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Biomedical subjects

M Revel

Publications and source records attributed to M Revel.

At least 109 records · Page 6Linked to original sources

Longus colli has a postural function on cervical curvature.

To determine the postural role of longus colli (LC) and dorsal neck muscles, we have studied the relationship between their cross-sectional areas related to their force of contraction and the lordosis and the length of the cervical spine. This study was carried out in 36 healthy subjects. Muscle cross-sectional areas were measured by computerized tomography. The index of lordosis and the length of the cervical spine were measured on an X-ray profile. The cross-sectional area of LC was correlated to the lordosis index (R = -0.432, p < 0.02) whereas all the other parameters were not correlated. The authors conclude that LC counteracts the lordosis increment related to the weight of the head and to the contraction of the dorsal neck muscles. Postural functions of LC and postcervical muscles are complementary. They form a sleeve which encloses and stabilizes the cervical spine in all positions of the head.

Adult↗

Changes in cervicocephalic kinesthesia after a proprioceptive rehabilitation program in patients with neck pain: a randomized controlled study.

Head repositioning accuracy (HRA) after full range active motion was evaluated in 60 cervicalgic patients. The mean angular error was 7.7 degrees +/- 3.3 (mean +/- SD) and 82% were outside a threshold value of 4.5 degrees. After randomization 30 patients followed a rehabilitation program based on eye-head coupling (RG) and 30 served as a control group (CG). At 10 week follow-up, a greater gain in HRA was observed in the RG (2 degrees +/- 2.7, mean +/- SD) than in the CG (0 +/- 2.6, mean +/- SD) (p = 0.005). Clinical parameters (pain, drug intake, range of motion, and self assessed functional improvement) were also more improved in the RG than in the CG. These data emphasize the role of a neck proprioception alteration in chronic neck pain and suggest that a rehabilitation program based on eye-head coupling should be included in most medical management of cervicalgic patients.

Adult↗

The human interferon alpha-receptor protein confers differential responses to human interferon-beta versus interferon-alpha subtypes in mouse and hamster cell transfectants.

The human interferon alpha-receptor (IFNAR gene product or IFN alpha R protein) was expressed in hamster CHO cells and in mouse A9 cells. The response of the IFN alpha R cDNA transfectants to human IFNs was studied by measuring induction of (2'-5') A synthetase (2'-5' AS). In the murine cells, the IFN alpha R protein conferred response to the human IFN-alpha-8 (alpha-B) subtype, but not to huIFN-alpha-2 (alpha-A) or to huIFN-beta. In murine huIFN alpha R cDNA transfectants, containing a hygromycin B resistance gene placed under the control of the 2'-5' AS gene Interferon Response Sequence (IRS), survival and growth of the cells in the presence of hygromycin B was induced by huIFN-alpha-8 but not by huIFN-alpha-2, indicating that the effect of huIFN alpha R is transcriptional. In hamster CHO cells, the huIFN alpha R protein conferred a completely different pattern of response to human IFN subtypes. Thus, the CHO-IFN alpha R transfectants responded to huIFN-beta by 2'-5' AS induction as well as by activation of the ISGF3 and IRF-1 transcription factors. In contrast, the CHO-IFN alpha R cells showed no response to huIFN-alpha-8. The differential response conferred by the huIFN alpha R protein in the two types of rodent cells, indicates that IFN subtype recognition is influenced by another component contributed by the rodent host cell. The ability of human cells, and of human-mouse hybrid cells containing human chromosome 21, to respond to all IFN subtypes is likely to depend also on interactions of the IFN alpha R protein with additional receptor components.

2',5'-Oligoadenylate Synthetase↗

[Current therapeutic options in sciatica caused by disk herniation].

The results of reliable therapeutic trials, experimental studies showing that compression is not the only mechanism of nerve root alterations, and mainly, the favorable spontaneous outcome of 95% of the sciatica command a critical approach of all the treatments of sciatica by disc herniation. A disc herniation can be observed in 20% of asymptomatic population. Except neurological complications requiring an early surgical decompression, the management of sciatica should begin by a 2 to 3 months period of medical treatment including analgesic drugs or NSAID, a 8 to 10 day bed rest, epidural corticosteroid injections validated in controlled studies, and a lumbar brace during 4 to 6 weeks. The reference treatment of disc herniation in patients whose conservative treatment failed is conventional surgery. The average rate of failure following decompressive surgery is 15 to 20% and the need for further surgery ranges from 5 to 15%. The main cause of failure is the absence of true compressive herniation before the initial operation. Microscope removal of disc herniation does not lead to better results than the standard procedure and there is a 20% risk of recurrence when only the herniated fragment is removed. The success rate of chemonucleolysis approaches 65-70% but the procedure need a strict care to prevent severe complications. Manual percutaneous discectomy, whatever the procedure are supported only by uncontrolled studies. The only randomized trial in automated percutaneous discectomy versus chemonucleolysis reported a 37% success rate with a one-year follow-up. Benefit/risk ratio should always be considered before every treatment of sciatica.

