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Biomedical subjects

Y Martinet

Publications and source records attributed to Y Martinet.

At least 55 records · Page 3Linked to original sources
PubMed1993

In vitro effects of pentoxifylline on smooth muscle cell migration and blood monocyte production of chemotactic activity for smooth muscle cells: potential therapeutic benefit in the adult respiratory distress syndrome.

The adult respiratory distress syndrome (ARDS) is a severe lung condition characterized by an acute lung injury leading to a massive intra-alveolar fibrosis with rapid lung failure. ARDS intra-alveolar fibrosis results from the migration of mesenchymal cells (mainly smooth muscle cells [SMC]) into the alveoli through alveolar epithelial basement membrane gaps resulting from the injury. SMC migration is followed by their replication and production of extracellular matrix, which leads to fibrosis. Thus, any pharmacologic agent able to prevent SMC migration should prevent, at least in part, intra-alveolar fibrosis. SMC migration is thought to be due to the presence, in the alveolar spaces, of chemotactic factors for mesenchymal cells, such as fibronectin and platelet-derived growth factor (PDGF). The local presence of these chemotactic factors can be due to plasmatic leakage, platelet degranulation, and mononuclear phagocyte activation. Pentoxifylline is a methylxanthine interacting with the biology of several types of cells, including red blood cells, neutrophils, blood monocytes, and endothelial cells. Pentoxifylline prescription has been suggested in ARDS with respect to its activity on neutrophils, its inhibition of tumor necrosis factor-alpha (TNF) release by mononuclear phagocytes, and its prevention of TNF-induced lung injury. Since pentoxifylline can modulate the migration of several cell types, we hypothesized that it could interfere with mesenchymal cell migration. SMC migratory response was measured in vitro with modified Boyden chemotactic chambers in the presence of PDGF, fibronectin, "platelet extract," and activated blood monocyte supernatants. Pentoxifylline, at therapeutic levels, significantly reduced SMC migration in response to the presence of these chemotactic activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed1993

Platelet-derived growth factor AA and AB dimers are present in normal human epithelial lining fluid.

Normal lung architecture is related to the presence of mesenchymal cells (fibroblasts and smooth muscle cells), and to the production by these cells of extracellular matrix. The turnover of mesenchymal cells is under a fine regulation due, at least in part, to the local presence of different mediators acting on their cell cycle. Since normal human alveolar macrophages obtained by bronchoalveolar lavage (BAL) spontaneously release platelet-derived growth factor (PDGF), a cytokine with chemotactic and growth activity on mesenchymal cells, we evaluated normal human epithelial lining fluid (ELF) for the presence of PDGF. Active only as a dimer, PDGF is a glycoprotein composed of two chains (A and B) and, thus, can be present in three forms: AA, AB, and BB dimers. Interestingly, normal ELF contains PDGF AA dimers, and to a lesser extent AB dimers, while no significant level of BB dimers is detected. Furthermore, ELF PDGF is biologically active and responsible for a significant part of the chemotactic activity and the "competence" growth activity for mesenchymal cells present in normal ELF. These findings suggest that ELF PDGF has a role in normal lung structure maintenance and tissue repair.

Adult↗
PubMed1993

Squamous metaplasia expression of proto-oncogenes and P 53 in lung cancer patients.

BACKGROUND: The question of whether bronchial squamous metaplasia is a true preneoplasia is important and demonstrated in animal for several carcinogens. We have now approached this problem in humans and in vivo. EXPERIMENTAL DESIGN: Squamous metaplasia in the close vicinity of surgically resected lung tumors were evaluated for their mitotic index and screened for proto-oncogenes and P 53 protein expression by immunohistochemistry and/or in situ hybridization. RESULTS: Among 16 patients, 4 had squamous metaplasia positive for either myc messages and/or for P 53 protein accumulation. In the same patients (3/4), the autologous bronchial tumors were also positive for the same markers. Squamous metaplasia positivity was observed essentially in patients with advanced diseases and only in squamous cell carcinomas. In addition, when evaluated with 5 iodo-2'-deoxyuridine systemic infusion, all patients presented hyperproliferative basal squamous metaplasic cells. CONCLUSIONS: These results are reminiscent of the typical preneoplastic changes observed in familial colic adenomatosis, where genetic changes accumulate in hyperproliferative cells. They also suggest that bronchial squamous metaplasia could be an authentic preneoplasia in, at least, squamous cell carcinomas.

Gene Expression Regulation, Neoplastic↗
PubMed1992

Mechanism for the recruitment of macrophages to cancer site. In vivo concentration gradient of monocyte chemotactic activity.

