R Roy

Centre Hospitalier Universitaire de Québec (CHUQ), Québec, Quebec, Canada

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Publications (70)210.92 Total impact

  • European Journal of Paediatric Neurology - EUR J PAEDIATR NEUROL. 01/2007; 11:76-76.
  • Transplantation 01/2004; 78. · 3.78 Impact Factor
  • Transplantation 01/2004; 78. · 3.78 Impact Factor
  • Human Immunology - HUM IMMUNOL. 01/2002; 63(10).
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    ABSTRACT: This study investigated the basic biocompatibility aspects of two types of polypyrrole (PPy)-coated polyester fabrics for possible use as vascular prostheses. These PPy-coated fabrics, PPy-Phos and PPy-Plas, were sterilized with ethylene oxide (EO) and the following characterizations were performed: surface morphology by scanning electron microscope, EO residuals analysis by the headspace method, acute systemic toxicity in the mouse model, hemolysis, blood coagulation time, viability and proliferation of endothelial cells measured with the WST-1 method, and activation of polymorphonuclear (PMN) cells indicated by the specific expression of interleukin 8 mRNA measured by reverse transcription polymerase chain reaction. Virgin polyester fabrics, expanded poly(tetrafluoroethylene) (ePTFE), and medical-grade Bionate 80A poly(carbonate urethane) were used as references in the cell culture experiments. The PPy-coated fabrics revealed different surface morphologies by showing more PPy lamina and clusters on the PPy-Plas. Neither of the PPy-coated fabrics had an adverse effect on hemolysis and coagulation time, and they did not cause any acute systemic toxicity. The EO residual level was as low as 5 ppm or less, which is considered quite acceptable. Although exhibiting a relatively low initial cell adhesion at 24 h, the two PPy-coated samples showed no cytotoxicity at 72 and 168 h. Bionate 80A and ePTFE recorded cytotoxicity at 72 and 168 h, respectively. The virgin fabrics also demonstrated a decrease of viable cells at 72 h that was not significant. The activation of PMN cells induced by both PPy-coated fabrics, the ePTFE, and the negative control was significantly lower than that induced by their respective tumor necrosis factor-alpha controls. These results therefore highlighted the potential of PPy-coated fabrics for use as cardiovascular prostheses. It was suggested that cell adhesion moieties should be incorporated into the PPy/fabric composite to increase cell adhesion and subsequent cell proliferation.
    Journal of Biomedical Materials Research 11/2001; 57(1):63-71.
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    ABSTRACT: Prevention of acute rejection is the most prevalent measure used to reduce the long-term risk of chronic allograft rejection. Until now, biopsy was the only useful diagnostic tool for monitoring allograft acute rejection, but invasiveness of this procedure limits its use. The aim of this study was to investigate the implication of peripheral blood immune markers as a predictive diagnostic tool preceding biopsy in acute renal allograft rejection determination. Of the 61 patients studied, 13 had no rejection episodes, 8 had a proven acute rejection, and 40 were excluded for graft dysfunction causes. Mitogen-induced peripheral blood mononuclear cells were tested for interleukin- (IL) 2, IL-4, IL-5, IL-6, IL-10, IL-15, Interferon-gamma, Perforin, Granzyme B, and Fas L using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). An up-regulated mRNA expression value was calculated in which a patient's sample was deemed positive if its differential expression value was equal or higher than the mean differential expression value calculated from the nonrejecting patients. IL-4, IL-5, IL-6, Interferon-gamma, Perforin, and Granzyme B mRNA levels were associated with acute rejection. When at least two of these cytokine markers were up-regulated in a given patient, 75% of the rejecting recipients were identified against 15% of the nonrejecting patients. We have shown that acute rejection episodes in renal transplant recipients were associated with an increase in mRNA expression of cytokines in mitogen-induced peripheral blood mononuclear cells. The evaluation of pro-inflammatory cytokines and cytotoxic molecules prove useful in the clinical identification of acutely rejecting transplant recipients and in the justification of concomitant antirejection therapy before histological diagnosis confirmation.
