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Biomedical subjects

B Desrues

Publications and source records attributed to B Desrues.

54 records · Page 3Linked to original sources

Immunoscintigraphy of human lung squamous cell carcinoma using an iodine-131 labelled monoclonal antibody (Po66).

Monoclonal antibody (McAb) Po66 has been obtained by immunisation of mice against a human lung squamous cell carcinoma. The in vitro reactivity of the antibody with cancer cells and its ability to localise in human lung cancer xenografts growing in nude mice have been reported earlier. Presented here is the first clinical evaluation of the antibody for scintigraphic detection of tumours. Thirty-three patients with histologically confirmed primary non-small cell lung carcinoma were investigated. Twenty-seven of them were explored at the preoperative stage and six at 6 months after surgery. Biodistribution results were obtained from seven operated patients by combining injections of 131I-radiolabelled Po66 and of 125I-labelled unrelated immunoglobulin. The localisation index was three times higher for this specific antibody. Immunoscintigraphy detected 78% of primary tumours and 100% of recurrences. In this short series of patients, immunoscintigraphy proved helpful in the assessment of tumour spread in four patients by visualising localisations in the mediastinum or the contralateral lung which the CT scan had failed to demonstrate. Immunoscintigraphy was also more efficient than plain chest X-ray for the detection of local tumour recurrences.

Adult↗

The hyperimmunoglobulinaemia E and recurrent infections syndrome in an adult.

A 27 year old white woman with a history of chronic eczema and episodes of serious infection of the chest, skin, and bone presented with acute respiratory failure. She was found to have a spontaneous right pneumothorax and a pneumatocele in the left upper lobe. Despite a left upper lobectomy she was left with chronic respiratory failure, bullous lung disease, and bilateral bronchiectasis. The hyperimmunoglobulinaemia E and recurrent infections syndrome was diagnosed only in adult life.

Adult↗

Characterization of the antigen identified by Po66. A monoclonal antibody raised against a lung squamous cell carcinoma.

The mouse monoclonal antibody (mAb) Po66 has been shown in previous work to be localized in nude mice xenografts of human lung tumours when injected intravenously [Dazord L et al. (1987) Cancer Immunol Immunother 24: 263-268] and to be suitable for the scintigraphic detection of lung cancers in patients [Dazord L, et al. (1987) in Klapdor (ed) New tumour markers and their monoclonal antibodies. Georg Thieme, Stuttgart, New York, pp 444-450]. The nature of the antigen recognized by Po66 has been investigated in the present work and comparisons are made with antigens recognized by other mAbs prepared in the laboratory. These mAbs were raised either against lung squamous cell carcinoma (mAbs Po43, Po60), or against a bronchio-alveolar carcinoma (mAbs BAM33, BAM45, BAM54 and BAM69). Radioiodinated purified Po66 did not compete for cell binding with any other mAb. All Po and BAM mAbs reacted with tumour cells both cultured in vitro and grown in vivo. They recognized cytoplasmic antigens as judged by immunofluorescence examination of fixed cells or by immunoperoxidase staining of cancer tissues, but could never be visualized by immunofluorescence on the surface membrane of culture cells. The mAbs of the BAM series reacted with vimentin as demonstrated by immunofluorescence staining, showing alterations in the aspect of the filaments under the effect of colchicine. Radiolabelled mAbs Po43, BAM33 and BAM45 bound to partially purified cytoplasmic cytoskeleton components. In contrast, Po66 was never seen associated with intermediary filaments. The sensitivity to enzyme digestion of the antigen associated with Po66 was studied in comparison with those associated with Po43, BAM33 and BAM45. All antigens were sensitive to protease digestion while only the Po66-identified antigen was sensitive to periodate, neuraminidase and alpha-fucosidase. Thus, mAb Po66 identified an antigen of 47 kDa (as determined before) present in the cytoplasm but not related to the cytoskeleton, not detected on the cell surface and glycoprotein in nature.

Adenocarcinoma↗

Distribution of radiolabelled monoclonal antibody Po66 after intravenous injection into nude mice bearing human lung cancer grafts.

