 nude rats. Ten days later, rats received in-scar injections of human SMs, CD133(+) progenitors, or culture medium. Left ventricular function was assessed before and one month after transplantation by echocardiography and pressure-volume loops. Immunofluorescence, polymerase chain reaction, and in situ hybridization were used to detect cells grafted in the hearts. RESULTS: One month after transplantation, left ventricular ejection fraction decreased by 8 +/- 4% in controls, whereas it increased by 7 +/- 3% in CD133(+)-grafted hearts (p = 0.0015 vs. controls) and further by 15 +/- 5% in SM-treated hearts (p = 0.008 vs. controls). Systolic indices yielded by pressure-volume loops paralleled these data. Engrafted myotubes were identified in all SM-treated hearts by immunofluorescence, whereas in CD133(+)-grafted hearts, few human cells were only detected by polymerase chain reaction. CONCLUSIONS: In the setting of postinfarction scars, the transplantation of bone marrow-derived CD133(+) progenitors improves cardiac function, but this benefit is not superior to that afforded by myogenic cells.

AC133 Antigen↗
PubMed2004

Plasticity of mouse renal collecting duct in response to potassium depletion.

Plasticity of mouse renal collecting duct in response to potassium depletion.--Renal collecting ducts are the main sites for regulation of whole body potassium balance. Changes in dietary intake of potassium induce pleiotropic adaptations of collecting duct cells, which include alterations of ion and water transport properties along with an hypertrophic response. To study the pleiotropic adaptation of the outer medullary collecting duct (OMCD) to dietary potassium depletion, we combined functional studies of renal function (ion, water, and acid/base handling), analysis of OMCD hypertrophy (electron microscopy) and hyperplasia (PCNA labeling), and large scale analysis of gene expression (transcriptome analysis). The transcriptome of OMCD was compared in mice fed either a normal or a potassium-depleted diet for 3 days using serial analysis of gene expression (SAGE) adapted for downsized extracts. SAGE is based on the generation of transcript-specific tag libraries. Approximately 20,000 tags corresponding to 10,000 different molecular species were sequenced in each library. Among the 186 tags differentially expressed (P < 0.05) between the two libraries, 120 were overexpressed and 66 were downregulated. The SAGE expression profile obtained in the control library was representative of different functional classes of proteins and of the two cell types (principal and alpha-intercalated cells) constituting the OMCD. Combined with gene expression analysis, results of functional and morphological studies allowed us to identify candidate genes for distinct physiological processes modified by potassium depletion: sodium, potassium, and water handling, hyperplasia and hypertrophy. Finally, comparison of mouse and human OMCD transcriptomes allowed us to address the question of the relevance of the mouse as a model for human physiology and pathophysiology.

Acid-Base Equilibrium↗
PubMed2004

Acute vascular humoral rejection in a sensitized cardiac graft recipient: diagnostic value of C4d immunofluorescence.

A 37-year-old female patient had a cardiac transplantation for dilated cardiomyopathy. She was sensitized by two pregnancies showing anti-human leukocyte antigen I and II antibodies. The pretransplantation crossmatch was negative, but she developed acute humoral rejection characterized by vascular C4d deposits, arteriolitis, and intravascular leukocyte accumulation and adhesion in venules. Although C4d deposits disappeared in 4 weeks, she had persistent endothelial cell activation (endothelial expression of ELAM-1, VCAM-1, or human leukocyte antigen class II) throughout the 6 months of follow-up. Although she received intensive immunosuppression, she presented three episodes of acute cellular rejection during that period of time. This case shows that C4d deposits represent a sensitive marker of acute humoral rejection in cardiac transplantation. Therefore, C4d immunofluorescence should be more frequently assessed in endomyocardial biopsies.

Acute Disease↗
PubMed2004

Homograft replacement of the mitral valve: eight-year results.

OBJECTIVE: The objective of this study was to assess whether the mitral homograft represents a valuable alternative for complete or partial mitral valve replacement. METHODS: Since 1993, 104 patients underwent mitral homograft replacement surgery. The mean age was 38 +/- 15 years. The causes of mitral valve disease were rheumatic disease (n = 76), infective endocarditis (n = 24), and others (n = 4). Sixty-five of these procedures were total homografts, and 39 were partial homografts. RESULTS: The mean follow-up was 52 +/- 35 months (maximum, 117 months). Overall hospital mortality was 4 (3.8%) of 104 patients and 2.5% versus 8.7% for patients without endocarditis and with endocarditis, respectively (P <.19). There were 9 late deaths (cardiac, 4; noncardiac, 5). There have been 5 early (<3 months) and 10 late reoperations. Of the remaining 77 patients, New York Heart Association class was I in 61, II in 14, and III in 2. Four patients had endocarditis, and 5 had an ischemic or hemorrhagic event. Freedom from major cardiac events was 71% +/- 6% at 8 years (partial at 81% vs total at 63%, P <.19). Among patients with a total homograft, freedom from major cardiac events was 61% +/- 9% and 85% +/- 8% at 6 years in patients younger than and older than 40 years, respectively (P =.09). CONCLUSION: The risk of early dysfunction related to a mismatch between the mitral homograft and the patient's valve is the main pitfall of the technique. Beyond that stage, the results were comparable with those of bioprostheses in a cohort of young patients.

