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[Pregnancy and labor in women over 40 years of age].

During the 1970-1989 period, there were 23,915 deliveries of which 278 (1.16%) occurred in women 40 years of age or older. The latter included 62 (22.3%) primiparas, 158 (56.8%) pluriparas and 58 (20.9%) multiparas. The control group consisted of 14,400 women 20-34 years of age (50% primiparas and 50% pluriparas) from the same period. There was no antenatal visit in 9.4% of the women 40 years of age or older. This group included more housewives, more unmarried women and more women with previous spontaneous and induced abortions than the control group (P less than 0.05). Threatened abortion (16.2%), EPH gestosis (22.3%), impaired glucose tolerance (8.3%), gestational diabetes (7.2%), delivery before 37 weeks (11.5%), delivery after 42 weeks (3.6%), premature rupture of the membranes (18.3%), meconium-stained amniotic fluid (19.8%), elective caesarean section (11.5%), caesarean section delivery (16.5%), vacuum extraction (4.7%), placental lysis or uterine exploration (4.3%) were more frequent in the study than in the control group (P less than 0.05). There were more cases with episiotomy (P less than 0.001) in the control group, whereas there were no differences as regards cervical cerclage, weight gain above 14kg, breech presentation, transverse presentation and assisted breech delivery between the two groups (P greater than 0.05). There was no case of uterine rupture or maternal death either in the study or the control group. The authors conclude that a woman 40 years of age and older is in an advanced age for pregnancy and delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Human placental low molecular weight factors inhibit the entry into cell cycle of murine pluripotent stem cells.

In 1977, Frindel et al. reported the presence in fetal calf bone marrow of a low molecular factor, the tetrapeptide Ac-N-Ser-Asp-Lys-Pro (AcSDKP), capable of inhibiting in vivo the hematopoietic pluripotent stem cell (CFU-S) recruitment into DNA synthesis and to increase the survival of mice which had received lethal doses of cytosine arabinoside (AraC), a phase-specific drug. Considering the potential clinical importance of CFU-S proliferation inhibitor during anticancer chemotherapy and the importance of monitoring the inhibitor by immunological methods, we tried to determine if a similar inhibitor is present in humans. Preliminary results indicate the presence in human placenta of an inhibitor coeluted with AcSDKP and which is effective in inhibiting murine CFU-S.

Amino Acid Sequence↗

Immunoactive products of human placenta (III): Characterization of an inhibitor affecting lymphocyte proliferation.

We have investigated the effects of supernatants from human placenta explant cultures on lymphokine dependent T cell proliferation using mainly the CTLL-2 reference murine cell line. A profound, dose dependent, inhibition of both IL-2 and IL-4-dependent cell proliferation was observed. In addition, supernatants from human placental cultures inhibited B cell proliferation, IL-5-driven proliferation of B13 cells, and IL-6-induced proliferation of 7TD.1. Conversely, the supernatants from human placental cultures enhance the growth of human embryonic fibroblasts. Characterization of the material by HPLC yielded a 68-70 kDa peak at pH 7.4, but the peak activity was at a smaller molecular weight (20-25 kDa) if pH 2.9 acetic acid, KC1 buffer was used. The same fractions were inhibitory for IL-2 and IL-4 driven proliferation of CTLL-2 cells. We conclude that the substances tested are acting as a general growth inhibitor for lymphocytes.

Animals↗

[Effect of chemotherapy combined with the use of tissue preparations on nonspecific immunity in patients with pulmonary tuberculosis].

General and local nonspecific immunity was studied in 143 new cases of pulmonary tuberculosis (71 and 72 persons, respectively). The results showed that combination of chemotherapy using desensitizing agents and tissue preparations according to V. P. Filatov (a suspension of placenta tissue and aloe) had an immunomodulating effect. The efficacy of the combined chemotherapy amounted to 87 per cent with an account of the general immunity status.

Adjuvants, Immunologic↗

Interferon- and sarcolectin-dependent cellular regulatory interactions.

