Showing papers by "Collège de France published in 1990"

An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels.

Abstract: A polymorphism consisting of the presence or absence of a 250-bp DNA fragment was detected within the angiotensin I-converting enzyme gene (ACE) using the endothelial ACE cDNA probe. This polymorphism was used as a marker genotype in a study involving 80 healthy subjects, whose serum ACE levels were concomitantly measured. Allele frequencies were 0.6 for the shorter allele and 0.4 for the longer allele. A marked difference in serum ACE levels was observed between subjects in each of the three ACE genotype classes. Serum immunoreactive ACE concentrations were, respectively, 299.3 +/- 49, 392.6 +/- 66.8, and 494.1 +/- 88.3 micrograms/liter, for homozygotes with the longer allele (n = 14), and heterozygotes (n = 37) and homozygotes (n = 29) with the shorter allele. The insertion/deletion polymorphism accounted for 47% of the total phenotypic variance of serum ACE, showing that the ACE gene locus is the major locus that determines serum ACE concentration. Concomitant determination of the ACE genotype will improve discrimination between normal and abnormal serum ACE values by allowing comparison with a more appropriate reference interval.

Perspectives in Supramolecular Chemistry—From Molecular Recognition towards Molecular Information Processing and Self‐Organization

Abstract: The selective binding of a substrate by a molecular receptor to form a supramolecular species involves molecular recognition which rests on the molecular information stored in the interacting species. The functions of supermolecules cover recognition, as well as catalysis and transport. In combination with polymolecular organization, they open ways towards molecular and supramolecular devices for information processing and signal generation. The development of such devices requires the design of molecular components performing a given function (e.g., photoactive, electroactive, ionoactive, thermoactive, or chemoactive) and suitable for assembly into an organized array. Light-conversion devices and charge-separation centers have been realized with photoactive cryptates formed by receptors containing photosensitive groups. Eleclroactive and ionoactive devices are required for carrying information via electronic and ionic signals. Redox-active polyolefinic chains, like the “caroviologens”, represent molecular wires for electron transfer through membranes. Push-pull polyolefins possess marked nonlinear optical properties. Tubular mesophases, formed by organized stacking of suitable macro-cyclic components, as well as “chundle”-type structures, based on bundles of chains grafted onto a macrocyclic support, represent approaches to ion channels. Lipophilic macrocyclic units form Langmuir-Blodgett films that may display molecular recognition at the air-water interface. Supramolecular chemistry has relied on more or less preorganized molecular receptors for effecting molecular recognition, catalysis, and transport processes. A step beyond preorganization consists in the design of systems undergoing self-organization, that is, systems capable of spontaneously generating a well-defined supramolecular architecture by self-assembling from their components under a given set of conditions. Several approaches to self-assembling systems have been pursued: the formation of helical metal complexes, the double-stranded helicates, which result from the spontaneous organization of two linear polybipyridine ligands into a double helix by binding of specific metal ions; the generation of mesophases and liquid crystalline polymers of supramolecular nature from complementary components, amounting to macroscopic expression of molecular recognition; the molecular-recognition-directed formation of ordered solid-state structures. Endowing photo-, electro-, and ionoactive components with recognition elements opens perspectives towards the design of programmed molecular and supramolecular systems capable of self-assembly into organized and functional supramolecular devices. Such systems may be able to perform highly selective operations of recognition, reaction, transfer, and structure generation for signal and information processing at the molecular and supramolecular levels.

Membrane protein folding and oligomerization: the two-stage model.

Abstract: We discuss the view that the folding of many, perhaps most, integral membrane proteins can be considered as a two-stage process. In stage I, hydrophobic alpha-helices are established across the lipid bilayer. In stage II, they interact to form functional transmembrane structures. This model is suggested by the nature of transmembrane segments in known structures, refolding experiments, the assembly of integral membrane protein from fragments, and the existence of very small integral membrane protein subunits. It may extend to proteins with a variety of functions, including the formation of transmembrane aqueous channels. The model is discussed in the context of the forces involved in membrane protein folding and the interpretation of sequence data.