Adult↗
PubMed2004

High prevalence of anal squamous intraepithelial lesions in HIV-positive men despite the use of highly active antiretroviral therapy.

BACKGROUND: The impact of highly active antiretroviral therapy (HAART) on the natural history of HPV infection and anal squamous intraepithelial lesions (SIL) in HIV-infected men who have sex with men (MSM) is poorly documented. GOAL The goal of this study was to evaluate the prevalence of anal HPV infection and SIL inpatients under HAART. STUDY DESIGN: Forty-five HIV-infected protease inhibitor-experienced MSM were enrolled in a cross-sectional study. Each patient provided anal samples for anal cytology, histology, and human papillomavirus (HPV) DNA testing. RESULTS: The patients had previously received HAART for a median of 32 months. Anal cytology was abnormal in 32 of 45 (71%) patients, including high-grade SIL in 10 patients (22%), low-grade SIL in 19 patients (42%), and atypical squamous cells of undetermined significance in 3 patients (7%). HPV DNA was detected 36/45 men (80%). The prevalence of anal SIL and HPV infection were similar in patients exhibiting a significant increase in CD4+ cell count after HAART initiation compared with those who did not. CONCLUSION: Our results demonstrate a high prevalence of anal SIL, including high-grade SIL, and anal HPV infection in HIV-infected MSM despite immune restoration under HAART.

Adult↗
PubMed2004

Metastatic juxtaglomerular cell tumor in a 52-year-old man.

Juxtaglomerular cell tumor is a rare renal neoplasm arising from the juxtaglomerular apparatus. Approximately 70 cases have been reported in the English literature since it was first described by Robertson et al in 1967. This tumor has been considered benign and resection has so far been curative. In this paper, we report the first metastatic juxtaglomerular cell tumor. The 15-cm tumor occurred in the right kidney of a 46-year-old man. It invaded the renal vein, and was treated by radical nephrectomy in 1995. The diagnosis at that time was renal cell carcinoma. The patient was well for 6 years and then developed bilateral lung masses, which were resected. Microscopically, the tumors from the kidney and the lungs were similar, consisting of solid sheets of uniformly round-to-polygonal cells intermixed with abundant delicate vasculature. Both renal and pulmonary tumors were positive for vimentin, renin, and only focally to CD34. Electron microscopic studies performed on the paraffin-embedded renal tumor and formalin-fixed lung tumor revealed the typical rhomboid crystals of proto-renin. In consideration of the characteristic morphologic features, immunohistochemistry, and the presence of rhomboid crystals of proto-renin, the diagnosis was modified to malignant juxtaglomerular cell tumor.

Biomarkers, Tumor↗
PubMed2004

Vascular smooth muscle cell endovascular therapy stabilizes already developed aneurysms in a model of aortic injury elicited by inflammation and proteolysis.

OBJECTIVE: To investigate the efficiency of endovascular smooth muscle cell (VSMC) seeding in promoting healing and stability in already-developed aneurysms obtained by matrix metalloproteases (MMPs)-driven injury. SUMMARY BACKGROUND DATA: VSMCs are instrumental in arterial healing after injury and are in decreased number in arterial aneurysms. This cellular deficiency may account for poor healing capabilities and ongoing expansion of aneurysms. METHODS: Aneurysmal aortic xenografts in rats displaying extracellular matrix injury by inflammation and proteolysis were seeded endoluminally with syngeneic VSMCs, with controls receiving culture medium only. Diameter, structure, and the destruction/reconstruction balance were assessed. RESULTS: Eight weeks after endovascular infusion, aneurysmal diameter had increased further, from 3.0 +/- 0.3 mm to 10.9 +/- 6.5 mm (P = 0.009), and medial elastin content had decreased from 36.5 +/- 8.5 to 5.2 +/- 5.5 surface-percent (S%; P = 0.009) in controls, whereas these parameters remained stable in the seeded group (3.0 +/- 0.3 to 2.7 +/- 0.2 mm, P = 0.08; 36.5 +/- 8.4 to 31.6 +/- 9.7 S%, P = 0.22). VSMC seeding was followed by a decrease in mononuclear infiltration. MMP-1, -3, -7, -9, and -12 mRNA contents were sharply decreased in the diseased wall in response to seeding. Tissue inhibitor of metalloproteinase-1, -2, and -3 mRNAs in the intima were increased in a 2 to 10 magnitude in comparison with controls. Gelatin zymography showed the disappearance of MMP-9 activity and reverse zymography a strong increase in tissue inhibitor of metalloproteinase-3 activity in the seeded group. VSMC-seeded aneurysms were rich in collagen and lined with an endothelium instead of a thrombus in controls. CONCLUSIONS: VSMCs endovascular seeding restores the healing capabilities of proteolytically injured extracellular matrix in aneurysmal aortas, and stops expansion.

Animals↗