Conformational changes and local events at the AMP site of glycogen phosphorylase b: a fluorescence temperature-jump relaxation study.
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Biomedical subjects
Publications and source records attributed to M Dreyfus.
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Using hydroxylamine mutagenesis in vitro, mutations were introduced into a short DNA fragment containing the two overlapping promoters of the Escherichia coli galactose operon and the start of the first gal gene, galE. The mutagenised fragment was inserted into a lac expression plasmid. In such a vector, lac expression is controlled by the gal promoter region. Amongst eighteen candidates in which expression was reduced due to mutations in the gal fragment, twelve contained promoter mutations and six carried mutations that reduce the initiation of galE translation. The candidates in which promoter activity was reduced contained mutations affecting the promoter P1, which is dependent on the cyclic AMP-receptor protein complex (cAMP-CRP) for activation. All carried mutations in the sequence 5'GTGA3' at the CRP binding site. One of the twelve also contained a second mutation affecting the second promoter, P2, which normally functions in the absence of cAMP-CRP. Amongst the six candidates affecting galE translation, two contained a mutation that changes the initiator codon from AUG to AUA and almost completely suppresses galE expression. The mutations in the other four candidates affect the ribosome binding sequence, 5'GGAG3'. However, multiple mutations that abolish this sequence do not totally suppress galE expression, showing that there must be another way to guide ribosomes to the correct initiation site.
OBJECTIVES: To assess tocolysis with nifedipine in preterm labour during actual clinical practice in terms of efficacy and safety. PATIENTS AND METHODS: Retrospective observational study during two years including preterm labour between 26 and 33+6 weeks of amenorrhea. Preterm labour was defined by the presence of three or more uterine contractions in 10 minutes associated to cervical modifications diagnosed by vaginal sonography (length<or=25 mm). Patients were excluded if they had more than two fetuses or other gestational pathologies. Tocolysis resulted in oral taking of 30 mg of nifedipine (3x10 mg) with continuous follow-up of blood pressure. Tocolysis was modified when contractions did not disappear. Success was defined when delivery was delayed more than 48 hours. Failure was defined either by a delivery occurring in the first two days of tocolysis or when a modification of treatment was required. RESULTS: Fifty-eight patients were included, 10 of whom having a twin pregnancy. Success was obtained in 84% of patients (49/58). All of these women did not deliver during the first seven days after introduction of tocolysis. Five patients delivered in the first two days after tocolysis and four others required a change in tocolysis. Mean gestational age at delivery was 37+5 weeks and 35 weeks for single and twin pregnancies, respectively. No maternal or fetal side effects were described. DISCUSSION AND CONCLUSION: Nifedipine could be prescribed for tocolysis in actual clinical practice because it seems to have safety and excellent tolerance.
The purpose of this study was to evaluate the foetal sonographic efficiency for prenatal diagnosis of osteochondrodysplasias. Forty-seven prenatal and postnatal cases diagnosed between January 1993 and December 1998 in the referral sonographic centres of Strasbourg were studied. All cases were reviewed retrospectively and the prenatal ultrasound findings and diagnosis were compared to the postnatal or post-mortem diagnosis. Each case was studied by ultrasonographers, geneticists, radiologists, and foetopathologists. Final diagnosis was based on clinical examination, skeletal survey and molecular testing as deemed necessary. Routine screening and dating was the indication for foetal sonography in 72% (32/47) of our cases. The most likely time of diagnosis was between 16 and 24 weeks of gestation (17 out of 47 cases, 36%), which corresponds to the time of foetal anomaly sonographic scan in France. The other cluster of cases (12 among 47, 26%) was disclosed before 16 weeks of gestation. These results illustrate the importance of a detailed evaluation of the limbs during sonographic examinations of first and second trimesters of pregnancy. While the identification of skeletal dysplasias was relatively easy in our study, the ability to make an accurate specific antenatal diagnosis was more difficult. An accurate diagnosis was proposed in 28 of the 47 cases (60%). In 19% of the cases (9/47), the prenatal diagnosis was not accurate; in 21% of the cases (10/47), the prenatal diagnosis was imprecise. In 45 of the 47 cases (96%) prenatal foetal scan correctly predicted the prognosis.
