[Pregnancy termination in Swiss hospitals. Results of a survey]. / La pratique de l'interruption de grossesse dans les établissements hospitaliers de suisse. Résultats d'une enquête.

Based on the response of 84 hospitals and clinics to a questionnaire, an overview is given of the practice of pregnancy termination in a hospital setting in Switzerland. A comparison to current practice in the Netherlands rouses the question whether for 1st trimester abortions Swiss hospitals might use more often local anaesthesia, minimal dilatation, aspiration without subsequent curettage and patient surveillance of less than four hours as well as dilatation and evacuation (D&E) for 2nd trimester abortions.

Expression of the three human major histocompatibility complex class II isotypes exhibits a differential dependence on the transcription factor RFXAP.

Major histocompatibility complex class II (MHCII) molecules play a pivotal role in the immune system because they direct the development and activation of CD4(+) T cells. There are three human MHCII isotypes, HLA-DR, HLA-DQ, and HLA-DP. Key transcription factors controlling MHCII genes have been identified by virtue of the fact that they are mutated in a hereditary immunodeficiency resulting from a lack of MHCII expression. RFXAP-one of the factors affected in this disease-is a subunit of RFX, a DNA-binding complex that recognizes the X box present in all MHCII promoters. To facilitate identification of conserved regions in RFXAP, we isolated the mouse gene. We then delimited conserved domains required to restore endogenous MHCII expression in cell lines lacking a functional RFXAP gene. Surprisingly, we found that 80% of RFXAP is dispensable for the reactivation of DR expression. Only a short C-terminal segment of the protein is essential for this isotype. In contrast, optimal expression of DQ and DP requires a larger C-terminal segment. These results define an RFXAP domain with an MHCII isotype-specific function. Expression of the three MHCII isotypes exhibits a differential requirement for this domain. We show that this is due to a differential dependence on this domain for promoter occupation and recruitment of the coactivator CIITA in vivo.

CIITA is a transcriptional coactivator that is recruited to MHC class II promoters by multiple synergistic interactions with an enhanceosome complex.

By virtue of its control over major histocompatibility complex class II (MHC-II) gene expression, CIITA represents a key molecule in the regulation of adaptive immune responses. It was first identified as a factor that is defective in MHC-II deficiency, a hereditary disease characterized by the absence of MHC-II expression. CIITA is a highly regulated transactivator that governs all spatial, temporal, and quantitative aspects of MHC-II expression. It has been proposed to act as a non-DNA-binding transcriptional coactivator, but evidence that it actually functions at the level of MHC-II promoters was lacking. By means of chromatin immunoprecipitation assays, we show here for the first time that CIITA is physically associated with MHC-II, as well as HLA-DM, Ii, MHC-I, and beta(2)m promoters in vivo. To dissect the mechanism by which CIITA is recruited to the promoter, we have developed a DNA-dependent coimmunoprecipitation assay and a pull-down assay using immobilized promoter templates. We demonstrate that CIITA recruitment depends on multiple, synergistic protein-protein interactions with DNA-bound factors constituting the MHC-II enhanceosome. CIITA therefore represents a paradigm for a novel type of regulatory and gene-specific transcriptional cofactor.

A gene encoding a novel RFX-associated transactivator is mutated in the majority of MHC class II deficiency patients.

Major histocompatibility class II (MHC-II) molecules are transmembrane proteins that have a central role in development and control of the immune system. They are encoded by a multigene family and their expression is tightly regulated. MHC-II deficiency (OMIM 209920) is an autosomal recessive immunodeficiency syndrome resulting from defects in trans-acting factors essential for transcription of MHC-II genes. There are four genetic complementation groups (A, B, C and D), reflecting the existence of four MHC-II regulators. The factors defective in groups A (CIITA), C (RFX5) and D (RFXAP) have been identified. CIITA is a non-DNA-binding co-activator that controls the cell-type specificity and inducibility of MHC-II expression. RFX5 and RFXAP are two subunits of RFX, a multi-protein complex that binds the X box motif of MHC-II promoters. Mutations in the genes encoding RFX5 (RFX5) or RFXAP (RFXAP) abolish binding of RFX (refs 7,8,12). Similar to groups C and D, group B is characterized by a defect in RFX binding, and although it accounts for the majority of patients, the factor defective in group B has remained unknown. We report here the isolation of RFX by a novel single-step DNA-affinity purification approach and the identification of RFXANK, the gene encoding a third subunit of RFX. RFXANK restores MHC-II expression in cell lines from patients in group B and is mutated in these patients. RFXANK contains a protein-protein interaction region consisting of three ankyrin repeats. Its interaction with RFX5 and RFXAP is essential for binding of the RFX complex to MHC-II promoters.

