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This study reports two experiments assessing the spelling performance of French first graders after 3 months and after 9 months of literacy instruction. The participants were asked to spell high and low frequency irregular words (Experiment 1) and pseudowords, some of which had lexical neighbours (Experiment 2). The lexical database which children had been exposed to was strictly controlled. Both a frequency effect in word spelling accuracy and an analogy effect in pseudoword spelling were obtained after only 3 months of reading instruction. The results suggest that children establish specific orthographic knowledge from the very beginning of literacy acquisition.

A simplified model using kinetic logic is proposed to approach the problem after Hepatitis B viral (HBV) infection. It accounts for several stable regimes or attractors corresponding to the essential dynamic behaviour of the replication of the Hepatitis B virus. Infection with the virus can result in viral clearance, fulminant hepatic failure and death, or chronic transmissible infection, that is multistationarity corresponding to the existence of the positive feedback circuit in our modelling. Another implication of this model is the existence of oscillations or homeostatic mechanisms, sometimes observed in the viral cycle, consistent with the existence of the negative feedback circuit. Thus, this report shows how a simple model of kinetic logic may be used to account for the variety of manifestations of HBV infection. This model implies the presence of the Hepatitis B e antigen, whose conservation suggests that it plays an important role in the life cycle of hepadnaviruses. Its function in the viral cycle is still unknown, but our model suggests that this antigen could explain the passage from one state of the viral infection (acute or latent) to another, as well as the oscillatory behavior which may account for the intermittent symptoms of hepatitis observed in some patients. Furthermore, this model shows a virgin state. This state is also reached after recovery. The model proposed demonstrates that starting from a viral acute infection, the host's immune response, depending on the immunological status of the patient, can lead to viral clearance, or to periodic spontaneous reactivation.

Introduction: The Muir-Torre Syndrome is a rare genodermatosis, defined by the occurrence of cutaneous tumors (such as sebaceous adenomas, epitheliomas, or carcinomas, and/or keratoacanthomas), and internal malignancies. Recently, molecular analysis in hereditary non polyposis colorectal cancer demonstrated a common genetic basis, linking these two disorders, with the observation of germline mutations in the hMSH2 gene (one of the DNA mismatch repair system genes) in both syndromes. Such molecular demonstration of a single nosological entity should be clinically used to improve the indications of molecular testings in oncogenetics, still restricted to highly stringent criteria for hereditary non polyposis colorectal cancer., Clinical Cases: We identified three patients from two different families, who fulfilled the criteria for both Muir-Torre Syndrome and hereditary non polyposis colorectal cancer. The search of a germline mutation of the hMSH2 gene was performed on an affected member from each family, and their relatives with their informed consent. Within each family, all individuals with colorectal cancer were carriers of the same mutation. In the first family, this mutation was a pathogenic microinsertion, usable for predictive testing. In the second family, a missense mutation was identified, requesting further demonstration of its pathogenicity before its use in a predictive purpose., Conclusions: The diagnosis of cutaneous tumors compatible with Muir-Torre syndrome should lead the dermatologist to suspect an hereditary non polyposis colorectal cancer that should bring to an oncogenetic approach: personnal and familial history of colorectal cancer, molecular analysis, recommendations for colonoscopic screening in at-risk relatives. In the case of a colorectal cancer at a young age, or in the case of familial cases, the gastroenterologist should screen for cutaneous lesions of Muir-Torre syndrome, which could add a criteria for an hereditary syndrome, and lead to molecular oncogenetic analysis.

The molecular biology of viruses can be effectively described by kinetic logic as several feedback loops are implicated in all viral cycles and as viral proteins generally display several functions. We applied this method to the study of the rhabdovirus cycle. Formally, the dynamics of the model are explored on the basis of a discrete caricature (kinetic logic), with special emphasis on the role of the constitutive feedback loops to determine the essential dynamical behaviour of the viral cycle. From a biological point of view, our model accounts for several stable regimes or attractors: healthy cells, acute infection and different kinds of persistent infections, a multistationarity in good agreement with the existence of several positive feedback loops in our system.

