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Biomedical subjects

A Gillet

Publications and source records attributed to A Gillet.

At least 19 recordsLinked to original sources
PubMed2004

[Allergy to ragweed in the Rhone-Alpes and consumption of anti-allergics].

AIMS: To measure evolution and cost consumption of anti-allergic medicines during ragweed pollen-period, geographic trend in the locations of anti-allergic consumers. Ragweed is highly spread in Rhone Alps. METHODS: We measured the ratio: number of boxes of anti-allergic medicines per one thousand patients between 6 and 64 years, refunded by twelve local health offices in the Rhone Alps area. We obtained statistical mapping for consumers of triamcinolone, we analysed in the relation to weakly ragweed pollen figures. RESULTS: Four geographic areas showed high increases of antihistaminic consumption from the middle of august to the end of september during the four years studied. A threefold increase of consumption of antihistaminic medicines, anti-allergic eye-drops and anti-allergic nasals topics was observed during ragweed pollen-period (week 33 to week 40). Antihistaminic consumption ratios increased in relation with ragweed pollen-period This study demonstrated that the anti-allergic medicines consumption reflected the image of ragweed allergy. This sanitary feature is easily obtained from the refunded databases of Medical Insurance.

Administration, Topical↗
PubMed2003

Comparison of two methods of cervical cerclage by ultrasound cervical measurement.

OBJECTIVE: To compare the effects of cerclage performed with a modified Shirodkar procedure or with McDonald's technique using transvaginal ultrasound measurement of the distance between the external os and the suture. MATERIALS AND METHODS: We performed a retrospective study of all patients who underwent a prophylactic cerclage with either the modified Shirodkar procedure or the McDonald's technique over a 3-year period. Physicians chose the cerclage technique according to their own preferences. Transvaginal ultrasound examination of the cervix was performed 2 weeks after the cerclage to measure its functional length and the distance between the external os and the cerclage. RESULTS: During the study period, 14 patients had a cerclage with the modified Shirodkar procedure and 19 patients with the McDonald's technique. Twelve of these 33 patients (36.4%) delivered before 37 weeks. The obstetric characteristics of the patients in both groups were similar. There were no significant differences between the Shirodkar and McDonald groups as to the functional cervical length before (31.3 +/- 8.7 vs. 35.6 +/- 9.7 mm, respectively) or after (37.0 +/- 7.3 vs. 36.1 +/- 7.9 mm) cerclage, the distance between the external os and cerclage (16.7 +/- 3.8 vs. 14.0 +/- 5.2 mm), or the number of deliveries before 32 (0 vs. 2) and 34 (1 vs. 3) weeks. CONCLUSION: The anterior colpotomy of the Shirodkar procedure increased the distance between the external os and the cerclage by a mean of 2.7 mm. This slight gain does not justify exposing the patient to the risks related to this procedure. When cerclage is necessary, McDonald's technique seems preferable.

Adult↗
PubMed2003

[Consumption of allergy medicines in 2000 and 2001: data from 12 Primary Medical Insurance Offices (CPAM) in the Rhône-Alpes region].

OBJECTIVES: Comparison of the annual consumption of different classes of antiallergy medicines in the Rhône-Alpes region and as a function of the pollen calendar. MATERIAL AND METHODS: Exhaustive review, over all the beneficiaries of the general system of social security aged from 6 to 65 years, of the number of weekly supplies: non-cholinergic oral antihistamines (antiH1), anti-allergy nasal sprays, anti-allergy eye lotions, delayed release injectable orticosteroids. In the twelve Primary Offices of Medical Assurance of the Rhône-Alpes region for the years 2000 and 2001. The results are expressed as the number of units (boxes)/100 beneficiaries. RESULTS: The principal reports are: Consumptions vary in a parallel way between the different regions with a south > north and plain > mountain gradient between the different therapeutic classes (per os > local administration); a fluctuation closely linked to the presence of allergizing pollens: ragweed is responsible for high consumption in all the departments except the two Savoie. The observed peak of pollinization of birch in 2001 was associated with a peak of deliveries. These data confirm the value of data of medicines consumption both economically and medically.