    Transplantation 11/2000; 70(7):1074-80. · 3.78 Impact Factor
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    ABSTRACT: Membranes made from 4 commercial poly(carbonate urethanes): Carbothane (CB), Chronoflex (CF), Corethane 80A (CT80), and Corethane 55D (CT55), and from 2 poly(ether urethanes): Tecoflex (TF) and Tecothane (TT) were prepared by solution casting and sterilized by either ethylene oxide (EO) or gamma radiation. Their biocompatibility was evaluated in vitro in terms of proliferation, cell viability, and adhesion characteristics of human umbilical veins (HUVEC), monocytes (THP-1), and skin fibroblasts, and by measuring complement activation through the generation of the C3a complex. Their hemocompatibility was determined by measuring the level of radiolabeled platelet, neutrophil, and fibrin adhesion in an ex vivo arteriovenous circuit study in piglets as well as via an in vitro hemolysis test. The results of this study showed no endothelial cell proliferation on any of the materials. The cell viability study revealed that the CB, CF, and TF membranes sterilized by EO maintained the highest percentage of monocyte viability after 72 h of incubation (>70%) while none of the gamma-sterilized membranes displayed any cell viability. The fibroblast adhesion and C3a generation assays revealed that none of the materials supported any cell adhesion or activated complement, regardless of the sterilization method. The hemolysis test also confirmed that the 4 poly(carbonate urethanes) were hemolytic while none of the poly(ether urethanes) were. Finally, the ex vivo study revealed that significantly more platelets adhered to the CB and CT55 membranes while the levels of neutrophil and fibrin deposition were observed to be similar for all 6 materials. In conclusion, the study identified the CF and TF membranes as having superior biocompatibility and hemocompatibility compared to the other polyurethanes.
    Artificial Organs 11/2000; 24(11):879-88. · 1.96 Impact Factor
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    ABSTRACT: We investigated whether organochlorine exposure is associated with the incidence of infectious diseases in Inuit infants from Nunavik (Arctic Quebec, Canada). We compiled the number of infectious disease episodes during the first year of life for 98 breast-fed and 73 bottle-fed infants. Concentrations of organochlorines were measured in early breast milk samples and used as surrogates to prenatal exposure levels. Immune system parameters were determined in venous blood samples collected from infants at 3, 7, and 12 months of age. Otitis media was the most frequent disease, with 80. 0% of breast-fed and 81.3% of bottle-fed infants experiencing at least one episode during the first year of life. During the second follow-up period, the risk of otitis media increased with prenatal exposure to p,p'-DDE, hexachlorobenzene, and dieldrin. The relative risk (RR) for 4- to 7-month-old infants in the highest tertile of p, p'-DDE exposure as compared to infants in the lowest tertile was 1. 87 [95% confidence interval (CI), 1.07-3.26]. The RR of otitis media over the entire first year of life also increased with prenatal exposure to p,p'-DDE (RR, 1.52; CI, 1.05-2.22) and hexachlorobenzene (RR, 1.49; CI, 1.10-2.03). Furthermore, the RR of recurrent otitis media ( [Greater/equal to] 3 episodes) increased with prenatal exposure to these compounds. No clinically relevant differences were noted between breast-fed and bottle-fed infants with regard to immunologic parameters, and prenatal organochlorine exposure was not associated with immunologic parameters. We conclude that prenatal organochlorine exposure could be a risk factor for acute otitis media in Inuit infants.
    Environmental Health Perspectives 04/2000; 108(3):205-11. · 7.26 Impact Factor
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    ABSTRACT: The electrically conductive properties of polypyrrole (PPy) as a coating on polyester material are very attractive for the manufacture of small diameter blood conduits. However, before these PPy-coated materials can be investigated for their capacity to generate endothelialized luminal surfaces, they must first be studied for their innocuousness in a living environment. The specific goal of the present study was to investigate the in vivo interactions of PPy-coated and noncoated woven polyester materials implanted subcutaneously in rats for prescheduled periods of 2, 5, 10, 20, and 30 days. The in vivo magnetic resonance (MR) relaxation times were computed for a small area of muscle tissue adjacent to the implants. A correlation was concurrently attempted with blood monocyte activation studies as well as histological observations of the tissue-material interface. The progressive pattern of the slower transversal relaxation time (T2s) values revealed a more persistent tissue reaction for the most conductive PPy-coated materials and a shorter acute tissue response as the surface resistivity increased. Similarly, the blood monocyte activation studies indicated that the thickness of the PPy coating, which correlated with the conductivity, was directly related to tissue response. Furthermore, both the MR and biological studies showed that the PPy-coated material with a high surface resistivity displayed the lowest tissue reaction over the entire period of implantation. The results obtained from the blood monocyte activation studies and histological observations correlate well with the noninvasive MR measurements of the body's healing process. The conductive materials with high surface resistivities must be further investigated. Finally, the noninvasive nature of MR relaxometry reveals its outstanding potential for future in vivo investigations of the body's tissue interactions with polymers and nonferromagnetic biomaterials.
