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Biomedical subjects

S Lafont

Publications and source records attributed to S Lafont.

At least 37 records · Page 2Linked to original sources

Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area.

Alcoholism is a possible cause of dementia, mainly through associated nutritional deficiencies and, rarely, through acute direct toxicity. However alcohol consumption was not found to be a risk factor in previous epidemiologic studies. We prospectively studied 3,777 community residents aged 65 and over, in the districts of Gironde and Dordogne. Average daily alcoholic consumption was recorded at baseline. Incident cases of dementia and Alzheimer's disease were screened at follow-up with explicit criteria. At 3 years, 2,273 subjects not demented at baseline were still available for follow-up. Wine was the only alcoholic beverage reported by more than 95 p. 100 of regular drinkers. In the 318 subjects drinking 3 to 4 standard glasses per day (> 250 and up to 500 ml), categorized as moderate drinkers, the crude odds ratio (OR) was 0.18 for incident dementia (p < 0.01) and 0.25 for Alzheimer's disease (p < 0.03), as compared to the 971 non-drinkers. After adjusting for age, sex, education, occupation, baseline MMSE and other possible confounders, the ORs were respectively 0.19 (p < 0.01) and 0.28 (p < 0.05). In the 922 mild drinkers (< 1 to 2 glasses per day) there was a negative association only with AD, after adjustment (OR = 0.55; p < 0.05). The inverse relationship between moderate wine drinking and incident dementia was explained neither by known predictors of dementia nor by medical, psychological or socio-familial factors. Considering also the well documented negative associations between moderate wine consumption and cardiovascular morbidity and mortality in this age group, it seems that there is no medical rationale to advise people over 65 to quit drinking wine moderately, as this habit carries no specific risk and may even be of some benefit for their health. Advising all elderly people to drink wine regularly for prevention of dementia would be however premature at this stage.

Aged↗

Use of mammography as a breast cancer screening tool in six districts in France.

Mass screening programs to detect breast cancer are currently under way in many countries. In France, several districts have been running mammographic screening programs since 1989. A survey was conducted in five of these districts and in a sixth district where no screening program was implemented. Using a self-addressed questionnaire mailed to a sample of 1500 women aged over 20 years, the survey was aimed at assessing women's use of mammography as well as their knowledge and perception of mammographic breast cancer screening. According to district, the compliance of the women replying to the questionnaire ranged from 72 to 82%. The proportion of women who had at least one mammography during their life ranged from 41 to 54%, according to district. The percentage of women aged 50 to 69 who had one mammography within 3 years before the survey ranged from 57 to 78% in the experimental districts and was only 48% in the control district. In all districts, women did not know exactly at what age it is recommended to start screening and with what periodicity, but, when invited to do so, they were satisfied with the program and intended to participate again.

Adult↗

Relationships of dehydroepiandrosterone sulfate in the elderly with functional, psychological, and mental status, and short-term mortality: a French community-based study.

In human beings of both sexes, dehydroepiandrosterone sulfate (DHEAS) circulating in blood is mostly an adrenally secreted steroid whose serum concentration (in the micromolar range and 30-50% higher in men than in women) decreases with age, toward approximately 20-10% of its value in young adults during the 8th and 9th decades. The mechanism of action of DHEA and DHEAS is poorly known and may include partial transformation into sex steroids, increase of bioavailable insulin-like growth factor 1, and effects on neurotransmitter receptors. Whether there is a cause-to-effect relationship between the decreasing levels of DHEAS with age and physiological and pathological manifestations of aging is still undecided, but this is of obvious theoretical and practical interest in view of the easy restoration by DHEA administration. Here we report on 622 subjects over 65 years of age, studied for the 4 years since DHEAS baseline values had been obtained, in the frame of the PAQUID program, analyzing the functional, psychological, and mental status of a community-based population in the south-west of France. We confirm the continuing decrease of DHEAS serum concentration with age, more in men than in women, even if men retain higher levels. Significantly lower values of baseline DHEAS were recorded in women in cases of functional limitation (Instrumental Activities of Daily Living), confinement, dyspnea, depressive symptomatology, poor subjective perception of health and life satisfaction, and usage of various medications. In men, there was a trend for the same correlations, even though not statistically significant in most categories. No differences in DHEAS levels were found in cases of incident dementia in the following 4 years. In men (but not in women), lower DHEAS was significantly associated with increased short-term mortality at 2 and 4 years after baseline measurement. These results, statistically established by taking into account corrections for age, sex, and health indicators, suggest the need for further careful trials of the administration of replacement doses of DHEA in aging humans. Indeed, the first noted results of such "treatment" are consistent with correlations observed here between functional and psychological status and endogenous steroid serum concentrations.

