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Biomedical subjects

M Revel

Publications and source records attributed to M Revel.

At least 73 records · Page 4Linked to original sources
PubMed1998

Interleukin-6 functions in autoimmune encephalomyelitis: a study in gene-targeted mice.

The encephalitogenic peptide pMOG 35-55 from the myelin oligodendrocyte glycoprotein was used to induce experimental autoimmune encephalomyelitis (EAE) in H-2b mice with the interleukin-6 (IL-6) gene intact or disrupted. The IL-6+/+ mice developed a chronic form of EAE ascending paralysis, whereas the IL-6-/- mice were resistant to the disease. Injections of recombinant IL-6 following pMOG immunization induced severe disease in the IL-6-/- mice. Histological examination of brain and spinal cord sections showed that the perivascular infiltration of inflammatory cells evident in IL-6+/+ mice was absent in the IL-6-/- animals and could be restored by exogenous IL-6 administration. Anti-MOG antibody levels were much lower in the IL-6-/- mice, but were not restored to high levels by IL-6 injections which elicited the development of pMOG 35-55-induced EAE. T lymphocytes reactive to the pMOG antigen were recovered from lymph nodes of both types of mice and Tcell lines could be established from both. Adoptive transfer of Tcell lines from IL-6+/+ mice induced EAE in the mice with the intact IL-6 gene but less in the IL-6-deficient mice, indicating that the resistant phenotype cannot be explained solely by lack of encephalitogenic Tcells. The absence of cell infiltrates in the brain and spinal cords of IL-6-/- mice upon adoptive transfer of the pathogenic Tcells from IL-6+/+ mice is consistent with a function of IL-6 in the local perivascular inflammatory process.

Adoptive Transfer↗
PubMed1998

Plantar flexion force is related to calcaneus bone ultrasonic parameters in postmenopausal women.

The aim of this report was to study the relationship between the plantar flexion strength produced by contraction of the triceps surae (gastrocnemii-soleus) muscle and the calcaneus bone parameters assessed by quantitative ultrasound in 45 healthy postmenopausal women. Plantar flexion strength was related to calcaneus broadband ultrasound attenuation (BUA) (r = 0.43, P = 0.003) and to speed of sound (SOS) (r = 0.3, P = 0.04). Plantar flexion appeared to predict ultrasonic properties, independently of body weight (R2 = 19% and 9% for BUA and SOS, respectively). These results suggest that the stresses related to locomotion locally enhance bone remodeling but further studies are needed to identify the respective role of the compressive strains related to ground reaction forces at heel-strike and the muscular tensile strains applied on the calcaneus where the calcaneal tendon is inserted.

Calcaneus↗
PubMed1998

Spondylarthropathy treatment: progress in medical treatment, physical therapy and rehabilitation.

The monitoring and treatment of the diseases belonging to the concept of spondylarthropathy are related more to their clinical presentation, for example axial versus peripheral involvement, than to the precise diagnosis, for example, ankylosing spondylitis versus psorìatic arthritis. For each clinical presentation the treatment comprises local and systemic routes of administration but also drug and non-drug therapies.

Antirheumatic Agents↗
PubMed1998

Increased sensitivity of IL-6-deficient mice to carbon tetrachloride hepatotoxicity and protection with an IL-6 receptor-IL-6 chimera.

Interleukin-6 (IL-6)-deficient mice were found to be much more sensitive to liver injury by carbon tetrachloride (CCl4) than mice with an intact IL-6 system. At doses of CCl4 ranging from 2 to 3.5 ml/kg body weight, mean mortality in the IL-6 gene knockout (IL-6-/-) mice was 71% at 24 hours versus 12% in normal IL-6+/+ mice. At sublethal doses, there was extensive parenchymal necrosis in the livers of IL-6-deficient mice, which was not seen in the control animals. Lipid peroxidation induced by CCl4 was up to 10-fold higher in the IL-6-/- mice. Injections of a chimeric protein containing IL-6 fused to its soluble receptor (IL-6R-IL-6 chimera) induced hepatocyte protection against CCl4 damage in both IL-6-/- and IL-6+/+ mice. Treatment with IL-6R-IL-6 restored the survival of the IL-6-/- mice to the level of IL-6+/+ animals. Free IL-6 was not effective in reducing CCl4-induced liver toxicity, but was as effective as IL-6R-IL-6 in reducing death from metastases in a murine melanoma model. Hence the IL-6R-IL-6 chimera appears to be particularly effective against chemical hepatotoxic injury.