Monoclonal antibody Po66, produced by immunization against a patient's lung squamous cell carcinoma was found suitable for the scintigraphic detection of human tumours. Surprisingly, the cellular antigen recognized by Po66 was abundant in the cytoplasm of tumour cells but could not be detected on the surface membrane. In the present work the biodistribution of radiolabelled Po66 and of an unrelated immunoglobulin were studied comparatively after intravenous injection into nude mice bearing lung squamous cell carcinoma grafts. Radioactivity distribution among mouse organs and tumour was analysed by gamma counting and autohistoradiography. After injection, radiolabelled Po66 decreased rapidly from the blood in tumour-bearing animals whereas, in controls, it remained at a level comparable to that of the unrelated immunoglobulin. The antibody seemed slowly trapped by the tumour and, 12 days after its injection, distribution ratios between tumour and mouse organs reached values of 20-30 as against 1 in animals injected with the non-specific immunoglobulin. Autohistoradiographic investigations in the tumour confirmed the slow diffusion rate of the antibody, which remained in the vascular spaces up to the 24th hour after injection and diffused afterwards throughout the clusters of tumor cells. Furthermore, radioactivity was detected in cells which, unexpectedly, seemed morphologically unaltered. These cells, the viability of which remains to be determined, were predominant in the central area of the tumours. The results presented constitute new evidence of the ability of an in vivo injected monoclonal antibody to reach a cytoplasmic target inside non-necrotic cells and suggest that the cells permeable to the antibody might be in defective nutritional conditions.

Animals↗

[Home care of tracheotomized infants].

Home care of tracheostomized infants was studied through the experience of 4 families. Medical, social, financial, technical and psychological problems were reviewed. Common main outlines loomed out: after an initial defensive response against tracheostomy, parents were involved in the care of the child. They learned to suction the child and change the tube. Home comeback of the baby produced most anxiety to the parents for a few nights then they coped with it. The mothers had to leave their outside work so the family income decreased in all cases. The family's activities were most altered too. But babies' psychomotor development was excellent, language was delayed but finally normal in three cases, school attendance was obtained and all families considered lucky with the overall development. The knowledge of this common background permits to plan the parental education and the intervention of social workers, speech therapist, kinesiotherapist and psychologist.

Costs and Cost Analysis↗

[Post-intubation right paratracheal abscess. Apropos of a case].

We report the case of a young woman who had undergone a difficult emergency intubation and rapidly developed a mediastinal collection of pus. Mediastinoscopy, requested for diagnostic purposes, was also therapeutic as it drained the abscess. The patient received a course of antibiotics and was cured without sequelae. Accidents of tracheal intubation are severe, especially when unrecognized. They often include perforation of the oesophagus resulting in mediastinitis or abscess with an estimated 30 to 40% mortality rate, and they constitute a medico-surgical emergency. In the case reported here mediastinoscopy was crucial, but the theoretical value of computerized tomography must be stressed since this method not only detects the lesion but is also used to perform a guided drainage.

Abscess↗

[Prescribing of long-term oxygen therapy and observation of its results].

It is accepted that long-term oxygen therapy should be given for at least 15 hours per day. We have assessed the value of domiciliary oxygen therapy for a mean period of two months in 127 patients under the care of the association for Aid to Respiratory Failure Patients in Brittany (A.I.R.B.). These patients have been equipped with oxygen concentrators. The mean duration of oxygen therapy is 11.8 +/- 5 hours per day. Only 30 patients (23.6%) achieved treatment of 15 hours or more. The patients were split into two groups on the basis of their usage of oxygen: group A (n = 97 = 76.4%) whose oxygen consumption was less than 15 hours per day; group B (n = 30 = 23.6%) whose consumption of oxygen was equal to or superior to 15 hours per day. There was no difference between the two groups as regards age, sex or cause of their respiratory failure nor as regards socio-professional classification, their habitat, or on the basis of respiratory function tests and tolerance of their treatment. On the other hand, patients having the longest duration of oxygen therapy were the most severe (PaO2 56.5 +/- 9.3, in group A and 50.4 +/- 7.3 in group B), they were also the most compliant (good compliance occurred in 27.8% in group A and 76.7% in group B) and were taking the prescribed therapy for the longest time (group A 13.8 +/- 2.7 hours, group B 17 +/- 2.7 hours). Then again, it is also these patients who had the best understanding and the best evaluation of the duration of oxygen therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Ornithine decarboxylase basal activity in liver, oesophagus and lung of vitamin A deficient rats, and the effect of retinoic acid.

Ornithine decarboxylase (ODC, EC 4.1.1.17) activity was measured, without exogenous stimulation, in the liver, oesophagus and lung of Wistar rats which were vitamin A deficient or supplemented with retinol or retinoic acid. The enzyme basal activity in such deficiency conditions was higher, when compared with controls, in the oesophagus and especially in the lungs. Retinoic acid normalized enzyme activity only at high doses (300 micrograms/day). In the liver, initial retinol deficiency did not sensitively modify ODC activity, and retinoic acid then stimulated the enzyme abnormally. This phenomenon could not be observed at later stages of vitamin deficiency (but there again without cytological abnormalities or thymidine incorporation disturbances): liver ODC response then became comparable to that of other tissues. These results highlight the particular basal hyperactivity of pulmonary ODC during the initial stages of vitamin A deficiency, indicative of an enhanced tendency to cell proliferation. A special stimulating effect of retinoic acid on ODC, contemporary with early deficiency, was observed in the liver; this effect was not observed at a later stage in normally fed rats.

