Innovative working schedule: introducing one short nap during the night shift.

In order to test the possible long-term effects of the implementation of a short nap during night shifts, an experiment was conducted over a period of 1 year with 12 volunteer shiftworkers operating in an industrial plant. They were authorized, under certain conditions, to use individual sleeping areas, for a maximum of 1 hour, between 23h30 and 3h30. The participants were asked to fill in a short questionnaire every day during the entire study. The questions concerned the schedule of the main sleep period, the afternoon nap and the night-time nap, if any, as well as the evaluation of mood and the quality of work. This daily questionnaire was supplemented by an extensive questionnaire applied every 2 months in order to assess the main changes introduced in the life of the participants by this new working schedule. Results showed that this new organization introduced a general satisfaction about the quality and the easiness of the work at night. The vigilance level was considered to be higher during the hours following the nap. The efficacy of the nap time progressively increased for most subjects. The general quality of life improved for most subjects. While a few of them considered that falling asleep was less easy on the following morning at home, the statistical analysis did not show any detrimental effect of the short rest period on the length of the immediately consecutive main sleep period. However, different statistical analyses allow us to reveal significant differences between the main sleep durations following the night shift compared with those following both the afternoon shift and the resting period. The main sleep duration following the night shift was not statistically different from that of the morning shift. These results are very encouraging. A short nap during the night shift can be considered as a positive way to counteract the low level of vigilance that normally occurs during the late part of the night.

Perception of the place of articulation of French stop bursts.

This paper deals with the perception of French natural stop bursts and with the role played by the following vowel in this perception. The first experiment verified the ability of listeners to identify long stimuli containing the burst and part of the subsequent vowel. The second and third experiments investigated the identification of stop bursts with and without a priori knowledge of the following vowel. In order to determine the discriminating power of spectral characteristics of the burst, these experiments used fixed-length burst stimuli of 25-ms duration with all traces of vocalic segment cut off. The bursts of initial voiceless stops were extracted from CVC isolated words. The burst provided very reliable information about stop place since listeners identified correctly 87% of the stops, without a priori knowledge of the following vowel. Performance however was context-dependent. Knowing the identity of the vowel led to a slight but statistically significant improvement in stop identification. Nevertheless, the effects of this knowledge were selective and varied with context. Finally, the first experiment proved that a near perfect identification of stops can be achieved only when all main cues (burst spectrum, burst duration, and onset of vocalic formant transitions) were present simultaneously.

Resistance of herpes simplex virus type 1 to peptidomimetic ribonucleotide reductase inhibitors: selection and characterization of mutant isolates.

Herpes simplex virus (HSV) encodes its own ribonucleotide reductase (RR), which provides the high levels of deoxynucleoside triphosphates required for viral DNA replication in infected cells. HSV RR is composed of two distinct subunits, R1 and R2, whose association is required for enzymatic activity. Peptidomimetic inhibitors that mimic the C-terminal amino acids of R2 inhibit HSV RR by preventing the association of R1 and R2. These compounds are candidate antiviral therapeutic agents. Here we describe the in vitro selection of HSV type 1 KOS variants with three- to ninefold-decreased sensitivity to the RR inhibitor BILD 733. The resistant isolates have growth properties in vitro similar to those of wild-type KOS but are more sensitive to acyclovir, possibly as a consequence of functional impairment of their RRs. A single amino acid substitution in R1 (Ala-1091 to Ser) was associated with threefold resistance to BILD 733, whereas an additional substitution (Pro-1090 to Leu) was required for higher levels of resistance. These mutations were reintroduced into HSV type 1 KOS and shown to be sufficient to confer the resistance phenotype. Studies in vitro with RRs isolated from cells infected with these mutant viruses demonstrated that these RRs bind BILD 733 more weakly than the wild-type enzyme and are also functionally impaired, exhibiting an elevated dissociation constant (Kd) for R1-R2 subunit association and/or reduced activity (kcat). This work provides evidence that the C-terminal end of HSV R1 (residues 1090 and 1091) is involved in R2 binding interactions and demonstrates that resistance to subunit association inhibitors may be associated with compromised activity of the target enzyme.

Implementation of napping in industry and the problem of sleep inertia.

It seems reasonable to believe that in specific situations napping at the work place would be possible and used if authorized and encouraged. Very short naps could have very positive long-term effects on biological functions. Training someone to sleep for short periods appears feasible if there is a high motivation to do so. Sleep inertia can be considered as one of the main limiting factors in napping strategy. Sleep inertia depends on different factors such as sleep stage preceding the awakening, temporal placement of the nap, duration of nap and wakefulness preceding it, etc. The effects of sleep inertia might be different depending on the type of task, and a reactivation technique applied immediately after awakening may remove it. Despite the fact that its implementation in industry raises some practical issues, napping can be considered as a possible strategy to increase the vigilance level of night workers.

