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Biomedical subjects

P Mathieu

Publications and source records attributed to P Mathieu.

At least 19 recordsLinked to original sources
PubMed2001

Matrix metalloproteinase-1, -3, -13 and aggrecanase-1 and -2 are differentially expressed in experimental osteoarthritis.

The aim of this study was to characterize the cellular phenotypes of articular cartilage and meniscus in rabbits with experimentally induced osteoarthritis (OA), by histological and molecular biological techniques. OA was induced by severing the anterior cruciate ligament of the knee and rabbits were killed 2, 4 or 9 weeks following surgery. Our histological observations show a progressive destruction of extracellular matrix in both tissues. To determine whether these morphological changes could be related to alterations in the regulation of gene expression for a subset of relevant molecules, levels of mRNA for proteinases and one inhibitor (MMP-1, -3 and -13, aggrecanase-1 and -2 and TIMP-1), matrix molecules and one chaperone (type II and X collagens, aggrecan, osteonectin, betaig-h3 and BiP) were assessed by reverse transcription-polymerase chain reaction. Our results indicate that for most markers expression profiles were similar in both tissues. In particular, matrix protein gene expression remained stable or varied little during progression of OA, suggesting a poor repair capacity of the tissues. MMP gene expression increased rapidly whereas aggrecanase gene expression remained stable. These findings suggest that differential regulation of mRNA levels of MMP-1, -3 and -13 on the one hand and aggrecanase-1 and -2 on the other, occurs during OA.

ADAM Proteins↗
PubMed2001

Tissue inhibitor of metalloprotease-1 (TIMP-1) serum level may predict progression of hip osteoarthritis.

OBJECTIVE: To determine the predictive value of serum levels of TIMP-1 and hyaluronic acid in a 1 year prospective study in hip osteoarthritis (OA). METHODS: Twenty-nine patients with OA of the hip were enrolled in a 1-year prospective study (median follow-up, 13 months). Biochemical analysis was used to assess TIMP-1 and hyaluronic acid at entry and at the end of the study. Radiographic evaluation with an assisted computed program was performed to calculate progression of joint space narrowing. Statistical tests served to determine correlations between observed serum levels and radiograph joint space narrowing. RESULTS: Among the 29 patients, 10 showed joint space narrowing greater than 0.6 mm per year. The initial concentration of TIMP-1 as well as delta value of variation in serum levels of TIMP-1 (difference between TIMP-1 concentration at entry and at the end) correlated with the progression of joint space narrowing. A cut-off value of 600 ng/ml of TIMP-1 allowed the patients who progressed slowly from those who progressed more rapidly. Hyaluronic acid serum level was not predictive of evolution. CONCLUSION: TIMP-1 serum level may serve to predict the evolution of patients with hip OA.

Adult↗
PubMed2001

Pulmonary metabolism of endothelin 1 during on-pump and beating heart coronary artery bypass operations.

BACKGROUND: Coronary artery bypass operations are associated with increased circulating levels of the powerful vasoconstrictor endothelin 1. The pulmonary circulation is an important site for both production and clearance of endothelin 1. Lung endothelial injury resulting from cardiopulmonary bypass could modify pulmonary endothelin 1 metabolism through an increase in production, a reduction in removal, or a combination of both. METHODS: Pulmonary endothelin 1 kinetics were quantified by using the indicator-dilution technique in patients undergoing coronary artery bypass grafting with (n = 11) or without cardiopulmonary bypass (ie, beating heart; n = 10). Mixed venous endothelin 1 levels were also measured in samples from the pulmonary artery, and systemic levels were obtained from the radial artery. RESULTS: Pulmonary artery endothelin 1 levels were similar before and after cardiopulmonary bypass, with means of 1.59 +/- 0.37 pg/mL and 1.33 +/- 0.15 pg/mL (P =.45), respectively. Systemic endothelin 1 levels, however, increased after bypass from 1.64 +/- 0.22 pg/mL to 2.07 +/- 0.16 pg/mL (P =.01). In the beating heart group, endothelin 1 levels before and after the operation were similar in the pulmonary artery (1.25 +/- 0.27 pg/mL and 1.45 +/- 0.31 pg/mL, respectively; P =.38), as well as in the radial artery (1.70 +/- 0.26 pg/mL and 1.73 +/- 0.35 pg/mL, respectively; P =.92). The capacity to clear endothelin 1 from the pulmonary circulation, as computed from the permeability-surface area product for endothelin 1, was not affected by cardiopulmonary bypass before and after the operation (25.19 +/- 2.67 mL/s and 23.12 +/- 4.39 mL/s, respectively; P =.49). It was similar and also unaffected in the beating heart group. CONCLUSION: Coronary artery bypass grafting with cardiopulmonary bypass is associated with an increase in systemic endothelin 1 levels. The mechanism involved is not related to a decreased pulmonary clearance of endothelin 1 from the systemic circulation but rather to an increased endothelin 1 release by the lungs.

