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Biomedical subjects

F Blanchard

Publications and source records attributed to F Blanchard.

At least 55 records · Page 3Linked to original sources

Epitope-function relationships of human leukemia inhibitory factor receptors using a novel set of anti-gp190 mAB.

The binding and functional properties of a set of six mAb directed against the human gp190 [leukemia inhibitory factor (LIF) receptor] signal transducing molecule were determined. Each of the antibodies reacted with a distinct epitope on gp190 expressed either by gp190-transfected Chinese hamster ovary cells or by the LIF receptor-positive choriocarcinoma JAR cell line. Two of the antibodies (1B4 and 6E6) had binding stoichiometries that were approximately 2-fold lower than those of other mAb (10B2, 12D9 and 7G7), suggesting either that gp190 is present as a pre-associated homodimer in the cell membrane or that part of gp190 is pre-associated with another component. Two mAb (1C7 and 1B4) were found to inhibit LIF binding on the two cell types studied. On JAR cells, this inhibition was, however, restricted to the high-affinity LIF component, suggesting different modes of LIF engagement with the low- and high-affinity receptor species. mAb 1C7 and 1B4 were also found to synergize for inhibiting LIF high-affinity binding. This synergy also extended to the inhibition of LIF- or oncostatin M (OSM)-induced proliferation of a Ba/F3 cell line co-transfected with human gp130 and gp190. However, this mAb combination inhibited LIF- but not OSM-induced haptoglobin secretion by HepG2 cells, suggesting that whereas haptoglobin secretion induced by LIF involves gp130/gp190 common LIF/OSM type I receptors, that induced by OSM mainly involves type II OSM receptors.

Animals↗

Life events and disability in rheumatoid arthritis: a European cohort.

The objective was to study the relationship between life events (LE) and the clinical status of patients suffering from recently diagnosed rheumatoid arthritis (RA) in a 2 yr follow-up. As part of a multicentre European cohort study, 370 French and Dutch patients were questioned three times at 1 yr intervals about LE which had occurred in the previous year. Three criteria were used to quantify the degree of disease activity (Ritchie's index), the level of functional disability [Health Assessment Questionnaire (HAQ)] and perceived health [Overall Evaluation of Health (OEH)]. Total LE and desirable LE showed a weak negative correlation with the HAQ scores. On the other hand, death-related LE did not seem to modify patient status. The higher the number of health-associated LE, the greater the deterioration in HAQ and OEH scores. The results indicate that LE do not affect the course of early RA in a spectacular manner.

Adult↗

Leukemia inhibitory factor (LIF) and oncastsin M (OSM) high affinity binding require additional receptor subunits besides GP130 and GP190.

The structure of Leukaemia Inhibitory Factor (LIF) and Oncostatin M (OSM) receptors is not completely resolved. Heterodimerization of gp190 and gp130 has been proposed to form a high affinity receptor (type I) shared by LIF and OSM, while heterodimerization of gp130 with an as yet unidentified subunit is proposed to form a high affinity OSM receptor (type II) not shared by LIF. We have analysed the binding stoichiometries, cross-competition properties and cross-linking patterns of LIF and OSM to the choriocarcinoma JAR cell line. The data obtained are not fully accounted for by the model proposed above. They indicate rather that third chains of 140-150 kDa molecular mass, in addition to the gp130 and gp190 subunits, enter in the structure of LIF and OSM high affinity receptors. These results were strongly supported by transfection experiments in CHO cells. CHO cells co-transfected with the human gp190 and gp130 cDNAs expressed high affinity LIF receptors but no high-affinity OSM receptors, indicating that an additional component is required for high affinity OSM binding. High-affinity LIF cross-linking on these cells also showed the association of LIF with a 150 kDa component in addition to the gp130 and gp190 subunits.

Animals↗

[Modulation of integrin alpha-v-beta-1 expression on human tumor cells by leukemia inhibitory factor (LIF) and oncostatin M (OSM)].

Integrins belong to a large family of heterodimeric membrane glycoproteins which mediate cell-cell or cell-extracellular matrix interactions. These interactions could play a major role during the migration of tumor cells across the extracellular matrix and vascular endothelium and would thus appear to be a requisite for the metastatic process. Treatment of the Foss human melanoma cell line with LIF or OSM, two cytokines involved in acute-phase response, increased the expression of membrane alpha v beta 1 by 1.5-2 fold. The same phenomenon was observed on the SK-N-SH human neuroblastoma cell line. This modulation, which was inhibited by specific monoclonal antibodies against alpha v or beta 1 integrin subunits, was concomitant with improved tumor cell attachment to the fibronectin matrix. Similar results were obtained after TNF-alpha treatment. Our findings demonstrate the ability of LIF and OSM to modulate tumor cell capacity to adhere to the matrix component, suggesting a potential role for these cytokines in modulation of tumoral progression.