A potent peptidomimetic inhibitor of HSV ribonucleotide reductase with antiviral activity in vivo.

Herpes simplex viruses (HSV) types 1 and 2 encode their own ribonucleotide reductases (RNRs) (EC 1.17.4.1) to convert ribonucleoside diphosphates into the corresponding deoxyribonucleotides. Like other iron-dependent RNRs, the viral enzyme is formed by the reversible association of two distinct homodimeric subunits. The carboxy terminus of the RNR small subunit (R2) is critical for subunit association and synthetic peptides containing these amino-acid sequences selectively inhibit the viral enzyme by preventing subunit association. Increasing evidence indicates that the HSV RNR is important for virulence and reactivation from latency. Previously, we reported on the design of HSV RNR inhibitors with enhanced inhibitory potency in vitro. We now report on BILD 1263, which to our knowledge is the first HSV RNR subunit-association inhibitor with antiviral activity in vivo. This compound suppresses the replication of HSV-1, HSV-2 and acyclovir-resistant HSV strains in cell culture, and also strongly potentiates the antiviral activity of acyclovir. Most importantly, its anti-herpetic activity is shown in a murine ocular model of HSV-1-induced keratitis, providing an example of potent nonsubstrate-based antiviral agents that prevent protein-protein interactions. The unique antiviral properties of BILD 1263 may lead to the design of new strategies to treat herpesvirus infections in humans.

Comparative analysis of the immunoprotective abilities of glycosylated and deglycosylated parainfluenza virus type 3 surface glycoproteins.

The role of carbohydrate moieties on the immunoprotective ability of parainfluenza virus type 3 (PIV-3) haemagglutinin-neuraminidase (HN) and fusion (F) glycoproteins was tested in hamsters. HN and F proteins were purified from detergent-solubilized virus by lentil-lectin affinity chromatography and deglycosylated by treatment with endoglycosidase F (endo F). Immunization of hamsters with either 1 or 5 micrograms of mock-treated (glycosylated) affinity-purified proteins elicited strong haemagglutination inhibition and neutralizing antibody responses 4 weeks after the primary injection. In contrast, titres were significantly lower with endo F-treated (deglycosylated) proteins. However, following the booster doses with at least 5 micrograms of antigen, glycosylated and deglycosylated proteins induced comparable antibody titres. There was no significant difference in the ability of the glycosylated or deglycosylated proteins to protect either the upper or lower respiratory tracts of immunized hamsters against PIV-3 challenge. These results suggest that the carbohydrate moieties of the HN and F proteins are not necessary for eliciting a protective response in hamsters.

Comparative analysis of the immunostimulatory properties of different adjuvants on the immunogenicity of a prototype parainfluenza virus type 3 subunit vaccine.

The immunogenicity of a parainfluenza virus type 3 (PIV-3) subunit vaccine consisting of affinity-purified haemagglutinin-neuraminidase (HN) and fusion (F) surface glycoproteins was tested in guinea-pigs and hamsters. The ability of several different immunopotentiating agents to enhance the antibody response of animals to the PIV-3 surface glycoproteins was evaluated. The immunity induced by HN and F alone was compared with the response elicited by purified proteins combined with Freund's complete adjuvant, aluminium phosphate, Syntex's threonyl-muramyl dipeptide (MDP) SAF-MF formulation, or Ribi's adjuvant formulation containing BCG cell wall skeleton (CWS), trehalose dimycolate (TDM) and monophosphoryl lipid A (MPL) in a 2% squalene-in-water emulsion. Purified proteins were also incorporated into three different liposome formulations prepared by the detergent dialysis procedure. Immunization of guinea-pigs and hamsters with two 15 micrograms doses of the PIV-3 surface glycoproteins administered in the absence of adjuvant elicited high haemagglutination inhibition, neutralization and anti-fusion titres. The liposome preparations failed to enhance the antibody titres. Ribi's adjuvant formulation was effective at inducing a good secondary response to the purified proteins while the immunostimulatory effects of aluminium phosphate, Syntex and Freund's adjuvants were clearly demonstrated in both primary and secondary responses. When administered without adjuvant, a 15 microgram dose of the HN and F mixture was capable of protecting hamsters against live virus challenge. The immunoprotective dose of the purified proteins could be reduced to at least 0.1 microgram by the addition of aluminium phosphate, Syntex or Freund's adjuvants.

Evaluation of the immunogenicity and protective efficacy of a candidate parainfluenza virus type 3 subunit vaccine in cotton rats.