BACKGROUND: Tumor stroma is characterized by the development of new blood vessels, an inflammatory cell infiltration, and a fibrotic reaction. The inflammatory component of tumor stroma plays an important role in the modulation of tumor expansion. In this respect, macrophages constitute a major part of the inflammatory cell infiltration and can exert cytotoxic activity against tumor cells. The accumulation of macrophages in the vicinity of the tumor suggests their recruitment from circulating blood monocytes through the local release of chemotactic factors for monocytes. METHODS: To detect the existence of a concentration gradient of monocyte chemotactic activity (MCA) between the tumor vicinity and blood vessels, malignant pleural effusions defined by the local presence of cancer cells were evaluated for quantification of MCA. RESULTS: Unlike nonmalignant pleural effusions, malignant pleural effusions were characterized by the presence of increased levels of MCA, and in lung adenocarcinoma (a cancer with high inflammatory cell infiltration), pleural levels of MCA were significantly greater than in small cell lung carcinoma (a cancer with low inflammatory cell reaction). An MCA concentration gradient between pleural fluid and plasma was present in malignant effusions because pleural MCA levels in all cancer types were significantly greater than MCA levels in the plasma of the same patients. CONCLUSIONS: Thus, an increased local level of MCA is a feature of cancers with high inflammatory cell infiltration, and the presence of an in vivo concentration gradient of MCA suggests the direct role of this biologic activity in recruiting blood monocytes to the cancer site.

Adenocarcinoma↗
PubMed1992

Differential expression of PDGF A- and B-chain genes and production of AA and AB dimers by activated human blood monocytes.

Platelet-derived growth factor (PDGF) is composed of two chains (A and B) bound by disulfide bridges. Blood monocytes (BM) express the c-sis proto-oncogene, the gene coding for PDGF B-chain, and release PDGF. To evaluate PDGF release and A- and B-chain gene expression by BM, normal BM were cultured with LPS and specific transcripts for PDGF A- and B-chain genes were detected by Northern analysis and PDGF dimers by specific Elisas. Normal BM did not spontaneously express either A- or B-chain gene while, when activated, PDGF B-chain expression was precocious (maximum at 1 h) and decreased over 24 h; PDGF A-chain transcripts were present after 4 h and progressively increased over 24 h. Furthermore, activated BM released more AB dimers than AA dimers and almost no BB dimers. This observation confirms the concept of PDGF A- and B-chain separate gene regulation, and defines the specific molecular pattern of PDGF released by activated BM.

Blotting, Northern↗
PubMed1992

Differential migratory response of U-2 OS osteosarcoma cell to the various forms of platelet-derived growth factor.

U-2 OS osteosarcoma cells are mesenchymal-derived transformed cells spontaneously expressing both platelet-derived growth factor (PDGF) A- and B-chain genes, and releasing PDGF AA dimers in culture. Using modified Boyden chemotactic chambers, platelet-purified PDGF was shown to be a chemoattractant for U-2 OS cells. More specifically, U-2 OS cells migrated in the presence of PDGF AB and BB dimers but not in the presence of PDGF AA dimers. This pattern of response was similar to that observed with human fibroblasts and this similarity is consistent with the fact that U-2 OS cells express PDGF receptor alpha- and beta-subunits in a similar fashion to human fibroblasts.

Chemotaxis↗
PubMed1992

Characterization of a tumor necrosis factor-alpha inhibitor activity in cancer patients.

To evaluate the feasibility of tumor necrosis factor-alpha (TNF-alpha) treatment of lung cancer patients, we chose the malignant cells contained in their pleural effusions as a first convenient target. We found, however, that a TNF-alpha inhibitor (TNF-alpha I) activity was present in both patient sera and pleural fluids. We therefore compared the TNF-alpha I activity present in patients with benign or malignant pleural effusions using a bioassay of TNF-alpha inhibition and partially characterized it. A high TNF-alpha I activity characterizes cancer patients with sera levels twice as high as the control level measured for blood bank donors (2.54 +/- 1.28 versus 1.19 +/- 0.38) and with even higher levels in pleural fluids (3.75 +/- 1.83). In contrast, patients with benign pleural effusions present similar levels of TNF-alpha I activity, at about the control level, in both their sera and pleural fluids (1.37 +/- 0.98 versus 1.16 +/- 0.85). A high TNF-alpha I activity is consistently found in cancer patients but is only released in vitro by leukocytes. It is most likely related to recently purified TNF-alpha inhibitors that, as soluble shed fragments of TNF receptors, may function as traps for TNF molecules. This study suggests that tumors may evade TNF cytotoxic action by modulating systemic levels of TNF and implies a reassessment of TNF therapy in cancer patients.

