Biomedical subjects
Publications and source records attributed to A Boudon.
A series of acyclic hydroxamic acids harboring strategically placed alpha-arylsulfonamido and thioether groups was synthesized and found to be potent inhibitors of various MMPs. An unprecedented cleavage of t-butyl hydroxamates to hydroxamic acids was found.
Molecular models of a pharmacophore for NK1 neurokinin antagonists and of ligand-receptor complexes for the human NK1 G protein-coupled receptor are presented. The models develop a structural rationale for the discovery of the recently described highly potent peptidomimetic NK1 antagonists S18523 and S19752 which were designed to be water soluble. Water solubility was conferred on these compounds by introduction of an anionic butyl-tetrazole substituent on the scaffold of dipeptide-derived NK1 antagonist analogues. The models provide convincing evidence that the anionic butyl-tetrazole moieties of S18523 and S19752 protrude outside the membrane-spanning domain of the receptor and do not interfere significantly with the core of the antagonist binding site. It is emphasized that this result could only be obtained through the combination of the two modelling approaches. The result suggest a general way to modify the transport properties of the peptidomimetic antagonists without altering the receptor-binding interaction, and it outlines the potential of including the combination of pharmacophore models and crude models of receptor-ligand complexes early in the drug design process.
Structural variations of P2 and P3 residues in tripeptidic boroarginine thrombin inhibitors led to compounds with similar potency than reference compound DuP 714, but with enhanced selectivity for thrombin compared to plasmin.
A new method is presented to calculate the Molecular Lipophilicity Potential (MLP). The method is validated by showing that the MLP thus generated on the solvent-accessible surface can be used to back-calculate log P. Because the MLP is shown to be sensitive to conformational effects, the MLP/log P relation is best sought by taking all conformers into account. The MLP method presented here can be used as a third field in CoMFA studies, as illustrated with two series of alpha 1-adrenoceptor ligands. In the first series, the steric, electrostatic and lipophilic fields are highly intercorrelated, and taken separately yield comparable models. In the second series of ligands, the best model is obtained with the lipophilic field alone, allowing insights into ligand-receptor interactions.
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The authors report two cases of acute myeloid leukemia with prevalent cutaneous lesions. The positivity of granulo-monocytic antibodies and the exclusive cutaneous site of the lesions drove them previously to the diagnosis of histiocytic sarcoma. These cases stress the problem of the immunological identification of cutaneous lymphomas of "histiocytic" type.
We report a case of a 68 years old male patient treated for chronic lymphocytic leukaemia, presenting a right inguino-crural tender lymphadenopathy with periadenitis. The histologic changes associated with adenitis were large foci of necrosis with regular crown of epithelioid cells, without giant cell. The presence of Herpes simplex virus 2 was confirmed by immunohistochemistry and culture. Occurrence, physiopathology, clinical and histological aspects of Herpes simplex lymphadenitis in patients with haematologic disorders, are discussed.
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Ultrastructural study of a case of granulomatosis disciformis occurring on the legs of a 62-year-old woman. The diagnosis is based upon the contrast between the clinical aspect of necrobiosis lipoidica and the histologic aspect of inflammatory granulomatous infiltrate of dermis without necrobiosis nor palisading. Electron microscopic findings are: perivascular mixed cell infiltrate and histiocytic granuloma with lysosomial and phagocytic activity; degenerative and necrotic cellular alterations; modifications of collagen fibres with two types of fibres: the thinnest are the most numerous and have a mean diameter of 50 nm, the thickest of 110 nm; no significant lesions of capillary walls. These findings suggest the following succession of pathological events: cellular necrosis, lysosomial and phagocytic activity, scarring. Some descriptions of necrobiosis lipoidica and granuloma annulare seem to be quite similar and our findings are in favour of the unity of these three illnesses.
Prevention of post-transfusion malaria remains a worrying problem. Until now it was very difficult to obtain homologous antigens, and immunologic methods used to detect malaria were expensive. We tested the ready-to-use Plasmodium falciparum prepared slides using the IFA (indirect fluorescent antibody) test on 866 selected potentially dangerous donors and known malaria cases. We found that it is a simple, quick, reliable and inexpensive method that can be easily used by blood banks and improve blood transfusion safety.
Several cases of chromoblastomycosis have been observed, for 7 years, in the laboratory of Pathology, in the IMTSSA . Their various aspects are described. The diagnosis includes three stages: clinic, mycology and pathology. The most frequent clinical lesions have been observed on the legs. Often, they were like a malignant tumour (carcinoma). The fungal investigation, by direct research of fungi in the lesions, is carried out scarcely, because it is difficult. It should be completed by cultures, in order to isolate the pathogenic agent, but its identification is not possible, if it is not carried out by a laboratory of mycology. The most simple technique , adapted to tropical areas, is the pathological examination. It reveals several points of interest: by analyzing the cutaneous lesions (in order to eliminate a carcinoma)--observing the intensity of the inflammatory reaction--but, first of all, the discovery of the thick-walled dark cells. Two techniques are usual, for staining, but they could be improved by using other special techniques, in order to analyse more carefully the lesions.
The smears of P. falciparum parasited blood ready to be employed, that we have tested in indirect immunofluorescence to detect blood donors who can be at the origin of post transfusional paludism, seem to offer a very important progress to us for the improvement of transfusion security. Their routine use can be recommended because their easy way of using allows their adoption by very many transfusion centers.
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