Interferons, via specific membrane-bound receptors, induce various cellular functions of which antiviral protection is the most extensively studied. We have previously reported the existence of interferon antagonists (referred to as sarcolectins) in various tissue extracts from placental blood, cartilage, brain, muscle, or from sarcomas. These sarcolectins have been fully characterized and purified to homogeneity. In interferon-treated cells, they restore virus sensitivity 4-6 h after the establishment of antiviral protection. In the present study we investigate the effect of sarcolectins on the steady state levels of two double-stranded RNA dependent enzymes, 2-5A (p chi (A2'p)nA) synthetase and protein kinase. Several authors have previously emphasized the role of these enzymes in the mechanism of interferon's antiviral action. Interferon promotes a 4-8 fold increase in protein kinase and 2-5A synthetase in cells. Addition of sarcolectin 5 h after interferon results in a dramatic reduction in the steady state levels of both these enzymes, as shown by their decreased activity and yield observed in Western blot assays. The degradation of the antiviral response in sarcolectin-treated cells might therefore be at least partially attributed to a reduced synthesis of protein kinase and 2-5A synthetase. Since there are no direct interactions between sarcolectins and interferon or its receptors, it can be postulated that sarcolectins exert their effect through these interferon-dependent proteins. We postulate that the opposing biological effects of interferon and sarcolectins strike a balance which may, however, be modified in one direction or the other, depending on their respective concentrations.

2',5'-Oligoadenylate Synthetase↗

Evidence for "low Km" and "high Km" soluble 5'-nucleotidases in human tissues and rat liver.

Two kinetically distinct purine 5'-phosphomono-esterase activities were isolated from soluble fractions of human placenta, cultured human T- and B-lymphoblasts and rat liver using AMP-sepharose chromatography. We have defined these activities as "high Km" and "low Km" 5'-nucleotidase. The relative content of "high Km" and "low Km" activities in the tissues studied ranged from 2 to 264. The optimum pH of "low Km" 5'-nucleotidases ranged from 7.4 to 9.0, Km for AMP from 7 to 15 uM and for IMP from 10 to 26 uM. ATP and ADP were inhibitors of "low Km" enzymes with the apparent Ki values of 55 to 20 uM and 8 to 20 uM for ATP and ADP, respectively. "High Km" 5'-nucleotidases had an optimum pH at 6.5, Km for IMP of 0.3 to 0.5 mM and Km for AMP of 1.0 to 9.4 mM. "High Km" enzymes were activated by ATP with A0.5 values, of 1.7 to 2.3 mM at 100 microM IMP. The data indicate that soluble "low Km" and "high Km" 5'-nucleotidases coexist in mammalian cells and fulfill different functions. These observations suggest a complex system for the regulation of AMP and IMP dephosphorylation.

5'-Nucleotidase↗

Platelet inhibitory activity in placentas from normal and abnormal pregnancies.

Retroplacental blood flow requires inhibition of coagulation in the absence of an endothelial lining. We confirmed that trophoblast releases an inhibitor of platelet aggregation which functions via degradation of adenosine diphosphate. This inhibitor appears to be deficient in some pregnancies with abruptio placentae and intrauterine growth retardation. Unimpeded retroplacental blood flow may depend upon the local inhibition of platelet aggregation. Placental tissue contains an inhibitor of platelet aggregation which appears to be an adenosine diphosphatase distinct from heat-stable alkaline phosphatase. Placental tissue from patients with abruptio placentae contains abnormally low amounts of this enzyme.

Abruptio Placentae↗

[A study on the role of DNA methylation within hCG and hPL genes in trophoblastic disease].

