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Biomedical subjects

A Grégoire

Publications and source records attributed to A Grégoire.

At least 19 recordsLinked to original sources

[CT guided neurolysis of the sphenopalatine ganglion for management of refractory trigeminal neuralgia].

The authors present the case of a patient with recurrent trigeminal neuralgia, refractory to medical treatment and ablation of the trigeminal ganglion, who underwent three separate CT guided injections for pterygopalatine ganglion ablation over a two year period. Ablation of the pterygopalatine ganglion may be an effective technique for pain management in patients suffering from atypical facial pain syndrome, cluster headache, or neuritis. The technique used for CT guided ablation using alcohol or radiofrequency is described. The advantages and pitfalls of this technique are reviewed.

Adult↗

[Symptomatic venous congestion of the brain stem after embolization for dural fistula of the cavernous sinus].

We report the case of a 60-year old woman presenting, 3 days after arterial embolization of a dural arteriovenous fistula, with diplopia and gait disturbance in relation with right oculomotor nerve palsy and cerebellar dysfunction. On T2 weighted MR images, several hyperintense areas appeared in the pons and the midbrain. After one month, clinical symptoms and diffuse hyperintense areas resolved spontaneously, as the patient was treated by anti-vitamin K. This complication probably corresponds to reversible pontine venous congestion caused by poor venous drainage of the dural arteriovenous fistula.

Brain Edema↗

Differential influence of Pomphorhynchus laevis (Acanthocephala) on the behaviour of native and invader gammarid species.

Although various species of acanthocephalan parasites can increase the vulnerability of their amphipod intermediate hosts to predation, particularly by altering their photophobic behaviour, their influence on the structure of amphipod communities and the success of invader species has so far received little attention. We compared the prevalence and behavioural influence of a fish acanthocephalan parasite, Pomphorhynchus laevis, in two species of amphipods, Gammarus pulex and Gammarus roeseli in sympatry in the river Ouche (Burgundy, eastern France). There, G. pulex is a resident species, whereas G. roeseli is a recent coloniser. Both uninfected G. pulex and G. roeseli were strongly photophobic. although less so in the invading species. However, there was no significant difference in reaction to light between infected and uninfected G. roeseli, whereas infected G. pulex were strongly photophilic. We discuss our results in relation to the parasite's ability to manipulate invading host species, the possibility that resistant individuals have been selected during the invasion process, and the role that acanthocephalan parasites can play in shaping the structure of amphipod communities.

Acanthocephala↗

Plasma serotonin level after 1 day of fluoxetine treatment: a biological predictor for antidepressant response?

RATIONALE: Antidepressant treatments present a delayed onset of action. OBJECTIVE: The present study investigated whether plasma or serum serotonin, 5-hydroxytryptamine (5-HT), could predict clinical improvement. METHODS: Biological parameters were determined after a 4-week drug-free period (day 0) and 1, 14 and 28 days after the beginning of the treatment with fluoxetine 20 mg daily in depressed patients. Clinical evaluations were assessed on days 0, 14 and 28. RESULTS: One day after a single dose, the mean values of plasma 5-HT (5.4 +/- 2.6 nmol/l) and serum 5-HT (484 +/- 215 nmol/l) were not statistically different from basal mean values (4.5 +/- 2.5 nmol/l and 523 +/- 263 nmol/l, respectively). The repeated treatment significantly reduced serum 5-HT to 34% (P = 0.002) and 17% (P = 0.0004) of pretreatment values after 14 and 28 days of treatment, respectively; plasma 5-HT was also reduced significantly to 28% and 15% of pretreatment values (P < 0.05 in both cases). At day 28, four of the eight patients responded by showing a reduction in MADRS score of at least 50% of the baseline score. No correlation was found between pretreatment values of serum or plasma 5-HT and clinical evolution, even if a tendency (P < 0.07) to lower serum 5-HT pretreatment values was observed in responders. Plasma 5-HT after 1 day of treatment was significantly different between responders and non-responders: the plasma 5-HT concentration in responders was 3.4 +/- 1.7 nmol/l versus 7.4 +/- 1.6 nmol/l in non-responders (P = 0.02). Moreover, plasma 5-HT levels after 1 day of treatment were positively correlated to the final MADRS score (r = +0.89, n = 8, P = 0.003) and inversely correlated to its change from the initial score (r = -0.76, n = 8, P = 0.02). CONCLUSION: These preliminary data show that fluoxetine and norfluoxetine might influence 5-HT peripheral venous blood parameters and that plasma 5-HT after 1 day of treatment might be a biological predictor for antidepressant response.

