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Biomedical subjects

P Blot

Publications and source records attributed to P Blot.

At least 19 recordsLinked to original sources
PubMed1996

A cell surface marker gene transferred with a retroviral vector into CD34+ cord blood cells is expressed by their T-cell progeny in the SCID-hu thymus.

Gene transduction into immature hematopoietic cells collected at birth from the umbilical cord could be useful for the treatment of genetic or acquired disorders of the hematopoietic system diagnosed during pregnancy. The SCID-hu mouse is a convenient model to investigate T-cell lineage gene therapy, since it allows replication of human intrathymic T-cell development. CD34+ cells isolated from cord blood were cocultured with CRIP MFG-murine CD2 (mCD2) cells that produce recombinant retroviruses encoding the mCD2 antigen, a cell surface marker easily detectable by flow cytometry. After 3 and 4 days in coculture, a mean of 19% and 39% human hematopoietic cells, respectively, expressed the mCD2 antigen. CD34+ cells cocultured for 4 days were used to reconstitute human fetal thymus implanted in SCID mice. Five to 10 weeks later, the mCD2 antigen was detected on approximately 10% of human thymocytes repopulating the thymic grafts in four of nine SCID mouse chimeras. Vector genomes were detected in graft cell DNA by Southern blot. Analysis of vector integration indicated that positive cells were of polyclonal origin in three animals and predominantly monoclonal in the other one. Our data show that foreign genes can be transduced into CD34+ cord blood cells endowed with T-cell differentiation potential, and suggest strategies for T-cell lineage gene therapy in the neonate.

Animals↗
PubMed1996

Direct and reversible inhibition of platelet factor 4 on megakaryocyte development from CD34+ cord blood cells: comparative studies with transforming growth factor beta1.

Mechanisms of the action of platelet factor 4 (PF4) on the growth of megakaryocyte (MK) progenitor cells in CD34+ cord blood (CB) cells were studied in comparison with transforming growth factor beta1 (TGFbeta1). Development of MK from CD34+ CB cells in both plasma clot culture and liquid culture was significantly inhibited by either purified human PF4 and by recombinant human TGFbeta1. Inhibition of MK colony formation by PF4 was reversible because CD34+ cells preincubated with PF4 could regenerate colonies after washing and replating into secondary cultures. In contrast, TGFbeta1-preincubated CD34+ cells gave rise to few colonies following replating. Moreover, incubation of CD34+ cells with PF4 in liquid culture caused the increased number of both stem cell factor (SCF)-binding cells and CD34 antigen-bearing cells. In addition, PF4-preincubated CD34+ cells exhibited a higher potential in MK colony formation in the presence of 5-fluorouracil (5FU). These results demonstrate that both PF4 and TGFbeta1 inhibit MK development from CD34+ CB cells by different mechanisms, and suggest that PF4, unlike TGFbeta1, exerts its inhibitory effect on the growth of the target cells in a reversible manner which results in a preservation of a more immature and 5FU-resistant cell population.

Antigens, CD34↗
PubMed1996

Growth factors and intrauterine growth retardation. I. Serum growth hormone, insulin-like growth factor (IGF)-I, IGF-II, and IGF binding protein 3 levels in normally grown and growth-retarded human fetuses during the second half of gestation.

The aim of this study was to relate human fetal growth retardation to specific hormone alterations. Serum levels of GH, IGF-I, IGF-II, and IGF binding protein (BP) 3 were measured during the second half of gestation after cordocentesis in 230 fetuses who were classified into normally grown (n = 166) and growth-retarded (n = 64) groups according to ante- and neonatal measurements. The normally grown group showed a progressive decline in serum GH levels toward term (r = -0.42, p = 0.0001), whereas serum IGF-I was increased (r = 0.55, p = 0.0001), as were serum IGF-II (r = 0.21, p = 0.008) and IGFBP3 levels (r = 0.19, p = 0.02), although less markedly. For all hormone levels, wide individual differences were found at any given age of gestation. The incidental presence of fetal malformations in either the normally grown group (n = 107 cases) or the growth-retarded group (n = 50 cases) had no apparent effect on these hormone levels as compared with members of the groups showing no fetal malformations (n = 73 cases). Comparison of the normally grown group with the growth-retarded group showed that serum IGF-I levels were significantly lower in the growth-retarded group (p = 0.001). No differences were found between the groups in serum GH, IGF-II, and IGFBP3 levels, although if data for the third trimester were taken alone, serum IGF-II levels were found to be lower in the growth-retarded group (p = 0.05). In conclusion, during the second half of gestation, fetal serum IGF-I levels may be influenced by nutritional factors controlling fetal growth. However, the wide individual differences in measurements make it a very poor biologic marker of intrauterine growth retardation.