RFXAP, a novel subunit of the RFX DNA binding complex is mutated in MHC class II deficiency.

Major Histocompatibility Complex class II (MHC-II) deficiency is a disease of gene regulation that provides a unique opportunity for the genetic dissection of the molecular mechanisms controlling transcription of MHC-II genes. Cell lines from MHC-II deficiency patients have been assigned to three complementation groups (A, B and C) believed to reflect the existence of distinct essential MHC-II regulatory genes. Groups B and C, as well as an in vitro generated regulatory mutant representing a fourth group (D), are characterized by a specific defect in the binding activity of RFX, a multimeric DNA binding complex that is essential for activation of MHC-II promoters. RFX5, a subunit of RFX, was recently shown to be mutated in group C. We have now isolated a novel gene, RFXAP (RFX Associated Protein), that encodes a second subunit of the RFX complex. RFXAP is mutated in the 6.1.6 cell line (group D), as well as in an MHC-II deficiency patient (DA). This establishes that group D is indeed a fourth MHC-II deficiency complementation group. Complementation of the 6.1.6 and DA cell lines by transfection with RFXAP fully restores expression of all endogenous MHC-II genes in vivo, demonstrating that RFXAP is a novel essential MHC-II regulatory gene.

A novel DNA-binding regulatory factor is mutated in primary MHC class II deficiency (bare lymphocyte syndrome).

Regulation of MHC class II gene expression is an essential aspect of the control of the immune response. Primary MHC class II deficiency is a genetically heterogeneous disease of gene regulation that offers the unique opportunity of a genetic approach for the identification of the functionally relevant regulatory genes and factors. Most patients exhibit a characteristic defect in the binding of a nuclear complex, RFX, to the X box motif of MHC class II promoters. Genetic complementation of a B-lymphocyte cell line from such a patient with a cDNA expression library has allowed us to isolate RFX5, the regulatory gene responsible for the MHC class II deficiency. This gene encodes a novel DNA-binding protein that is indeed a subunit of the RFX complex. Mutations in the RFX5 gene have been characterized in two patients. Transfection of the patient's cells with the RFX5 cDNA repairs the binding defect and fully restores expression of all the endogenous MHC class II genes in vivo.

Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or bare lymphocyte syndrome).

Hereditary major histocompatibility complex (MHC) class II deficiency (or bare lymphocyte syndrome) is a form of severe primary immunodeficiency with a total lack of MHC class II expression. It is due to a defect in the regulation of MHC class II genes. A novel gene was isolated by complementation cloning, using an MHC class II-negative mutant cell line. This gene (CIITA) functions as a transactivator of MHC class II gene expression and restores expression of all MHC class II isotypes in mutant cells. In addition, CIITA fully corrects the MHC class II regulatory defect of cells from patients with bare lymphocyte syndrome. In this disease we have identified a splicing mutation that results in a 24 amino acid deletion in CIITA, resulting in loss of function of the transactivator. Hence, the CIITA gene is essential for MHC class II gene expression and has been shown to be responsible for hereditary MHC class II deficiency.

[The risks of the natural family planning methods]. / Les risques des méthodes de continence périodique.