Adrenal Cortex Hormones↗
PubMed2002

Transvaginal sonographic examination of the cervix in asymptomatic pregnant women: review of the literature.

Different strategies have been developed to refine the prediction of the risk of preterm delivery in asymptomatic patients. Transvaginal sonography has been used for this reason to measure and examine the length and shape of the cervix. In this review, we focus on clinical studies involving transvaginal sonographic assessment of the cervix in asymptomatic women at high risk of preterm delivery and in the general pregnant population. Three ultrasound signs are suggestive of cervical incompetence, namely, dilatation of the internal os, sacculation or prolapse of the membranes into the cervix (with shortening of the functional cervical length) either spontaneously or induced by transfundal pressure, and short cervix in the absence of uterine contractions. Transvaginal sonography has clearly demonstrated that cerclage leads to a measurable increase in cervical length which may contribute to the success of this procedure in reducing the risk of preterm delivery. Several non-randomized interventional studies among patients with cervical incompetence have been published. They have defined a new group of patients requiring cerclage when the women show progressive cervical modifications on transvaginal sonography, while in other studies, cerclage performed on the basis of cervical changes on transvaginal sonography did not prevent premature delivery. One prospective randomized trial in asymptomatic high-risk women has shown two benefits of cerclage following indications for transvaginal sonography: (1) it would generate fewer prophylactic cerclages in high-risk women; (2) therapeutic cerclage before 27 weeks may reduce the incidence of premature delivery before 34 weeks. The risk of preterm delivery is inversely correlated with cervical length. Routine transvaginal sonography of the cervix performed between 18 and 22 weeks can help identify patients at risk of preterm delivery. However, given the low prevalence of preterm births, screening would generate either a high false-positive rate or a low sensitivity. One non-randomized interventional study among patients with a short cervix on routine ultrasound examination found a lower risk of delivery before 32 weeks in the cerclage group than in the expectant management group. However, to date, there have been no prospective randomized trials in a general population. Although evidence is still lacking, there does appear to be a benefit in performing a cerclage rather than continuing with expectant management in cases with sonographic appearance of cervical incompetence in asymptomatic women at high risk of preterm delivery. Ultrasound can be offered to reduce the indications of cerclage for cases in which the situation is uncertain. Within the general obstetric population, transvaginal sonography might help in the selection of asymptomatic but high-risk women. However, the benefit associated with cerclage for sonographic indication has not been demonstrated.

Cervical Ripening↗
PubMed2001

T cell development and T cell responses in mice with mutations affecting tyrosines 292 or 315 of the ZAP-70 protein tyrosine kinase.

After stimulation of the T cell receptor (TCR), the tyrosine residues 292 and 315 in interdomain B of the protein tyrosine kinase ZAP-70 become phosphorylated and plausibly function as docking sites for Cbl and Vav1, respectively. The two latter proteins have been suggested to serve as substrates for ZAP-70 and to fine-tune its function. To address the role of these residues in T cell development and in the function of primary T cells, we have generated mice that express ZAP-70 molecules with Tyr to Phe substitution at position 292 (Y292F) or 315 (Y315F). When analyzed in a sensitized TCR transgenic background, the ZAP-70 Y315F mutation reduced the rate of positive selection and delayed the occurrence of negative selection. Furthermore, this mutation unexpectedly affected the constitutive levels of the CD3-zeta p21 phosphoisoform. Conversely, the ZAP-70 Y292F mutation upregulated proximal events in TCR signaling and allowed more T cells to produce interleukin 2 and interferon gamma in response to a given dose of antigen. The observation that ZAP-70 Y292F T cells have a slower rate of ligand-induced TCR downmodulation suggests that Y292 is likely involved in regulating the duration activated TCR reside at the cell surface. Furthermore, we showed that Y292 and Y315 are dispensable for the TCR-induced tyrosine phosphorylation of Cbl and Vav1, respectively. Therefore, other molecules present in the TCR signaling cassette act as additional adaptors for Cbl and Vav1. The present in vivo analyses extend previous data based on transformed T cell lines and suggest that residue Y292 plays a role in attenuation of TCR signaling, whereas residue Y315 enhances ZAP-70 function.