Posttranslational glutamylation of alpha-tubulin

Abstract: The high degree of tubulin heterogeneity in neurons is controlled mainly at the posttranslational level. Several variants of alpha-tubulin can be posttranslationally labeled after incubation of cells with [3H]acetate or [3H]glutamate. Peptides carrying the radioactive moiety were purified by high-performance liquid chromatography. Amino acid analysis, Edman degradation sequencing, and mass spectrometric analysis of these peptides led to the characterization of a posttranslational modification consisting of the successive addition of glutamyl units on the gamma-carboxyl group of a glutamate residue (Glu445). This modification, localized within a region of alpha-tubulin that is important in the interactions of tubulin with microtubule-associated proteins and calcium, could play a role in regulating microtubule dynamics.

Perspektiven der Supramolekularen Chemie – von der molekularen Erkennung zur molekularen Informationsverarbeitung und Selbstorganisation

Abstract: Der erste Schritt der selektiven Bindung eines Substrats an einen Rezeptor unter Bildung eines supramolekularen Verbandes (eines „Ubermolekuls” oder „Uberkomplexes”) ist die molekulare Erkennung, die durch die in den beteiligten Molekulen gespeicherte Information ermoglicht wird. Die Funktionen von supramolekularen Einheiten umfassen sowohl Erkennung als auch Katalyse und Transport. In Verbindung mit der Organisation von molekularen Einheiten zu geordneten Systemen eroffnen sich so Wege zu molekularen und supramolekularen Funktionseinheiten fur die Informationsverarbeitung und Signalerzeugung. Die Entwicklung solcher Funktionseinheiten erfordert die Herstellung von Molekulen, die bestimmte Funktionen (z. B. Photoaktivitat, Elektroaktivitat, Ionenaktivitat, Thermoaktivitat oder Chemoaktivitat) erfullen konnen und die auserdem fur den Einbau in geordnete Systeme geeignet sein mussen. Molekulare Funktionseinheiten zur Lichtumwandlung und zur Ladungstrennung konnten mit photoaktiven Cryptaten verwirklicht werden, die aus Rezeptoren mit lichtempfindlichen Gruppen wie Bipyridinen und Porphyrinen bestehen. Zum Transport elektronischer und ionischer Signale sind elektroaktive und ionenaktive Systeme erforderlich. Redoxaktive langkettige Polyene wie die „Caroviologene” konnen als molekulare Drahte fur den Elektronentransport durch Membranen betrachtet werden. Push-pull-Polyene haben ausgepragte nichtlineare optische Eigenschaften. Geordnete tubulare Stapel geeigneter Makrocyclen in Mesophasen sowie Makrocyclen mit langkettigen Substituenten und funktionellen Gruppen an deren Enden („Chundles”) sind Prototypen von Ionenkanalen. Mit lipophilen Makrocyelen konnen Langmuir-Blodgett-Filme hergestellt werden, die eine molekulare Erkennung an der Luft-Wasser-Grenzflache ermoglichen konnten. Die Supramolekulare Chemie war bisher auf mehr oder weniger vorgeformte („praorganisierte”) Rezeptoren fur die molekulare Erkennung, Katalyse und Transportprozesse angewiesen. Einen Schritt weiter geht der Entwurf von Systemen, bei denen auf molekularer Ebene eine Selbstorganisation moglich ist und die spontan eine genau definierte supramolekulare Struktur annehmen. Mehrere selbstorganisierende Systeme wurden beschrieben: 1. Helicale Metallkomplexe/doppelstrangige Helicate: Zwei lineare Polybipyridine koordinieren bestimmte Metall-Ionen unter spontaner Bildung einer Doppelhelix. 2. Mesophasen und flussigkristalline Polymere: Durch molekulare Erkennung entstehen aus komplementaren Komponenten supramolekulare Verbande mit entsprechenden makroskopischen Eigenschaften. 3. Geordnete Festkorperstrukturen: Durch molekulare Erkennung kann der Aufbau geordneter Festkorper gesteuert warden. Baut man in Molekule mit Photo-, Elektro- oder Ionenaktivitat Erkennungselemente ein, so eroffnet sich die Perspektive, „programmierte” molekulare und supramolekulare Systeme herzustellen, die sich selbst — gesteuert durch die molekulare Erkennung — zu geordneten supramolekularen Funktionseinheiten zusammensetzen. Diese Funktionseinheiten konnten dann selektive Erkennung, Reaktion, Ubertragung und Strukturerzeugung bei der Signal- und Informationsverarbeitung auf molekularer Ebene ubernehmen.

