[Hemorrhage during the first pregnancy trimester. Diagnostic assessment].
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Adult↗
Biomedical subjects
M Dreyfus
Publications and source records attributed to M Dreyfus.
In the absence of translation, RNase E can bypass 5' mRNA stabilizers in Escherichia coli.
In Bacilli, ribosomes or 30 S ribosomal subunits that are stalled or bound on mRNAs can stabilize downstream regions, hence the view that the degradation machinery scans mRNAs from their 5' end. In E. coli, several mRNAs can also be stabilized by secondary structures involving their 5' end. To test whether a bound 30 S subunit can act as a 5' stabilizer in E. coli, we compare here the stabilities of two untranslated variants of the lacZ mRNA, the decay of which is controlled by RNase E. In the first variant, a 35 nt region including the Ribosome Binding Site (RBS) is deleted, whereas in the second it is replaced by an 11 nt-long Shine-Dalgarno (SD) sequence lacking an associated start codon. In the latter variant, an 80 nt fragment encompassing the SD and extending up to the mRNA 5' end was stable in vivo (t1/2>one hour), reflecting 30 S binding. Yet, the full-length message was not more stable than when the SD was absent, although two small decay intermediates retaining the 5' end appear somewhat stabilized. A third variant was constructed in which the RBS is replaced by an insert which can fold back onto the lac leader, creating a putative hairpin involving the mRNA 5' end. The fragment corresponding to this hairpin was stable but, again, the full-length message was not stabilized. Thus, the untranslated lacZ mRNA cannot be protected against RNase E by 5' stabilizers, suggesting that mRNA scanning is not an obligate feature of RNase E-controlled degradation. Altogether, these results suggest important differences in mRNA degradation between E. coli and B. subtilis. In addition, we show that mRNA regions involved in stable hairpins or Shine-Dalgarno pairings can be metabolically stable in E. coli.
Base Sequence↗
NTP concentration effects on initial transcription by T7 RNAP indicate that translocation occurs through passive sliding and reveal that divergent promoters have distinct NTP concentration requirements for productive initiation.
The hypothesis that active site translocation during initial transcription occurs by a passive sliding mechanism which allows the pre- and post-translocated states to equilibrate on the time scale of bond formation was tested by evaluating the effects of NTP concentration on individual transcript extension steps in the presence of translocation roadblocks created by proteins bound immediately downstream of a T7 promoter, as well as by evaluating the effects of NTP concentration on competing transcript extension pathways (iterative synthesis and "normal" extension). Results are consistent with a passive sliding mechanism for translocation which is driven by NTP binding, and are inconsistent with mechanisms in which the pre- and post-translocated states fail to equilibrate with each other on the time scale of bond formation or in which translocation is driven by NTP hydrolysis. We also find, in agreement with many previous studies, that divergence from consensus in the ITS (initially transcribed sequence) of the T7 promoter decreases productive initiation. However, this appears to be largely due to increases in the NTP concentration requirements for efficient transcription on the divergent ITSs.
Adenosine Triphosphate↗
Translation inhibitors stabilize Escherichia coli mRNAs independently of ribosome protection.
Translation inhibitors such as chloramphenicol in prokaryotes or cycloheximide in eukaryotes stabilize many or most cellular mRNAs. In Escherichia coli, this stabilization is ascribed generally to the shielding of mRNAs by stalled ribosomes. To evaluate this interpretation, we examine here how inhibitors affect the stabilities of two untranslated RNAs, i.e., an engineered lacZ mRNA lacking a ribosome binding site, and a small regulatory RNA, RNAI. Whether they block elongation or initiation, all translation inhibitors tested stabilized these RNAs, indicating that stabilization does not necessarily reflect changes in packing or activity of translating ribosomes. Moreover, both the initial RNase E-dependent cleavage of RNAI and lacZ mRNA and the subsequent attack of RNAI by polynucleotide phosphorylase and poly(A)-polymerase were slowed. Among various possible mechanisms for this stabilization, we discuss in particular a passive model. When translation is blocked, rRNA synthesis is known to increase severalfold and rRNA becomes unstable. Meanwhile, the pools of RNase E and polynucleotide phosphorylase, which, in growing cells, are limited because these RNases autoregulate their own synthesis, cannot expand. The processing/degradation of newly synthesized rRNA would then titrate these RNases, causing bulk mRNA stabilization.
