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Biomedical subjects

Y Martinet

Publications and source records attributed to Y Martinet.

At least 73 records · Page 4Linked to original sources
PubMed1990

[Application of molecular biology techniques to pneumology].

Over the past ten years there has been fundamental progress in molecular biology, i.e. concerning the structure and function of genes. The understanding and diagnosis of several diseases, in particular those of the respiratory system, have been profoundly affected and changed. For example alpha-1-antitrypsin deficiency and the emphysema which results have now been dissected down to a molecular level and characterised by anomalies of certain critical portions of the gene coding for this protein. The same thing is found in cystic fibrosis where, thanks to recent technical progress, it is now possible to make a positive diagnosis in most unaffected carriers. The importance of molecular biology in lung cancer is equally established, and in small cell lung cancer one can already isolate a sub group of cancers presenting with an abnormal amplification of the c-myc oncogene. Finally, the role of inflammatory cells, in particular macrophages, in pulmonary fibrosis is best understood by studying the expression by macrophages of the genes coding for mediators which alter the replication of fibroblasts.

Carcinoma, Small Cell↗
PubMed1990

[Chemotaxis and cellular migration in respiratory pathology].

Numerous types of cells have a capacity for movement in physiological or pathological situations. For example, this is the case for inflammatory cells in the lung, during acute lobar pneumonia, sarcoidosis and idiopathic pulmonary fibrosis. Cellular migration is a general process which rests on the interaction between different chemotactic factors and specific receptors which are present on the target cells. On the other hand the addition of inhibitors can significantly decrease the cellular migration in the presence of chemotactic factors. In respiratory pathology, congenital chemotactic defects are exceptional (and the Chediak-Higashi syndrome and Job syndrome are examples). In contrast during the course of lung cancer, circulating monocytes often show a significant decrease in their chemotactic responsiveness.

Chemotactic Factors↗
PubMed1988

High levels of transforming growth factor-beta are present in the epithelial lining fluid of the normal human lower respiratory tract.

Transforming growth factor-beta (TGF-beta), a mediator capable of modulating a broad range of effects on the behavior of many normal cells, was found in high concentrations in the epithelial lining fluid (ELF) of the normal human lower respiratory tract. Although plasma contained small amounts of TGF-beta, the concentrations of TGF-beta in normal ELF were in the 200 to 300 pM range, more than 15-fold higher. This ELF TGF-beta had similar physical characteristics to purified human platelet TGF-beta, competed with platelet TGF-beta for its receptor on A549 carcinoma cells, and stimulated the anchorage-independent growth of NRK cells in soft agar in the presence of epidermal growth factor. Furthermore, ELF TGF-beta suppressed diploid lung fibroblast proliferation in a dose-dependent fashion similar to platelet TGF-beta. In the context of these observations and with the known biologic properties of this molecule, TGF-beta in ELF has the potential to play a role in a variety of cellular processes in the lower respiratory tract.

Adult↗
PubMed1988

Differential expression of the tumor necrosis factor/cachectin gene by blood and lung mononuclear phagocytes.

Tumor necrosis factor (TNF), also called cachectin, is a mononuclear phagocyte-derived mediator with a broad range of biologic activities contributing to antineoplastic and antiviral defenses as well as mediating a variety of processes associated with acute and chronic inflammatory states, including endotoxin-induced shock. To evaluate the relative capacity of human tissue macrophages to produce this mediator, alveolar macrophages and blood monocytes from the same normal individuals were activated with lipopolysaccharide (LPS) and evaluated for TNF release and TNF mRNA transcript levels. Resting alveolar macrophages did not express TNF mRNA transcripts or release TNF. However, when activated, alveolar macrophages expressed TNF transcripts and synthesized and released TNF as evidenced by the presence of a 28 kDa mediator in LPS-activated alveolar macrophage supernatants that had cytotoxic activity for L-929 cells that was abrogated by anti-TNF antibodies and that coeluted with a pure TNF standard on a molecular sieve column. Interestingly, activated alveolar macrophages released severalfold more TNF than did autologous blood monocytes stimulated in a similar fashion and, in parallel, the alveolar macrophages expressed more TNF mRNA transcripts than activated blood monocytes. Thus, the ability to express the TNF gene and to release TNF apparently increases during maturation of blood monocytes into alveolar macrophages, suggesting that the release of TNF in the local milieu by activated tissue macrophages may be much more significant than the release of this mediator by circulating blood monocytes.