Animals↗
PubMed1999

Crippling of CD3-zeta ITAMs does not impair T cell receptor signaling.

We evaluated the importance of CD3-zeta ITAMs in T cell responses by breeding the P14 transgenic TCR into mice in which CD3-zeta chains lacking all or part of their ITAMs were genetically substituted for wild-type CD3-zeta chains. In contrast to the H-Y TCR, the P14 TCR permitted the development of peripheral CD8+ T cells harboring signaling-defective CD3-zeta subunits. The absence of functional CD3-zeta ITAMs did not reduce the spectrum of activation events and effector functions that constitute the normal attributes of mature CD8+ T cells. The only detectable differences were quantitative and noted only when T cells were challenged with suboptimal peptide concentrations. Therefore, the ITAMs present in the CD3-gammadeltaepsilon module are sufficient for qualitatively normal TCR signaling and those present in CD3-zeta have no exclusive role during T cell activation.

Animals↗
PubMed1998

Insulin receptor substrate 1 antisense expression in an hepatoma cell line reduces cell proliferation and induces overexpression of the Src homology 2 domain and collagen protein (SHC).

In mammalian cells, the insulin receptor substrate 1 protein (IRS-1) is a specific substrate for insulin and IGF-1 receptor tyrosine kinases which is involved in mediating metabolic and mitogenic actions of insulin and IGFs. In order to determine if IRS-1 is also essential in a chicken derived hepatoma cell line (LMH cells), IRS-1 gene has been invalidated in these cells. For this, we subcloned chicken IRS-1 gene in an antisense orientation into a mammalian expression vector driven by the cytomegalovirus early promoter. LMH cells were stably transfected with this construct or with the empty vector carrying only the neomycin resistance gene and selected for cIRS-1 expression. One subclone, C2, showed a complete repression of cIRS-1 expression at both protein and mRNA levels. Proliferation of C2 cells was dramatically reduced (54%) compared with Neo(r) cells. Furthermore this reduction was accompanied by a decrease in insulin-dependent [3H]thymidine incorporation, indicating a reduction in DNA synthesis. Insulin-dependent [U-14C]glucose incorporation into cellular lipids was also significantly reduced in C2 cell line suggesting an alteration in lipogenesis. In wild type LMH cells, SHC which is involved in Ras pathway, also served as a substrate for insulin receptor tyrosine kinase. In C2 cells, SHC expression, its association with the insulin receptor and its tyrosine phosphorylation were largely increased. Two forms of the regulatory subunit of PI 3-kinase were present: p85 and p55 forms. Furthermore, C2 cells displayed increased basal phosphatidylinositol (PI) 3'-kinase activity. This report demonstrates a role for cIRS-1 in the metabolic and mitogenic actions of insulin in LMH cells. However, the overexpression of cIRS-1 antisense did not completely abolish cell proliferation. This may be explained by the exacerbation of an alternative pathway that only partly compensate for the knocking out of cIRS-1 gene: the overexpression of SHC.

Adaptor Proteins, Signal Transducing↗
PubMed1997

The single positive T cells found in CD3-zeta/eta-/- mice overtly react with self-major histocompatibility complex molecules upon restoration of normal surface density of T cell receptor-CD3 complex.

CD3-zeta/eta-deficient mice have small thymuses containing cells that show a profound reduction in the surface levels of T cell receptors and terminate their differentiation at the CD4+CD8+ stage. Rather unexpectedly, CD3- or very low single positive T cells accumulate over time in the spleen and lymph nodes of CD3-zeta/eta-deficient mice after a process dependent on MHC expression. Fusion of these peripheral T cells with a CD3-zeta-positive derivative of the BW5147 TCR-alpha-/beta- thymoma resulted in hybridomas that do express an heterogeneous set of T cell receptor alpha/beta dimers at their surface and at density comparable to those found in hybridomas derived from wild-type peripheral T cells. We have investigated the specificities of these T cell receptors using spleen cells from congenic and mutant mouse strains, and showed that the majority of them readily recognized self-MHC class I or class II molecules. These results demonstrate that by increasing the density and/or output of the T cell receptors expressed in peripheral T cells, one can confer them with the capacity to respond to normal density of self-MHC molecules.