Fingering instability of thin spreading films driven by temperature gradients

Abstract: THE dynamics of spreading of thin liquid films are important to many technological and biological processes, including tertiary oil recovery, coating processes, the formation and protection of microchips and biological cell interactions. The spontaneous spreading of thin liquid films under capillary forces alone is typically a slow process. An applied force—gravitational or centrifugal, or a surface shear stress—can be used to drive the spreading more quickly1,2. Recent experimental3,4 and theoretical5 studies have revealed that in all of these cases of forced spreading, the liquid front undergoes a fingering instability. Here we report another example of such unstable driven flow, this time caused by the Marangoni effect6, in which a temperature gradient induces a gradient of surface tension which drives the spreading process.

Activation of NMDA receptors induces dephosphorylation of DARPP-32 in rat striatal slices.

Abstract: IN the caudate-putamen the glutamatergic cortical input and the dopaminergic nigrostriatal input have opposite effects on the firing rate of striatal neurons l–4. Although little is known of the biochemical mechanisms underlying this antagonism, one action of dopamine is to stimulate the cyclic AMP-dependent phosphorylation of DARPP-32 (dopamine and cAMP-regulated phospho-protein, of relative molecular mass 32,000 (32K))5. This phos-phorylation converts DARPP-32 from an inactive molecule into a potent inhibitor of protein phosphatase-1 (ref. 6). Here we show that activation of the NMDA (TV-methyl-D-aspartate) subclass of glutamate receptors reverses the cAMP-stimulated phos-phorylation of DARPP-32 in striatal slices through NMDA-induced dephosphorylation of DARPP-32. Thus, the antagonistic effects of dopamine and glutamate on the excitability of striatal neurons are reflected in antagonistic effects of these neurotransmitters on the state of phosphorylation of DARPP-32. Our results indicate that stimulation of NMDA receptors leads to the activation of a neuronal protein phosphatase, presumably the calcium-dependent phosphatase calcineurin, and show, in an intact cell preparation, that signal transduction in the nervous system can be mediated by protein dephosphorylation.

Differential expression of two neuronal intermediate-filament proteins, peripherin and the low-molecular-mass neurofilament protein (NF-L), during the development of the rat.

Abstract: The expression of peripherin, an intermediate filament protein, had been shown by biochemical methods to be localized in the neurons of the PNS Using immunohistochemical methods, we analyzed this expression more extensively during the development of the rat and compared it with that of the low-molecular-mass neurofilament protein (NF-L), which is expressed in every neuron of the CNS and PNS The immunoreactivity of NF-L is first apparent at the 25-somite stage (about 11 d) in the ventral horn of the spinal medulla and in the posterior part of the rhombencephalon The immunoreactivity of peripherin appears subsequently, first colocalized with that of NF-L Both immunoreactivities then spread out along rostral and caudal directions, but whereas the immunoreactivity of NF-L finally becomes noticeable in every part of the nervous system, that of peripherin remains localized to (1) the motoneurons of the ventral horn of the spinal medulla; (2) the autonomic ganglionic and preganglionic neurons; and (3) the sensory neurons These results demonstrate that, in the neurons that originate from migrating neural crest cells, the immunoreactivities of peripherin and of NF-L become apparent only when they have reached their destination The results also show that peripherin is expressed more widely than has been previously observed and that this protein occurs in neuronal populations from different lineages (neural tube, neural crest, placodes) with different functions (motoneurons, sensory and autonomic neurons) The common point of these neurons is that they all have axons lying, at least partly, at the outside of the axis constituted by the encephalon and the spinal medulla; this suggests that peripherin might play a role in the recognition of the axonal pathway through the intermediary of membrane proteins

