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Biomedical subjects

F Le Roy

Publications and source records attributed to F Le Roy.

16 recordsLinked to original sources
PubMed2003

[Inflammation markers in daily practice].

Cardiovascular diseases and infections remain the first mortality causes in ESRD patients. European recommendations for good clinical practice in the hemodialysis field advocate to use the inflammation markers in daily practice. These markers foretell both cardiovascular and global mortality. They also enable to detect the silent infections (parodontitis, Heliobacter pilory infection, shunt infection in PTFE), to make sure of the dialysis biocompatibility (microbiological quality of the dialysate, use of biocompatible membrane). The C-reactive protein is the most current and used marker. Its use, combined with the procalcitonin measurement, specific marker for bacterial infection, would enable the diagnostic and therapeutic strategy improvement.

Biomarkers↗
PubMed2001

The 2-5A/RNase L/RNase L inhibitor (RLI) [correction of (RNI)] pathway regulates mitochondrial mRNAs stability in interferon alpha-treated H9 cells.

Interferon alpha (IFNalpha) belongs to a cytokine family that exhibits antiviral properties, immuno-modulating effects, and antiproliferative activity on normal and neoplasic cells in vitro and in vivo. IFNalpha exerts antitumor action by inducing direct cytotoxicity against tumor cells. This toxicity is at least partly due to induction of apoptosis. Although the molecular basis of the inhibition of cell growth by IFNalpha is only partially understood, there is a direct correlation between the sensitivity of cells to the antiproliferative action of IFNalpha and the down-regulation of their mitochondrial mRNAs. Here, we studied the role of the 2-5A/RNase L system and its inhibitor RLI in this regulation of the mitochondrial mRNAs by IFNalpha. We found that a fraction of cellular RNase L and RLI is localized in the mitochondria. Thus, we down-regulated RNase L activity in human H9 cells by stably transfecting (i) RNase L antisense cDNA or (ii) RLI sense cDNA constructions. In contrast to control cells, no post-transcriptional down-regulation of mitochondrial mRNAs and no cell growth inhibition were observed after IFNalpha treatment in these transfectants. These results demonstrate that IFNalpha exerts its antiproliferative effect on H9 cells at least in part via the degradation of mitochondrial mRNAs by RNase L.

ATP-Binding Cassette Transporters↗
PubMed2000

Characterization of RNABP, an RNA binding protein that associates with RNase L.

The 2',5'-oligoadenylate (2-5A)/RNase L pathway is one of several enzymatic pathways induced by interferons (IFN). RNase L is a latent endoribonuclease that is activated on its binding by 2-5A and inhibited by the ribonuclease L inhibitor (RLI). We have shown previously by coimmunoprecipitation that RNase L may be associated with a 90-kDa RNA binding protein (RNABP), identified with a monoclonal antibody (mAb) raised against an RNase L complex purified under native conditions on 2-5A-sepharose. Here we confirm, by gel-filtration and pull-down analysis, the association of RNase L and RNABP, and we demonstrate that this association is significantly increased in the presence of 2-5A. Moreover, we found that RNABP protein levels decrease during terminal differentiation in various cell lines but do not vary during vesicular stomatitis virus (VSV) or encephalomyocarditis virus (EMCV) infection or following IFN-alpha/beta treatment. In this latter case, although total cellular RNABP levels do not vary, the amount of RNABP found in the cytoplasm increases in comparison to that found in the nucleus, indicating a cytoplasmic localization of RNABP after IFN-alpha/beta treatment. Finally, we demonstrate the interaction between RNase L and RNABP in intact cells. Microinjection of an mAb against RNABP into HeLa cells inhibits RNase L antiviral activity and partially inhibits the IFN-alpha/beta-induced antiviral activity.

Adenine Nucleotides↗
PubMed2000

The 2'-5' oligoadenylate/RNase L/RNase L inhibitor pathway regulates both MyoD mRNA stability and muscle cell differentiation.

The 2'-5' oligoadenylate (2-5A)/RNase L pathway is one of the enzymatic pathways induced by interferon. RNase L is a latent endoribonuclease which is activated by 2-5A and inhibited by a specific protein known as RLI (RNase L inhibitor). This system has an important role in regulating viral infection. Additionally, variations in RNase L activity have been observed during cell growth and differentiation but the significance of the 2-5A/RNase L/RLI pathway in these latter processes is not known. To determine the roles of RNase L and RLI in muscle differentiation, C2 mouse myoblasts were transfected with sense and antisense RLI cDNA constructs. Importantly, the overexpression of RLI in C2 cells was associated with diminished RNase L activity, an increased level of MyoD mRNA, and accelerated kinetics of muscle differentiation. Inversely, transfection of the RLI antisense construct was associated with increased RNase L activity, a diminished level of MyoD mRNA, and delayed differentiation. In agreement with these data, MyoD mRNA levels were also decreased in C2 cells transfected with an inducible RNase L construct. The effect of RNase L activity on MyoD mRNA levels was relatively specific because expression of several other mRNAs was not altered in C2 transfectants. Therefore, RNase L is directly involved in myoblast differentiation, probably through its role in regulating MyoD stability. This is the first identification of a potential mRNA target for RNase L.

ATP-Binding Cassette Transporters↗
PubMed1997

[Interstitial nephropathies of toxic or drug origin. New causes, new prospects].

