Role of the Maillard reaction in aging and age-related diseases. Studies at the cellular-molecular level.

Increase in life expectancy concerns most populations but more importantly developed countries. This increase is accompanied by the shift of chronic diseases to the senior population, especially cardiovascular diseases and diabetes type II. Aging mechanisms, mostly post-genetic, comprise among others the Maillard reaction which strongly contributes by several harmful processes to the age-dependent decline of tissue structure and function. Several of these mechanisms were studied in our laboratory at the cellular-molecular level and will be described in this review with respect to their role in aging and age-related pathologies, especially cardiovascular diseases.

The role of the NP in primary care of adults with autism spectrum disorder.

ABSTRACT: Adults with autism spectrum disorder have poorer physical and psychological health outcomes compared with individuals who are neurotypical and benefit from exceptional primary care. NPs are uniquely positioned to reform primary care and eliminate inequities, and can help influence practice standards and optimize care for these patients through education, advocacy, and health promotion.

The effect of cell-matrix interactions and aging on the malignant process.

The malignant process, transformation of normal cells, proliferation, and metastasis formation, was considered as if originating from one single cell. Although the intrinsic mechanisms of transformation from the normal to the malignant state were both confirmed, an increasing body of evidence points to the surrounding matrix and cell-matrix interactions as major players in this process. Some of the most important arguments in favor of this contention are cited and commented in this chapter. Another important question concerns the relationship between the aging process and malignant transformation. A few decades ago, the frequency of clinically manifest tumors of several organs and tissues appeared to increase with age. As, however, average life expectancy increased rapidly over the last decades, clinical frequency of malignant tumors did not follow this tendency. It was argued that late in life the malignant process appears to decline. This justly inspired several teams to study the relationship between cellular senescence and malignant transformation. This is now an actively growing field which deserves special attention. Some of the pertinent experimental and theoretical arguments in favor of an antioncogene-mediated switch between these two processes are also reviewed with the caveat that this important and new subject of basic and clinical research on the malignant process is just at its beginning. It will certainly take an increasing importance during the coming years and decades with the hope to contribute to answer one of the most burning questions concerning the aging process: will life expectancy continue to increase linearly as predicted by some gerontologists, or will life expectancy level off or even decline as predicted by other epidemiologists. The relationship between cellular senescence and malignant transformation will play in this respect an important role.

Effect of intrapartum antibiotic prophylaxis against group B streptococcal infection on comparisons of rates of endometritis and urinary tract infection in multicenter surveillance.

OBJECTIVE: To establish whether antibiotic prophylaxis against group B streptococcal infection may be a confounding factor in comparisons of rates of endometritis and urinary tract infection after vaginal delivery. DESIGN: Prospective study. SETTING: Maternity units at 48 hospitals in a regional surveillance network in France during 2001-2004. METHODS: The maternity units used a common protocol to establish whether antibiotic prophylaxis was indicated. Risk factors for endometritis and urinary tract infections were evaluated using multiple logistic regression. RESULTS: We analyzed 49,786 vaginal deliveries. The percentage of women receiving antibiotic prophylaxis varied widely and significantly among the maternity units (range, 4.4%-26.0%; median, 15.8%; 25th percentile, 12.1%; 75th percentile, 19.0%) (P < .001, by Mantel-Haenszel chi(2) test). The incidence rate of endometritis was significantly reduced from 0.25% to 0.11% by antibiotic prophylaxis (P = .001). There was a decrease in the incidence of urinary tract infection from 0.37% to 0.32%, but it was not statistically significant (P = .251). CONCLUSIONS: A reduction in the incidence of endometritis was observed when intrapartum antibiotic prophylaxis against group B streptococcal infection was used. However, the proportion of women considered to be at risk of infection varied widely among institutions. Comparisons of rates of endometritis among maternity units, but not urinary tract infection rates, should take into account antibiotic prophylaxis as a significant confounding factor.

Cryptic deletion involving the ATM locus at 11q22.3 approximately q23.1 in B-cell chronic lymphocytic leukemia and related disorders.