Animals↗
PubMed1995

Altered T cell development in mice with a targeted mutation of the CD3-epsilon gene.

To determine which CD3 components are required for early T cell development, we generated mice with a targeted mutation of the CD3-epsilon gene and characterized their T cell populations relative to those found in CD3-zeta/eta-and recombinase activating gene (RAG)-deficient mice. In the absence of intact CD3-epsilon subunit, thymocytes do not progress beyond the CD44-/lowCD25+ triple-negative stage and appear to be arrested at the very same developmental control point as RAG-deficient thymocytes. In contrast, the disruption of the CD3-epsilon/eta gene does not totally abrogate the progression through this control point. CD3-epsilon-deficient thymocytes do rearrange their T cell receptor (TCR) beta gene segments and produce low levels of full-length TCR beta transcripts. Taken together, these results establish an essential role for the CD3-epsilon gene products during T cell development and further suggest that the CD3-epsilon polypeptides start to exert their function as part of a pre-TCR through which CD44-/lowCD25+ triple-negative cells monitor the occurrence of productive TCR beta gene rearrangements. Finally, the absence of intact CD3-epsilon polypeptides had no discernible effect on the completion of TCR gamma and TCR delta gene rearrangements, emphasizing that they are probably not subjected to the same epigenetic controls as those operating on the expression of TCR alpha and beta genes.

Animals↗
PubMed1995

Normal development and function of natural killer cells in CD3 epsilon delta 5/delta 5 mutant mice.

The CD3 epsilon polypeptide contributes to the cell surface display as well as to the signal transduction properties of the T-cell antigen receptor complex. Intriguingly, the distribution of CD3 epsilon is not restricted to T cells, since activated mouse, human, and avian natural killer (NK) cells do express intracytoplasmic CD3 epsilon polypeptides. CD3 epsilon is also present in the cytoplasm of fetal thymic T/NK bipotential progenitor cells, suggesting that it constitutes a component of the NK differentiation program. We report here that the genetic disruption of CD3 epsilon exon 5 alters neither NK cell development nor in vitro and in vivo NK functions, although it profoundly blocked T-cell development. These results support the notion that CD3 epsilon is dispensable for mouse NK cell ontogeny and function and further suggest that the common NK/T-cell progenitor cell utilizes CD3 epsilon as a mandatory component only when differentiating toward the T-cell lineage.

Amino Acid Sequence↗
PubMed1993

T cell development in mice lacking the CD3-zeta/eta gene.

The CD3-zeta and CD3-eta polypeptides are two of the components of the T cell antigen receptor (TCR) which contribute to its efficient cell surface expression and account for part of its transducing capability. CD3-zeta and CD3-eta result from the alternative splicing of a single gene designated CD3-zeta/eta. To evaluate the role of these subunits during T cell development, we have produced mice with a disrupted CD3-zeta/eta gene. The analysis of thymocyte populations from the CD3-zeta/eta-/- homozygous mutant mice revealed that they have a profound reduction in the surface levels of TCR complexes and that the products of the CD3-zeta/eta gene appear to be needed for the efficient generation and/or survival of CD4+CD8+ thymocytes. Despite the almost total absence of mature single positive thymocytes, the lymph nodes from zeta/eta-/- mice were found to contain unusual CD4+CD8- and CD4-CD8+ single positive cells which were CD3-. In contrast to the situation observed in the thymus, the thymus-independent gut intraepithelial lymphocytes present in zeta/eta-/- mice do express TCR complexes on their surface and these are associated with Fc epsilon RI gamma homodimers. These results establish an essential role for the CD3-zeta/eta gene products during intrathymic T cell differentiation and further emphasize the difference between conventional T cells and thymus-independent gut intraepithelial lymphocytes.