Adult↗
PubMed1988

Evaluation of the in vitro and in vivo effects of cyclosporine on the lung T-lymphocyte alveolitis of active pulmonary sarcoidosis.

Pulmonary sarcoidosis is a granulomatous disorder characterized by the accumulation of activated helper/inducer T-lymphocytes in the lower respiratory tract, a process thought to be central to the pathogenesis of the disease. Because cyclosporine, a fungus-derived cyclic peptide, has specific inhibitory effects on T-lymphocyte activation, it should suppress activated sarcoid lung T-cells, and thus it should theoretically be an ideal therapeutic agent for sarcoidosis. This was confirmed in vitro: the addition of cyclosporine to T-cells recovered from the lungs of patients with active sarcoid suppressed the spontaneous release of interleukin-2 (IL-2) and monocyte chemotactic factor by these cells and inhibited their exaggerated spontaneous replication. In contrast, the oral administration of conventional doses (10 mg/kg/day) of cyclosporine to eight of these patients over a 6-month period was not accompanied by suppression of sarcoid lung T-cell activation. On the average, the spontaneous release of IL-2 and monocyte chemotactic factor, the proliferation of lymphocytes, and the number of helper/inducer T-cells present in the lungs of these subjects remained elevated and similar to their pretherapy values. Consistent with this lack of effect on sarcoid lung T-cell activation, no improvement in lung function was observed over the trial period. Thus, although cyclosporine is effective in vitro in suppressing the exaggerated activation of sarcoid lung T-cells, it does not do so in vivo, suggesting this agent will not be useful in the therapy of active pulmonary sarcoidosis, at least when administered in a conventional fashion.

Adult↗
PubMed1987

Exaggerated spontaneous release of platelet-derived growth factor by alveolar macrophages from patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a fibrotic lung disease characterized by an increased number of mesenchymal cells in the alveolar walls. Alveolar macrophages constitutively express low levels of c-sis, the protooncogene coding for the B chain of platelet-derived growth factor, a protein with chemotactic and mitogenic activity toward mesenchymal cells. We therefore hypothesized that alveolar macrophages in patients with idiopathic pulmonary fibrosis may release increased amounts of platelet-derived growth factor, which might help to explain the accumulation of mesenchymal cells and the fibrosis of the lower respiratory tract in the disease. Evaluation of alveolar macrophages recovered from the lungs of patients with idiopathic pulmonary fibrosis demonstrated that these cells spontaneously released four times more platelet-derived growth factor than did alveolar macrophages recovered from normal persons (P less than 0.01). That the platelet-derived growth factor molecules were potentially active was shown by their chemotactic activity for smooth-muscle cells and their ability to act as a "competence" factor for fibroblast growth. These observations suggest the possibility that the accumulation of mesenchymal cells within the alveolar walls in patients with idiopathic pulmonary fibrosis may result partly from the exaggerated release of the potent mitogen platelet-derived growth factor by mononuclear phagocytes in the lower respiratory tract.

Biological Assay↗
PubMed1987

Modulation of fibronectin gene expression in human mononuclear phagocytes.