    Artificial Organs 11/1999; 23(10):910-9. · 1.96 Impact Factor
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    ABSTRACT: The use of aortic allografts for the management of vascular prosthetic infections has recently been reintroduced. Impressive results have been obtained; however, the possibility of late degeneration remains a major concern. The healing behavior of aortic allografts, either fresh or preserved, in antibiotic-supplemented nutrient medium at 4 degrees C for 1 week and used as thoracic aorta substitutes in dogs was investigated after 6 months of implantation. Four dogs received a fresh aortic allograft from four different donors, and four dogs received a preserved allograft from two different donors. Autografts in two dogs were performed as controls. The in vivo investigation was conducted to describe (1) the histological characteristics of the arterial wall, (2) the macroscopic and thrombogenic aspect of the luminal surface, (3) the integrity of the endothelial lining by scanning electron microscopy, and (4) its biochemical function by prostacyclin (PGI2) and thromboxane A2 (TXA2) secretion. Immune-mediated reactions directed toward the grafts were measured by sequential screening of donor-specific serum antibody development. All donor-recipient pairs of dogs were major histocompatibility complex (MHC)-incompatible according to a mixed lymphocyte reaction (MLR) assay. From the results of this study we concluded that although preserved arterial allografts exhibited similar surface characteristics as those of fresh allografts in terms of re-endothelialization and long-term graft function, an elicited immune response, a degenerative process in the media, and a hyperplasic reaction in the intima could not be prevented using this method of preservation.
    Annals of Vascular Surgery 04/1999; 13(2):130-40. · 0.99 Impact Factor
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    ABSTRACT: The process of supercritical fluid extraction (SFE) using carbon dioxide as the mobile phase is finding increasing numbers of applications in a wide variety of industries for the extraction, separation, and cleaning of materials. This study assessed the usefulness of this approach in removing surface contaminants from a knitted polyester anterior cruciate ligament (ACL) prosthesis before packaging and sterilizing the product during manufacture. The physical, dimensional, and chemical properties of SFE treated compared with commercially scoured control samples were characterized using a number of textile test methods: electron spectroscopy for chemical analysis, Fourier transform infrared spectroscopy, differential scanning calorimetry, and solvent extraction analysis. The biocompatibility of the samples was measured in terms of their ability to generate CD18 integrin expression on activated human polymorphonuclear cells, and their inflammatory response when implanted for up to 30 days in the knee joint of rats. SFE treatment was successful in removing most of the nonpolar contaminants from the ACL prosthesis and reducing the amount of residuals to a commercially acceptable level. However, some nitrogen containing compounds and polar salts were not removed by the SFE process. The results from the biocompatibility tests demonstrated that the cleaner SFE treated prosthesis induced significantly lower CD18 expression than the scoured control fabric, and was also associated with a milder inflammatory response and a more rapid rate of healing during the 30 day animal trial. Another effect of SFE processing was to cause the polyester device to shrink and lose porosity because of yarn contraction and modification of the polymer's microcrystalline structure.