Antineoplastic Agents↗

[Outcome predictive factors at six months for patients over 75 years admitted for emergency care].

A sample of 199 elderly patients (over 75) admitted to emergency care sections of the Marne's (French department) public hospitals were monitored over six months. The purpose of this study was to assess the factors predicting death or institutionization of elderly patients, in order to improve patient care. Surveys were carried out to collect information on health, standards of living, family surrounding and background, social support and level of dependence. After 6 months, 63 (32%) have died and 19 (12.5%) have been directed to institutions. Risk of death factors are primarily connected with the environment. The risk was multiplied by three for patients placed in institutions and absence of children's visit increased the risk by seven. Dependence was also a risk factor. On the other hand, age and clinical diagnosis had little effect. Risk factors for institutionalization were: admission over the week end (OR = 29), non-accompanied (OR = 31), altered mental abilities (OR = 14), absence of children's visit (OR = 22). These predictors will render possible the rapid identification of high risk patients in every day practice. The improvement of gerontological competences in emergency care sections should enable quicker, more inclusive and adapted care. Measures to stimule or substitute for the failing natural relational network of elderly patients are also needed.

Activities of Daily Living↗

Upmodulation of alpha v beta 1 integrin expression on human tumor cells by human interleukin for DA cells/leukemia inhibitory factor and oncostatin M: correlation with increased cell adhesion on fibronectin.

Integrins belong to a large family of heterodimeric membrane glycoproteins which mediate cell-cell or cell-extracellular matrix interactions. These interactions could play a major role during the migration of tumor cells across the extracellular matrix and vascular endothelium and would thus appear to be requisite for the metastatic process. Pretreatment of the Foss human melanoma cell line with HILDA/LIF or OSM, two cytokines involved in acute-phase response, increased the expression of membrane alpha v beta 1 1.5-2-fold. The same phenomenon was observed on the SK-N-SH human neuroblastoma cell line. alpha v beta 1 upmodulation was concomitant with improved tumor cells attachment to the fibronectin matrix. This greater adhesion of tumor cells to fibronectin was inhibited by specific monoclonal antibodies against alpha v or beta 1 integrin subunits. Similar results were obtained after TNF-alpha treatment. Our findings demonstrate the ability of HILDA/LIF and OSM to modulate tumor cell capacity to adhere to the matrix component, suggesting a potential role for these cytokines in modulation of tumoral progression.

Cell Adhesion↗

Human interleukin for DA cells/leukemia inhibitory factor and oncostatin M enhance membrane expression of intercellular adhesion molecule-1 on melanoma cells but not the shedding of its soluble form.

ICAM-1-mediated cell-cell adhesion is essential for different immunologic functions including non-MHC-restricted cytotoxicity. The shedding of a soluble form of ICAM-1 from melanoma impairs immune recognition and leads to tumour escape. Pretreatment of the Foss human melanoma cell line with HILDA/LIF or OSM, two cytokines involved in acute-phase response, increased the expression of membrane ICAM-1 twofold without inducing sICAM-1 shedding. Conversely, TNF-alpha, in the same conditions, strongly stimulated membrane ICAM-1 expression and the shedding of the soluble form. The same phenomenon was observed on the A375 human melanoma cell line. ICAM-1 upregulation was concomitant with an increase in the non-MHC-restricted cytotoxicity of tumour cells mediated by LAK cell.s This higher sensitivity to LAK lysis was abolished by RR1/1, a specific monoclonal antibody against ICAM-1. Our results demonstrate for the first time the ability of HILDA/LIF and OSM to upregulate ICAM-1 expression on the melanoma cell surface, suggesting a potential role for these cytokines in human immune surveillance during tumour progression.

Binding Sites↗

Modulation of LIF expression in human melanoma cells by oncostatin M.

Oncostatin M (OSM) and leukemia inhibitory factor (LIF) are involved in stimulation of acute-phase protein during inflammatory processes. We recently suggested that these two cytokines may play a role in human immune surveillance during tumor progression. The present study was designed to determine the capacity of OSM in modulating LIF production by human tumor cells and to provide a better definition of the interactions between these two molecules during inflammatory reaction due to neoplasia. LIF content in culture supernatants was assayed by a specific ELISA (sensitivity: 25 pg/ml). In vitro exposure to recombinant OSM increased LIF production 2 to 6-fold in all human melanoma cell lines tested. This effect was not limited to melanoma cell types since LIF production was also enhanced by an MDA breast undifferentiated adenocarcinoma line. Moreover, a synergistic effect was observed for OSM and TNF-alpha. LIF increase was apparently due to up-modulation through LIF synthesis since LIF transcript expression was also enhanced in these tumor cell lines. It is concluded that OSM can induce inflammatory reaction not only directly but also via LIF production by tumor cells.