Our clinic has fortuitously developed the therapeutic use of the association of mianserin (maximum daily dose 90 mg) and carbamazepine (maximum daily dose 400 mg) in opiate withdrawal management. If animal studies have suggested efficacy of mianserin in such indication, no human studies have been performed. To test the efficacy of such an association, a comparison was made to clonidine (maximum daily dose 0.600 mg) in a one week treatment period according to a double blind pilot study design. Thirty-two patients were included (16 in each treatment group). The two treatments did not differ in the intensity of the withdrawal, according to the rate of retention in treatment and symptoms, and the psychic distress which were auto-evaluated every other day with the Opiate Withdrawal Questionnaire and several Visual Analog Scales (VAS). The clonidine group, however, scored significantly higher (P < 0.05) on the VAS rating of the global feeling of satisfaction on the last day. The patients in the mianserin group fortuitously had a moderately lower number of daily heroin intakes but there was no significant correlation between this variable and the global OWQ scores on Days 1, 3, 5 and 7. Given the size of the groups, we cannot conclude that the association carbamazepine-mianserin is as effective as clonidine, but a real effectiveness is probable. A study versus placebo would be necessary to draw more definitive conclusions.

The authors report the results of a systematic study of the skin conducted during three months in 306 neonates born in a hospital maternity unit in the Hauts-de-Seine departement, France. Two hundred and ninety-nine infants could be examined: 91 (30.5 p. 100) developed erythema toxicum neonatorum; 102 (34 p. 100) had port wine naevus; 42 (14 p. 100) mongolian spot, and 10 (3.5 p. 100) pigmented epidermal naevus. Various other abnormalities were found. These findings are compared with those of previous French (5, 14) and foreign (1, 3, 7-11, 13, 16, 17-19) studies.

TsO82, a spontaneous temperature-sensitive (ts) mutant of vesicular stomatitis virus (VSV) isolated in chick embryo fibroblasts (CEFs), complements the five prototype ts mutants of the virus. The data presented here indicate that the defect in tsO82 is localized in the M gene. The mutation changed a methionine to an arginine at position 51 of the M protein. Only true revertants could be isolated, and their frequency was low, perhaps due to the type of substitution required to return to the wild-type phenotype. TsO82 does not exhibit hypertranscription, in contrast to the data reported for all of the other ts mutants affected in the M protein. Moreover, tsO82 is conditionally ts, since it grows normally in BHK-21 cells at all temperatures. It exhibits no c.p.e. at the non-permissive temperature in CEFs. Our data argue for multiple functions of the M protein of VSV, the domain affected by the tsO82 mutation possibly being implicated both in the shut-off of cellular RNA synthesis, and for the recognition of a cellular factor required for efficient viral RNA synthesis.

The prototype member of the complementation group II temperature-sensitive (ts) mutants of vesicular stomatitis virus, ts II 052, has been investigated. In ts II 052-infected HeLa cells at the restrictive temperature (39.5 degrees C), reduced viral RNA synthesis was observed by comparison with infections conducted at the permissive temperature (30 degrees C). It was found that for an infection conducted at 39.5 degrees C, no 38S RNA or intracytoplasmic nucleocapsids were present. For nucleocapsids isolated from ts II 052 purified virions or from ts II 052-infected cells at 30 degrees C, the RNA was sensitive to pancreatic RNase after an exposure at 39.5 degrees C in contrast to the resistance observed for wild-type virus. The nucleocapsid stability of wild-type virus when heated to 63 degrees C or submitted to varying pH was not found in nucleocapsids extracted from ts II 052 purified virions. The data suggest that for ts II 052 there is an altered relationship between the viral 38S RNA and the nucleocapsid protein(s) by comparison with wild-type virus. Such results argue for the complementation group II gene product being N protein, so that the ts defect in ts II 052 represents an altered N protein.

Temperature-sensitive (ts) mutants of vesicular stomatitis virus belonging to complementation groups III and V were investigated for their in vivo RNA synthesis. The sucrose gradient patterns of the RNA species which they produced at nonpermissive temperature (39.2 degrees C) were systematically compared under different experimental conditions: variation of input multiplicity and of time of infection, superinfection with T particles, and temperature shifts. Finally, a more precise analysis of the various RNA species synthesized was carried out. It appeared that the characteristics of RNA synthesis specified at 39.2 degrees C by tsIII or tsV mutants differed from the normal RNA synthesis of vesicular stomatitis virus wild type. Their common depression at 39.2 degrees C in virion-like RNA (38S) production--i.e., so-called genome replication--was tentatively paralleled with the concomitant ts events which have been previously shown to affect the two viral envelope proteins. An overproduction of the RNA transcripts was described for mutants in group III and posed the question of a regulation process to determine the amount of RNA to be transcribed.