Aldehydes↗
PubMed1997

Unmasking by soluble IL-6 receptor of IL-6 effect on metastatic melanoma: growth inhibition and differentiation of B16-F10.9 tumor cells.

Interleukin-6 (IL-6) inhibits the growth of melanocytes and of early stage melanoma cells, but not that of advanced melanoma cells. The in vitro IL-6 response can be restored in the highly metastatic melanoma B16-F10.9 by addition of recombinant soluble IL-6 receptor alpha-chain (sIL-6R). The F10.9 cells then undergo irreversible growth-arrest and show increased adherence with changes from epithelioid to spindleoid morphology. The sIL-6R is required for IL-6 to induce a sustained activation of the various Stat transcription factors which bind to specific IL-6 inducible enhancers. The sIL-6R and IL-6 combination causes an increase in the level of the anti-oncogenic transcription factor IRF-1 protein and DNA-binding, which remain elevated for 24 h. The promoter activity of the anti-oncogenic p21/Waf-1/Cip-1 gene is induced and accumulation of the p21 protein is observed. These results illustrate the potent agonist activity of sIL-6R on molecular pathways which could mediate the growth-arrest and differentiation of the metastatic melanoma cells. Previously observed antimetastatic effects of IL-6 therapy in mice bearing F10.9 tumors may be at least partly due to direct growth inhibition and differentiation elicited by sIL-6R present in biological fluids.

Animals↗
PubMed1997

Interferon-beta and -gamma, but not tumor necrosis factor-alpha, demonstrate immunoregulatory effects on carcinoma cell lines infected with human papillomavirus.

BACKGROUND: Mechanisms whereby cells infected with human papillomavirus (HPV) escape immune surveillance, ultimately leading to invasive cervical carcinoma, may involve changes in local cytokine production, loss of responsiveness to cytokines, and alterations in the expression of immune-regulatory molecules such as histocompatibility-related leukocyte antigen (HLA) Class 1 and 2 and ICAM-I. This study examined the separate and combined effects of immune-activating cytokines, interferon (IFN)-gamma, IFN-beta, and tumor necrosis factor (TNF)-alpha, on the expression of these molecules. METHODS: Membrane protein expression and cellular mRNA levels were analyzed in cervical carcinoma-derived cell lines, SiHa and CaSki (with low and high HPV16 copy number, respectively), after exposure to cytokines. RESULTS: Both cell lines demonstrated constitutive expression of HLA Class 1 but not HLA Class 2 membrane antigens. IFN-gamma and -beta induced changes in Class 1 mRNA levels but not in membrane molecule expression. IFN-gamma induced dose-dependent expression of Class 2 membrane and mRNA molecules in both cell lines (more pronounced in SiHa than in CaSki cells), which was antagonized by IFN-beta. Constitutive ICAM-I membrane expression was observed only on CaSki cells, although ICAM-I mRNA was expressed in both cell lines. IFN-gamma up-regulated the membrane expression of this molecule, whereas IFN-beta led to its suppression. Differential modulation of ICAM-I mRNA was observed in both cell lines. A lack of response to TNF-alpha was observed throughout the experiments. CONCLUSIONS: The findings of this study point to possible mechanisms leading to suppression of local immune response in the pathogenesis of HPV-associated neoplasia. They also emphasize the complexity of developing an efficient cytokine therapy for patients with premalignant cervical disease.

Adjuvants, Immunologic↗
PubMed1997

A protein-arginine methyltransferase binds to the intracytoplasmic domain of the IFNAR1 chain in the type I interferon receptor.