Adjuvants, Immunologic↗

Genetic risk factor in primary open-angle glaucoma: a case-control study.

PURPOSE: To evaluate the link between primary open-angle glaucoma (POAG) and potential genetic and environmental risk factors. METHODS: A case/control study was carried out using 175 POAG patients and 175 controls, all Caucasians of at least 40 years of age. The diagnosis of POAG was established based on the presence of characteristic defects in the visual field and on glaucomatous cupping. The presence of risk factors was established by means of a questionnaire. RESULTS: Using a conditional logistic regression, we found that a family history of POAG in first-degree relatives was a major risk factor (OR = 7.67; 95% CI: [3.25-18.1]; p < 10(-5)). We found no link between diabetes and POAG, high blood pressure and POAG, heart disease and POAG, myopia and POAG, or the use of alcohol or tobacco and POAG. CONCLUSION: Our results indicate a strong genetic influence in the development of POAG and suggest the hypothesis of a polygenic or multifactorial mechanism.

Adult↗

[Patient-controlled analgesia and postoperative pain].

Patient controlled analgesia improves titration of analgesic drugs, minimizing individual pharmacodynamic differences between patients, during the postoperative period. We describe the efficacy and the safety of intravenous PCA, based on the follow-up of 300 patients, recovering from upper and lower abdominal surgery. Successful use of PCA requires the choice of two important parameters: the PCA bolus and the lock-out period. In our experience, we only prescribed morphine, with a PCA bolus of 0.5 or 1 mg and a lock-out period of 5 or 10 minutes. Nurses were educated to change the syringes and to assess analgesia and the respiratory function. Patients were mostly hospitalized in surgical wards and only 16% of patients were treated in an intensive care unit. Patient's acceptance proved to be excellent and only 4 patients were not satisfied with PCA therapy. The incidence of respiratory depression was low (0.02%) and only one patient required naloxone. The side effects were dysphoria, nausea, pruritus and urinary retention; their incidence was low.

Analgesia, Patient-Controlled↗

[Epidemiological data on primary open-angle glaucoma and treatment in the department of Marne].

A descriptive cross-sectional epidemiological survey of primary open-angle glaucoma (POAG) was carried out in the department of Marne, France, between October 1990 and May 1991. The aim of the study was to obtain socio-medico-demographic data on glaucoma patients who were treated for a period of one year or more. Fifty per cent of the ophthalmologists in the department of Marne participated in the study by having their patients complete an anonymous questionnaire at home. Eighty-five per cent of the 407 patients replied. This response rate to the investigation did not vary significantly (p > 0.90) with respect to the ophthalmologist. However, forgetting to distribute the questionnaires to the patients was variable from one physician to the other. The prevalence of POAG cases undergoing treatment was between 0.15 and 0.36% for the whole population; between 0.37 and 0.89% for patients over the age of 40 years; 0.67 and 1.67% after the age of 60. The same number of women and men are affected, but the risk is 1.33 times greater for men after the age of 60. The geographical distribution of the patients is identical to that of the general population. Sixty-two per cent of the patients take other drugs as well and this proportion increases with age (p < 0.0001); 24% of the subjects have hypertension and 10.6% are diabetic. Half of the patients have received anti-glaucoma therapy for 6 years or less; 94% take beta-blockers, 18% take miotics and 12% use adrenergic drugs. More women instil their eyedrops on their own (79% vs 57%; p < 0.0001). Ten per cent of patients have had glaucoma operations and this proportion increases with age (p < 0.03). The frequency of laser treatment is 20%. Glaucoma patients seem to be faithful to their ophthalmologist as 65% of them go to the same one for follow-up. Our study shows that this type of investigation is well received by the patients.

Adult↗

[Therapeutic observance and life of patients with primary open-angle glaucoma. Apropos of 341 cases in the department of Marne].