PIP: Risks of 5 natural family planning (NFP) methods are compared. The main risk of these methods is the risk of pregnancy stemming from method failure, errors in instruction, error in application of the method, and failure to observe abstinence during the entire fertile period. The calendar rhythm method, the oldest NFP method, is based on calculation of likely fertile days in the preceding 6-12 menstrual cycles. The method is seldom taught at present because of its high failure rate, but it continues to be used, often by individuals with an incomplete understanding of the calculations. The principle of the basal body temperature method is well known. The thermal shift affirms the beginning of the infertile period but does not allow prediction of ovulation. Instructions provided by different organizations to identify the third day of the hyperthermal plateau are not standardized; the various interpretations applied to the same cycle do not necessarily lead to identification of the same day as the start of the infertile period. Comparisons of efficacy between methods are therefore difficult. Well-conducted prospective studies have demonstrated high theoretical efficacy, but failure rates in practice appear to be higher. Women often do not know how to interpret a temperature curve correctly, and the curve may be influenced by illness, sleeping late, a change of life style or thermometer. Some authors have reported that 3-20% of ovulatory cycles have monophasic temperature curves. The temperature method requires lengthy abstinence lasting until the third day of higher temperature, which may create conflicts in some couples. To ease the difficulties of interpretation of the temperature method, a Swiss architect developed an electronic thermometer programmed according to rules of the calendar rhythm method for cycles of 19-39 days. The woman's 6 most recent cycle lengths remain in the memory to indicate probable infertile days. Although no formal evaluations have appeared in the literature on the Bioself thermometer, the method appears to entail risks including registration of incorrect temperature due to humidity or rundown batteries, and inadequate programming to identify the safe period. The Billings or cervical mucus method is based on observation by the woman of the thickness, wetness, and other characteristics of mucus secretions in the vulva to predict ovulation. Various studies have shown high theoretical efficacy but practical efficacy is lower. Vaginal infections, some ovarian pathologies, and postpartum hormonal changes are among factors that can alter mucus patterns. The method does not confirm ovulation, and false "peak days" may occur. The symptothermal method is based on all the principles of the cervical mucus and temperature methods as well as autopalpation of the cervix and any other signs of ovulation. Effectiveness rates are high. In general pregnancy risks are the same as those for the cervical mucus and temperature methods. A theoretical heightened risk of abortion or fetal malformation common to all the methods due to fertilization of aging gametes has not been definitively evaluated. Another possible risk results from timing of abstinence at the phase of the menstrual cycle when the woman's sexual desire is likely to be greatest.^ieng

[Real and false risks of local contraception: spermicides and the diaphragm]. / Risques vrais et faux de la contraception locale: spermicides, diaphragme.

A critical analysis of recent publications about spermicides and their side-effects has been made. The modern spermicides consist principally of nonoxynol-9 and benzalkonium chloride. The products are harmless and efficient when used correctly at each sexual intercourse. Experiments on rabbits and rats show that nonoxynol-9 is absorbed through the vaginal wall. Benzalkonium chloride is not absorbed, as shown by tests in women and rats. The diaphragm as a method of contraception does present several psychosomatic drawbacks. It appears harmless; allergy to rubber or the septic shock syndrome are extremely rare.

[Post-coital contraception using a combination of d-norgestrel and ethinyloestradiol]. / Interception post-coïtale avec une association de d-norgestrel et d'ethinyloestradiol.

This study was conducted to assess the efficacy of d-Norgestrel associated with Ethinylestradiol (Neogynon 21) as postcoital contraception and to report on the clinical experience obtained with this type of contraception. 323 women were treated during 72 h. period following unprotected intercourse. All subjects received 0,2 mg Ethinylestradiol and 1 mg d-Norgestrel (Levonorgestrel) in 2 equally divided doses 12 hours apart. - 1 mg Levonorgestrel was observed to be as effective as 2 mg of the racemic Norgestrel. PCC given during the first part of the cycle, shortened the latter in 80% of relevant cases. Nausea occurred in 30.3% of all patients; among these 14.2% also mentioned vomiting. Three pregnancies occurred of which only one could be attributed to method failure. The corrected failure rate is thus estimated at 0.3%.

