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D Gendron

Publications and source records attributed to D Gendron.

34 records · Page 2Linked to original sources

Preferred crossover sites on polyomavirus DNA.

RmI is a hybrid replicon consisting of polyomavirus (Py) and mouse sequences that yields unit-length polyomavirus DNA via recombination between two directly repeated viral sequences of 182 base pairs (S repeats). To define the contribution of the S repeats in this intramolecular recombination, we derived from RmI a series of replicons containing the original S repeats as well as additional direct viral repeats which were 1 to 2 kilobases in length (L repeats). After mouse 3T6 cells were transfected with these constructs, recombination products that displayed the physical properties of homologous recombinants were detected. The structures of these recombinants indicated that whereas repeat length influences the likelihood of recombination, crossover occurs preferentially near the S repeats, provided that one of them is proximal to the viral origin of replication. This finding suggests that recombination near the S repeats depends on a process initiated near the viral origin of replication.

Animals↗

Learning caring behavior in an integrated manner.

We can see that by transferring caring behaviors from previous experiences, by imitation of role models, and by multiple experiential activities, learners form and utilize schemata of caring. By finding ways to stimulate learners to think about the feeling of caring and to imagine caring for others, caring becomes a psychophysiological or psychokinesthetic experience. A broad aim or high-level purpose, that is, to care, to have interest in and concern for others, or union and separation toward growth could serve as an inner context that would automatically evoke associated networks of learned, integrated caring actions. The caregiver would not usually be aware of each separate action. These broad aims would organize procedural knowledge, or "know how," in the motor areas of the brain. Let us return to Gardield's predicament. Can we help him walk again? Perhaps someone will call him in a friendly voice, someone whom he knows will give him a little chow and lots of stroking on his head. I suspect he would forget about his feet and just hurry over.

Awareness↗

Myoclonus epilepsy and ragged-red fibres (MERRF). 2. Electrophysiological studies and comparison with other progressive myoclonus epilepsies.

Electrophysiological studies (EEG, evoked potentials, nerve conduction and EMG) in 13 patients with myoclonus epilepsy with ragged red fibres (MERRF) are presented. The most notable findings are the presence of atypical irregular generalized spike and wave discharges arising from an abnormal EEG background (9 patients), focal epileptiform abnormalities (6 patients) most commonly over the occipital regions and giant cortical SEPs (4 of 6 patients tested). Similar findings of disturbed EEG background activity, generalized spike and wave discharges and giant cortical SEPs appear to be shared by the group of diseases characterized by progressive myoclonus epilepsy.

Adolescent↗

A substitution in a nonconserved region of polyomavirus large T antigen which causes a thermosensitive mutation.

The temperature-sensitive defect of the tsP155 mutant of polyomavirus (Py) maps in the large T antigen (LT) coding sequence of a viral DNA diverging markedly from that of extensively characterized wild-types (WTs) such as A2 and CSP. We have sequenced about 600 base pairs (bp) "early" DNA encompassing the mutated site in tsP155, as well as the corresponding DNA segment from a revertant virus (RtsP155). As expected, tsP155 was found to be more closely related to CSP than to A2. Out of 3 single bp differences between tsP155 and CSP, 2 were common to tsP155 and RtsP155. The only substitution exclusive to tsP155 was a G----C transversion at bp 2658 which canceled the HaeIII site at bp 2657. Heteroduplexes inclusive of tsP155 DNA and of a 312-bp-long fragment of RtsP155 DNA yielded recombinant viruses growing under restrictive conditions whose DNAs had all regained the HaeIII site at bp 2657. These findings clearly identify the ts mutation with the tranversion at bp 2658, which is expected to change Ala 701 for a Pro in LT. We discuss this substitution in relation to the phenotype of tsP155.

Amino Acid Sequence↗

Treatment of spasticity with tizanidine in multiple sclerosis.

