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Biomedical subjects

J Paris

Publications and source records attributed to J Paris.

At least 19 recordsLinked to original sources

A critical review of the role of childhood sexual abuse in the etiology of borderline personality disorder.

A number of recent reports have indicated that there is a high incidence of sexual abuse during childhood among patients with borderline personality disorder. Although these findings are important, a simple association between abuse and the disorder is an oversimplification. Community studies of the long term effects of abuse indicate that the parameters of abuse are crucial to the patient's outcome. In addition, correlations have been found between sexual abuse during childhood and factors related to the family environment. A multifactorial model of the etiology of borderline personality disorder is proposed in which biological vulnerability, psychological factors and social influences are considered along with their interactions.

Adolescent

Social risk factors for borderline personality disorder: a review and hypothesis.

A number of behaviours associated with borderline personality disorder (including attempted suicide, suicide, substance abuse, and antisocial behaviour) are on the increase among the young. The common factor in these disorders is impulsiveness. Evidence is reviewed suggesting that social disintegration reduces the threshold of impulsive behaviours. It is proposed that this is the mechanism through which social risk factors effect the prevalence and morbidity of borderline personality. A number of ways of testing this hypothesis are suggested.

Borderline Personality Disorder

Prevention of fetal growth retardation with low-dose aspirin: findings of the EPREDA trial.

The efficacy of low-dose aspirin in preventing fetal growth retardation was tested in a randomised, placebo-controlled, double-blind trial. A secondary aim was to find out whether dipyridamole improves the efficacy of aspirin. 323 women at 15-18 weeks' amenorrhoea were selected at twenty-five participating centres on the basis of fetal growth retardation and/or fetal death or abruptio placentae in at least one previous pregnancy. They were randomly allocated to groups receiving placebo, 150 mg/day aspirin, or 150 mg/day aspirin plus 225 mg/day dipyridamole, for the remainder of the pregnancy. In the first phase of the trial all actively treated patients (n = 156) were compared with the placebo group (n = 73). Mean birthweight was significantly higher in the treated than in the placebo group (2751 [SD 670] vs 2526 [848] g; difference 225 g [95% CI 129-321 g], p = 0.029) and the frequency of fetal growth retardation in the placebo group was twice that in the treated group (19 [26%] vs 20 [13%]; p less than 0.02). The frequencies of stillbirth (4 [5%] vs 2 [1%]) and abruptio placentae (6 [8%] vs 7 [5%]) were also higher in the placebo than in the treated group. The benefits of aspirin treatment were greater in patients with two or more previous poor outcomes than in those with only one. In the second analysis, of aspirin only (n = 127) vs aspirin plus dipyridamole (n = 119), no significant differences were found. There was no excess of maternal or neonatal side-effects in the aspirin-treated patients.

Adult

Cloning by differential screening of a Xenopus cDNA coding for a protein highly homologous to cdc2.

Fertilization of Xenopus laevis eggs triggers a period of rapid cell division comprising 12 nearly synchronous mitoses. Protein synthesis is required for these divisions, and new proteins appear after fertilization. Others proteins however, which are synthesized in the unfertilized egg, are no longer made in the early embryo. To identify such proteins, a differential screen of an egg cDNA library gave nine clones corresponding to mRNAs that are deadenylylated soon after fertilization. The sequence of one of these clones (Eg1) revealed a high homology to p34cdc2, the kinase subunit of maturation-promoting factor. Only 12 amino acids in the deduced amino acid sequence were unique to Eg1 when its sequence was compared to all other known examples of cdc2. Despite this strong similarity, however, Eg1 was unable to complement a yeast cdc2- mutant in Schizosaccharomyces pombe or a cdc28 mutant of Saccharomyces cerevisiae. Four Eg1 transcripts, two major and two minor, were found in Xenopus oocytes and early embryos. These RNAs appeared very early (stage I) in oogenesis and their level remained constant until the midblastula transition, at which time they declined. Eg1 RNA is found in the poly(A)+ fraction of oocytes only between the time of meiotic maturation and fertilization--that is to say, in the unfertilized egg. At fertilization the RNA loses its poly(A) tail and at the same time leaves the polyribosomes.

Amino Acid Sequence

Interaction of [3H]nomegestrol acetate with cytosolic progesterone receptors from the rat uterus.