The Scholastic Point of View

Abstract: I would like first to analyze what, borrowing an expression of Austin, I will call the "scholastic point of view," the point of view of the skhole, that is, the academic vision. What does the fact of thinking within a scholastic space, an academic space, imply? What does our thinking owe to the fact that it is produced within an academic space? Isn't our deepest unconscious related to the fact that we think in such an academic space? This would be the first question. From there, I will try to give some indications on the particular problem (it was present throughout the discussion, particularly around the notion of mimesis but also, obviously, this morning, in the presentation of Jacques Bouveresse [1989]) that the understanding of practice poses and which makes for such a difficult task for the human sciences. Does the very ambition of understanding practice make any sense? And what is involved in understanding and knowing a practice with an approach that is intrinsically theoretical? Then, if time allows, I would like to raise the issue that has been up in the air since the birth of the social sciences: the problem of the relations between reason and history. Isn't sociology, which apparently undermines the foundations of reason and thereby its own foundations, capable of producing instruments for forging a rational discourse and even of offering techniques for waging a politics of reason, a Realpolitik of reason? The scope of the problematic I adumbrate here is disproportionate to the time at my disposal. This is why I welcome the idea of "workshop," which fits perfectly what I want to do and can do today.

Introduction to polymer dynamics

Abstract: This book, based on lectures given at the Polytechnic of Milan, gives a broad overview of the field of polymer dynamics. In these lectures the aim is to stress the fundamental concepts of the behaviour of polymers without drawing on the more advanced mathematical formalism which often obscures the natural elegance of the subject matter. Professor De Gennes is one of the most distinguished workers in the field of material science. Therefore this book will be welcomed by both the experienced researcher in the area and the interested layman. It will be of particular value to graduate students.

A numerical approach to the exact boundary controllability of the wave equation (I) Dirichlet controls: Description of the numerical methods

Abstract: In this paper we discuss the numerical implementation of a systematic method for the exact boundary controllability of the wave equation, concentrating on the particular case of Dirichlet controls. The numerical methods described here consist in a combination of: finite element approximations for the space discretization; explicit finite difference schemes for the time discretization; a preconditioned conjugate gradient algorithm for the solution of the discrete problems; a pre/post processing technique based on a biharmonic Tychonoff regularization. The efficiency of the computational methodology is illustrated by the results of numerical experiments.

Quantitative estimation of minor mRNAs by cDNA-polymerase chain reaction. Application to dystrophin mRNA in cultured myogenic and brain cells.

Abstract: Amplification of the mRNA polymerase chain reaction is a very sensitive technique to detect low-abundance transcripts. We describe in this paper conditions necessary to make this technique quantitative. Quantification is performed in the exponential phase of the amplification process and the results are standardized with respect to those obtained with an exogenous mRNA which is co-reverse-transcribed and co-amplified in the same reaction as the analyzed transcripts. The primers are chosen in different exons to distinguish the amplification of mRNA fragments from the amplification of contaminating DNA. Analysis of the kinetics of amplification and parameters influencing this kinetics shows that: (a) in the exponential phase of amplification, the amount of amplified fragments is proportional to the initial amount of transcripts; (b) in a certain range of length fragment, the yield of amplification is inversely proportional to the length of the amplified fragments. Using this method we have demonstrated that the dystrophin gene is already activated at the myoblastic stage. A quantitative estimation of the transcript showed that the expression of this gene increases strongly in the course of in vitro myogenesis. In primary culture of mouse brain cells, the dystrophin gene was found to be more expressed in neuronal than in glial cells.