B-cell chronic lymphocytic leukemia (B-CLL) follows a heterogeneous clinical course, and several biological parameters have been investigated to try to predict its clinical outcome. New staging systems including cytogenetics and CD38 expression as predictive values have been developed. Deletions of 11q22.3 approximately q23.1 detected at diagnosis in cases of CLL patients have been associated with a relatively aggressive disease. This region, which contains the ataxia telangiectasia mutated (ATM) locus, may be implicated in the pathogenesis of lymphoid malignancies. We developed a set of dual-color specific probes to evaluate the ATM deletion by means of fluorescence in situ hybridization (FISH). We also used flow cytometry to investigate CD38 expression. Forty-one patients with CLL or low-grade B-cell lymphomas were studied at diagnosis or before treatment. FISH showed that only three CLL patients had deletions in the 11q23 locus; all three had progressive disease and were resistant to treatment. These data show that our FISH set of probes efficiently detects ATM deletions in CLL. No correlation was found between ATM deletions and CD38 expression level. These results confirm the prognostic significance of ATM deletions in CLL.

[The mechanisms of aging. From genetic to epigenetic]. / Les mécanismes du vieillissement. Du génétique vers l'épigénétique.

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.

[Information exchanges between cells and extracellular matrix. Influence of aging]. / Échange d'informations entre cellules et matrice extracellulaire. Influence du vieillissement.

Our interest, since a number of years, has focalized on the worldwide rapid expansion of the aging population, accompanied by a progressive increase of age-related pathologies. Most of these concern connective tissues, that are rich in extracellular matrix (ECM), such as osteoarticular, cardiovascular and pulmonary diseases. Therefore age-related modifications of connective tissues become of increasing importance for the understanding of these diseases. In this article, we shall recapitulate some of our (and others') experiments on fibronectin, an important matrix glycoprotein mediating cell-matrix interactions. We studied the effect of age on fibronectin biosynthesis and also the effect of UV-radiation. Both conditions, age and radiation, produce a significant increase of fibronectin biosynthesis. Some results, when in vitro aging of skin fibroblasts was studied, exhibited also a passage-dependent regulation of fibronectin biosynthesis. A few studies, quoted in this review, were reported about the effect of age on integrin expression and function. An important finding was that novel biological fragments of fibronectin have proteolytic activities, pro-inflammatory activity in articular tissues, enhance malignant transformation as well as other activities. Proteolytic activity also increases with age-dependent increase of fibronectin fragmentation. This process exhibits positive feedback properties, forming a vicious circle, possibly important for the age-dependent aggravation of connective tissue diseases. Besides these observations, the recent demonstration of fibronectin elasticity suggests its implication in novel biological regulation as for instance mechano-transduction.

[Eye connective tissues: cornea and vitreous body]. / Recherches sur les tissus conjonctifs oculaires. La cornée et le corps vitré

The authors, ophtalmologist (Y.P.) and basic scientists (J.L.-R and L.R.), collaborated on eye-research since 1962 on normal and pathological aspects of eye tissues, considered as specialized forms of connective tissues, and on specific aspects of the physiology and pathology of the eye. This date coincides with the foundation of the French Society of Connective Tissues, which celebrates the 50th anniversary of its creation. We shall present here some of our work on the ontogenetic and phylogenetic aspects of the cornea, on its structure, function and regulation in normal and pathological states, taken from a large number of publications of our laboratories. Our work on cornea started with the study of the morphogenesis of its lamellar structure, made of collagen fibers and proteoglycans. This led us to the isolation and characterization of structural (or matrix) glycoproteins, a new class of matrix components, present also in all other connective tissues, and to the study of their biosynthesis by keratocytes. Corneal wounds and regeneration were also studied, as well as some corneal pathologies such as keratoconus. The confrontation of quantitative morphological methods with biochemical procedures were to yield important results on the mechanisms of the maintenance of corneal structure and function. Another series of studies concerned the vitreous where we detected, besides previously characterized components, such as hyaluronan and collagens, fibronectin which plays an important role in the adhesion of hyaluronan to the collagen network. Its age-dependent modifications were also studied, with a special focus on the role of reactive oxygen species (ROS)-mediated degradation of hyaluronan, especially important for the aging of the vitreous.

[Fiftieth anniversary of the French Society for Connective Tissue Research]. / Cinquantenaire de la Société Française des Tissus Conjonctifs--introduction.

The Society was founded in 1962, at an international meeting organized at the Biomedical Institute rue des Saints-Pères, in Paris in the Department of Biochemistry headed at that time by Pr. Max F. Jayle, and published in the "Exposés Annuels de Biochimie Médicale" in 1963. At its beginnings a "Club", with a limited number of participants, it expanded rapidly into a Society, renamed recently "French Society of the Biology of Extracellular Matrix", with approximately 200 members working on a variety of subjects. Only six of these teams could present an oral report at the meeting of the Biological Society on January 18, 2012, celebrating this anniversary at the Curie Institute. A few more could send written contributions for this special issue of "Biologie Aujourd'hui". In this short introduction we shall recall some important stages of the developing connective tissue science. Besides such classical subjects, as the macromolecular components of connective tissue matrix, this discipline incorporated progressively receptors, integrins and other molecules, that mediate cell-matrix interactions.