Adult↗

Masc2, a gene from Ascobolus encoding a protein with a DNA-methyltransferase activity in vitro, is dispensable for in vivo methylation.

We have shown previously that masc1, a gene encoding a putative C5-DNA-methyltransferase (MTase), was necessary for the de novo 'Methylation Induced Premeiotically' (MIP) process and sexual reproduction in Ascobolus, whereas it was dispensable for maintenance methylation. A second MTase gene from Ascobolus, masc2, encodes a protein, Masc2, which possesses the large amino-terminal part characteristic of eukaryotic maintenance MTases. In vitro assays have shown that Masc2 displays a methylation activity, suggesting that it might be the MTase responsible for maintenance methylation. To check its function in vivo, we engineered a disruption of the masc2 gene. The resulting mutant strains did not exhibit any particular phenotype during either vegetative growth or sexual reproduction. Neither the masc2 mutation nor the double masc1 masc2 mutation had any detectable effect upon the maintenance of the pre-existing methylation of single gene copies previously subjected to MIP, natural retroelement-like repeats and tandemly repeated rDNA. The masc2 mutation did not alter either MIP or the other de novo methylation process that operates in vegetatives cells. Nor did it impair the meiotic process of methylation transfer. These results suggest that at least a third MTase gene responsible for maintenance and vegetative de novo methylation is present in Ascobolus.

Ascomycota↗

An in vivo and in vitro structure-function analysis of the Saccharomyces cerevisiae U3A snoRNP: protein-RNA contacts and base-pair interaction with the pre-ribosomal RNA.

The structure and accessibility of the S. cerevisiae U3A snoRNA was studied in semi-purified U3A snoRNPs using both chemical and enzymatic probes and in vivo using DMS as the probe. The results obtained show that S. cerevisiae U3A snoRNA is composed of a short 5' domain with two stem-loop structures containing the phylogenetically conserved boxes A' and A and a large cruciform 3' domain containing boxes B, C, C' and D. A precise identification of RNA-protein contacts is provided. Protection by proteins in the snoRNP and in vivo are nearly identical and were exclusively found in the 3' domain. There are two distinct protein anchoring sites: (i), box C' and its surrounding region, this site probably includes box D, (ii) the boxes B and C pair and the bases of stem-loop 2 and 4. Box C' is wrapped by the proteins. RNA-protein interactions are more loose at the level of boxes C and D and a box C and D interaction is preserved in the snoRNP. In accord with this location of the protein binding sites, an in vivo mutational analysis showed that box C' is important for U3A snoRNA accumulation, whereas mutations in the 5' domain have little effect on RNA stability. Our in vivo probing experiments strongly suggest that, in exponentially growing cells, most of the U3A snoRNA molecules are involved in the 10-bp interaction with the 5'-ETS region and in two of the interactions recently proposed with 18S rRNA sequences. Our experimental study leads to a slightly revised version of the model of interaction proposed by J. Hughes. Single-stranded segments linking the heterologous helices are highly sensitive to DMS in vivo and their functional importance was tested by a mutational analysis.

Animals↗

Prevention of bleomycin-induced pulmonary fibrosis after adenovirus-mediated transfer of the bacterial bleomycin resistance gene.