Thymic Epithelium Tolerizes for Histocompatibility Antigens

Abstract: The role of thymic epithelium in the establishment of tissue tolerance was analyzed with a murine chimeric system All T cells differentiated from birth onward in a thymus comprising allogeneic epithelium and syngeneic hematopoietic cells Embryonic thymic rudiments that contained no hematopoietic cells from C3H (H-2k) donors were grafted to newborn athymic (nude) BALB/c (H-2d) mice Chimeras that had normal T cell numbers and function rejected third-party skin grafts, but permanently accepted grafts syngeneic to the thymic epithelium In vitro functional assays did not always correlate with the state of tolerance in vivo Thus, pure thymic epithelium induces tolerance to histocompatibility antigens

Dynamics of wetting: local contact angles

Abstract: We discuss the motion of a triple line for a fluid spreading on a flat solid surface in conditions of partial wetting: the equilibrium contact angle θe is assumed to be finite but small: 0 < θe [Lt ] 1. We distinguish four regions: (1) a molecular domain of size a (≈ a few Angstroms) very near the triple line, where the continuum description breaks down; (2) a proximal region (of length a/θ2e and height a/θe) where the long-range Van der Waals forces dominate; (3) a central region, where capillary forces and Poiseuille friction are the only important ingredients; (4) a distal region where macroscopic features (related to the size of the droplet, or to gravitational forces) come into play. In regions (2, 3, 4) the flow may be described in a lubrication approximation, and with a linearized form of the capillary forces. We restrict our attention to low capillary numbers Ca and expand the profiles to first order in Ca near the static solution. The main results are: (a) the logarithmic singularity which would have occurred in a simple wedge picture is truncated by the long-range forces, at a fluid thickness a/θe. This effect is more important, at small θe, than the effects of slippage which have often been proposed to remove the singularity, and which would lead to a truncation thickness comparable with the molecular size a; (b) in the central region, the local slope θ(x) grows logarithmically with the distance x from the triple line; (c) one can match explicitly the solutions in the central and distal region: we do this for one specific example: a plate plunging into a fluid with an incidence angle exactly equal to θe. In this case we show that, far inside the distal region, the perturbation of the slope decays like 1/x2.

Changes in muscle stiffness produced by motor units of different types in peroneus longus muscle of cat.

Abstract: 1. The effects of maximal tetanic contractions of varying numbers of motor units of the same type [slow (S), fast fatigue-resistant (FR), or fast fatigable (FF)] on the mechanical responses to muscle stretch were studied in the peroneus longus muscle of anesthetized cats. 2. Two types of stiffness measurements were made: 1) an average stiffness, defined as the tension change from the beginning to end of a 0.5-mm ramp stretch; and 2) a dynamic stiffness, defined as the ratio of peak-to-peak tension to amplitude of a maintained 85-microns sinusoidal stretch at frequencies of 10-80 Hz. 3. Contractions of slow and fast units elicited different increases in average stiffness. Type S units, although developing much smaller tetanic tensions than fast ones, produced a resistance to stretch comparable with or greater than that of fast units developing much higher tensions. 4. For comparable tetanic tensions, slow units also elicited a greater dynamic stiffness than fast units. During sinusoidal stretch, changes in muscle tension led changes in muscle length during contraction of S units, but the reverse was observed for frequencies 30-50 Hz during contraction of FF units. This suggests that the latter perform oscillatory work on the driving apparatus. 5. Type S units, whose low-threshold motoneurons are the first to be recruited, appear well adapted to play a role in posture and in slow movements because of the resistance they offer to forces tending to change joint position or to oppose the progression of slow movements.

Dystrophin gene transcribed from different promoters in neuronal and glial cells

Abstract: It has been shown that the dystrophin gene, which is defective in patients with Duchenne and Becker muscular dystrophy (reviewed in ref. 1), is transcribed in brain from a specific promoter that is different from the one used in muscle, and so the two types of transcripts differ at least in their first exon. We recently found that the dystrophin gene is expressed at a higher level in primary cultures of neuronal cells than in astro-glial cells derived from adult mouse brain. Here we investigate the use of two different promoters in each cell type. Our results demonstrate that the brain-type promoter of the dystrophin gene is highly specific to neurons, in which there is a significant increase in the amount of brain-specific messenger RNA during the course of in vitro maturation. By contrast, the muscle-type promoter is active in a wider range of cell types, including not only striated and smooth muscle, but also glial cells to a lesser extent, and probably neurons.

