The Ceratitis capitata homologue of the Drosophila sex-determining gene sex-lethal is structurally conserved, but not sex-specifically regulated.

In Drosophila, Sxl functions as a binary switch in sex determination. Under the control of the primary sex-determining signal, it produces functional protein only in XX animals to implement female development. Here we report that, in contrast to Drosophila, the Sxl homologue in the Medfly, Ceratitis capitata, expresses the same mRNAs and protein isoforms in both XX and XY animals irrespective of the primary sex-determining signal. Also, experiments with two inducible transgenes demonstrate that the corresponding Ceratitis SXL product has no significant sex-transforming effects when expressed in Drosophila. Similar results have been obtained for the Sxl homologue of Musca domestica (Meise, M., Hilfiker-Kleiner, D., Brunner, C., DLbendorfer, A., N¿thiger, R. and Bopp, D. (1998) Development 125, 1487-1494). Our findings suggest that Sxl acquired its master regulatory role in sex determination during evolution of the Acalyptratae group, most probably after phylogenetic divergence of the genus Drosophila from other genera of this group.

Dense cluster of genes is located at the ecdysone-regulated 3C puff of Drosophila melanogaster.

The 3C11-12 polytene bands of the Drosophila melanogaster X chromosome give rise to a prominent puff, whose regression is triggered by the increase in the titre of the steroid hormone 20-hydroxyecdysone occurring before the metamorphosis. Here, we report the molecular characterization of three genes, named ng-2, ng-3 and ng-4, which we found to be closely linked to each other and to Sgs-4, Pig-1 and ng-1, three other genes previously mapped at this polytene region. All six genes are, in fact, arranged in a tightly linked cluster spanning a DNA segment of only 11 kb. With the exception of ng-4, all the clustered genes are highly expressed only during the larval life and share the same tissue-specificity, being mainly transcribed within the salivary glands. In addition, two members of the cluster, ng-1 and ng-2, show a very high degree of sequence homology, clearly indicating that they are related to each other by means of a duplication event. Interestingly to note, the entire cluster shows a peculiar genomic location, extending across two introns of the memory gene dunce, a large gene of Drosophila whose organization has proved to be remarkably complex.

Opa-like repeats in the genome of the Medfly Ceratitis capitata.

The sequence determination of several genomic clones isolated from the Mediterranean fruitfly Ceratitis capitata identified the existence of opa-like repeats, often more than one being clustered in small chromosomal segments. These repeats have previously been shown to consist of stretches of tandemly reiterated glutamine-encoding residues, and they are found in multiple genes of several organisms. Most of the repeats described here are flanked or interrupted by stop codons in all reading frames and, thus, could not possibly be part of protein-coding sequences. Furthermore, these repeats, of which there are several hundred in the genome of the Medfly, can be used effectively for the determination of sequence polymorphisms, providing a convenient approach to obtain additional landmarks for the construction of genomic maps of this economically important insect.

Molecular characterization of a Drosophila melanogaster variant strain defective in the Sgs-4 gene dosage compensation.

The X-linked Sgs-4 gene of Drosophila melanogaster encodes a salivary glue protein. Here we report the molecular characterization of a non-dosage compensated variant strain, named Karsnas, in which males accumulate only about half of the Sgs-4 polypeptide amount as do females. The results obtained show that significant nucleotide sequence alterations are accumulated within the Sgs-4 coding and 3' untranslated region of the variant strain, thus suggesting a possible role of these sequences in the Sgs-4 dosage compensation.

Molecular organization of the Drosophila melanogaster Pig-1 gene.

The Pre-intermoult gene-1 (Pig-1) of Drosophila melanogaster maps on the X chromosome, at polytene bands 3C11-12, and is nested within the 79 kb intron of the dunce gene. Pig-1 has so far been characterized only preliminarily and its function is still unknown. We analysed the molecular organization of the gene by cDNA clone isolation and sequencing as well as S1 mapping and primer extension analyses. The results obtained reveal that the gene is colinear with its genomic sequence and define the usage of both 5' and 3' alternative sites for Pig-1 transcription; two continuous open reading frames (ORFs) are fully contained within the Pig-1 transcribed region, although several lines of evidence suggest that only the longer ORF is likely to be translated. We also report that the level of Pig-1 transcript is nearly fourfold reduced in a variant strain carrying a deletion within the Pig-1 upstream sequence, thus identifying a regulatory element required for high level gene expression.

A new gene nested within the dunce genetic unit of Drosophila melanogaster.

The molecular organization of the dunce gene of Drosophila melanogaster has proved to be particularly complex, with two divergently transcribed genes, Sgs-4 and Pig-1, nested within its 79 kb intron (1). Here we report the identification and the molecular characterization of a third gene nested within the transcription unit of dunce. This newly identified gene is located nearly 6 kb downstream Pig-1, within a more upstream dunce intron. The gene is developmentally regulated and transcribed with the same polarity of dunce; several lines of evidence indicate that it might encode for a salivary gland secreted (Sgs) protein.