The intracytoplasmic domain (IC) of cytokine receptors provides docking sites for proteins which mediate signal transduction. Thus, in interferon-alpha,beta receptors (IFNAR1 and 2), the IC region binds protein-tyrosine and -serine/threonine kinases which phosphorylate the receptor and the associated Stat transcription factors. A two-hybrid screening was carried out to identify additional proteins which could interact with the IC domain of the IFNAR1 chain of the IFN-alpha,beta receptor. Several positive clones representing a protein sequence designated IR1B4 were recovered from a human cDNA library. IR1B4 was identified as the human homolog of PRMT1, a protein-arginine methyltransferase from rat cells. Flag-IR1B4 fusion proteins bind to the isolated IFNAR1 intracytoplasmic domain produced in Escherichia coli, as well as to the intact IFNAR1 chain extracted by detergent from human U266 cell membranes. S-Adenosylmethionine-dependent methyltransferase activity was precipitated by anti-IFNAR1 antibodies from untreated human cells. IR1B4/PRMT1 is involved in IFN action since U266 cells rendered deficient in this methyltransferase by antisense oligonucleotides become more resistant to growth inhibition by IFN. Methylation of proteins by enzymes which can attach to the IC domains of receptors may be a signaling mechanism complementing protein phosphorylation. Among substrates methylated by PRMT1 are RNA-binding heterogeneous nuclear ribonucleoproteins (hnRNPs) which are involved in mRNA processing, splicing and transport into the cytoplasm.

Animals↗
PubMed1997

Selective electromyography of dorsal neck muscles in humans.

The patterns of activation of splenius capitis, semispinalis capitis, transversospinalis, and levator scapulae muscles were studied during various head-neck positions, movements, and isometric tests in 19 healthy human subjects. Myoelectric activities were recorded with intramuscular bipolar wire electrodes. Cervical computerized tomography of each subject was performed before the electromyography session in order to guide electrode insertion. Head motion was recorded using an electromechanical device. This report demonstrates that head motion results from a complex interaction of active muscular forces, passive ligamentous forces, and gravity. Splenius capitis has two main functions, i.e., cervical extension and ipsilateral rotation. Semi spinalis capitis and the transversospinalis are mainly extensors, and levator scapulae acts primarily on the shoulder girdle. Splenius capitis, semispinalis capitis, and transversospinalis play a subordinate part in ipsilateral tilting. In addition, most subjects' semispinalis capitis were gradually recruited during ipsilateral rotation. No signal was detected from the transversospinalis during rotation tests.

Adult↗
PubMed1997

Effect of psoas training on postmenopausal lumbar bone loss: a 3-year follow-up study.

The present study completed a previous randomized trial that demonstrated the protective effect of 1-year psoas training on lumbar bone loss in postmenopausal women. Computerized tomography had been carried out at the beginning (CT1) and at the end (CT2) of this trial. In the present study, 67 women having completed the first trial were asked to practice psoas exercises (60 hip flexions in sitting position with a 5 kg weight on the knee) for 2 additional years with a third CT control at the end of this period (CT3). The aim of this complementary study was to assess the compliance rate and long-term effect on bone of daily psoas muscle training over a longer period. Twenty-one women performed this daily psoas training for 3 years from CT1 to CT3, and 14 acted as controls during the same period. Fourteen women were controls during the first year (from CT1 to CT2) but practiced psoas training during the following 2 years (from CT2 to CT3). Four women were psoas trained during the first year (from CT1 to CT2) and subsequently crossed over to the control group for the last 2 years. The compliance rate was 42%, with an attendance rate of 88%. The lumbar bone loss was lower in the 21 women trained over the 3 years (-3.26 +/- 28.45 mg/cm3) than in the 14 untrained women (-16.79 +/- 8.51 mg/cm3) (P = 0.02). The bone loss was not significantly reduced between the two periods of the study in the 12 women having been controls from CT1 to CT2 and having crossed over to the active training group from CT2 to CT3. Psoas training may be effective against lumbar bone loss. We conclude that specific training may play a contributing role in the preventive strategy to avoid osteoporosis.

Anthropometry↗
PubMed1997

Prolonged effects of 3 week therapy in a spa resort on lumbar spine, knee and hip osteoarthritis: follow-up after 6 months. A randomized controlled trial.

