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Biomedical subjects

E Rondeau

Publications and source records attributed to E Rondeau.

At least 55 records · Page 3Linked to original sources
PubMed1998

Soluble latent membrane-type 1 matrix metalloprotease secreted by human mesangial cells is activated by urokinase.

BACKGROUND: Matrix metalloprotease 2 (MMP2) is secreted in a latent inactive form (pro-MMP2) that is activated on the cell surface by a membrane-type 1 MMP (MT1-MMP) in the presence of the tissue inhibitor of MMP (TIMP2). In spite of evidence for the synthesis of MT1-MMP shown by immunoblotting, immunocytochemistry and RT-PCR, and of TIMP2, MMP2 was found exclusively in a latent form in human mesangial cells (HMC) serum-free culture medium. METHODS AND RESULTS: On purified membranes of HMC, MT1-MMP was found in a 63 kD latent form and as a faint band of 55 kD. The 55 kD band was also present in the ultracentrifuged conditioned medium and likely represented MT1-MMP cleaved from its transmembrane domain, since Northern blot analysis showed only one transcription product. The addition of urokinase plasminogen activator (uPA, 100 nM) to HMC membranes induced the activation of pro-MMP2 via the activation of latent membrane-associated MT1-MMP as reflected by the cleavage of the 63 and 55 kD forms. In addition, when the conditioned medium was successively incubated with uPA and alpha 2-macroglobulin and analyzed by immunoblotting, MT1-MMP decreased, indicating that the soluble MT1-MMP was in a latent form and was activated by uPA. CONCLUSION: Our results provide the first evidence, to our knowledge, of the existence of a soluble latent form of MT1-MMP secreted by primary human cells in culture, confirming that MT1-MMP is an ectoenzyme, and show that uPA can regulate MT1-MMP activity in a soluble phase.

Cell Membrane↗
PubMed1998

Tissue-type plasminogen activator activity in HIV-associated HUS.

BACKGROUND: In children, haemolytic uraemic syndrome (HUS) is associated with high plasma plasminogen activator inhibitor type 1 (PAI-1), which may contribute to the persistence of renal glomerular and arteriolar thrombi. HUS has been described in HIV-infected patients, but the pathophysiology of HUS in these patients is poorly understood. The aim of the study was to investigate plasma fibrinolytic activity in 18 patients with HIV-associated HUS. METHODS: We measured tissue type plasminogen activator (t-PA) and PAI-1 activities in the plasma of 18 HIV-infected patients with biopsy-proven HUS (HIV+/HUS+) and 48 HIV-infected patients without HUS (HIV+/HUS-). RESULTS: Patients with HUS had a significantly higher serum creatinine, a lower platelet count and an increased incidence of cytomegalovirus (CMV) infection (72% of patients HIV+/HUS+, vs 25% of patients HIV+/HUS-). Unexpectedly, plasma PAI-1 activity was similar in both groups. However, t-PA activity was significantly higher in HUS cases (11.5 vs 4.5 U/ml, P=0.001). Patients with CMV infection, with or without HUS, had significantly increased t-PA level (P=0.01). Multivariate analysis identified high t-PA (RR=9.21) and CMV infection (RR=3.36) as risk factors for HUS. CONCLUSION: This study provides evidence that HIV-infected patients with HUS have high plasma t-PA activity. PAI-1 plasma activity is not significantly increased, as opposed to non-HIV-associated HUS. Thus, in the setting of HIV infection, HUS cannot be attributed to decreased fibrinolytic activity.

Adult↗
PubMed1998

Communication of risks: organization of a methylmercury campaign in the Cree communities of James Bay, Northern Quebec, Canada.

In the James Bay region of Canada, with the advent of extensive hydroelectric development, methylmercury contamination of fish has become a serious problem, having a direct impact on the Cree way of living. In 1982, the Cree Board of Health and Social Services of James Bay implemented a methylmercury exposure surveillance program in all Cree communities. Since that time, it has developed several educational tools on methylmercury contamination, including posters, pamphlets, and a video. In 1993 and 1994, Cree leaders, Community Health Representatives, medical staff, and other selected band members were consulted to identify the needs of the population regarding information on mercury. All questions and comments were listed, and a summary was sent to those consulted to double check the type of information required by the population. This led to the preparation of a brochure on mercury in a question and answer format, as well as creation of posters. The brochure and the posters were published in French, English and Cree and distributed in each community. A radio message was broadcast in all communities, and individual and group meetings were also held. Cree involvement in the mercury information program has been essential to its success.

Animals↗
PubMed1998

[Evidence of a renin receptor on human mesangial cells: effects on PAI1 and cGMP].