A serious limitation in the use of the DNA-cleaving, antitumoral-antibiotic, bleomycin during chemotherapy is pulmonary toxicity. Lung injury induced by bleomycin is characterized by an increased deposition of interstitial extracellular matrix proteins in the alveolar wall that compromises respiratory function. Several drugs have been tested in animal models to prevent the pulmonary toxicity of bleomycin, but have not led to a useful clinical treatment because of their adverse effects on other tissues. We have shown that transgenic mice expressing Streptoalloteichus hindustanus (Sh) ble bleomycin resistance protein in pulmonary epithelial cells in the lungs are protected against bleomycin-induced toxicity in lungs. In the present study, we used intranasal administration by adenovirus-mediated gene transfer of the bleomycin resistance Sh ble gene to mouse lung for prevention of bleomycin-induced pulmonary fibrosis. We constructed recombinant adenoviruses Ad.CMVble and Ad.RSVble harboring the bleomycin resistance Sh ble gene under the control of the cytomegalovirus early promoter and the Rous sarcoma virus early promoter, respectively. Transgene expression was detected in epithelia of conducting airways and alveolar septa by immunostaining with a rabbit polyclonal antibody directed against the bleomycin resistance protein and persisted for the duration of drug treatment; i.e., up to 17 d. No toxic effect was seen in adenovirus-treated mice. Pretreatment of mice with Ad.CMVble or Ad.RSVble completely prevented collagen deposition 42-133 d after bleomycin treatment, as measured by lung OH-proline content. Histologic studies indicated that there was little or no lung injury in the adenovirus/bleomycin-treated mice compared with the bleomycin-treated mice. These observations may lead to new approaches for the prevention of bleomycin-induced pulmonary fibrosis.

Acetyltransferases↗

A unique U5-->A substitution in the Physarum polycephalum U1 snRNA: evidence at the RNA and gene levels.

The 5' terminal sequence of U1 snRNA that base-pairs with the intron 5' splice site in the course of spliceosome assembly was considered to be universally conserved. A study of the P polycephalum U1 snRNA at both RNA and gene levels shows that there are exceptions to this rule: the P polycephalum U1 snRNA has a U to A substitution at position 5, that is partially compensated by a high frequency of T residue at position +4 of introns. In contrast to the yeast genome, the P polycephalum genome contains several U1 snRNA coding sequences (about 20). They either encode the U1A snRNA expressed in microplasmodia or correspond to the previously cloned U1B coding sequence. Both coding sequences show the U5A substitution. The ratio of U1A versus U1B coding sequences is of about 3. A U1A gene was cloned. The 60 nt region upstream of the coding sequence has the same sequence as in the U1B gene. The U1B gene is probably expressed at another stage of the P polycephalum life cycle.

Amino Acid Sequence↗

Methylation of DNA repeats of decreasing sizes in Ascobolus immersus.

In Ascobolus immersus, DNA duplications are subject to the process of methylation induced premeiotically (MIP), which methylates the cytosine residues within the repeats and results in reversible gene silencing. The triggering of MIP requires pairing of the repeats, and its detection requires maintenance of the resulting methylation. MIP of kilobase-size duplications occurs frequently and leads to the methylation of all C residues in the repeats, including those belonging to non-CpG sequences. Using duplications of decreasing sizes, we observed that tandem repeats never escaped MIP when larger than 630 bp and showed a sudden and drastic drop in MIP frequencies when their sizes decreased from 630 to 317 bp. This contrasted with the progressive decrease of MIP frequencies observed with ectopic repeats, in which apparently the search for homology influences the MIP triggering efficiency. The minimal size actually required for a repeat to undergo detectable MIP was found to be close to 300 bp. Genomic sequencing and Southern hybridization analyses using restriction enzymes sensitive to C methylation showed a loss of methylation at non-CpG sites in short DNA segments, methylation being restricted to a limited number of CpG dinucleotides. Our data suggest the existence of two distinct mechanisms underlying methylation maintenance, one responsible for methylation at CpG sites and the other responsible for methylation at non-CpG sites.

Ascomycota↗

Secondary structure of the yeast Saccharomyces cerevisiae pre-U3A snoRNA and its implication for splicing efficiency.

