Straight core structure of DNA replication origins in the mammalian AMPD2 locus.

Identification of the nucleotide consensus sequence in mammalian replication origins is a difficult and controversial problem. The hypothesis that local DNA topology could be involved in recognition by replication proteins is an exciting possibility. Secondary DNA structures, including intrinsically bent DNA, can be easily detected, and they may indicate a specific pattern in or near mammalian replication origins. This work presents the entire mapping of the intrinsically bent DNA sites (IBDSs), using in silico analysis and a circular permutation assay, of the DNA replication origins oriGNAI3, oriC, oriB, and oriA in the mammalian amplified AMPD2 gene domain. The results show that each origin presents an IBDS that flanks the straight core of these DNA replication sites. In addition, the in silico prediction of the nucleosome positioning reveals a strong indication that the center of an IBDS is localized in a nucleosome-free region (NFR). The structure of each of these curved sites is presented together with their helical parameters and topology. Together, the data that we present here indicate that the oriGNAI3 origin where preferential firing to the replication initiation events in the amplified AMPD2 domain occurs is the only origin that presents a straight, narrow region that is flanked on both sides by two intrinsically bent DNA sites within a short distance (~300 bp); however, all of the origins present at least one IBDS, which is localized in the NFR region. These results indicate that structural features could be implicated in the mammalian DNA replication origin and support the possibility of detecting and characterizing these segments.

Transient electrocardiographic changes suggesting myocardial ischaemia in newborn infants following tocolysis with beta-sympathomimetics.

Serial electrocardiograms (ECGs) were studied prospectively in 80 apparently healthy newborn infants; 30 infants exposed in utero to prolonged tocolytic therapy (21 to ritodrine and 9 to isoxsuprine) and 50 infants non-exposed in utero to drugs (control group) matched for gestational age, Apgar score, and birth weight. Duration of exposure to tocolysis was at least 30 days (30-180 days) with an oral dosage of 10 mg 3 times daily. ECGs were graded for changes suggestive of ischaemia using the arbitrary grading system described by Jedeikin et al. In all infants with ECG features of myocardial ischaemia, serum creatine-phosphokinase iso-enzyme (CK-MB) activity was measured. Six out of 21 infants to ritodrine and six out of nine infants exposed to isoxsuprine showed a degree of ECG ischaemia which persisted for several weeks. No control infant presented grade 2 or 3 ECG changes after the 5th day of life. The results of this study seem to show that prolonged tocolytic therapy with beta-sympathomimetics has side-effects on the fetal myocardium and suggest that this treatment be reserved only for selective cases and/or for short periods of time.

Electropharmacological test with pentisomide (CM 7857) in patients with sustained ventricular tachycardia.

Pentisomide (CM 7857) is a new class I antiarrhythmic drug whose effect on sustained ventricular tachycardia has only been slightly investigated to date. The aim of this paper is to examine the pentisomide action on selected patients with ventricular tachycardia inducible during intracavitary electrophysiological study. Thus, 12 patients (9 M, 3 F, mean age: 45.2 years, range: 24-78), all but two with detectable heart disease, underwent electropharmacological tests with pentisomide after they had resulted "non responders" (8 patients) or had had a proarrhythmic worsening effect (3 patients) to electropharmacological tests with amiodarone or flecainide or propafenone or mexiletine. After the inducibility and the reproducibility of ventricular tachycardia has been assessed in the basal state, all patients underwent several attempts to reinduce ventricular tachycardia, during the i.v. infusion of pentisomide 1.5 mg/kg/5 min followed by continuous infusion of 1 mg/kg/h, at the same time drug plasma level was assessed. Ventricular tachycardia inducibility was still inducible after pentisomide, but with a longer cycle length (446 +/- 88 versus 337 +/- 82 msec) than in the basal state (p less than 0.0025). No patients had proarrhythmic worsening effects. The pentisomide plasma level (available in 5 patients) ranged from 3.4 to 22.3 (mean 8.9 micrograms/ml). Four patients underwent chronic oral treatment (in 1 pt in association with amiodarone) with a good clinical outcome (mean follow-up 6.25 months, range 1-12). We stress the absence of proarrhythmic worsening effects and the powerful effect of the drug on ventricular tachycardia cycle length.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian blood pressure pattern in full-term newborn infants.

A fully automatic noninvasive device (Dinamap) was used for monitoring blood pressure (BP) and heart rate repetitively over 48 h in 21 full-term newborn infants (9 males and 12 females), aged 4 days in order to clarify the occurrence of a circadian rhythm (CR). The data collected were analyzed by computer statistical analysis. Mean values and standard error of BP and heart rate measured at hourly intervals in males and females were computed and plotted as chronograms. However, each newborn infant was analyzed for a CR of BP and heart rate by the single cosinor fit of a 24-hour cosine curve. The analysis of the chronograms revealed that the values of systolic and diastolic BP show an hour-by-hour significant fluctuation in male infants, but not in female infants. CR development of BP is present only in a minority of newborn infants and reveals sex and interindividual differences. CR of heart rate is absent in all infants. The physiological significance of these findings was discussed, and the importance of knowing the physiological variances of BP in infants in order to obtain a correct clinical evaluation was stressed.