Studies of Modern Man

Une approche écoanthropologique de la santé publique

Abstract: Under the joint influences of anthropology and ecology, medical thinking is being steered into radical new avenues in which simple linear approaches (a given cause produces a given effect, a germ generates a disease) are no longer adequate In the philosophy of what may be termed ‘eco-medicine”, disease can only be understood by taking into account the full complex of relations - cultural, social and biological - between Man and the environment The unit of study in these approaches is no longer the individual but the total population Beyond purely medical issues, questions about Man's adaptability to the environment and the environment's adaptability to Man are explored New geographic and ecological concepts, such as the pathogenic complex, epidemiological landscape or pathocenosis, need to be integrated into the medical reasoning process This interdisciplinary conception, grounded in the nature-biology-society triangle, concerns all aspects and branches of public health: the relations between food, health and development, cultural attitudes regarding the perception of the physical and social environment and their changes, the genetic or acquired predisposition to diseases, interbreeding and migrations and their epidemiological consequences, population growth, the rise of new diseases due in particular to urbanisation, etc The article demonstrates the need for future public health policies to take these new approaches into consideration

Retard de croissance intra-utérin et vulnérabilité au syndrome métabolique : recherche de marqueurs placentaires dans un modèle de dénutrition maternelle prénatale et chez l'Homme

Abstract: De nombreuses donnees indiquent qu’un petit poids a la naissance, resultant en partie d’une sous-nutrition materno-fœtale, est associe a une augmentation de la morbidite et de la mortalite durant la periode neonatale, et conduit egalement a un risque accru de developper a l'âge adulte un syndrome metabolique (diabete de type 2, obesite, hypertension arterielle et dyslipidemie). Les mecanismes de cette programmation prenatale sont encore mal connus et impliqueraient plusieurs molecules et systemes physiologiques distincts. De nombreuses etudes suggerent que le placenta serait implique dans la programmations de ces pathologies metaboliques. En effet, celui-ci constitue un organe de communication entre la mere et son fœtus et participe a la regulation de l'homeostasie fœtale. En raison de la proportion croissante de femmes presentant des troubles de la nutrition durant la grossesse et en lien avec leurs repercussions potentielles chez la descendance, il est necessaire de mieux comprendre les interactions entre l’alimentation maternelle et l’unite fœto-placentaire et d’identifier les mecanismes impliques dans les alterations de la croissance fœtale. En consequent, le placenta constitue un organe de choix pour etudier les interactions entre l’alimentation maternelle et le fœtus au cours de la grossesse. Durant cette these, nous avons tente d’identifier de nouvelles voies moleculaires placentaires impliquees dans le controle de la croissance fœtale chez le rat, puis d'etudie l'expression de ces facteurs dans des placentas humains provenant de grossesses impliquant des anomalies de la croissance fœtale. Comme la malnutrition maternelle constitue une part importante dans l'etiologie de la restriction de croissance intra-uterine (RCIU), nous avons utilise un modele experimental effectue chez le rat, qui consiste en une reduction (de 50% a 70%) de la ration alimentaire quotidienne maternelle durant la gestation. Ces regimes conduisent a des troubles de la croissance de l'unite fœto-placentaire reveles par des reductions drastiques du poids du placenta et des poids de naissance a terme. Afin d'identifier de nouvelles voies placentaires impliquees dans RCIU, nous avons utilise deux methodologies differentes: une approche proteomique et une evaluation de deux proteines recemment caracterisees.Premierement, nous avons etudie le proteome placentaire chez le rat RCIU provenant de meres denutris par une analyse proteomique (2D-PAGE et spectrometrie de masse). Cette strategie nous a permis de decouvrir de nouvelles voies modulees par le RCIU et, etonnamment, des modulations importantes ont ete observees pour plusieurs proteines mitochondriales, suggerant un effet cible de la denutrition sur ces organites. Par la suite, en utilisant diverses techniques d'analyses moleculaires, proteomiques et fonctionnelles, nous avons montre que ces organites elaborent une reponse adaptative a la restriction alimentaire maternelle qui pourrait avoir des consequences sur la regulation de la croissance fœtale. Deuxiemement, nous avons etudie deux autres proteines atypiques: le brain-derived neurotrophic factor et l'hormone apeline. Nos resultats suggerent que ces deux facteurs pourraient etre impliques, au niveau placentaire, dans le controle de la croissance fœtale a la fois chez le rat et chez l'homme. En conclusion, comme les techniques cliniques actuelles ne permettent pas de diagnostiquer avec precision un RCIU, nos resultats pourraient permettre une meilleure comprehension de la physiopathologie placentaire et permettre de developper de nouveaux marqueurs de diagnostique et/ou de traitement dans le but d'ameliorer la croissance placentaire et fœtale en conditions pathologiques.