It has been shown that the extent of methylation of cytocine in DNA is inversely correlated with gene expression in many cases. The DNAs extracted from placental tissue, hydatidiform mole and choriocarcinoma tissue were examined to see whether the extent of cytocine methylation is correlated to the gene expression of placental peptide hormones and the transformation of trophoblast. First of all we measured the amount of methylated cytocine per total DNA with HPLC. We then examined cytocine methylation in hCG alpha,beta and hPL genes using methylation sensitive (Hha I, Hpa II) and non sensitive (Msp I) restriction enzymes and molecular hybridization. During pregnancy the total amount of methylated cytocine measured with HPLC increases gradually from 0.72 mol.% at first trimester to 0.92 mol.% at term. The DNA of WBC showed a higher level of methylated cytocine than placental DNA. The extent of DNA methylation in the peptide hormone genes increases during placental development. Hypomethylation in the hCG alpha gene was also seen in molar tissue which expresses a high amount of hCG. Therefore it is inversely correlated that gene expression of hCG alpha,beta and the extent of DNA cytocine methylation. Furthermore some restriction polymorphisms were observed with Msp I in hCG alpha and hPL genes which might be related to malignant transformation of the trophoblast.

5-Methylcytosine↗

Biosynthesis of the human base excision repair enzyme uracil-DNA glycosylase.

The biosynthesis of the human DNA repair enzyme uracil-DNA glycosylase has been characterized by the reaction of in vitro- and in vivo-produced protein with an anti-human placental uracil-DNA glycosylase monoclonal antibody. In vitro synthesis of the DNA repair enzyme was examined after the translation of human placental polyadenylated [poly(A)+] RNA by immunoprecipitation of the [35S]methionine-labeled translation products. As defined by sucrose density analysis, immunoprecipitable in vitro products were translated from 16S poly(A)+ RNA and 11S poly(A)+ RNA. While the products of the 11S poly(A)+ RNA were smaller than purified uracil-DNA glycosylase, the product of the 16 S poly(A)+ RNA had a molecular weight of 37,000, identical to the size previously observed for purified human placental uracil-DNA glycosylase. Immunoblot analysis of human placental cell extracts and of normal human fibroblast cell extracts demonstrated the recognition of one Mr 37,000 protein. Immunoprecipitation of [35S]methionine-labeled normal human cell extracts with the anti-glycosylase monoclonal antibody specifically detected only the Mr 37,000 uracil-DNA glycosylase protein. Pulse-chase analysis demonstrated that the 35S radioactivity in the Mr 37,000 uracil-DNA glycosylase decreased over a 5-h interval. These results show that immunoreactive human uracil-DNA glycosylase protein was synthesized at its enzymatically active molecular weight of 37,000 as the primary translation product of a 16S polyadenylated messenger RNA.

Cells, Cultured↗

Biochemical fractionation of conditioned media containing factors which support in vitro proliferation of high proliferation potential colony forming cells.

Synergistic activity (SA), which is the capacity to support the in vitro proliferation of High Proliferation Potential Colony Forming Cells (HPP-CFC's), has been fractionated from conditioned media by standard biochemical techniques. On fractionation of both Wehi conditioned medium (Wehi CM) or human placental conditioned medium (HPCM) by several techniques, multiple peaks of SA were observed. Protein from HPCM expressing SA, ranged from 9,000-28,000 in molecular weight as determined by gel filtration. Chromatofocusing crude HPCM separated two activities possessing isoelectric points of 5.7 and 5.3. In crude Wehi CM, inhibitors or toxicity occasionally masked SA which partially adsorbed to Con-A sepharose and could be eluted with competing sugar. Further fractionation of this material on DEAE-sepharose separated three peaks of activity. Pooling the active fractions from the first two peaks gave a preparation that was up to 179 fold more active than the crude material.

Animals↗

The occurrence of human placental alkaline phosphatase (PLAP) in extracts of normal, benign and malignant tissues of the female genital tract.

In addition to its presence in extracts of carcinomatous tissues from the vulva, endometrium and ovary, PLAP can also be found in tissue extracts of benign conditions of the endometrium and myometrium. We detected slightly elevated levels of PLAP in patients with myoma, raised levels in 2/2 patients with endometrial polyps and high values in 2/2 patients with glandulocystic hyperplasia. Moreover, normal endometrium and fragments of normal Fallopian tube also contained fairly high amounts of endogenous PLAP. These results have important implications with regard to the possible use of PLAP as a tumour marker or of anti-PLAP monoclonal antibodies in radioimmunolocalization or radioimmunotherapy.

Adolescent↗