Aged↗
PubMed2000

Depletion of cellular glutathione by conditions used for the passaging of adherent cultured cells.

Cultured cells are commonly exposed to trypsin-containing solutions in order to prepare cell suspensions suitable for subculture. Conditions used to release and disperse monolayers of cultured murine hepatoma 1c1c7 and human breast epithelial MCF10A cells caused the loss (40-95%) of cellular glutathione (GSH), but did not affect viability. Glutathione contents returned to pretrypsinization values within 24 h of replating. In contrast, the GSH contents of cultured rat hepatoma 5L cells were not affected by trypsinization. Exposure of 1c1c7 cultures to H(2)O(2) or etoposide 1 or 24 h after replating resulted in concentration-dependent cytostatic and cytotoxic effects. The concentration-response curves defining the cytostatic and cytotoxic effects of etoposide, and the cytostatic effects of H(2)O(2) were not influenced by the timing of toxicant addition. However, 1c1c7 cultures treated with H(2)O(2) 1 h after replating were more susceptible to the cytotoxic actions of the peroxide than cultures treated 24 h after plating. These studies show that conditions commonly used for the passaging of cultured cells can lead to a transient, but profound loss of GSH in some cell lines. Furthermore, the outcome of cytotoxicity analyses can be influenced by the time elapsed between the plating of cultures and the addition of toxicant.

Animals↗
PubMed2000

Tolerance to cardiac allografts via local and systemic mechanisms after adenovirus-mediated CTLA4Ig expression.

Blockade of the CD28/B7 T cell costimulatory pathway prolongs allograft survival and induces tolerance in some animal models. We analyzed the efficacy of a CTLA4Ig-expressing adenovirus in preventing cardiac allorejection in rats, the mechanisms underlying heart transplant acceptance, and whether the effects of CTLA4Ig were restricted to the graft microenvironment or were systemic. CTLA4Ig gene transfer into the myocardium allowed indefinite graft survival (>100 days vs 9 +/- 1 days for controls) in 90% of cases, whereas CTLA4Ig protein injected systemically only prolonged cardiac allograft survival (by up to 22 days). CTLA4Ig could be detected in the graft and in the serum for at least 1 year after gene transfer. CTLA4Ig gene transfer induced local intragraft immunomodulation at day 5 after transplantation, as shown by decreased expression of the IL-2R and MHC II Ags; decreased levels of mRNA encoding for IFN-gamma, inducible NO synthase, and TGF-beta; and inhibited proliferative responses of graft-infiltrating cells. Systemic immune responses were also down-modulated, as shown by the suppression of Ab production against donor alloantigens and cognate Ags, up to at least 120 days after gene transfer. Alloantigenic and mitogenic proliferative responses of graft-infiltrating cells and total splenocytes were inhibited and were not reversed by IL-2. In contrast, lymph node cells and T cells purified from splenocytes showed normal proliferation. Recipients of long-term grafts treated with adenovirus coding for CTLA4Ig showed organ and donor-specific tolerance. These data show that expression of CTLA4Ig was high and long lasting after adenovirus-mediated gene transfer. This expression resulted in down-modulation of responses against cognate Ags, efficient suppression of local and systemic allograft immune responses, and ultimate induction of donor-specific tolerance.

Abatacept↗
PubMed2000

Ventriculotomy and resection for left ventricular thrombus infection with Salmonella.

We report the case of a patient with a left ventricular thrombus infected by Salmonella. The diagnosis was suspected from a gallium scan demonstrating an intense activity in the lower left parasternal area. A transesophageal echocardiogram confirmed a calcified left ventricular aneurysm with a mural thrombus containing pus and heterogeneous material. The patient underwent a successful left ventricular aneurysmectomy, thrombectomy and endocardial resection under cardiopulmonary bypass which brought the infection under control.

Diagnosis, Differential↗
PubMed2000

Serum levels of YKL-40 and C reactive protein in patients with hip osteoarthritis and healthy subjects: a cross sectional study.