A parainfluenza virus type 3 (PIV3) subunit vaccine consisting of detergent-solubilized, affinity-purified haemagglutinin-neuraminidase (HN) and fusion (F) surface glycoproteins was tested in cotton rats for immunogenicity, short-term effects on virus-induced immunopathology and protective efficacy. Groups of animals were immunized twice, 4 weeks apart, with graded doses of vaccine administered either alone or with aluminium phosphate (AlPO4). The minimum immunogenic dose of vaccine was 0.1 microgram HN and F when the vaccine was given alone and 0.01 microgram when the vaccine was administered with AlPO4 adjuvant. Antibody responses in animals immunized with 1 microgram HN and F mixed with adjuvant were similar to those in control animals infected with live PIV3 intranasally. Pulmonary and nasal wash PIV3 titres generally were inversely correlated with serum antibody levels. Virus titres were significantly reduced in all groups of animals immunized with greater than or equal to 0.1 microgram HN and F compared with control animals immunized with vehicle only. Four days after virus challenge, there was no evidence of enhanced histopathology in lung sections from animals immunized with the candidate vaccine.

[Arrhythmia and vago-sympathetic equilibrium in athletic divers]. / Troubles du rythme et équilibre vago-sympathique chez le plongeur sportif.

Two series of electrocardiographic recordings by the Holter method were performed in 16 athletic divers : the first series in a man-made tank 15 m deep and containing water at 28 degrees C, with only exercises in apnoea ; the second series in a natural environment, with exercises in both apnoea and aqualung. Bradycardia was recorded in the second part of the apnoea. It was more marked and long-lasting in the artificial environment than in the natural one, and its degree correlated with the degree of experience of the driver (r = 0.90 ; p less than 0.001) . In 70 p. 100 of the cases, bradycardia was associated with atrial and/or ventricular extrasystoles in the artificial environment. In the natural environment, tachycardia was globally predominant and could reach maximum heart rate during exercises in the aqualung. The authors discuss the shift observe in vasosympathetic balance and its electrophysiological consequences when diving.

Electrocardiographic aspects of skin diving.

Electrocardiographic (ECG) aspects of skin diving were monitored by means of continuous ECG recording in a pool 15 m deep. Ten regularly trained divers with different levels of experience divid a minimum of three consecutive times, holding their beath, reaching depths of 6 m, 9 m, and 12 or 15 m. The water temperature was 28 degrees C. During the ascending part of these dives, bradycardia was observed in all skin-divers. Minimal heart rate correlated negatively with the diver's experience (number of dives previously performed). In six divers cardiac arrhythmia was observed. Atrial arrhythmias were sometimes isolated occurrences, but more frequently they were multiple. Ventricular arrhythmias tended to be bigeminal. Apparently, forced expiration through the snorkel when surfacing precipitated these rhythmic disorders.

Involvement of the 24-kDa cap-binding protein in regulation of protein synthesis in mitosis.

The rate of protein synthesis in metaphase-arrested cells is reduced as compared to interphase cells. The reduction occurs at the translation initiation step. Here, we show that, whereas poliovirus RNA translation is not affected by the mitotic translational block, the translation of vesicular stomatitis virus mRNAs is. In an attempt to elucidate the mechanism by which initiation of protein synthesis is reduced in mitotic cells, we found that the interaction of the mRNA 24-kDa cap-binding protein (CBP) with the mRNA 5' cap structure is reduced in mitotic cell extracts, consistent with their lower translational efficiency. Addition of cap-binding protein complex stimulated the translation of endogenous mRNA in extracts from mitotic but not interphase cells. In addition, we found that the 24-kDa CBP from mitotic cells was metabolically labeled with 32P to a lesser extent than the protein purified from interphase cells. These results are consistent with a hypothesis that the 24-kDa CBP is implicated in the inhibition of protein synthesis in metaphase-arrested cells. Possible mechanisms for this inhibition are offered.

Proteolysis of the p220 component of the cap-binding protein complex is not sufficient for complete inhibition of host cell protein synthesis after poliovirus infection.

Infection of cells with poliovirus results in the complete shutoff of host protein synthesis. It is presumed that proteolysis of the p220 component of the cap-binding protein complex that is required for the translation of host mRNAs is responsible for the shutoff phenomenon. In this paper, we show that when cells are infected with poliovirus in the presence of guanidine or 3-methylquercetin, both inhibitors of poliovirus replication, complete cleavage of p220 occurs by 3.5 h postinfection. However, under these conditions only 55 to 77% of host protein synthesis is suppressed. Results obtained with extracts prepared from poliovirus-infected cells were similar to those obtained in vivo. These results suggest that complete inhibition of host protein synthesis after poliovirus infection requires at least one event in addition to proteolysis of p220. Thus, proteolysis of p220 is probably necessary but not sufficient for total suppression of host protein synthesis after poliovirus infection.