Patient compliance with treatment is an important factor in chronic diseases such as primary open-angle glaucoma (POAG). Among the 404 glaucoma patients included in our study in the department of Marne (France), 341 patients responded by completing an anonymous questionnaire at home in which the psychological effect of the illness, their knowledge about it, compliance with treatment and their relationships with the physician were explored. Sixty-eight per cent of these patients confirmed strict compliance with the treatment prescribed; this rate does not vary with respect to either the ophthalmologist (p = 0.57), or the duration of treatment (p = 0.42). Half of the remaining patients only alter the hours of their treatment and 6% forget to instill the eyedrops on certain days. According to our survey, the principal causes of poor compliance are forgetfulness, time constraints with other duties, poor doctor-patient relationship and lack of sufficient knowledge about the disease and its treatment. The majority of patients (59%) are minimally disturbed by the treatment; 2/3 of the subjects do not feel any change in their moral whereas 15% are more depressed or weakened since the time the illness was discovered. Fifty-six per cent of them observed little or no change in their vision; 32% believe to have a moderate or considerable repercussion and 6% claim a very severe visual deterioration. Generally, patients appear to have a positive attitude towards their illness and do not try to deny it. Thirty-eight per cent of them consider it as a handicap which they can overcome and 42% have either no particular opinion or take it as a minor event.

Activities of Daily Living↗

[Comparative study of antitoxoplasmic IgG isotypes titrated by high sensitivity direct agglutination and indirect immunofluorescence: consequence of the choice of methods on the expression of results in international units].

The use of International Units per ml (IU/ml) to express antitoxoplasmic IgG antibody titers in the various diagnostic systems presently proposed, is misleading owing to discrepancies in the values found from one test to the other for a given serum. The authors compared the results of high sensitivity direct agglutination (HSDA) to those of indirect immunofluorescence (IIF) in two studies, systematic and longitudinal, dealing with 158 sera stratified for values ranging from 102,400 to 5 IU/ml. Discordances between the methods, which are greater for high values, prompt the use of low-titer sera for standardization. From the systematic study, a correlation table was established and proposed to convert the HSDA results into the theoretical corrected values close to those that would be obtained by IIF. Although this may be of interest in maintaining a coherent language, this table has its limits, particularly in acute episodes where the various antibody kinetics vary and amplify further the discrepancies. In such situations, it seems advisable for both clinicians and biologists to raise any equivocal kept going by what is termed as International Units. Consequently, if the titers obtained by one method cannot be correlated to those of the technique of reference (IIF, Dye test), on the basis of using I.U., it would be appropriate to express the results in units related to the method or kit used (e.g. U/ml/HSDA for high sensitivity direct agglutination). Finally, whatever the technique, it is still mandatory to conserve a significant threshold value of protective immunization, common and identical to those classically adopted (8-12 IU/ml).

Adult↗

[Epidemiology of minor electrocardiographic anomalies predictive of the occurrence of ischemic cardiopathy].

Common electrocardiographic manifestations (CEM) are predictors of ischemic heart disease (IHD). If precursors of the disease, their risk factors should be similar to those of IHD. This hypothesis has been assessed on results of multiphasic screening recorded in 1976 and 1981, in 1,347 45-65 year old men. Risk factors are social class (blue collar relative risk rr = 2.3), physical activity at work (sedentariness rr = 2.4), systolic blood pressure, no beer consumption and blood urea nitrogen with an exponential risk curve. Cholesterolemia, smoking, diabetes mellitus, overweight and uricemia are not predictors of CEM incidence within 5 years. These results support the idea that CEM are partially asymptomatic expression of IHD; they also have another significance. Subgroups should be individualized and analysis yielded on larger samples. Correlation analysis has been performed between IHD mortality and beer consumption on basis of French counties. A positive correlation (r = 62, p less than 0.01) is opposed to individual results.

Coronary Disease↗

[Class II HLA antigens and rheumatoid factors in rheumatoid polyarthritis. Inverse influence of DR4 and DR7 antigens?].

A linkage disequilibrium was searched for between HLA-DR antigens and rheumatoid factor level both measured using latex agglutination and a solid phase immuno-enzymic assay (FR-PAP) among 251 sera from patients suffering from classical rheumatoid arthritis for at least 5 years, recorded in the Cooperative Swiss Study on Rheumatoid Arthritis. An association between the presence of HLA-DR7 and low levels of rheumatoid factor was found. This association was stronger when the DR4, 7 heterozygous subjects were excluded. The comparison of the DR7, not equal to 4 and DR not equal to 4, not equal to 7 subjects demonstrated that the DR7 effect was independent of DR4. Although the association between DR4 and high levels of rheumatoid factor was not statistically significant in this study, these data suggested an opposite influence of DR4 and DR7 on rheumatoid factor level among rheumatoid arthritis suffering patients. The influence of DR4 appeared to be dominant among heterozygous DR4, 7 patients.

Arthritis, Rheumatoid↗