Developmental changes and polymorphism in human alcohol dehydrogenase

Abstract: Ann. H u m . Genet., Lond. (1971), 34, 251 Printed in Great Britain Developmental changes and polymorphism in human alcohol dehydrogenase BY MOYRA SMITH, D. A. HOPKINSON AND HARRY HARRIS M.R.C. Human Biochemical Genetics Unit, Galton Laboratory, University College London I n man, alcohol dehydrogenase (alcohol: NAD oxidoreductase E.C. 1 . 1 . 1 . 1 ) occurs princi- pally in liver, though low levels of activity have aIso been found in lung, kidney and the gastro- intestinal tract (Moser, Papenberg & von Wartburg, 1968). Evidence for at least three distinct isozymes has been obtained by chromatography of liver extracts on CM cellulose (Blair & Vallee, 1966) and also by electrophoresis (Moser et al. 1968; Pikkarainen & Raiha, 1969; Murray & Motulsky, 1970). Von Wartburg, Papenberg & Aebi (1965) reported that certain individuals have an atypical form of alcohol dehydrogenase associated with an increased level of activity. The usual and atypical forms of the enzyme were shown to differ markedly in pH activity curves with ethanol as substrate. The pH optimum for the usual form was found to be pH 10.8 and for the atypical form pH 8.5. The enzymes also differed in the relative rates at which they oxidized various other alcohols, and in the degree of inhibition produced by various metal binding agents. On the other hand no significant differences were observed in Michaelis constants for the substrates ethanol or acetaldehyde or for the corresponding coenzymes NAD or NADH. Also the pH activity curve with acetaldehyde as substrate was essentially the same for both enzymes, having an optimum at pH 6.0-6.5. A simple screening test to distinguish the usual from the atypical enzyme in crude liver homo- genates was designed (von Wartburg et al. 1965). This involves determining the ratio of the activity at pH 11.0 to that at pH 8-8 with ethanol as substrate under standard conditions. The usual enzyme gives a value for this ratio greater than 1.0, and the atypical enzyme less than 1.0. In a survey of 59 liver samples from different individuals in Switzerland, 12 were found to have the atypical alcohol dehydrogenase, and in another series of 50 individuals from London, 2 were found to be atypical (von Wartburg & Schiirch, 1968). The atypical enzyme occurred in indi- viduals varying from 16 to 82 years of age. Pikkarainen & Raiha (1967) reported that alcohol dehydrogenase activity in liver is low during foetal life and reaches adult levels about 5 years after birth. Changes in electrophoretic pattern have also been noted during development (Pikkarainen & Raiha, 1969; Murray & Motulsky, 1970). In the earliest stages only a single isozyme is observed but later further iso- zymes appear. I n adult liver individual variations in the relative contribution of the different isozymes to the total activity have been noted (von Wartburg & Schiirch, 1968), but no clear electrophoretic differences between the usual and atypical alcohol dehydrogenases as determined by the ratio of activity at pH 11.0 and pH 8.8 were detected. The present paper is concerned with a study of human alcohol dehydrogenase in which liver, lung, kidney and intestinal material from foetuses, infants and adults has been examined. The en- zyme has been investigated both by spectrophotometric assay at different pH’s and by starch-gel

Serotyping for Homotransplantation

Abstract: During the past four years 104 patients who had received kidneys from either living unrelated or cadaver donors were typed and analyzed, to assess the effect of matching on endogenous crea...

Further data on the adenosine deaminase (ADA) polymorphism and a report of a new phenotype

Abstract: In a study of human red cell adenosine deaminase (ADA) three different types of isozyme patterns were identified (Spencer, Hopkinson & Harris, 1968). One phenotype designated ADA 1 was found in about 89 % of the English population, the second phenotype, ADA 2-1, was found in about 11 yo of the population and the third phenotype, designated ADA 2, was seen only once in a survey of 580 unrelated English people. Sixty-seven families were studied and the family data suggested that the three ADA phenotypes were determined by two autosomal alleles ADA1 and ADA2; phenotypes ADA 1 and ADA 2 corresponding to the homozygous genotypes ADAlADAl and ADAaADA2 respectively and phenotype ADA 2-1 corresponding to the heterozygous combination ADA1ADA2. This paper contains further family data and more extensive population data on the ADA polymorphism and also a description of a new phenotype.