[A swollen leg disclosing a popliteal cyst. Apropos of a misleading case]. / Une grosse jambe révélatrice d'un kyste poplité. A propos d'un cas trompeur.

A patient was admitted with a clinical suspicion of left sural thrombophlebitis. Analysis of the clinical features and the results of rheoplethysmography, phlebography, arteriography and, most importantly, ultrasonography led to the diagnosis of popliteal synovial cyst and demonstrated the vascular repercussions of this lesions responsible for the swollen leg. A review of the literature confirms the frequently misleading clinical features of popliteal cysts. The authors present a strategy for the investigation of these cases, based on vascular functional investigations and in particular ultrasonography.

Effect of viral infection on host protein synthesis and mRNA association with the cytoplasmic cytoskeletal structure.

We studied the association of several eucaryotic viral and cellular mRNAs with cytoskeletal fractions derived from normal and virus-infected cells. We found that all mRNAs appear to associate with the cytoskeletal structure during protein synthesis, irrespective of their 5' and 3' terminal structures: e.g., poliovirus that lacks a 5' cap structure or reovirus and histone mRNAs that lack a 3' poly A tail associated with the cytoskeletal framework to the same extent as capped, polyadenylated actin mRNA. Cellular (actin) and viral (vesicular stomatitis virus and reovirus) mRNAs were released from the cytoskeletal framework and their translation was inhibited when cells were infected with poliovirus. In contrast, actin mRNA was not released from the cytoskeleton during vesicular stomatitis virus infection although actin synthesis was inhibited. In addition, several other conditions under which protein synthesis is inhibited did not result in the release of mRNAs from the cytoskeletal framework. We conclude that the association of mRNA with the cytoskeletal framework is required but is not sufficient for protein synthesis in eucaryotes. Furthermore, the shut-off of host protein synthesis during poliovirus infection and not vesicular stomatitis virus infection occurs by a unique mechanism that leads to the release of host mRNAs from the cytoskeleton.

[Angiodysplasia of the ileum and cardiomyopathy]. / Angiodysplasie de l'iléon et cardiomyopathie.

A patient aged 73 had repeated episodes of melaena and a systolic murmur suggesting mitral insufficiency. An obstructive cardiomyopathy was diagnosed on echocardiography, while the gastro-intestinal tract investigations proved negative (gastro-duodenal endoscopy, barium meal and follow-through), until ileal vascular tumours were diagnosed by selective mesenteric arteriography. Diagnosis could only be confirmed on exploratory laparotomy, and definitive treatment was undertaken at the same time. The authors discuss the practical and theoretical consequences, including the need for thorough gastro-intestinal investigations in patients with repeated intestinal haemorrhage, particularly in the presence of a systolic murmur which is not necessarily the sign of aortic stenosis.

[Treatment of atrial fibrillation with fenoxedil hydrochloride. Apropos of 112 cases]. / Traitement de la fibrillation auriculaire par le chlorhydrate de fénoxédil. A propos de 112 observations.

One hundred and twelve patients with atrial fibrillation of different causes were treated with fenoxedil chlorhydrate. Sinus rhythm was restored in 81 cases (72.3 p. 100). The best results were obtained in the following conditions: hypertensive heart disease (77.6 p. 100), ischemic heart disease (75 p. 100), idiopathic atrial fibrillation (76.4 p. 100), senile lone fibrillation (78.2 p. 100). The results were average in valvular heart disease (57.1 p. 100) and in hyperthyroidism (40%). Age did not appear to be a deciding factor, the overall results being comparable in patients under 70 years of age (70.8 p. 100) and over 70 years of age (73.4 p. 100). Although recent atrial fibrillation was reduced more easily (83.3 p. 100), the results were satisfactory in chronic arrhythmias (over 3 years) (77.7 p. 100). The success rate was 76.3 p. 100 when the cardiothoracic index was over 0.60, and 66.6 p. 100 when less than 0.60. The antiarrhythmic effect of fenoxedil chlorhydrate is related to its electrophysiological properties as it depresses sinus node activity and atrioventricular conduction. No arrhythmic or conduction complications were observed during a short period (maximum 5 days) of close monitoring. However, lengthening of the QT and PR intervals was a common phenomenon. The advantages of fenoxedil chlorhydrate over electrical cardioversion (atraumatic, possibility of associating digitalis) and the results obtained whilst respecting the prescribing advice, justify its adoption as a method of converting atrial fibrillation.

Identification of rubella virus structural proteins by immunoprecipitation.

Immunoprecipitation of [3H]amino acid labelled virus with monoclonal or human convalescent rubella sera and subsequent analysis by electrophoresis and fluorography, revealed three structural proteins of rubella virus: VP3: 59,000; VP2: 44,800; and VP1: 33,000.