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Biomedical subjects

A Renaud

Publications and source records attributed to A Renaud.

At least 55 records · Page 3Linked to original sources
PubMed1987

[Scleroderma].

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Female↗
PubMed1987

[Autoimmunity].

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Autoimmune Diseases↗
PubMed1983

Mapping of the S' subsites of porcine pancreatic and human leucocyte elastases.

Trifluoroacetyl dipeptide anilides have been synthesized and used to map the S' subsites of porcine pancreatic elastase and human leucocyte elastase. A confident mapping of these subsites, at least for the porcine enzyme, was possible since the x-ray crystallographic study of its complex with CF3CO-Lys-Ala-NH-Ph-p-CF3 at a resolution of 2.5 A (Hughes, D. L., Sieker, L. C., Bieth, J., and Dimicoli, J. L. (1982) J. Mol. Biol. 162, 645-658) shows the CF3CO group at the S1 subsite and the dipeptide anilide bound at sites close to the S'1-S'3 subsites. Furthermore the effect of substitution was easy to investigate since these ligands are reversible competitive inhibitors of elastases, whose mode of binding to the porcine enzyme has been shown by nuclear magnetic resonance spectroscopy (Dimicoli, J. L., Renaud, A., and Bieth, J. (1980) Eur. J. Biochem. 107, 423-432) to be essentially unique and common to all CF3CO peptide anilides. The total number of S' subsites was found to be three for both enzymes. The individual subsites have the following specificities: subsite S'1, in porcine pancreatic elastase this subsite prefers Lys to Ala or Glu. In human leucocyte elastase this subsite is less specific; subsite S'2, in porcine pancreatic elastase, this subsite has a marked specificity for Ala. It accommodates bulkier residues with some difficulty. In human leucocyte elastase there is a remarkable specificity for Leu at this subsite; subsite S'3, in porcine pancreatic elastase, this subsite has a high aromatic specificity. In human leucocyte elastase there is no such affinity in S'3 but favorable local interaction exists. These specificities are examined on the basis of the coordinates of the CF3CO-Lys-Ala-NH-Ph-p-CF3 . porcine pancreatic elastase complex. Furthermore the different specificities of the S'2 subsite found in our own work and proposed by Atlas (Atlas, D. (1975) J. Mol. Biol. 93, 39-53) are briefly discussed.

Anilides↗
PubMed1983

A training pack. Field programme management: food and nutrition.

One of the main barriers to development is the lack of adequately trained field staff. It is now widely recognized that the field worker plays a crucial role in implementing community development programmes. National development plans may look promising on paper but without the staff in the field, capable of managing the programmes, there is little chance for substantial gain from development efforts. To help address the problem of training for field workers, the Food Policy and Nutrition Division has produced the Training Pack. Its aim is to help field workers develop simple management skills which can be used in their daily work. The material in the Pack stresses those management techniques required by all field workers, whether their primary responsibility is agriculture, health, nutrition or community development. The Pack uses aspects of food and nutrition to illustrate the basic management skills, without attempting to turn the field workers into nutritionists. The emphasis of the Course is on the planning, implementation and evaluation of community activities. The practical approach advocated by these training materials is described in detail here.

Community Health Workers↗
PubMed1981

Kinetic parameters and the course of the disease in breast cancer.

The correlation between the labeling index (LI) of the primary mammary tumor and the course of the disease after initial treatment was studied prospectively on 128 patients. The surgical specimens of breast tumors were incubated in vitro with tritiated thymidine and autoradiographies were performed. Patients were treated by a simple mastectomy and axillary lymph nodes dissection; patients in whom one or more lymph nodes were found to be involved received postoperative radiotherapy. None of the patients received adjuvant chemotherapy. As the LIs were not known at the time of treatment, their values did not influence the choice of therapy. The follow-up period is greater than six years for all patients. The higher the LI, the shorter were the time intervals from initial treatment to first relapse or from first relapse to death. Moreover, significant correlations were found between the LI and the relapse-free survival and the survival rates. The proportion of relapses was particularly small in the group with the low LI. The shape of the curve suggests that the outcome in this group will be better than that in the group with a high or a median LI. The LI kept its prognostic value after multiple adjustments for other prognostic factors such as the staging, the size of the tumor, the number of metastasis bearing axillary lymph nodes, the presence of an inflammatory reaction, and hormonal status. The LI is significantly correlated with the histologic grading and in particular with its mitotic components. Thus, proliferative activity assessed by LI or the mitotic index appears to provide significant independent prognostic information.

Breast Neoplasms↗
PubMed1980

The indirect mechanism of action of the trifluoroacetyl peptides on elastase. Enzymatic and 19F NMR studies.

Trifluoroacetyl (CF3CO) dipeptide anilides are potent reversible inhibitors of elastase. Their 19F NMR spectra in the presence of the enzyme correspond therefore to slow chemical exchange. Their characteristics are very similar to those previously reported for other CF3CO-peptides. This should correspond to a single binding mode, in which the CF3CO group lies in a specific site in close contact with protein protons. Elastase, irreversibly inhibited by alkylation of Ser-195 with phenylsulfonyl fluoride derivatives, binds the CF3CO-Ala-containing dipeptide anilides still more tightly than the native enzyme. It no longer binds the dipeptide anilides containing a bulky CF3CO-Lys group, suggesting a location of the CF3CO site near the S1 subsite. On the other hand, the chemical shift of the CF3CO 19F resonance in the complex is the only NMR property affected by the enzyme sulfonylation, the T1 and nuclear Overhauser effect values being unmodified as compared to those in the complexes with the native enzyme. The observation of the NMR characteristics of elastases inhibited by phenylsulfonyl groups substituted with fluorine shows that complexation with CF3CO-peptides induces a change of conformation of the catalytic site which should correspond to a displacement of His-57 toward the ortho position of the phenylsulfonyl ring. Such a transconformation is not observed with corresponding acetylated peptides. The phenylsulfonyl fluoride derivatives are still able to react with elastase in the presence of a large excess of CF3CO-peptides. In such conditions the rate of inactivation is much slower but still at least 5% of that measured in the absence of the reversible inhibitors. This residual activity is hardly compatible with the presence of two exclusive modes of interaction of the CF3CO-peptides with native elastase. On the contrary, these observations are better interpreted by a single and identical mode of binding of the peptide to the native and sulfonylated enzymes. According to this mode of binding, the reversible inhibition of elastase by CF3CO-peptides should correspond to an indirect mechanism by which a change of conformation at the active site results in a reduced catalytic activity.

Animals↗