PubMed Health⌕ Search

Biomedical subjects

Ladislas Robert

Publications and source records attributed to Ladislas Robert.

8 recordsLinked to original sources
PubMed2003

[The mechanisms of aging. From genetic to epigenetic].

HUNDREDS OF THEORIES: The mechanisms of aging have been intensively studied since the middle of the last century on cellular and molecular level in experimental studies, case reports and epidemiological estimations. They have also generated a number of speculations and over 300 theories. THE ROLE OF GENES: Genetic data suggest an indirect determinism through the enhancement of antiradical defense mechanisms or by the presence of genes enhancing age-related diseases. One of the best examples is the dose-effect of genes coding for apolipoprotein E(4) (epsilon (4)), its presence in 0, 1 or 2 copies proportionally increases the risk of Alzheimer-type dementia but also atherosclerotic diseases. THE UNFORESEABILITY OF NATURE: However, it appears more and more clearly that epigenetic mechanisms (escaping direct genetic control) would be more directly implied in the decline of physiological functions with age. Several examples of such mechanisms are discussed and may be attributed to "negligence of nature' during the development of multicellular eukaryotic organisms. However, their very nature makes it possible to propose specific therapeutic interventions in order to slow down the effects of such mechanisms indirectly coded in the genome.

Adolescent↗
PubMed2002

Serum elastase activity, serum elastase inhibitors, and occurrence of carotid atherosclerotic plaques: the Etude sur le Vieillissement Artériel (EVA) study.

BACKGROUND: In the last decades, interest has increased in the potential deleterious atherogenic effects of some cellular elastase activities. The results of experimental and clinical investigations were inconsistent. In this report, we assessed the associations of serum elastase activity and serum elastase inhibitors with carotid plaque occurrence during the 4-year follow-up in a population of 859 subjects free of coronary heart disease and stroke (age, 59 to 71 years). METHODS AND RESULTS: Serum elastase activity and serum elastase inhibitors were measured at baseline examination. Carotid B-mode ultrasound examination was performed at baseline and 2 years and 4 years later. The occurrence of carotid plaques in subjects with the lowest serum elastase activity values (quartile 1), in those with the intermediate values (quartiles 2 to 3), and in those with the highest values (quartile 4) was, respectively, 24.6%, 18.9%, and 12.2% (P<0.001 for trend). The multivariate odds ratios of carotid plaque occurrence associated with the three groups (adjusted for major known cardiovascular risk factors) were, respectively, 1.00, 0.67 (CI, 0.44 to 1.02; P<0.06), and 0.40 (CI, 0.23 to 0.70, P<0.001). For serum elastase inhibitors, the occurrence of carotid plaques in quartile 1 (lowest values), quartiles 2 to 3, and quartile 4 (highest values) was, respectively, 11.7%, 18.8%, and 25.2% (P for trend<0.001). The corresponding multivariate adjusted odds ratios were 1.00, 1.98 (CI, 1.19 to 3.31, P<0.01), and 3.18 (CI, 1.80 to 5.60, P<0.001). CONCLUSIONS: Low values of serum elastase activity and high values of serum elastase inhibitors were strongly and independently associated with increased 4-year carotid plaque occurrence. Further studies are necessary to elucidate the nature of the associations between elastase parameters and atherosclerosis.

Aged↗
PubMed2002

Cell-matrix interactions in cancer spreading--effect of aging.

Passage of connective tissue barriers is a compulsory step in cancer spreading. This process involves a series of steps involving cell-matrix interactions. The complexity of these steps increased considerably during the last decades as a result of the identification of a large number of newly discovered macromolecular components of the extracellular matrix (ECM). It was also recognized that malignant cells can and do modify the production as well as the degradation of ECM components. The rapid development of aging biology during the second-half of the last century also contributed to the complexity but also to the importance of the newly emerging picture of cancer progression as a function of age. The structure and composition of the ECM is strongly age-dependent and may well represent one of the important factors influencing the age-distribution of human malignancies. As will be evident from the following reviews this relatively new and rapidly increasing picture of the age-dependence of cell-matrix interactions and cancer spreading should trigger more intense efforts on this relatively new discipline in cancer research.

Aging↗
PubMed2002

Extracellular matrix components in breast carcinomas.

A malignant process interferes with the normal 'programme' of extracellular matrix biosynthesis and can modify extensively the structure and composition of the matrix. This effect appears to be attributable to several processes such as direct production of some selected matrix macromolecules by malignant cells or indirectly by the production of factors by malignant cells interfering with the regulation of normal matrix production. Other possibilities may also exist, such as the direct action of an environmental carcinogen on otherwise normal mesenchymal cells. The result is a more or less profound modification of tissue structure and composition with possible feedback effects on the malignant process. Some examples will be discussed such as elastin production by some tumours as well as the biosynthesis of some other selected matrix macromolecules as tenascin and osteopontin by breast tumours. Although the detailed mechanisms of these specific matrix productions is not yet completely elucidated, the rapidly increasing knowledge on the regulation of specific matrix production process and deranged matrix production might represent a new area of crosstalk between cancer research and matrix biology.

Animals↗
PubMedDate not supplied

The age-dependent vasodilatation and endothelial calcium influx induced by elastin peptides are modulated by extracellular glucose level.

Elastin peptides have been shown to produce many biological effects on various cell types, including an endothelium- and NO-dependent vasodilatation mediated by extracellular calcium influx and intracellular calcium elevation. Under normal concentration of extracellular glucose, the vasodilatory effect is observed in adult rats and is lost with age. Here, we have studied the consequences of extracellular glucose level changes on these effects triggered by elastin peptides (10(-4)-10(-3) mg ml(-1)), on 6- and 30-month-old rats, using the tension myography and the patch-clamp techniques. Our results show that low (0 mM) or high (33 mM) extracellular glucose concentrations abolish the extracellular calcium influx induced, under normal glucose level (11 mM), by the elastin peptides in cultured human endothelial cells. Also, low or high glucose abolish the vasodilatory action of elastin peptides observed on aorta rings from adult rats under normal glucose concentration. On the contrary, a dilation of aged rat aorta is observed in the presence of elastin peptides and high glucose, whereas such dilation is not observed when the elastin peptides are added in the presence of normal glucose concentration. In aging, a restoration by high glucose of the NO-dependent vasodilatation induced by elastin peptides could enhance the production of damaging peroxynitrite, potentially altering the structure and function of the blood vessels. These results could be of importance in the evaluation and treatment of aged patients with pathophysiological dysregulations of the circulating glucose level, such as in diabetes, age-related glucose intolerance, or low glucose levels caused by inappropriate glucose control treatments.

Aging↗