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Biomedical subjects

J Paris

Publications and source records attributed to J Paris.

At least 145 records · Page 8Linked to original sources
PubMed1991

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↗
PubMed1991

Parents' emotional neglect and overprotection according to the recollections of patients with borderline personality disorder.

OBJECTIVE: The purpose of this study was to test clinical hypotheses about the role of emotional neglect and overprotection in the childhood of patients with borderline personality disorder. METHOD: The subjects were male and female borderline (N = 62) and nonborderline (N = 99) patients from a general hospital psychiatric clinic and a university student mental health clinic. Both groups were administered the Parental Bonding Instrument, which measures subjects' recollections of parenting on dimensions of care and protection. RESULTS: The findings showed that the patients with borderline personality disorder remembered both their fathers and their mothers as having been significantly less caring and more controlling than did the nonborderline patients. The results were the same for male and female subjects and for subjects from both sites. CONCLUSIONS: The recollections provide support for psychodynamic theories about the childhood of borderline patients and for a theory of biparental failure in the development of borderline pathology.

Adult↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

In vivo morphological damage induced by a new benzimidazole prodrug in Echinococcus multilocularis metacestodes.

Benzimidazoles are the most widely used compounds in chemotherapy of alveolar hydatid disease (AHD), but long-term administration is required to reach detectable plasma levels. N-Methoxycarbonyl N'-2-nitro 4-trifluoromethyl phenyl thiourea (2) was prepared as a potential prodrug of (5-trifluoromethyl-1H-benzimidazole-2-yl)-carbamic acid methyl ester. Biological effects of 2 were evaluated in gerbils (Meriones unguiculatus) against the causative agent of AHD, Echinococcus multilocularis metacestodes, through a transmission electron microscopy study. Significant morphological damage of tegument and protoscolices occurred after an 18-day treatment. The treatment of AHD by using the prodrug form of the benzimidazole deserves further study.

Animals↗
PubMed1990

Structure-activity and structure-affinity relationships of 19-nor-progesterone derivatives in rat uterus.

19-nor-progesterone (19NP) is a potent progestagen which possesses a high affinity for the progesterone receptor (PgR). In contrast, 17 alpha-hydroxylated-progesterone (17OHP) shows no hormonal activity and does not compete with progesterone (P) for the PgR. The aim of the present work was to analyse in parallel the structure-affinity and the structure-activity relationships for new molecules obtained by modifications of 19NP and 17OHP. The attachment of a 17 alpha-hydroxyl group on 19NP led to a dramatic decrease in both affinity and activity for the end-product, 17 alpha-hydroxylated-19-nor-progesterone (17OH-19NP). The further addition of a methyl group combined with the formation of a double-bound at C6 on 17OH-19NP results in nomegestrol (NOM), the relative affinity of which remained low. Negligible activity was also associated with this affinity in comparison to the parent 19NP. Strikingly, the protection of the free 17 alpha-hydroxyl group of NOM by an acetate led to a potent progestin with high affinity for PgR. It is concluded that the sum of the modifications brought into the 17OHP-19NP molecule reestablishes both affinity and activity of the original 19NP molecule. The same conclusion holds if P is considered as the parent compound, as already stated in the literature.

17-alpha-Hydroxyprogesterone↗
PubMed1990

Poly(A) metabolism and polysomal recruitment of maternal mRNAs during early Xenopus development.

Up to the midblastula stage, cell division in Xenopus is directed by maternal mRNAs and proteins that are inherited by the fertilized egg. We have isolated cDNA clones for mRNAs that undergo either adenylation or deadenylation during this developmental period. Coincidental with this poly(A) metabolism are changes in polysomal localization. The relationship between polyadenylation and translation is discussed.

Animals↗
PubMed1990

Kinetic analysis of the binding of nomegestrol acetate to the progesterone receptors in rat uterus by competition studies.