The binding characteristics of the progestin 17 alpha-acetoxy-6-methyl-19-[3H]norpregna-4,6-diene-3,20-dione, nomegestrol acetate ([3H]NOM-Ac) to progesterone receptors (PgRs) of uterus were determined in the rat. Scatchard plot analysis of the equilibrium binding data showed that [3H]NOM-Ac binds to uterine PgR with a Kd of 5.44 +/- 1.27 nM and a Bmax of 1.51 +/- 0.11 pmol/mg protein. Analysis of dissociation kinetics showed that [3H]NOM-Ac dissociates slowly from the PgR, k - 1 = 4.9 +/- 0.5 10(-5) s-1. Competition experiments against [3H]NOM-Ac showed the specificity of the binding with a sequence in relative affinity as follows: ORG 2058 greater than P greater than NOM-Ac greater than medroxyprogesterone acetate greater than megestrol acetate greater than cyproterone acetone greater than NOM.

Animals

Xenopus c-raf proto-oncogene: cloning and expression during oogenesis and early development.

We have isolated and characterized a cDNA which contains the entire coding sequence of Xenopus laevis raf protein. raf mRNA is identified as a member of the class of maternal RNAs. It is already relatively abundant at the beginning of oogenesis and is stable at least until the midblastula transition. The RNA is also detected later during embryogenesis in particular in gastrula, neurula, tailbud and feeding tadpole. We have also found the RNA in several adult tissues (skin, testis, stomach, intestine) at different levels.

Amino Acid Sequence

Maturation-specific polyadenylation: in vitro activation by p34cdc2 and phosphorylation of a 58-kD CPE-binding protein.

During Xenopus oocyte maturation, poly(A) elongation controls the translational recruitment of specific mRNAs that possess a CPE (cytoplasmic polyadenylation element). To investigate the activation of polyadenylation, we have employed oocyte extracts that are not normally competent for polyadenylation. Addition of cell lysates containing baculovirus-expressed cyclin to these extracts induces the polyadenylation of exogenous B4 RNA. The involvement of p34cdc2 kinase in cyclin-mediated polyadenylation was demonstrated by p13-Sepharose depletion; removal of the kinase from oocyte extracts with this affinity matrix abolishes polyadenylation activation. Reintroduction of cell lysates containing baculovirus-expressed p34cdc2, however, completely restores this activity. To identify factors of the polyadenylation apparatus that might be responsible for the activation, we employed UV cross-linking and identified a 58-kD protein that binds the B4 CPE in oocyte extracts. In polyadenylation-proficient egg extracts, this protein has a slower electrophoretic mobility, which suggests a post-translational modification. A similar size shift of the protein is evident in oocyte extracts supplemented with lysates containing baculovirus-expressed cyclin and p34cdc2. This size shift, which is reversed by treatment with acid phosphatase, coincides temporally with cyclin-induced polyadenylation activation. We propose that p34cdc2 kinase activity leads to the phosphorylation of the 58-kD CPE-binding protein and that this event is crucial for the cytoplasmic polyadenylation that occurs during oocyte maturation.

Animals

Cloning by differential screening of a Xenopus cDNA that encodes a kinesin-related protein.

By differential screening of a Xenopus egg cDNA library, we selected nine clones (Eg1 to Eg9) corresponding to mRNAs which are deadenylated and released from polysomes soon after fertilization. The sequence of one of these clones (Eg5) revealed that the corresponding protein has the characteristic features of a kinesin-related protein. More specifically, Eg5 was found to be nearly 30% identical to a kinesin-related protein encoded by bimc, a gene involved in nuclear division in Aspergillus nidulans.

Adenosine Triphosphatases

The dangerousness criterion for civil commitment: the problem and a possible solution.

The dangerousness criterion for civil commitment fails to specify which mental disorders justify commitment. This ambiguity is highlighted by the fact that there are patients with personality disorders or substance abuse who may be dangerous but for whom we have few effective treatments. A possible solution might be provided by adopting the American Psychiatric Association guidelines which consider severity of mental disorder and treatability in its criteria.

Commitment of Persons with Psychiatric Disorders

Lipolytic activity of progesterone and synthetic progestins on rat parametrial adipocytes in vitro.

