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The purpose of this study is to measure the impact of an educational program to raise awareness of the increased spending energy in two different population of patients with breast cancer by using the questionnaire POPAQ (Population Physical Activity Questionnaire). This is a prospective study including two groups of 15 consecutive breast cancer patients (≤ 50 years Group 1 and Group 2 > 50 and < 70 years) followed in the department of radiotherapy at the Institute of Cancer of the Loire from January to July 2011. A questionnaire of physical activity assessment was used at two different times before the diagnosis/treatment of breast cancer (t0) and at 6 months (t6) to measure the impact of the awareness method. Comparison of different measures of daily energy expenditure (t0) between groups 1 and 2 was statistically significant (1,1803 and 9434 kJ/24 h, respectively, p = 0.0005). Daily energy expenditure of professional activity was statistically different between the two groups (1437 and 457 kJ/24 h, in groups 1 and 2, respectively; p = 0.003). Between t0 and t6, we observed a significant decrease in total energy consumption in group 1 (1,1803 to 1,0876 kJ/24 h) while there was no significant change between the group 2, except energy expended at rest (basal metabolism). There were differences in daily energy expenditure based on age may influence behavioral patterns deal with energy expenditure in physical activities. Tomorrow's challenges are to provide re-entrainment programs tailored to targeted populations.

Oxidative damage to mitochondrial DNA (mtDNA) has been implicated as a contributing factor to the origin of many pathological processes. Among the major DNA lesions generated by oxidative stress, 8-oxoguanine (8-oxoG) has a strong mutagenic potential. The main pathway for the repair of this lesion is the base excision repair (BER) initiated by the OGG1 DNA glycosylase. In human cells alternative splicing of the hOGG1 transcript yields two forms of the protein, alpha and beta, that are localised in the nucleus and the mitochondria, respectively. We describe here a hOGG1 somatic mutation, found in a kidney cancer, that modifies the intracellular localisation of beta-hOGG1. The glycine 12 to glutamic acid substitution does not affect the enzymatic activity of the enzyme but lies in what was predicted to be a mitochondrial targeting sequence (MTS). Immunocytochemical localisation experiments show that the G12E mutant protein has diffuse cytoplasmic distribution instead of the mitochondrial localisation found for the wild-type, providing an example of a single amino acid substitution capable of disrupting a MTS. These results imply that these cancer cells are deficient in their mitochondrial 8-oxoG DNA repair activity., (Copyright 2002 Elsevier Science B.V.)

Subtle modulation of antibody-binding properties by protein engineering often lies with an accurate structural and energetic description of how an antigen is recognised. Thus, with the intent to increase the affinity and add a bias in favour of natural estradiol compared with its chemically modified immunogen, we have determined the crystal structure of two anti-estradiol monoclonal antibodies, 10G6D6 and 17E12E5. Although generated against the same estradiol derivative, these antibodies share little sequence identity, which is reflected in dissimilar binding pockets and in different positioning of the steroid. In both antibodies the characteristic 17-hydroxyl group is buried deeply at the bottom of hydrophobic pockets and stabilised by hydrogen bonds. Apart from this similarity, the steroid is oriented differently in the respective binding pockets. The high specificity of both antibodies has been mapped out, and even closely related steroids show low cross-reactivity. The structural studies of the complex formed between 10G6D6 and 6-CMO-estradiol have identified contacts between the 6-CMO coupling linker and an arginine residue from the heavy chain CDR2 segment. This segment is now being targeted by random mutagenesis to select mutants with a preference for natural estradiol compared to the branched hapten., (Copyright 2002 Academic Press.)

The antibody D2.3 catalyzes the hydrolysis of several p-nitrobenzyl and p-nitrophenyl esters with significant rate enhancement; product inhibition is observed with the former compounds but not with the latter. Whereas enzyme specificity has been extensively studied by X-ray crystallography, structural data on catalytic antibodies have thus far related only to one of the reactions they catalyze. To investigate the substrate specificity and the substrate relative to product selectivity of D2.3, we have determined the structures of its complexes with two p-nitrophenyl phosphonate transition state analogs (TSAs) and with the reaction product, p-nitrophenol. The complexes with these TSAs, determined at 1.9 A resolution, and that with p-nitrobenzyl phosphonate determined previously, differ mainly by the locations and conformations of the ligands. Taken together with kinetic data, the structures suggest that a hydrogen bond to an atom of the substrate distant by eight covalent bonds from the carbonyl group of the hydrolyzed ester bond contributes to catalytic efficiency and substrate specificity. The structure of Fab D2.3 complexed with p-nitrophenol was determined at 2.1 A resolution. Release of p-nitrophenol is facilitated due to the unfavourable interaction of the partial charge of the nitro group of p-nitrophenolate with the hydrophobic cavity where it is located, and to the absence of a direct hydrogen bond between the product and the Fab. Catalytic specificity and the manner of product release are both affected by interactions with substrate atoms remote from the reaction center that were not programmed in the design of the TSA used to elicit this antibody. Selection of a catalytic antibody that makes use of TSA unprogrammed features has been made practical because of the screening for catalytic efficiency incorporated in the procedure used to obtain it., (Copyright 1998 Academic Press)

Angular pregnancies which result from implantation of the fertilised oocyte in the mucosa of a uterine horn are very rare. They are usually demonstrated by a picture of rupture which is associated with severe abdominal pain, the syndrome of internal haemorrhage, often a state of shock and all occurring usually between the 6th and the 12th week of pregnancy. Although many authors have shown that there is congenital abnormality of the uterus in these cases this does not always happen and the aetiology of "idiopathic angular pregnancies" is ill understood. The treatment is carried out according to the clinical state: endometrial curettage under laparoscopic control, removal of the uterine horn together with the tube on the same side or even hysterectomy.