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Biomedical subjects

F Forestier

Publications and source records attributed to F Forestier.

At least 37 records · Page 2Linked to original sources

[Diagnosis of materno-fetal toxoplasmosis].

The antenatal diagnosis of congenital toxoplasmosis represents today an important application of molecular diagnostic methods such as PCR. Done directly in amniotic fluid, the PCR for T. gondii is able to detect in utero infected foetus with high probability. Doing so, it precludes to obtain foetal blood and to use more cumbersome and lengthy procedures such as inoculation to cell lines or to mice. Although it is use today in many centres, the molecular diagnosis of T. gondii by PCR is neither commercialized nor standardised. The objective of this report is to present the methodology used in our institution and to establish its degree of validation.

Female↗

Inhibition of platelet aggregation by abciximab but not by aspirin can be detected by a new point-of-care test, the hemostatus.

We have investigated the type of platelet defect that can be detected with the Hemostatus test performed with the Hepcon/HMS instrument (Medtronic) designed to investigate platelet function during and after surgery. This assay is based on the comparison of the activated clotting time of whole blood measured in cartridges containing kaolin or kaolin and platelet-activating factor in different concentrations. Addition of platelet-activating factor shortened the blood activated clotting time when the platelet counts were normal. However, when platelet counts were below 70000/microL, the activated clotting time was prolonged in all channels including those without platelet-activating factor showing the influence of platelets in the formation of the clot under the conditions tested. Inhibition of platelet aggregation with c7E3 (abciximab, ReoPro) also induced a much-prolonged activated clotting time, and a similar finding was seen with blood from a patient with Glanzmann's thrombasthenia confirming the need for platelet aggregation and/or the glycoprotein (GP) IIb-IIIa complex. In contrast, the interaction of GP Ib with von Willebrand Factor was not of major importance, since inhibition of this interaction with the anti-GP Ib murine monoclonal antibody, ALMA-12, did not modify the activated clotting time. Furthermore, the activated clotting time measured for patients with an acquired defect in von Willebrand Factor activity were unchanged. Finally, inhibition of thromboxane A2 formation by aspirin did not influence the results of this test. Globally, the Hemostatus test was able to detect major abnormalities of GP IIb-IIIa function in the presence or absence of platelet-activating factor.

Abciximab↗

Haematological parameters of parvovirus B19 infection in 13 fetuses with hydrops foetalis.

Thirteen cases of fetal parvovirus B19 infection with hydrops foetalis are reported. Viral DNA was identified by polymerase chain reaction (PCR) of amniotic fluid sampled between the 19th and the 29th week of gestation. Haematological examination revealed severe anaemia in all cases and thrombocytopenia in 11/13 cases, which was severe in two cases. Six fetuses died in utero; two after intrauterine transfusion. Complete recovery was observed in seven fetuses; five cases were treated by intrauterine transfusions, and in two cases spontaneous recovery occurred. Upon follow-up, no case of congenital anaemia was observed.

Anemia↗

Immunoglobulins of the human amniotic fluid.

PROBLEM: Except for the description of a secretory immunoglobulin (S-Ig) of a low size, no recent study has investigated the molecular status of antibodies in the human amniotic fluid. METHOD: After separation with a high performance chromatography, we analyzed the different isotypes of amniotic Igs by immunoblotting and ELISA. RESULTS: IgG is found to be the major isotype and to contain mother-derived tetanus antitoxins. IgA is much less abundant, whereas no IgM can be detected. IgA is monomeric, with a low level of secretory IgA and with various amounts of free secretory component (SC). The presence of a low level of SC-containing immunoglobulin of a low size is confirmed during the last trimester of pregnancy. This molecule contains no alpha chain but includes a Fabgamma fragment noncovalently associated with SC. IgG, IgA, and SC are detected in the fetal urine and, therefore, can reach the amniotic fluid by this route. CONCLUSION: In addition to the predominant maternal IgG, the amniotic fluid contains different molecular forms of fetal immunoglobulins. Their function as an immune barrier against infection and against mother-derived autoantibodies is discussed.