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Cystic adrenal masses are unusual in the fetus. The most common diagnosis for adrenal cyst is hemorrhage. We report 2 cases of cystic neuroblastoma diagnosed prenatally by ultrasound. In each case, diagnosis was confirmed in the neonatal period first by scintigraphy, then by histology. Differential diagnosis and management after delivery are discussed.
We report the prenatal diagnosis of a hepatic hemangioma presenting as a heterogeneous mass (6 x 5 cm) of the fetal liver, thickly septated with calcifications. Pulsed Doppler confirmed the vascular pattern of the mass. Subsequent postnatal examinations and follow-up have documented the spontaneous regression of this benign tumor. Antenatal diagnosis of fetal liver masses and management after delivery are discussed.
OBJECTIVE: To compare the reliability of cytology with that of cervicography and with the use of both tests when screening for neoplasia of the cervix and to analyze the causes of false positive and false negative results with both methods. STUDY DESIGN: The results of cytology and cervicography in 1,709 patients (1,447 seen for routine screening, 82 for follow-up after treatment for cervical neoplasia and 180 referred because of cytologic anomalies) were correlated with colpohistologic findings. RESULTS: Cervicography entailed more defective examinations than did cytology (8.9% vs. 0.2%, P < .0001). It was less sensitive (51% vs. 59%, P = .320) and less specific (96% vs. 98%, P = .004). Whatever the clinical criteria (patient's age, parity, pregnancy or history of cervical treatment), the rate of false positives with cervicography was always higher than with cytology, as was the rate of false negatives, except in pregnant women. CONCLUSION: Cervicography does not seem to offer a worthwhile alternative to cytology for cervical screening.
OBJECTIVE: To compare the cytologic history of patients with cervical cancer with that of patients with high grade cervical intraepithelial neoplasia (CIN) in order to analyze the causes of screening failure. STUDY DESIGN: In 337 patients treated for high grade CIN and 86 women treated for cancer of the cervix, all cytologic reports from the last five years before diagnosis were reviewed, and slides of normal smears taken within three years of diagnosis were reexamined. RESULTS: Among patients with cancer, 32/86 (37.2%) never had a smear, for 28/86 (32.6%) the time interval between screenings was greater than three years, 12/66 (18.2%) were incorrectly managed after the first abnormal smear, and 7/69 (10.1%) had a normal smear within three years of diagnosis. Conversely, among patients with high grade CIN, 45/337 (13.4%) never had a smear, 60/337 (17.8%) had a time interval between screenings greater than three years, 120/337 (35.6%) were incorrectly managed after the first abnormal smear, and 100/333 (30.0%) had a normal smear within three years of diagnosis. When compared with high grade CIN, cancer of the cervix was associated with absent or insufficient screening (adjusted odds ratio [aOR] = 3.28, 95% confidence interval (95% CI) = 1.86-5.80) but neither with incorrect management of the first abnormal smear (aOR = 1.32, 95% CI = 0.46-3.75) nor with a normal smear within three years of diagnosis (aOR = 0.22, 95% CI = 0.10-0.50). CONCLUSION: Better participation of patients is necessary to improve the efficacy of screening. Conversely, reducing the interval between smears to less than three years would cause a major increase in cost and earlier diagnosis of high grade CIN, but not a significant decrease in the number of cancers.
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A retrospective study enabled us to evaluate the "wait-and-see" attitude adopted in our department in case of premature rupture of the membranes at term. The series included 88 patients (9.74%) who delivered spontaneously or after induction. The following maternal parameters were studied:time between rupture and delivery, pyrexia and chorioamnionitis number of vaginal digital examinations, histology and placental bacteriology. Neonatal criteria were based upon an infection assessment. Our results showed that approximately 80% of patients were in labor within 24 hours following rupture. Cesarean section rate remained stable (13%) in comparison with the overall rate for the department. Neonatal infectious morbidity (5.7%) showed no increase. The incidence of chorioamniotitis did not vary (7 cases) but appeared to be related to the number of vaginal examinations before labor. In conclusion, our attitude of temporization did not result in any increase in the number of cesarean sections nor of neonatal infections in comparison with the general population in the department. Prostaglandins might be useful in unfavorable obstetric situations.