Experiments on wetting on the scale of nanometers: Influence of the surface energy.

Abstract: Via ellipsometry, the time-dependent profiles of liquid droplets spreading completely on plane solid substrates are measured in the range 0--200 \AA{} Two different surfaces are used, a ``high-energy'' surface (wettable by water) and a ``low-energy'' surface (Langmuir-Blodgett layer of a double-bond-terminated fatty acid), respectively We have observed that the shape of spreading droplets of the same fluid (polydimethylsiloxane) are quite different on these two surfaces: On the low-energy surface, the spreading occurs by the macroscopic lateral spreading of essentially one monolayer, away from the central part of the drop On the contrary, for the high-energy surface, spreading occurs by the macroscopic lateral spreading of several monolayers in a kind of hierarchical process Nevertheless, in both cases there is a signature of molecular structuring in the fluid flow at the center of the drop

Reflective UV photocathodes with gas-phase electron extraction: solid, liquid, and adsorbed thin films

Abstract: The photoemission quantum efficiency of reflective photocathodes in methane gas has been investigated in the spectral range between 140 and 250 nm. The spectral response of solid metals and CsI, as well as of liquid and solid TMAE film, have been measured. The high quantum efficiency of CsI (35% at 170 nm) makes it attractive for BaF 2 or xenon scintillation detection. A BaF 2 crystal coupled to an ionization chamber with a reflective CsI photocathode has been successfully tested. Adsorbed TMAE films can significantly increase the quantum yields of metal and CsI (to 46% at 170 nm), making them suitable for fast RICH and other applications.

Targeted replacement of the homeobox gene Hox-3.1 by the Escherichia coli lacZ in mouse chimeric embryos.

Abstract: Through gene targeting based upon homologous recombination in embryonic stem cells, a chosen gene can be inactivated and eventually a strain of mutant mice created. We have devised a procedure to specifically replace a targeted gene by another gene. A murine homeobox gene was disrupted at high frequency in embryonic stem cells by its replacement with Escherichia coli lacZ. Injection of such stem cells into blastocysts yielded chimeric embryos in which beta-galactosidase activity was driven by the Hox-3.1 promoter. This technique will allow the visual assessment at the cellular level of gene inactivation effects in transgenic mice.

A widely distributed antigen developmentally regulated in the nervous system.

Abstract: We have identified a glycoprotein (BEN) of 95–100 × 10(3) Mr using a monoclonal antibody. This protein is transiently expressed at the cell surface of the peripherally projecting neurons, i.e. motoneurons of the spinal cord and cranial nuclei, sensory neurons of the dorsal root and cranial sensory ganglia and sympathetic, parasympathetic and enteric neurons. In vitro cultures of dorsal root and sympathetic ganglia have shown that BEN is expressed on neurons but not on glial cells. On motor and sensory neurons, BEN first appears at the level of the cell body just after withdrawal from the cell cycle. Soon afterwards, expression of the antigen extends to the elongating axon. After a few days, BEN is no longer expressed by the motor and sensory neurons, disappearing first from the cell body and then progressively from the fibres. The loss of expression is concomitant with the onset of intense proliferation of satellite and Schwann cells. This modulated expression within the nervous system is unlike that of any surface glycoprotein so far described in vertebrates. Preliminary biochemical analysis indicates that, although it bears the adhesion-associated epitope HNK-1, BEN does not share characteristics with any previously described axonal glycoprotein. Consequently, we speculate that this glycoprotein might be a novel molecule implicated in selective adhesion phenomena, such as axonal fasciculation.

Spreading of liquids on highly curved surfaces.

Abstract: Because of surface tension, liquid films coating fibers or the insides of capillary tubes are usually unstable and break up into a periodic array of droplets. However, if these films are very thin (of thickness in the range of tens of angstroms), they can be stabilized by long-range van der Waals forces. A simple method for making such wetting films consists of slowly drawing the fiber out of a bath of liquid; the thickness of the film is then measured using a method based on gas chromatography. If these liquid films are thick, and are forced to flow, they may then not break up: the instability becomes "saturated."