Biomarkers↗
PubMed1995

Spectral analysis of fetal heart rate in flat recordings.

Flat heart rate recordings may be observed in different fetal states such as chronic distress and sleep. Their visual analysis do not allow the distinction between these two states. We used spectral analysis to study the heart rate patterns in 25 fetuses. Two significant (P < 5 x 10(-5)) groups were apparent from the determination of the position of the maximum energy peak (PMEP) in the high-frequency band (0.20-0.50 Hz): a PMEP at about 0.20 Hz (group 1), and another around 0.30 Hz (group 2). The two groups did not differ in spectral density (SD). The outcome of neonates showed that group 1 fetuses made good progress and produced healthy neonates; whereas group 2 comprised cases of chronic fetal distress, or even death in utero, and neonatal distress. The significance of this difference in PMEP between fetal heart rate patterns in chronic distress and sleep is unclear. Studies combining the assessment of fetal movements and the determination of PMEP are planned.

Female↗
PubMed1995

Inter-individual variation of selenium in maternal plasma, cord plasma and placenta.

Selenium (Se) in high doses has been known to cause injury to the fetus and newborn. The major difficulty in assessing the effects of selenium on human reproduction stems from the need for a suitable means of estimating maternal and fetal exposure. The present investigation, therefore, examines the respective reliability of maternal plasma, cord plasma and placenta as epidemiological indicators as well as inter-individual variation of this trace element. An unselected population of 128 pregnancies was studied. Obstetrical characteristics were noted. Selenium concentrations were determined for maternal plasma, cord plasma, and placental tissue by fluorometric analysis. Maternal plasma selenium concentrations (Se-Bm) were significantly greater than fetal concentrations (Se-Bc). Placental selenium (Se-Pl) levels were four times that of fetal levels. Variability of Se-Bc is best explained by placental concentrations. Maternal weight and ethnic origin are significantly correlated with Se-Bc. Female newborn have higher selenium levels than male newborn. The present study demonstrates the significance of the placenta as an indicator of fetal selenium exposure.

Adult↗
PubMed1995

Effects of neuromuscular blockade on fetal heart rate variability: a power spectrum analysis.

Spectral analysis of fetal heart rate variability allows quantitative determination of the main components that affect this variability. The physiological significance of these components is unclear; however, movements appear to contribute to variability. We studied six fetuses in which immobility required for in utero magnetic resonance or invasive fetal procedures was achieved by fetal intravascular injection of curare between 32 and 36 amenorrhea weeks. For each fetus, we compared spectral density parameters of heart rate variability. After curare administration, mean spectrum power was halved. We did not observe a larger significant decrease in any (very low, low, or high) frequency band. The other parameters of spectral analysis of variability were unaltered. Fetal movements accounted for a significant proportion of human fetal heart rate variability but did not constitute a unique frequency component.

Curare↗
PubMed1995

Defective cytokine expression but adult-type T-cell receptor, CD8, and p56lck modulation in CD3- or CD2-activated T cells from neonates.

Expression of IL-2, interferon-gamma, and IL-3 mRNA and proteins was investigated in peripheral blood mononuclear cells from cord blood after activation with phytohemagglutinin, CD2, or CD3 MAb. The results showed that interferon-gamma and IL-3 expression was decreased in cord peripheral blood mononuclear cells when compared with expression observed in adult peripheral blood mononuclear cells, irrespective of the stimulation used. In addition, in newborn cells a defect in IL-2 secretion and mRNA expression was observed in response to CD2 or CD3 MAb but not in response to phytohemagglutinin-mediated activation. We further analyzed the modulation of nonlymphokine genes under the same protocol of stimulations. The results indicate that in newborn cells, despite a reduced lymphokine expression observed after CD2 or CD3 MAb activation, the up-regulation of the T-cell receptor, CD8, and p56lck was similar to that found in adult cells, as was also found after phytohemagglutinin activation of both types of cells. These data are in favor of a deficient T-cell responsiveness to CD2 or CD3 MAb in newborn cells. This impairment of the T-cell response appears to selectively affect lymphokine gene expression because the modulation of other genes also implicated in T cell activation is not altered.

Adult↗
PubMed1995

Relationship between maternal folate status and foetal hypotrophy in a population with a good socio-economical level.