Under some conditions, mononuclear phagocytes spontaneously synthesize and release fibronectin, an extracellular matrix glycoprotein with versatile effects on cell-matrix interactions. To gain insight into the processes that modulate the level of fibronectin secretion by these cells, we used monocytes, in vitro matured monocytes and alveolar macrophages as models to compare fibronectin mRNA levels and fibronectin secretion in a variety of circumstances. Using Northern analysis and dot-blot analysis with a 32P-labeled human fibronectin cDNA probe, we evaluated steady-state mRNA levels and a human fibronectin-specific ELISA was used to evaluate fibronectin secretion. In all cases the amounts of fibronectin secreted paralleled fibronectin mRNA levels. Specifically (a) when fibronectin mRNA was undetectable, as in the case of normal blood monocytes, no fibronectin was secreted, but whenever fibronectin mRNA was present, as in normal alveolar macrophages, fibronectin was secreted by the cells; (b) as monocytes matured into macrophages in vitro, the cells began to express fibronectin mRNA and the cells secreted fibronectin; (c) when alveolar macrophages were activated with surface stimuli such as lipopolysaccharide (LPS) or immune complexes, fibronectin mRNA levels decreased and in parallel, the cells secreted less fibronectin; (d) in idiopathic pulmonary fibrosis (IPF), alveolar macrophages contained severalfold more fibronectin mRNA transcripts that normal and the cells spontaneously secreted severalfold more fibronectin than normal; and (e) when IPF alveolar macrophages were placed in culture the fibronectin mRNA levels in the cells decreased with time, and concurrently the amounts of fibronectin produced per unit time continually decreased. The observation of a strict concordance of fibronectin mRNA levels and fibronectin release by mononuclear phagocytes suggests that, at least in many circumstances, fibronectin secretion by mononuclear phagocytes is controlled by steady-state levels of fibronectin mRNA.

Adult↗
PubMed1986

Expression of the alpha-1-antitrypsin gene in mononuclear phagocytes of normal and alpha-1-antitrypsin-deficient individuals.

To evaluate the contribution of mononuclear phagocytes, and particularly alveolar macrophages, to alpha-1-antitrypsin (alpha 1AT) production in normal and alpha 1AT-deficient individuals, Northern analysis with a human alpha 1AT complementary DNA was used to demonstrate that alpha 1AT messenger RNA (mRNA) can be detected in liver, blood monocytes, and alveolar macrophages. Quantification of alpha 1AT mRNA expression demonstrated that: (a) type PiMM monocytes and alveolar macrophages expressed, respectively, 200-fold and 70-fold less alpha 1AT mRNA per cell than the liver; (b) the level of expression of the alpha 1AT gene was increased during the in vitro maturation of blood monocytes; and (c) blood monocyte and alveolar macrophage levels of expression of the alpha 1AT gene were the same in PiMM and PiZZ individuals. However, the amount of newly synthesized alpha 1AT secreted by ZZ alveolar macrophages was 10 times lower than that secreted by MM alveolar macrophages. Thus, mononuclear phagocytes of PiZZ individuals express a secretory defect in alpha 1AT in a fashion similar to hepatocytes. Not only do mononuclear phagocytes provide a readily accessible cell to evaluate the regulation of alpha 1AT gene expression, but these cells may contribute to the levels of alpha 1AT present in the lower respiratory tract in the normal and ZZ states.

Adult↗
PubMed1986

Spontaneous expression of the c-sis gene and release of a platelet-derived growth factorlike molecule by human alveolar macrophages.

Alveolar macrophages from normal individuals and patients with interstitial lung diseases spontaneously expressed a 4.2-kilobase mRNA complementary to the c-sis gene, a proto-oncogene coding for one of the chains of platelet-derived growth factor (PDGF). Concomitantly, these cells released a mediator with the properties of PDGF, including: chemotactic factor for smooth muscle cells whose activity was resistant to heat and acid, but sensitive to reduction; mitogenic (competence) activity for fibroblasts; ability to compete with PDGF for its receptor; and precipitated by an anti-PDGF antibody. While blood monocytes did not contain c-sis mRNA transcripts, monocytes matured in vitro expressed c-sis, consistent with the concept that expression of c-sis occurs during the differentiation of monocytes into alveolar macrophages. Together with the known actions of PDGF, these observations suggest that the c-sis proto-oncogene and its PDGF product are part of the armamentarium available to the alveolar macrophages for normal lung defense and participation in lung inflammation.