Animals↗
PubMed1990

Beta 2-microglobulin restriction of antigen presentation.

Antigens are generally thought to be recognized by cytotoxic T lymphocytes as peptides in the context of class I major histocompatibility proteins complex, which are heterodimers of heavy chains noncovalently associated with beta 2-microglobulin (beta 2m). The highly polymorphic nature of the heavy chains and their resulting ability to present different sets of peptides has presumably evolved to allow potent immune responses against most pathogens. By contrast, the polymorphism of beta 2m is limited; seven alleles are known in the mouse and only one has been identified in humans. beta 2-Microglobulin was consequently thought to have only structural functions: namely, to ensure correct folding of class I molecules and their transport to the cell surface. Although beta 2m is not implicated directly in the formation of the peptide binding site, we report here that it participates in the selection of MHC class I molecule-associated peptides.

Amino Acid Sequence↗
PubMed1989

Analysis of the HLA-Cw3-specific cytotoxic T lymphocyte response of HLA-B7 X human beta 2m double transgenic mice.

The cytolytic responses of either normal (non transgenic), HLA-B7 (single transgenic) or HLA-B7 x human beta 2 microglobulin (double transgenic) DBA/2 mice induced by transfected HLA-Cw3 P815 (H-2d) mouse mastocytoma cells were compared, to evaluate whether the expression of an HLA class I molecule in responder mice would favor the emergence of HLA-specific, H-2-unrestricted CTL. Only 8 of 300 HLA-Cw3-specific CTL clones tested could selectively lyse HLA-Cw3-transfected cells in an H-2-unrestricted manner, all having been isolated after hyperimmunization of double transgenic mice. These clones also lysed HLA-Cw3+ human cells. Unexpectedly, the lysis of the human but not that of the murine HLA-Cw3 cells was inhibited by Ly-2,3-specific mAb. Despite significant expression of HLA-B7 class I molecules on transgenic lymphoid cells, including thymic cells, limiting dilution analysis and comparative study of TCR-alpha and -beta gene rearrangements of the eight isolated clones (which suggested that they all derived from the same CTL precursor) indicated that the frequency of HLA-Cw3-specific H-2 unrestricted cytotoxic T lymphocytes remained low (even in HLA-B7 x human beta 2-microglobulin double transgenic mice). This suggests that coexpression of HLA class I H and L chain in transgenic mice is not the only requirement for significant positive selection of HLA class I-restricted cytotoxic mouse T lymphocytes.

Animals↗
PubMed1989

Influence of hyperlipidic food on the kinetics of slow-release formulations of theophylline.

A cross-over study of kinetics has been undertaken in 12 healthy adults volunteers using two sustained-release theophylline products that allow once a day dosing (Theo-Dur tablets and Dilatrane A.P. bead filled capsules) to compare the i.v. pharmacokinetic profiles when taken with an hyperlipidic meal and a balanced standard meal. Each subject took part in four phases in randomised order, corresponding to all possible combinations of the products and the types of meal. Each phase involved a single dose of 9 to 11 mg.kg-1 theophylline administered at 20.00 h, at the beginning of the meal, with 100 ml water. The two formulations were found to be bioequivalent with both types of meal. Taken with a balanced meal, the mean parameters were similar; for Theo-Dur and Dilatrane A.P. they were respectively: Cmax: 11.32 mg.l-1 which plateaued from 8 to 10 h after dosing and 10.9 mg.l-1, which plateaued after 6 to 10 h; AUC 230 mg.h.l-1 and 220 mg.h.l-1; and MRT 18.2 h and 17.7 h. After the hyperlipidic meal the values for Theo-Dur and Dilatrane A.P. respectively, were: Cmax 10.9 mg.l-1 at 12 h and 11.3 mg.l-1 at 10 h; AUC 237 mg.h.l-1 and 227 mg.h.l-1; and MRT 19.2 h and 18.9 h. In spite of a decrease in the absorption rate, which led to a shift to the right of about 2 h of the plasma concentration-time curve, the bioavailability of both formulations were not significantly modified by a hyperlipidic meal as compared to a balanced meal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