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Biomedical subjects

F B Michel

Publications and source records attributed to F B Michel.

At least 91 records · Page 5Linked to original sources
PubMed1995

Interleukin-1 alpha and soluble interleukin-2 receptor during small cell lung cancer chemotherapy: comparison of high chemotherapy dose with rhGM-CSF and standard chemotherapy dose without rhGM-CSF.

This study was designed to analyze the possible immunomodulation induced in vivo by haematopoietic growth factors following anti-cancer chemotherapy. Haematologic and cytokine kinetics (IL-1, IL-6, TNF alpha and soluble interleukin-2 receptor (sIL-2R)) were studied in patients with SCLC receiving high dose regimens of chemotherapy and recombinant human GM-CSF (group A), or standard doses of chemotherapy without rhGM-CSF (group B). Six patients were prospectively enrolled and randomized in each group. The kinetics of haematopoiesis following chemotherapy did not significantly differ between the two groups. In group A, the plasma sIL-2R level increased regularly during rhGM-CSF treatment reaching a 2.5-fold elevation at day 12 whereas it remained stable in group B. Conversely, IL-1 alpha decreased to an undetectable level in group A whereas it increased slightly from day 14 to day 18 in group B. As sIL-2R could compete with lymphocyte surface receptors and as IL-I is an important cytokine involved in acute phase response, our results might be regarded as reflecting a transient decrease in the cell-mediated immune response in small cell lung cancer patients receiving high dose chemotherapy combined with rhGM-CSF.

Adult↗
PubMed1995

[Evaluation of tumor response during chemotherapy of bronchial cancer].

Chemotherapy of lung cancer is still an experimental approach requiring careful evaluation. Tumour response (marker of anticancer activity) is not perfectly correlated to survival (marker of chemotherapy efficacy), but its evaluation remains a milestone inasmuch as reporting a wrong tumour response rate might lead to the rejection of active new treatments. This review deals with the method of tumour response measurements and its use during a chemotherapy protocol. Recommendations drawn from the analysis of the literature are: 1) to assess and classify all lesions which can be identified at the beginning of the treatment; 2) to define the target lesions, mainly the ones which can be bidimensionally measured; 3) to use the World Health Organization recommendations for reporting the overall response; 4) to confirm complete response by negative rebiopsies; 5) to avoid second fiberoptic bronchoscopy to patients with stable or progressive disease on CT-scan, and finally; 6) to assess response quality by evaluating response duration and improvement of quality of life.

Antineoplastic Agents↗
PubMed1995

Fos immunoreactivity assessment on human normal and pathological bronchial biopsies.

The transcription factor Fos is involved in cell proliferation and differentiation. Its expression in normal and pathological adult human tissues and cells has rarely been studied. We therefore studied bronchial biopsies obtained from 14 normal subjects (NS), 18 non-steroid-treated asthmatics, 10 corticosteroid-treated asthmatics and 10 patients with chronic bronchitis (CB), in addition to 34 patients with lung cancer (LC), by immunofluorescence for Fos immunoreactivity, using a highly specific polyclonal antibody. Bronchial tissue of 0/10 NS, 11/18 non-steroid-treated asthmatics, 1/10 steroid-treated asthmatics, 0/10 CB and 1/34 LC expressed Fos. In asthmatic patients, the expression was heterogeneous, localized to epithelial cells and correlated with the epithelium shedding (tau = 0.45, P = 0.0001). Corticosteroid-treated patients rarely expressed Fos, suggesting a role for this proto-oncogene in asthmatic bronchial inflammation. Fos was rarely expressed in the normal and pathological (CB, LC) proliferative compartment of the human bronchi, suggesting its low role in cell proliferation of the large airways.

Adenocarcinoma↗
PubMed1995

Platelet-derived growth factor in asthma.

Platelet-derived growth factor (PDGF) controls cellular growth, migration, and differentiation. It is secreted by various cell types, including macrophages, and participates in tissue repair and epithelial regeneration. PDGF may therefore be involved in airway remodeling in asthma. This study compared the immunoreactivity of PDGF and its receptors (R alpha and R beta) in bronchial biopsies and the levels of PDGF in bronchoalveolar lavage (BAL) fluid of asthmatics and control subjects. Bronchial biopsies were done in a subsegmental bronchus of 11 asthmatics and 11 control subjects by flexible bronchoscope. PDGF AA and BB, and PDGF receptors R alpha and R beta were studied with monoclonal antibodies and revealed by immunoperoxidase staining. The percentage of subjects presenting positive staining with PDGFs and its receptors was studied in the epithelium and submucosa. PDGF AA, AB, and BB were measured in BAL fluid of 18 asthmatics and 10 controls by specific ELISA. In biopsies, there was no significant difference between asthmatics and controls for PDGF AA, BB, PDGF-R alpha and R beta (Fisher's exact test and Bonferroni's correction). Moreover, the levels of PDGF, AA, AB, and BB were similar in asthmatics and controls. This study does not support a role for PDGF in the repair processes of asthma.