The characteristics of binding (Kinetic and equilibrium binding analysis) of nomegestrol acetate (NOM, 17 alpha-acetoxy-6 alpha-methyl-19-nor-pregna-4.6-diene-3.20-dione) to the progesterone receptor (PgR) in rat uterine cytosolic fraction were determined in comparison to progesterone (P), to fully appreciate the amplitude and specificity of the induced biological response. Since an appropriate radio-labelled form of this steroid molecule was not available, competition studies were performed against the synthetic progestin: [3H]-Organon 2058 [( 3H]-ORG). This allowed a direct comparison between the unlabelled forms of NOM and P, the kinetic constants of which were respectively: Inhibition constant (Ki): 22.8 and 34.3 nM; Association rate constant (k1): 0.39 X 10(3) and 0.21 X 10(3) M-1.s-1; Dissociation rate constant (k-1): 1.81 X 10(-5) and 2.16 X 10(-5) s-1. These results are much more informative than the mere determination of relative binding affinities which only reflect the specificity of the PgR. It was concluded that NOM behaves like the natural hormone in the cytosol of rat uterus.

Animals↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

Maternal mRNA expression in early development: regulation at the 3' end.

Early development in many animals is programmed by maternal mRNAs inherited by the fertilized egg. Many of these RNAs are translationally dormant in immature oocytes, but are recruited onto polysomes during meiotic maturation or fertilization. Polyadenylation plays a major role in controlling the translation of maternal mRNA during these times of development. Polyadenylation, in turn, is dependent upon two cis elements that reside in the 3'-terminal region of responsive mRNAs. In two cases, the factors that interact with these regions have been examined. The half-life of maternal mRNA also is regulated by polyadenylation, which again is controlled by 3'-terminal cis elements. The recent literature covering these topics is reviewed.

Animals↗
PubMed1990

Post-transcriptional regulation of ornithine decarboxylase in Xenopus laevis oocytes.

The level at which ornithine decarboxylase expression is regulated in growing oocytes has been investigated. Immunoprecipitation of the in vivo labelled proteins showed that ornithine decarboxylase accumulated less rapidly in stage IV oocytes than in previtellogenic stage I + II oocytes. Quantitative Northern analysis showed that ornithine decarboxylase mRNA is abundant in oocytes (about 8 x 10(8) transcripts/cell) and this number does not significantly change during oogenesis. Polysome analysis showed that this mRNA is present in polysomes in stage I + II oocytes but has passed into puromycin-insensitive mRNP particles by stage IV of oogenesis. Therefore, during the growth phase of oogenesis, ornithine decarboxylase expression is regulated at a translational level. These results are discussed relative to the temporal expression of ornithine decarboxylase and of other proteins whose expression also decreases during oogenesis. In order to perform these experiments, the cDNA (XLODC1) corresponding to Xenopus laevis ornithine decarboxylase mRNA was cloned and sequenced.

Animals↗
PubMed1990

[Acetylenic enzyme inhibitors: their role in anticancer chemotherapy].

Suicide inhibitors of acetylenic structure can inactive many enzymes playing an important role in the cancer cell metabolism. This type of inhibitors presents a fantastic interest because of its original inhibition mode: it is the catalytic mechanism of the enzyme itself which make the inhibitor reactive. In this way, thymidylate synthetase, ornithine decarboxylase, aldehyde dehydrogenase, aldehyde reductase are inhibit by acetylenic substrates. These very efficient compounds will allow to envisage a more selective chemotherapy of cancer.

Acetylene↗
PubMed1990

Synthesis of acetylenic spirobutenolide derivatives and evaluation of their growth inhibitory effect on cells in culture.

Acetylenic spirobutenolide amides and esters and their Mannich bases were synthesized to evaluate their growth inhibitory effect. The biological tests have used both normal and transformed cells and they have shown the selectivity of the prepared compounds. The ester derivatives presented the best selectivity comparable to that of daunorubicin.

Antineoplastic Agents↗