A longitudinal study was conducted on 2 groups of pregnant women according to the presence (n = 8) or absence (n = 13) of IUGR through echography at the 3rd trimester of pregnancy. Mothers answered a general questionnaire, including some alimentary data. Anthropometric measures from the newborns were recorded. Haematological parameters and folate status of the women at 32 weeks of pregnancy and of the mother and child at delivery were assessed. Although a significant cross correlation (p < 0.02) between the newborns' folate status and the mother's one, including folate intake, was obtained, no relationship was found between birthweight and folate status at delivery. In contrast, the study evidences significant correlations between birthweight and both folate status of the mother at the third trimester of pregnancy (p < 0.02) and the decrease of her erythrocyte folate level before delivery (p < 0.01). In our sample, folate status of the pregnant woman at the third trimester offers a predictive value of the newborn weight, but this result remains to be confirmed in a larger study.

Anthropometry↗
PubMed1994

Evaluation of X, Y, 18, and 13/21 alpha satellite DNA probes for interphase cytogenetic analysis of uncultured amniocytes by fluorescence in situ hybridization.

The major aneuploidies diagnosed prenatally involve the autosomes 13, 18, and 21, and sex chromosomes. Fluorescence in situ hybridization (FISH) allows rapid analysis of chromosome copy number in interphase cells. This prospective study evaluated the use of four commercially available centromeric DNA probes (DXZ1, DYZ1, D18Z1, and D13Z1/D21Z1) for direct analysis of uncultured amniocytes. One hundred and sixteen amniotic fluid samples were analysed by FISH and standard cytogenetics. This evaluation demonstrated that FISH with X, Y, and 18 alpha satellite DNA probes could accurately and rapidly detect aneuploidies involving these chromosomes and could be used in any prenatal clinical laboratory. In contrast, the 13/21 alpha satellite DNA probe hybridizing both chromosomes 13 and 21 was unreliable for prenatal diagnosis in uncultured amniocytes.

Amniotic Fluid↗
PubMed1994

Quantification of the fetal heart rate variability by spectral analysis of fetal well-being and fetal distress.

Our objectives were to increase the discrimination between fetal distress and fetal well-being, using fetal heart rate spectral analysis. Monitoring of the heart rate from 259 fetuses was done between 26 and 42 weeks, interpreted with classical criteria, and analysed with the spectral analysis method we developed. The fetal heart rate spectrum analysis performed on these recordings allow discrimination of fetal distress from the normal state using the energy value and frequency of the maximal energy in the high frequency band. We can conclude that the spectral analysis produces two significant parameters which could contribute to a multivariate approach to assessments of the physiological mechanisms of heart rate variability.

Female↗
PubMed1994

Alterations of human placental epidermal growth factor receptor in intrauterine growth retardation.

We studied human placental microvillous EGF receptor (EGFR) and its relationship with maternal and placental features in 14 cases of intrauterine growth retardation. Placental EGFR phosphorylation was significantly decreased or absent in 12 cases of small for gestational age neonates, as shown by SDS-PAGE, autoradiography, and scanning analysis. Specific [125I]EGF binding and Scatchard plots of the binding data showed a decreased number of EGFR in 6 of the 12 cases, with a mean maximal binding capacity of 1.09 +/- 0.32 pmol/mg for high affinity sites (mean control value = 2.30 +/- 0.23 pmol/mg). Most of the hypertensive women and smokers belonged to this subgroup. In three of the remaining six cases of small gestational age placentas with low EGFR phosphorylation, there was no maternal pathology or significant parenchymatous placental lesions. Five showed a 175-kD EGFR species when probed by [125I]EGF cross-linking and Western blotting with RK2 and C-Term, two polyclonal anti-EGFR antibodies, suggesting abnormal transduction of the EGF-induced signal. The sixth placenta yielded a single 145-kD EGFR band consistent with an abnormal EGFR structure; Western blot analysis showed no immunoreactive band. In conclusion, maternal and placental pathologies in intrauterine growth retardation are associated with various alterations of placental EGFR, pointing out the importance of EGFR ligands in the regulatory pathway of placental and fetal growth.

Binding Sites↗
PubMed1994

[Evaluation in gynecology and obstetrics. Propositions for routine evaluation of professional practices].