Despite the known lipogenic properties of progesterone (P) in vivo, one study had previously reported a direct in vitro lipolytic activity of P on isolated adipocytes from rat parametrial adipose tissue (Sutter-Dub et al., 1981). The aim of the present study was to further investigate this finding. Parametrial, but not retroperitoneal adipocytes, isolated from 6-week-old female rats, showed an increase in glycerol release under P stimulation. Estrone, estradiol, estriol and testosterone were inactive. At 12 weeks of age, parametrial adipocytes were bigger and failed to respond to P. P-stimulated glycerol release was concentration-related between 10(-7) M and 10(-5) M. Compared to norepinephrine, P activity displayed less potency (EC50 around 5 X 10(-7) M vs. 10(-6) M, and 4-fold vs. 2-fold maximal stimulation, respectively). Compared to P, synthetic progestins used in therapeutics (medroxyprogesterone acetate, norethindrone acetate, megestrol acetate and nomegestrol acetate) were more active at 10(-7) M but did not induce a greater response at 10(-5) M. Some 17 alpha-hydroxy and 17 alpha-acetoxy derivatives of P or 19-norprogesterone were also tested at 10(-5) M. General agreement was found between experimental lipolytic activities and known progestative agonist properties, with the exception of 19-norprogesterone, which showed a reduced lipolytic activity compared to P, in contrast with its usually higher progestative potency. The direct in vitro lipolytic activity of P was characterized as specific of age and of the parametrial adipose tissue, concentration-related, and common to synthetic progestins.

Adipose Tissue

Maturation-specific polyadenylation and translational control: diversity of cytoplasmic polyadenylation elements, influence of poly(A) tail size, and formation of stable polyadenylation complexes.

Early embryonic development in Xenopus laevis is programmed in part by maternally derived mRNAs, many of which are translated at the completion of meiosis (oocyte maturation). Polysomal recruitment of at least one of these mRNAs, G10, is regulated by cytoplasmic poly(A) elongation which, in turn, is dependent upon the cytoplasmic polyadenylation element (CPE) UUUUUUAUAAAG and the hexanucleotide AAUAAA (L. L. McGrew, E. Dworkin-Rastl, M. B. Dworkin, and J. D. Richter, Genes Dev. 3:803-815, 1989). We have investigated whether sequences similar to the G10 RNA CPE that are present in other RNAs could also be responsible for maturation-specific polyadenylation. B4 RNA, which encodes a histone H1-like protein, requires a CPE of the sequence UUUUUAAU as well as the polyadenylation hexanucleotide. The 3' untranslated regions of Xenopus c-mos RNA and mouse HPRT RNA also contain U-rich CPEs since they confer maturation-specific polyadenylation when fused to Xenopus B-globin RNA. Polyadenylation of B4 RNA, which occurs very early during maturation, is limited to 150 residues, and it is this number that is required for polysomal recruitment. To investigate the possible diversity of factors and/or affinities that might control polyadenylation, egg extracts that faithfully adenylate exogenously added RNA were used in competition experiments. At least one factor is shared by B4 and G10 RNAs, although it has a much greater affinity for B4 RNA. Additional experiments demonstrate that an intact CPE and hexanucleotide are both required to compete for the polyadenylation apparatus. Gel mobility shift assays show that two polyadenylation complexes are formed on B4 RNA. Optimal complex formation requires an intact CPE and hexanucleotide but not ongoing adenylation. These data, plus additional RNA competition studies, suggest that stable complex formation is enhanced by an interaction of the trans-acting factors that bind the CPE and polyadenylation hexanucleotide.

Animals

Stability of maternal mRNA in Xenopus embryos: role of transcription and translation.

The first 12 cell divisions of Xenopus laevis embryos do not require gene transcription. This means that the regulation of gene expression during this period is controlled at post transcriptional levels and makes Xenopus early development a potentially interesting biological system with which to study the mechanisms involved. We describe here the stability characteristics of several maternal Xenopus mRNAs which are deadenylated soon after fertilisation (J. Paris and M. Philippe, Dev. Biol., in press). We show that these mRNAs were only degraded in the embryo after the midblastula transition (MBT), when gene transcription was initiated. The kinetics with which the deadenylated maternal mRNAs decreased in the post-MBT embryos showed sequence specificity. The degradation of these mRNAs after the MBT was inhibited by cycloheximide but was not affected by dactinomycin. Therefore, the destabilization of these mRNAs does not appear to be initiated by new embryonic gene transcripts. Sequence comparisons of the 3' untranslated region of these mRNAs identified several motifs which may be involved in the posttranscriptional control of these gene products.

Animals