Humans↗

Inhibition of CT-26 murine adenocarcinoma growth in the rectum of mice treated with recombinant human interleukin-6.

In the present study we evaluated the antitumor effects of recombinant human interleukin-6 (rhIL-6), expressed in Chinese hamster ovary cells, in a murine primary tumor model. We showed that treatment with rhIL-6 substantially inhibited the implantation and growth rates of CT-26 adenocarcinoma tumor cells in the rectal submucosa of syngeneic mice. This effect was achieved by injecting rhIL-6 for 7 consecutive days starting 1 day prior to tumor inoculation. No obvious antitumor effect was noted when rhIL-6 injections started 5 days after tumor inoculation. Analysis of the mechanisms by which rhIL-6 exerts its antitumor effects did not reveal a direct antitumor effect on CT-26 tumor cells or the up-regulation of major histocompatibility complex antigens on these cells. However, infiltration of lymphocytes at the tumor site was observed. Increase of carcinoembryonic antigen by IL-6 was clearly seen in human HT-29 colon carcinoma cells. The possible application of these results for adjuvant immunotherapy of selected colorectal patients and prevention of reimplantation of tumor cells disseminated during surgery is discussed.

Adenocarcinoma↗

Interleukin-6 activates and regulates transcription factors of the interferon regulatory factor family in M1 cells.

Activation of (2'-5') A synthetase gene expression in interleukin-6 (IL-6)-treated myeloleukemic M1 cells correlates with protein binding to the interferon response sequence enhancer (IRS). A new interferon response sequence complex, F6, is induced by IL-6 independently of interferon and is identified here as comprising the interferon regulatory factor-1 (IRF-1) and IRF-2, by use of specific antibodies in DNA mobility shift assays with probes containing IRF binding sites. IRF-1 and IRF-2 have, respectively, positive and negative transcriptional effects on interferon-beta and interferon-inducible genes. In the IL-6-treated M1or cells, IRF-1 binding is activated early and maximally at 1 h, whereas the onset of IRF-2 binding is delayed. In a cell variant M1res, where (2'-5') A synthetase is no more induced, IRF-2 binding is constitutive, and IRF-1 binding is not seen before or after IL-6 treatment. In sensitive M1or cells, IL-6 rapidly induces IRF-1 mRNA, but in M1res cells, IRF-1 mRNA is constitutively high and not changed by IL-6. IRF-2 mRNA levels are also constitutive and not inducible by IL-6 even in M1or cells. The dissociation between induction of mRNAs and of protein binding observed suggests that the activity of the IRF proteins is regulated by IL-6. Transcripts of a third member of the IRF gene family, ICSBP, encoding a protein known to act as repressor, were found to be strongly down-regulated by IL-6. The rapid activation of IRF-1 and the modulation of the other transcription factors of this family may play a role in the early phase of IL-6 action on the M1 cells.

Animals↗

Interleukin-6 inhibits the proliferation of B-chronic lymphocytic leukemia cells that is induced by tumor necrosis factor-alpha or -beta.

Tumor necrosis factor (TNF-alpha) acts as a growth stimulatory factor on leukemic B lymphocytes from many patients with chronic lymphocytic leukemia (CLL). Because TNF induces production of interleukin-6 (IL-6), which has been shown to be a growth factor for myeloma and other transformed B cells, we examined the possibility that IL-6 mediates the growth-stimulatory effect of TNF on B-CLL cells. In fact, we found that IL-6 is an inhibitor of B-CLL growth. The addition of recombinant human IL-6 markedly decreased the TNF-induced B-CLL growth, and this decrease was even greater when soluble IL-6 receptor, known to act as IL-6 agonist, was added with recombinant IL-6. Conversely, neutralizing monoclonal antibodies to IL-6 and to the IL-6 receptor potentiated the growth stimulation of TNF on B-CLL cells, in line with the possibility that IL-6 functions as a negative feedback regulator of an autocrine TNF action on these B-leukemic cells. Evidence is presented that production of IL-6 by monocytes and B cells of CLL patients is low, suggesting that administration of IL-6 may be beneficial in CLL to reduce the eventual growth stimulation by TNF and, possibly, also the deficiency in platelets and Ig production in this disease.

Animals↗

Combined therapy with IL-6 and inactivated tumor cells suppresses metastasis in mice bearing 3LL lung carcinomas.