    ASAIO Journal 06/1998; 44(4):278-88. · 1.49 Impact Factor
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    ABSTRACT: Dog myoblasts obtained from muscle biopsies were infected in vitro with a defective retroviral vector containing a cytoplasmic beta-galactosidase (beta-Gal) gene. These myoblasts were initially transplanted in the irradiated muscles of SCID mice and beta-Gal positive muscle fibers were observed. beta-Gal myoblasts were also transplanted back either in the donor dogs (autotransplantation model) or in unrelated recipient dogs (allotransplantation model). Following these myoblast injections, a rapid inflammatory reaction developed within the muscle as indicated by an expression of P-selectin and of pro-inflammatory cytokine mRNAs (interleukin 6 (IL-6) and transforming growth factor beta (TGF-beta), and by a neutrophil infiltration. Following either auto- or allotransplantation in inadequately or non-immunosuppressed dogs, a specific immune reaction also developed within 2 weeks as indicated by the infiltration of CD4+ and of CD8+ lymphocytes, the increased expression of IL-10 and granzyme B mRNAs and the presence of antibodies reacting with the injected cells. Some dogs were immunosuppressed with several combinations of FK506, cyclosporine (CsA) and RS-61443. In dogs immunosuppressed with CsA combined with RS-61443, only a few myoblasts and myotubes expressing beta-Gal were observed 1-2 weeks after the transplantation, but no muscle fibers expressing beta-Gal were observed after 4 weeks, and antibodies against the injected cells were formed. In dogs immunosuppressed with FK506 alone, although no antibodies against the injected cells were produced, there were no small cells and no muscle fibers expressing beta-Gal 1 month after the transplantation. However, FK506 triggered diarrhea and vomiting in dogs. When the dogs were immunosuppressed with FK506 combined with CsA and RS-61443, muscle fibers expressing beta-Gal were present 4 weeks after the transplantation and no antibodies reacting with donor myoblasts were detected. These results indicate that the combination of three immunosuppressive agents (i.e., FK506, CsA and RS-61443) is effective in controlling the specific immune reactions following myoblast transplantation in dogs and they underline that the outcome of myoblast transplantation is dependent in part on an adequate immunosuppression. These results obtained here in normal dogs may justify myoblast transplantation in dystrophic dogs despite the side effects of FK506.
    Neuromuscular Disorders 05/1998; 8(2):95-110. · 3.46 Impact Factor
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    ABSTRACT: The CD8+CD38+ T-cell subset can predict progression to acquired immune deficiency syndrome among human immunodeficiency virus-positive subjects. This T-cell subset usually increases during other active viral infections (cytomegalovirus [CMV], Epstein Barr virus). We report on its usefulness in the early detection of CMV infection in kidney transplant recipients. Quantitation of CD8+CD38+ T cells was monitored by dual-color flow cytometry analysis on 77 patients during the posttransplantation period. Seventeen of the 52 patients at risk for CMV disease (33%) had primary infection or reactivation and three patients had herpes simplex virus infection only. In every patient with CMV disease, high values for the CD8+CD38+ subset were detected with a 90% positive predictive value for the primary infections. Elevated values were observed at the very first clinical signs of the viral disease or within the few preceeding days. Acute rejection episodes did not provoke false-positive results. This immunologic marker is sensitive and easily obtainable on a daily basis. It may help to direct therapy during rejection or serve as a tool for early detection of clinical viral diseases.
    Transplantation 02/1998; 65(2):279-82. · 3.78 Impact Factor
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    ABSTRACT: Myoblast transplantation is a potential treatment for Duchenne muscular dystrophy. One of the problems possibly responsible for the limited success of clinical trials is the rapid death of the myoblasts after transplantation. To investigate this problem, myoblasts expressing beta-galactosidase were injected in the tibialis anterior muscles of mice. Beta-galactosidase activity was reduced by 74.7% after 3 days. Myoblast death observed at 3 days was reduced to 57.2% when the hosts were irradiated. This result suggested that host cells were contributing to this phenomenon. Transplantation in SCID and FK506-treated mice did not reduce cell death, indicating that mortality was not due to an acute specific reaction. In contrast, administration of the anti-LFA-1 (TIB-213) mAb markedly reduced myoblast death at 3 days without altering leukocyte tissue infiltration. We postulated that neutrophils were mediating myoblast mortality by an LFA-1-dependent mechanism. To test this hypothesis, IL-1beta-activated myoblasts were loaded with 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate, di(acetoxymethylester) (DCFH), a marker for oxidative stress. Addition of neutrophils and zymosan-activated serum resulted in a time-dependent DCFH fluorescence; this neutrophil-induced oxidation was considerably inhibited by TIB-213. These results indicate that an effective control of the inflammatory reaction will be necessary for any new clinical trials of myoblast transplantation and suggest that neutrophil-mediated myoblast injury occurs by an LFA-1-dependent pathway.