Amniotic Fluid↗

High levels of circulating thrombomodulin in human foetuses and children.

Thrombomodulin (TM) is an endothelial cell surface proteoglycan with anticoagulant functions, also implicated in cell proliferation, cell-cell adhesion and differentiation. In this study we determined circulating plasma TM (pTM) levels in human foetuses at different stages of pregnancy, at birth and in childhood. TM levels increased with gestational age, the median level reaching a peak of approximately 165 ng/ml between the 23rd and 26th week, thereafter decreasing gradually, reaching a value of 108 ng/ml at birth. pTM continues to decrease progressively during childhood, reaching in the 5-15 years group a median of 56 ng/ml which approaches the adult value. The pTM peak was statistically significant and represents a specific foetal phenomenon as it was independent of the corresponding maternal values. As a whole, the pTM pattern during foetal maturation appears totally different from that of protein C, prothrombin and other coagulation activators and inhibitors and thus, TM may play in the foetus another role in addition to its well-known anticoagulant function.

Adolescent↗

The intestinal microflora regulates cytokine production positively in spleen-derived macrophages but negatively in bone marrow-derived macrophages.

Besides its role as a barrier against potential pathogens, intestinal flora is presumed to protect the host by priming the immunological defense mechanisms. In this respect, the influence of intestinal flora on macrophage precursors was examined, and its modulating effect was compared on LPS-induced cytokine production by macrophages derived from bone marrow and spleen precursors (BMDM and SDM respectively). The regulation of IL-1, IL-6, TNF-alpha and IL-12 production in macrophages from germ-free and from three groups of flora-associated mice, conventional, conventionalized and E. coli-mono-associated mice, was investigated. The whole flora inhibited IL-1, TNF-alpha and IL-12 secretion by BMDM, whereas it had a stimulatory effect on IL-12 secretion by SDM. Implantation of E. coli alone enhanced cytokine secretion by BMDM but had a more limited effect than whole flora on SDM, enhancing only TNF-alpha and IL-12 secretion. Study of expression of mRNA showed a correlation with protein secretion for IL-6 but not for TNF-alpha and IL-1. IL-12 enhancement in BMDM seemed to be dependent on regulation of p35 mRNA expression while it was correlated to increased p40 mRNA expression in SDM. The results demonstrated that intestinal flora modulated bone marrow and spleen macrophage cytokine production in a differential manner and suggested a role for bacteria other than E. coli among the whole flora. The contrasting effects exerted by the intestinal flora on bone marrow and spleen precursors are an interesting observation in view of the different functions of these organs in immunity. The finding that intestinal flora enhanced IL-12 production in spleen is also potentially important since this cytokine is implicated in the determination of the relative levels of Th1 and Th2 responses and plays a pivotal role in host defense against intracellular microorganisms.

Animals↗

Human amniotic IgA inhibits natural IgG autoantibodies of maternal or unrelated origin.

We show that the natural autoantibody activity of amniotic IgG dramatically increases after purification, and that the IgG-depleted fraction can suppress the activity of IgG natural antibodies from amniotic fluid or from the maternal serum. This suppression is also observed towards serum IgG from unrelated adults but does not impair the tetanus antitoxin activity of serum-derived IgG. Absorption experiments and immunoglobulin separation by gel permeation demonstrate that this suppression is due to monomeric immunoglobulins of the IgA isotype. The inhibition is associated with an anti-F(ab')2 activity of the amniotic IgA, involving hypervariable regions of the IgG as demonstrated by different reactivities towards monoclonal IgG sharing the same family of VH and Vkappa domains. These results indicate that the inhibition of natural autoantibodies not only occurs with fetal and adult serum IgM, as reported by other groups, but also with amniotic IgA, suggesting a general and important phenomenon. In the case of the amniotic fluid, IgA could protect the fetus against maternal IgG autoantibodies without interfering with simultaneously translocated antigen-induced IgG antibodies to pathogens.

Adult↗

Influence of intestinal microflora on murine bone marrow and spleen macrophage precursors.