Animals↗

[Idiopathic pulmonary hemosiderosis and rheumatoid arthritis. Apropos of a case].

A 38-year-old woman was known to have had a histologically proven "idiopathic" pulmonary hemosiderosis for 7 years; the authors report the onset in this patient of polyarthralgias with articular swelling and positivity of rheumatoid factor, all features consistent with the diagnosis of rheumatoid arthritis, whose beginning was certainly hidden by steroid therapy. This case, as some others previously published, outlines the possibility of the association of pulmonary hemosiderosis and rheumatoid arthritis: is this a casual association, or may pulmonary hemosiderosis be a rare manifestation of rheumatoid arthritis?

Adult↗

[Current therapeutic attitudes on pneumothorax in adults].

Recent advances in thoracoscopy and surgical procedures have led to modifications in therapeutic approaches to easily diagnosed pneumothorax. These procedures make it possible to adjust therapy to the severity and underlying causes of the disease which may vary from simple bullous dystrophy to neoplasia. For simple pneumothorax, a suitable treatment may be to put the patient under observation or exsufflation, but thoracoscopy has the advantage of visualizing the lesion and, in certain cases, enables it to be treated. Surgery is indicated when an extensive bullous system is seen at thoracoscopy or when this technique is unsuccessful. A considerable reduction in the risk of relapse of this usually benign condition should be expected.

Emergencies↗

[Post-traumatic pneumatocele and hemato-pneumatocele of the lung. Apropos of 3 cases].

Pneumatocele and haemato-pneumatocele are air or air/fluid cavitary lesions which develop in the lung parenchyma after thoracic trauma. The formation of this lesion requires a direct violent impact on the pliable lung wall which explains its frequency in young adults. They are preferentially localised in the lung bases. The importance of associated lesions often marks the pneumatocele. Though rarely described, its frequency is certainly underestimated. If haemoptysis is the most frequent clinical sign it is the chest x-ray which demonstrates the early abnormality in the form of a rounded translucent image with a fine contour and variable diameter. The existence of a fluid level suggests the presence of blood (haemato-pneumatocele). The differential diagnosis with a localised pneumothorax, a diaphragmatic hernia and a pre-existing cystic lesion is easy as a rule but an evacuated pulmonary haematoma may lead to the discussion, especially as the mechanism of their formation may be the same. In isolation their clinical implications are minimal, their evolution favourable and after several weeks with a restitution of the integrity of the pulmonary parenchyma the absence of therapeutic intervention is justified.

Adolescent↗

[T lymphocyte subsets in alveolar lavage and peripheral blood in sarcoidosis and extrinsic allergic alveolitis].

Accumulation of inflammatory and immune cells within lung parenchyma would constitute the initial step in producing the alveolar structural abnormalities. It is usually assumed that alveolitis, as assessed by broncho-alveolar lavage (BAL), represents a biological assessment of lung disease activity. The aim of this study, using monoclonal antibodies, is to characterize the T lymphocytes alveolitis in the lung and in peripheral blood in 3 well-defined populations: 1 degree) control subjects (n = 7); 2 degrees) patients with biopsy proven mediastino-pulmonary sarcoidosis (sarc) (n = 73), classified according to their clinical activity as active, inactive, chronic, and treated; 3 degrees) patients with extrinsic alveolar alveolitis (EAA) (n = 19). For the same BAL volume, the % of CD4+ cells and the CD4/CD8 ratio are increased in chronic and active sarc, contrasting with an increase in the % of CD8+ cells and a decrease in the CD4/CD8 ratio in the EAA. In absolute values, there are 2 times as many CD4+ cells and 5 times as many CD8+ cells in EAA than in sarcoidosis. In sarcoidosis, corticotherapy tends to normalize the CD4/CD8 ratio although the intensity of the lymphocytic alveolitis is not affected. In the peripheral blood, lymphopenia is observed only in the active form of sarc. in the CD4+ population, without any significant change in the CD4/CD8 ratio compared to the other groups. The number and distributions of BAL. T lymphocytes subsets may constitute a biological indicator for diagnostic orientation, but they do not distinguish sufficiently between the different groups of sarcoidosis to be of any prognostic value.