    The Journal of Immunology 10/1997; 159(5):2522-31. · 5.52 Impact Factor
  • Transplantation Proceedings 07/1997; 29(4):1932-4. · 0.95 Impact Factor
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    ABSTRACT: The Dialine graft, a new prototype of knitted vascular prosthesis that uses a different brand of polyester fibers as an alternative to Dacron fibers, has been shown to offer excellent in vitro physical performance and in vivo healing. Although it still requires preclotting, the Dialine prosthesis was made impervious by impregnation of bovine type I collagen cross-linked with vapors of formalin. The purpose of the present investigation was to compare the in vitro physical characteristics of the Dialine II graft with those of the collagen-impregnated Hemashield graft. In addition, we studied the healing performance as a thoracoabdominal bypass in dogs for prescheduled periods of implantation ranging from 4 hours to 6 months. In vitro, the bursting strength, resistance to dilatation, and suture retention strength properties of the Dialine II prosthesis were all shown to exceed those of the Hemashield control graft. In the first weeks after implantation, the Dialine II grafts induced a discrete inflammatory response, as shown by the constant leukocyte counts observed both before implantation and when the animals were killed, as well as by the histologic observation of a few inflammatory cells in contact with the collagen. Consequently, the Dialine II grafts showed a slow rate of bioresorption of cross-linked collagen. At 1 month, a thin internal collagenous capsule was present at both anastomoses, laying over the original collagen coating. At 3 and 6 months, areas of thrombotic deposits and endothelialized areas were observed on the luminal surface. Because results of early clinical trials have been highly satisfactory, this prosthesis may be recommended for use without restriction as a medium- and large-diameter blood conduit.
    Annals of Vascular Surgery 04/1997; 11(2):133-40. · 0.99 Impact Factor
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    ABSTRACT: Myoblasts obtained from donors histoincompatible for several non-major histocompatibility complex antigens (i.e., including minor histocompatibility antigens) and from syngeneic donors were transplanted without any immunosuppression into the muscles of male dystrophic C57BL/10J mdx/mdx mice. Myoblasts from syngeneic mice resulted in the formation of a high percentage of dystrophin-positive fibers 16 weeks after the transplantation. There was no evidence of a cellular immune reaction against the donor myoblasts, i.e., no infiltration by CD4 or CD8 lymphocytes and no increased expression of granzyme B and interferon-gamma mRNAs. Transplantation of myoblasts obtained from donors histoincompatible only for non- major histocompatibility complex antigens produced a transient increase of dystrophin-positive fibers at 4 weeks after transplantation for some donor strains but not for others. For donor strains that did produce an increase at 4 weeks, the number of dystrophin-positive fibers was reduced 16 weeks after the transplantation. There was evidence of a cellular immune reaction-infiltration by CD4 and by CD8 lymphocytes and increased expression of granzyme B and interferon-gamma mRNAs. Transplantation of myoblasts obtained from male C57BL/10J +/+ mice into female C57BL/10J mdx/mdx mice also led to the presence of only a few dystrophin-positive fibers with the same signs of cellular immune reaction. In this later case, the cellular immune response was attributed to the H-Y minor antigens. Finally, antibodies against fetal calf serum were detected after both syngeneic and nonsyngeneic transplantations, indicating that the culture medium may also be a source of antigens. In mice, the presence of these antibodies against culture medium did not reduce the success of a first syngeneic transplantation.