Spa therapy is frequently used in daily rheumatological practice, but its benefit remains to be evaluated. A prospective randomized controlled study was conducted in 1993 in patients with osteoarthritis of the hip, knee or lumbar spine. Treatment was either spa therapy at Vichy (France) of 3 weeks duration (spa group) or usual therapy (control group). Assessment criteria were pain (visual analogue scale), functional impairment (Lequesne's index for hip or knee disease, Main and Waddell's for lumbar spinal diseases), quality of life index [revised Arthritis Impact Measurement Scale (AIMS2)], and analgesic and/or non-steroidal anti-inflammatory drug (NSAID) consumption. Patients were included by randomization into one of the two arms (spa or control) and assessment criteria were collected before spa therapy or the control period, and 3 and 24 weeks thereafter. A total of 188 patients (lumbar spine 95, knee 64, hip 29) were included in the study (spa group 91, control group 97). Changes in the assessment criteria after a 6 month follow-up period showed improvement in terms of pain, functional impairment and quality of life, with a reduced intake of symptomatic drugs (NSAID and analgesic drugs) in the spa group. This study suggests that spa therapy of 3 weeks duration has a prolonged, beneficial, symptomatic effect in osteoarthritis.

Aged↗
PubMed1997

Incidence of antibodies to interferon-beta in patients treated with recombinant human interferon-beta 1a from mammalian cells.

Patients receiving recombinant human interferon-beta 1a (IFN-beta 1a) produced in Chinese hamster ovary (CHO) cells were tested for the formation of neutralizing antibodies (NABs) to IFN-beta. Samples were tested in an enzyme-linked immunosorbent assay (ELISA), and if positive were then tested for neutralization of antiviral activity in an IFN-beta bioassay. A total of 793 patients with viral diseases, premalignant and malignant diseases, and multiple sclerosis received IFN-beta 1a in clinical studies. Long-term studies included 56 patients with cancer treated for 6 or 12 months and 334 patients with multiple sclerosis (MS) at the end of one year of treatment. All of the NAB-positive patients were found in the latter. Positivity in a single specimen was found in 14.4% of the MS patients. The incidence of sustained neutralizing antibody titres (i.e. positive in two tests at least 6 months apart) was 6.9% in this group. Comparison with results from other studies suggests that CHO-derived IFN-beta 1a induces less neutralizing antibody than IFN-beta 1b produced in E. coli.

Animals↗
PubMed1997

Interleukin-6 receptor-interleukin-6 fusion proteins with enhanced interleukin-6 type pleiotropic activities.

An sIL-6R/IL-6 chimera, directly fusing the natural forms of soluble IL-6 receptor and IL-6, as found in human body fluids, was produced in transfected human cells. The secreted p85 glycoprotein was active at a concentration of 120 pM to produce growth-arrest and spindleoid differentiation of murine melanoma F10.9 cells, which do not respond to IL-6 alone. This fusion protein was as active as the yeast-produced p56 fusion protein containing a shortened sIL-6R, linked through a flexible peptide chain to IL-6 (Hyper IL-6). The concentration of Hyper IL-6 needed to arrest the growth of F10.9 cells was much lower than that needed of a combination of IL-6 and sIL-6R, added separately. Hyper IL-6 was also more active than IL-6 in stimulating growth of murine plasmacytoma T1165 cells, the half maximal stimulation being obtained at 2 pM Hyper IL-6 versus 23 pM for IL-6. In order to evaluate the effect of the fused sIL-6R/IL-6 proteins on human hematopoietic primitive progenitor cells, they were added to suspension cultures of CD34+ cells from human cord blood in addition to both flt3/flk2 ligand (FL) and stem cell factor (SCF). Fused sIL-6R/IL-6 produced a marked stimulation of cell expansion and a marked increase in the number of colony forming units when subsequently plated in semi-solid medium with IL-3, GM-CSF, SCF and erythropoietin. Ex-vivo maintenance and expansion of early progenitor cells in bone marrow transplantation protocols may be a potential application for the sIL-6R/IL-6 chimeric glycoproteins.