The Saccharomyces cerevisiae U3 snoRNA genes contain long spliceosomal introns with noncanonical branch site sequences. By using chemical and enzymatic methods to probe the RNA secondary structure and site-directed mutagenesis, we established the complete secondary structure of the U3A snoRNA precursor. This is the first determination of the complete secondary structure of an RNA spliced in a spliceosome. The peculiar cruciform structure of the U3A snoRNA 3'-terminal region is formed in the precursor RNA and the conserved Boxes B and C are accessible for binding the U3 snoRNP proteins. The intron forms a highly folded structure with a long central stem-loop structure that brings the 5' box and the branch site together. This is in agreement with the idea that secondary structure interactions are necessary for efficient splicing of long introns in yeast. The 3' splice site is in a bulged loop and the branch site sequence is single-stranded. Surprisingly, the 5' splice site is involved in a 6-base pair interaction. We used in vitro splicing experiments to show that, despite a noncanonical branch site sequence and a base paired 5' splice site, transcripts that mimic the authentic pre-U3A snoRNA are spliced very efficiently in vitro. Sequestering the 5' splice site in a more stable structure had a negative effect on splicing, which was partially compensated by converting the branch site sequence into a canonical sequence. Analysis of spliceosomal complex formation revealed a cumulative negative effect of a base pair interaction at the 5' splice site and of a deviation to the consensus sequence at the branch site on the efficiency of spliceosome formation in vitro.

Base Composition↗

Secondary structure conservation of the U3 small nucleolar RNA introns in Saccharomyces.

Using a strategy based on PCR amplification of DNA and sequence analysis, we showed that the presence of introns with the characteristic features of introns spliced in a spliceosome, in the U3A and U3B snoRNA genes that code for the U3 small nucleolar RNA, is not a property restricted to Saccharomyces cerevisiae. It is probably an ancient property of yeasts from the genus Saccharomyces. We detected the U3A and U3B snoRNA genes in Saccharomyces bayanus and in a lager brewing yeast strain. The U3A and U3B intronic sequences are highly conserved. Two additional "U3B-like" snoRNA genes were detected in the lager brewing yeast. Their intronic sequences show several differences, when compared to the U3B intronic sequence. However, despite the numerous mutations, the intron secondary structure is conserved, especially, the central structure. This strongly suggests an important role of this central stem/loop structure for spliceosome assembly and efficient splicing.

Base Sequence↗

Clustering of multiple transgene integrations in highly-unstable Ascobolus immersus transformants.

A large proportion of Ascobolus immersus transformants are highly unstable in crosses: the phenotype conferred by the transgene is not transmitted to the progeny, irrespective of the endogenous or foreign origin of the transgene. They all have integrated multiple transgene copies, clustered at a single chromosomal site or at tightly-linked sites. Clustered non-homologous integrations are always rearranged. Yet they never escape the "methylation induced premeiotically" (MIP) process. This always results in gene silencing, even when the transgene is partially repeated, accounting for the high instability of these transformants.

Ascomycota↗

Long-term correction of mouse dystrophic degeneration by adenovirus-mediated transfer of a minidystrophin gene.

Duchene muscular dystrophy (DMD) is a fatal progressive X-linked muscle disorder, caused by mutations in the dystrophin gene. We have investigated adenovirus-mediated transfer of a dystrophin minigene in a mutant mouse lacking dystrophin, the mdx mouse. We report here that six months after a single intramuscular injection of a recombinant adenovirus containing a human dystrophin minigene, a large number of dystrophin-positive fibres are still detected in the injected muscles. Moreover, although the minigene encodes a truncated protein, its expression is able to protect the fibres efficiently against the degeneration process that affects the dystrophin-deficient mdx myofibres.

Adenoviridae↗

An experimental study of Saccharomyces cerevisiae U3 snRNA conformation in solution.