[Comparative evaluation using an ergometric test of the efficacy of the 3 major calcium antagonists on exertion stable angina]. / Valutazione comparativa mediante test ergometrico dell'efficacia dei tre maggiori calcio-antagonisti sull'angina stabile da sforzo.

Nifedipine, diltiazem and verapamil are three effective calcium-antagonists in the treatment of angina pectoris. We compared their effects on effort angina to evaluate whether one of them is more efficacious. The data were collected from 42 patients (37 males, 5 females; mean age 51 +/- 4) entering one of 3 different trials; the beginning of all trials comprised a two-week, single blind, placebo run-in phase. An exercise stress test was performed at the end of this period and it was considered as basal test for the statistical analysis. Then the 42 patients were divided in 3 groups of 14 and entered a double-blind, randomized phase of drug treatment. The 3 groups started 3 parallel trials: 1) placebo/nifedipine 60 mg/day; 2) placebo/verapamil 360 mg/day; 3) placebo/diltiazem 240 mg/day. The duration of each trial was of 6 weeks (3 weeks of treatment with placebo and 3 weeks with active substance). Exercise stress tests were performed at the end of each phase of the trials, and the resulting data were compared with the data of the test performed at the end of run-in period. Parameters evaluated were: heart rate, blood pressure and rate pressure product at basal conditions, at submaximal and peak exercise; moreover we considered workload, maximal ST segment depression, total exercise duration and frequency of exercise-induced angina. Verapamil reduced rate pressure product at basal condition; all three drugs reduced rate pressure product at submaximal exercise, but a significant statistical difference was found only for verapamil and diltiazem.(ABSTRACT TRUNCATED AT 250 WORDS)

Non-invasive evaluation of autonomic tone changes during isometric exercise in normal subjects and in patients with coronary artery disease.

In order to evaluate the clinical implications of QT/QS2 ratio during manoeuvres of sympathetic stimulation we studied the effects of handgrip (75% of maximal voluntary contraction) in 18 middle-aged normal subjects and in 16 patients with previous myocardial infarction. We also evaluated the effects of propranolol (0.1 mg/kg i.v.) in all normal subjects and in 10 of the 16 patients with coronary artery disease. At rest the two groups had similar heart rate, blood pressure, QT, QS2 and QT/QS2 ratio values. A significant increase in heart rate and systolic blood pressure was recorded during handgrip both in normal subjects and in patients with coronary artery disease; QT/QS2 significantly increased in normal subjects but did not show significant variations in patients with coronary artery disease, with significant differences between the two groups at peak exercise. Handgrip-induced QT/QS2 changes showed a marked variability both in normal and diseased subjects. After propranolol, QT/QS2 showed no significant difference at peak exercise in the two groups. The variability of ratio changes was nullified by the administration of the drug. These findings suggest that handgrip-induced QT/QS2 changes might be an expression of beta-adrenergic discharge. The clinical value of handgrip-induced QT/QS2 changes in detecting patients with coronary artery disease is limited by the variability of the response of the ratio observed in the two groups.

[Effect of beta-receptor block on QT/QS2 behavior during isometric and dynamic exercise]. / Effetti del blocco beta-recettoriale sul comportamento del rapporto QT/QS2 in corso di esercizio isometrico e dinamico.

Our study is aimed to evaluate the change of QT/QS2 ratio in normal subjects during both isometric and dynamic exercise before and after propranolol administration. We studied 10 young volunteers healthy subjects who performed an isometric exercise by squeezing a grip dynamometer at 70% of their maximal voluntary contraction as long as possible. They also performed a dynamic exercise undergoing a submaximal bicycle stress test. Both tests were performed before and after administration of propranolol (0.15 mg/Kg e.v.) QT and QS2 intervals were measured at rest, during exercise and in the recovery period. Heart rate and blood pressure were also determined. Isometric exercise induces a significant shortening of both intervals although minor for QT so that the ratio significantly increases in comparison to baseline (p less than .001). At rest propranolol induces a significant decrease of heart rate and only a slight lengthening of QT and QS2 so that the ratio is unchanged. During exercise propranolol does not influence the increase of heart rate and blood pressure and the shortening of QT interval but prevent exercise-induced QS2 shortening so that the ratio after beta-blockade is significantly reduced at the peak of exercise (p less than .005). During dynamic exercise QT and QS2 behaviour is similar to that of isometric exercise; in fact both intervals are shortened and QS2 decrease is major than QT so that the ratio increases (p less than .001). These results confirm that QT/QS2 ratio can monitor the effects of adrenergic stimulation on the heart during physiological manoeuvres enhancing sympathetic discharge like occurs during both isometric and dynamic exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

[Influence of the angiocardiographic severity of ischemic heart disease on QTc duration]. / Influenza della severità angiocardiografica della cardiopatia ischemica sulla durata del QTc.