Acute infection of cloned BHK21 cells with rabies virus (CVS strain) resulted in a reduction in the amount of cellular RNA, not so rapid and pronounced as with another rhabdovirus, vesicular stomatitis virus (VSV). This decrease in the amount of cellular RNA was shown to be caused by a differential membrane permeability of infected and uninfected BHK21 cells to [3H]-uridine and by a real inhibition of cellular RNA synthesis.

A case of Kaposi's disease is reported with a lesion in the buccal mucosa, and the history, classification, signs and symptoms, and treatment of this disease are described.

Temperature-sensitive (ts) mutants of vesicular stomatitis virus belonging to the RNA(-) complementation group IV were investigated under various conditions to study both their RNA and protein syntheses. In infected cells maintained at 39.2 C, viral RNA species were recovered only in the 13 to 15S region of the gradient in an amount depending on the ts mutant used. In the presence of cycloheximide at 39.2 C, the primary transcription was deficient, especially for 28S mRNA production. When mutant-infected cells were shifted to nonpermissive temperature, a shutoff of 28S mRNA synthesis occurred as a general feature. On the contrary under this condition, the two mutants chosen, ts IV100 and ts IV111, behaved very differently in their 13 to 15S and 38S RNA production. However, treatment with cycloheximide at the time of the transfer to 39.2 C resulted in a similar recovery of 13 to 15S RNA in both mutants, whereas the 28S remained very depressed. The viral proteins synthesized by cells infected with the same two mutants also showed a distinct pattern, especially regarding the N protein; a correlation between 38S RNA and protein N syntheses was tentatively drawn. The whole set of data suggested that the lesion in group IV mutants concerned a viral structural protein required for the process of in vivo transcription and which probably intervened in the replication mechanism.

Vesicular stomatitis virus (VSV) subviral particles (nucleocapsids and G-depleted particles) were used to infect various cells (chicken embryo, HeLa, and BHK21 cells). These particles bind to and penetrate into host cells; the association of G-depleted particles to cells was even better than that of normal virions. The parental genomes of subviral particles and virions were degraded at the same rate in the infected cells. Nevertheless, these subviral particles had a very low infectivity, synthesized very little viral macromolecules, and had very little, if any, effect on the various host cells used. Furthermore , subviral particles could be rescued in chicken embryo cells by uv-irradiated VSV virions, demonstrating that subviral particles actually penetrated into cells, and that their arrested cycle could be unblocked up to a certain point. On the other hand, subviral particles were not rescued in HeLa cells, suggesting a dependence on the host cell system.

A temperature-sensitive (ts) mutant, tsG1, has been isolated from the CVS (Challenge Virus Standard) strain of rabies virus. The ts mutation affects the glycoprotein (G protein); it consists of an amino acid substitution (leucine to phenylalanine) at position 132. tsG1 exhibits a slightly reduced pathogenicity when administered via the intracerebral route and complete avirulence after intramuscular inoculation, associated with a very high protective power for adult mice. The ts mutation does not seem to block the transport of the G protein to the plasma membrane at the non-permissive temperature (39.6 degrees C). It abolishes the c.p.e. of the virus in cell cultures.

The viral ribonucleic acids (RNA species) synthesized in HeLa cells infected with temperature-sensitive (ts) mutants and with the wild type of vesicular stomatitis virus at permissive (30 C) and nonpermissive (39.2 C) temperatures were compared by sucrose gradient centrifugation. Two ts mutants (ts 5 and ts 100) representing two separate complementation groups (respectively, groups I and IV), each concerned with viral RNA synthesis, were chosen. Mutant ts 5 failed to synthesize any RNA at 39.2 C. Under the same conditions, mutant ts 100 showed a low, but easily detectable, synthesis of RNA without characteristic peaks. The in vitro transcriptase activity was tested with mutants ts 5 and ts 100 at 39.2 C: normal activity, compared with wild-type virus, was detected with purified ts 100, but no activity was detected with purified ts 5. From all our data we conclude that mutant ts 5 is defective in transcription. The defect could be in the structural transcriptase enzyme or at the level of template for transcription. Results with mutant ts 100 were not so clear-cut. However, we suggest that this mutant is concerned with some aspect of transcription in vivo. In addition, our results lead us to postulate some linkage between transcription and replication.