Adolescent↗
PubMed1995

Evaluation of a composite scoring system in conjunctival challenge with allergen: reproducibility and evolution during loratadine treatment.

The reproducibility of any challenge and its sensitivity to change during therapeutic interventions should always be examined before any drug trial is conducted. Conjunctival challenge has been widely used to assess objectively the efficacy of antiallergic treatments. A double-blind, placebo-controlled, crossover study was carried out in 26 patients allergic to grass pollen to test the reproducibility of a composite symptom score during placebo and control days, and to check the ability of loratadine to increase the provocative dose inducing a positive challenge. Conjunctival challenge was carried out with increasing concentrations of a standardized orchard grass pollen extract until a composite symptom score of 5 was reached. The provocative dose inducing a positive challenge was similar for the baseline (6.94 +/- 8.7 index of reactivity (IR)) and placebo days (20.0 +/- 32.5 IR) and was significantly increased (P < 0.01 and P < 0.001) when patients received loratadine (117.3 +/- 136.8 IR). This study shows that the composite score used was reproducible and sensitive to change, making it possible to use in drug trials.

Adult↗
PubMed1995

[Asthma: a world problem of public health].

Bronchial asthma, one of the most common illnesses in the western world, affecting between 8-10% of children and 3-5% of the adult population, is increasingly becoming a public health problem in the developing world. Its incidence continues to rise throughout the world and, indeed, it has been estimated that it has increased by approximately 50% over the last 10 years. The reasons underlying this alarming trend are probably related to the many possible interactions between allergens and pollution be they domestic (eg passive smoking) or atmospheric (most notably motor vehicle exhaust emissions). The severity of asthma is also increasing as is witnessed by the higher levels of hospitalization of sufferers and the increased death rate (approximately 2000 fatalities per year in France alone). Asthma changes the quality of life of patients whatever their age and is an important cause of school absenteeism and lost working days. The costs due to asthma, which currently represent approximately 1% of direct and indirect health care costs (7 thousand millions French francs), are also steadily mounting. These pessimistic facts and statistics have inspired the drafting of an "International Consensus" on the treatment of asthma sufferers and have caused the WHO to take a position drawing maximum public attention to this disease and measures for its control and prevention.

Adult↗
PubMed1995

IFN-gamma activates superoxide anion production in blood monocytes from allergic asthmatic patients.

BACKGROUND: Peripheral blood monocytes may participate in allergic diseases by releasing inflammatory mediators. We have recently shown enhancement of nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase activity in adherent human peripheral blood monocytes from allergic patients when immunoglobulin E (IgE) binds to its low affinity receptor. Interferon-gamma (IFN-gamma), a monocyte-activating lymphokine, has been shown to prime monocytes for superoxide anion release. OBJECTIVE: We hypothesized that IFN-gamma could directly activate blood monocyte superoxide anion release and evaluated its modulatory effect on IgE-induced superoxide anion release from those cells. METHODS: Seven patients with allergic asthma, 6 patients with allergic rhinitis, and five nonallergic controls were studied. We measured superoxide anion release from their blood monocytes using a chemiluminescence assay. Cells were either nonstimulated, or stimulated for 30 minutes with IFN-gamma and/or serum IgE. RESULTS: We found that IFN-gamma stimulated superoxide anion production and decreased the IgE-induced superoxide anion production after 30 minutes of IFN-gamma preincubation only in blood monocytes from patients with allergic asthma. CONCLUSIONS: These data suggest that IFN-gamma receptors may be increased and/or coupled to NADPH oxidase in allergic asthmatic patients.

Adult↗
PubMed1995

[CYFRA 21-1 and bronchial cancer].

CYFRA is a new marker which measures a fragment of cytokeratin 19 in the serum by an immune radiometric method. The test is based on the preservation of the cytokeratin expression on the epithelial cells during the course of malignant transformation. In immuno-histochemistry the antibodies which selectively recognise cytokeratin react with all histological types of bronchial cancer. The presence of cytokeratin in the serum of patients suffering from cancer would be linked to their liberation during the course of cellular death. The threshold of specificity for CYFRA 21-1 is 3.3.3.6 ng/ml in a population suffering from benign respiratory diseases. The study performed in bronchial cancer produced the following conclusions: the marker is, above all, useful for epidermoid cancer; it is more discriminating than other markers to separate bronchial cancers and non-malignant respiratory disease. An elevated level of CYFRA 21-1 is predictive of advanced disease but does not permit any prediction as to inoperability. In 65% of cases, variations of CYFRA 21-1 are concordant with the stage of the disease during chemotherapy. Finally, elevated levels of CYFRA 21-1 predict a poor prognosis independent of the state of the disease.