Chemotaxis↗
PubMed1985

Chemoattractants in fibrotic disorders.

Fibrosis represents an excessive deposition of connective tissue which impedes the normal functions of an organ or tissue. The mechanisms leading to this increased deposition of connective tissue may be similar to those occurring in normal wound repair. We have previously shown that the repair process involves the migration of connective tissue cells to the site of injury and their subsequent proliferation. One of the principal factors controlling these events appears to be the platelet-derived growth factor (PDGF). PDGF acts as a potent chemoattractant and mitogen for connective tissue cells but not other cell types. In addition to PDGF, factors produced by monocytes and tissue macrophages also act as chemoattractants for connective tissue cells. These observations suggest that such activities may be abundant in areas of inflammation. In normal repair these factors would be present for a relatively short period of time, whereas in fibrosis the chronic inflammatory response could maintain a constant or repeated release of such factors. This would recruit additional connective tissue cells to the area of inflammation, changing the cellular composition of the affected organ or tissue, resulting in an expansive and permanent nodule of connective tissue.

Animals↗
PubMed1985

[Surgical pulmonary biopsy in diffuse interstitial pneumopathies].

On the basis of 81 cases of surgical lung biopsy performed in the course of diffuse interstitial lung disease, the authors report the yield and the tolerance which they observed with this technique in comparison with data from the literature. Like other authors, they obtained an excellent histological yield, as only one case was uninterpretable in this present series. However, they emphasise the "final yield", which consists of a precise aetiological diagnosis, i.e. the exclusion of the diagnosis of diffuse interstitial fibrosis. The analysis of the tolerance of the procedure revealed a higher morbidity and mortality than those generally reported in the literature.

Adolescent↗
PubMed1984

Clinical significance of circulating immune complexes in 'lone' cryptogenic fibrosing alveolitis and those with associated connective tissue disorders.

The clinical, radiographic and physiological features, and progression rates of forty unselected patients with cryptogenic fibrosing alveolitis (CFA) have been studied in relation to serum immune complexes measured by a C1q binding technique. Twenty (50%) had levels greater than normal. Those with associated connective tissue disorders (twenty-four) had a higher frequency of raised C1q binding than those with 'lone' CFA (sixteen) (63% compared to 31%). As observed previously in this group, those with associated disorders also had higher titres of immune complexes. Twelve of thirteen with polyarthritis had immune complexes and a considerably shorter duration of disease compared with those without joint symptoms (P less than 0.01). Several other observations suggest that immune complexes are especially associated with earlier disease. These include a trend towards a younger age and a lesser radiographic profusion score; a shorter duration of symptoms in relation to titres of immune complexes amongst those with raised values (P less than 0.05) and a higher transfer factor coefficient (Kco) (P less than 0.02). The relationship between Kco and the presence of immune complexes was still observed when those with 'lone' CFA were analysed separately. Other clinical features including sex, severity of dyspnoea and lung volumes did not distinguish those with and without complexes, either for the whole group of patients or when those with and without associated connective tissue disorders were analysed separately. Analysis of eighteen patients followed to death showed no correlation between length of survival from first symptoms and immune complexes, neither was there any clear association with corticosteroid responsiveness and immune complexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-Antibody Complex↗
PubMed1982

[Gerstmann-Sträussler-Scheinker disease. Anatomoclinical and genealogical study].