Activities of Daily Living↗

Determinants of chronic bronchitis prevalence in an elderly sample from south-west of France.

This paper attempts to estimate by means of a cross-sectional study in subjects aged 65 yrs and over the determinants of the prevalence of chronic bronchitis according to age, gender, smoking history, educational level, former occupation and associated morbidity. Data were examined from the third year of a cohort (Personnes àgêes QUID (PAQUID)) and concerned 2,406 subjects. Identification of chronic bronchitis was based on a direct question asking for the presence of phlegm on most days during at least 3 months per year for at least the two previous years. Of the sample, 13% reported chronic bronchitis (20% of males, and 8% of females). A multivariate analysis was performed and showed that chronic bronchitis was linked to sex, smoking history and professional category. Independent of these factors, asthma history and digitalic drug therapy were also closely associated to chronic bronchitis. These results underline the long-term effect of smoking and occupation on chronic bronchitis, and also illustrate the strong association with asthma and cardiac morbidity over 65 yrs of age.

Age Factors↗

Influence of polydispersity on protein crystallization: a quasi-elastic light-scattering study applied to alpha-amylase.

The early stages of the crystallization process of porcine pancreatic alpha-amylase were investigated by quasi-elastic light scattering. It is shown that at 288 and 293 K the diffusion coefficient does not monotonically change with increasing protein concentration but passes through a maximum at 10 mg ml(-1). In supersaturated solutions, prior to nucleation, the protein is strictly monodisperse. Nucleation induces the formation of aggregates and a polydispersity of, for example, 18% for an initial supersaturation C/C(e) = 5.8. Monodispersity is restored after the nuclei have grown and partially consumed the solute. On the other hand, polydispersity increases up to 20% at 298 K if the protein concentration decreases to 3-4 mg ml(-1), values at which the solutions are under-saturated. When the protein concentration exceeds 5-6 mg ml(-1) the protein becomes monodisperse again. These results, confirmed by those of another system we are studying (bovine pancreatic trypsin inhibitor), are at variance with the statements that supersaturation is always at the origin of aggregation and polydispersity, and that in undersaturated solutions the diffusion coefficient should remain constant for obtaining crystals once the solutions are supersaturated.

Journal Article↗

Elevation of cyclic adenosine monophosphate levels independently down regulates IL-1, IL-2, and IL-2 receptor (CD25) syntheses.

In view of the central involvement of interleukin-1 (IL-1) in T-cell functions and the negative effects exerted by cyclic adenosine monophosphate (cAMP) on T-cell responses, we wondered whether these inhibitions rely on defects in IL-1 generation. We investigated the effect of a known cAMP elevating agent, cholera toxin (CT), on the generation of IL-1 from peripheral blood adherent cells as well as the role of IL-1 whenever IL-2 synthesis and IL-2 receptor (CD25 antigen) expression are inhibited. While augmenting intracellular cAMP concentration, CT inhibits from 20 to 40% the generation of IL-1 activity from E. coli lipopolysaccharide (LPS)-stimulated adherent cells. Theophylline (TH), a cAMP degradation blocking agent, induces the same decrease in IL-1 activity. The B chain of CT, devoid of cAMP activating potency, is not inhibitory. In systems where CT and TH dramatically inhibit the generation of IL-2 activity (80%), addition of exogenous IL-1 does not restore the ability of T-cells to produce or release IL-2. Moreover, CT- and dibutyryl (db)cAMP-induced inhibition of CD25 antigen expression is not overcome by exogenous IL-1, IL-2, nor by both interleukins. It is concluded that inhibition of IL-1 and IL-2 production are independent and that inhibition of CD25 antigen expression is independent of IL-1 and IL-2 modulation. Cholera toxin and cAMP influences on interleukin synthesis are discussed.