Most proteases a receptor or a binding site that serves to concentrate the proteolytic activity on the cell surface and to mediate cellular effects. We looked for such a receptor for renin, an aspartyl protease. The binding of recombinant human renin labelled with 125I was studied on primary and immortalized human mesangial cells. The binding of renin was specific, saturable and was characterized by Kd = 0.4 nM and 8,000 sites/cell and Kd = 1 nM and 2,000 sites/cell for primary and immortalized cells, respectively. The binding did not depend on the active site of the enzyme, was not followed by internalization and degradation of renin and did not modify intracellular Ca2+. Stimulation of primary cells with 100 nM induced a significant increase of 3H thymidine incorporation but was not associated with an increase of the cell number. Furthermore, incubation of mesangial cells 24 h with 100 nM renin provoked an increase of tPA and of PAI1 in the conditioned medium. This increase was not modified neither by captopril nor by angiotensin II receptors antagonists. The tPA antigen elevation was confirmed by fibrin zymography showing an increase of tPA/PAI1 complexes. But, surprisingly, the reverse zymogram showed that PAI antigen increase was associated with decreased PAI activity which was due to PAI clivage in an inactive form. PAI clivage by renin required the presence of the cells and could not be obtained by incubating renin and recombinant human PAI alone. When primary mesangial cells were cultured in the presence of a specific inhibitor of renin active site, RO 42-5982, PAI accumulation in the conditioned medium was reduced by 50-60%, suggesting that endogenous renin plays a role in PAI synthesis and/or secretion. The binding of renin does not induce cAMP and cGMP generation. However, in the presence of renin (100 nM and 1 microM) the extent of cGMP generated by CNP (10 and 100 nM) was reduced by 50%. Preliminary results of the renin receptor purification by affinity chromatography indicate that the receptor Mr is about 57 kDa.

Calcium↗
PubMed1997

Alterations in human glomerular epithelial cells interacting with nonenzymatically glycosylated matrix.

The glomerular epithelial cells and the glomerular basement membrane are important constituents of the permselective barrier in the kidney. These are affected in diabetic nephropathy, one of the long-term complications in diabetic patients. Nonenzymatic glycosylation resulting in the accumulation of advanced glycosylation end products correlates with the development of long-term complications in diabetes. The interaction of cells with extracellular matrix proteins plays a critical role in a variety of biological processes. Recent studies show that cell-matrix interactions mediated by integrins can transduce biochemical signals to the cell interior and regulate cell behavior. In this paper we demonstrate that interactions of human glomerular epithelial cells with a nonenzymatically glycated matrix are altered with defective cell spreading, reduced phosphorylation of focal adhesion kinase and reduced activity of mitogen-activated protein kinase. These data suggest that matrix glycation interferes with normal cell-matrix interactions and intracellular signaling that can potentially result in differential gene expression contributing to the changes seen in diabetic nephropathy.

Cell Adhesion↗
PubMed1997

Long-term prognosis of renal transplantation after preemptive treatment of cytomegalovirus infection.

A role for cytomegalovirus (CMV) infection in the etiologies of acute and chronic rejection in renal allograft recipients has been suggested. We previously reported that preemptive treatment of CMV infection with ganciclovir in kidney transplant patients was safe and effective. We now present a retrospective analysis of 169 consecutive renal transplant patients, of whom 87 (51.5%) received preemptive treatment with ganciclovir (CMV(+) group). No patient died of CMV infection. Actuarial graft and patient survival rates were not different between the CMV(+) and the CMV(-) groups (graft survival: 68% and 69%; patient survival: 89% and 88%, respectively). At the end of the study, the mean plasma creatinine levels were not statistically different between the two groups (185+/-13 and 166+/-12 micromol/L for the CMV(+) group and the CMV(-) group, respectively). These results suggest that preemptive treatment of CMV infection with ganciclovir may prevent the CMV-induced renal injury and graft loss.

Adolescent↗
PubMed1997

Systemic capillary leak syndrome: report on 13 patients with special focus on course and treatment.

BACKGROUND: Systemic capillary leak syndrome (SCLS) is a rare condition characterized by unexplained episodic capillary hyperpermeability due to a shift of fluid and protein from the intravascular to the interstitial space. This results in diffuse swelling, weight gain, and renal shut-down. From the first publication in 1960, only 34 cases have been reported. OBJECTIVE: To collate enough patients to observe the natural history of the disease and evaluate the efficacy of empiric treatments. DESIGN: Multicentric retrospective study. RESULTS: Thirteen patients (6 women and 7 men) were collated with a mean follow-up of 6.4 years. Eight patients are still alive after a mean of 5.6 years (range 1 to 15). Three patients out of the 11 who were not lost to follow-up died; 1 during an attack and 2 because of a progression towards multiple myeloma. CONCLUSIONS: Our series shows an improvement in the prognosis of SCLS due most likely to improved management during attacks. Some patients' disease could evolve into a multiple myeloma. Treatment is still empiric and no prophylactic therapy, including terbutaline associated with aminophylline, has clearly proven its efficacy.

Acute Disease↗
PubMed1997

Endothelial and macrophage upregulation of urokinase receptor expression in human renal cell carcinoma.