The influence of severity of coronary artery disease (CAD) on the duration of corrected electrical systole (QTc) and the prognostic value to predict sudden death of this index were retrospectively evaluated in 123 non-consecutive patients with history of stable angina who underwent cardiac catheterization. Fifteen patients had no angiographic evidence of CAD (O-V group). The 108 patients with a greater than or equal to 70% luminal diameter narrowing of a major coronary artery were further subdivided: 23 patients had 1-vessel (1-V group), 40 patients had 2-vessel (2-V group) and 45 had 3-vessel (3-V group) coronary artery disease; 26 patients showed normal left ventricular (LV) wall motion (A group), 57 patients showed asynergic contraction of 1 or 2 LV areas (B group) and 25 patients showed 3 or more areas of asynergy and/or aneurysm. Sixty-one patients had a previous myocardial infarction (MI). QT interval, calculated in the lead where it was longer, on 12-lead resting electrocardiograms recorded at a paper speed of 25 mm/sec, was corrected by the formula: QTc = QT/square root R-R. The follow-up was performed by telephone. At the time of angiography there was no significant difference in QTc duration between the different groups according to the severity of CAD (O-V, 1-V, 2-V and 3-V groups). Patients showing three or more areas of abnormal segmental wall motion and/or aneurysm (C group) had a significantly longer QTc (p less than 0.05) than patients with normal LV wall motion (A group).(ABSTRACT TRUNCATED AT 250 WORDS)

QT/QS2 ratio as an index of autonomic tone changes.

The effects of changes in sympathetic tone on QT/QS2 ratio were studied in 10 healthy subjects aged 21 to 24 years. The subjects underwent a bicycle ergometer exercise, a tilt test, a decrease in carotid transmural pressure induced by means of pneumatic neck chamber, an i.v. injection of phenylephrine. A phonocardiogram and ECG were simultaneously recorded at a paper speed of 100 mm/s to evaluate QT and QS2 intervals in each test. In basal conditions, the QT/QS2 ratio was less than 1, whereas it increased progressively during the physical exercise and became greater than 1 at peak exercise. Both the upright position and the increase in neck-tissue pressure induced a significant increase in the QT/QS2 ratio as compared with the basal values, whereas i.v. administration of phenylephrine reduced significantly the QT/QS2 ratio. These results demonstrate that those stimuli which induce a rise in adrenergic activity may increase the QT/QS2 ratio. In contrast, the reflex inhibition of the adrenergic activity induced by phenylephrine is accompanied by a reduction in QT/QS2 ratio. Therefore, the QT/QS2 ratio might represent a reliable index of sympathetic cardiac tone.

[Relation between the QT interval and the severity of ventricular arrhythmias in the early phases of myocardial infarct]. / Relazioni tra l'intervallo QT e la severità delle aritmie ventricolari nelle prime fasi dell'infarto miocardico.

The purpose of our research was to evaluate the relationship between the severity of ventricular arrhythmias in the first hours of myocardial infarction and the duration of electrical systole (QT). Twelve-lead resting electrocardiograms (ECGs) of 66 non-consecutive patients admitted to our Coronary Care Unit for myocardial infarction were retrospectively evaluated. Criteria for retrospective selection of patients were the following: 1) admission to the coronary care unit within 12 hours from the onset of myocardial infarction symptoms; 2) appropriate ECG changes suggesting acute transmural infarction (pathologic Q waves, envolving ST changes) and diagnostic elevation of serum enzymes activity; 3) good-quality ECG recordings with sinus rhythm and no conduction defects, recorded before the beginning of therapy and within the first hours after the onset of symptoms. After this first selection, the following criteria of exclusion were applied: 1) abnormal values of serum Ca++ and K+; 2) historical and/or electrocardiographic findings of a previous myocardial infarction; 3) chronic treatment with antiarrhythmic or beta-blocking drugs, digitalis or other drugs affecting the QT interval; 4) administration of drugs affecting the QT interval before admission; 5) clinical signs of left ventricular failure or cardiogenic shock at admission or during the hospitalization; 6) development of severe ventricular arrhythmias after 24 hours from the onset of symptoms. Three subgroups were individuated : group A: 39 patients with non life-threatening ventricular arrhythmias; group B: 12 patients with episodes of ventricular tachycardia within the first 12 hours of myocardial infarction; group C: 15 patients with episodes of ventricular fibrillation within the first 12 hours of myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)