All the scientific prerequisites for auditing Gynaecology-Obstetrics clinics are currently available. Nevertheless, it is often difficult to usefully evaluate routine decision making. The aim of this paper was to offer matter for thought concerning the choice of methods and themes to be used in evaluating routine management in Gynaecology-Obstetrics clinics. Several methods are discussed, including monitoring synthetic indicators and complex evaluation of routine decision making (relationship between recruitment, practices and results). Details of this latter method were presented with several examples: prematurity prevention, perinatal mortality and morbidity, screening tests and antenatal diagnosis, cesarean section.

France↗
PubMed1994

[Has the use of indomethacin during pregnancy consequences in newborn infants? Prospective study of 83 pregnant women and 115 newborn infants].

BACKGROUND: Prolonged exposure of pregnant women to indomethacin for tocolysis may have significant effects on the fetus or neonate, but their incidence is still debated. POPULATION AND METHODS: From January 1990 to July 1991, 83 pregnant women were prospectively given indomethacin for treatment of premature labor, after ineffective course of salbutamol. The initial dose of indomethacin was 100 mg, then the daily dose was 50 mg while salbutamol was continued. Indomethacin was discontinued beyond the 33rd week of gestational age. Efficacy of indomethacin was judged upon the disappearance of uterine contractions and the increased duration of pregnancy from the onset of treatment until delivery. Adverse effects of treatment were evaluated in the neonates. RESULTS: The mean duration of indomethacin administration was 16 days (range: 1-62 days); the mean total dose was 900 mg (range: 100-4500 mg). The reason for discontinuation of the treatment was its efficacy (41 patients), a gestational age of 33 weeks (12 patients), oligoamnios (21 patients), demonstration of fetal abnormalities (two patients). The mean interval between discontinuation of treatment and delivery was 5 weeks. Fourty three of the 58 patients who were given indomethacin before the 30rd week were delivered after the 33rd week. There was no adverse effect in the women and babies; all oligoamnios were spontaneously reversible. One hundred and fifteen babies were born including 12 who died during the first post-natal days. The rate of admission in an intensive care unit was similar to that of untreated pregnancies. CONCLUSIONS: Indomethacin can be safely used for treatment of premature labor provided that its administration is carefully monitored.

Female↗
PubMed1993

Environmental exposure to cadmium and human birthweight.

Fetal toxicity of cadmium (Cd) is well documented in rodents. However, little information is available regarding the human fetus. To investigate the effect of low levels of Cd on the human placenta and the consequences on birthweight, we conducted a study of 102 mothers and their newborns in an obstetrical care unit. Placental and hair samples were collected at delivery to determine Cd concentrations. The main finding of this study was the relationship between a decrease in birthweight and an increase of newborn hair Cd which varied in the presence of placental calcification. In cases of parenchymal calcifications, placental Cd levels were higher (Wilcoxon test, P < 0.05) and newborn hair Cd levels were lower (Wilcoxon test, P < 0.01) than in the absence of calcification. These relationships remained significant even after taking into account smoking habits and gestational age. In the presence of calcification, an increase in the level of Cd in newborn hair was related to a decrease in birthweight which was independent of placental Cd concentration (rpartial = -0.49, P < 0.01). In the absence of calcification, a decrease in birthweight was observed for the upper values of newborn hair Cd (r = -0.44, P < 0.05 when Cd > or = 0.3 ppm). The difference in birthweight between infants in the first and last quartiles of newborn hair Cd was 472 g in cases of calcifications and 122 g in the absence of calcification. Other placental parameters were not significantly related to placental Cd concentration.

Birth Weight↗
PubMed1993

Pharmacokinetics and clinical study of cefotetan in bile: prophylactic use in biliary tract surgery.

The excretion of cefotetan, a 7 alpha-methoxy-cephalosporin, was studied in 27 patients undergoing biliary surgery. Pharmacokinetic parameters were determined after a single intravenous bolus dose of 1 g (10 patients) or 2 g (17 patients). Rapidly excreted in bile, cefotetan concentrations were considerably higher in bile [range: 92-2,594 mg.l-1 (1 g); 35-4,610 mg.l-1 (2 g)] than in plasma despite the presence of gall stones. Bile bactericidal activities against Staphylococcus aureus (MIC 8 mg.l-1) and Bacteroides fragilis (MIC 2 mg.l-1) correlated well with gall bladder cefotetan levels [r = 0.888 (1 g); r = 0.971 (2 g)]. No cefotetan was detected in the bile of 3 patients with nonfunctioning gall bladders. One other patient with very low activity and these three aside, the inhibitory quotients (cefotetan concentration/MIC) were > 4 for both doses against both bacteria.

Adult↗