Chloramphenicol↗
On the mechanism of inhibition of phage T7 RNA polymerase by lac repressor.
We study here the effect on phage T7 RNA polymerase activity of lac repressor bound downstream of the T7 promoter. When repressor binds in vitro at an operator centered at +13 or +15 with respect to transcription start, it does not prevent initiation, though the transcript yield is reduced. However, the processivity of the polymerase is depressed and transcript extension is blocked at positions +4 and +6, respectively. These results indicate that repressor and polymerase do not simply exclude each other from the promoter. Rather, they would come into steric conflict and compete for establishment or retention of interactions with the same segment of DNA, without this leading to the immediate displacement of either polymerase or repressor. The resulting destabilization of the transcription complex would depress both initiation rate and enzyme processivity. In contrast to the above results, little reduction in runoff transcription is observed when operator is centered at +47. The decreased sensitivity of polymerase to repressor bound at +47 versus +13 or +15 is likely to be due to the higher stability of the elongation complex during the transcription of downstream regions in comparison with the first transcribed nucleotides. We also show that under conditions of leaky repression and with operator centered at +13, a mutant T7 RNA polymerase showing normal promoter affinity but a slower elongation rate is more sensitive to repression than the wild-type enzyme, both in vitro and in vivo. In vitro, this higher sensitivity is largely due to a reduced ability of the mutant to overcome the elongation block at position +4. The parallel between the in vitro and in vivo data suggests that in vivo the repressor also does not prevent polymerase from binding to promoter, but interferes with subsequent steps in initiation and transcript extension, in this case presumably largely extension beyond +4.
Bacterial Proteins↗
Prenatal diagnosis of Walker-Warburg syndrome in three sibs.
Walker-Warburg syndrome (WWS) is an autosomal recessive condition characterized by diffuse neurodysplasia, resulting in brain and eye abnormalities. We report on 3 prenatally diagnosed cases of this syndrome born to a consanguineous couple. An ultrasonographic examination showed hydrocephalus at the 27th week of the first pregnancy. Amniocentesis documented a normal male karyotype. The couple opted for termination of the pregnancy but declined an autopsy. Seven months later, hydrocephalus was observed at 20 weeks of the second pregnancy. Termination of pregnancy was performed at the 22nd week. Autopsy of this male fetus showed dilated ventricles, thin cortex, and type II lissencephaly with microscopic evidence of chaotic architecture. Eye examination showed retinal dysplasia. Notwithstanding the lack of demonstrable muscle change, the diagnosis of Walker-Warburg syndrome was made. Ten months later, hydrocephalus was discovered in the third fetus, a female, at 13 weeks of gestation. Termination of pregnancy was performed at 20 weeks. At autopsy, brain, eye, and muscular findings were similar to those of the previous case. In addition, cystic changes and a stenosis of the pyelo-ureteral junction were found in the right kidney. Type II lissencephaly and retinal dysplasia are characteristic of WWS. Muscular dystrophy has been pointed out as an additional abnormality in postnatal cases. By contrast, the lack of demonstrable muscle changes in the fetal period must be emphasized. Those cases illustrate practical problems in the ultrasound and pathologic diagnosis of WWS in the fetal period.
Abnormalities, Multiple↗
Cytology and colposcopy after loop electrosurgical excision: implications for follow-up.
OBJECTIVE: To analyze risk factors associated with residual and recurrent lesions after loop electrosurgical excision procedure and to assess the reliability of cytology and colposcopy in detection of these lesions. METHODS: Cytology and colposcopy were used to follow up 288 women after treatment by loop electrosurgical excision 3-6 months, 9-15 months, and 24-36 months after the procedure. RESULTS: The mean (+/-standard deviation) postoperative follow-up was 39+/-13 months (range 24-68 months). Treatment failure, defined as the persistence or recurrence of a cervical lesion, was observed in 20 patients (6.9%). The endocervical localization of the initial lesion (adjusted relative risk [RR] 13.7; 95% confidence interval [CI] 1.3, 150.1; P < .05) and incomplete excision (adjusted RR 9.1; 95% CI 3.0, 27.3; P < .001) were the only independent risk factors for treatment failure. In six cases, a second treatment was performed before the first cytologic and colposcopic visit because of incomplete excisions. The remaining 14 treatment failures were diagnosed by postoperative cytology and colposcopy, ten after the first visit, three after the second, and one after the third. To diagnose the treatment failures, colposcopy and cytology provided complementary information at the first (P < .001) and second postoperative visits (P < .05). Although the sensitivity of cytology was not significantly improved by the association of both methods, the latter decreased the number of residual lesions overlooked by cytology alone and contributed to the diagnosis of 95% of treatment failures in less than 2 years. CONCLUSION: The high detection rate obtained by combining cytology and colposcopy during the first 2 postoperative years may allow more leisurely follow-up schedules after that time and may reduce the consequences of subsequent loss to follow-up.