Organization of a functional chicken class II B gene

Abstract: Five class II (B-L) B genes are encoded in the major histocompatibility complex (MHC) of chickens of the B12 haplotype. We report here the nucleotide sequence of one of these genes, B-LBII, as well as the primary structure of a corresponding cDNA. The organization of B-LBII, its 5' flanking region including the promotor region, and the amino acid sequence of its product are compared to mammalian class II B genes and to the previously described B-LBIII gene, which probably is a pseudogene since no B-LBIII transcript could be identified. The 5' flanking region of B-LBII exhibits homologs of transcription-controlling sequence motifs, namely S, X, X2, and Y boxes, of class II A and B genes of rodents and man. However, the promotor region of B-LBIII lacks an equivalent of the S box, displays two nucleic acid substitutions in the core sequence of the Y box, and exhibits a 16 base pair (bp) deletion upstream of the site of initiation of transcription. Therefore, an aberrant promotor region is likely to account for the pseudogene-like nature of B-LBIII, which displays open-reading frames in all exons. The data obtained with the functional B-LBII gene are in line with our previous interpretation that both genomic organization and tertiary structure of class II beta molecules are remarkably conserved between birds and mammals.

Similar frequencies of renin gene restriction fragment length polymorphisms in hypertensive and normotensive subjects.

Abstract: A prospective study was conducted to compare the frequency of renin gene polymorphisms in normotensive and hypertensive subjects. Hypertensive (n = 102, blood pressure 168 +/- 17/103 +/- 9 mm Hg) and normotensive (n = 120, blood pressure 122 +/- 10/75 +/- 9 mm Hg) subjects were white, had similar age and sex distributions (hypertensive group, 45 +/- 10 years old and 52% female; normotensive group, 44 +/- 9 years old and 55% female) and similar body mass index (hypertensive group, 23.2 +/- 2.6; normotensive group, 22.5 +/- 2.4 kg/m2, p = 0.048). The familial susceptibility to hypertension was defined as at least one parent and one sibling who were hypertensive before age 65; subjects in the normotensive group had no familial history of hypertension. Renin gene polymorphisms located throughout the renin gene were identified by using three restriction enzymes (Taq I, HinfI, HindIII). For each polymorphic restriction site, allele frequencies were similar in the hypertensive and the normotensive groups. In the absence of parental genotypes, the haplotype frequencies combining the three restriction fragment length polymorphisms were estimated by using maximum likelihood techniques and were similar in both groups (hypertensive group, 0.429, 0.277, and 0.177; normotensive group, 0.453, 0.245, and 0.195 for the three most common haplotypes). A rare haplotype detected by Taq I/Hind III was apparently more frequent in the hypertensive than in the normotensive group (hypertensive group, tH 0.086, th 0.022; normotensive group, tH 0.038, th 0.050), but the difference was not statistically significant. In conclusion, no association between renin gene polymorphisms and essential hypertension was demonstrated in the present study.

Extracellular dehydration during pregnancy increases salt appetite of offspring.

Abstract: The propensity to prefer and to consume salty foods varies considerably from person to person, and excessive salt intake has been linked to a number of pathological conditions. Extracellular dehydration occurs in humans after vomiting or diarrhea and is commonly observed during pregnancy. Because the hormonal responses to extracellular dehydration are known to increase salt appetite, we tested the hypothesis that extracellular dehydration during pregnancy increases the propensity of offspring to consume salt. Pregnant rats were treated with polyethylene glycol, which is known to produce extracellular dehydration and to exaggerate sodium appetite. The offspring of these treated pregnant rats showed an increase in salt appetite as compared with the offspring of control untreated dams. These results demonstrate that extracellular dehydration during pregnancy can enhance the natriophilic propensity in offspring and suggest that gravidic vomiting may contribute to the epidemiological factors of hypertension and other pathologies.