Adult↗

Elevation of 3'5' cyclic adenosine monophosphate alters CD3 and CD25 antigens expression in activated T lymphocytes.

Modulation of CD3 molecules and expression of receptors for IL-2 (CD25) are pivotal events of lymphocyte activation and proliferation. Knowing the inhibitory effect of cAMP elevating agents on T lymphocyte activation, we investigated the effect of cholera toxin (CT) and dibutyryl cyclic AMP (dbcAMP) on the modulation of the CD3/Ti complex and on the appearance of the CD25 antigen on PHA-activated human lymphocytes. Cytofluorometry analysis of indirectly anti-CD3 labelled cells showed that CT accelerated the disappearance of CD3 molecules and slowed their reappearance. CT or dbcAMP inhibited the expression of CD25 antigen. In both cases, not only the relative number of CD3+ or CD25+ cells decreased, but the number of CD3 or CD25 antigens per cell as well. Exogenous rIL-2 did not reverse the inhibition of IL-2R expression by CT, showing that this effect is independent of the inhibition of IL-2 production already demonstrated. We conclude that augmenting cAMP levels might affect early steps of activation such as antigen receptor modulation, but do affect more profoundly late IL-2 dependent steps especially the autocrine IL-2 pathway of IL-2 receptor upregulation and the production of IL-2.

Antigens, Differentiation, T-Lymphocyte↗

Intestinal secretory antibody response induced by an oral cholera vaccine in human volunteers.

The ability is reported of a new oral cholera vaccine composed of Vibrio cholerae antigenic fractions to induce a serum and mucosal antibody response after three oral administrations of microgranules to 18 French volunteers according to different protocols of immunization. Specific antibodies were detected in the three different fluids studied (saliva, jejunal fluid, serum) in one third of volunteers before vaccination. An increase of specific IgA antibody level was observed in jejunal fluids of most volunteers after oral vaccination. An augmentation of specific antibodies against vaccine antigenic components was also observed in serum and in saliva after vaccination but in fewer volunteers.

Administration, Oral↗

Induction of murine B cell proliferation and immunoglobulin synthesis by some bacterial ribosomes.

Ribosomal preparations from Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, and Streptococcus pneumoniae were investigated with respect to their activating capacity towards murine lymphoid cells. The proliferation of BALB/c spleen cells was induced in a dose-dependent fashion (from 1 to 100 micrograms/ml) by ribosomes of K. pneumoniae, H. influenzae, and S. pyogenes with a peak activity at 48 or 72 hr of culture. The majority of the blast cells induced by these ribosomal preparations were positive for surface-immunoglobulin (S-Ig) and negative for Thy 1.2. Furthermore, K. pneumoniae, H. influenzae, and S. pyogenes ribosomes induced the synthesis of IgM and some IgA. Cell proliferation and induction of IgM production were also demonstrated with the 3 ribosomal preparations using spleen cells from athymic nude (nu+/nu+) mice, Lyb-5-defective CBA/N spleen cells, B cell-enriched and T cell-depleted BALB/c spleen cell suspensions, as well as spleen cells from the Ips gene-deficient C3H/HeJ strain. Cell culture supernatants contained specific anti-ribosome IgM antibodies. Antibodies of other specificities (anti-sheep erythrocytes) were also demonstrated in supernatants from K. pneumoniae-stimulated cultures. Evidence against a possible role of contamination of K. pneumoniae and H. influenzae ribosomes by lipopolysaccharide- or lipid A-associated proteins in this effect is discussed. Ribosomes from S. pneumoniae did not induce 3H-thymidine incorporation nor Ig production. None of the 4 ribosomal preparations was found to stimulate T cell blastogenesis or to induce interleukin-2 production by naive BALB/c spleen cells. Finally, ribosomes from H. influenzae, S. pyogenes, S. pneumoniae but not those of K. pneumoniae stimulated interleukin-1 production by adherent spleen cells, from BALB/c mice.