[Theodor Huzella and the initiation of research on the interactions between cells and the extracellular matrix]. / Theodor Huzella et l'origine de la recherche sur l'interaction entre cellules et matrice extracellulaire.

Interactions between cells and the surrounding "biomatrix", mediated by receptors as integrins or the elastin receptor is the most important topic in up to date research on connective tissues. Looking for the origin of this concept, one finds the pioneering work of Theodor Huzella, professor of histology-embryology at the Medical University of Budapest during pre-world war II decades. Using time-laps micro-cinematography in reflected light, he visualized the important role of connective tissue fibers, prepared in his laboratory, for the oriented migration of normal and malignant cells. His theoretical explanations, attributing an "active" role to the elasticity of the argyrophilic fibrous network in the coordination of cell societies, can now be reinterpreted in the light of recent work on the mechanotransduction of "messages" from the extracellular matrix to the cell inside. We propose a succinct review of Huzella's work and theories reinterpreted in the light of up-to-date knowledge on cell-matrix interactions.

Introduction: matrix biology in the 21st century. From a static-rheological role to a dynamic-signaling function.

These introductory remarks contain a succinct reminder of the developmental history of matrix biology, from the descriptive biochemistry of connective tissues to the up to date cell biology of extracellular matrices. The rapid growth of this discipline makes it prohibitive to give a complete coverage of recent results on all aspects of matrix biology and pathology. The articles in this special issue concern several of the ECM-macromolecules and some of their functional characteristics. No space remained for reviews on matrix related pathologies. As a partial compensation some recent aspects of cell-cell and cell-matrix interactions in malignant growth are mentioned in this introduction.

[Thirty years after fibronectin discovery: role in malignant transformation and in ageing]. / Trente ans de fibronectine, rôle dans la transformation maligne et le vieillissement.

1973 was the year of a major discovery: two proteins were shown to disappear from cell surface when cells were transformed by tumor viruses. Later on a large number of glycoproteins were recognized as identical and coined as fibronectin. In spite of 30 years of studies, interest in fibronectin remains vivid. Thanks to its study, understanding of extracellular matrix organisation, cell-matrix interactions and signalling through integrins, formation of fibronectin based fibrillar matrix made great progress. Furthermore importance of matricryptic sites emerged as well as matricryptins. Such peptides show properties that original proteins do not possess. Some of these peptides are used as therapeutic agents. On the contrary others appear to be involved in vicious circles underlying age-dependent decline of tissue function. This fascinating molecule and the parent molecules will certainly remain of interest for some time.

[Cryptic sites and matrikines: cellular effects of fibronectin and laminin peptides]. / Sites cryptiques et matrikines: effets cellulaires des peptides de fibronectine et de laminine.

Structural glycoproteins such as fibronectin and laminin play a dual role in the organisation of extracellular matrix and by acting through integrins with cell surfaces. Cell-matrix interactions are crucial for the regulation of cell behaviour which depends strictly on matrix composition. Structural glycoproteins do contain cryptic sites which can be revealed during fibrillogenesis, adsorption, alteration of conformation and proteolysis. Fibronectin and laminin fragments present new properties by comparison with the native molecule. Matrix remodeling and production of matrikins were shown to be of great importance for cell differentiation and cell behaviour and in pathological conditions.

[Idiopathic granulomatous hepatitis with bilateral orchiepididymitis and skin eruption]. / Hepatitis granulomatosa idiopática con orquiepididimitis bilateral y erupción cutánea.

We report a 52 years old male admitted for fever lasting one month, dry cough, headache and malaise. Initial laboratory work up showed an AST of 172 U/l, and ALT of 252 U/l, a GGT of 353 U/l and alkaline phosphatases of 952 U/l. An abdominal CAT scan disclosed a mild hepatosplenomegaly. A liver biopsy showed a granulomatous hepatitis. During the evolution, the patient had a left testicle swelling with darkening of the surrounding skin. A testicular ultrasound showed a bilateral orchiepidydimitis. The patient was treated with non steroidal anti-inflammatory drugs and fever subsided. Three months later, these drugs were discontinued and the patient remained asymptomatic and with normal laboratory values until 36 months of follow up.

Linfoma gástrico primario de células T: descripción de 2 casos / Primary gastric T-cell lymphoma: report of 2 cases

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