The conformation of Saccharomyces cerevisiae U3 snRNA (snR17A RNA) in solution was studied using enzymatic and chemical probes. In vitro synthesized and authentic snR17A RNAs have a similar conformation in solution. The S. cerevisiae U3 snRNA is folded in two distinct domains. The 5'-domain has a low degree of compactness; it is constituted of two stem-loop structures separated by a single-stranded segment, which has recently been proposed to basepair with the 5'-ETS of pre-ribosomal RNA. We demonstrate that, as previously proposed, the 5'-terminal region of U3 snRNA has a different structure in higher and lower eukaryotes and that this may be related to pre-rRNA 5'-ETS evolution. The S. cerevisiae U3 snRNA 3'-domain has a cruciform secondary structure and a compact conformation resulting from an higher order structure involving the single-stranded segments at the center of the cross and the bottom parts of helices. Compared to tRNA, where long range interactions take place between terminal loops, this represents another kind of tertiary folding of RNA molecules that will deserve further investigation, especially since the implicated single-strands have highly evolutionarily conserved primary structures that are involved in snRNP protein binding.

Base Composition↗

Effect of a macrolide (spiramycin) on the pharmacokinetics of L-dopa and carbidopa in healthy volunteers.

In one well-equilibrated parkinsonian patient treated with combined L-dopa and carbidopa (Sinemet), we have observed changes in treatment efficacy while receiving spiramycin (Rovamycine) for an intercurrent respiratory infection. A preliminary study of the pharmacokinetics of L-dopa and its main metabolites 3-O-methyldopa (3-OMD) and dihydroxyphenylacetic acid (dopac) in two parkinsonian patients treated with Sinemet has revealed a marked decrease in the AUC0-360 of these two metabolites after a 3-day course of Rovamycine. In order to confirm this interaction, we have studied the modifications of the pharmacokinetics of L-dopa, 3-OMD, dopac, and carbidopa in eight male healthy volunteers after a single dose of Sinemet 250 (L-dopa, 250 mg and carbidopa, 25 mg) before and after a 3-day course of Rovamycine. Our study confirms this interaction. After spiramycin, we observed a marked reduction in AUC0-360 for L-dopa (p less than 0.001), 3-OMD (p less than 0.001), and carbidopa (p less than 0.001), and an increase in AUC0-360 for dopac (p less than 0.01). The L-dopa elimination half-life was increased (p less than 0.012); differences in peak plasma concentrations did not attain statistical significance. We think that these modifications in L-dopa pharmacokinetics after spiramycin are due to nonabsorption of carbidopa secondary to modified gastrointestinal motility.

Adult↗

Stable allele replacement and unstable non-homologous integration events during transformation of Ascobolus immersus.

An homologous transformation system for the filamentous fungus Ascobolus immersus has been developed, based on the complementation of a met2 mutation by the wild-type (wt) allele gene encoding homoserine O-transacetylase. Transformation of A. immersus met2 mutants occurs with moderate frequencies (about 50 transformants per microgram input DNA). Analysis of the DNA of the met2+ transformants showed that transformation resulted either in a single integration of the donor DNA into the genome by many different nonhomologous recombination events or in the substitution of the endogenous met2 mutation by the wt transforming allele. The relative frequencies of both events depended on the vector sequences carrying the cloned met2 gene. Whereas the substitution event led, as expected, to genetically stable transformants, the non-homologous integration was always associated with a strong instability when transformants were crossed and underwent meiosis.

Acetyltransferases↗

Pyocolon: an unusual manifestation of colon ischemia.

An unusual manifestation of a large bowel ischemia was observed in two patients. Both had a left flank tubular fluid collection demonstrated respectively by computed tomography (CT) and ultrasonography (US). At surgery, pyocolon (i.e. ischemic, dilated large bowel segments filled with pus) was discovered and resected. Pyocolon should be suspected in patients with ischemic colitis and sepsis. US, although useful, may be misleading; CT is the investigation of choice to establish the diagnosis.

Aged↗

[Inflammatory aneurysm of the aorta. Value of x-ray computed tomography and ultrasonography in the diagnosis of a case and review of the literature].

Until recently inflammatory aneurysm of the aorta was discovered only at the time of surgery and confirmed by the pathologist. New imaging modalities, such as ultrasound and CT-scan now enable the radiologist to diagnose this entity before surgery, thus leading to a better surgical planning and reducing the operative morbidity. The authors report a case of inflammatory aneurysm of the aorta and review the literature on this entity.

Aged↗