Animals↗

Proliferative response of human T lymphocytes to a vaccinal preparation of ribosomes from Streptococcus pyogenes.

The in vitro lymphocyte-activating properties of a ribosomal preparation of Streptococcus pyogenes were investigated. The preparation was mitogenic for human lymphocytes with a peak of 3H-thymidine incorporation occurring after 3-5 days of culture. The response was abolished by removal of CD3-positive cells and by alteration of accessory cells by exposure to L-leucine methyl ester. Most of the cells synthesizing DNA at the end of the culture expressed CD4 or CD8 but not CD20 antigens. No immunoglobulin synthesis was demonstrable. Although the same preparation was shown to be a T-independent polyclonal B-cell activator of murine cells, it preferentially triggers T cells in humans.

Bacterial Vaccines↗

Polyclonal activation of murine B cells by a membrane proteoglycan of Klebsiella pneumoniae.

The lymphocyte activating properties of a membrane proteoglycan (MPG) extracted from a mutant non-encapsulated strain of Klebsiella pneumoniae (Kp) (biotype a I-145) were investigated. Kp MPG induced a strong proliferative response of BALB/c spleen cells and Peyer's patches cells. Thymidine incorporation was dose-related (from 1 to 100 micrograms Kp MPG/ml) and reached a maximum at day 3. It was not reduced by removal of most adherent cells, nor by depletion of Thy1-2 positive cells, but it was abrogated by removal of surface immunoglobulin bearing cells. Spleen cells from nude mice and those from C3H/Hej mice were strongly stimulated by Kp MPG. Conversely Kp MPG did not induce interleukin 2 production and did not trigger the proliferation of thymocytes but stimulated interleukin 1 production by adherent spleen cells. Finally, unfractionated or B-enriched spleen cells cultured with Kp MPG synthesized IgM and, to a lesser extent, IgG and IgA. It is concluded that Kp MPG is a T-independent polyclonal B cell activator and an inducer of interleukin 1 production.

Animals↗

Elevation of cyclic 3'5' adenosine monophosphate levels by cholera toxin inhibits the generation of interleukin 2 activity.

Several molecules can interact with membrane receptors on mononuclear cells to increase intracellular levels of cyclic adenosine monophosphate (cAMP). We used the cholera toxin (CT), a cAMP elevating agent, to study the influence of this nucleotide on the production of interleukin 2 (IL-2) by human peripheral blood mononuclear cells stimulated by phytohemagglutinin and phorbol myristate acetate. Stimulated generation of IL-2 activity was inhibited by CT but not by its B subunit. The inhibition was potentiated by addition of theophylline. Therefore the synthesis and/or release of IL-2 is controlled by intracellular cAMP levels and may be modulated by agents active on this nucleotide system, such as bacterial toxins, glycoprotein hormones, or neurotransmitters.

Adult↗

[Fetal death in utero].

152 cases of fetal death in utero are reported. The most frequent etiologies were: vasculorenal syndromes: 28.3 p. cent, idiopathic DPPNIs and RCIUs: 28 p. cent, accidental causes (trauma, funicular syndromes): 19.5 p. cent. Cause of death was unknown or imprecise in 18.4 p. cent of cases. Repeated fetal deaths in utero were rare: 5 observations. The authors consider the management of fetal death in utero, associated immunological problems and how to deal with subsequent pregnancies.