To investigate the adjuvant effect of intestinal flora on macrophage-colony-stimulating factor-responsive macrophage progenitors from spleen and bone marrow, we compared progenitor numbers and phenotypic characteristics of in vitro matured macrophages in germ-free and flora-associated mice (conventional, Escherichia coli-monoassociated and conventionalized mice). The data obtained show that the flora affected differentially bone marrow and spleen progenitors. It increased the numbers of progenitors in the spleen but not in the bone marrow. It did not modify the expression of F4/80, Mac-1 and major histocompatibility complex (MHC) class II on bone-marrow-derived macrophages (BMDM), while it clearly up-regulated MHC class II expression on spleen-derived macrophages (SDM). This effect was more pronounced in flora-associated ex germ-free mice than in conventional mice and it was greatly enhanced in the absence of M-CSF. In vitro stimulation by lipopolysaccharide had no effect on marker expression of BMDM, while it decreased F4/80 and enhanced MHC class II molecules on SDM from germ-free and flora-associated mice. However, the expression of MHC class II remained lower in germ-free mice. Enhancement of MHC class II molecule expression on SDM may contribute to the protective role of flora, because successful immune responses are dependent on the expression of these molecules.

Animals↗

Effects of intravenous anesthetics on normal and passively sensitized human isolated airway smooth muscle.

BACKGROUND: General anesthetics may modify airway responsiveness. The authors investigated the effect of thiopental, propofol, and etomidate on airway smooth muscle. METHODS: Contraction experiments were done in human airway rings that were either normal or passively sensitized with asthmatic serum. The effect of propofol and etomidate was also studied on both [Ca2+]i increase measured by microspectrofluorimetry in isolated myocytes and isometric contraction in the rat trachea. RESULTS: In human bronchi, thiopental (10[-7] to 10[-4] M) induced a concentration-dependent contraction. Neither propofol nor etomidate altered baseline tone, but both anesthetics reduced histamine-induced contraction. In human immunologically sensitized isolated bronchi, propofol (3 x 10[-4] M) reduced histamine reactivity (deltaFmax in %) to a greater degree than in nonsensitized tissues (64.4 +/- 15.7% and 16.4 +/- 8.5%, respectively; n = 6, P < 0.05), whereas the effect of etomidate (10[-4] M) was similar in both types of tissue (24.1 +/- 6% and 22.3 +/- 15%, respectively, n = 6). In rat isolated tracheal myocytes, propofol (3 x 10[-4] M) and etomidate (10[-4] M) altered the [Ca2+]i signal in response to the depolarizing agent potassium chloride and the muscarinic agonist acetylcholine. Accordingly, the two anesthetics also reduced the mechanical response of rat tracheal rings to these agonists. CONCLUSIONS: Whereas thiopental contracts human isolated bronchi, propofol and etomidate reduce histamine-induced contraction in human isolated airway smooth muscle that were either not sensitized or passively sensitized with asthmatic serum. This effect involves inhibition of both electro- and pharmacomechanical coupling.

Anesthetics, Intravenous↗

Rotavirus infection reduces sucrase-isomaltase expression in human intestinal epithelial cells by perturbing protein targeting and organization of microvillar cytoskeleton.

Rotavirus infection is the most common cause of severe infantile gastroenteritis worldwide. These viruses infect mature enterocytes of the small intestine and cause structural and functional damage, including a reduction in disaccharidase activity. It was previously hypothesized that reduced disaccharidase activity resulted from the destruction of rotavirus-infected enterocytes at the villus tips. However, this pathophysiological model cannot explain situations in which low disaccharidase activity is observed when rotavirus-infected intestine exhibits few, if any, histopathologic changes. In a previous study, we demonstrated that the simian rotavirus strain RRV replicated in and was released from human enterocyte-like Caco-2 cells without cell destruction (N. Jourdan, M. Maurice, D. Delautier, A. M. Quero, A. L. Servin, and G. Trugnan, J. Virol. 71:8268-8278, 1997). In the present study, to reinvestigate disaccharidase expression during rotavirus infection, we studied sucrase-isomaltase (SI) in RRV-infected Caco-2 cells. We showed that SI activity and apical expression were specifically and selectively decreased by RRV infection without apparent cell destruction. Using pulse-chase experiments and cell surface biotinylation, we demonstrated that RRV infection did not affect SI biosynthesis, maturation, or stability but induced the blockade of SI transport to the brush border. Using confocal laser scanning microscopy, we showed that RRV infection induces important alterations of the cytoskeleton that correlate with decreased SI apical surface expression. These results lead us to propose an alternate model to explain the pathophysiology associated with rotavirus infection.