We investigated the anti-tumor effects of human recombinant interleukin-6 (hrIL-6) on the highly metastatic Lewis lung-carcinoma clone, D122. These cells express high-affinity IL-6 receptors at numbers comparable to the IL-6-dependent murine hybridoma B9 cells; however, IL-6 did not affect D122 cell proliferation or expression of MHC-class-I antigens in vitro. In vivo, treatment of mice bearing D122 tumors in the footpads, with a low dose of IL-6 in 3 daily injections, 4 days a week for 3 weeks, significantly decreased spontaneous metastases. However, only combined treatment of IL-6 and irradiated tumor cells resulted in almost complete protection against spontaneous metastases. Histological analysis confirmed the absence of micrometastases in most of the animals treated by this combination protocol. Analysis of the cytolytic activity of splenocytes at various time points during combined IL-6 and immunotherapy of tumor-bearing mice revealed significant and sustained lysis of the poorly immunogenic D122 carcinoma cells, while splenocytes of control mice could not lyse D122 target cells. Activation of specific immunity was also demonstrated when mice were pre-immunized with hrIL-6 and inactivated D122 cells and challenged with live carcinoma cells 10 days later. Significant growth inhibition of the primary tumor was observed.

Animals↗

One-year psoas training can prevent lumbar bone loss in postmenopausal women: a randomized controlled trial.

On the premise that bone response to exercise is locally controlled, we conducted a randomized trial to evaluate the effects of a 1-year training of psoas muscles (treatment group: TG) versus a 1-year training of deltoid muscles (control group: CG) on the lumbar trabecular bone mineral density (TBMD). TBMD was measured with computed tomography scan. Seventy-eight subjects were included and 67 completed the study. Intention to treat analysis revealed no significant change in TBMD from 0 to 12 months. Data analysis in the 67 remaining women, including both assiduous and nonassiduous subjects, revealed greater bone loss in CG than in TG although the difference was not significant. Similar analysis in a subgroup of subjects who performed the exercises assiduously (TG: n = 23, CG: n = 26) showed that the mean bone loss of all four vertebrae from 0 to 12 months was significantly greater in the CG (-8.87 +/- 12.75 mg/cm3, mean +/- SD) than in the TG (0.14 +/- 11.21 mg/cm3, mean +/- SD, P = 0.01). These results suggest that continuous 1-year psoas training can prevent lumbar bone loss in postmenopausal women and support the hypothesis of local action of physical activity.

Bone Density↗

Abrogation of B16 melanoma metastases by long-term low-dose interleukin-6 therapy.

We investigated the antitumor effects of human recombinant interleukin-6 (hrIL-6) on the highly metastatic B16 melanoma clone F10.9. These tumor cells were found to have very low levels of IL-6 receptors and in vitro IL-6 had no effect on cell proliferation or on the expression of MHC class I antigens. However, in vivo IL-6 was active against the metastatic growth of this tumor in mice, presumably through indirect immune effects. Low-dose IL-6 (1-10 micrograms/day), in three daily injections, 4 days a week, for 3 weeks, strongly inhibited the formation of experimental lung metastases following intravenous tumor cell inoculation. IL-6 therapy could be started even 10 days after tumor injection, when metastases are already established. Moreover, IL-6 treatment of mice bearing F10.9 tumors in the footpads resulted in complete protection against pulmonary spontaneous metastasis and in long-term survival. Histology confirmed the absence of micrometastases in most of the IL-6-treated animals. Analysis of the cytolytic activity of splenocytes at different times during therapy of tumor-bearing mice revealed significant lysis (up to 42%) of the melanoma F10.9 cells in the mice receiving IL-6 but not in the control mice.

Animals↗

Automated percutaneous lumbar discectomy versus chemonucleolysis in the treatment of sciatica. A randomized multicenter trial.

A randomized clinical trial was conducted to compare the results of automated percutaneous discectomy with those of chemonucleolysis in 141 patients with sciatica caused by a disk herniation; 69 underwent automated percutaneous discectomy and 72 were subjected to chemonucleolysis. The principle outcome was the overall assessment of the patient 6 months after treatment. Treatment was considered to be successful by 61% of the patients in the chemonucleolysis group compared with 44% in the automated percutaneous discectomy group. At 1-year follow-up, overall success rates were 66% in the chemonucleolysis group and 37% in the automated percutaneous group. Within 6 months of treatment, 7% of the patients in the chemonucleolysis group and 33% in the discectomy group underwent subsequent open surgery. The complication rates of both treatment groups were low, with the exception of a high rate of low-back pain in the chemonucleolysis group (42%). The results of this trial confirm previous controlled studies on chemonucleolysis and suggest that controlled studies should be carried out before automated percutaneous discectomy can be considered a useful intervention.