Autoimmune Diseases↗

Improvement of enzyme-linked antiglobulin test by using an antiglobulin linked to glucose oxidase: description of the technique.

The classic enzyme-linked antiglobulin test (ELAT) used to detect and quantify the amount of IgG antibodies on red blood cells (RBC) is sensitive to hemolysis and erythrocyte enzymatic activities. We describe a new ELAT by using glucose oxidase (GO) linked to antihuman IgG. The optical density base line of GO-ELAT, alkaline phosphatase-ELAT and peroxidase-ELAT were, respectively, 0.180, 0.350 and 0.550. This very low baseline of GO-ELAT was due to the absence of hemolysis (the pH of the GO substrate is 6.5). This technique is ten times more sensitive than the indirect antiglobulin test and detects up to 1 ng/ml of anti-D alloantibodies. Additional advantages of the technique are (1) there is no intrinsic GO enzyme in RBC, and (2) it is not necessary to fix the RBC.

Alkaline Phosphatase↗

Role of the polysaccharide and of the lipopolysaccharide in the immunoprotective capacity of Klebsiella pneumoniae ribosomes.

Ribosomes, ribosomal RNA (r-RNA), capsular polysaccharide (PS-K) and lipopolysaccharide (LPS) were isolated and purified from Klebsiella pneumoniae, type I. The protective capacity of these different fractions was investigated in function of their analytical composition. The results show that ribosomes, and in particular, ribosomal RNA have the greatest protective activity at the lowest concentrations. The role of PS-K in the specific immune response to ribosomes was also investigated. Even at very high levels PS-K failed to afford any significant protection. LPS gave no protection. A stable r-RNA/PS-K complex was isolated by means of affinity chromatography. This complex was uncontaminated by LPS and its existence indicated strong bonding between surface polysaccharide antigens and r-RNA. The r-RNA/PS-K complex was not antigenic in itself but conferred good protection when combined with an adjuvant.

Animals↗

Pesticide-containing diets augment anti-sheep red blood cell nonreaginic antibody responses in mice but may prolong murine infection with Giardia muris.

The effects of oral ingestion of different pesticides (lindane, phosalone, carbaryl) and of a polychlorinated biphenyl (pyralene) on nonreaginic antibody production in BALB/c mice and also on the duration of Giardia muris infection have been studied using the animal model of this disease. Only lindane and carbaryl produced significant effects on systemic antibody production following oral immunization with sheep red blood cells (SRBC). Lindane ingestion led to a twofold increase in IgG2b antibody titer to SRBC (P less than 0.05) and carbaryl significantly increased both IgG1 and IgG2b titers. No reduction was seen in the synthesis of any antibody class. The effect of feeding with lindane was to increase the duration of giardiasis significantly (P less than 0.002), and these mice developed systemic anti-Giardia antibodies more frequently than Giardia-infected mice on normal diets. These results suggest that in the doses used these pesticides may increase systemic antibody responses to orally ingested antigens, and by inference that spontaneous elimination of giardiasis is independent of the systemic nonreaginic antibody response to the parasite.

Animals↗

Abrogation by subsequent feeding of antibody response including IgE, in parenterally immunized mice.

We have investigated the possibility of oral administration of ovalbumin (OVA) to prevent a secondary antibody response and interrupt reaginic antibody production. Repeated feeding seems necessary for both. Quality of results was dependent on the number of ingestions. Differences in abrogation of antibody response between mice strains were observed. Best results were obtained with AKR mice, good suppression was seen in C3H strain, and inconsistent results were obtained with DBA/2. 10 OVA oral doses were necessary to prevent a secondary antibody response in parenterally immunized mice, but 4 doses interrupted reaginic production in sensitized AKR mice. These results demonstrate that antigen feeding can prevent a secondary antibody response and interrupt reaginic antibody production.

Administration, Oral↗