BACKGROUND: YKL-40 is a 40 kDa glycoprotein secreted by chondrocytes and synoviocytes. It has been suggested that it is a surrogate marker of synovial inflammation and joint destruction in rheumatoid arthritis (RA) and osteoarthritis (OA) and related to C reactive protein (CRP) serum levels in RA. OBJECTIVE: To study serum levels of YKL-40 in patients with hip OA and its relation with CRP. METHODS: YKL-40 and CRP were assayed in serum samples from 45 patients (24 women, 21 men, mean age 65) with symptomatic OA of the hip and 33 healthy controls. YKL-40 was assayed by immunoassay and CRP by ultrasensitive immunonephelometry. OA severity was assessed by the measurement of joint space width with a computer analysis system of digitised hip radiographs. Statistical analysis was performed to determine correlations between serum markers and radiological joint space width. RESULTS: The mean (standard error) YKL-40 level was 90.3 (8.2) ng/ml in patients with hip OA and 66.9 (8.2) ng/ml in controls (p=0.03). The mean CRP level was 2.93 (3.03) mg/l in OA and 1.40 (1.61) mg/l in controls (p=0.006). The serum levels of YKL-40 and CRP increased with age and were significantly correlated (Spearman test: r(s)=0.42, p=0.005) in patients but not in controls. Neither YKL-40 nor CRP correlated with radiographic joint space width. CONCLUSIONS: Serum YKL-40 was significantly increased in patients with hip OA. The correlation between YKL-40 and CRP suggests that YKL-40 may be a marker of joint inflammation in OA. Longitudinal studies are required to assess the usefulness of YKL-40 in the monitoring of patients with hip OA.

Adipokines↗
PubMed2000

Determinants of the apoptotic response to lysosomal photodamage.

Studies with mouse leukemia L1210 cells revealed that selective lysosomal photodamage caused by any of three photosensitizing agents was followed by a gradual loss of the mitochondrial membrane potential (delta psi m), release of cytochrome c into the cytosol, increased DEVDase activity (a measure of levels of caspase-3) and a limited apoptotic response. Similar effects were observed in the murine hepatoma 1c1c7 cell line. Immunofluorescence techniques employing 1c1c7 cells demonstrated the immediate release of the lysosomal enzyme cathepsin B following lysosomal photodamage. These studies suggest that the cytotoxic effects of lysosomal photodamage are initiated by released lysosomal proteases that either directly and/or indirectly activate caspases as a consequence of the induction of mitochondrial damage.

Animals↗
PubMed2000

Effect of mycophenolate mofetil in heart transplantation.

OBJECTIVE: To study the effect of mycophenolate mofetil (MMF), a new immunosuppressive drug that acts by inhibiting de novo pathways of purine synthesis, and rabbit antithymocyte globulin (RATG) on the lymphocyte subpopulation after heart transplantation. DESIGN: A review of clinical and laboratory records. SETTING: The Montreal Heart Institute. PATIENTS: Thirty-one patients who underwent heart transplantation. In 9 patients, neoral cyclosporine, prednisone and azathioprine were administered (group 1). In 14 patients RATG was added during the first 3 postoperative days (group 2) and in 8 patients RATG and combination immunosuppression was given, but MMF was used instead of azathioprine (group 3). The demographic characteristics of donors and recipients were similar among the 3 groups. MAIN OUTCOME MEASURES: The proportion of CD2, CD4 and CD8 receptor-positive lymphocytes, expressed as a mean (and standard deviation) percentage of the total lymphocyte population, measured at 7, 15 and 30 days and 6 months after transplantation. RESULTS: At 7 days after transplantation, CD2 lymphocytes averaged 55% (18%), 16% (15%) and 14% (11%) in groups 1, 2 and 3 respectively (p < 0.05), CD4 averaged 36% (11%), 9% (12%) and 7% (8%) in groups 1, 2 and 3 (p < 0.05), and CD8 averaged 14% (6%), 4% (3%) and 4% (3%) in groups 1, 2 and 3 (p < 0.05). At 15 days after transplantation CD2 averaged 69% (10%), 42% (16%) and 47% (20%) in groups 1, 2 and 3 respectively (p < 0.05), and CD8 averaged 16% (7%), 16% (6%) and 19% (7%) (p = NS). At 30 days after transplantation the percentages of CD2, CD4 and CD8 lymphocytes were similar among the groups. The freedom rate from acute rejection averaged 22% (14%), 9% (8%) and 50% (18%) (p < 0.05) in groups 1, 2 and 3 at 6 months after transplantation, and the freedom rate from infection averaged 56% (17%), 36% (13%) and 38% (17%) for the 3 groups at this time period (p = NS). CONCLUSIONS: A short course of RATG causes severe, transitory depletion of CD2, CD4 and CD8 lymphocyte subpopulations. MMF decreases the incidence of early acute rejection after heart transplantation without affecting the lymphocyte subpopulation when compared with azathioprine.

Animals↗
PubMed2000

[Osteo-articular ultrasonography of the hip and the knee].

Experience in the field of musculoskeletal diseases and advanced technology of medical sonographers allow increasing accuracy in US investigations of most lesions of both hip and knee superficial tendons. In this field, US is more and more widely replacing other imaging modalities, including MR imaging. Ultrasonography may now be used also for articular diseases purpose, including joint effusion, synovitis, intraarticular loose bodies, ligamentous injuries, articular cysts, as well as for certain osseous lesions like stress or insufficiency fractures of superficial bones. However, ultrasonography has still to be evaluated for these latter indications.