The binding of urokinase-type plasminogen activator (u-PA) to a specific cell surface receptor (uPA-R) has been shown to enhance plasminogen activation, a process involved in extracellular matrix degradation and cell migration during angiogenesis and tumor growth. We investigated the expression of u-PA and uPA-R in renal cell carcinomas (n = 11). By immunohistochemistry using monoclonal and polyclonal anti-uPA-R antibodies, we found that tumoral capillary endothelial cells (von Willebrand factor and CD31 positive cells) overexpressed uPA-R, whereas vascular endothelial cells of the normal human kidney do not. In addition, tumor-associated macrophages (CD68-positive cells) strongly expressed uPA-R. In contrast, few tumoral cells and stromal fibroblasts expressed uPA-R. By in situ hybridization using a cDNA S35-labeled probe specific for uPA-R, we confirmed the local expression of uPA-R messenger RNA. We also detected the induction of u-PA in tumoral capillary endothelial cells and in tumor-associated macrophages. In two cases, tumoral cells themselves were also stained by anti-u-PA antibodies in focal areas. Finally tissue-type plasminogen activator (t-PA) was also overexpressed by tumoral capillary endothelial cells as compared with endothelial cells of normal human kidney vessels. These findings indicate an active invasive phenotype of endothelial cells in renal cell carcinoma and suggest a role for the plasminogen activation system in tumoral angiogenesis and invasion.

Carcinoma↗
PubMed1997

Endothelial cells of the kidney vasa recta express the urea transporter HUT11.

The cell specific expression of the human urea transporter HUT11 in human and rat kidneys was investigated by immunochemistry and in situ hybridization. Using specific rabbit polyclonal antibodies directed against the N-terminal part and the C-terminal part of HUT11, we found that endothelial cells of medullary vasa recta (outer and inner medulla) express HUT11. In addition, an HUT11-related protein expressed by smooth muscle cells of cortical arterioles can be detected by the anti-HUT11 N-terminal peptide antibody but not the anti-HUT11 C-terminal peptide antibody. The endothelial expression of HUT11 was confirmed by double labeling with anti-CD31 and anti-von Willebrand factor antibodies. No HUT11-positive cells expressed alpha smooth muscle actin, Tamm Horsfall protein, cytokeratin 18, or CAM-L1, a marker of the principal cells of collecting ducts. Medullary vasa recta of developing and mature rat kidneys were also stained with the anti-HUT11 C-terminal peptide antibody. By in situ hybridization using a specific HUT11 35S-cDNA probe on human kidney sections, medullary vasa recta but not other renal structures were found to express HUT11 mRNA. We conclude that endothelial cells of medullary vasa recta express HUT11, a specific urea transporter, which may play a role in urea recycling within the kidney and in the mechanisms of urinary concentration and urea excretion.

Animals↗
PubMed1997

Thrombotic microangiopathy and cytomegalovirus disease in patients infected with human immunodeficiency virus.

Thrombotic microangiopathy (TMA) can occur during the course of human immunodeficiency virus (HIV) infection. Clinical and pathological data for 29 patients with TMA and HIV infection were recorded. In a retrospective case-control study, we analyzed the link between opportunistic infections or drug therapies and TMA. Twenty-five patients (mean CD4+ cell count +/- SD, 71.9 +/- 18.3/mm3) had renal impairment, and four had neurological dysfunction. In one-half the cases, the disease was progressive with isolated fragmentation anemia appearing several months before the clinical symptoms. The diagnosis of TMA was confirmed by histological examination of kidney biopsy specimens (18 cases). Endothelial cytomegalovirus (CMV) inclusions were associated with TMA in nine of 18 cases, whereas histological examination did not detect CMV in any control specimens (P < .001). The case-control study demonstrated a link between TMA and clinical CMV infection (odds ratio, 3.9; 95% confidence interval, 1.1-14). We conclude that TMA is a late complication of HIV infection and can be associated with systemic CMV infection in this setting.

AIDS-Related Opportunistic Infections↗
PubMed1997

[Severe preeclampsia: management. Is conservative treatment justified?].

Severe preeclampsia is a major contributor to maternal and perinatal morbidity and mortality. This review was performed to assess the fetal and maternal benefits of allowing women presenting with severe preeclampsia between 24 and 32-34 weeks of amenorrhea to continue their pregnancy following antihypertensive treatment. After ultrasound scanning to assess growth and biophysical state of the fetus, patients without deteriorating maternal conditions, were managed with volume expansion, antihypertensive drugs (as hydralazine, labetalol, nifedipine), anticonvulsants and prophylactic steroids to promote fetal pulmonary maturity. Previous studies have indicated that this conservative management is also possible with the HELLP syndrome, without an increase in maternal morbidity.

Anticonvulsants↗
PubMed1997

[Autosomal dominant polycystic kidney. Apropos of 2 cases. Review of the literature].

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary disease. Genetic molecular methods can make the diagnosis of at least three different types of ADPKD. ADPKD concerns young people and complications such as hypertension and decreased renal function occur more frequently if onset is early, if it is a type 1, and if the patient is a woman. The pregnant woman with autosomal dominant cystic disease is at particular high risk of obstetrical complications. Prenatal diagnosis is possible.

Adult↗