Adult↗

Purification of a tumoral marker recognized by monoclonal antibody Po66 and associated with human lung squamous cell carcinoma.

Monoclonal antibody (MAb) Po66, a murine IgG1, was raised by immunization against human lung squamous cell carcinoma. When injected intravenously, Po66 showed prolonged retention in the tumor. It recognized an intracellular antigen. The human lung squamous carcinoma cell line SK-MES-1 expresses the antigen recognized by MAb Po66 and was used as a source of biological material for its purification. The SK-MES-1 cell line was labeled in culture with [35S]methionine and its lysate was immunoprecipitated with Po66 immobilized on Protein G-Sepharose. The precipitate contained three proteins (47, 50 and 69 kDa) absent in the controls. The 69 kDa polypeptide was further purified by anion exchange and immunoaffinity chromatographies. To date, no other tumor marker expressed in non-small cell lung cancer with these characteristics has been described and as such this marker is interesting for future use in immunotherapy and in diagnosis.

Animals↗

Expression of Po66-CBP, a galectin-8, in different types of primary and secondary broncho-pulmonary tumors.

The monoclonal antibody Po66 is an IgG1 immunoglobulin isolated from a human bronchial squamous carcinoma and directed against a carbohydrate binding protein, Po66-CBP, belonging to the galectin family involved in neoplastic processes. This Po66 antibody has been shown to be useful for immunoscintigraphic detection of squamous cell carcinoma metastasis. We examined the expression of Po66-CBP in a wider range of primary or secondary malignant tumors of the lung of various histological types. We studied 52 specimens of broncho-pulmonary tumors including 41 primary squamous, glandular or neuro-endocrine tumors and 11 secondary tumors of glandular, connective tissue, melanocytic or germinal origin as well as 9 extra-pulmonary primary tumors with histological types similar to lung metastases. An immunohistochemical study was performed using an amplification system on paraffin-embedded sections. All histological types were positive for Po66 antibody, the cell origin giving no influence on the expression of Po66-CBP. There was however a relation between Po66-CBP expression and the degree of differentiation notably for squamous cell cancer and neuro-endocrine tumors. The metastatic character of the tumor tissue did not affect Po66-CBP expression.

Adult↗

Expression of Po66-CBP, a type-8 galectin, in different healthy, tumoral and peritumoral tissues.

UNLABELLED: A monoclonal antibody, Po66, recognized an antigen named Po66 carbohydrate binding protein (PO66-CBP), which was homologous to the galectin-8 protein. Two additional isoforms previously not described were characterized. The aim of this study was to compare the expression of Po66-CBP and its isoforms in different healthy, tumoral and peritumoral tissues and at last to determine the localization of the protein in tumors and distant tissues. MATERIALS AND METHODS: Reverse transcriptase PCR of Po66-CBP was performed on total RNA extract from eleven healthy and eleven tumoral and peritumoral tissue specimens. Antibody Po66 was used to localize the protein in the tumors and distant tissues by an immunohistochemistry method. RESULTS: Po66-CBP was expressed by half of the healthy tissues. One of the isoforms, the last often present in healthy tissues, was found in all tumoral and peritumoral tissues studied. Immunohistochemistry evidenced a gradient of protein expression in normal cells depending on the vicinity of tumoral tissue. Po66-CBP expression was modified in cancerous tissue, suggesting the implication of galectins in carcinogenesis.

Base Sequence↗

Uptake and release of radiolabelled monoclonal antibody Po66 by multicellular aggregates obtained from a lung squamous carcinoma cell line.

Po66, a monoclonal antibody (MAb) directed against lung squamous cell carcinoma, has been shown, when injected intravenously, to be retained for a long time in tumors. This property encouraged trials to use Po66 as an agent of metabolic radiotherapy. The suitability of multicellular spheroids to reproduce the in vivo conditions of irradiation of tumors by Po66 was investigated in the present work. Spheroids were formed from the lung carcinoma cell line SK-MES-1. They resembled morphologically small carcinoma nodules with desmosome-like intercellular junctions at the periphery and a central necrotic core. The cells expressing the antigen recognized by Po66 had a heterogeneous distribution and were predominant in the outer layers of the cell aggregates. Spheroids were exposed to radiolabelled Po66. The MAb diffused slowly and reached a maximal incorporation after 4-12 hours incubation. A control unrelated antibody did not penetrate appreciably. Autohistoradiographic experiments suggested that the antibody accumulated in most cells expressing the antigen. The rate of MAb release from the spheroids was very low (T 1/2 = 163 h). Taken together, the data indicate that spheroids might be a relevant model to investigate the parameters controlling Po66-mediated immunoradiotherapy.

Animals↗