Adenocarcinoma↗
The prediction of preeclampsia: reassessment of clinical value of increased plasma levels of fibronectin.
OBJECTIVE: To determine whether assessment of plasma fibronectin in primigravidae could predict the pregnant women expected to become preeclamptic. METHODS: We performed a prospective blinded analysis of 156 apparently normotensive primigravidae in an outpatient clinic. Blood samples were taken at 6 week intervals from the 18th week and immediately after delivery or at the onset of preeclampsia. Plasma fibronectin was evaluated by ELISA. Evolution with gestational age was studied using regression curves. RESULTS: We had 148 normal primigravidae (592 determinations). In three women, increased fibronectin anticipated preeclampsia by 3-4 weeks. Five women showed high levels only at the onset of preeclampsia. Sensitivity, specificity, positive and negative predictive values of increased fibronectin levels were 37.5% (95% CI=3.3-71.7), 96.6% (95% CI=93.7-99.6), 37.5% (95% CI=3.3-71.7) and 96.6% (95% CI=93.7-99.6), respectively. CONCLUSIONS: This study shows that plasma fibronectin levels could represent a specific marker for preeclampsia. Its sensitivity has to be improved but its high negative predictive value strongly argues against the development of preeclampsia within the next 4 weeks after the blood sampling.
Adult↗
Prevalence of antiphospholipid-related antibodies in unselected patients with history of venous thrombosis.
Antiphospholipid antibodies (aPL) are heterogeneous and are now accepted to be mainly phospholipid-protein-dependent antibodies. Although these antibodies are classically associated with thrombosis, their clinical relevance remains to be established. The subgroups of antibodies characterized by their proteic targets were reported to be more appropriate thrombotic markers. We analysed the prevalence of a large panel of antiphospholipid-related antibodies (aPLR), comprising antibodies directed to phospholipid-protein complexes and to different protein cofactors (beta2GPI, prothrombin, annexin V and protein S), in 122 consecutive unselected patients who had experienced at least one venous thrombotic event. The presence of lupus anticoagulants was assessed with an integrated assay using hexagonal phase phospholipids. Two types of aPL (APA and anti-beta2GPI-PL) were measured using a mixture of phospholipids containing cardiolipin and goat serum or human beta2GPI, respectively, as a source of protein cofactor. Our results show a similar prevalence, close to 15%, of lupus anticoagulants, APA and anti-beta2GPI-PL. In contrast, antibodies to beta2GPI were detected in only 8% of the patients, and very few patients had antibodies directed to other proteins. Of the 35 patients having at least one positive aPLR, 17 were classified as severe, because they had recurrent or early onset of thrombosis (< 35 years). The distribution of aPLR between severe and mild cases was not significantly different except for lupus anticoagulants. Our results clearly indicate that lupus anticoagulant is the only aPLR test to be strongly associated with the severity of thrombosis.
Annexin A5↗
[Networks in perinatology. The French experience].
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France↗
Factor VII qualitative deficiency and pregnancy.
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Adult↗
[Color Doppler in the prenatal diagnosis of umbilical cord hernia].
Pathologies of the fetal ventral abdominal wall are easily diagnosed by antenatal ultrasonography. The most common anomalies are omphalocele, often associated with other malformations or chromosomal abnormalities, and gastroschisis. We describe an antenatal diagnosis of umbilical cord hernia which could be confirmed by color Doppler. This entity is important to know not to put the umbilical clamp on a bowel loop after delivery.
Adult↗
Frequency of immune thrombocytopenia in newborns: a prospective study. Immune Thrombocytopenia Working Group.