Hip Joint↗
PubMed2000

[Ultrasonography of tendons and ligaments of foot and ankle].

UNLABELLED: The main ligaments and tendons of the ankle and the hind-foot can now be studied by US. This simple and safe technic constitutes a more and more reliable alternative to MRI and CT scan. AIMS: Know the normal US appearance of the tendons and ligaments of the ankle and the hind-foot, and how to study them with US. Know their main usual pathological appearance.

Ankle Joint↗
PubMed1999

Perivalvular abscesses associated with endocarditis; clinical features and prognostic factors of overall survival in a series of 233 cases. Perivalvular Abscesses French Multicentre Study.

AIMS: The purposes of this study were to determine the clinical features and to identify prognostic factors of abscesses associated with infective endocarditis. METHODS AND RESULTS: During a 5-year period from January 1989, 233 patients with perivalvular abscesses associated with infective endocarditis were enrolled in a retrospective multicentre study. Of the patients, 213 received medical surgical therapy and 20 medical therapy alone. No causative microorganism could be identified in 31% of cases. Sensitivity for the detection of abscesses was 36 and 80%, respectively using transthoracic and transoesophageal echocardiography. Surgical treatment consisted of primary suture of the abscess (38%), insertion of a felt aortic or mitral ring using Teflon or pericardium (42%), or debridment of the abscess cavity (20%). The 1 month operative mortality was 16%. Actuarial rates for overall survival at 3 and 27 months in operated patients were 75 +/- 10% and 59 +/- 11%, respectively. Increasing patient age, staphylococcal infection, and fistulization of the abscess were found to be independent risk factors in both 1 month and overall operative mortality. Renal failure was a risk factor predictive of operative mortality at 1 month, whereas uncontrolled infection and circumferential abscess were regarded as risk factors predictive of overall operative mortality. CONCLUSION: The data determined prognostic factors of abscesses associated with infective endocarditis.

Abscess↗
PubMed1999

Evaluation of the 'Lequesne's false profile' of the hip in patients with hip osteoarthritis.

OBJECTIVES: To compare the value of Lequesne's false profile (LFP) radiograph of the hip and antero-posterior (AP) X-ray of the pelvis in the assessment of joint space narrowing (JSN) and osteophyte (Ost) in patients with hip osteoarthritis (OA). METHODS: AP and LFP radiographs of the hip were performed using a standardized method in 50 consecutive patients with hip OA. JSN and Ost were graded at different days by a single observer blinded for patients identity, using a six point scale (JSN:0-5) and a four point scale (Ost:0-3) from AP and LFP respectively. Scores obtained from AP and LFP were compared. RESULTS: Mean JSN grade was significantly higher for LFP (2. 7+/-1.0) than AP (2.4+/-1.2) (P=0.001). It was identical for AP and LFP in 28 patients (56%) while the highest grade was found on LFP in 16 (32%) and on AP in 6 (12%). No significant difference between LFP and AP was found for osteophyte grading. CONCLUSION: These data suggest that the combination AP+LFP provide more information than AP alone for the evaluation of joint space narrowing in about one third of patients. LFP may be helpful for the radiographic assessment of OA changes particularly in structure modifying drugs evaluation.

Aged↗
PubMed1999

Suppression of cell cycle progression by flavonoids: dependence on the aryl hydrocarbon receptor.

Some flavonoids are ligands of the aryl hydrocarbon receptor (AHR) and cause cell cycle arrest. The dependency of the cytostatic effects of five flavonoids (flavone, alpha-naphthoflavone, apigenin, 3'-methoxy-4'-nitroflavone and 2'-amino-3'-methoxyflavone) on a functional AHR was examined in AHR-containing rat hepatoma 5L cells and an AHR-deficient cell line (BP8) derived from the 5L line. The potent AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was cytostatic to the 5L line due to the induction of a G(1) arrest and dramatically elevated steady-state levels of CYP1A1 mRNA. TCDD affected neither the proliferation nor CYP1A1 mRNA contents of BP8 cells. With the exception of apigenin, the flavonoids under study induced G(1) arrest in both 5L and BP8 cells when used at concentrations at which they functioned as AHR agonists, but not antagonists. Apigenin-treated 5L and BP8 cultures primarily arrested in G(2)/M. The AHR-containing murine hepatoma cell line 1c1c7 arrested following exposure to AHR agonist concentrations of flavone and alpha-naphthoflavone, but not TCDD. Unlike the G(1) arrest observed in 5L cultures, the latter two flavonoids caused principally G(2)/M arrest in 1c1c7 cells. These studies demonstrate that the cytostatic activities of flavonoids do not require the AHR and the site of checkpoint arrest with a specific flavonoid can vary with cell type.

Animals↗