Spasticity is a frequent and often disabling symptom in MS patients. Current drugs used as antispastic agents include Dantrolene Sodium, Baclofen and Diazepam. Tizanidine (5-chloro-4-(2imidazolin-2 yl amino)-2,1,3-benzothialdiazole) is a new antispasticity agent that has purported central action. A double blind placebo controlled trial was performed to study the efficacy of this drug in MS patients. Sixty-six patients entered an eight week therapeutic trial and fifty-nine completed the trial. Patients were assessed at 0, 2, 3 and 8 weeks of therapy for clinical effects. Electrophysiologic tests were performed at 0 and 8 weeks. A statistically significant benefit was noted in spastic muscle groups in the legs with concomitant significant reduction in hyperactive stretch reflexes and ankle clonus. Side effects most frequently cited included dry mouth and drowsiness. Two patients developed elevated liver function test that decreased with cessation of therapy. Other clinical details, side effects and electrophysiologic data will be presented. Tizanidine appears to reduce clinical spasticity and hyperreflexia in MS patients although no change in functional status was detected. Tizanidine may well serve as an alternate antispastic agent, alone or in combination with other agents.

Adolescent↗

An amplified genome that may have resulted from recombination within bidirectionally replicating DNA.

Temperature shift-down of permissive mouse cells transformed by a temperature-sensitive (ts) polyomavirus (Py) genome has been shown to induce the accumulation of free copies of the viral DNA. We report here on an unusual product from such induction. The structure of this product is that expected from the occurrence of recombination between growing points in a bidirectionally replicating Py-mouse DNA molecule. This observation may be relevant to the mechanism of gene amplification in mammalian cells.

Animals↗

An excision event that may depend on patchy homology for site specificity.

In mouse cells transformed by a mutant polyomavirus genome, recombination between integrated viral DNA and flanking cellular DNA resulted in the excision of two readily amplifiable chimeras, designated RmI and RmII. The crossing-over that generated RmII was unique in that it involved a simple cellular sequence in which the triplet 5'-CTG-3' was repeated many times. We show that the sequence across the junction resulting from excision was identical in several molecules of RmII, as if the cross-over generating this junction always involved exactly the same two sites on the viral and cellular DNA. We also show that the cellular site mapped where the replacement of a G by an A in one of many successive 5'-CTG-3' triplets generated a homology of five nucleotides (5'-CTACT-3') with the viral site. Oligonucleotides on both sides of these sites are probably involved in matching the two DNAs prior to recombination.

Animals↗

Mouse cells surviving polyoma virus infection generally retain the whole viral genome.

Permissive mouse 3T6 cells were exposed to polyoma virus--either wild-type or early mutant--at high multiplicities of infection. From colonies arising from surviving cells, so-called lines and clones were derived under conditions precluding superinfection. These lines and clones were examined for the presence of viral genetic information, using a variety of techniques. Two salient findings were made: most lines or clones analyzed had retained viral genetic material; generally, this material was nondefective, as evidenced by the production of virus and/or viral DNA molecules of genomic size. These findings indicate that mouse cells can survive for many generations while carrying a complete, infectious, and potentially cytocidal polyoma virus genome.

Animals↗

Inducible permissive cells transformed by a temperature-sensitive polyoma virus: superinfection does not allow excision of the resident viral genome.

After exposure of mouse embryo cells to the early temperature-sensitive mutant tsP155 of polyoma virus (Py), a transformed cell line (Cyp line) that can be readily induced to synthesize Py by transfer to 33 degrees C was isolated at 39 degrees C (7). Virus production and synthesis of free viral DNA occurring after temperature shiftdown or superinfection with wild-type Py or both were studied in several clonal isolates of the Cyp cell line. Measurements of virus yields indicated that, although some could be induced more effectively than others, all cell clones behaved as highly permissive when subjected to superinfection. We analyzed the origin of free viral DNA accumulating in the superinfected cultures, taking advantage of (i) the unique physical properties of the low-molecular-weight DNA which, in the case of one of the Cyp clones, accumulates during temperature shiftdown, and (ii) the differences between resident and superinfecting viral genomes in their susceptibilities towards restriction endonucleases. At 33 degrees C, both viral genomes were found to accumulate in all clones studied whereas in the case of the clones with lower inducibility, the replication of the resident genome appeared to be enhanced by superinfection. At 39 degrees C, however, accumulation of the superinfecting genome was not accompanied by that of the resident genome, unless it had already been initiated before superinfection. These findings demonstrate that, when routinely cultivated at 39 degrees C, Cyp cells contain few viral DNA molecules readily available for autonomous replication and that, upon transfer to 33 degrees C, therefore, excision must first take place before the resident genome can accumulate as free viral DNA. Our findings also suggest that, unlike the P155 gene product provided by the resident viral genome upon induction, the allelic gene product supplied by the superinfecting genome may be less effective in triggering excision than in promoting replication.

Animals↗

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