Thrombocytopenia is a common condition in distressed newborns, but little is known about thrombocytopenia in an unselected cohort of neonates. In an attempt to address this issue, a multicenter prospective study was conducted in three obstetrical wards of AP-HP in Paris. We found the frequency of neonatal thrombocytopenia (<150 x 10(9)/L) to approximate 0.9% (48 of 5,632 appropriate samples). An immune mechanism was likely to be the cause of thrombocytopenia in 10 of the 33 cases studied, implying an incidence of 0.3% of immune neonatal thrombocytopenia in the general population. The frequency of alloimmune thrombocytopenia was 1.5/1,000 liveborn neonates, and 1/1,000 when considering anti-HPA-1a allo-immunization. Because thrombocytopenia, whatever its cause, was often silent and delayed, it appears that the only way to detect neonatal thrombocytopenia in time to prevent its potential disastrous complications would be to perform a systematic neonatal blood sampling for platelet count. All cases of ascertained thrombocytopenia should then be screened for an immune mechanism to enable early detection of autoimmune diseases in mothers and careful monitoring of subsequent pregnancies and deliveries, leading to appropriate prevention of potential severe deleterious effects in the offspring.
Adult↗
The low processivity of T7 RNA polymerase over the initially transcribed sequence can limit productive initiation in vivo.
In vitro, after binding to the promoter to form a catalytically active complex, RNA polymerases abortively cycle over the first transcribed nucleotides (initial transcribed sequence or ITS) before leaving the promoter. With the bacteriophage T7 enzyme, the extent of abortive transcription varies with the nature of the ITS and with the elongation speed of the polymerase. Here, we compare in vitro and in vivo the yield of long transcripts from T7 promoters, with two different ITSs, the T7 gene10 and the lactose operon ITSs, and two different T7 RNA polymerases, the wild-type and a 2.7-fold slower mutant (G645A). The use of non-cognate ITS and/or slow polymerase decreases the yield of long transcripts in vitro and in vivo in a parallel fashion, with low polymerase speed and non-cognate ITS acting synergistically. In vitro, this decrease is mirrored by an increase in the average number of abortive cycles the enzyme undergoes before leaving the promoter; specifically, with the G645A mutant, transcript release is favored at any ITS position, whereas with the lac ITS it is particularly frequent at positions five and six following the incorporation of uridine residues. Hence, the more abortive cycles per long transcript synthesis in vitro, the lower the yield of long transcripts in vitro or in vivo. We conclude that the duration of abortive cycling can limit long transcript synthesis in vivo, as in vitro. Under conditions where cycling is minimal (wild-type polymerase, gene10 ITS), T7 promoter drives the synthesis of three long transcripts per second at 37 degrees C in vivo, a figure higher than for any Escherichia coli promoter.
Base Sequence↗
The pregnant ewe: an animal model for fetoscopic surgery.
OBJECTIVE: To develop an animal model for fetal endoscopic surgery which could be feasible and reproducible. The aim of this work was to perform a fetoscopy without the need of a laparotomy. METHODS: Pregnant ewes underwent under general anesthesia laparoscopy with the creation of a maternal pneumoperitoneum. After localizing the placenta by transillumination, we carried out fetoscopy through a 5 mm trocar using a perfusion of Ringer's solution. RESULTS: Five video-assisted procedures have been performed. None of the cases has shown any bleeding from myometrial wounds and no suture was necessary. There was no leakage of amniotic fluid. Intrauterine space was large enough to manipulate instruments without producing any fetal damage. Sharp visualization and anatomical description of the fetus were precise without the use CO2. There were no miscarriages and postnatal examinations of the lambs were normal. CONCLUSION: Fetoscopic surgery can be performed in the pregnant sheep without any complications but preterm labor which is the main problem in human fetal surgery, is infrequent in the sheep. Our model is reproducible and simulates the surgical endoscopic procedures which will occur in a close future in the human species.
Animals↗
An analysis of the factors involved in the diagnostic accuracy of colposcopically directed biopsy.