Adult↗
PubMed1992

Presence of elevated levels of platelet-derived growth factor (PDGF) in lung adenocarcinoma pleural effusions.

Significant tumor stroma development is a specific feature of adenocarcinoma of the lung in comparison to small-cell lung cancer (SCLC). The fibrotic component of tumor stroma is thought to result from the migration and local replication of mesenchymal cells in response to the presence of cytokines. One of them, platelet-derived growth factor (PDGF), is a chemotactic and growth factor for mesenchymal cells. Since several lung adenocarcinoma cell lines, but not SCLC cell lines, have been shown in vitro to express PDGF genes, we evaluated pleural effusions for the presence of PDGF in patients with adenocarcinoma of the lung, SCLC, or nonmalignant pleural effusions. In adenocarcinoma of the lung, PDGF levels in pleural effusions were higher than in SCLC and in nonmalignant pleural effusions and were associated with the presence of a growth-promoting activity for fibroblasts due, in part, to the presence of PDGF. This observation suggests the role of PDGF in tumor stroma formation in adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed1992

[Effects of coffee on the respiratory system].

The consumption of coffee is a very old and popular habit. It is possible that it may have an effect on the respiratory system and on the regulation of respiration. Apart from the manifestations of hypersensitivity linked to the handling of green coffee, the consumption of coffee can have different effects. On the one hand it has a beneficial effect on bronchospasm. On the other hand its consumption has been suspected of contributing to the development of chronic airflow obstruction (COPD) and also in the genesis of bronchial cancer, without, however, its responsibility being proven in a clear fashion. In fact, in these two latter pathological circumstances, the causal relationship is probably indirectly linked to the fact that there is a strong positive correlation between the consumption of coffee and of tobacco. Finally the consumption of coffee increases ventilatory frequency in normal subjects and also in the course of COPD, and if taken in large quantities by pregnant women, there is an increased risk of neonatal apnoea in the newborn, by an abrupt cessation in the caffeine level.

Adult↗
PubMed1992

[Significance of the level of carcinoembryonic antigen in the alveolar lavage fluid in cancerous and non-cancerous bronchopulmonary pathology].

In a prospective study the level of carcinoembryonic antigen (ACE) were simultaneously measured in plasma and bronchoalveolar lavage liquid (LBA), in fifteen patients suffering from bronchopulmonary cancer and fifteen patients suffering from non-malignant pulmonary disease. In these two groups the level of ACE in LBA liquid (cancer 8,990 +/- 4,050 ng/ml; controls 2,510 +/- 1,060 ng/ml) were clearly more elevated than the corresponding plasma levels (cancer 1,931 +/- 1,760 ng/ml; controls 8.2 +/- 2 ng/ml) and the plasma levels of ACE were more elevated in the cancer group; in the same group the ACE levels in the LBA liquid were more elevated in the tumour group (4,770 +/- 2,180 ng/ml versus 808 +/- 300 ng/ml). This study has also shown the elevated levels of ACE in the LBA liquid in patients suffering from chronic bronchial inflammation (2,510 +/- 1,060 ng/ml) and during the course of acute bacterial pneumonia. The contribution of the ACE level in LBA liquid in relation to the plasma levels in the diagnosis of bronchopulmonary cancer would thus appear to have no clinical value, but the exact relationships between the phenomenon of chronic bronchial inflammation and metaplasia of the bronchial epithelium merit further study.

Biomarkers, Tumor↗
PubMed1992

Dexamethasone modulation of tumour necrosis factor-alpha (cachectin) release by activated normal human alveolar macrophages.

Recurrent infections of the lower respiratory tract are a frequent and serious side-effect of chronic corticosteroid treatment. Since alveolar macrophages (AM) are currently thought to play a central role in the protection of the lower respiratory tract against infectious agents, it is likely that a steroid-induced deficiency of AM is involved in this process. In this respect, when activated, AM are major producers of tumour necrosis factor-alpha (TNF or cachectin), a versatile cytokine with several biological properties including antiviral and anti-infectious activities. A deficit of TNF production induced by corticosteroid may be one mechanism of the sensitivity to infections. Thus normal human AM obtained by bronchoalveolar lavage were pretreated with dexamethasone (DXM) before activation with lipopolysaccharides (LPS) and the amounts of TNF released in culture were quantified. Pretreatment with DXM resulted in a marked decrease of TNF release in a dose-dependent fashion. In contrast, when AM were activated with LPS before DXM treatment, TNF release by AM was suppressed in a more limited fashion. Thus DXM suppression of LPS-activated AM ability to release TNF may play a role in the susceptibility to infections of patients chronically treated with corticosteroids.