    Transplantation 04/1997; 63(6):893-9. · 3.78 Impact Factor
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    ABSTRACT: There are conflicting results regarding the role of human leukocyte antigen (HLA) matching and ABO compatibility in corneal graft rejection for low- and high-risk patients. Lewis blood group antigens could be an important histocompatibility system. Beneficial effects of Lewis antigens matching have been reported in renal transplantation, but its effect is still unknown in corneal allografting. Between 1987 and 1993, ABO, Lewis and HLA phenotypes were determined in 697 consecutive grafts of corneal transplantations. The effect of Lewis matching on corneal endothelial rejection was evaluated over a 3-year period. Data analysis was done by plotting survival curves with the Kaplan-Meier method for survivorship data and performing statistical analysis with the log-rank test (Mantel-Haenszel test) for curve comparison. In vascularized recipients, the ABO, Lewis, and HLA systems did not influence the graft outcome. However, for the unvascularized recipients, the endothelial 3-year rejection rate was significantly lower for both Lewis compatible patients (84% vs. 68%; log rank = 0.03) and HLA compatible patients (86% vs 72%; log rank = 0.001), but not for the ABO-matched patients (82% vs. 79%; log rank = 0.56). The authors' study suggests that Lewis antigens and HLA matching could positively influence corneal graft survival for the unvascularized recipients, but it did not seem to have any effect in vascularized recipients.
    Ophthalmology 04/1997; 104(3):508-12. · 5.56 Impact Factor
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    ABSTRACT: Myoblasts from C57BL/10SnJ+/+ were transplanted in major histocompatibility complex (MHC)-compatible mice (i.e., C57BL10SnJ+/+ and C57BL/10SnSc mdx/mdx) and in MHC-noncompatible (BALB/c+/+) mice. The recipients were killed 1-21 days after transplantation. C57BL10SnJ+/+ myoblasts were also transplanted in a few BALB/c+/+ mice treated with FK506 and killed 7 days thereafter. Our results showed that after MHC-noncompatible transplantation, interferon-gamma (IFN-gamma) mRNA expression is increased from day 5 to day 21, indicating the presence of a cellular immune reaction. Short-term immunosuppressive treatment with FK506 inhibited the transcription of IFN-gamma mRNA compared with that in untreated mice. Myoblast-specific antibodies were also detected 2 and 3 weeks after MHC-incompatible transplantation, indicating that the cellular immune reaction, revealed by the increase in IFN-gamma, was followed by a humoral reaction.
    Muscle & Nerve 08/1996; 19(7):829-35. · 2.31 Impact Factor
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    ABSTRACT: Myoblasts were grown from monkey muscle biopsies and infected in vitro with a defective retroviral vector containing a cytoplasmic beta-galactosidase (beta-gal) gene. These myoblasts were then transplanted to 14 different monkeys, 6 of which were immunosuppressed with FK506. Without immunosuppression, only a few myoblasts and myotubes expressing beta-gal were observed 1 week after the transplantation, but no cells expressing beta-gal were observed after 4 weeks. This result was attributed to immune responses since infiltration by CD4+ or CD8+ lymphocytes was abundant 1 week after transplantation but not after 4 weeks. The expression of interleukin 6 (IL-6), interleukin 2 (IL-2), granulocyte/macrophage colony stimulating factor (GM-CSF), transforming growth factor-beta (TGF-beta) and granzyme B mRNAs was increased in the myoblast-injected muscle indicating that the infiltrating lymphocytes were activated. Moreover, antibodies against the donor myoblasts were detected in 3 out of 6 cases. When the monkeys were immunosuppressed with FK506, muscle fibers expressing beta-galactosidase (beta-gal) were present 1, 4 and 12 weeks after the transplantation. There was neither significant infiltration by CD4 or CD8 lymphocytes, nor antibodies detected. The mRNA expression of most cytokines was significantly reduced as compared to the nonimmunosuppressed monkeys. These results indicate that FK506 is effective in controlling short-term immune reactions following myoblast transplantation in monkeys and suggest that it may prove useful for myoblast transplantation in Duchenne Muscular Dystrophy patients.
    Journal of Neuropathology and Experimental Neurology 07/1996; 55(6):687-97. · 4.35 Impact Factor

Publication Stats

2k Citations
210.92 Total Impact Points

Institutions

  • 1997–2000
    • Centre Hospitalier Universitaire de Québec (CHUQ)
      Québec, Quebec, Canada
  • 1990–1999
    • Laval University
      • Département de Chirurgie
      Québec, Quebec, Canada
  • 1995–1996
    • Université du Québec
      Québec, Quebec, Canada
  • 1981–1994
    • Centre hospitalier de l'Université de Montréal (CHUM)
      Montréal, Quebec, Canada
  • 1993
    • Centre d'enseignement et de recherche en foresterie de Sainte-Foy
      Québec, Quebec, Canada