The patient has been examined clinically and his brain examined. Four related patients are known by hospital records, and two others by history. The mode of transmission is compatible with a mendelian autosomic dominant mechanism through three generations, but the line appears to be broken at the further ascending generation with both parents dying too old to be affected. The disease begins in the early thirties, with tremor and frequent falls; intellectual impairment is soon obvious. Later on, the patients are demented, unruly; a marked dysarthria and severe intention and opposition tremor in the trunk and the extremities are present. Midline reflexes are brisk, other reflexes are normal, a Babinski response is not obtained. Laboratory and E.E.G. data are non contributive. At a terminal stage, the patient is bedridden, cachectic, with extensor hypertonia of the lower extremities and flexor hypertonia of the upper extremities. Total course is about seven years. Neuropathological findings in the propositus were almost entirely restricted to the cerebellar cortex, the molecular layer of which is moderately atrophic and gliotic, and contains numerous plaque-like formations without neuritic component, but differing from kuru plaques by the absence of amyloid characteristics. The condition may be nevertheless ascribed to Gerstmann-Sträussler-Scheinker disease, understood as a provisional clinicopathology group, pending further transmission experiments.

Adult↗
PubMed1980

[Diagnosis of diffuse pneumopathies (author's transl)].

The authors analyze their proceeding in the etiological diagnosis of 40 diffuse pneumopathies in patients admitted to hospital. In 31 cases, diagnosis was made 10 times at the radioclinical stage, 14 times at the endoscopical stage, 6 times at the surgical stage, and once at autopsy. After, they analyze the problems of interpreting the data obtained at each stage, particularly the limited contribution of the X-ray, the necessity of discussing the anatomo-pathological diagnosis (the problem of fibrosis, of sarcoidosis reactions and of pneumoconioses). They insist on the multiplicity of tests to be done on each sample and on the importance of systematic research of K.B. Finally, all the difficulties in diagnosing toxic pneumopathies (whether iatrogenic or not) are recalled.

Adult↗
PubMed1980

["Plastic lung". Broncho-pulmonary pathology related to plastics (author's transl)].

Plastics can induce three main groups of respiratory accidents.--Acute and subacute intoxications related to the inhalation of volatil substances from decomposing plastics (mostly during burning and pyrolysis) or on the contrary during synthesis. They are accidental chemical broncho-pneumopathies (acute tracheo-bronchitis and pulmonary edema).--Chronic broncho-pneumopathies following repeated inhalation of dusts or suspension of plastics: pneumoconioses and thesaurismoses leading to pulmonary fibrosis.--Broncho-pneumopathies related to the irritant and sensitizing action of some components of plastics: professional asthma and sensitization pneumopathies. Diagnosis of such diseases therefore imposes a careful study of working conditions. Proof rests on two arguments:--curing by risk eviction;--analysis of the products in order to reveal their toxicity.

Humans↗
PubMed1980

[Emergency fibroscopy (author's transl)].

Emergency bronchial fibroscopy is often asked for by intensive care units. It is usually easy to make examination. The authors tried to evaluate its diagnostic and therapeutical efficiency. They gathered 48 observations of endoscopies performed in the intensive care unit. The diagnostic efficiency is valued at 70% and the therapeutical one at 85%. The main indication is the pulmonary obstruction besides tracheal stenoses, tracheal ruptures, hemoptysis and searching for opportunistic germs.

Bronchoscopy↗
PubMed1980

[Evaluation of diagnostic means in pleural effusions (from two hundred observations) (author's transl)].

From 200 observations, the authors study the results of laboratory examinations and paraclinical testings of the pleura. Neoplastic etiologies represent a 1/3 of all pleurisies. In 20% of cases a definite etiological diagnosis could not be obtained in spite of exploring thoracotomies. The limit of 30 g/l of proteins for the differentiation of mechanical transsudates and inflammatory exsudates was inaccurate. Cytodiagnosis was efficient in 75% of mesotheliomas but the percentage fell to 53 in secondary cancers. For needle biopsy results were respectively of 66% and 57%. Thoracotomy (24 cases) enabled a diagnosis in half the cases where it was performed. Thorascopy seems to bring similar results.

Evaluation Studies as Topic↗