Biological Transport↗

Serum C24 bile acids in the developing human fetus.

The C24 bile acids (BA) in the serum of 22 healthy human fetuses between weeks 20 and 37 of gestation were determined by capillary GC-MS. Fetal blood samples were taken in utero from the umbilical cord monitored by echography. There was no correlation between total bile acids (TBA) and gestational age. The TBA concentration was 5.14 +/- 2.13 microM. Primary BA (cholic acid and chenodeoxycholic acid) were the main BA (66.78 +/- 13.47%) with chenodeoxycholic acid being the main one. There were low concentrations of secondary BA (deoxycholic acid and lithocholic acid) (10.28 +/- 7.85%), which formed by intestinal bacterial 7 alpha-dehydroxylation of primary BA in the adult, despite the germ-free gut. The tertiary BA (ursodeoxycholic acid) was also detected (12.06 +/- 9.64%). There was 6 alpha-hydroxylation of chenodeoxycholic acid and of lithocholic acid to produce hyocholic acid and hyodeoxycholic acid respectively. Two 1 beta-hydroxylated BA were detected at different times of gestation. Cholic acid was rarely found in the 6 alpha- and 1 beta-hydroxylated forms. These additional hydroxylations could help to protect the fetal liver against the accumulation of cytotoxic bile acids at a time when other detoxification pathways are poorly developed. Traces of unsaturated bile acids like 3 beta-hydroxy-5-cholenoic acid were detected, showing that 27-hydroxylation of cholesterol does occur.

Alkaline Phosphatase↗

Management of fetal and neonatal alloimmune thrombocytopenia.

Fetal and neonatal thrombocytopenia can be induced by a maternal alloimmunization against fetal platelet antigens. Alloimmune thrombocytopenia occurs with an incidence of 1/1,000 livebirths and may present either with evidence of damage from a prenatal hemorrhage such as porencephaly or intrauterine death, or with active life-threatening bleeding during the neonatal period. It is due to the destruction of fetal platelets by alloantibodies reacting on specific antigenic sites. In Caucasians, the human platelet antigen 1a (HPA-1a) is the most frequently involved in alloimmune thrombocytopenias, accounting for 80-90% of the cases. Anti-HPA-5b is responsible for a further 5-15% of the cases. This article reviews the clinical aspects, the biological diagnosis and the management, including prenatal sampling and maternal therapy.

Antigens, Human Platelet↗

[Results of a National survey on antibiotic prophylaxis and antisepsis in cataract surgery].

PURPOSE: We present the results of a national survey carried out in 1997 among French ophthalmologists on prophylactic antibiotic and antiseptic therapy in cataract surgery. METHOD: Among the 6050 questionnaires sent by post, 1082 answers recorded between January and February 1997. RESULTS: The results give precise details on French surgeons attitude as regards prophylactic antibiotics for: topical, subconjunctival, intra-ocular and systemic administration. CONCLUSION: This kind of study is frequent in English-speaking countries and is useful to help our profession to formulate important current questions and to collect answers.

Administration, Topical↗

Hematological features of fetal triploidy: a report of 11 cases.

Using fetal blood sampling, the diagnosis of triploidy can be strongly suspected on the basis of the peculiar hematological picture. Triploid fetuses present with anemia, marked anisopoikilocytosis, and grossly increased mean corpuscular volume, associated with thrombocytopenia and significant platelet anisocytosis. These findings are of considerable immediate diagnostic value. They allow physicians to immediately counsel parents about the prognosis of the fetus. In case of fetal or neonatal distress, this information could orientate decisions about obstetrical and pediatric management while waiting for the definitive diagnosis.

Blood Cell Count↗