Adult↗
PubMed1991

[Mechanisms of pulmonary fibrosis].

Lung fibrosis is characterized by the accumulation of extracellular matrix and mesenchymal cells leading a progressive loss of respiratory functional units. The accumulation of mesenchymal cells results from their migration and local replication. These cellular events are dependent upon the local presence of cytokines with chemotactic and/or mitogenic activity. The sequence of events leading the lung fibrosis is thought to result from a stereotyped response: after an initial injury, an inflammatory reaction develops and controls tissue repair through local production of cytokines. The permanency of these processes results in the development of fibrosis.

Acute Disease↗
PubMed1991

[Biopathology of fibrosing alveolitis].

Fibrosis is a condition where the functional tissue of an organ has been replaced by mesenchymal cells and their extracellular matrix. The process is frequent and may be regarded as univocal and independent of aetiology. An initial tissue damage is responsible for an inflammatory reaction which modulates and controls tissue repair with accumulation of mesenchymal cells, an accumulation which results from their migration and replication under the influence of chemotactic and/or mitogenic mediators (cytokines). Fibrosis occurs as an accentuation of this physiological process and may be understood as a healing process that has succeeded beyond normal expectation. Studies of idiopathic pulmonary fibrosis have improved our understanding of the physiopathology of pulmonary fibrosis. Alveolitis sets in response to an initial injury of undetermined nature, and from then on lymphocytes, neutrophils and macrophages intervene in the pathological process: (1) lymphocytes contribute to the perpetuation of the process by local production of immune complexes and coactivation of other inflammatory cells; (2) neutrophils and, to a lesser extent, eosinophils worsen the initial tissue injury by producing proteases and oxydants; (3) finally, macrophages control the local accumulation of mesenchymal cells by producing chemotactic and growth factors and by modulating the secretion by these cells of extracellular matrix.

Cytokines↗
PubMed1991

Presence of platelet-derived growth factor in normal and fibrotic lung is specifically associated with interstitial macrophages, while both interstitial macrophages and alveolar epithelial cells express the c-sis proto-oncogene.

Normal lung structure is maintained by the presence of mesenchymal cells and their extracellular matrix products. The slow normal turnover of these cells is disrupted in fibrotic disorders, resulting in the in situ accumulation of mesenchymal cells and their extracellular matrix leading to a progressive alveolar wall thickening. Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic disorder of the lung characterized by a diffuse interstitial and intra-alveolar inflammation dominated by macrophages and polymorphonuclear neutrophils. Evaluation of alveolar macrophages (AM) obtained by bronchoalveolar lavage has previously shown that AM from normal individuals spontaneously release small amounts of platelet-derived growth factor (PDGF), a chemotactic and growth factor for mesenchymal cells, whereas AM from IPF patients spontaneously release increased amounts of biologically active PDGF, suggesting its involvement in mesenchymal cell accumulation. However, other cells such as endothelial cells and vascular smooth muscle cells can also release PDGF in vitro. In order to specify PDGF location in lung parenchyma, open lung biopsies from normal individuals and IPF patients were examined by immunohistochemistry using an anti-PDGF antibody and by in situ hybridization using PDGF A-chain and B-chain gene probes. In normal as well as in fibrotic lung, PDGF was only present in relation with interstitial macrophages but not with any other inflammatory cells or mesenchymal cells. Furthermore, the percentage of PDGF-positive macrophages in IPF was 3-fold increased in comparison to normal lung. In addition, the percentage of PDGF-positive macrophages was the same in fibrotic and nonfibrotic areas of IPF lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

[Diagnostic pitfalls, artefacts and difficulties of thoracic radiography].

The antero-posterior X-ray film of the chest is still a basic examination in everyday clinical practice. It supplies multiple data but reading of the image is difficult and requires much accuracy and method. In this review paper we examine all the artefacts, pitfalls and diagnostic problems we have encountered in many years of experience, irrespective of their cause (technical, iatrogenic) or origin (parietal, intrathoracic, pleural, vascular, gastrointestinal, mediastinal, pulmonary). We consider that all pneumologists should have in mind these problems when faced with doubtful or abnormal radiographs of the chest.

Aorta, Thoracic↗