Biomarkers, Tumor↗
PubMed1994

[Oncogenes and anti-oncogenes in lung cancer].

In all normal cells, two type of genes, oncogenes and anti-oncogenes, are expressed and control cell proliferation and differentiation. Cell growth is stimulated by oncogenes and inhibited by anti-oncogenes. Cancerization involves loss of control due to defective gene expression either by overexpression of a normal protein (loss of quantitative control) or expression of an abnormal protein (loss of qualitative control). Several oncogenes have been identified. They include three oncogenes, c-myc, N-myc and L-myc, known to be overexpressed in small-cell carcinomas of the lung. Point mutations of the oncogene K-ras is found in 15 to 30% of adenoma carcinomas, especially in smokers. Loss of anti-oncogene function has also been described in processes leading to lung cancer. Chromosome abnormalities, for example the 3p14-23 deletion described in 1982, are found in 100% of small-cell carcinomas and in 50% of non-small-cell carcinomas. This deletion is never found in normal tissue. The gene involved has not yet been cloned. Other mutations or deletions include the RB gene, necessary for neuroendocrine differentiation, and the p53 gene which has undergone mutation in 50% of the non-small-cell carcinomas and 70% of the small-cell carcinomas. These acquired mutations are strongly associated with tobacco smoking. Oncogenes and anti-oncogenes play an important role in the complex step-wise process leading to cancerization. As tumour characterization becomes more precise and precancerous states better controlled, future treatments may relief on inhibiting tumoural growth by using drugs which would substitute for the lost effect of anti-oncogenes or inhibit activation of an oncogene. But at the present time, it is still difficult to define criteria predicting high risk of postoperative relapse or resistance and further studies investigating the correlation between genetic abnormalities and clinical staging and survival curves are required.

Cell Transformation, Neoplastic↗
PubMed1994

Assessment of inflammation in noninfectious chronic maxillary sinusitis.

BACKGROUND AND AIM: Pathologic examination of the sinus mucosa and titration of inflammatory mediators in the sinus fluid were carried out to characterize inflammation in chronic sinusitis and determine whether patients with chronic allergic rhinitis (CAR) and sinusitis differ from patients with chronic nonallergic rhinitis (CNAR) and sinusitis. METHODS: Nine control subjects (patients requiring ear, nose, and throat surgery not related to sinusitis), 12 patients with CAR and sinusitis, and 13 patients with CNAR and sinusitis were investigated. Eosinophil cationic protein, tryptase, myeloperoxidase, histamine, and prostaglandin D2 were measured in the sinus lavage fluids, and cells were enumerated. The cellular infiltrate was studied by immunohistochemistry with monoclonal antibodies against eosinophil cationic protein (eosinophils), tryptase (mast cells), neutrophil elastase (neutrophils), CD3 (lymphocytes), CD68 (macrophages), and proliferating cell nuclear antigens. RESULTS: Neutrophils were not increased in sinusitis. In comparison with control subjects, patients with CAR and CNAR with sinusitis showed significant increases in eosinophils and macrophages in biopsy specimens and in eosinophil cationic protein in sinus lavage fluids. In comparison with patients with CNAR, patients with CAR had an increased number of intraepithelial mast cells and lymphocytes. CONCLUSIONS: These findings suggest that patients with CNAR and sinusitis can be distinguished from patients with CAR and sinusitis, which resembles nonallergic rhinitis with eosinophilia syndrome.

Adolescent↗
PubMed1994

Modulation by interleukin-4 of cytokine release from mononuclear phagocytes in asthma.

BACKGROUND: Interleukin (IL)-4 is involved in IgE upregulation and downregulates cytokine release by mononuclear phagocytes. Mononuclear cells release greater amounts of IL-1, tumor necrosis factor-alpha, and IL-6 in patients with asthma than in control subjects, but the effect of IL-4 on cells from patients with asthma is unknown. The effects of IL-4 on the release of IL-1, tumor necrosis factor-alpha, and IL-6 by monocytes and alveolar macrophages were compared in 19 patients with asthma and 18 control subjects. METHODS: The release of IL-1, tumor necrosis factor-alpha, and IL-6 from unstimulated and lipopolysaccharide stimulated monocytes and alveolar macrophages was measured by ELISA. The effect of 30 U of IL-4 on the release of these cytokines was studied. RESULTS: Lipopolysaccharide-stimulated monocytes released significantly fewer cytokines in patients with asthma than in control subjects. IL-4 significantly inhibited cytokine release by monocytes of both groups. Unstimulated alveolar macrophages from patients with asthma released more cytokines than those of control subjects. Lipopolysaccharide induced a significantly greater increase in cytokine release in alveolar macrophages of control subjects in comparison with asthmatic subjects. IL-4 abolished the release of cytokines in alveolar macrophages from control subjects and had a minimal inhibitory effect on alveolar macrophages from patients with asthma. CONCLUSIONS: Alveolar macrophages from patients with asthma are hyperreactive but less prone to lipopolysaccharide stimulation and IL-4-downregulation than those from normal subjects.