PHENOTYPING INTERSTITIAL INFILTRATIONS: Recent progress has led to the distinction between type I and type II fibroblasts in the renal interstitium. The cellular phenotype of pathological infiltrations can be identified with monoclonal antibodies. DRUG-INDUCED INTERSTITIAL NEPHROPATHIES: Extrarenal manifestations (skin eruptions, fever, joint pain) often suggests the diagnosis but may be absent, in which case renal histology is required. CAUSAL DRUGS: Among the different causal agents, nonsteroid anti-inflammatory drugs cause abnormal leakage from glomerular capillaries favoring the development of a nephrotic syndrome associated with renal failure and major cell infiltration into the interstitial tissue. CHRONIC DISEASE: Chronic interstitial nephropathy is nearly asymptomatic and may only be discovered at an advanced stage. Briefly, there are three categories which result from long-term administration of 5-aminosalicylate, use of Chinese herbal medicines to lose weight, and chronic intoxication with ochratoxin (a mycotoxin). COMPLEX PHYSIOPATHOLOGY: Immunological mechanisms are involved although it is not always easy to distinguish between manifestations of humoral and cellular reactions. Both could be implicated as indicated in recent experimental animal models which throw more light on the pathological process in humans. RENAL PROGNOSIS: Different strategies can be used to halt or limit the development of fibrosis and thus improve prognosis of toxic interstitial nephropathies: counteract cellular immunity reactions, inhibit fibroblast proliferation and activation, reduce synthesis and stimulate degradation of the extracellular matrix, and inhibit collagen formation.

Acute Disease↗
PubMed1997

Altered flow-dependent vasodilatation of conduit arteries in maintenance haemodialysis.

BACKGROUND: An altered arterial nitric oxide (NO) pathway could partly explain the damage to arteries observed in haemodialyzed (HD) patients. The present study was designed to non-invasively evaluate the NO pathway of peripheral conduit arteries in HD patients. METHODS: Twelve normotensive, non-diabetic HD patients treated with erythropoietin and 12 matched healthy controls (C) were included in the study. The effect of endogenous release of NO was assessed by measuring the flow-dependent vasodilatation of the radial artery (post-ischaemic hyperaemia), and the response to exogenous NO assessed using sublingual glyceryl trinitrate administration (GTN). RESULTS: Radial artery diameter (echo-tracking), radial blood flow (RBF: Doppler) and mean arterial pressure (Finapres) were identical at baseline in HD patients and in healthy subjects. The flow-dependent vasodilatation of the radial artery was decreased in HD patients (C: 9 +/- 1% vs HD: 3 +/- 05%, P < 0.05). The decrease in radial vascular resistance (C: -44 +/- 4% vs HD: -24 +/- 2%, P < 0.05) and the increase in radial diameter (C: 31 +/- 2% vs HD: 25 +/- 2%, P < 0.05) after GTN administration were less in HD patients than in controls. The ratio between the increase in diameter after hyperaemia to the increase in diameter after GTN, was also diminished in HD patients (C: 30 +/- 3% vs HD: 13 +/- 2%, P < 0.001). CONCLUSIONS: The flow-dependent vasodilatation of peripheral conduit arteries is altered in HD patients and is associated with a slight but significant decrease in the vasodilating response to exogenous NO. These results suggest, in the absence of changes in basal radial vascular resistance and arterial diameter, more a decrease in endothelial NO bioavailability, than an increase in basal vascular tone.

Administration, Sublingual↗
PubMed1996

[Nephrotic syndrome complicating treatment with interferon alpha].

UNLABELLED: We report two cases of nephrotic syndrome with minimal glomerular change complicating alpha-interferon therapy. CASE REPORTS: The first patient was a 60-year-old man with Waldenström's disease who was given 1 million units of alpha-interferon three times a week for 22 months. Acute renal failure developed when a second protocol was started. Renal biopsy revealed intraglomerular deposits and no cellular proliferation. Total remission could not be achieved with corticosteroids. The second case was a 46-year-old man given high dose alpha-interferon (15 million units 3 times a week) for lymph node metastasis of a malignant melanoma. A nephrotic syndrome without renal failure developed during the third month of treatment. Minimal glomerular involvement was seen. Symptomatic treatment led to resolution of the nephrotic syndrome. DISCUSSION: Nine other cases of nephrotic syndrome complicating alpha-interferon therapy have been reported in the literature.

Acute Kidney Injury↗
PubMed1995

[Functional acute kidney failure].

Prerenal acute renal failure is defined as a reduction in the glomerular filtration rate due to a primary disturbance in renal hemodynamics in the absence of any structural kidney damage. In case of moderate hypotension or hypovolemia, a number of adaptative systemic and intrarenal responses preserve renal perfusion and filtration rates, particularly by inducing a marked reduction in preglomerular arteriolar resistance and an increase in postglomerular resistance. However, these mechanisms are inherently limited. In the presence of advanced circulatory failure or iatrogenic pharmacologic interventions compromising these renal defense mechanisms, prerenal failure becomes evident. Therefore, prerenal failure may occur during acute hemodynamic disturbances due to hypovolemia or systemic vasodilatation, in severe cardiac failure, in cirrhosis with ascites, and in certain clinical situations following administration of nonsteroidal antiinflammatory agents or angiotensin converting enzyme inhibitors. The treatment depends on the underlying cause.

Acute Kidney Injury↗