Animals↗
PubMed1996

[Lumbar osteoarthritis].

Lumbar osteoarthritis involves both the disc and the facet joints. Measurements of the disc space evaluates the degeneration. There is no radio-clinical correlation at a given time. There are however inflammatory phases in facets arthrosis and discolysis with disc narrowing within few months. These attacks are responsive to NSAID'S and local injections of corticosteroids. The chronic back pain needs only analgesics and rehabilitation. Osteophytes can narrow the spinal canal and induce back and leg pains. Except neurological weakness and bladder dysfunction the medical treatment should be prolonged before the indication of surgery.

Back Pain↗
PubMed1996

A soluble interleukin 6 receptor isolated from conditioned medium of human breast cancer cells is encoded by a differentially spliced mRNA.

The human interleukin 6 receptor (IL-6R) is expressed on cells as a transmembrane protein of 80 kDa (gp80, ligand binding unit), or as a smaller soluble counterpart (sIL-6R, approximately 55 kDa). Recombinant or natural sIL-6Rs bind IL-6 and stimulate biological activity by association with the signal transducing subunit gp130 at the cell surface. The origin of sIL-6Rs is not clear. Haematopoietic cells express, in addition to the gp80 mRNA, an IL-6R mRNA where the transmembrane domain is spliced out, predicting a shorter protein with a modified basic sequence at the C-terminus. We show that the spliced mRNA is expressed in human T47D breast carcinoma cells and soluble IL-6R protein is indeed secreted by these cells. An antibody against the C-terminus of the spliced protein detects a 55-65 kDa glycosylated species in sIL-6R purified from T47D supernatant by classical and immunoaffinity chromatography. The spliced T47D IL-6R, glycosylated or after removal of O- and N-linked polysaccharides, has the same size as a recombinant spliced IL-6R from CHO cells. The recombinant spliced IL-6R acts on cells as an IL-6 agonist to stimulate transcription from IL-6 inducible enhancers.

Antigens, CD↗
PubMed1996

Immunoregulatory effects of interferon-beta and interacting cytokines on human vascular endothelial cells. Implications for multiple sclerosis autoimmune diseases.

The mechanism(s) of action responsible for the anti-inflammatory effects mediated by interferon (IFN)-beta are still elusive although suggestions include anti-viral effects, the enhancement of natural killer (NK) or suppressor T cell activity and opposition to the effects of inflammatory cytokines. As vascular endothelial cells are active participants in inflammatory and demyelinating processes, we decided to examine the effects of IFN-beta on the expression of major histocompatibility complex (MHC) gene products and intercellular adhesion molecule (ICAM)-1 on human vascular endothelial cells (ECs). Human umbilical ECs demonstrated constitutive expression of ICAM-1 and MHC class I molecules but did not express MHC class II molecules. Basal expression of ICAM-1 molecules was enhanced by TNF alpha and to a lesser extent by IFN-beta, but was not affected by IFN-gamma. MHC class I expression on ECs was enhanced by IFN-beta, IFN-gamma, and tumor necrosis factor (TNF)-alpha. Furthermore, a synergistic effect was observed to combinations of these interacting cytokines. Incubation of ECs with IFN-gamma, but not IFN-beta, induced class II expression in a dose dependent manner. Moreover, co-incubation of ECs with IFN-beta and IFN-gamma resulted in significant down-regulation of class II molecules expression which was directly dependent on IFN-beta concentration. Northern blot analysis of DR alpha and Beta 2-microglobulin mRNA expression suggested that cytokine-mediated regulation of MHC molecules is at the transcriptional level, while modulation of ICAM-1 expression appears to be at the transcriptional as well as post-transcriptional level. Thus, our study demonstrated that IFN-beta and interacting cytokines exert complex immunoregulatory effects on endothelial cells with differential modulatory effects on various cell surface markers. Understanding the biological significance of these immunomodulatory effects mediated by IFN-beta may have important implications for cytokine-based strategies in the treatment of inflammatory and autoimmune diseases.

Autoimmune Diseases↗