Adolescent↗
PubMed1994

IgE produces monocyte superoxide anion release: correlation with CD23 expression. Comparison of patients with asthma, patients with rhinitis, and normal subjects.

Allergic inflammation involves many different cell types among which mononuclear cells, such as macrophages and monocytes, play an important role. These cells release numerous chemical mediators, including superoxide anion (O2.-). We evaluated the capacity of atopic serum to stimulate peripheral blood monocyte O2.- release. Thirteen untreated allergic patients (seven with asthma and six with rhinitis), and five nonallergic control subjects were studied. O2.- was measured in a photon-counting camera with Lucigenin-enhanced (Sigma Chemical Co., St. Louis, Mo.) chemiluminescence. Results were expressed (mean +/- SEM) in relation to basal values (peak/basal chemiluminescence values). Spontaneous production of O2.- was greater in allergic patients. Moreover, atopic serum stimulated O2.- production of blood monocytes in all subjects, but this was greater in subjects with allergic asthma than in subjects with allergic rhinitis and normal subjects. Anti-IgE immunoadsorption of atopic serum completely abrogated this effect, which was restored by the IgE-rich eluted fraction. IgE-induced O2.- release decreased as adherence duration increased and was correlated with surface CD23 expression. These results indicate that monocytes from allergic patients are in an activated state and that binding of IgE to their receptors generates O2.-, possibly by direct activation of blood monocyte reduced nicotinamide adenine dinucleotide phosphate oxidase.

Adult↗
PubMed1994

Detection of lymph node metastases in lung cancer: comparison of 131I-anti-CEA-anti-CA 19-9 immunoscintigraphy versus computed tomography.

Mediastinal lymph node metastasis is one of the most important prognostic variables of lung cancer. We designed a study to compare immunoscintigraphy (IS) using iodine-131 anti-carcinoembryonic antigen (CEA) and anti-carbohydrate 19-9 (CA 19-9) monoclonal antibody and computed tomography (CT-scan), in the setting of mediastinal staging. Seventeen patients were involved in a prospective, blind study, to compare IS with CT-scan imaging of the mediastinum. Sensitivity and specificity of both methods were analyzed with reference to pathological staging by mediastinal lymph node sampling. IS imaging was not possible in two patients owing to a thyroid uptake and one patient refused surgery. Among the 14 evaluable patients, sensitivity and specificity were 0.83 and 0.12 for IS, and 0.66 and 0.50 for CT-scan, respectively. We used different thresholds of positivity for both methods in order to evaluate the sensitivity-specificity relationship. When compared with that of IS, the area under the receiver operating characteristic (R.O.C.) curves of the CT-scan was bigger. Although one patient had pathologically confirmed N2 with negative CT-scan and positive IS, the results of IS were hampered by a very high level of false positivity. Finally, there was no relationship between positivity of IS and a high serum CEA level. Lack of specificity and the insufficient sensitivity of the iodine-131 anti-CEA-anti-CA 19-9, lead to the conclusion that IS adds weak information to a CT-scan, in the non-invasive mediastinal staging of lung cancer. More efficient radionuclides and markers are needed in the setting of lung cancer staging.

Adult↗
PubMed1994

Clinical evaluation of serum tissue polypeptide-specific antigen (TPS) in non-small cell lung cancer.

M3 is an epitope of the tissue polypeptide antigen detectable in the serum by immunoradiometric assay. This epitope is referred to as tissue polypeptide-specific antigen (TPS). We examined the pretreatment TPS level of 160 non-small cell lung cancer (NSCLC) patients and 71 patients who suffered from non-malignant pulmonary diseases. The upper limit of normal values was 140 U/l. Using this cutoff, the sensitivity and specificity were 36 and 90%, respectively. The TPS was significantly higher in NSCLC patients with an advanced stage, a mediastinal lymph node involvement or a poor performance status. This level was significantly higher in the group of patients for whom the disease proved to progress during chemotherapy. In univariate analysis, patients with a high TPS level proved to have a shorter survival than patients with a TPS < or = 140 U/l. In Cox's model analysis, performance status, stage of the disease and serum TPS were the only significant prognostic variables. The low sensitivity of TPS precludes its use for diagnosis. However, the pretreatment TPS level adds information to the management of NSCLC inasmuch as it predicts a low sensitivity to chemotherapy and a poor prognosis.

Adult↗