Adult↗

Interleukin 6 gene transfection into Lewis lung carcinoma tumor cells suppresses the malignant phenotype and confers immunotherapeutic competence against parental metastatic cells.

To investigate the influence of interleukin 6 (IL-6) production on malignancy of tumor cells we transfected cells of the high-metastatic, low-immunogenic D122 clone of the Lewis lung carcinoma with a mammalian expression vector containing the human IL-6 complementary DNA. In vitro, IL-6 positive transfectants showed growth inhibition that was directly correlated with the levels of IL-6 production. The in vitro growth arrest did not seem to be a function of an autocrine system mediated via the secreted human IL-6 acting on the tumor cell surface receptors since neutralizing antibodies to human IL-6 did not prevent the growth inhibition. Neither did exogenous human recombinant IL-6 affect the growth of D122 cells. In vivo, IL-6 positive transfectants showed reduction of tumorigenicity and significant suppression of metastatic competence in syngeneic, immunocompetent mice. In mature T-cell deficient nude mice, the IL-6 transfectants showed some arrest of local growth but no suppression of lung metastasis. It seems therefore that the reduction of metastatic competence of IL-6 transfectants is primarily a function of stimulation by the transfectants of host T-cell immune responses. Immunization with inactivated high-positive IL-6 transfectants induced high levels of anti-tumor cytotoxic T-lymphocytes and protected mice against metastatic growth of a subsequent graft of parental tumor cells. Moreover, reduction of metastatic growth of parental highly metastatic D122 cells was also achieved when immunization of mice was begun after establishment of the primary parental tumors. Thus, inactivated IL-6 transfectants were effective when used as a cellular vaccine for experimental immunotherapy of metastasis.

Adolescent↗

Antitumor effects of human recombinant interleukin-6 on acute myeloid leukemia in mice and in cell cultures.

Interleukin-6 (IL-6) has been shown to inhibit growth and induce differentiation of several myeloid leukemia cell lines. In this work, two in vivo models of acute myeloid leukemia (AML) in mice have been used to test the therapeutic potential of recombinant human IL-6. In mice inoculated by a transplantable AML tumor, IL-6 injections inhibited the development of leukemia and increased survival. The effect was related to dose and length of treatment. In a model of radiation-induced leukemogenesis in SJL/J mice, administration of low-dose IL-6 for 10 days, 4 months after irradiation, reduced the incidence of leukemia observed during 1 year, whereas granulocyte-macrophage colony-stimulating factor (GM-CSF) increased the incidence of leukemia. In vitro liquid cultures of leukemic blood cells obtained from AML patients showed that IL-6 slowed growth and decreased the proportion of blasts with an increase in more mature myeloid elements in 72% of M1, M2, M4 AML cases. In contrast, GM-CSF less often produced differentiation but stimulated leukemic cell growth in liquid cultures, without synergism by IL-6.

Animals↗

[Sciatica or herniated disk].

Lumbar radiculalgia may be due, beside the disc-nerve root conflict, to stenosis of osteoarticular canals, wide dural sac, epidural lipomatosis, segmental arachnoiditis, malignant or benign tumours and meningoradiculitis. Extraspinal truncular or radicular sciatica is usually due to compression by an expansive process. Some types of pain referred from articular structures may mimic sciatica.

Back Pain↗

Enhancement of interleukin 6 cytostatic effect on human breast carcinoma cells by soluble IL-6 receptor from urine and reversion by monoclonal antibody.

Interleukin 6 receptor soluble urinary protein (IL-6-R-SUP), a purified urinary protein binding IL-6 and identified as a truncated 50 kDa soluble form of the 80 kDa IL-6 cellular receptor, was tested for its biological activity. Addition of IL-6-R-SUP enhances the growth stimulation of mouse plasmacytoma T1165 by subliminal concentrations of human recombinant IL-6. Since this effect could be due to a lower affinity of human IL-6 for the mouse cell receptor, we tested the effect of IL-6-R-SUP on human cells. We show that the growth-inhibitory effect of IL-6 on breast carcinoma cells is enhanced by addition of IL-6-R-SUP to these human cells although they possess abundant IL-6 receptors. With IL-6-R-SUP, complete growth inhibition by IL-6 could be achieved and the cells became more sensitive to low levels of IL-6. These effects were prevented by a monoclonal antibody against IL-6-R-SUP which blocks IL-6 binding to cells. The naturally occurring IL-6-R-SUP may help to increase the growth-regulatory action of IL-6.

Animals↗