Maturation of the hypothalamo-pituitary-ovarian axis in adolescent girls.

The first menstrual cycles after menarche are irregular and anovulatory. To determine whether these cycles reflect immature pituitary responsiveness to gonadotropin-releasing hormone (GnRH) in relationship to ovarian steroid secretion, we measured basal plasma estradiol (E2), progesterone (P), and gonadotropins as well as LH and FSH responses to GnRH in 90 healthy girls during the first 5 yr after menarche. During the first year postmenarche, sex steroids, basal gonadotropins, and responses to GnRH had not yet reached adult values. During the second year, the increase in E2 was accompanied by a higher secretion of gonadotropins, both basally and in response to GnRH, which was similar to that observed in control adult women during both phases of the menstrual cycle, although P remained low. From the third to the fifth postmenarchal years, there was a progressive increase in the luteal LH and FSH responses to GnRH, resulting in significantly higher responses than in adult controls. Despite the progressive increase in sex steroids there was still a low percentage of ovulatory cycles over the 5 postmenarchal yr (0-63%). When the data were classified according to luteal P levels, it was found that anovulatory cycles (P less than 0.9 ng/ml) with normal E2 levels (100 pg/ml) resulted in exaggerated responses to GnRH, while in ovulatory cycles with P levels greater than 10 ng/ml and normal E2 concentrations, a lower response was observed, suggesting that high concentrations of P exerted a negative feedback on LH and FSH secretion. In contrast, the association of lower E2 (less than 100 ng/ml) and P (less than 5 ng/ml) levels resulted in a synergistic positive action on gonadotropin secretion. These data extend to endogenous sex steroids the dose-dependent positive and negative actions on gonadotropin secretion previously demonstrated with exogenously administered steroids in women.

The sensibility of the hypophysis, the gonads and the thyroid of adolescents before and after the administration of oral contraceptives. A resume.

This research shows that the adenohypophysis of the adolescent differs from that of the adult by sensibility variations vis-a-vis of LHRH and TRF in relation to the growing rates of the ovarian steroids and their actions on the steroid and peptide receptors of the hypophyseal cells. During the first few years after the menarche, the increasing secretion of estradiol provokes a greater secretion of the four adenohypophyseal hormones both before and after LHRH and TRF. As the adolescent grows older, the increasing amounts of progesterone in relation to the increasing amounts of estradiol reduce the sensibility of the hypophysis to the releasing hormones; the release of its trophic hormones and prolactin is diminished. This would indicate that the hypothalamic-pituitary-ovarian system undergoes progressive maturation for a number of years after the menarche. The sensibility of the adolescent pituitary, ovary, and thyroid during the luteal phase of the first menstrual cycle after oral contraceptives have been discontinued is the same in girls who have taken oral contraceptives for 24 months or longer as it is in girls who are five to six years after the menarche and have not taken oral contraceptives.

[Sensibility of pituitary, gonadal and thyroid function in adolescence without and after hormonal contraception].

PIP: The maturation of the hypothalamo-hypophyso-ovarian system comes about gradually, through an increase of the sensibility of the hypophysis to the action of estrogens. To measure this sensibility 76 adolescents aged 2-5 years after menarche were administered continuous hormonal contraception during a period of 3-24 months. Between the 21st and the 25th day of the cycle after contraception had been stopped, all basal values of gonadotropins, thyrodropins, prolactin, and their responses to injections of 50 mg. of luteinizing hormone-releasing hormone, and of 200 mg. of thyrodropin-releasing hormone were measured. Results were compared to those of another group of adolescents who had had no treatment, and to a group of young nulliparous women with ovulatory cycles, and who had had no treatment. Results showed that between menarche and adult age there is a significative rise in basal level of estradiol and of luteinizing hormone; progesterone secretion also increases. However, even 6 years after menarche basal levels are very far from being similar to those of adult women. Prolactin level also augments, varying according to menstrual cycle phase and according to age. Oral contraceptives do not seem to inhibit the regular functions of the hypothalamo-hypophyso-ovarian system if taken at this early age.^ieng