OBJECTIVE: To compare the results of colposcopically directed biopsy with the final diagnosis established by the analysis of the surgical specimen, and to determine the clinical and colposcopic factors on which the reliability of biopsy is based. MATERIAL AND METHODS: Five hundred and sixty-seven women were seen by the same colposcopist who also performed the directed biopsies and/or the endocervical curettage. The final histological diagnosis identified 29 normal aspects (5.2%), 58 low-grade cervical intraepithelial neoplasias (CIN) (10.2%), 448 high-grade CINs (79.0%), 16 microinvasive cancers (2.8%) and 16 occult invasive cancers (2.8%). The influence of several factors--such as age, parity, menopause, pregnancy, history of cervical treatment, site of the squamocolumnar junction, localization, size and severity of the lesions--on the pertinence of the biopsy was studied in a uni- and multifactorial analysis. RESULTS: Colposcopy was satisfactory in 399 patients (70.4%) in whom the colposcopic aspect was consistent with the final histological diagnosis in 81.2% of cases. The global agreement between biopsy diagnosis and final diagnosis was observed in 89.6% of cases. It was 84.2% for low-grade CINs, 95.8% for high-grade CINs, 31.2% for microinvasive cancers and 81.2% for invasive cancers. No clinical or colposcopic factor could be identified as independent factor associated with the diagnostic agreement with the directed biopsy. Conversely, concordance of biopsy was related to the final diagnosis since the only independent risk factors were a high-grade CIN (adjusted risk ratio (ARR)=1.52, 95% CI=1.11-2.08; p=0.006) and a microinvasive or invasive cancer (ARR=0.56, 95% CI=0.39 0.81; p=0.002). CONCLUSION: To ensure that a microinvasive cancer has not been overlooked, the excision of high-grade CINs seems to be justified, whatever the clinical status and the colposcopic aspect.
Adolescent↗
[Consequences and treatment of cervical stenoses after laser conization or loop electrosurgical excision].
OBJECTIVE: To assess the frequency and the consequences of cervical stenosis in patients treated by laser conization or loop electrosurgical excision procedure (LEEP) and to analyse the results of cervical enlargement plastic surgery or neostomia. METHODS: Two hundred and fifty-five women treated by laser conization and 277 by LEEP were regularly followed by postoperative colposcopy, for a mean period of 38 and 16 months, respectively. Stenosis was defined as cervical narrowing which could not admit a 2.5 mm-diameter Hegar's dilator. RESULTS: Stenosis complicated 10.2% of the laser conizations and 4.3% of the LEEP. Thus, 38 cases of cervical stenosis of which 7 were complete were diagnosed 2 to 40 months after treatment. Among the 34 non-menopaused women who developed a stenosis, 5 had a secondary amenorrhea, 6 a severe dysmenorrhea and one an infertility related to oligoamucorrhea. In the patients with stenosis, endocervical cell retrieval was possible in 21 (55%) cases and in none the squamocolumnar junction was visible at colposcopy. Seven patients underwent an enlargement plastic surgery of the cervical canal for incomplete stenosis and two a neostomia for complete stenosis. Cervical restenosis has been observed in 7 of 9 cases in a mean delay of 12 months (3 to 48 months). Nevertheless, the endocervical cell retrieval remained possible in 8 of 9 cases and after a mean follow-up of 26 months no menstrual troubles recurred. CONCLUSION: LEEP provides fewer cervical stenosis than laser conization. The enlargement plastic surgery allows to correct durably the menstrual troubles in spite of the very frequent restenosis.
Adult↗
[HELLP syndrome. Review and update].
Whether HELLP syndrome is a distinct entity or a severe form of preeclampsia, it remains a factor of gravity. Described by Weinstein in 1982, it associates hemolysis, cytolysis (elevated liver enzymes) and thrombopenia (low platelets). The cut off for the biological parameters have to be strictly defined to avoid overdiagnosis of HELLP syndrome. The difficulty to diagnose this syndrome is real because most of the associated clinical signs are aspecific. The errors of diagnosis are more frequent when the syndrome is not associated to preeclampsia (10%), in the mid-trimester (15%) and in the postpartum (30%). The mean term of delivery is 32 weeks, the prematurity being widely induced because of the fear of maternal complications. Maternal deaths (1.1%) do not seem to be directly related to the HELLP syndrome. Subcapsular hematomas of the liver are unfrequent (0.9%). Rapid termination of pregnancy, by vaginal delivery or by cesarean, is generally recommended when the fetal lung maturity is obtained or when maternal complications appear. Conversely, conservative management is acceptable before 32 weeks. Corticosteroid therapy or hemodynamic therapy could allow to obtain fetal lung maturity. A conservative approach requires permanent materno-fetal follow-up which can only be achieved in a perinatal center integrating a neonatal intensive care unit.
Adrenal Cortex Hormones↗